Lupus - Hope Through Understanding - Aladjem, Henrietta, 1917 (Orthomolecular Medicine)

UJt^
Hope Throu^ Understanding
by
Hennetta
Aladiem
Author of
“The Sun Is My Enemy”
Introduction by Peter H. Schur, M.D.
LUPUS — HOPE THROUGH UNDERSTANDING
Henrietta Aladjem with one of Dr. Robert Swartz's dogs with Lupus-like disease. Photograph by
Martha Aladjem Climo.
11
Lupus
Hope Through Understanding
HENRIETTA ALADJEM
LUPUS FOUNDATION OF AMERICA, INC.

ST. LOUIS, MISSOURI 63141
Copyright © 1982 by Henrietta Aladjem
TX4 83-152
Books By Henrietta Aladjem

The Sun Is My Enemy, 1972
Lupus — Hope Through Understanding — Monograph on Lupus
All rights reserved

First published as a Lupus Foundation of America paperback in 1982
Library of Congress Cataloging in Publication Data

82-80912
ISBNO-9608660-0-0
Printed in the United States of America
Typography and Printing, Acme Printing Company,

Medford, Massachusetts
IV
This book is dedicated to Lisa Hamel* and Gina Finzi.** Per¬
ceptive, intelligent and sensitive . . . They were both in their
early twenties. What do we know about their ‘real’ life? What
do we know about lupus?
*Lisa Hamel died of lupus at the age of 23. She was an honor student in the
Biology Department at Simmons College, Boston.
**Gina Finzi died of lupus at the age of 22. She was an honor student at Fairleigh
Dickinson University in New Jersey where she was studying to be a medical technician.
The funds from this book will benefit the Lisa Hamel and Gina
Finzi SLE Fund for Education and Public Awareness.
Digitized by the Internet Archive
in 2018 with funding from
Kahle/Austin Foundation
https://archive.0rg/details/lupushopethroughOOOOalad
ACKNOWLEDGEMENTS
Lupus — Hope Through Understanding is for the lupus patient,
for the health care professionals and for the general reader who
would like to learn more about this disease. It is based on my
own experiences with systemic lupus erythematosus, on the
more than three thousand letters I have received from lupus
patients in response to The Sun Is My Enemy, and on my conver¬
sations with eighteen medical investigators and psychiatrists. In
the three years since beginning this monograph, I have inter¬
viewed these scientists and doctors many times. I made an effort
to avoid redundancy while attempting to preserve the integrity of
the individual chapters, but repetition is inevitable in a book of
this nature.
I would like especially to thank Dr. Peter H. Schur. Without
his friendship and his enthusiastic efforts to improve understand¬
ing of this elusive disease, I could not have completed this
work. My gratitude to Dr. Sheldon G. Cohen is inexpressible,
and I shall always remember his patience and his kindness. I feel
much indebted to Mrs. Dorothy Newman, who, over the past
twelve years, has offered continued encouragement in our com¬
mitment to help the lupus patient and to increase prior awareness
of this disease. Upon reading the manuscript, Mrs. Newman
suggested that I modify the medical terminology. And I must
thank Susan Sepenak, Marla Lustbader and Dr. Caren A. Heller
for helping me make such changes whenever possible.
My thanks also go to Otto Zausmer, Associate Editor of the
Boston Globe, for whom I have special feelings. Otto has spent
many hours working with me, making suggestions that arise
from his sound journalistic sense of organization. From Otto I
have learned to be clear and straightforward.
I must also thank C. Michael Curtis, Senior Editor of the
Atlantic Monthly, who has been my teacher in creative writing
for many years. With the help of Michael, I won the battle
Vll
against dangling participles, prepositions, and unruly English
language.
And finally, my deep love to my family for their patience and
understanding which enabled me to do my work.
The choice of physicians in this monograph has been my own.
I cannot here acknowledge the many physicians who have con¬
tributed to this work, but this does not diminish my gratitude for
all their help. These physicians and I share the belief that the
greatest gift one can bestow on the lupus patient today is a sense
of hope — hope through understanding. I would like to believe
that we have achieved this goal.
H.A.
FOREWORD
The use of the word “Lupus” to describe the chronic inflamma¬
tory disease which preferentially affects women illustrates the
subconscious apprehension felt by generations of physicians
who have managed these patients. The trepidation fostered by
lupus is illustrated in the very term used to describe the condi¬
tion. Some of the first observers compared the facial lesions to
the bite of a wolf while others likened the rash to the facial mask
of a wolf.
The patients who live with this malady are no less fearful.
The weight of unanswered questions presses heavily on them.
“What causes lupus?” This is usually the first of many frustrat¬
ing questions without an answer. Patients who are told, “You
have a mild form of lupus,” correctly inquire, “Will it get
worse?”. As the patient endures a prolonged flare she (or he)
may ask, “When will I ever get better?”. An uneasiness also
punctuates the existence of the lupus patient who has been free
of symptoms for months or years and gives rise to the inquiry,
“How long will this remission last?”
Medical researchers, lupus clinicians and lupus patients are
working diligently to solve the complex puzzle of lupus. They
are combining their efforts to provide more answers. “Lupus —
Hope Through Understanding” epitomizes this joint endeavor.
Patricia A. Fraser, M.D.

Harvard Medical School
IX
The Following Physicians Answered my Questions Concerning
Lupus Research and the Problems of the Lupus Patient
Chester Alper, M.D., Professor of Pediatrics, Harvard University Medi¬

cal School, and Scientific Director of the Blood Grouping Laboratory,
Boston, Massachusetts.
Yves Borel, M.D., Associate Professor of Pediatrics, Harvard Medical
School; Director of Rheumatology Services, Children’s Medical Center,
Boston, Massachusetts.
Ronald V. Carr, M.D., Associate Professor of Medicine, University of
Colorado Medical School, Member Department of Medicine, National
Jewish Hospital and Research Center, Denver, Colorado.
Edgar Cathcart, M.D., Professor of Medicine, Boston University
School of Medicine; Chief of the Arthritis and Gerontology Center, Bed¬
ford Veterans Hospital, Bedford, Massachusetts.
Sheldon G. Cohen, M.D., Director of Immunology, Allergic and Im¬
munologic Diseases Program at the National Institute of Allergy and Infec¬
tious Diseases, Bethesda, Maryland.
Elizabeth S. Cole, M.D., Chief of Dermatology and Venereology,
Newton-Wellesley Hospital in Newton, Massachusetts and Lecturer in
Medicine, Tufts University School of Medicine, Boston, Massachusetts.
Stephen Kaplan, M.D., Associate Professor of Medicine, Brown Uni¬
versity Medical School; Chief of Rheumatology, Roger Williams General
Hospital, Providence, Rhode Island.
Richard A. Kaslow, M.D., Research Medical Epidemiologist, National
Institute of Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, Maryland.
Thomas Medsger, Jr., M.D., Associate Professor of Medicine, Univer¬
sity of Pittsburgh Medical School.
Fred Quimby, M.D., Director of Laboratory Animal Resources, Cornell
University School of Medicine, Ithaca, New York.
Theodore Nadelson, M.D., Chief of Psychiatry, Boston Veterans Ad¬
ministration and Clinical Professor of Psychiatry, Tufts Medical School.
Gerald Rodnan, M.D., Professor of Medicine, University of Pittsburgh
Medical School, Chief Department of Rheumatology.
Naomi Rothfield, M.D., Professor of Medicine, University of Connecti¬
cut School of Medicine; Director, Division of Rheumatic Diseases, Con¬
necticut Health Center, Framington, Connecticut.
Peter H. Schur, M.D., Professor of Medicine, Harvard Medical School,
Director of Lupus Research, Robert Breck Brigham Hospital, Boston,
Massachusetts.
Robert Schwartz, M.D., Professor of Medicine, Tufts University Medi¬
cal School; Director of Cancer Research, New England Medical Center,
Chief of Hematology, Boston, Massachusetts.
X
Charles Steinman, M.D., Associate Professor of Medicine, Mount Sinai
School of Medicine of the City of New York and Director of Rheumatol¬
ogy Research.
Norman Talal, M.D., Professor of Medicine, University of Texas
Health Center, San Antonio, Texas.
Robert B. Zurier, M.D., Professor of Medicine, Chief of Rheumatol¬
ogy, University of Pennsylvania, Philadelphia, Pennsylvania.
H.A.
XI
TABLE OF CONTENTS
Dedication v
Acknowledgements vii-viii
Foreword, Patricia Fraser, M.D. ix
Milestones in the History of Systemic Lupus Erythematosus xv

prepared by Gerald Rodnan, M.D.
1 Introduction 1
2 The Physician, The Psychiatrist and 15

The Lupus Patient
3 The Epidemiology of Lupus 41
4 SLE In Children and Other Research 49
5 Lupus and Photosensitivity 59
6 Why is Lupus More Common in Women 73
7 SLE and Pregnancy 79

(Part One)
8 SLE and Pregnancy 83

(Part Two)
Xlll
9 Lupus and Medications 91
10 Ingested Antigens May Play a Role in 111

the Pathogenesis of SEE
11 Unravelling Some of the Mysteries of Lupus 123
12 The Kidneys and Other Aspects of S.L.E. 131
13 Prostaglandin Offers Hope in Lupus 137
14 The Genetics of Lupus 141
15 Dogs as Well as People Suffer Prom Lupus 151

(Part One)
16 Update on the Lupus Dogs 157

(Part Two)
17 Pulse Therapy 165
18 Of NIAID-NIH, In Search of a Cure for Lupus 169
Bibliography for Additional Reading and Explanations 181
Glossary 197
XIV
Milestones in the History of Systemic Lupus Erythematosus
Prepared by Gerald Rodnan, M.D.
Year Author(s) Contribution

1838 Pierre Cazenave & Credit Beitt with early recognition of
Henry Schedel lupus erythematosus (erytheme centri¬
fuge)
1845 Ferdinand Detailed description of skin changes of
Van Hebra lupus erythematosus under the desig¬
nation seborrhoea congestiva — “One
sees at the beginning of this illness —
mainly on the face, on the cheeks and
the nose in a distribution not dissimilar
to a butterfly an excessive sebaceous
secretion ...”
1851 Pierre Cazenave Introduces term lupus erythemateux
1869, Moritz Kaposi Early description of systemic features
1872 of lupus erythematosus
1903 Sir William Osier Reports two patients with systemic
lupus erythematosus and involvement
of the kidneys
1924 Emanuel Libman & Description of atypical verrucous en¬
Benjamin Sacks docarditis (heart valve involvement)
1935 George Baehr, Paul First comprehensive clinical and
Klemperer & Arthur pathological description of systemic
Schifrin lupus erythematosus
1948 Malcolm Hargraves, Discovery of the “L.E. cell’’ phenom¬
Helen Richmond & enon
Robert Morton
1950 George Baehr & Treatment of systemic lupus erythema¬
Louis Softer tosus with cortisone and ACTH
1955 George Frion Discovery of the immunofluorescent
ANA test
1959 Marianne Mouse models for lupus (NZB/NZW)
Bielschowsky
1959 Helmuth Deicher, Demonstration of anti-DNA antibody
Halsted Holman &
Henry Kunkel
1972 Hugh McDevitt Genetics, HLA and SEE
1978 Norman Talal Sex hormones and SEE
XV
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Introduction 1
Introduction
‘'And probably no one as much as the

patient has managed to give the disease
such insights and profound understand¬
ings/'
— BARBARA FEINBERG*
^Barbara Feinberg is the President of the Lupus

Erythematosus Foundation of Massachusetts.
2 Lupus — Hope Through Understanding
The Relationships Between
Treatment Patient
Research Doctor
his book was written for the persons with lupus, for their
families, and for the medical professionals who take care of
them. It was written to improve our understanding of lupus,
and, perhaps as important, to improve our understanding of the
person who suffers from lupus. Readers who are also patients
will gain, we hope, a better understanding of their affliction. If
the reader is a physician, we hope that this book will assist him
in being better able to recognize, diagnose, and treat people with
lupus.
This introductory chapter will acquaint one with systemic
lupus erythematosus (SLE or lupus, as it is better known), its
management and treatment, and the role of the patient and his
physician in these decisions. Later chapters will go into greater
detail in more specific areas.
What is lupus? Lupus is a chronic, inflammatory disease of
unknown cause which can affect virtually any part of the body.
Patients with SLE also develop distinct abnormalities of the im¬
mune system; that is, in addition to making antibodies against
bacteria and viruses, lupus patients make antibodies to their own
cells, the so-called antinuclear antibodies. A diagnosis of SLE is
likely to follow the discovery of these antinuclear antibodies,
especially antibodies to DNA.
Although SLE can affect any part of the body, most patients
experience symptoms in only a few organs. The Table below
lists the frequency of certain symptoms found in patients with
SLE.
Introduction 3
Table I
Fever (over lOOF) 90%
Skin rashes 74%
Butterfly rash 42%
Arthritis (swollen Joints) 90%
Arthralgia (achy joints) 95%
Raynauds 17%
Hair loss 27%
Mouth ulcers 12%
Photosensitivity 30%
Kidney involvement 50%
Pleurisy 45%
Seizures 15%
Anemia 71%
As the statistics clearly indicate, most lupus patients will not

experience all of the symptoms, or even many of them. For most
patients, symptoms in organs that will eventually be affected are
usually evident within the first year or two after diagnosis.
Most patients have skin and joint involvement. We usually
associate the sun with good things: life, nourishment, and
growth of the soil, warmth. However, for lupus patients the sun
is more often an enemy to be avoided, because exposure to
sunlight might cause a rash. This rash is caused by the ultravio¬
let rays which can come not only from the sun, but also from
artificial sources such as sun lamps, or from ultraviolet or flu¬
orescent lights.
The rash most typical of SLE is called the butterfly rash be¬
cause it appears in the shape of a butterfly on the cheeks and
bridge of the nose. This characteristic rash develops in less than
half of patients with lupus. Some patients may experience a
blush and swelling, or a scaly red, slightly raised rash on both
cheeks, and the bridge of the nose. This may clear spontane¬
ously, only to reoccur after exposure to the sun. Other skin
areas, particularly those exposed to the sun, such as the neck,
chest, and forearms, may also be involved. The rash is rarely
itchy. Most rashes go away, but continued recurrence can result
in permanent scars.
These lupus rashes fall into two categories: discoid lupus

which can cause ulcers, scabs, and white or brown blotches on
the skin; or telangiectasia, small blood vessels that appear as red
streaks in the skin, especially on the face. These streaks do not
represent an active lesion.
In some patients, the skin is involved in other ways. Some
may develop patchy hair loss on their scalps (alopecia); this
usually grows back in most patients. Raynaud’s phenomenon
(the fingers or toes turn white or blue, with or without tingling
or pain) may occur, especially on exposure to the cold. Ray¬
naud’s also develops in patients with other connective tissue
diseases, such as scleroderma or rheumatoid arthritis and in
many young or middle-aged people who do not have any associ¬
ated disease at all. Patients with lupus also occasionally develop
painless, or sometimes painful, ulcers in their mouth or nose.
Most patients complain of aches and pains in their joints
(arthralgia) at some time, and arthritis, or swollen inflamed
joints, is also seen frequently. This arthritis often affects the
hands, causing the fingers and the back of the hand to swell. It
can occasionally affect the elbows, wrists, hips, knees, or an¬
kles. Other joints are rarely affected. The arthritis often lasts just
a day or so in one joint before moving on to another. The
arthritis rarely becomes chronic in one joint, and it rarely causes
deformities. Swelling of the foot is more likely caused by fluid
retention (edema) than by arthritis of the foot.
Muscle pain is a frequent complaint, and is accompanied,
occasionally, by muscle wasting, a feeling of weakness. Bones
are rarely affected, but a few people do develop wasting of part
of some bones (called aseptic necrosis). If this happens, it most
likely affects the hips, but occasionally also the knees, wrists, or
shoulders. It occurs in about 5 - 15% of patients receiving
chronic cortisone-like treatment. Aseptic necrosis also can occur
in lupus patients who have never been on cortisone treatment,
but it is less likely to occur.
Kidney involvement develops in about 50% of patients. Why
it develops in some patients and not in others is not clear. Fur¬
thermore, if it develops, it usually happens during the first two
years of illness. Most kidney involvement causes no symptoms
Introduction 5
but is detected by routine blood and urine tests. The urine tests
look for either protein, red cells (“blood”), or white blood cells
(“pus”); while the blood tests measure the concentration of ei¬
ther creatinine or urea. Although the vast majority of lupus pa¬
tients with kidney involvement have mild disease and no symp¬
toms, these abnormalities need to be treated in order to prevent
permanent kidney damage or failure, which now rarely devel¬
ops. Only in that uncommon instance when the kidney function
is less than 25% of normal will individuals become sympto¬
matic, by developing nausea, fatigue, or edema (swelling of the
legs). Moreover, these symptoms often have other causes, and
not all kidney disease in patients with SLE is caused by the
lupus. A kidney specialist (nephrologist) should be consulted by
any patient in doubt.
In lupus, the heart is rarely affected. However, when the heart
is involved, the most common abnormality is some form of
electrocardiographic (ECG, EKG) changes; clinical symptoms
of the heart are infrequent.
The lung is involved in about one-half of lupus cases. The
most common symptom is inflammation of the lining of the
lung, causing fluid to accumulate in this space around the lung.
Sometimes this is painless, and is detected by chance on a chest
x-ray. At other times, the fluid may cause chest pain during a
deep breath (pleurisy). This is often the first clue to the diagno¬
sis of SLE. Sometimes a lupus patient with lung involvement
develops a chronic cough. Lupus-caused lung problems may
also show up on a chest x-ray. In those circumstances, however,
the attending physician ought to make absolutely certain that the
cough or abnormal x-ray is not due to an infection.
Some SLE patients may develop gastrointestinal tract (eso¬
phagus, stomach, intestines) problems, manifested as nausea,
vomiting, or abdominal pain due to inflammation of the intes¬
tines or pancreas. These symptoms can also be caused by
illnesses unrelated to SLE, and clearly warrant attention by a
physician. Lupus-related diarrhea is also possible, but this con¬
dition is usually due to other causes, such as infections. Blood in
the stool is rare.
The liver is occasionally enlarged in SLE patients, but this is
usually temporary. However, persistent liver enlargement and

abnormal liver function blood tests may be caused by a disease
called lupoid hepatitis. This is a disease primarily of young
women, who develop many of the symptoms of lupus (such as
fever, arthritis, rashes, pleurisy) and have positive LE cell tests.
Despite these similarities, lupoid hepatitis bears no other rela¬
tionship to SEE, in which persistent liver abnormalities are rare.
Lymph nodes are characteristically enlarged in patients with
SEE, especially in the neck but also elsewhere. They are more
likely to be enlarged in patients with active disease than in those
in remission. Enlarged nodes, however, can also be caused by
other conditions, of which the most common is a recent infec¬
tion. An enlarged spleen is seen in many patients, again more
often in those with active disease.
The neurological system consisting of the brain, spinal cord,
and peripheral nerves, is affected in about 25% of patients. This
neurological involvement may cause behavioral disturbances, in¬
cluding irritability, confusion, hallucinations, obsessional and
paranoid reactions, and frank psychosis. Symptoms caused by
organic brain disease may be difficult to differentiate from corti¬
sone drug-induced psychosis or from the natural fears and anxie¬
ties any person might have when told that he or she has a
chronic life-threatening illness. The cause must be accurately
diagnosed, however, because the treatment for each is very dif¬
ferent.
When organic brain disease is present, usually the lupus is
active elsewhere in the body. In this case, the EEG (brain wave
test) is likely to be abnormal, but a brain scan test will be nor¬
mal. Organic brain disease may also cause seizures or convul¬
sions in 15% of patients; other symptoms, such as peripheral
neuropathy (loss of sensation or very marked weakness in the
arms or legs), hemiparesis (paralysis on one side of the body),
or double vision (diplopia), are uncommon.
Many patients with SEE have anemia (too few red blood
cells), a low white blood cell count, or a low platelet count.
These may cause no symptoms and simply show up in blood
tests, but recognition of these conditions is important. Anemia is
one of the causes of fatigue. A low white blood cell count is
Introduction 1
common in patients with lupus, and it is often the first clue that
SLE may be causing such symptoms as unexplained fever,
arthritis, or rashes. A very low white blood cell count may
predispose an individual to bacterial infections. A low platelet
count may cause easy bruising or bleeding.
As noted earlier and repeated here for emphasis, most patients
do not develop even most of these symptoms. This list is de¬
signed to describe all of the things that could go wrong, and to
alert people to clues that might indicate the presence of lupus in
an undiagnosed patient, or the worsening of the disease in diag¬
nosed lupus patients.
The typical patient comes to the doctor complaining of fa¬
tigue, low grade fevers, rashes, and achy, slightly swollen
joints. Although the disease is ten times more common in
women than men, the symptoms in both sexes are the same.
Diagnosis, however, is often difficult in early mild cases, espe¬
cially if the patient has only a few symptoms. Frequently, pa¬
tients are told only that they might have lupus because they do
not have enough symptoms and signs to firmly establish the
diagnosis. If the symptoms persist, the person should be checked
periodically. In such circumstances, the patient should consult
an expert with experience in dealing with lupus patients. Patients
with persistent mild symptoms rarely develop severe organ in¬
volvement. In any case, a patient with suspected SLE and per¬
sistent or intermittent symptoms should be treated, appropri¬
ately, with understanding.
How does a physician arrive at a diagnosis in the absence of
specific clues? In the early seventies, physicians in the American
Rheumatism Association sought to resolve that dilemma. They
surveyed a large number of lupus patients, and found 14 symp¬
toms and signs that would help differentiate SLE patients from
those with other conditions. To warrant a diagnosis of SLE, a
patient must have four or more of the following symptoms at
some time during his or her illness: butterfly rash, discoid lupus,
Raynaud’s phenomenon, hair loss, photosensitive rash, mouth
or nose ulcers, arthritis, a positive LE cell test, repeated false
positive blood tests for syphilis (i.e. a blood test incorrectly
indicating the presence of syphilis), profuse protein in the urine.
casts in the urine, pericarditis and/or pleurisy, psychosis and/or

convulsions, hemolytic anemia, low white blood cell count, or
low platelet count.
A number of laboratory tests are useful in the diagnosis of
SLE, but each has advantages and drawbacks.
The first laboratory test ever devised was the LE cell test. It
involves taking blood from an individual, mixing it with glass
beads, and then examining the white blood cells under a micro¬
scope. A positive test means that one sees intact white blood
cells that have ingested nuclei from damaged cells. When the
test is repeated many times, it is eventually positive in about
90% of patients with SLE. Unfortunately, the LE cells test is not
specific for SLE (despite the official sounding name). The test
can also be positive in up to 20% of patients with rheumatoid
arthritis, in some patients with other rheumatic conditions like
Sjorgren’s syndrome or scleroderma, in patients with liver dis¬
ease, and in persons taking certain drugs (such as procainamide,
hydralazine and others).
In an attempt to develop a better and more specific test for
SLE, immunologists investigated the nature of the LE cell phe¬
nomenon. Recognizing the test was dependent on antibodies to
nuclei, they used the recently discovered method of fluorescent
tagging to develop a more direct way of detecting these antibo¬
dies to nuclei. It is called the immunofluorescent antinuclear
antibody test, or ANA (also called the antinuclear factor, or
ANF test). The ANA test is positive in virtually all patients with
SLE, and is the best test if SLE is suspected. If the test is
negative, the patient will likely not have SLE, but the test can be
positive in conditions other than SLE, such as scleroderma,
rheumatoid arthritis, infectious mononucleosis, and liver dis¬
ease. However, the test tends to be more positive — that is,
have higher titers or concentrations — in patients with SLE.
Recognizing the lack of specificity of the ANA test, immunol¬
ogists are working to develop additional tests based on the anti¬
nuclear factor that will better differentiate SLE from these other
conditions. One such test takes advantage of the fact that nuclei
contain many different substances. Immunologists extracted
these substances from nuclei and tested them with sera from
Introduction 9
patients who had a positive ANA test. They found that if a

patient has antibodies to DNA (deoxyribonucleic acid) or to a
nuclear protein simply called Sm (in memory of a lupus patient)
he probably has SLE. Although, of all SEE patients, only 75%
have antibodies to DNA and only 25% to Sm, the presence of
these antibodies, in addition to a positive ANA test, strongly
indicates the presence of SLE. However, the absence of these
antibodies, in the presence of a positive ANA test, does not
exclude a diagnosis of SLE.
Antibodies to another nuclear substance called NP (nuclear-
protein) are frequently found in patients with SLE and rheuma¬
toid arthritis. Antibodies to single-stranded DNA (ss DNA) or
heat-denatured DNA (HDNA) are found in patients with SLE,
rheumatoid arthritis, and liver disease, and in persons taking the
drug pronestyl. Anitbodies to the nuclear substance RNP (ri-
bonuclearprotein) are frequently found in patients with SLE,
scleroderma, and rheumatoid arthritis.
Some patients, with symptoms of SLE, scleroderma, and
polymyositis, have mixed connective tissue disease (MCTD). It
is called this because they have a relatively unique combination
of clinical and laboratory findings. Some authorities argue that
these patients have either SLE or scleroderma. Nevertheless,
they have generalized arthritis, arthralgia, myositis (muscle in¬
flammation), Raynaud’s phenomenon, swollen hands, difficulty
swallowing, and/or lung disease. These patients rarely have ei¬
ther kidney disease or brain involvement, and usually respond to
cortisone type drugs. Patients with this syndrome always have a
positive ANA test and a high concentration of antibodies to this
RNP, but usually do not have antibodies to DNA.
Other tests may be needed to help diagnose SLE. Serum com¬
plement levels are often ordered. Levels are low in most SLE
patients when the disease is active. However, complement levels
may decrease in many other conditions as well.
Often physicians will perform skin biopsies both of rashes and
of normal skin. When examined under a regular microscope or a
special fluorescent microscope, these biopsies can help diagnose
SLE in about 75% of patients. A biopsy of the kidney is often
made when kidney damage is suspected, to determine whether

abnormal function is due to SLE or to some other condition.
The interpretation of all these positive or negative tests, and
their relationship to symptoms, is frequently difficult. Some¬
times a test may be positive one time and negative another time,
reflecting the relative activity of the disease or other variables.
When questions cannot be resolved, and doubt remains regard¬
ing a diagnosis, consult an expert in lupus.
What causes SLE? We do not know, but the investigations
being made by many physicians and scientists are getting closer
to the answers. Already many clues and facts point to the fol¬
lowing hypothesis. Increasing evidence suggests that genetics
plays a role in SLE and that people inherit the tendency, or
predisposition to develop SLE. One piece of evidence for this is
that if one identical twin has SLE, the other twin has a very
great chance of eventually developing the disease. Also, among
close relatives (that is, parents, children, siblings, and first cous¬
ins) of a lupus patient, the chance of detecting another individual
with SLE is 1 out of 20. In contrast, only about 1 in 400 people
in the United States have SLE.
Laboratory tests have shown that certain proteins found in the
blood, or on the cells in the blood, are inherited. Recent investi¬
gations indicate that some of these inherited characteristics are
found much more frequently in patients with SLE. Scientists are
confident that this research ultimately will lead to a test that can
predict whether someone has an inherited predisposition to de¬
velop SLE.
But if the tendency to develop SLE is inherited, why does it
develop in young people, especially in young women? Again we
do not know, but recent studies of sex hormones suggest that
female hormones (present also in males, but in less concentra¬
tion) play some role. This role is being actively studied in mice
who develop SLE. Clinically, however, SLE is the same in men
and women.
What triggers an attack of SLE in a susceptible person?
Again, we are not sure, but scientists have noted certain features
in many patients. In some, exposure to the sun causes sudden
development of a rash and then possibly other symptoms. In
Introduction 11
Others an infection, perhaps a cold or a more serious infection,

does not get better and then complications ensue; these compli¬
cations, in fact, may be the first signs of SLE. In still other
cases, a drug taken for some illness produces the signalling
symptoms. In some women, the first symptoms and signs de¬
velop during pregnancy; in others, they appear soon after deliv¬
ery of their babies. Many patients cannot remember or pin down
any one factor. Obviously, however, many seemingly diverse
factors can trigger the onset of the disease.
Immunological investigations have also provided clues to the
cause of SLE. We know that virtually all SLE patients make
antibodies to their own tissues. These antibodies are not found in
other persons. Some researchers have shown that this allergy¬
like reaction is associated with a deficiency of certain cells in the
blood called suppressor lymphocytes.* Others have found that
that after certain virus infections, some animals, and even some
people, develop antibodies to their own tissues. Patients with
SLE often have in their blood high levels of antibodies to a
number of viruses.
Given all this information, scientists now believe that SLE
develops in individuals predisposed to it, and that a viral infec¬
tion or similar stress can alter the delicate balance between nor¬
mal immunity to foreign substances and reaction to one’s own cells.
How do these antibodies cause tissue damage? Somewhere in
the body they combine with antigens (substances to which the
antibody reacts). Many of these antibody-antigen reactions actu¬
ally occur in the blood where antinuclear antibodies react with
the nuclei (or nuclear substances) of the cell. Nuclei normally
get into the circulation in very small amounts but when tissue is
injured, this amount can increase greatly. Small amounts of anti-
gen-antibody, or immune complexes, are generally cleared from
the body’s circulatory system by the liver and spleen. But if
their numbers are large and the liver and spleen are overloaded
or defective, these immune complexes can persist in the circula¬
tion. They can be detected by newly developed laboratory tests.
*This will be discussed in a later chapter.

These immune complexes can also be deposited in various or¬

gans, causing inflammation and damage. In the kidney, these
deposits cause nephritis; in the joints, arthritis; and in the skin,
rashes.
Immune complexes deposited in tissues attract a group of
proteins called complement. In blood tests, this protein can be
detected as activated complement or low levels of complement.
Complement proteins signal white blood cells to invade the or¬
gans which, in turn, causes more inflammation. Because of this
research, we now call SLE an immune complex disease. Under¬
standing some of these immunological mechanisms of tissue in¬
jury has also helped develop better ways of treating patients.
When someone has many symptoms and signs of lupus and
has positive tests, physicians have little problem making a cor¬
rect diagnosis and initiating treatment. However, a more com¬
mon problem is a young person who seeks help from the medi¬
cal community for vague, seemingly unrelated symptoms of
achy joints, fever, fatigue, or pains. Some doctors may think the
person neurotic. Others may try different drugs in the hope of
suppressing the symptoms, while an increasing number of physi¬
cians will patiently investigate the case, performing laboratory
tests until the correct diagnosis is made.
All too often, the physician is faced with the dilemma of
prescribing drugs for a disease of unknown cause, trying one
drug after another, hoping that one will work. Some drugs un¬
fortunately do harm, a fact that is often unrecognized. Finding a
doctor who chooses and evaluates drugs carefully is often difficult.
A patient can help the doctor (although one usually thinks of
it the other way around) by being open and honest. Lupus has
many facets, some of which are mysterious to the patient and
some to the doctor; some symptoms may create great concern in
one individual but not in another. A sense of psychological well¬
being in the patient will help lead to recovery and part of this
well-being comes from learning more about the illness and creat¬
ing an open line of communication between the patient and to
the doctor. A healthy dialogue between patient and doctor re¬
sults in better medical care, not only for SLE suffers but also for
people afflicted with other diseases.
Introduction 13
To whom should an SLE patient go for treatment? Physicians

of different specialties can treat SLE patients. Some physicians
specialize in the diagnosis and treatment of patients with SLE
and related disorders; these are generally either Rheumatologists
or Clinical Immunologists. Most patients usually seek the help
of their family doctor first. This is often sufficient. However,
when unresolved questions arise or complications develop, an¬
other opinion from a specialist may be advisable. The choice of
specialist may depend on the problem. For example, one would
see a nephrologist for a kidney problem or a dermatologist for a
skin problem. Most often, however, a Rheumatologist or Clini¬
cal Immunologist specializing in SLE is recommended. Refer¬
rals can be made through the family doctor, the local Medical
Society, or the local Lupus Foundation.
Because of better diagnosis, evaluation, and management of
patients, as well as more judicious use of medications, the prog¬
nosis for SLE patients has dramatically improved in the last two
decades. While 20 years ago only 40% of SLE patients were
expected to live three years following diagnosis, now over 90%
will survive 10 years or more. Optimistically, one can extrapo¬
late from these statistics and predict that increasingly more ef¬
fective treatment will continue to improve not only life expect¬
ancy, but, more importantly, the quality of life as well.
Each patient with SLE is an individual, and the treatment
must be adjusted to the problems of that person. However, a few
general guidelines can be stated:
1. Regular rest is worthwhile when the disease is active, and
increased physical activities are desirable when the disease is
in remission or quiescent.
2. For the patient who is photosensitive, the regular use of sun¬
screens will help prevent rashes and exacerbations. For those
who still develop rashes, treatment with local cortisone
creams is very helpful.
3. Arthralgia and arthritis generally respond to aspirin or aspi-
rin-like drugs.
4. The antimalarial drugs chloroquin (“Aralen”) or hydroxy¬
chloroquine (“Plaquenil”) are often prescribed for more se¬
vere joint or skin involvement.
5. Cortisone drugs (the most commonly prescribed in predni¬

sone) are often used for more severe organ involvement. Not
everyone with SLE needs cortisone. Cortisone, particularly
in higher doses, is potentially hazardous.
6. If you have a fever (over lOOF), call your doctor.
7. Go to your doctor for regular checkups, usually including
blood and urine tests.
8. When in doubt, ask. Call your doctor.
The Physician, The Psychiatrist and The Lupus Patient 15
The Physician,
The Psychiatrist
And The Lupus Patient
'To fully understand and know lupus one

‘
must feel if s havoc from within. Until

medicine produces the solutions, we must
survive together and draw strength from
one another.”
— Susan Golick, a patient*
*Susan Golick is a patient and the Founder of the SLE Foundation, Inc. She is also a
Director of the Lupus Foundation of America, Inc.
I ' n 1953, when I was diagnosed as having systemic lupus

erythematosus, it was a frightening experience. I had never
. heard the word lupus before, or known of anyone who had
a similar disease. On my own, all I could find out was that the
word lupus comes from Latin and means ‘wolf; and that
erythema comes from the Greek meaning “to be red.” I was
told that I was suffering from a rare, mysterious disease that
affects predominantly blue-eyed blondes with a light complexion
like mine. At that time lupus was considered to be uniformly
fatal. If the patient did not die, the physician questioned the
diagnosis. Today we know that this is far from true. Lupus is not
a rare disease. It is more prevelant than muscular dystrophy,
multiple sclerosis, cystic fibrosis, rheumatic fever, pernicious
anemia, Hodgkins disease or leukemia and it is not uniformly
fatal.
Dr. Chester Alper was a member of the team directed by Dr.
Frank Gardner that took care of me many years ago when I had
active disease. Dr. Alper is currently Scientific Director of the
Center for Blood Research, and Professor of Pediatrics at Har¬
vard Medical School. I asked Dr. Alper how diseases are classi¬
fied, an issue of particular relevance to lupus.
“No single system of classification of human disease is ac¬
cepted and used by all physicians,” said Dr. Alper. “There are
very broad categories, such as infectious disorders, neoplasms
(cancers), congenital anomalies, inherited diseases, abnormali¬
ties due to toxic exposure, and, that very large category, dis¬
eases of unknown cause. As we learn more and more, it is clear
that these distinctions are to some extent based on ignorance.
Take as an example certain tumors of the lymphatic system.
Some of these neoplasms may result from viral infection in
genetically susceptible individuals. It is also clear that some
congenital anomalies result from viral infection or toxic expo¬
sure of the mother during pregnancy.” After a brief pause. Dr.
Alper said, “In some cases, diseases can be classified by organ
of involvement. Pneumonia, emphysema, bronchitis, and laryn¬
gitis all clearly involve the respiratory system, and hepatitis,
cirrhosis, and gallstones undeniably affect the liver-biliary tract.
If we try to use such a classification, we must be aware that

hepatitis, for example, can be caused by toxic, infectious or
inherited means.”
“What about focusing on a symptom or physical sign of dis¬
ease?” I asked him. “For example, headache.”
“That approach may be useful for certain diseases with a
single prominent sign or symptom, but by and large, it is not a
helpful basis for classification,” Dr. Alper said. “Even with
headaches — and you picked one of the best examples where the
approach is useful — one ends up listing meningitis with mi¬
graine and lead poisoning, all of which have headache as a
major or at least prominent symptom. ’ ’
I wanted very much to hear how these questions affected our
thinking about lupus in both the systemic and discoid forms, so I
asked Dr. Alper to discuss this.
“The problems of classification are particularly severe when
you deal with systemic lupus and, since we now think of discoid
lupus as a form of systemic lupus, it has the same problems,”
Dr. Alper said. “It would be hard to imagine a disease with
more varied clinical manifestations, and therefore signs and
symptoms and multiple organ involvement, than lupus. As we
all know, any single patient may have only mild disease, with
few symptoms or signs or many different symptoms and signs,
all at once, or spread out over many years. At any given
moment, a group of patients in relapse might have totally differ¬
ent signs and symptoms, and nothing in common but the diagno¬
sis of lupus. We also know that no single laboratory test is
abnormal only among patients with lupus, the presence of anti¬
body to double-stranded DNA comes closest to filling this role.
Since virtually every organ and organ system of the body may
be affected in lupus patients, it is clearly unsatisfactory to call
lupus a skin disease, or a heart disease, or a lung disease, or a
blood disease, even though it is all of these and more. Every
once in a while someone attempts to do just this. A recent refer¬
ence to lupus as a form of arthritis is particularly misleading
since, although some lupus patients may have arthritis, this is
typically short-lived and not crippling. In short, arthritis may be
a minor manifestation at the bottom of a long and varied list of

major symptoms, signs, and organ involvements.”
Dr. Alper continued, “Classifications may also vary with the
viewpoint and background of the medical scientists studying a
specific disease. The result is not unlike the description of the
elephant as reported by the blind men. For some years, lupus
was called a ‘connective tissue’ disease, because biopsy sections
of many organs from patients with systemic lupus showed ab¬
normal stained microscopic appearance of the supporting tissue
present throughout the body. Later, this rubric was changed to
‘collagen-vascular’. Collagen is the primary component of con¬
nective tissue, and the word ‘vascular’ was added to stress in¬
volvement of blood vessels. This classification is in current use.
Immunologists, on the other hand, were initially struck by the
presence of apparent ‘autoantibodies’ directed against normal
body constituents, and called lupus an autoimmune disorder.
More recently, it has become clear that that nature of the antigen
may be secondary, but that major damage to tissue in lupus may
be mediated by antigen-antibody complexes irrespective of the
nature of the specific antigen. Therefore, lupus is referred to as
an ‘immune-complex’ disorder.”
I had many more questions to ask Dr. Alper. I was eager to
learn how lupus relates to other kinds of immune-complex dis¬
ease, and I had some questions about genetics in relation to
lupus. Dr. Alper suggested that we resume our talk at another
date and work on a chapter on the role of genetics in lupus.
For those of us who are patients, lupus remains a bizarre,
cruel disease with a difficult name to pronounce. It is a disease
of unknown cause/causes, with an unpredictable prognosis and
symptoms difficult to explain. It is intermittent, recurrent, and it
can destroy the will to live and the ability to cope. It can
threaten life and prevent its victim from functioning as a normal
human being.
Despite a growing awareness of lupus, and the increased
knowledge that the scientists have gained about it, the disease
can still be a lonely experience. Many patients still go from one
doctor to another, only to be told that they suffer from a recur¬
ring cold, or a lingering virus. Some patients are told that the
disease is in their mind, since they could not possibly have so

many unrelated symptoms. Some patients have even been asked
by their physician, “Where did you catch it?” when lupus is
known not to be contagious. In their search for understanding,
some patients become increasingly confused and emotionally
distraught, questioning even their own sanity.
The lupus patient needs immediate help in dealing with the
unpredictable and devastating assaults of the disease on one’s
psychological state. But where does one look for this help?
I went to Countway Medical Library at Harvard Medical
School to see what information was available about the psycho¬
social and emotional problems of the lupus patient. I found very
few papers on the subject. Most articles in psychiatric literature
focus on systemic lupus erythematosus with central nervous sys¬
tem involvement. I found nothing that would give the human
story of the lupus patient, either from the patient’s point of view
or from that of the physician. I found nothing to reflect the fears
and apprehensions of the individual, the very core of the dis¬
ease. And this was brought home to me quite clearly in the three
thousand letters that I have received since I wrote The Sun Is My
Enemy}
One such woman with lupus,^ who is also a physiologist,
aptly described the lack of understanding of this disease:
At numerous occasions, I have been painfully reminded of the
enormous lack of understanding and ordinary knowledge not only by
the public sector, but also by medical personnel as well as the doc¬
tors. The young internists and residents are so sorrowfully lacking in
this area. The reason apparently is that there is simply too much to
learn and absorb. So the battle for awareness must go on — not only
because the lupus patient needs sympathy and understanding (which,
of course, they do), but, much more importantly, because of the
life-threatening situations which occur regularly within hospitals and
clinics because of lack of understanding by both paramedical and
medical people.
A lupus patient who has central nervous system involvement

wrote:
I barely manage by an effort of will to keep from speaking, which
to me means screaming and crying all day long. Even at night I
cannot rest or relax. I find it hard to sleep; then I wake up abruptly
and every time I want to go back to sleep I see bright flashes of light
which vanish only when I turn on the light. ... I am losing my
memory and sometimes even my judgment. I do things and I don’t
remember about them. ... I tell people things I don’t remember
telling them. Like Flannery O’Connor’s^ heroes, I am constantly
judged and accused of crimes I don’t remember. . . [Flannery
O’Connor (1925-1964) died of lupus and so did her father.]
In lupus, the body and the soul are enmeshed in a web of pain
and desperation, and through it all many patients say no one
understands, no one is willing to listen. Neuropsychiatric symp¬
toms in lupus are often unclear, and confuse even the most
knowledgeable physician. Doctors are often at a loss to distin¬
guish whether they are dealing with a neurotic patient who has
developed lupus, or with a lupus patient who has developed a
neurosis because of the disease.
With this observation fresh in my mind, I attended a small
informal psychiatric meeting on lupus at Beth Israel Hospital in
Boston. The meeting was conducted by Dr. Theodore Nadel-
son,"^ Assistant Professor of Psychiatry at Harvard Medical
School, and Head of the Psychiatric Consultation Service at the
same hospital.
Dr. Nadelson showed a videotape of a lupus patient talking to
the psychiatrist. Dr. Nadelson’s approach was gentle, philosoph¬
ical. He allowed the patient to reminisce as long as she wanted,
giving her the feeling that he would gladly listen even if she
rambled and even philosophized a little.
The patient described her struggle with lupus in simple terms.
She spoke of her lack of concentration in school, her profound
fatigue, the changes of mood, her anxieties and depressions. She
said that her mother did not believe that she was ill, and she
herself had wondered if she was sick or simply lazy. ‘T needed
my mother’s understanding,” the patient said. “I needed her
love.” The woman remained quiet for a moment, and then her
face unexpectedly lit up with a smile.
“You are smiling for the first time,” Dr. Nadelson said.
“What are you thinking of?”
“My children,” the woman said.
“What about your children?” Dr. Nadelson asked.
The woman’s smile broadened. “I am happy that I can still

love my children in my own way,” she said.
Will this woman’s love help her to overcome the emotional
trauma of this disease? I wondered. Many patients develop self-
hatred because of what the disease has done to their body and
soul. And often this self-hatred projects itself.to every part of the
patient’s life, including the people they love.
A few days later, I again met with Dr. Nadelson and we
talked about the frustrations of the lupus patient. I asked some of
the questions asked by patients, and about the problems that
puzzle the physicians. I asked Dr. Nadelson how a psychiatrist
can help a patient with lupus.
First of all, he explained, lupus is a chameleon-like disease.
He emphasized that behavioral manifestations range all the way
from mild depressions to severe psychosis. “The issue is further
confounded by the fact that patients with lupus are receiving
very strong medication, some of which cause behavioral or emo¬
tional changes,” he said. “Steroids, when given in high doses,
often cause people to become quite elated and excited. When the
dose of steroids is rapidly increased or decreased, abnormal
kinds of behavior occur, so that what we are sometimes seeing is
a ‘steroid psychosis.’ ” He stressed that lupus itself may pro¬
duce a “lupus cerebritis,” an irritation of the brain tissue which
brings on severe changes in perception. When a patient has a
lupus psychosis, whether from drugs or from the irritation
caused by disease, the patient may hallucinate. The degree of
the hallucination is usually random. The hallucinations are usu¬
ally without structure, depending mostly on the stimuli in the
environment. Dr. Nadelson continued that, although steroids can
sometimes cause unusual behavioral changes in the patient, they
also can be helpful in reducing general inflammation in the
body, and therefore decrease behavioral changes caused by local
brain inflammation.
Patients do generally benefit from supportive psychotherapy.
This is not necessarily best delivered by a psychiatrist. He be¬
lieves that understanding and compassion for the individual on the
part of the internist can be extremely helpful in helping the patient
through the long process of adaptation to his chronic illness.
“The physician should not be ignorant of the fact that the

disease itself leads to emotional stress,” Dr. Nadelson said.
“Very often the patient cannot distinguish the behavioral and
emotional difficulties imposed by the lupus from those problems
that existed previously. Patients very often tend to blame them¬
selves for that which cannot be helped. The understanding assur¬
ance of the doctor, presented without censure or blame, can
greatly help the patient. This is the dose that the doctor should
deliver with every medication that he prescribes.
“Often,” Dr. Nadelson said, “the shifting of the patient to a
psychiatrist for psychotherapy can have a negative rather than a
positive effect. The patient may feel that he is being discarded
because he is unacceptable or even ‘crazy.’ Sometimes the pa¬
tient may feel he is being sent to someone who can tolerate
craziness because the physician who has been trusted to deal
with the physical disease cannot.”
“When I was first diagnosed as having lupus, I was scared,”
I told Dr. Nadelson. “The first question that came to mind was:
‘What does the wolf and lupus have in common?’ The question
kept hammering in my mind. By its identification with the pre¬
dator, the disease became lethal. Months later, when I learned
that wolves have a reddish lupus-like mask across their snouts
that resembles the butterfly-shaped redness over the bridge of
my nose and cheeks, my fears increased. Help with such fears
requires much of the physician’s time, and it requires a real
understanding of the patient’s stresses.”
“Well,” Dr. Nadelson said, “obviously your question relates
to what I have just stated. Yes, it is true that the patients develop
emotional problems in reaction to their illness. As long as we
have psychosomatic illness, that is, illness arising from emo¬
tional problems, we also have somatapsychic illness; that is,
psychological problems which result from a difficult time with
physical disease. The patient with lupus is always wondering
about the course of the disease. She often feels as if she were in
a dark tunnel with no light at the end. Or she wonders what her
eventual situation will be. Troubled by such thoughts, and often
without the support of the family or in the midst of an environ-
ment that may aggravate the very strain from which they seek
relief, she turns to the doctor.”
“Who should be the main physician to help the patient with
these problems?” I asked.
“I think that it would be best for the internist to treat the lupus
patient,” Dr. Nadelson said. “However, a psychiatrist or coun¬
selor can be helpful to the patient at times. It may even be
helpful to have the psychiatrist see the patient once or twice with
the idea that the patient is going to the psychiatrist in order to
‘help’ the internist. It can also be of great help to the internist to
know that a psychiatrist could be available to counsel him in the
management of such patients.”
After a moment Dr. Nadelson said, “You know our conversa¬
tions suggest that the problem belongs not only to the patient;
physicians have a real problem in dealing with chronic illness.
What they cannot cure (they, all of us, have a reparative need),
makes them frustrated by degrees and sometimes even angry at
the patient who is not cured. Physicians may be helped to come
to terms with this by talking among themselves or with a coun¬
selor,” Dr. Nadelson continued.
“You point out also that you were very influenced by the
meaning of the unique name given to your disease. Although not
every patient would be caught up in that particular metaphor,
you highlight the issue of ‘meaning.’ Doctors should ask the
patient what meaning the disease has for them. Patients may see
themselves as victims of a predator, but also may see themselves
as destructive, turned into the destructive predator that attacked
them. This is not a crazy thought, but one to which everyone is
subject; it is a normal reaction under the stress of being sick.
The normality of such a reaction is underlined by the popularity
of myths like Dracula, for example. ”
“A friend of mine,” I said, “a cardiologist, who is also a
lupus patient, is very ill and discouraged. She was told by her
doctor, ‘Have some equanimity. Most people in this world have
to cope with worse.’ In order to show her how ‘en rapport’ he
was with her state, he described his own sufferings with asthma
and told her about his father who was dying of cancer. My
friend left the doctor’s office feeling disgusted with herself. She
was depressed and worried, thinking that she had become a

burden not only to herself and to her family, but also to her
physician.
The lupus patient is often exposed to veiled criticism for hav¬
ing and dealing with such a bizarre, little-understood disease.
When the physician emphasizes neurosis, it becomes destructive
to the whole family, because neurosis implies that the patient
has control over the illness, which is not so. What a patient must
do in such a situation is call upon energies, however limited,
and force oneself to live as do people who have a wealth of
healthy energy.^ It’s often difficult. Friends and family see the
patient looking well one moment and distressed the next. They
begin to wonder whether he may be a hypochondriac or, even
worse, a person who is no longer productive, someone who can
no longer be depended upon. The families feel annoyance, an¬
ger, and guilt. This creates a vicious circle for patient and fam¬
ily, and it leads to much stress and depression. A young woman,
whose mother died of lupus, describes how it was to grow up in
a house with a mother sick with lupus:
Perhaps the most anguished part of my childhood in relationship
to having a mother with Lupus can be summarized by ‘not know¬
ing.’ This lack of knowledge, lack of awareness, manifest itself
constantly as I would wonder from day to day what the next one
held. ‘Good days’ presaged optimism, ‘bad ones’ something to get
through. But, all the time the question of how long the good ones
would be there, how bad the bad would get, made it difficult to
plan, or to just assume that life would go on as it always had. And,
‘as it always had’ meant with fear that my mother might die at any
time, guilt that my actions might contribute to it, anger that my
mother was not like all the rest, overprotectiveness so that her com¬
fort would be maximized, confusion because she seemed so healthy
as she never let her appearance symbolize how she felt, and resent¬
ment because she was always the center of attention. Though my
mother valiantly tried to keep the family life within the realm of
normal, I always felt guilty*when a birthday party or PTA meeting
caused her to tire, disappointment when she could not go, deprived
when another went with me instead.
As I grew older and more responsible I became more protective as
she became weaker. I became the ‘chief telephone answerer,’ I in¬
tercepted visitors, I anticipated when a rough day would require an
afternoon nap. I understood the words ‘my mother is not feeling
well today,’ that I repeated so often. Yet, I never quite understood

why. Though I had knowledge of the doctors’ reports, all I could see
was a willful woman who refused to play a sick role, whose beauty
and grace spoke to a vitality she wanted to have ‘with health,’ but
whose restrictions on life’s activities seemed capricious. After a
while I began to wonder whether she was really sick because the
symptoms seemed erratic. Then I felt guilty that I doubted her. I was
confused because of the many times that the lupus went into remis¬
sion; frightened when it returned. Not knowing what was happening
or what would happen, when and why, or whether it would even
happen again. I spent a lot of time frightened. Nobody else seemed
to know, either.
Though I realize that I feel deprived because Lupus took some¬
thing from my childhood, from my family, from my mother, her
struggle with it left me with a respect for her that I would not have
been forced to develop. Seeing what my mother went through time
and time again in the hospitals, knowing that she wanted desperately
to be well, watching her give up activities gradually over many
years, and feeling her worry that we should not suffer, left me with a
feeling of awe. There were a number of times when I heard doctors
say to one another that they could figure out no reason why she was
still alive except that she had an incredible will to live — one which
kept her alive for over 20 years after she had been informed she had
only three more. My mother was a fighter, she waged a war coura¬
geously, she lost it with dignity, but she never gave up.
Dr. Nadelson and I were quiet for a moment. “Twenty years

is a long time,” I said. “Through the years all pleasures become
shallow, all longings for fulfillment erode. There are days when
you feel like an old person, who will never enjoy anything
again. The exhaustion and hopelessness shatter all wishes and
desires save the one for rest. The poet, Emily Dickinson,® who
is believed to have had lupus, wrote these words: ''But She and
Death Acquainted, meet tranquilly as Friends.” Such state¬
ments will doubtless seem to many a gloomy and depressing
exaggeration,” I said. “Yet, some patients do experience such
feelings caused by the disease. I feel that one should bring this
deep despair into the open, and tell the physicians about it. The
patient should not only feel confident of the physicians’ ex¬
pertise, but also feel his desire to share this information and be
openminded about the deeper problems caused by the disease.
“You outline with great vividness the kind of situation which

occurs with a chronic illness and particularly with a disease that
is so misunderstood,” Dr. Nadelson said. “This vicious cycle is
one that is very difficult to break; it does seem to feed on itself.
One other way to gain understanding may be through some self-
help groups for patients and for physicians. Michael Balint,^ in
England, has started a number of physician groups where the
doctors talk about their own difficulties in dealing with patients.
Physicians often loathe to reflect on their own feelings about
patients. They seem to do better talking among themselves with
a group leader. We have found that such groups are extremely
helpful here; but fitting it into a busy practice is, of course,
difficult. Doctors simply have to see that this is important. Only
some do, and the others are hard to convince.”
“The best descriptions of the problems come from patients,”
I said. I showed him excerpts from letters in my possession. A
professor of theology wrote:
One thing that hurts me is the attitude of many people who avoid
me because they seem to be scared because I have a terrible illness.
People feel threatened. I noticed, for instance, when I broke two
ribs, everyone would inquire about them and ask if they could help.
They were much more solicitous about the ribs than they were when
I got my diagnosis of lupus, which is very interesting — very inter¬
esting indeed.
Another patient, a professor of literature wrote:

People began to think of me as a hypochondriac which made me
extremely self-conscious about discussing my problems with any¬
one. My husband could not possibly understand, as I didn’t know
enough to explain to him about my illness.
And in another letter the same patient wrote:

I am frustrated by labels such as ‘possible collagen disease’ and
‘90% chance of lupus.’ I do not blame my physician for not provid¬
ing me with a convenient neat label for my disease. I blame him for
not entering into an active struggle with me to search for such a
label. . . . No one would believe me at this time. Even my husband
thought my vague complaints the product of a distorted and overly
sensitive imagination, and what else could he think? The medical
profession had ‘proven’ that there was nothing wrong with me. They
had labelled me a neurotic. I began to perceive myself as one. I still

suffer from the destructive professional attitude of the physicians
during these years. I needed so much to define my problems or at
least to have someone grope for a definition with me. The medical
profession had defined my complaints this way; in the presence of
mystery, I had nothing better to offer. . . .
Dr. Nadelson said, “Patients who have absolute manifesta¬

tions of disease have a much easier time. In a way, lupus is one
of those insidious diseases which produce symptoms before
signs. And even when the disease is full-blown, patients may
feel simply lousy and not be able to ‘show anything’ to the
doctor. It is as if two parallel languages are going on — the
patient’s feelings and subjective impressions of their bodies and
themselves, and the physician’s way of looking at disease.” Dr.
Nadelson paused, “Physicians usually view disease in terms of
the ‘body space.’ Some doctors follow the tenet of the great
pathologist, Virchow, who said that where there is disease, there
is a bodily organ affected. If a change in an organ cannot be
found at any particular time, the physician may tend to say no
real disease is present. Of course, our experience in clinical
medicine is such that we can only deal with what we know. In
other words, we should accept the fact that, when we are ig¬
norant, the symptom the patient describes should be the prevail¬
ing one; and we should assume that when the patient says he
feels tired or has pain, that he is tired or in pain. The fact that we
cannot find any objective evidence for it in his body at the time
does not mean that he doesn’t have those two subjective symp¬
toms. As one patient (a theology professor with broken ribs)
noted, two broken ribs are often easier to handle than a kind of
insidious, low-level pain without an objective finding. An x-ray
plate is very convincing to a doctor and everyone becomes very
supportive.” After a moment Dr. Nadelson continued. “It is
also very difficult for the patients themselves to know whether
they are simply tired, or disease is responsible. I think that the
physician’s approach should be, first of all, to assume that if the
patient has lupus, fatigue is part of the disease. It does not
matter if the doctor is right or wrong; no one in the world can
tell. The most helpful strategy then, is to assume that the
patients are complaining about something that troubles them,

that probably something is going on in their bodies if they say
so, and to take it from there. ’’
“I’ve heard physicians say there is something strange about
the typical lupus patient, something that is very disturbing to
them. They note that many patients are hysterical, nagging,
highly inquisitive, demanding, anxious and depressed. The doc¬
tor doesn’t know what this represents, or how to deal with such
patients.”
Dr. Nadelson said, “I don’t really know what that represents,
except that when the immune system is not behaving normally,
there can be a whole lot of neurological side effects. As a matter
of fact, we are beginning to find that many symptoms we once
assumed were separate, almost autonomous, do in fact interact
with each other. So, yes, I would say that probably lupus itself
leads to behavioral changes. But I would also emphasize that
patients with lupus are worried people. They have difficulty
managing their everyday affairs, because of the uncertainty and
deterioration the disease inflicts on them. If the physician were
to think of himself struggling through his day weighted down
with two forty-pound valises, one in each hand, and, at the same
time, asked to perform a marathon of household duties and ac¬
tivities that include maintaining close loving relationships be¬
tween himself and family and friends, he would get a sense,
perhaps, of what it is like to be a lupus patient; but only from a
psychological point of view. Add to that the interaction of the
nervous system, which is somewhat out of whack because of the
disease, and one gets a sense of what it is like to have lupus.
Even when the patient is seemingly in remission, there is still a
grim worry of what the future holds and when the next acute
attack will come.”
“A lupus patient told me that her husband left her because he
was afraid of catching her disease. He stopped kissing her and
went to sleep in a separate room. Once, when he developed an
allergic rash on his chest, he went from doctor to doctor con¬
vinced that he had lupus, and he blamed his wife for his prob¬
lems. Many people who deal with lupus patients react the same
way as people used to react to lepers.”
“I think that’s very interesting, at least for me,” Dr. Nadel-

son said. “I have always thought of diseases as ‘clean’ or ‘dirty’
diseases. For example, a clean disease is something like heart
disease. These are diseases that are unseen, inside the body.
Any disease which shows any outward manifestations — partic¬
ularly on the skin — is always a disease that people worry
about. I guess you get the drift of it — we spend a lot of our
childhood learning to become neat and tidy. Toilet training, par¬
ticularly in this society, is often stringent, even among permis¬
sive parents. That which is inside the body is meant to stay
inside. We are shamed into believing that we must keep the
body contents inside.”
I stressed that the divorce rate is high among lupus patients,
and women have told me that sex plays a role in this drama. The
woman senses the spouse’s need for sexual gratification, but, in
her drained state, she cannot always be the charming and fulfill¬
ing partner she was in the past. The spouse feels unfairly denied.
He is healthy, with healthy urges, and, although he might not
talk about it in the beginning, the woman fears that he will
eventually become open about it — which certainly may hap¬
pen. This is very frightening to a woman who has lost her vital¬
ity and looks, and who, at such times, needs the affection and
the care of her spouse or friends. The woman makes the mistake
of thinking that she is depriving her spouse, when the culprit is
really her illness. Some become desperate and begin to resent
the husband whose life they have complicated.®
Patients complain that the physicians are more than willing to
discuss their physical problems with sex, and they are given
prescriptions for ointments and medications, but very few have
been able to help with the more complex psychological prob¬
lems. One patient told me that, even in remission, she needed
the physician’s help. She had sublimated her sexual feelings for
long stretches of times, so that healthy urges and desires were
deeply buried. Another patient told how, while she was in re¬
mission, her husband became hostile and resentful. The sexual
energy that he had repressed while waiting for her to be well
again was suddenly released in anger and violence. She wished
she were ill again rather than have to cope with such a new
painful situation.” I paused for a moment, then I said, “Physi¬

cians note that the majority of patients do not want to speak
about sex because they develop a dishonesty about it. Patients
feel that physicians ought to help them to discuss the problem.
Your thoughts on this subject. Dr. Nadelson, will help many
young patients.”
“Well, your statements clearly outline the great difficulty,”
Dr. Nadelson said. “It really is best for both partners to accept
that the problem of lupus exists between them. It may be in the
woman’s body, but it is a problem that must be handled in the
marriage because it affects their relationships to each other.
There is no wish to engage in the sexual act, which is, after all,
an expression of exchange and interchange with another person,
because there is a sense that the body itself is not worthy of such
an interchange,” Dr. Nadelson said, and then he continued. “I
think that the question of sex, or more importantly, sexual and
affectionate relationships, is extremely important for the lupus
patient,” he said. “It is a disease that afflicts young people,
particularly women. They are in the generative, youthful and
libidinal portion of their lives and, for the most part, not sex, but
sexuality is most important. The sexual act itself, coitus, the
usual culmination of a sexual interaction, is not or does not have
to be the purpose or the goal in the mutual pleasure in each
other’s company. Sexuality can be expressed in touching, in
embracing, and in holding.
For some lupus patients, sexual intercourse itself or any kind
of overly energetic expression, may be too much. The partner
may be too demanding or the patient too resisting. Both have to
adapt, and take into account the limitations and restraints im¬
posed by the facts of lupus,” Dr. Nadelson continued. “I want
to emphasize that mutual pleasure can be given within the limits
imposed by the disease. A partner’s acceptance of this will begin
with the understanding that the disease does set limitations. Re¬
duced sexual ardor should not be interpreted as lack of interest
in the other person,” Dr. Nadelson said. “Sexual interest may
wane, but the need for the other person will continue as before.
This is not to say that everybody can withstand such difficul¬
ties. Young people especially may find it extremely difficult. A
husband of a woman physically disabled by lupus, or whose

sexual interest has decreased because of it, may question his
partner’s interest in the relationship, and even his own. At this
point, a physician or counselor or psychiatrist may be helpful. I
would hope that the physician could act as counselor and sex
therapist. There may be less strenuous ways in which sexual
interaction can continue. What is needed is a physician who is
not afraid to talk about sex and who is knowledgeable enough to
counsel in it.” Dr. Nadelson continued, “I certainly believe that
not just the patient, but both partners need counselling on this.
In other words, the relationship itself is the subject of dis¬
course.” After a moment. Dr. Nadelson said, “Perhaps, the
doctor, as a counselor, can discuss the problem with both par¬
ties, making it easier for both to understand and appreciate that
at times neither may want to have a sexual relationship. That
does not have to be the point at which they slip away from each
other. Such moments can be times of quiet exchanges, of tender¬
ness and an affirmation that the couple is going to get through
this together. However, some people still see marriage only as a
love relationship. It is wonderful if there is love in the mar¬
riage,” he said, “but there are other components, too. The fam¬
ily, possibly children, are one facet of marriage. More important
are all of the many intertwining relationships that develop over
the years between a man and a woman. These, from the point of
view of advancing years, are really much more relevant than the
physical love which was present in the beginning. Sexual inter¬
course is not the purpose of marriage, although it is one of its
important facets. It is possible, and I have seen it happen, for
lupus, or another disease for that matter, to make a marriage
stronger and better. I would not recommend the interposition of
such a difficult disease for that purpose, but some people do
better with it.”
“You mean that some couples do better, almost as a result of
the disease?”
“Indeed,” Dr. Nadelson answered. “However, most people
need some kind of counselling, not only to deal with the disease,
but with the relationship which is troubled by the disease. For
this purpose, I think that the internist or the specialist needs to
be more than purveyor of medication. Again (and I repeat

myself), he needs to deliver a ‘dose of the doctor’ with his
medication.” Dr. Nadelson paused and continued, ‘‘And to do
that the physician needs to know himself. Perhaps the physician
himself could benefit from some counselling — not for himself
only, but because he might be able more effectively to help the
patient deal with his everyday problems. Such issues sometimes
transcend even those monumental ones caused by deficits in the
immune system response.”
‘‘One doesn’t hear much about the problems of the male lupus
patient,” I said. The wife^ of a lupus patient wrote:
Lupus is usually diagnosed among young women of childbearing
age. How many times do we all hear or read this statement ... or a
variation of it! Although the statement is essentially true, I wonder
how many of us have stopped to consider its effect on the male lupus
patient . . . For a married man with children, the need to ‘prove’
himself has been satisfied before lupus became severe. It is the
young male lupus patient who is still subject to the intense ‘peer’
pressures at a time when being different in any way is particularly
undesirable . . . there is nothing written about the need to create
self-confidence and to avoid identity problems.
And a male^^ lupus patient wrote:

I would like to point out that all the publicity about lupus is
slanted towards women. I am not a male chauvinist, but I resent the
fact that it is rare that SLE is spoken about men!
I would like to point out that since 1976 I started having prob¬
lems; going from doctor to doctor, to be told, as many other lupus
patients have, it’s all in your head. You talk about self-esteem, ego,
morale, value, sexual needs and how they will affect housekeeping
and mothering! Well, let’s talk about how it affects men for a
change!
How we can keep our wives and children happy and fulfilling
their needs as well as ours. How do I as a ‘broken man’ tell my two
year old child that Daddy can’t play with her, walk with her, play in
the sun with her, or quite often, communicate with her?!!!
I’m having trouble accepting all the articles I read which are
directed only to women. I’ve had problems with the medical profes¬
sion and the social security system; probably more so because I am a
male!!
Not until 1978-79, when my wife rushed me to ‘Emergency’ at
the hospital and my doctor put me in ‘Intensive Care’ did I start to
get minor results. Finally in 1979 my doctor wanted to give me more

antibiotics to lower my blood count, which was quite elevated! I
refused to take any additional medication until they read my critique
which was taken from all my hospital stays. I underlined the high
points after my wife typed up four pages condensing my medical
history. Then and only then was a proper course of action taken. It
has been one year since I’ve been put on steroid program; finally I’m
down to Prednisone every other day, but I have not had a remission
period. I must take quite a bit of medication: minpress - 4mg daily,
lasix - 20mg daily, transene - 22.5mg daily, amitriphylene - 50 to
lOOmg daily, nitroglycerin as needed, tedral for asthma as needed,
imadium as needed, tylenol #3 as needed!! Plus constant infections
where antibiotics are necessary!! My resident shrink tells me I han¬
dle my disease well, but he’s not in my shoes; he’s not feeling the
emptiness, torment, inadequacies, memory losses, and stuttering
which continues to make me want to withdraw into my own little
world!!
The best thing I’ve learned about this disease is that doctors love
to incorporate, fill out prescriptions and hand out hefty bills know¬
ing full well you’re not covered by insurance and know that just
being approved by Social Security, you’re also not covered by
Medicare because there is a 24 month waiting period!! What the
hell. I’ve been fighting Social Security since 1977, was finally ap¬
proved in July of 1980 — when 1982 rolls around I will have had
lupus for 7 years! Let’s hope we have a cure by then!
I would love to go back to work as a floor broker on the Chicago
Board Options Exchange and regain my Vice President’s title!!
We must remember that SLE is a personal, individual disease
which includes men as well as women!!
Dr. Nadelson said, “There may be many fantasies on the part

of men who have been told that it is a disease predominantly of
women. When the disease takes its toll, they also feel fatigued,
and may believe they are losing their masculine sexuality. For
some men this becomes too great a burden. They feel alienated,
damaged, and emasculated. They also need a sturdy counselor-
physician to guide them through many difficulties, and to reas¬
sure them that their fatigue is not caused by changing sexuality,
but by their immune system. I believe that one important issue
with this disease, then, is that patients with it need support —
support from the medical profession, support from their fami¬
lies, and support from each other. They need that until a remis¬
sion occurs or a cure can be found. Such support, of course.
assumes knowledgeable physicians; doctors who know about the

disease and who know and understand human despair and who
can respond to both these aspects in a human way. That is
asking a lot, but this disease asks a lot of the sufferer as well.”
“The problems of lupus are not limited to adults only,” I
said. Children with lupus are like birds with broken wings. They
miss the freedom to run and play in the bright sunshine and they
experience pain and fatigue. Some teenagers become preoccu¬
pied with religion, while others abandon their studies, their
friends, and their dreams. Still others refuse to rest or stay out of
the sun. Sometimes, despite adverse changes in the laboratory
tests, they will insist they feel fine, determined not to take the
steroids and avoid the moon face caused by the retention of
fluids.
Parents find it hard to deal with this situation because they
don’t want to be overprotective or even despotic. These parents
are often in a bind, especially if other siblings are in the family.
Sometimes the healthy children cannot understand why their
brother or sister, who frequently looks well, gets all the atten¬
tion. They fail to understand why they are scolded for having
certain grades in school while the lupus patient is praised for a
similar performance. The parents become especially worried if
their healthy child begins to change in personality and behavior
and emulates the lupus patient.
I have a letter from an eleven-year-old girl which underlines a
massive dilemma which confronts any patient with lupus. The
fact of the disease occurring at the point of sensitivity or inten¬
sity of development lightens the problem of the patient (and the
parents). This is what Lisa Chin of Newton wrote:
You asked me how does it feel to be eleven and have lupus. I am

grumpy and in pain and I don’t want to admit it. One can ask me a
simple question and I’ll burst into tears for no reason. I am bed¬
ridden one day and I feel better the next. When I am too tired to do
something, I wonder, is this feeling really true or am I just using
lupus as an excuse not to do my homework. I want to be treated like
a nonnal girl, but I also have to be dealt with depending on how I
feel that day. I need understanding! I need somebody willing to hear
out my problems. My only support system is my three-year-old
brother Mike. He listens when I tell him how tired and sick I feel
and he gives me the kisses and hugs I need that everyone else says I
am “too old for.’’ I would like a friend or someone to give me
support, but my parents always say, “Nobody wants to listen to a
girl who eomplains all the time.” Sometimes, if I feel rotten, I think
of how easy it would be “to get it over with.” I also say, “Why
should I try to be on top of the class? I could be dead tomorrow!”
I quickly put these thoughts aside and say to myself “Why kill
yourself? If you’re dead when they find a cure you’ll never know
about it. If you commit suicide how will Mom and Dad feel? You’re
dead so it doesn’t matter but Mom and Dad would be pretty upset.
Be at the top of the class! If you drop dead tomorrow you’ll die a
smart kid who didn’t give up. ”
For someone who’s got nothing to live for I’ve got a lot of reason
to keep living. I just have to take each day as it comes.
Dr. Nadelson said: “The fact is of course that if the youngster

is given what she wants at the time when she wants it, (warmth,
or encouragement or hugs and kisses) what might be missed is
the encouragement for discipline and increased resolve, and the
parents dilemma is if they are straining the youngster beyond her
capacity.”
“How can one help the young lupus patient to rebuild deter¬
mination and strive for continual growth?” I asked. “How can
one help the parents?”
Dr. Nadelson said, “It is extremely difficult for any child to
feel ‘different’ while growing up. To be the same as others is to
be acceptable. Children who are perceived as ‘different’ are of¬
ten ostracized and ridiculed. This is the reason they all want to
dress alike, to eat the same foods, have the same likes, etc. If
they don’t they risk being thought of as strange or ‘weird.’ The
fact is that the disease does make them different, at times
markedly. If it is not the lesions, then it is the fact that they
cannot, for example, sunbathe like the rest of the kids. Develop¬
ing adolescents,” Dr. Nadelson said, “are terribly concerned
about their appearance. To be different means to risk being shut
out from others in the group and being shut out is tantamount, in
the adolescent, to abandonment and even death. This disease,
almost certainly, pushes them into a category of not belonging.
Their frequent fatigue and the perspective of a long chronic
illness serves also to make it difficult for them,” Dr. Nadelson
paused. “Of course, it is true, as you say, that the parents might
tend to overprotect the child with lupus, and that leads to inequi¬
ties perceived within the family. The addition of disease in an
individual with the family setting and, of course, the effect on
the other family members, makes it doubly hard.” He contin¬
ued, “Much of the work has to do with the parents’ determina¬
tion to raise youngsters in a ‘normal’ way, yet they recognize
that in many ways the youngster is not normal. As the young
person grows older there is also the question of whether or not
he or she should marry; whether he or she would be able to deal
with the difficulties of marriage along with the difficulties of the
disease. Parents need to be firm in their resolution to build
within the youngsters the determination to help themselves. The
young person must learn to deal with reality and that includes
the fact of lupus. It does add another burden to an adolescent
already weighed down by the difficulties of growing up. The
parents must acknowledge this and at the same time keep firm in
the idea that the youngster can and must continue to develop as
normally as possible.”
“Do some youngsters fare better than others?” I asked.
“Sometimes they do,” Dr. Nadelson answered. “Sometimes
a child gains certain distinctions so that he is regarded as ‘spe¬
cial’ without having to be ‘special’ because of his disease. But
most parents need the help of a knowledgeable physician to
guide and advise them on the development of the child. The
parents can gain a ‘cognitive handle’ on the problem by consult¬
ing with the physician on matters that might be difficult for them
to see clearly. For example,” Dr. Nadelson said, “the issue of
sexuality is even more difficult for the child with the disease.
Again, I focus on this area because it is an important area for the
developing adolescent. It can be more of a problem for the
teenaged lupus patient who may feel potentially deprived of the
pleasures of normal interaction between the sexes. This can lead
to artificial behavior, perhaps excessive promiscuity, for exam¬
ple. It can also go the opposite direction — a kind of sexual
retardation or inhibition. Parents should discuss this with the
physician. At times, doctors must promote such discussions by
asking questions, as it often is not enough to be passively recep-
tive to such questions in the face of some family inhibitions.”

Dr. Nadelson continued, “The Lupus Foundation, too, can con¬
tinue to help arm the physician for such questions through litera¬
ture emphasizing this need for the doctor to be not only the
dispenser of medication, but also a counselor and supporter to
the family in trouble. I would also wonder,” Dr. Nadelson said,
“and this is absolute conjecture, whether an adolescent female
might feel more comfortable talking to a woman physician than
she would to a male.”
“How can one help to prevent depression in these young¬
sters?” I asked.
“The way to prevent depression is to assemble helping, car¬
ing, yet firm and constant figures who will be supportive and, at
the same time, encourage independence,” Dr. Nadelson said.
“Adolescents have quite a job to do in terms of maturation and
development, and we can try to keep that process as normal as
possible despite the burden of lupus. For some people, and this
may sound strangely optimistic, just having the disease does not
retard development; it may lead, instead, to greater strength for
the individual. This is always an extremely exciting and refresh¬
ing thing to see.”
“I feel that my own usefulness in life has been enhanced as a
result of this illness,” I said. “My whole person has changed,
perhaps because of it. Looking back over my experiences with
lupus, I believe that it has constituted an unusual human experi¬
ence which instilled in me not only a sense of balance, but a
commitment to balance in my life.”
I was fortunate, I had good doctors. I am still with the same
doctor after all these years. He invested a great deal of time on
my case and a lot of caring. Recovery was slow; continual sur¬
veillance by the physician was needed at every step in order to
meet the physical emergencies. When my disease became more
visible, he explaiend my sudden kidney involvement and ex¬
plained as best he could about the antibodies that he found circu¬
lating in my blood. He also told me about the few white cells
that had eaten up some kind of strange material that is now the
LE cell. He drew a picture of an LE cell for me to see and he let
me observe my own cells under a microscope. My doctor is a
hematologist and, for him, it was not unusual to see white cells
that engulf bacteria, but the material engulfed by my cells was
not bacterium, but antibody that had reacted with damaged cells.
He told me that antibodies were made to resist some foreign
substance. A person had to be infected with something. But I
was not infected with anything and the question was, what were
these antibodies trying to destroy? The fact that antibodies could
cause disease was a challenging thought to my physician. He
was excited about the first studies of serum sickness and the
Aleutian Mink Disease. He had a hunch that someday the physi¬
cians will control lupus through immunologic manipulation. For
many years I clung to his trust in medicine and medical research;
and I clung to his optimism that my condition will be better
understood in time, and properly treated.
My doctor helped me to understand the disease and accept it.
This was important. It was a necessary step towards a positive
psychological growth. It helped me to defend myself against
misapprehension and unnecessary fears, and it helped me to
avoid situations that could affect my illness and make it worse.
Once I was able to understand my limits and explain them to my
family, life became easier and happier for all of us.
One day my doctor said, “You can’t think of your illness all
the time. You will become depressed and nothing will make
sense anymore. But, I know how you feel. I’ve had tuberculosis
myself, and I have spent many months in isolation and soli¬
tude.” After this revelation, communication between us became
even more relaxed. I could more easily tell him how I related to
the disease, intellectually and emotionally. I could also tell him
how I was spending my time and how I was responding to
human adversity. This information, along with the diagnostic
data, helped the doctor to determine how the disease would
affect my day-to-day life, so he could help me. In my case, what
medicine could not do, my doctor did with his humanity.
For the past seventeen years I have been in complete remis¬
sion. My tests are consistently negative and I am on no medica¬
tion. However I am realistic — I know that my disease can come
back. I am also aware of the lack of resistance to infections,
severe reactions to mosquito bites, to drugs, to stress, to the
environment, to who knows what, and the sun will always be

my enemy.
^The Sun Is My Enemy by Henrietta Aladjem, Prentice-Hall, Englewood, Cliffs,

New Jersey, 1972, Beacon Press, Boston, 1978.
Êmily Heller, physiologist. Board member. Lupus Foundation of America.
^The World of Flannery O’Connor, by Josephine-Hendin, Indiana University Press,
Bloomington/London, 1971.
^Dr. Theodore Nadelson was recently appointed Chief of Psychiatry, Boston Veter¬
ans Administration Medical Center and Clinical Professor of Psychiatry, Tufts Univer¬
sity Medical School.
®In conversation with Lucille Carter, psychiatrist, Boston, Massachusetts.
^Studies of Emily Dickinson’s life show that she might have had lupus. A new look
at her life and poetry through her physical illness, A Thesis Submitted by Barbara Jerry
Reynolds in partial fulfillment for a Degree of Master of Arts, University of Paget
Sound,1974.
^Micahel Balint, p. 47 and p. 52; Balint, M., The Doctor The Patient and His
Illness, N.Y. International Press, 1972.
®Ideas expressed by Lucille Carter, M.D., psychiatrist.
^Nancy Hubbart, Michigan Lupus Foundation.
^“Angelo Miranda, Palm Beach, Florida.
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The Epidemiology of Lupus 41
The Epidemiology
of Lupus
“In a sense the epidemiologist is the phy¬

sician to the community, whereas the
family physician and surgeon are doctors
to the individual patient. ’ ’
— Richard M. Krause, M.D.,* The Restless Tide
*Richard Krause, Director, National Institute of Allergy and Infectious Diseases, Na¬
tional Institute of Health, Bethesda, Maryland. The Restless Tide, p. 61. Published by
THe National Foundation for Infectious Diseases.
a meeting of the National Advisory Council of the Na¬

tional Institute of Allergy and Infectious Diseases
A jL(NIAID), at the National Institute of Health, I met Dr.
Richard A. Kaslow. Dr. Kaslow is an epidemiologist, and for¬
mer Chief of the Arthritis and Immunologic Disease Activity,
Bureau of Epidemiology, Centers for Disease Control, Atlanta.
Recently, he became Research Medical Epidemiologist in the
Epidemiology Branch of NIAID.
“What is epidemiology?” I asked Dr. Kaslow.
“Literally, the term comes from a combination of two Greek
words — epi, meaning “on,” and emos, meaning “people.”
Epidemiology, then, is the science of effects “on people,” and,
more specifically, the health effects on people. What we do is
try to observe, study, and, when we feel particularly bold,
predict what the rates and patterns of diseases are or may be in
entire populations of people.
Because disease rates and patterns are often determined by
many factors that come together to produce a given disease,
epidemiologists spend a lot of time attempting to identify causes
and risk factors such as heredity or exposures to chemical, phys¬
ical, or infectious agents. In lupus, for example, multiple factors
undoubtedly interact to initiate and worsen the condition.”
“Do enough physicians have the skills necessary to study the
epidemiology of SEE?” I asked.
“Epidemiology is no longer an infant science,” Dr. Kaslow
said. “As it matures, it is attracting good physicians. However,
because it is one of a growing number of biomedical disciplines
that do not have, as an immediate objective, the care of individ¬
ual patients, it has been given relatively little emphasis in most
medical school curricula and even less during the medical stu¬
dents’ clinical training period. Unfortunately, those are the times
when career goals and plans are being formulated. However,
increasing attention and support is being given to epidemiology
in schools and public health,” Dr. Kaslow paused. “Here is
where many capable epidemiologists without M.D. degrees are
training. For physicians, a Master’s Degree in epidemiology can
be earned in the equivalent of one year with appropriate field
experience. But, to come back to your original question, an
epidemiological study of SLE probably requires persons with a

more solid medical background. I am afraid that, without ade¬
quate support, little attention will be devoted to the area in the
near future.”
“One hears so many different theories about the cause(s) of
lupus. What is your opinion?” I queried.
“We have good reason to believe that many causal factors can
be identified,” Dr. Kaslow said. “One factor or set of factors
may be important for certain lupus patients; another set may be
important for others. The disease itself may vary, depending on
which causal factors are operating. We already know, for in¬
stance, that drug-induced lupus is a somewhat distinctive syn¬
drome partly because of the way it originates.”
“Who gets lupus and why. Dr. Kaslow?” I asked.
“That is a difficult question to answer,” he replied. “First,
we need to agree on how to define, identify, and count the
cases. The very attempt to establish the frequency of the illness
in a particular population is more difficult, or at least more
tedious, than one first imagines, even when we agree, generally,
about the definition of the disease. And yet, determining how
many and which persons in a given place and time have a dis¬
ease is an important element in the search for causal factors, and
this is the unique contribution of epidemiology.”
“Are there any case control studies to determine the pattern of
HLA (human luekocyte antigen system A) types in lupus pa¬
tients, or of the possible contribution of viral infection or hered¬
ity to the disease?” I questioned.
“The role of HLA types, genetic factors similar to blood
types, is just now being probed,” Dr. Kaslow answered. “We
have enough evidence now to be fairly confident that the HLA
genes, or something close to them on the 6th chromosome, are
associated with lupus and other autoimmune diseases. But HLA
is Just part of the picture. A number of other influences — sex
hormones, for example — need further study.”
“Many lupus patients are told they have rheumatoid arthritis
before finally being diagnosed as having SLE, and sometimes it
happens in the reverse,” I said. “Shouldn’t this relationship of
lupus to rheumatoid arthritis be studied in greater depth?”
“Yes,” Dr. Kaslow said. “The relationship is puzzling since

the large majority of patients with each condition share very
distinctive features. We are learning more about the mechanisms
of each, but their relationship is not clear.”
“Recently investigators have studied the frequency of lupus
in a large number of pairs of identical twins,” I said. “They
have shown that if one twin develops lupus, then the other twin
develops lupus two-thirds of the time. However, the onset of the
disease might be different in the twins, occurring even years
apart. Would you comment on that?”
Dr. Kaslow explained that aside from the genetic influences
of the HLA system, numerous studies have been done of fami¬
lial or genetic traits in lupus. He said that involvement of these
other traits is clearly indicated, but the nature of that involve¬
ment is poorly understood. Allergy is one aspect that has been
studied, although perhaps not thoroughly enough; others are
being examined, but again, not enough. I also asked if one could
identify factors associated with the onset of lupus, as well as
factors that influence the outcome of the disease. I wondered if
studies of survivors of a community sample of ambulatory and
hospitalized lupus patients might provide some perspective on
this disease, and if such studies could be done on lupus, I felt
that it was important to determine the frequency of complete
long-lasting remissions such as mine?
Dr. Kaslow said, “At least two issues are wrapped together
here. When you speak of studying the course of the disease in its
full spectrum, including hospital and ambulatory patients, you
are in the realm of epidemiologic follow-up. You are dealing
with the pattern occurrence of disease, and with determinants of
its outcome. Even with the significant alterations that physicians
make in the course of the disease, this information could be
useful; but it is hard to come by, especially by the means that are
typically used to study lupus. On the other hand, correlation of
remission, and other events in the patient’s disease, with
measurable laboratory indicators can be done more easily in the
clinical context. Considerable effort has and is being applied to
that issue.”
“We need better information on the frequency of lupus,” I

said, and I asked if any organized effort was underway to study
the epidemiology of lupus.
“I know of no government program directed specifically at
some of the basic epidemiologic questions in lupus, and I know
of only about a half dozen limited attempts at population studies
of systemic lupus in the U.S. I suspect the two main reasons
why more work has not been done are: 1) uncertainty about the
definition and diagnosis of the disease, and 2) the lack of epi¬
demiologic attention paid to rheumatic and immunologic disease
in general. Even the studies that have been done have not always
used the most precise methods. Some foundations must be laid;
it will require the willingness of clinical rheumatologists, immu¬
nologists, and others, to make data available to people who can
employ epidemiologic methods.”
“What else can be done to encourage epidemiologic investi¬
gations?” I asked.
“Support for such work will have to be increased,” Dr.
Kaslow answered. “Other more difficult or expensive epide¬
miologic investigations are needed, but basic incidence and
prevalence surveys are important, both in their own right and for
the clues they usually provide about the origins of the disease.”
“What is known at this point?” I inquired. “Are more
women than men afflicted with this disease?”
Dr. Kaslow answered, “I don’t think there is any question
about that. Taking all age groups in account, the ratio is proba¬
bly somewhere around five to one.”
“Would you say the same difference exists in young boys and
girls?”
“During the childbearing years,” Dr. Kaslow said, “the dif¬
ference is greatest, perhaps nine or ten females to one male, but
in children the data are sparse. Some data suggest that in chil¬
dren under twelve years the ratio is two or three girls to one
boy.”
“Is there a difference in elderly patients?”
“Again, the information is limited, but the female-to-male
ratio appears to decline somewhat after age fifty-five.”
“Is the lupus incidence higher in blacks than in whites?”
“The evidence accumulated so far is fairly convincing that

lupus is two to three times more common in blacks.”
“Statistics indicate that the mortality rate may be approxi¬
mately three times higher for black females than for white fe¬
males,” I said. “If so, why is that?”
“We don’t know whether blacks have a higher mortality rate
because they develop the disease more frequently, or because
they die more frequently once they develop it. Either or both
could explain the higher mortality rates. ’ ’
“Is lupus more frequent in Hispanics?” I asked.
“There was an early suggestion that lupus occurred more fre¬
quently in Hispanics,” Dr. Kaslow said. “Of course, both of
use have heard unconfirmed clinical reports of higher frequency
in Puerto Ricans, Mexicans, and others. However, the question
can really only be answered directly by systematic epidemiolo¬
gic study in the populations of interest. I don’t see any easy way
to obtain the necessary data in those populations.”
“Do you have any idea about people of Oriental back¬
ground?”
“One recently published study from Hawaii suggests that Asi¬
ans experience an increased prevalence of lupus. Results from a
study in the mainland U.S. are not yet available.”
“Do you have statistics on patients with discoid lupus who
eventually developed systemic disease?”
“Again, I would say that the statistics that have been col¬
lected are not entirely adequate.”
“Is it the same disease?”
“Yes and no,” Dr. Kaslow said. “Discoid lupus may be just
one manifestation of a process which, when certain factors are
operating, goes on to involve other organs, but, when those
factors are absent, is confined to the skin.”
“There are so many needs for accurate statistics,” I said.
“The number and severity of complications such as infection are
not fully appreciated. But overemphasis can be harmful, too.
Without accurate data on the side effects of immunosuppressive
drugs, they can be withheld from patients who could benefit
from them.”
“You’ve put your finger on a recurring dilemma in medical

science as well as public policy,” Dr. Kaslow said. “Take your
own example of immunosuppressive drugs. In addition to their
use for autoimmune disorders, they are used widely to treat
cancer and to prevent rejection of transplanted organs. A decade
ago it was clear that long and intensive use of certain of these
agents in cancer patients was associated with development of
lymph gland cancer. Subsequently, we learned that the same
phenomenon occurred after suppressive therapy in some of the
kidney transplant patients who had underlying predisposition to
cancer. But it has been harder to determine how much, if at all,
those same drugs will increase the risk of cancer when used
intermittently or in lower doses.”
“How can we get more information in these areas?” I asked.
“Clinical investigators can and do supply some of this infor¬
mation from their routine follow-up studies. Longitudinal stud¬
ies that extend over periods of time long enough to assess com¬
plication rates accurately are quite difficult and costly. Epidem¬
iologic tools can be helpful in this area too, but we have no
substitute for the cooperative efforts of a group of clinical cen¬
ters to look at long-term effects.”
Dr. Kaslow continued, “Drug evaluation is one of the more
difficult areas. Very exacting regulations legally bind the Food
and Drug Administration to a sequence of studies and steps
toward licensing of new drugs or approving new uses of drugs
already in existence. This process does not end with marketing
of a drug. We have superb epidemiologic evaluations of adverse
effects of drugs already in wide use. But even now we have too
few trained investigators involved in the continued monitoring
of drug effects. For that reason, we have no comprehensive
approach to the problem as a whole. So, we have better informa¬
tion about some drugs than we have about others.”
Dr. Kaslow then added, “I don’t want to oversell the poten¬
tial of epidemiology. Many facets of lupus can be perfectly well
studied with nothing other than the meticulous laboratory and
clinical science applied by many excellent investigators now en¬
gaged in such research. Unravelling the significance of heredity
and viral infection in the New Zealand mouse model of lupus
does not require epidemiologic thinking or methods. The tech¬

niques used by epidemiologists might be helpful, but they are
not always essential. Clinical follow-up studies are an exam¬
ple,” Dr. Kaslow said. “However, in a few areas epidemiologic
and biostatistical methods are absolutely necessary: large-scale
screening for disease, measuring the rates of occurrence, look¬
ing for uncommon attributes of patients, or confirming the im¬
portance of certain causal and preventive factors.”
Dr. Kaslow paused. “Some epidemiologic questions could be
answered if it weren’t for social and political barriers. We’d like
to know, for example, whether the predisposition to lupus
among blacks is the same for African as well as American
blacks, but truly comparable data from Africa would not be easy
to obtain without exorbitant cost and effort. Or, as I suggested
earlier, certain types of studies require cooperation of the prac¬
ticing medical community. Yet, the climate for requesting a
practicing physician to supply information on medical records to
legitimate investigators is not particularly favorable as long as
malpractice and privacy protection are at the surface of society’s
thoughts about the health care system.” Dr. Kaslow paused
again.
“To summarize, I would just say that I believe epidemiology,
like so many other disciplines used to study lupus (immunology,
pathology, dermatology, etc.) can play a role in improving our
understanding of the disease. We must, however, recognize the
boundaries of the field. We must ask ourselves what epidemiol¬
ogy can and cannot contribute, and then simply begin with what
is possible.”
SLE In Children and Other Research 49
SLE In Children,
And Other Lupus Research
At Children’s Hospital
Medical Center in Boston
‘'Every patient you see is a lesson in

much more than the malady from which
he suffers/'
— Sir William Osier, M.D.
Acquanimitas.
O ne day I went to see Dr. Yves Borel at Children’s Hospi-

|tal Medical Center in Boston and asked him to tell me
something about lupus in children.
Dr. Yves Borel is an Associate Professor in Pediatrics at the
Harvard Medical School, and Director of Rheumatology Ser¬
vices at Children’s Hospital. I had read Dr. Borel’s paper on
“Prevention of Murine Lupus Nephritis by Carrier-Dependent
Induction of Immunologic Tolerance to Denatured DNA,” and I
was also eager to ask him about the New Zealand mice, and
about the progress of his research.
Dr. Borel said, “Systemic Lupus strikes children and adults
alike, although the natural cause of the disease seems to be
milder in children.” The disease is extremely rare before five
years of age. There are only a few cases reported in the litera¬
ture. Before puberty, the incidence is distributed equally be¬
tween the sexes. In contrast, during the adolescent years, there
is a greater preponderance of girls than boys. The sex ratio is
about four to five girls to one boy, suggesting that female hor¬
mones modulate disease activity. Not only is Lupus more com¬
mon in girls than in boys, but the incidence in girls is greater
among blacks than among whites. Furthermore, the disease ap¬
pears also to be more severe in black girls. Thus, both sex and
race play a role in the natural course of the disease.
How does the disease begin? “In the great majority of cases,
the mode of onset is the same in children and adults. They
complain of a typical butterfly skin rash on the face, weakness,
fever, and joint pain. But in about twenty percent of the cases,
the mode of onset is atypical. The first symptoms can be ex¬
tremely different. For example, weakness may be experienced if
anemia or abdominal bleeding are present; cloudy urine may
occur if there are white blood cells and albumin in the urine; or
signs of a petit mal seizure if there is involvement of the central
nervous system. Thus, the mode of onset can reflect blood,
kidney, or central nervous system disease. In rare instances Sys¬
temic Lupus in girls follows Juvenile Rheumatoid Arthritis. Be¬
cause of these atypical clinical manifestations it is important to
see a specialist who can recognize the disease early.”
“What are some of the most common questions asked by a

mother or father who fears for their youngster who might be
afflicted with lupus?” I asked.
“Perhaps one of the most common questions asked by parents
and pediatricians alike is: ‘I have a 16-year-old girl with a rash
on her face and positive antibody to nuclear antigens in her
serum. Does she have Lupus?’ A skin rash and a positive antinu¬
clear antibody by themselves are insufficient to make a diagnosis
of Systemic Lupus. One needs at least four criteria, including
clincial signs and laboratory tests, to establish the diagnosis.
Some of these may include hair loss, albumin in the urine with a
low white cell count, and anitbody to DNA in the blood. Anti¬
nuclear antibody, although quite a sensitive test, is non-specific.
In children it is seen in other diseases such as Juvenile Rheuma¬
toid Arthritis, mixed connective tissue disease, or scleroderma.
In addition, a skin rash is not necessarily a Lupus skin rash,
particularly if there is no sun sensitivity. Therefore, one has to
be careful before making a diagnosis of Systemic Lupus, since it
carries important implications.”
“If a child has lupus what happens later in life? Will he or she
have lupus as an adult? Will he or she recover completely, or is
he or she going to be sick from time to time? ” I asked.
“It all depends on the individual,” Dr. Borel answered. “The
disease can strike many organs at different times during its
course or the disease may go into remission spontaneously. Is a
patient ever ‘cured’ of Lupus or does one enter only remission?
This is a difficult question to answer because if one is com¬
pletely well for one or two years, the disease may still come
back again. However, the longer the remission, the better the
chance that the disease is ‘cured.’ By in large, it seems that
children will follow one of two opposite natural courses. Their
disease will either remain active after adolescence and the
child’s life expectancy might and in most cases will be short¬
ened, or the disease can enter a permanent remission. These
opposite outcomes appear to be determined by a number of fac¬
tors. Three of them are outstanding: First, whether the disease is
systemic with a multi-organ involvement; second, whether the
disease involves the central nervous system; and third, whether
the disease is manifested by a progressive unremitting kidney

disease. Although these three major clinical manifestations are
not encouraging, I have to stress that by no means do they
necessarily carry a fatal prognosis. Five years after the diagno¬
sis, ninety-five percent of all children with Lupus are alive. It
seems that in most instances the disease is somewhat milder in
children than it is in adults.”
I asked Dr. Borel to tell me something about the management
of the disease.
Dr. Borel said: “The management of the disease is dictated
by the severity of its natural course. If the disease is mildly
active with pain and joint swelling and low grade fever, anti¬
inflammatory agents such as salycilates (for example aspirin)
might be sufficient. But if the disease is active, involving the
kidney, heart, or the central nervous system, one might be
forced to prescribe cortisone or another steroid-related hormone
such as prednisone. Prednisone, aside from its powerful anit-
inflammatory effects suppresses autoimmunity. If steroids are
the preferred drug, it is unfortunate because they have many side
effects. One has to emphasize that the side effects are both time
and dose dependent. Furthermore, they vary from one patient to
another and many young women can take prednisone for a long
period (years) without any major side effects. But for a teenage
girl, perhaps one of the most difficult side effects to bear is
esthetic. Prednisone can produce weight gain, a so-called,
‘moon face,’ or red striae on the skin of the abdomen or the
upper and lower limbs. I remember one of my teenage patients
was a cheerleader. Despite the fact that she had red striae on her
legs, she wore skin-colored pantihose and was still cheerleading.
One has to weigh the side effects of prednisone against the
benefit of successfully treating the disease. Steroids remain the
drug of choice for controlling disease activity.”
“Now, Dr. Borel,” I said, “could you tell me how you feel
about the psychological implications of the disease? What does
it mean for a child and a parent to have lupus?”
“As you have probably learned from your talk with Dr. Na-
delson, this is a complicated question,” Dr. Borel said. “If I
could sum it up in a few sentences, I would say that first one has
to learn to accept the disease and realize that the cause of the
disease is still unknown. One of the most difficult things to
accept is that the disease is no one’s fault. Parents often feel
responsible for the illness of their child. One has to convince
them that there is absolutely no fault on their part, since the
disease is not hereditary. If both parents and patient accept the
disease, this is already a great step forward which facilitates
communication between parents, doctors, and children. For the
parents, there are usually four psychological stages they have to
go through: 1) guilt, 2) frustration, 3) anger, and finally 4)
acceptance. It is only at the last stage that their relationship with
their child’s illness will be successful.
“For the young adult, the disease arrives at a time where
many other problems of adolescence have to be faced and
solved. The child is experiencing difficulties with personal iden¬
tity, dependence, and sexual awareness, just to mention a few of
the problems facing teenagers. Their treatment should reflect an
understanding of these issues. For instance, adolescent girls
understandably prefer to be examined by a female physician
with whom they feel more comfortable.
“How the young adult deals with his or her illness varies
enormously from one teenager to another. The response also
depends largely on how serious the illness is. Parents should
encourage their sick child to lead a normal life, to attend school
and to participate in social and physical activities to the fullest
extent possible. Children are much more direct and spontaneous
than adults. In some instances, to be sick will depress them, but
in others it will help motivate them. Most young adults with
lupus are intelligent and perceptive and have an inborn capacity
to adjust to what is still an unknown and confusing illness.”
I gave Dr. Borel a letter to read written by Vicki Croke, one
of his patients, whom I have known since she was a sophomore
in high school. Vicki is now a graduate from the University of
Massachusetts with a degree in Journalism. This is what Vicki
wrote:
I learned that I had lupus in the Fall of 1971, just after my thir¬
teenth birthday, and oddly enough, just after receiving the Presiden¬
tial Physical Fitness Award. At the time, my only symptom was a
butterfly-shaped rash stretching across the bridge of my nose and

onto my cheeks. Although I felt fine physically, emotionally I felt
disabled by the restrictions my doctor put on my lifestyle.
Adjusting to the disease was just impossible for me. I was only
thirteen and while all my friends tried out for cheerleading. I sat
under the bleachers and out of the sun. As my physical condition
worsened I became more distraught. I became violently ill the winter
of 1973 when I was fifteen years old.
I had gaping mouth sores, aching swollen joints, fever, weight
loss, irritated butterfly rash, an unrelenting fatigue, low white blood
cell count and inflammation of the membrane surrounding the lungs.
For the first time I had to face my disease. I discovered that systemic
lupus erythematosus is a powerful force to be reckoned with. I was
too weak and too ill to refuse my medication — prednisone. From
my sparse bits of information I viewed it with vague dread, knowing
that the dangers of prolonged intake of massive doses are shocking.
And the side effects I experienced lived up to my expectations. I
gained weight, I became a ‘moon face’ due to retention of fluids, I
suffered high blood pressure, a hip disorder, and mysterious knee
pains. I also recorded dried skin, stretch marks, I stopped growing
in height, had dizzy spells, nausea, and other day-to-day annoy¬
ances.
The disease had chased me into the shadows, and now too weak
to fight back I was given a medication which distorted my face and
wiped away much of my identity. Although I knew that this disfig¬
urement was only temporary, the experience of seeing someone else
in the mirror left me devastated. When I got out of the hospital, I did
not attend school, but had tutors. I did not allow my friends to visit,
and I refused to leave the house.
I went out once on the encouragement of a friend over the phone.
I went to see a school production of Camelot — I met all my friends
in the balcony, and not one of them recognized me. I went home
with a spirit even more changed than my face.
Dependence on medical caretakers, and parents, and a monitored
lifestyle all set the regression in motion.
I had read that the normal development of children includes a
movement from passivity to activity, from dependence to independ¬
ence, from ambiguous sexual identity to a definite one, and from
total involvement with self to concern for others as well. Whatever
progress I had made with these steps not only stopped but reversed
itself.
I hid from the world inside my home. I was passive, dependent,
sexually ambiguous, and self-centered. I was content with the situa¬
tion for a few months, happily absorbing the unconditional, doting
love of my parents. My mother took a leave of absence from work.
and would ride buses on freezing February days to spend every one
of my hospital days beside me. My father would arrive late, grimy
and exhausted from a full day’s labor as a truckdriver. They would
drive home together in the chilled darkness, long after visiting hours
were over. Their devotion did not end when I returned home from
the hospital.
I left all decisions up to my family. My sister then working at
Filene’s bought all my clothes and brought them home to me. I
would cook, but someone had to tell me what to make, and if I
disagreed with someone, I just gave in, which was not at all like
myself.
When the few friends I hadn’t scared away called, their talk of
‘the boys’ was alien to me, I just felt too unattractive to think of
myself as a sexual being. I saw myself, more, as some sort of
eunuch.
Finally I was totally self-centered. I spent much of my day alone
in the house. I was my only companion, and rumination my only
activity.
I did very well with my school work, it was a life preserver to
hang on to and eventually a base to build on. But, I was very
depressed. I was dependent, fragile, and passive, I felt that for some
reason God chose to punish me, and there was nothing I could do
about it.
At some point, I don’t know when and I don’t know why, the
depression focused — I was too tired of being sick, too tired of
being fat, too tired of being passive, dependent, friendless and self-
centered. I suddenly realized that I was a straight A student, I went
on a diet, my medication was reduced, gradually, and I even began
to see a few Mends on a regular basis.
It is here that for the second point in my life there was a move¬
ment from passivity to activity, the other steps of the emotional
progression did not occur as rapidly, however. I built up my cour¬
age, and returned to school in the fall of 1974. It was during the next
two years that my disease went into remission, my dependence
shifted from parents to friends to approaching independence, my
sexual identity became more definite as I began to mingle with “the
boys’’ and as my concern for others grew, my unhealthy involve¬
ment with self withered.
There is a symbiosis between mind and body. And the growth of
my social life reinforced, and was reinforced by, my rapidly improv¬
ing health. I was voted class wit, I graduated with honors, with
friends, and in remission.
I think that a vital part of a chronically ill patient’s well being is
the doctor-patient relationship. My relationship with my doctor was
a nasty one. She was cold, bullying, and at times downright sadistic.
She once gave me an injection in my upper lip without a painkiller,

and without a warning about the pain. To this day I shudder when I
think of that clinic visit.
I viewed my doctor as the personification of the disease, and
therefore with hatred. She kept my family in the dark about aspects
of the disease, side effects of some of the drugs, and even once
about the type of surgery about to be performed on me! Yet we
knew of few doctors treating lupus at the time, and scientifically,
she was one of the best.
I spent my clinic visits telling her she just couldn’t understand
what it was like to have lupus. We might have spent even more
visits this way, but she died in the fall of 1974. It was after her death
that I learned that she had been suffering from lupus herself!
We could have shared a knowledge of a common suffering if only
she had told me. But instead, at age 16, I was left with the enigma
of a doctor, a healer, too uptight about the disease she was treating
me for to tell me that she had it also. She denied the disease, went
out in the sun, exerted herself, and died very young. Perhaps I, as a
lupus patient, represented the disease she could not control as a
sufferer, or as a physician, as much as she personified lupus to me.
But, this is just one of the many questions I have which will remain
unanswered.
My current physician is known as a leader in the field of immuno¬
logical research, however, his candor, warmth, and emotional sup¬
port are as important to me as his scientific reputation. He has taught
me to relax with lupus, and so my good health continues.
I am now at ease with lupus, it is part of me, I do not ignore that,
but it does not define who lam. lam not shattered by aching joints,
fevers, or fatigue (which all exist when the disease is in remission)
and I am not afraid to tell people about it. I face a sunny future . . .
umbrella in hand, of course.
Dr. Borel read the letter and returned it to me with a slight

nod of his head. During the moment of silence which ensued, I
took the opportunity to ask him how he was going to bring to the
bedside his basic research in immunology.
Dr. Borel suggested that we go to his laboratory across the
hall where I could observe his lupus mice in their own habitat.
Dr. Borel’s mice were housed in several cages set on top of a
long counter.
Dr. Borel explained that strains of New Zealand and other
mice are helping scientists find out more about lupus. The off-
Spring of the New Zealand black and white varieties develop a

disease remarkably similar to human SLE. “To what extent the
abnormalities of the animal model are similar to humans with
lupus is not completely understood,” he said.
Looking into one cage, I saw a black mouse and a white
mouse moving at a swift pace. Their pointed pink-lined ears,
their pink-snouted faces, and their long skinny tails made them
actually pleasant to watch. The mice paused from time to time to
eat pellets or to drink water. In the sunlit room, their small
round eyes, a startling black, shone like glass.
Dr. Borel pointed to a comer of the cage. As I looked closer,
I saw a litter of newly-bom pink mice. They were as small as
hornets, all snuggled together for warmth and security. Dr.
Borel observed the mice attentively. “For a long time, I have
been interested in the induction of immunologic tolerance in
adult animals, because lupus is an autoimmune disease in which
natural tolerance to nucleic acid antigen is impaired. Conse¬
quently, patients with lupus make antibody to DNA. The anti¬
body combines with the nucleic acid antigen, and causes tissue
damage. One main goal of the therapy is to restore immunologic
tolerance to DNA.”
Dr. Borel explained that the principle of carrier-determined
tolerance is based on the concept that small antigentic determi¬
nants (called haptens), linked to non-immunologic carriers (nat¬
ural substances tolerated alone),are tolerated when combined to¬
gether. The role of isolgous (naturally formed) IgG, a protein
naturally tolerated by the host, has to be emphasized as a toler¬
ance-inducing carrier. Haptens linked in a certain way to this
IgG (called the tolerogen) can induce tolerance to the same hap¬
ten linked to a foreign carrier (the immunogen).
This principle was applied to the treatment of murine lupus
nephritis in an attempt to suppress antibody to denatured DNA
in these mice. The rationale was to induce tolerance to nucleic-
acid antigens prior to the development of the disease. This was
done by binding the four nucleosides of DNA; (the units that
make up DNA) to isologous NBZ IgG as a tolerogen. This
complex was used because nucleosides are haptens, and antibo¬
dies to denatured DNA cross react with nucleosides.
Dr. Borel, in a collaborative effort with B. David Stollar and

Dr. Robert W. Lewis, was successful in his attempts to prevent
the appearance of the disease by inducing immunologic toler¬
ance to DNA in mice. Recently, Dr. E. Diener (Chairman, De¬
partment of Immunology, University of Alberta, Canada) has
shown that cortisone facilitates immunologic tolerance. Dr.
Borel and his colleagues have applied this observation to the
treatment of animals with lupus. They have shown that corti¬
sone, together with the induction of tolerance to nucleoside, can
prolong the life of these animals and treat the disease.
Dr. Borel further explained that one of the advantages of this
therapy is its capacity to prevent development of the nephrotic
syndrome and prolong survival without the hazards of long-term
steroid therapy. He emphasized that the results obtained thus far
are still preliminary. The hope is that one might be able to
induce immunologic tolerance, not only to small pieces of the
DNA molecule, but also to larger fragments as well, using a
similar approach. This approach attacks, for the first time, the
cause of the tissue damage in mouse lupus, and may provide a
way to prevent the formation of antibody to DNA, the main
cause of tissue damage. Although an enormous amount of time,
effort, and money will be needed before we learn to suppress
antibody to all nucleic acid antigens, not only in mice, but also
in humans, scientists are hopeful that in the near future they will
be able to apply this knowledge to the treatment of lupus pa¬
tients. They hope that the induction of tolerance to nucleic acid
antigens will replace, at least in part, the need for steroid
therapy.
In addition, if doctors eventually learn to identify those indi¬
viduals most susceptible to lupus, they may be able to prevent
the disease by inducing tolerance to nucleic acid antigens before
tissue damage occurs.
Lupus and Photosensitivity 59
Lupus and Photosensitivity
“In the meantime, patients should con¬

tinue to stay indoors when too hot the eye
of heaven shines. ’ ’
— NORMAN TALAL, M.D.*
*Norman Talal, M.D., from the Introduction of Proceedings of the Kroc Foundation
Conference of Sex Factors, Steroid Hormones and the Host Response, Santa Inez Val¬
ley, California, February 12-16, 1979. Editor, Norman Talal, M.D.
Ultraviolet Light Screens for Lupus Patients
1. Single agent containing both UVA and UVB protection

(American rating system, SPF 15, European system SPF 8 and
above)
SPF 15 Active Agents

Total Eclipse lotion ^PABA - ester & benzophenone
Supershade lotion PABA - ester & benzophenone
Presun 15 lotion PABA - ester & benzophenone
Sundown 15 PABA - ester & benzophenone
M!M!M! What a Tan PABA - ester & benzophenone
Piz Buin Exclusiv Extrem Cinnamate & benzophenone
Creme
2. Agents which can be used in combination to provide UVA and

UVB protection
UVB protecting agents Active Agents

Eclipse lotion ^PABA - ester
Presun lotion PABA - ester
Pabanal lotion PABA - ester
Sundown PABA - ester
UVA protecting agents Active Agents

Sol Bar Benzophenone
UVal Benzophenone
Pan Ultra Benzophenone
All the above should be replaced after swimming or 2 hrs. of

sweating
3. Opaque screens protecting from UVA and UVB
Clinique (makeup)
Reflecta (makeup)
Covermark (makeup)
Zinc oxide
Titanium dioxide
TAB A containing lotions are most effective when applied 1 hour before exposure.
Persons allergic to thiazides, sulfonamides, ’caines, or paiaphenylenediamine should not
use PABA; Piz Buin, Maxafil, Solbar or UVal can be substituted, as can opaque screens.
P I art of my plan in presenting this monograph on systemic

'lupus erythematosus was to speak to Dr. Elizabeth Cole
about the senstitivty to sunlight experienced by many lupus
patients, a sensitivity which implicates ultraviolet radiation as a
possible factor in triggering or exacerbating the disease. Skin
rashes and lesions often appear on parts of the body exposed to
the sun, and a patient’s symptoms in general may become aggra¬
vated. Dr. Cole is Chief of Dermatology and Venereology at
Newton-Wellesley Hospital in Newton, Massachusetts, and Lec¬
turer in Medicine, Tufts University School of Medicine in Bos¬
ton.
I went to see Dr. Cole in her office, which is located in a
small brick building on the hospital premises. Dr. Cole is an
attractive young woman who seems to have a special interest in
lupus because of her own experiences with photosensitivity.
I said, “You can understand how the lupus patients feel when
they wish that they could walk in the bright sunshine without
dread of getting the butterfly rash.”
“In lupus it may be more than the rash that one gets from
the sun,” Dr. Cole answered. “The changes of lupus can occur
inside as well.”
I asked her to explain how the sun’s rays penetrate the skin
and trigger or unmask the disease.
Dr. Cole said: “The pathogenic role of ultraviolet radiation is
not entirely understood. Ultraviolet irradiation is thought to en¬
hance the immune response and disrupt the natural tolerance to
DNA. Lupus skin lesions or systemic illness may follow other
noxious stimuli, including thermal bums and insect bites; sun¬
burn may act as a non-specific trauma to cells. Specific antibod¬
ies to UV-altered DNA can be induced in experimental animals
with exposure to UV radiation. Some researchers have proposed
that patients with systemic LE were immunized to UV-altered
DNA, and that the antibodies subsequently produced in their
bodies cross-reacted with DNA of their own living cells.”
I mentioned my sensitivity to mosquito bites and my severe
reaction to the black migie flies in New Hampshire. The bites
get infected, blister, and I run a fever. I hate spraying myself
with insect repellant. I can’t stand the smell, and even if I spray
myself for mosquitoes they get into my hair and devour my
scalp. One of my doctors suspected the insect bites were a possi¬
ble cause for the onset of my lupus.
“I am not surprised,” Dr. Cole said. “Although such reac¬
tion to insect bites is not specific, multiple areas of cell injury
could conceivably flare lupus.”
I asked Dr. Cole if all lupus patients are photosensitive.
She answered that one-third to one-half of all patients with
lupus erythematosus (LE) are photosensitive. “But I don’t sup¬
pose we would know the real answer to that question unless we
could prevent all dangerous radiation exposure. That sunburn
can precipitate or exacerbate systemic LE, with or without skin
changes, is well recognized,” she said. She mentioned that in
one laboratory experiment new cutaneous lesions followed expo¬
sure to solar and artificial UV-A and UV-B in patients with
cutaneous lupus. These lesions lasted for many months follow¬
ing the exposure. This generous group of patients with lupus did
submit to light testing with single wave length light sources,”
Dr. Cole paused. “They were very brave, because they risked
becoming ill from the testing. Lupus patients can sometimes
react to even small amounts of radiation of UV-A and UV-B
ranges.”
“What do you mean by artificial UV-A or B?” I asked.
“By artificial ultraviolet (UV) light, I mean radiation from a
special source called a monochronometer which is used in a
laboratory to produce energy of a single wave length. Its pur¬
pose is to try to determine which wave lengths produce which
effects when human skin is exposed to it. UV-B is the name
given to the portion of the sunrays that cause sunburn and tan¬
ning reaction and this includes the range 290-320 nanometer
(nm). UV-A is the spectrum of sunrays which causes immediate
tanning of skin and includes wave lengths of 320-400 nm,” Dr.
Cole said.
“What is a nanometer?”
“It is a very tiny measurement of length used to measure x-
ray waves, ultraviolet light, visible light, and infrared. These
latter are words we use to separate the different qualities of
energy which different wave lengths of the electromagnetic

spectrum possess,” she said.
“When I use the photostating machine, I develop a burning
sensation and I become unduly stiff and tired as if I were going
to become ill again.”
Dr. Cole said, “The light source you are using at the machine
has visible light (wave lengths 400-760 nm) which normally
does not harm you or any lupus patient we know of, but it also
has some waves of ultraviolet (UV-A) which you cannot see,
and are of lengths to which your particular body is sensitive,”
Dr. Cole said. “You probably wouldn’t feel ill from a very short
time at the machine, but the more flashes, the more exposure to
ultraviolet radiation. Actually, you are very close to the light
source when you use the machine. The distance from the source
of radiation, and the length of time of exposure, are as important
to you as the wave length. For instance, if you have a single
fluorescent light emitting some ultraviolet waves in your kitchen
or bathroom, you might or might not be bothered by it, because
photosensitivity varies from one individual to another. Also,
different wave lengths are produced by different types of light
bulbs. However, if you were a draftsman, for instance, or an
office worker with lupus where banks of fluorescent bulbs line
the ceiling, maybe also with a high intensity bulb on your desk,
you might spend eight to ten hours a day with intensive, even
relatively distant exposure, and be made very sick by it. Still
other patients with lupus might not be bothered at all. It is quite
an individual matter. Tolerance to UV light in a lupus patient
tends to remain stable, but I have seen cases where it changed
dramatically and suddenly.”
“I wonder if colored television has an adverse effect on
photosensitive lupus patients?”
“In some cases it does,” Dr. Cole said. She explained that,
until two to four years ago, very little attention was paid to how
much UV emission came from TV sets to viewers’ bodies. Since
then, however, an effort has been made to change the screen’s
design to eliminate ultraviolet emission. “Here again,” she
said, “the length of time of exposure is important; four to six
hours in front of an older UV-emitting screen definitely could

harm a LE patient.
“One really has to know what specific radiation sources are
potentially harmful to LE patients to prevent exacerbations,” I
said.
“You are right, of course,” Dr. Cole said. “Although most
photosensitive lupus patients are sensitive to the UV-B range,
some patients are sensitive to UV-A. These waves go through
glass; when one is on a plane at 35,000 feet, and is on the sunny
side of the plane, there is a lot of UV-A exposure if you are not
protected.” She pointed out that anyone on a glass porch or in a
car, without a UV-A protective light screen, is being exposed to
visible radiation and UV-A as well.
“How about plain electric bulbs?” I asked.
“You mean incandescent bulbs?”
“Yes,” I said.
“They produce no significant UV-A or UV-B — though lots
of visible light and some infrared energy, which is the heat from
the sun and light bulbs. Visible light will do no harm, but of
course, infrared can produce a thermal bum. Do you begin to
understand more about radiation now?” Dr. Cole smiled.
“I hope so,” I smiled back, and I asked if lupus patients
should be aware of other sources of UV-A or UV-B.
“Oh, yes,” Dr. Cole said. “Welders’ arcs produce lots of
UV-A and B, depending on the amount of heat produced. Tung¬
sten iodide light sources, such as are used in movie or slide
projectors, have lots of UV-A, and so do the hot furnaces of the
steel industry. A movie house projectionist or a teacher who
uses films might have problems if unprotected. The high-inten¬
sity lights used in photographic, TV, and other studios, might
also have UV-A emission.”
“I have developed bluish spots on my face after appearing on
TV talk shows. I have been wondering about that.”
“Em surprised at you for not protecting yourself,” Dr. Cole
said. “Remember the pictures you showed me of yourself when
you first developed the butterfly rash after being in the sun in
Florida? Even though you were constantly playing tennis with-
out a problem in your earlier life, once your photosensitivity

began, the lesions continued for six long years. There were all
those hardships you went through including the steroids you
took and from which you developed a ‘moon face’. Obviously,
Hennie, it will pay you in particular to be very careful — al¬
ways.”
Mrs. Aladjem on the tennis court before she realized that she was photosensitive.
I pointed to the two new spots that I got on my cheeks after I

was in the sun for half an hour waiting for a taxi.
“The damage has been done very innocently,” Dr. Cole said,
examining the spots. “You must train yourself to use your light
screens, the way others take pills for their illnesses. I know this
is difficult. I am photosensitive myself,” she said, “and I use
UV blocking agents religiously when skiing or hiking in the
mountains, but last week I completely forgot and mowed my
lawn in the midday without any protection at all! ”
“How do you feel about some of the sun screens which are
being recommended now?” I asked.
The butterfly rash appeared on Mrs. Alad- Mrs. Aladjem developed a ‘moon face’ from
jem’s cheeks and nose after she had spent time the steroid therapy.
in the warm Florida sun. The rash is one of
many signs that may appear in lupus patients
prior to medical therapy.
When the medication was stopped, the rash

disappeared and a withdrawn expression was
visible on Mrs. Aladjem’s face.
“Recently I have been talking to my good friend, Dr. Madhu

A. Pathak, of the Department of Dermatology, Harvard Medical
School at Massachusetts General Hospital in Boston. Dr. Pathak
is writing a serious monograph to help every light sensitive pa¬

tient learn about how to protect themselves. His work will be an
inspiration to patients and physicians. I hope this work will get
the industry and other medical researchers busy developing even
better sun screen lotions, and creams which contain light-ab¬
sorbing chemical agents that will keep UV-A and UV-B from
penetrating skin.”
I questioned why doctors don’t prescribe lotions or creams to
patients to protect them from wave lengths to which they are
specifically sensitive.
“None of the screens available require prescription,” Dr.
Cole said. “But to test each individual patient is not safe or
practical. The sun screen industry makes products which sell to
as many people as possible. They tend to cater to the person who
‘wants a little color’ and that is not good enough for our pa¬
tients. Only recently they have become aware that many people
have limited tolerance to ultraviolet light for serious medical
reasons. Doctors need education, too, about which agents shut
out which UV radiation sufficiently to protect lupus patients.”
“Is there much research in photosensitivity?” I asked.
“Not enough,” Dr. Cole said. “There are about forty other
diseases affected by light, including skin cancer.” Dr. Cole
stressed the importance of increasing research in this area. And
she emphasized how important it was for every lupus patient,
light sensitive or not, to be protected with daily use of the most
potent available UV-A and UV-B-blocking agents, even if that
means putting on two creams or lotions every day, and replen¬
ishing them. It is seldom necessary any more to wear two lotions
since combined potent protection has progressively become
more available. She said that all light blockers except the opaque
ones are easily washed off, and actually disappear from the skin
in a short time (about 90 minutes) out of doors in the air, and
after swimming or sweating. “One can easily forget that,” Dr.
Cole said, “so carry your lotion with you at all times.”
“How would you protect your scalp?” I asked.
Dr. Cole pointed out that hair itself is some protection, though
often it is thin in lupus patients. A hat provides good protection.
she said, but hats are not sufficient protection for the face be¬
cause radiation is reflected from sand, concrete, and other sur¬
faces. She remarked that the protection provided by hats, like all
clothing, depends on the tightness of weave. “I’m not sure peo¬
ple realize that a see-through blouse is almost no protection at
all,” she said. Dr. Cole prefers to call the light screens “block¬
ing agents” in order to emphasize that visible light is not the
enemy. “As many ‘light screens’ or ‘sun tan’ lotions as lipstick
colors are on the market,” she said, “but most of them are for
normal people, and they really are not very effective.” She
stressed that we were talking about people with special needs.
She pointed out that only a small handful of useful agents are
available and that doctors wish for even better ones. “At present
we have only five chemical classes of potent protecting agents,”
she said. “They are: Para-aminobenzoic acid, which guards
against UV-B as do cinnamates, homo-menthyl salicylate, and
anthranilate, the latter of which are too weak to be of much use
to lupus patients, and benzophenones, which guard against UV-
A and UV-B. Dr. Cole continued, “The important thing to
know is that the vehicle into which one or more of these chemi¬
cals is put can modify its efficacy. In other words, even the most
effective blocker can be rendered useless to a lupus patient, or
other person who needs a sun screen for medical reasons by the
presence of other combined chemicals, which destroy its activ¬
ity. We also have opaque screens, which put a visible physical
barrier in the way. They are probably the most effective block¬
ing agents we have. However, they are not as cosmetically ac¬
ceptable. Right now the madeup look is not in vogue. The un¬
tinted are stark white, the tinted ones like heavy makeup. But
those would be ideal for your times under TV lights, Hennie.”
Dr. Cole pointed out that several very recent studies allow
researchers to rank sun blocking agents by number, in order of
their protective ability (sun protection factor). The designation
SPF is being put on labels by the industry and may not always
be standard. In fact, the European products, such as Piz Buin are
numbered differently. One of the most exciting recent advances,
she said, has been the combination of UV-A and UV-B block¬
ers, together in the same gel, cream or lotion, one that has been
specially selected to provide maximum efficacy. Where the

newer agents are not available, combining two lotions or gels is
still a reasonable and necessary maneuver to protect oneself. She
stressed that the new agents containing both PABA and benzo-
phenones which can be used singly are: Total Eclipse and Im¬
proved Supershade lotions and others which have an SPF of 15.
Piz Buin Exclusiv Extrem Creme also is a complete blocker. The
best UV-A blockers are UVal and Sol Bar, both benzophenones.
She said that they can be used over the best UV-B blockers,
such as Eclipse, Presun, Sunbrella, Sundown and Pabanol, all
PABA-containing substances. Dr. Cole emphasized that both
variety and flexibility are important, because patients can de¬
velop contact dermatitis, especially from PABA. Sometimes this
contact dermatitis needs light to develop. She explained also that
cross-reactions can occur, and individuals allergic to some drugs
or hair dyes cannot use PABA without developing a rash. In this
case patients can use Piz Buin 6 ox 8, which contain benzophe-
none and cinnamate, or those products containing benzophenone
alone.
I expressed surprise that some physicians still did not warn
lupus patients to be more careful about avoiding the various
types of radiation.
“This is an area of some disagreement among physicians,”
Dr. Cole said. “I know some will feel I am coming on way too
strong about the role of light in lupus. But I do not know before¬
hand, nor do I have a satisfactory way of testing to find out who
will get new skin lesions, or who may feel or become systemi-
cally ill from ultraviolet light from any source. There is no safe
way to test. One patient in particular comes to my mind. She
was a very pretty young girl with barely visible lesions. Her skin
biopsy was positive for lupus, and her minimal skin lesions were
a window to her asymptomatic systemic lupus. For a long time
she was very careful to use blocking agents, but she slipped up
just one afternoon at a flea market. She came back to me many
weeks after these new lesions first appeared. We have been
struggling to clear her of these lesions for the past two years, but
I’m sorry to say, they will be scarring forever. I am so sorry she
did not let me know soon enough to help prevent the scars. She
was just lucky not to get sick, as others have, from one day of
too much UV light. We are learning every day,” Dr. Cole said.
“The main idea is to keep informing both patients and physi¬
cians.” She stressed to me the need to wear both a UV-A and
UV-B screen every single day, whether I am indoors or out,
whether I am in the shade or in direct light and letting her know
immediately if a skin lesion appeared so that treatment could
start right away. “Even if you feel like you have a lot on, don’t
take any chances,” she said. “It is not worth it.” She reasoned
that wearing ultraviolet radiation screens was like buying insur¬
ance. One never knew when one would need it. Only recently
has she advised such universal use of screening in lupus pa¬
tients. “Patients like you have had to learn the hard way,” she
said. Even though all patients are not obviously photosensitive.
Dr. Cole believes they would all be wise to protect themselves.
Those who are not light sensitive, she said, can then go about
outdoors, in the sun or shade, with a greater feeling of safety. A
few patients who are exquisitely sensitive, even with our best
current screens, still may not be safe in the hours of intense sun
radiation, 9 a.m. to 4 p.m.
I wondered if the seasons of the year or the latitude made any
difference.
“In New England the sun is intense enough to damage be¬
tween March 15 to October 15,” Dr. Cole said, “but further
toward the equator, the sun is always dangerous. This is because
the distance traveled in the ozone layer affects the amount of
radiation reaching earth from the sun and varies with the sea¬
sons, as well as the time of the day.”
“Patients are asking if they may safely stay close to a burning
fire, and if surgical lights are harmful.”
“No UV-A or UV-B, but the injury can happen through ther¬
mal (heat) energy,” Dr. Cole said. “And, yes,” she noted,
“surgical lights can injure the lupus patient, because of the
emission of UVC (200-290 nm) — a germicidal range of ultra¬
violet radiation. And, of course, x-ray radiation is damaging and
no topical protection is possible for that. As I have stressed
already, all skin injury can lead to a skin lesion of lupus, and
certain types of injuries from ultraviolet light radiation can dam¬

age lupus patients by triggering their systemic illness.”
While I was collecting my papers, Dr. Cole said, “I didn’t
mention the fact that radiation also is reflected from surfaces
such as water, snow, and sand, just as visible light is reflected
from a mirror. A lot of UV is around, even on a cloudy day. At
such times you need to realize that you are exposed, not only to
incident radiation, but also to light reflecting from the other
surfaces.” Dr. Cole continued, “I certainly do not want to cre¬
ate neuroses in any patients, especially lupus patients, about
light. But I strongly feel that until we understand exactly how
one lupus patient is photosensitive, we cannot afford to ignore
the importance of UV radiation for all lupus patients. What I am
trying to say is, what has any lupus patient to lose by knowing
the rules of radiation, where it is, how to protect from it, and
doing it without fail.
By the way, I must tell you that I’m an enthusiast for the use
of potent sun screens for all my patients. That’s because wrin¬
kles and some of the other things of aging including solar kera¬
toses and skin cancers come from the same source. These dis¬
eases occupy much more of my time by far than lupus! ’ ’
Dr. Cole adjusted her glasses and said, “In medicine, one
should never say, T think I’ve covered everything’. I hope I
have been of some help.”
“You have,” I said, “and I thank you.”
When I left Dr. Cole’s office, I called Dr. Madhu A. Pathak
at Massachusetts General Hospital in Boston and asked him for a
brief comment on lupus and photosensitivity. Dr. Pathak is Sen¬
ior Associate in Dermatology (Biochemistry) at Harvard Medi¬
cal School. This is what Dr. Pathak said: “I agree with Dr.
Cole. A number of factors are known to induce the appearance
of skin lesions in chronic lupus patients. The agent most often
incriminated is sunlight. Also exposure to radiation from artifi¬
cial light sources such as the high-intensity fluorescent bulbs,
can induce exacerbation of the disease. The lesions of some
patients also appear to become worse with infra-red radiation
(e.g. electric heaters that emit heat). Patients develop skin
lesions with the onset of hot weather or under the influence of

cold and wind.
The role of immune complexes in the pathogenesis of lupus is
well recognized. The patient should know that ultraviolet radia¬
tion causes specific chemical transformation in the genetic mate¬
rial of the skin, the DNA molecules. This ultraviolet-altered
DNA is antigenic. It has been shown that sera of patients with
systemic lupus react with ultraviolet-altered DNA. This ultravio¬
let-altered material, when released in circulation can lead to the
induction of antibodies directed against skin or other tissues.
Thus, to avoid this possibility, the most important measure
which should be taken by the patient includes the avoidance of
sun exposure. However, in daily life, one cannot avoid exposure
to sunlight. He/she must, therefore, resort to regular use of ef¬
fective sunscreen creams and lotions. The face, the neck, the V
of the chest, the arms and the hands should be shielded with
effective sunscreens that have sun protection value of 15 or
more. He/she should know that sweating, swimming or washing
removes the protective film of the sunscreen. The sunscreen
therefore must be re-applied. I wish we could provide to lupus
patients a systemic sunscreen, that once a day taken by mouth,
distributes evenly in the skin and provides a day-long protection
to the DNA molecules of the skin.”
“Is there hope for such a pill to be developed?” I asked.
“We are working diligently in this area and hope that in the
near future our research will enable us to prescribe an oral sun¬
screen.”
Why is Lupus More Common in Women 73
Why Is Lupus
More Common In Women?
‘‘So safer guess— With just my soul!

Upon the window pane
Where other creatures put their eyes—
Unconscious of the Sun/’

— From a poem by EMILY DICKINSON
I meeting of the Bay Area Lupus Foundation in San Fran¬

cisco, I had the pleasure of meeting Dr. Norman TalaF,
A ]m.Professor of Medicine at the University of California,
Chief, Clinical Immunology/Arthritis Section, Veteran’s Ad¬
ministration, Medical Center in San Francisco, California.
I asked Dr. Talal to explain briefly his opinion of the relation¬
ship between immunology and autoimmune diseases, such as
systemic lupus erythematosus. He answered that autoimmune
diseases might arise as an abnormality in a system based on self¬
recognition. These diseases can be linked to many factors, in¬
cluding genetic, environmental, hormonal, and other factors.
Not all of the factors are known yet, nor how they interact, nor
which ones are most important.
He further noted that immune regulation depends upon the
proper functioning of immune response genes, and upon main¬
taining a balance between subsets of T and B lymphocytes. In
systemic lupus erythematosus (SLE), T cell function tends to be
decreased and B cell activity tends to be excessive. He stressed
that clinical medicine provides numerous examples of autoanti¬
body production without autoimmune disease. Certain drugs,
some infectious diseases, and the process of aging itself may be
associated with a limited form of autoimmunity; upon successful
eradication of the infection, or discontinuation of the offending
drug, the symptoms of the autoimmune disease disappear.
I asked Dr. Talal what was meant by immunoendocrinology.
Was it a new area of medical research? What was the relation¬
ship between immunology and endocrinology and the ability of
sex hormones to modulate the autoimmune disorder?
Dr. Talal said, “Immunoendocrinology refers to the science
of studying the interactions between these two important sys¬
tems.” He first became interested in this area of research when
he and his colleagues worked on studies showing that male and
female hormones influence the lupus-like disease in a strain of
mice called B/W. He went on to explain the role of hormones in
affecting the immune response.
“Androgens are male hormones,” Dr. Talal said, “and estro¬
gens are female hormones. They are small molecules that enter
cells and influence their behavior. A single male hormone is
necessary for developing male characteristics. Many studies of

sex hormones have shown greater immune responses in females
than in males.”
“Is this why lupus is more common in women?” I asked.
“This is a very important question,” Dr. Talal said. “It has
escaped explanation for many decades, although we noted from
the earliest days, when lupus was first being diagnosed, a dra¬
matic sex difference in this disease. Moreover, this sex differ¬
ence seemed to depend upon the presence or absence of the
menstrual cycle. For example, if one considered young children
prior to the onset of menses or post-menopausal women, the
ratio of female to male patients with lupus is approximately two
and one-half to one. However, women are ten times more likely
to develop SLE than men. These clinical observations suggest
that sex hormones play an important role in contributing to the
disease.”
The classical animal model for studying lupus is the NZB/
NZW Fi (B/W) mouse. This strain of mice was first introduced
into experimental medicine in the 1950’s, and has been an im¬
portant mainstay of research on lupus ever since. As in human
patients, the disease in B/W mice also shows a marked female
predominance. For example, female B/W mice develop the clin¬
ical and laboratory features of lupus several months earlier than
males. This gives the medical investigator an opportunity to
study the influence of sex hormones on lupus.
Dr. Talal has been investigating the role of hormones in lupus
for the past several years. His first experiments were designed to
see whether the presence of the testes might be protective, and
explain the delayed disease in male B/W mice. In order to study
this question, he performed prepubertal castration on both male
and female mice, and observed the effect on the lupus disorder.
The castrated males developed an accelerated form of lupus
which was, however, indistinguishable from the disease form in
their female counterparts. By contrast, the elimination of the
ovary did not significantly influence the course of disease in the
females.
Next Dr. TalaTs researchers injected male hormone into
female mice. For the first time, they observed a significant
therapeutic influence. The female mice receiving androgen were

protected and developed very few features of lupus, whereas
mice of both sexes given estrogen developed accelerated dis¬
ease. These results confirmed the concept that androgens were
protective, and that estrogens accelerate lupus in mice.
To explore the applicability of these results to the clinical
situation, they performed a series of experiments in which an¬
drogen treatment was delayed until an age when disease was
already established. Dr. Talal said that even under these circum¬
stances in which the “cards were stacked against them,” the
therapeutic effect of male hormone was again observed. Thus,
the total body of their experimental findings strongly point to the
conclusion that androgen has a protective influence.
I asked whether their experiments were designed to find out
how these sex hormones worked.
“They are,” Dr. Talal said. “For example, we are exploring
the influence of androgen on specific lymphocyte functions and
subpopulations, the effect on macrophages, and the effect on
immune complexes and on how they are cleared from the im¬
mune system. The most interesting results to date suggest that
androgens promote the clearance of immune complexes, and
may prevent the deposition of immune complexes in the kidney.
Such a mechanism would result in less glomerulonephritis and
might prevent the development of uremia. ”
“Is androgen therapy a possibility for human lupus?” I asked.
Dr. Talal answered that androgen therapy has not yet been
tried in patients with lupus because of the masculinizing side
effects of such treatment. However, they have investigated the
possibility that a non-masculinizing androgen might have thera¬
peutic effects in B/W mice. Unfortunately, this preparation was
not effective, and therefore they could not endorse its use in
patients.
Dr. Talal mentioned another study being conducted in Austra¬
lia, in which an anti-estrogen drug was being used to treat pa¬
tients with lupus. This medication had also been effective in B/
W mice and had been administered to patients with cancer of the
breast. The lupus study was just underway, and the results
would not be available for about one year.
“Are patients with lupus likely to be more sterile or impotent

than the average person?” I asked.
“I don’t believe that the lupus patient is more likely to be
sterile or impotent than the average person,” Dr. Talal an¬
swered. He stressed, however, that the risk of spontaneous abor¬
tion in pregnant women is increased for lupus patients. Further¬
more, he said, some lupus patients may experience some prob¬
lems if they become pregnant; such patients need to be followed
very carefully in order to avoid any flare-up of the disease that
might be imposed by the added stress of the pregnancy.
Since time was short, and Dr. Talal’s studies were so interest¬
ing, we agreed that he should write an article on the subject for
Lupus News}
^Dr. Norman Talal was recently made Professor of Medicine, University of Texas
Health Center, San Antonio, Texas.
Lupus News, a quarterly publication; published by the Lupus Foundation of Amer¬
ica, Inc.
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SLE and Pregnancy (Part One) 19
Systemic Lupus
Erythematosus and
Pregnancy
(Part One)
‘‘It pays a woman to take joy in mother¬

hood, her biological destiny, however
imposed she feels it might be/’
— LUCILLE CARTER, M.D.
Psychiatrist
[ seminar on SLE, sponsored by the Pittsburgh Chapter of

the Pennsylvania Lupus Foundation, and the University
A ôf Pittsburgh Division of Continuing Medical Education,
I had a chance to ask Dr. Tom Medsger, Jr. a few questions
about his research on lupus and pregnancy. Dr. Medsger is an
Associate Professor of Medicine at the University of Pittsburgh
Medical School, and he has a keen interest in systemic lupus
erythematosus.
I told Dr. Medsger that, in the past, studies of the relation
between systemic lupus erythematosus and pregnancy often pro¬
duced contradictory literature. Depending on the data, preg¬
nancy either affected lupus patients adversely, or had a benefi¬
cial effect.
Dr. Medsger explained that since SLE is known to affect
primarily young women in their childbearing years, the interre¬
lationship of the disease and pregnancy has been a much dis¬
cussed question in the medical literature. “Pregnancy affects
lupus variably,” he said, “but we can make a few generaliza¬
tions: in over half of the cases the disease activity is either
unchanged or actually less. In more than one-third, however, a
definite flareup of lupus occurs. These episodes are especially
frequent in the post-delivery period.” Dr. Medsger believes that
medical researchers are more knowledgeable in this respect to¬
day than they were several years ago. “We know,” he said,
“that immunologic abnormalities, such as a fall in the level of
serum complement, often antedate clinical evidence of disease
activity in patients with SLE. In our experience, alterations in
these serum levels in pregnant women tend to precede SLE ex¬
acerbations and fetal complications.”
I asked him to explain how this works.
Dr. Medsger said: “We were able to determine that instead of
rising steadily during pregnancy, as is normal, the blood com¬
plement levels in certain lupus patients tended to fall or to re¬
main unusually low. Almost all of the complicated pregnancies,
such as those associated with severe exacerbations of lupus,
premature or still birth deliveries, had one of these abnormal
complement patterns during the course of pregnancy. Although
we do not necessarily treat the abnormal laboratory tests alone.
SLE and Pregnancy (Part One) 81
they add to our ability to supervise the use of medications during

pregnancy.
“What other problems can affect the mother and her unborn
child?”
“First of all, the frequency of miscarriage is increased in
lupus patients,” Dr. Medsger said. “It is probably twice as
common as in women without SLE. Secondly, both prematurity,
and complications surrounding the time of delivery, are encoun¬
tered more frequently. Regardless of these potential problems,
we encourage many women with lupus to have families, if they
so desire.”
Dr. Medsger pointed out that the great strides made during the
past decade in management of pregnant SLE patients have been
due in large part to the combined care of the patient by the
obstetrician, and by the internist or rheumatologist. He ex¬
plained that a number of decisions need to be made, shortly after
a pregnancy is confirmed. Is a continued pregnancy safe or de¬
sirable? Are any problems predictable? If so, how can they be
avoided? Are medication changes necessary? Dr. Medsger be¬
lieves that the soundest advice can be given by combining the
experience and judgment of both an obstetrician and a lupus
specialist. He stressed that these two need to work closely to¬
gether with the patient and family to make decisions during the
entire course of the pregnancy and well into the postpartum
period.
I stressed that the period following delivery could be a very
trying one for lupus patients.
Dr. Medsger agreed, citing both the physical activity, and the
emotional stresses of having the responsibility for the care of a
new infant. “This is a time when the patient needs extra sup¬
port, both from the family and from the physician,” Dr.
Medsger said. “Our custom is to have our nurse speak with a
new mother weekly about her physical and home situation, and
actually to visit the home to observe how the patient is feeling
and coping.”
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SLE and Pregnancy (Part Two) 83
Systemic Lupus
Erythematosus and
Pregnancy
(Part Two)
— Ah Seigneur! Donnes moi la force et le

courage de contempler mon coer et mon
corps sans degout.
— CHARLES BAUDELAIRE
Les Fleur Du MaD
*Les Fleur Du Mai, Charles Baudelair, Jean Landru, Editeur, Chamonix, Mont-Blanc.
Q n the way back to Boston on the plane, I thought about

Ithe conversation I had had with Dr. Tom Medsger, Jr.,
and I wished that we had had more time to talk about
lupus and pregnancy. The young lupus patient has many prob¬
lems and many worries before and after she conceives. She is
concerned about the advisability of pregnancy while her lupus is
active. She worries about the potent drugs she has to take while
pregnant, and about what pregnancy will do to alter the long¬
term course of her illness. After a woman becomes pregnant, her
next concern is, ‘Will I be able to cope with undue fatigue after
the baby is bom?’ ‘Will I be able to breast feed?’ ‘Will I be able
to take adequate care of my child?’ The patient wonders if her
child will be stricken with lupus some day, and she wonders
about her own life expectancy. If the woman cannot have any
children because of her illness, she worries whether her spouse
can look ahead to a life with her, but without a growing family.
The lupus patient feels guilty; guilt and uncertainty are part of
the lupus patient’s daily life.
Some days later, I had the opportunity to talk to Dr. Robert
Zurier\ professor of Medicine at the University of Connecticut
School of Medicine. Dr. Zurier has written several papers on
lupus and pregnancy, so I asked him about research in progress
to help establish which lupus patient can become pregnant with
minimal risk involvement.
Dr. Zurier said: “I know of no work that addresses this issue
specifically. In broader terms, however, much thought has been
given to tests which might predict a flare, or detect who is at risk
for renal disease.”
“Does an abortion pose a threat to the SUE patient’s life?”
“Abortion in the first trimester is not life threatening in lupus
patients, provided their SEE is managed appropriately. Years
ago, midtrimester abortions were not uncommonly fatal in SEE
patients. With better understanding of the disease and its treat¬
ment that is no longer the case. Nonetheless, the procedure car¬
ries some risk and should not be undertaken lightly.”
“When is an abortion recommended?”
“If a lupus patient has a severe exacerbation of her disease,
has nephritis, is not responding well to treatment, and is in the
first trimester, then abortion may be considered. One may argue

in such a case that the risks to patient and fetus are too great to
continue the pregnancy. In general, however, vigorous cortico¬
steroid therapy, rather than abortion, is the treatment of choice
for a flare of disease activity. Since exacerbation of SLE is most
common in the initial postpartum period, evacuation of the
uterus may not necessarily, by itself, have a salutary effect upon
the patient.”
I thought about the potent drugs lupus patients have to take,
about their side effects, and about the fears that one experiences
while swallowing one medication after another. I asked Dr. Zu-
rier if any research was being conducted on the effects of drugs
used in the treatment of lupus during pregnancy; I asked him if
risks were involved for the mother and the unborn child.
Dr. Zurier said, “We have no evidence that treatment of preg¬
nant women with corticosteroids (such as prednisone) has an
adverse effect on the fetus. The drug might induce premature
labor, but rarely causes adrenal failure in the neonate. Aspirin or
other nonsteroidal anti-inflammatory drugs should be avoided
near term, since they might cause increased bleeding at time of
delivery, or might actually inhibit labor.”
“How about antimalarial drugs, such as chloroquine or hy¬
droxychloroquine (Plaquinil); do they have any adverse effects
during pregnancy?”
“Most physicians stop the drugs during pregnancy, but pa¬
tients have taken these drugs through their pregnancy and have
delivered normal healthy infants.”
“Should women with lupus who are taking immunosuppres¬
sive drugs (like Imuran, Cytoxan) get pregnant?”
“Drugs of this type are potentially teratogenic (causing con¬
genital abnormalities), and the benefits and risks must be
weighed before use in women of childbearing potential.”
I recalled when I had my own children, especially the fatigue
and exhaustion and its effects on the actual act of delivery. I
asked Dr. Zurier if physicians are aware of the unusual lupus
fatigue, and of its effects at such crucial moments.
“Probably not,” Dr. Zurier said. “This is an important point
which we often overlook, and the obstetrical team should be
aware that the SLE patient might tire more easily than they
expect.”
“Is delivery by caesarean recommended?” I asked. “Are any
risks involved?”
“Normal vaginal delivery is recommended,” Dr. Zurier said.
“The indications for caesarean section should be no different
than for any other woman. However, lupus patients are probably
at greater risk during any surgical procedure. ’ ’
“The pregnant patient often fears she may not be able to cope
physically with the care of a newly bom child,” I said. “And
even though I have posed this question to others, I would also
like to hear your view. ’ ’
“Motherhood will, in fact, place increased physical and psy¬
chological demands upon the patient,” Dr. Zurier said. “During
the postpartum period, the patient may find rest difficult, and, as
the child begins to crawl, to explore, to walk, the patient’s
energy will be sorely taxed, and undue exertion may lead to
flare in disease activity.”
“Should an SLE patient wait for a period of remission before
becoming pregnant?”
“The course of the mother’s lupus is most favorable during
pregnancies associated with complete remission at the onset of
pregnancy,” Dr. Zurier said. “Some evidence, however, sug¬
gests that duration of remission before the onset of pregnancy
has no relation to the occurrence of exacerbations or remissions
during pregnancy. Thus, if disease remits in a patient who has
felt a certain urgency about having a child, it may be well for
her to seize the moment and, for those caring for her, not to
insist that remission persist for a protracted and necessarily arbi¬
trary period before conception.”
“Should a lupus patient avoid pregnancy if she has signifi¬
cantly elevated blood pressure or nephritis?”
“I would never tell anyone, categorically, to avoid preg¬
nancy. However, the nephritis will probably get worse during
pregnancy. In addition, the frequency of premature births (with
attendant risks to the newborn) is much greater in SLE patients
in whom the lupus is not well controlled. All these problems
must be outlined to the patient and her husband.” Dr. Zurier
paused. And then he said, “In some cases adopting a child is

probably more prudent. ’ ’
I stressed the legal problems lupus patients encounter when
they seek to adopt children, and the fact that some agencies are
reluctant to allow them to adopt a child. I asked Dr. Zurier if the
physician could help by explaining the nature of the illness to
adoption agency representatives.
“Reason, of course, does not always prevail,” Dr. Zurier
said. “Adoption agencies look askance at potential parents —
not just those with lupus, but also many others, including par¬
ents over 40 years of age. Many agencies frown on any devia¬
tion from their code of rules. But to answer your question: yes,
physicians should help lupus patients with adoption.”
“Do patients with mild disease conceive more often than
those patients with more active disease? Does pregnancy alter
the long-term course of SLE?”
“Pregnancy does not alter the long-term course of SLE. In
fact, patients who have been pregnant have a better prognosis as
a group than patients who do not become pregnant. That is
probably because patients with mild disease more often become
pregnant.”
“Can you predict from the course of the disease during one
pregnancy how SLE will affect a subsequent pregnancy?”
“We can’t make such predictions,” Dr. Zurier said.
“Should a lupus patient breast feed the baby?”
“That question has two aspects,” Dr. Zurier said. “One,
since the patient may be treated with corticosteroids during the
early postpartum period, the effect of such treatment on the
breast-fed infant must be considered; and two, how breastfeed¬
ing affects SLE in the patient. We don’t yet have studies on
corticosteroid levels in breast milk of patients treated with these
hormones. Although the mammary gland is a relatively unim¬
portant route for total drug excretion for the mother, some drug
surely gets into the milk. Nevertheless, infants of corticosteroid-
treated mothers have suckled with no ill effects.”
“How does the breast feeding affect the mother’s energy?” I
asked.
Dr. Zurier said, “Breast feeding demands a good amount of

the mother’s energy, and in some patients it might result in
undue fatigue. On the other hand,” he said, “a mother who is
comfortable with breast feeding, and who can get appropriate
rest, should not, in my view, be discouraged from breast feeding
her infant.”
“During my third pregnancy, I developed a low platelet
count. It created a problem during delivery. I bled excessively.
For a while, both the physician and the patient were in dis¬
tress.”
“Platelet counts fall during normal pregnancy,” Dr. Zurier
said, “but the lower counts present no problem. That is usually
true in SLE as well. Some lupus patients, though, exhibit throm¬
bocytopenia (abnormally low platelet counts) which is poten¬
tially dangerous to both mother and child. The birth process is
quite traumatic and you can imagine how vulnerable the baby
with thrombocytopenia (the baby’s platelet count usually reflects
the mother’s) is to bleeding — especially to brain hemorrhage.
The mother is also clearly at risk for uterine bleeding, as I
assume happened in your case. Thus, the patient’s platelet
counts need to be monitored during pregnancy, and especially as
she approaches term. A particularly low platelet count would
dictate delivery by caesarean section rather than by vaginal de¬
livery.”
“Are some birth control pills contraindicated for lupus pa¬
tients?”
Dr. Zurier said, “One oral contraceptive is not better or worse
than another for lupus patients. The best studies indicate that
birth control pills do not induce abnormal antibodies or lupus
like symptoms. These agents are certainly used by SLE patients
without apparent adverse effects. Nonetheless, since evidence is
available of an increased incidence of thrombosis, vasculitis,
and hypertension in women using these drugs, I think SLE pa¬
tients would be prudent to consider other methods of contracep¬
tion.”
I thought of the young lupus patient who is afraid to get
married, who is concerned about involving another person in a
life full of uncertainties. Marriage has worked for many, but
some patients still need advice and support. I asked Dr. Zurier
what he tells the young lupus patient who comes to ask his
advice?
“In general, I encourage them to lead lives as full as possi¬
ble,” Dr. Zurier answered. “The long-term outlook, even for
patients with renal disease, is so good that I would not counsel
against marriage. However,” he said, “the potential mate
should be aware of the possible problems. In addition, the spe¬
cial risks associated with pregnancy in SLE must be made
known to the patient and to the future spouse.” One note of
caution is that children bom to SLE mothers have a higher than
usual incidence of heart block. This condition, in which the
tissues, which conduct the signals that keep the heart beating are
damaged, is very rare, but its possibility cannot go unmen¬
tioned. When heart block is discovered in a newborn, then the
mother should be evaluated for the possibility of lupus.
^Dr. Robert Zurier is now Professor of Medicine, and Chief, Rheumatology Section
University of Pennsylvania School of Medicine.
^ ..8d|^ iv>? ilr;|-iv
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Lupus and Medications 91
Lupus and Medications
The lupus patient dreads the medication

as much as the disease itself.
Marilyn Sousa — A PATIENT*
*Marilyn Sousa is a patient and the Founder of the Connecticut Lupus Foundation.
I ooking into the distant past, I wonder whether I was bom

with the genetic background to develop recurrent illnesses,
-êspecially lupus. In adolescence, my parents attributed
some of my afflictions to a delicate constitution — constant
strep throats, susceptibility to colds, recurring pneumonia, and
the overreaction to mosquito bites. The dmgs I took, instead of
helping, caused problems which were never interpreted cor¬
rectly. The reaction should have been received as a warning
signal from nature, not just for some dmgs, but for all. In my
case, the dmgs led to new complaints and the problems were
treated with more dmgs. I was treated with large doses of corti¬
sone, which led to retention of fluids. To alleviate the discom¬
fort, I was given diuretics. The diuretics contained sulfonam¬
ides, which I suspect were causing more harm than good. For
the pains and aches I was taking aspirin, sometimes as many as
16 per day. For the stomach distress, I took atropine, pyrabenza-
mine, gelusil, and others. . . . For the chronic sore throat which
I could not describe because it hurt and didn’t, I was given small
doses of penicillin and tetracycline.
Along with these dmgs, the doctors instituted white cell injec¬
tions (5 cc each time), niacin injections (I cc per day) and
autologous injections. I also took potassium chloride, vitamin
B6, B12, ascorbic acid and folic acid. Today, doctors are adding
to the list of dmgs, and tranquilizers are often recommended.
The lupus patient remains a consumer of medical services of
the most experimental nature. The patient becomes a voluntary
human guinea pig through necessity. One has to accept the im¬
mediate side effects of the dmgs and the possible side effects
that may or may not appear until years after the specific dmg
was taken.
In lupus, the list of experimental dmgs is frightening, and
very often the question of what dmgs are prescribed by the
physician depends on which research center you go to, and who
the attending physician is.
I asked Dr. Stephen Kaplan to identify some of the dmgs
being used in the treatment of lupus today. Dr. Kaplan is an
Associate Professor of Medicine at Brown University Medical
School, and Chief of Rheumatology at Brown and the Roger

Williams General Hospital.
Dr. Kaplan said, “I think we ought to address several general
issues before discussing some of the specific characteristics of
the drugs that are used in the treatment of systemic lupus
erythematosus (SLE). Remember, many of the manifestations of
SEE are treatable. Some medications affect the mechanisms of
the disease and alter the signs and symptoms of SLE. Many of
these therapeutic agents actually treat the disease process and
should not be considered just symptomatic treatment. In addition
to the use of medications to treat the mechanisms of SLE, we are
also able to treat some of the complications of SLE through
advances in other areas of medical science, such as the recogni¬
tion and treatment of infectious diseases and improved care in
intensive or critical care units. The treatment of SLE is compli¬
cated by the wide variety of signs and symptoms of SLE, as well
as by the varying degrees of severity manifested in different
individuals at any time. Unfortunately, among those patients
with SLE who get involvement of their kidneys or central ner¬
vous system, are some whose disease will not be affected or
controlled with currently available medical means. In dealing
with these severe problems we reach the frontiers of modem
therapeutics and, when faced with such critical medical circum¬
stances, we must carefully judge the point at which the chances
of helping the individual with the aggressive use of potent medi¬
cations become outweighed by the chances of doing harm.
These considerations of “doing no harm,” even in apparently
extreme situations, have taken an added significance as we ap¬
preciate that improvement, such as in the supportive care of
patients with central nervous system disease, may provide a crit¬
ical period of time to pass so that some spontaneous improve¬
ment may occur. In patients with the severest forms of renal
disease in SLE, these considerations have assumed added impor¬
tance with the development of long-term artificial means of per¬
forming the job of the kidneys (kidney dialysis) and even the
hope of eventually successful kidney transplantation.”
“Can one speak of a cure for SLE at this time?” I asked.
“Unfortunately, we have no cure for SLE at this time. How¬

ever, curability is not always a simple concept, and most serious
illnesses, such as diabetes mellitus or common types of heart
disease, may not be curable today but can frequently be con¬
trolled sufficiently to permit a normal lifestyle. Treatability,
therefore, should be emphasized in disorders like SLE, so that
patients and their physicians can work towards realistic expecta¬
tions, and not be unnecessarily tormented or driven by overly
optimistic or pessimistic notions.”
“What are the important components for the active treatment
ofSLE?”
Dr. Kaplan said, “Whatever the treatment, it should include
the intelligent use of preventative measures by the patient, such
as appropriate screening from the sun when photosensitivity is a
problem, and maintaining the warmth of the hands when Ray¬
naud’s phenomenon (spasm of the arteries of the fingers) is pres¬
ent. Medications and drugs, however, play a central role in deal¬
ing with the treatable manifestations of SLE. Without doubt,
most medications that are used in SLE and other serious medical
problems are double-edged swords. Their potential for pro¬
ducing significant beneficial effects must be considered in bal¬
ance with their potential for also producing adverse effects and
added problems for the patient. We are all aware of the great
feats a skilled mechanic can accomplish in repairing complex
machinery with the proper tools and, in contrast, we can also
imagine the harm that can be done by the same tools, including
the proverbial monkey wrench, when they have been applied
improperly or carelessly. In medical therapeutics, we can con¬
sider medications as highly developed specialized tools that have
the capacity to alter complex reactions in a way that benefits the
patient. Since these tools must ‘do their thing’ without the aid of
an ‘on the spot’ mechanic running around inside our body, the
skill in their use comes in choosing the appropriate medication
for the appropriate problem and prescribing the proper dosage to
produce a beneficial effect.”
“Because of the side effects of the various drugs given in the
treatment of lupus, the patient often does not take the medica¬
tions in the proper dosage. How important is it for the patient to
follow the physician’s instructions about taking the medications

as prescribed?”
“Patients need to maintain a level of the prescribed medica¬
tions sufficient to affect the mechanisms of SLE,” Dr. Kaplan
said. “Since the body is continually inactivating and eliminating
the drugs, maintaining a desirable effect by a drug depends upon
cooperation by the patient. Taking the medication so that the
effect is fairly continuous prevents the activity of SLE from
returning or gaining the upper hand. This must be balanced, of
course, by the potential for each drug to produce adverse or side
effects. One must keep the potential for these side effects in
proper perspective. The principle in selecting the specific medi¬
cation, and the strength of the dosage, for the appropriate medi¬
cal problem should be in keeping with a sentiment expressed in
Gilbert and Sullivan’s Mikado, Let the (potential) punishment fit
the crime. Clearly, all patients should be knowledgeable about
the medications they are administering to themselves. If a side
effect does appear, changing the dosage or shifting to an equiva¬
lent but different medication should follow deliberation involv¬
ing both patient and physician. ”
“What specific medications are used in the treatment of
SLE?”
“Before answering I should explain that I am going to refer to
all drugs by their generic names. Every medication has three
names. Each drug has a precise chemical name that is usually
very complicated and generally not well known except to chem¬
ists working in the laboratory. Thus, each drug is also given a
generic name which is, in a sense, a shorthand for the compli¬
cated chemical name. The generic name refers to a specific
medication regardless of manufacturer. The third name for each
drug is the trade name, which is the name a manufacturer uses to
identify his particular product. In some states, laws mandate that
if a drug is prescribed by its generic name, the least expensive
generic equivalent carried by the drugstore, etc., must be used to
fill the prescription,” Dr. Kaplan said. “Now let us discuss the
specific medications that are used in the treatment of SLE. One
group of widely used drugs that suppress inflammation are unre-
lated to any form of cortisone and therefore are referred to as the

non-steroidal anti-inflammatory drugs (NSAID). NSAID’s can
be further divided into smaller groups depending on their chemi¬
cal structures. One group, salicylates, includes the most widely
known and used NS AID, aspirin. Despite a wide range of newer
potent prescription drugs, aspirin remains the treatment of
choice to counter some of the painful inflammation caused by
lupus in many patients, not only because aspirin is so effective,
but also because it can be taken by most people day in and day
out for a long time without serious ill effects.”
“People don’t consider aspirin a serious drug,” I said. “We
take aspirin only on occasion, when pain and discomfort are
acute. Could you explain why aspirin is helpful in the treatment
of lupus and when it is most effective. ”
“Aspirin is an anti-inflammatory drug,”^ Dr. Kaplan said.
“In order for it to work, it must be taken regularly, usually four
times a day or approximately every four hours so that a certain
level of the drug is maintained in the bloodstream. All drugs are
changed by chemical systems in the body, and eliminated so that
if one takes the medication sporadically, the adequate level of
the drug that is required for its anti-inflammatory effect is rarely
obtained and no improvement could be expected. This is an
important difference, therefore, from just taking a couple of
aspirin to alleviate an annoying pain or headache. It is also
important to know, especially with aspirin, that when anti-in¬
flammatory doses of the drug are being used, increasing the
dosage must be done very gradually, and the new blood level
and improvement may not occur for four to five days after rais¬
ing the dosage. Aspirin as a NS AID has been used to treat some
limited forms of inflammation in lupus, such as the arthritis of
SLE.”
“What are some of the side effects of aspirin?”
“Several years ago we learned that some, but by no means
all, patients with lupus who receive aspirin regularly may de¬
velop changes in their liver tissue which produce abnormalities
in the blood tests that are used to measure liver function. For this
reason, some physicians are tending to substitute other
NSAID’s, which were developed primarily for use in other rheu-
matic disorders. Other, more generally known adverse effects

can result from treatment with aspirin, such as gastrointestinal
distress. Occasionally, gastrointestinal distress from taking aspi¬
rin can lead to an ulcer of the stomach wall. This can sometimes
be avoided by always taking the medication right after meals,
with a large glass of water, and using special preparations with
very adequate amounts of a buffering agent in the same tablet or
coated so that they will not dissolve until they pass through the
stomach. Most widely advertised over-the-counter preparations
are mainly aspirin. Some preparations, whose names suggest
they contain added buffers to the aspirin, do not have sufficient
buffering strength to make a difference. Other widely advertised
over-the-counter preparations that do not contain aspirin or any
other salicylate, usually contain acetominophen (e.g. Tylenol).
Acetominophen is less likely to bother the stomach, but has little
or none of the anti-inflammatory activity that calls for taking
aspirin or aspirin-like drugs in the first place. Aspirin can also
cause other common side effects, including impact on the ner¬
vous system. An early sign of this effect is a buzzing sound
(called tinnitus) heard by the patients. This harmless effect can
be eliminated by decreasing the dosage, and thus avoiding the
possibility of more serious side effects on the nervous sytem.
Older individuals who may lack the ability to hear this ‘early
warning sign’ should receive special care, and monitoring for
adverse effects, such as a change in personality, when they are
on an aspirin program. Aspirin also affects the ability for an
important factor in blood clotting, the platelets, to function nor¬
mally, and should be avoided when the effects of SLE or the use
of other drugs decrease the blood’s ability to clot properly,” Dr.
Kaplan continued. “Despite all these concerns, aspirin still re¬
mains a very inexpensive and potentially effective medication
for dealing with some forms of inflammation in SLE. A dose of
two aspirin, taken occasionally to alleviate a headache or a mi¬
nor pain, is still one of the best bargains in health care for most
people, including individuals with SLE.”
“Recently, some new types of salicylates, such as choline
magnesium salilcylate and salsalate, have been introduced into
medical practice. Could you comment on that?”
“These drugs are claimed to produce less adverse effects on

the stomach, and, because they stay in the blood stream longer,
fewer pills must be taken in order to maintain the anti-inflamma¬
tory level in the blood,” Dr. Kaplan said. “However, they are
much more expensive than aspirin, and they can be obtained
only by a prescription since the dosage must be carefully con¬
trolled. The level of this drug must not be allowed to build up to
a point where serious side effects on the nervous system and the
metabolism can occur.” After a moment. Dr. Kaplan said,
“The experience with these newer forms of salicylate is still
very limited in patients with SLE. Effects on metabolism with
high blood levels of salicylate are especially dangerous for chil¬
dren. People with SLE taking any salicylate regularly must be
extremely careful to keep this medication where children will
not inadvertently get it and possibly poison themselves.
The second group of NSAID includes a drug called in-
domethacin, which has been available for a number of years,
and two newer medications of somewhat similar structure, tolec-
tin and sulindac. The third group of NSAID’s now available
includes three relatively new medications, called ibuprofen,
fenoprofen calcium, and naproxen. Any of the drugs in these
two groups might be used for minimal or moderate inflammation
of the joints as manifestations of SLE. Individuals vary widely
as to which medication may successfully control this inflamma¬
tion and be well tolerated. Each medication must be taken regu¬
larly at a proper dosage in order to maintain the desired level in
the body and have the proper effect, and they are, of course,
never interchangeable. ’’
“How long must one take salicylates before they establish the
desired level in the body and have an anti-inflammatory effect?”
“NSAID’s can work fairly rapidly compared to some other
drugs. The patient may use the NSAID’s for 2 or 3 weeks before
experiencing the full benefit. Two of the medications, sulindac
and naproxen, normally stay longer in the body and, therefore,
require fewer daily dosages to have an anti-inflammatory effect.
All of these medications are relatively expensive, and this
should be a consideration in choosing which one to try in a given
situation.”
“Can these medications cause gastrointestinal problems?”

“As I mentioned earlier, all of these medications can cause
gastrointestinal problems.”
“Can other adverse effects occur?”
“Other adverse effects that can occur include mild dizziness
and blurring of vision with any of the drugs; indomethacin has a
particularly higher incidence of producing morning headaches,
or a dulling of the senses and forgetfulness. Using any of these
drugs has sometimes resulted in fluid retention, as well as the
common types of allergic reactions that can occur with any
medication. Actually, we have no extensive well-documented
experience with any of these drugs in large numbers of patients
with SLE, although they are used, with some success, in se¬
lected clinical situations with the rheumatic manifestations of
lupus.”
“What is the best source of information about the proper use
and precaution about all medications?”
“The best source of information about the proper use and
precaution about all medications, in my opinion, is the dispens¬
ing information published by the U.S. Pharmacopiae, which has
been using panels of experts to organize, thoughtfully, informa¬
tion about each drug for patients. ”
“What other medications are used in the treatment of SLE?”
“Hydroxychloroquine is an altogether different type of medi¬
cation which is widely used in the treatment of SLE. It is related
to a group of compounds first found to be useful in treating
malaria, and then discovered to have unique anti-inflammatory
properties of their own. While other members of this family of
drugs are occasionally used in treating SLE, hydroxychloroquine
is the most widely prescribed of these agents. It has been found
effective in controlling some of the inflammation and, in partic¬
ular, many of the skin manifestations of SLE.”
“What are some of the side effects of hydroxychloroquine?”
“Although it occurs rarely, one of the more serious adverse
effects of the anti-malarial drugs is the tendency of these medi¬
cations to accumulate in the pigmented tissues in the retina of
the eye. This is definitely related to the total dose of the medica¬
tion taken over a period of time, thus the recommended dosage
of this drug should not be exceeded. Deposition in the lens of

the eye may also occur, and an early sign of that problem is
when the individual taking the drug complains about seeing
halos about street lights or lamps. These disappear if the drug is
reduced or stopped, and is independent of the potential problem
of the drug accumulating in the retina. If a patient benefits from
this drug and continues to use it, we recommend a careful exam¬
ination of the eye, by an opthalmologist acquainted with the
drug’s toxicity, every 4 to 6 months. Other side effects include
gastrointestinal distress, skin rashes, and occasionally weakness
of the muscles or decreased hearing acuity. Again, most individ¬
uals taking any one of these medications, and using proper and
adequate dosages, do not experience any of the adverse effects.
Hydroxychloroquine can be very effective in selected problems
in lupus patients, but it does take effect slowly.”
“What do you mean by that?”
“Improvement seldom occurs before a month, and three to six
months may pass before the maximum benefit may be noted. ”
“Many lupus patients are taking various forms of cortisone,”
I said, “and many have experienced adverse effects that have
resulted from long-term regular usage. Are drugs available to
replace the cortisones?”
“After the cortisone and its actions were discovered, many
different forms of this drug were created in the laboratory, such
as prednisone, predisolone, triamcinalone, etc. These are gener¬
ally stronger than the original chemical, but all have the same
problems with respect to adverse effects. Physicians refer to all
these forms of cortisone as steroids or corticosteroids and these
forms of corticosteroids are among the most potent drugs known
to suppress inflammation.”
“Besides the suppression of inflammation, do the cortico¬
steroids have any other beneficial effects on the disease?”
“Some studies demonstrate that steroids may also have ef¬
fects on the cells of the immune system. This may be very
important since in lupus a disturbance in the regulation of the
immune system eventually results in the inappropriate inflamma¬
tory activity responsible for many of the signs and symptoms of
lupus. Because of this powerful anti-inflammatory effect.
steroids may be used in various manners in the management of

lupus.”
“Do creams that contain steroids succeed in controlling skin
rashes that may be part of lupus?”
“They are successful in controlling skin rashes of lupus in
addition to the ulcers that may appear in the nose. Adequate use
of the creams can often completely prevent the serious scarring
that once characterized the progression of this manifestation of
SLE.”
“Can prolonged usage of such creams damage the skin?”
“Prolonged use of some of the newer and more powerful
forms may, over a period of time, do injury to the skin. Patients
should remember to discuss the situation with their physicians,
therefore, when physicians require prolonged usage of this topi¬
cal medication. Some steroid preparation may be injected di¬
rectly into a joint, if the arthritis of SLE continues to be active in
spite of other measures. The concern with doing harm to the
patient with steroid therapy is not so much with its topical or
intraarticular use as it is when the medication is administered on
a regular basis over a long period of time. ’ ’
“What are cortisone compounds?”
“Cortisone compounds are hormones which are normally pro¬
duced in each of us by the adrenal gland every day. Most of the
time a fairly constant amount is produced each day, but, when
placed under stress, our bodies require increased amounts of
these materials to maintain the metabolism that supports the
blood pressure, maintains a normal balance of chemicals in the
blood, etc. A primary control for the amount of cortisone the
adrenal glands produce is another hormone called adrenocortico¬
tropic hormone (ACTH), produced by a small gland at the base
of the skull called the pituitary gland. One way to produce in¬
creased amounts of cortisone, therefore, is to administer in¬
creased amounts of ACTH by injection. This simply substitutes
for giving steroids, but has little or no particular advantage over
the more easily administered steroid pills. Cortisone is an im¬
portant part of the metabolic systems in our body, and has ef¬
fects on the stores of body sugar, protein, and fats, so as to help
maintain an adequate supply and balance of these nutrients, as
well as effects on the balance of chemicals in the blood which

are important in maintaining normal blood pressure and hydra¬
tion. Although many of these side effects are not dependent on
exactly the same actions as the anti-inflammatory effects of the
steroids, it has not been possible to isolate the anti-inflammatory
activity from the activity on the metabolic systems. In particular,
when an individual must take high doses of steroids in order to
control the inflammation of a disease like SLE, the dosage pro¬
duces an exaggerated effect on the various metabolic systems
with many consequences for the patient. Thus steroid use should
be thoroughly discussed by the patient and physician when re¬
quired to manage SLE.”
“In a letter to a friend, Flannery O’Connor wrote that after
she was put on steroids, her face became round like a water¬
melon. At one time my face, too, looked like the moon. What
causes the face of the patient to become round when taking
steroids?”
“The impact of steroids on the metabolic system may include
redistribution of the fatty stores of the body, causing the face to
become round. The steroids can also increase the blood sugar
above normal, increase appetite, cause some weakening of the
bony structures because of interference with calcium metabo¬
lism, increase the risk of developing infections, producing ca¬
taracts, etc. Many people, however, do take therapeutically ben¬
eficial amounts of steroids, and experience relatively few of
these many potential adverse effects.”
“Do individuals vary greatly in their ability to tolerate the
same dose of steroid medication? Do you think individuals can
accept these potential risks more easily if they understand the
benefits that are being sought and achieved with steroid therapy
for them? And still another question — is the general practi¬
tioner aware of the importance of the judicious use of these
drugs?”
“We teach physicians planning to use steroid therapy that
they should develop a clear list of problems that they are seeking
to improve so that after the treatment is started an objective
analysis of the success of the treatment can be made and com¬
pared against the risks of the treatment. The patient can only be
a cooperating partner if he or she can appreciate the benefits of

the treatment objectively as well as subjectively. This under¬
standing also helps to put the ways we have of measuring the
activity of a disease like SLE in perspective so that the patient
can share the appropriate concern or lack of concern about the
change in laboratory values that may occur. Thus, steroid
therapy must be gradually tapered once it has produced satisfac¬
tory results so that we can maintain the beneficial effects, while
trying to reduce the chance of adverse effects. As many know,
this is often a difficult as well as a delicate task. ”
“Are children affected by steroids in the same way as
adults?”
“Children face some additional problems, since steroids may
effect the rate of growth. If an individual is receiving steroids,
the normal potential of the adrenal gland to make cortisone, and
be stimulated by ACTH, is suppressed and dulled. This dove¬
tails with the other major reason why an individual who has
been receiving steroids for a prolonged period of time must re¬
duce the dosage gradually. Particularly with the lower doses of
steroids, a gradual reduction of dosage will permit the adrenal
gland to gradually regain its sensitivity to the ACTH, and its
normal controlling influences.”
“Is it safe for patients to take steroids over a long period of
time — many months or years?”
“We do know that one way to retain many of the beneficial
effects of steroids, and reduce some of the unwanted adverse
effects, is to provide the treatment over the briefest possible
period over the course of one or two days. Therefore, as long as
the therapeutic benefits can be maintained, the steroid medica¬
tion should be taken at one time in the morning, rather than
spaced out over the day, and taken only every other day (alter¬
nate-day therapy). Again, this should be done only with careful
and specific directions from the physician, and only if the use¬
fulness of the therapy is retained. Occasionally, a physician may
decide to eliminate the steroid therapy altogether after a very
prolonged period of excellent control of the disease. This also
requires an extremely close working and honest relationship be¬
tween physician and patient, since careful judgements must be
made about what to do with minor symptoms that may appear

not as manifestations of SLE, but as a result of reducing depend¬
ency on steroid therapy.”
“When should steroids be used?”
“Steroid therapy is the epitome of the double-edged sword
image of medical treatment, even when it is life-saving. It
should be used for those manifestations of lupus that must be
controlled and that cannot be treated adequately by some other
less potent means. Clinical researchers are trying to document
the circumstances when steroid therapy is most helpful and ap¬
propriate, and to develop newer compounds that will achieve the
anti-inflammatory effects, without the potential for the serious
adverse effects of the currently available steroids. ’ ’
“Are any other medications adopted for use in SLE, not be¬
cause of any potential to suppress inflammation directly, but
because of their ability to affect the cells of the immune sys¬
tems? You stressed earlier that a basic problem responsible for
producing the inflammation and injury to tissues and organs that
we call SLE is a disturbance in the proper functioning of the
immune system.”
“As yet, we do not understand all we need to know about the
factors producing this kind of disturbance although they are the
object of a good deal of current research,” Dr. Kaplan said.
“When drugs were developed to treat malignant diseases, they
were designed to injure cells fatally, with the hope that the
tumor cells would be more sensitive than the normal cells of the
body. Researchers soon noted that the cells of the immune sys¬
tem, the lymphocytes, were particularly susceptible to some of
these medications, and the ability of the immune system to func¬
tion was altered. When we observed that the function of the
immune system might be suppressed by these compounds, they
were tested in patients with very severe forms of disorders like
SLE, where the immune system appeared to be abnormal and
contributing to the disease process. In one specific situation,
namely, controlling the immune system after a kidney transplan¬
tation, these drugs have proven to be essential for a satisfactory
result.” Dr. Kaplan continued, “Over the years two medica¬
tions have been used with variable success in both patients with
severe SLE unresponsive to other treatment or those patients

requiring unacceptably high doses of steroids. One of these
drugs is azathioprine, and the other is cyclophosphamide. The
use of these drugs with SLE patients who have serious kidney
involvement remains one of the most discussed issues among
physicians with expertise in treating lupus. Some physicians feel
that these patients will tend to do at least as well by being on one
of these medications, and lower doses of steroids, rather than on
higher doses of steroids alone.”
“Do these drugs produce certain serious adverse effects, and,
if they do, are they the same adverse effects as the ones pro¬
duced by steroids?”
“They are not the same effects, thus we believe that the inci¬
dence and seriousness of the side effects from the treatment can
be reduced using this approach. Because these drugs, which are
described as cytotoxic (killers of cells), can affect the normal,
rapidly dividing cells in the bone marrow, the blood counts must
be carefully monitored. As is true with all medications, and
particularly with these drugs, the prescribing of drugs and the
proper monitoring of their use is a serious contractual arrange¬
ment between physician and patient. Not only does the patient
have the right to be well informed about his or her medication,
but the patient must also understand and be committed to the
necessary monitoring procedures so that the medication can be
administered as safely as possible.”
“How does a physician react when a patient rejects any of
these medications?”
“Just as the patient has the right to reject any medication, the
physician may not wish to prescribe a medication without a
commitment by the patient to adhere to an appropriate monitor¬
ing program. We are dealing with potent drugs. In addition to its
effects in the blood count, azathioprine sometimes produces
other adverse effects when it is first administered, including an
effect on the liver, or gastrointestinal distress. The dose may be
reduced if an individual has pre-existing liver disease, or is tak¬
ing a drug called allopurinal to reduce uric acid. In such cases,
the dosage of azathioprine must be very greatly reduced, and the
patient’s blood tests followed with great care. Cyclophospham-
ide, which some people feel may be preferable to azathioprine in

similar circumstances, must also be given with extreme care and
close monitoring. In addition to serious effects on the blood
count and occasional gastrointestinal distress, regular usage may
cause the hair to fall out, although this is generally reversible.
Another potential problem is the tendency to produce bladder
irritation; people tîng cyclophosphamide, with relatively nor¬
mal functioning of their kidneys, are encouraged to drink 10 to
12 extra glasses of water each day so that the irritating break¬
down products of cyclophosphamide are not allowed to concen¬
trate in the bladder. ”
“Does cyclophosphamide produce any long-term side effects,
in addition to these relatively immediate potential complica¬
tions?”
“Unfortunately, long-term complications are possible,” Dr.
Kaplan said. “These include scarring of the bladder, and steril¬
ity, which may not be reversible. Another concern with these
cytotoxic drugs are other effects on the genetic material of the
body. Although the delivery of normal babies has been recorded
among parents who were taking a drug like azathioprine, we are
concerned about the development in utero of a fetus conceived
and maturing while a parent was taking one of these cytotoxic
drugs. In addition, we have reason to believe that individuals
taking these medications may face an increased risk of develop¬
ing certain malignancies later in life. While this risk has not
been established for patients with SUE, information from other
types of patients raise this as, at least, a theoretical possibility
for the SEE patient receiving azathioprine or cyclophospham¬
ide.”
“When should these drugs be given to the lupus patient?”
“The recommendation is that these drugs be considered for
use in SEE only in the severest form of the disease, and in an
attempt to evade other unacceptable adverse effects from high
doses of steroids,” Dr. Kaplan said. “Advances in an under¬
standing of the metabolism of lymphocytes has recently led re¬
searchers to work towards the development of a new group of
cytotoxic agents that may manipulate the immune system in a
more specific manner than is possible with currently available
drugs. As knowledge of these drugs is developed in the investi¬

gational setting, we hope they will be looked at with regard to
the serious problem of SLE. In this conversation you have
touched upon a number of sensitive and sobering issues relating
to the treatment of SLE. I believe it is important, therefore, to
reiterate several general principles to take into account when
relating any of this material to any one individual case.”
“Unfortunately the lupus patient is often afraid to ask too
many questions because the symptoms appear silly and
confused.”
Dr. Kaplan smiled. “The only silly question is the one that
does not get asked. This atmosphere of trust and understanding
must be reciprocated, and the physician must feel confident that
the patient has aired his or her concerns and will follow out the
agreed-upon treatment and monitoring schedule. When discuss¬
ing the potential for adverse effects, we must keep in mind that
most of the time these distressing problems do not arise in the
management of an individual patient. Only fully informed con¬
sent and dialogue can achieve the collaboration between physi¬
cian and patient necessary for dealing with the complex nature
of SLE and its treatment. ’ ’
“The pharmaceutical profession has been very successful in
making new drugs in the past few decades. And when drugs are
around, doctors will prescribe them and patients will use them,”
I said. “Some doctors are concerned about the widespread use
of over-the-counter drugs. Can such self-dosage of a variety of
medications, many times unknown to the physician, cause se¬
rious problems?”
“You are quite right to raise the issue of drugs that exacerbate
true or bonafide lupus. Sulfa-type drugs are among those which
have been most clearly implicated. That is why, in dealing with
a urinary tract infection in anyone with lupus, one should and
can find equally effective antibiotic treatment using non-sulfa
antibiotics. Many other drugs, including diuretics and dyes
given for radiographic studies, have also been found, in isolated
circumstances, to exacerbate true lupus. However, even though
a drug such as penicillin has been implicated in this way, its use
in the patient with lupus may still be considered if the particular
infection is best treated by that particular drug. The potential for

any of a long list of drugs to exacerbate lupus on rare occasions
should, however, keep us very cautious about administering any
medication casually to any patient with lupus without specific
and important indications.
“Can any drug, given routinely, cause lupus?”
“Let’s distinguish between the situation we have just dis¬
cussed, where certain medications can exacerbate true or
bonafide lupus, and the different but interesting problems of
drugs producing an unusual complex type of adverse drug reac¬
tion that we refer to as drug-induced lupus syndromes. In drug-
induced lupus syndromes we recognize that some drugs, includ¬
ing some commonly used medications, may result in the patient
developing signs and symptoms we commonly associate with
active systemic lupus erythematosus. This unfortunate develop¬
ment is totally unrelated, as far as we know, to any potential for
that individual to develop true or bonafide lupus. In fact, in
some circumstances these drugs have been used, when indi¬
cated, in patients with true lupus, and did not appear to cause
any difficulties or worsen the problems of the lupus patients.
One of the first of these drugs to be noted to produce a “lupus¬
like” drug reaction was hydralazine, when it was being used in
fairly high doses for the treatment of hypertension. The studies
of the lupus-like reaction with this drug are fairly old, since the
higher dosages of hydralazine associated with producing the re¬
action are generally no longer used. The reports in the medical
literature indicate that, in addition to anti-nuclear antibodies,
some patients may be found to have anti-DNA antibodies, al¬
though this finding is controversial. Low complements are rare,
and it is difficult to evaluate the rare patients who were said to
develop some findings of renal disease. Clearly, the develop¬
ment of renal disease is extremely rare in any drug-induced
lupus syndromes. One of the most widely used drugs that may
produce the lupus-like drug reaction is procainamide, which is
used to help control abnormal heart rhythms. Patients receiving
procainamide regularly induce anti-nuclear antibodies forma¬
tion, even if they don’t get other signs and symptoms of a lupus¬
like reaction,” Dr. Kaplan continued. “In fact, if no clinical
problems appear, developing anti-nuclear antibodies is not con¬

sidered a sufficient reason to stop the medication when it is
needed. Such patients essentially never develop anti-DNA anti¬
bodies, low complement, or renal disease. They commonly de¬
velop joint symptoms and pleurisy, and do develop rashes, al¬
though with less frequency than in bonafide lupus. In both of
these situations the lupus-like drug reaction clears, generally
within weeks, once the offending drug is removed, and, as far as
we know, having such a drug reaction is unrelated to any sus¬
ceptibility for true lupus. Another widely prescribed drug, isoni-
azid, which is used in the treatment of tuberculosis, may also
induce the development of anti-nuclear antibodies and, rarely, a
lupus-like drug reaction which ceases after the drug is stopped.”
Dr. Kaplan paused. “We have an older literature also suggesting
that some effective, commonly used anti-convulsants, such as
dilantin, mesantoin, and tridione may induce a lupus-like drug
reaction; I have reviewed these reports and find them confusing
and a little anecdotal, based solely on retrospective observa¬
tions. These reports, however, should probably not alter the use
of these drugs with patients who have true lupus, when their use
is indicated for central nervous system problems. We have no
reason to believe they are at all harmful to the patient with true
lupus.”
“I have shown lupus-like symptoms after taking penicillin
and tetracycline. The symptoms included fever, joint pains, the
butterfly rash, and nausea. This was confusing to me because
these drugs were prescribed to control infections and avert an
exacerbation of lupus. ’’
“What you have raised here, is the possibility that certain
medications, even penicillin or tetracycline, may exacerbate
lupus,” Dr. Kaplan said, “and I must re-emphasize that this is
altogether different from the drug-induced lupus' syndrome we
have just been talking about. Even antibiotics as effective and
important as the one you have named rarely produce problems in
patients with lupus. Therefore, any such reaction to medication
in a patient with lupus should be noted by the patient and made
known to the physician. I also re-emphasize the importance of
using any medication judiciously and only for clearcut indica-
tions in the patient,” Dr. Kaplan said. “Remember, viral infec¬

tions, such as the common cold and uncomplicated flu, are unaf¬
fected by antibiotics and their casual use in these circumstances
adds no benefit and only creates the potential for a complication
from the drug itself. On the other hand, as you point out, infec¬
tions are a real problem for the lupus patient, and effective
antibiotics may be required to treat them. If any individual with
lupus is known to react poorly to any one antibiotic, we are
fortunate today to have an impressive array and menu of such
drugs to choose from in handling most forms of bacterial infec¬
tion, and this type of infection must be adequately treated.”
After a long pause. Dr. Kaplan said, “I don’t think any drug
‘causes’ lupus. Rather, some drugs exacerbate pre-existing true
lupus, and other drugs, generally different ones, can cause a
lupus-like reaction to the drug, a reaction unrelated, as far as we
know, to susceptibility to true lupus. Discontinuance of such a
drug results in complete clearing of all the signs and symptoms
of the syndrome.”
^For many yeas, aspirin was considered a folk medicine and even today, many
patients don’t take aspirin seriously. Aspirin’s activity is based on chemicals derived
from the willow and other plants used as medications since the time of Hippocrates two
thousand years ago. Through the centuries people have chewed willow bark to counter
the pain of childbirth and postpartum fever. And they have also used poplar bark,
another salicylate source to counter rheumatic pains. In 1853, a German chemist syn¬
thesized pure salicylic acid, the base chemical for salicylate. And in 1893, Hoffman
came up with acetylsalicylic acid, the aspirin we know today. In 1899, Bayer devised a
system to mass produce the chemical, which today is derived not from plants, but from
coal tar and petroleum products. The way aspirin works has not been well understood
although in 1971 Dr. John R. Vane and his colleagues at the Royal College of Surgeons
in Britain discovered that aspirin inhibits the synthesis of prostaglandins, a hormone-like
substance produced by cells throughout the body.
Ingested Antigens May Play a Role in the Pathogenesis ofSLE 111
Ingested Antigens may
Play a Role in the
Pathogenesis of SLE
''To see what everyone else has seen,

and think what no one else has thought.”
— ALBERT SZYENT-GEORGY
At a Board meeting of the Lupus Foundation of America, in

/\ Washington, Dr. Ronald Carr spoke of his research, an
1. Vinvestigation of ingested antigens that could play a role
in pathogenesis of systemic lupus erythematosus. Dr. Ronald
Carr is an Associate Professor, Department of Medicine at the
University of Colorado Medical School, and a member of the
Department of Medicine, National Jewish Hospital and Research
Center, Denver, Colorado. His major scientific interest is the
role of immune complexes in diseases and regulation of mucosal
immunity. (Mucosa is the term used to describe the tissue lining
the mouth, nose, respiratory tract, and other sites v/here the
inside of the body comes in contact with the outside environ¬
ment.)
Dr. Carr is a red-headed man in his early forties, soft-spoken
and relaxed, who likes talking about medical research with much
enthusiasm.
I asked him if the subject of his research had been studied
before. Dr. Carr was not aware of any other such studies. I
asked him what led him to start this research.
Dr. Carr answered that the idea came to him when he and his
colleagues found that sera from certain SLE patients contained
antibodies to BGG (Bovine Gamma Globulin) and BSA (Bovine
Serum Albumin), presumably as a consequence of the ingestion
of milk and beef.
I listened to Dr. Carr with strangely mixed feelings. I remem¬
bered my own difficulties with milk, and my aversion to beef.
When I eat beef or drink milk, I develop the same discomfort I
do when I stay out in the sun or take certain medication. I
recalled the time when I had active lupus and I was tested for an
intolerance to milk. The test showed that after taking lactose
sugar I had no elevation of my blood glucose, the normal sugar
of the blood. I tolerated a mixture of glucose and galactose
without stress. My doctor had explained to me that lactose could
not be taken up directly by the intestine. He said that it first had
to be broken down by an enzyme called lactase into two simple
sugars — glucose and galactose. These smaller molecules could
be absorbed more easily. Now I wondered if my intolerance to
milk was more complicated. My problem was not the same as
the one Dr. Carr was trying to define, but I was curious. I asked
him what makes one person react adversely to milk and beef,
and not another, but he could only answer with a small shrug of
his shoulders.
I asked Dr. Carr if adequate nutrition was vital to the lupus
patient.
“Adequate nutrition is vital,” Dr. Carr said. “It is vital not
only for people with an illness like SLE, but for everyone.” He
explained that his studies are not directed at nutrition, but at the
possibility that some of the abnormalities seen in SLE are a
result of an immunologic reaction to food antigens. That is, on
exposure to certain foods, patients with SLE may absorb food
material into their blood stream which will react with antibodies
directed against these foods. The resultant immune complexes
might then circulate, become trapped in certain tissues like the
skin or kidneys, and cause an inflammatory reaction. This, in
turn, could damageThe organ, and perhaps lead to a rash in the
skin or nephritis in the kidney. Lupus patients are known to have
more antibodies to certain milk proteins than most people. Stud¬
ies also have shown that related food antigens (in their studies,
bovine gamma globulin — BGG — and/or cow’s milk casein)
do enter the circulation, and, in some patients, researchers have
found BGG or casein, and specific antibodies to BGG or casein
in the blood, simultaneously, leading them to suspect that im¬
mune complexes of these foods can and do form. “However,”
Dr. Carr said, they have not yet demonstrated immune com¬
plexes containing food antigens in the kidneys or skin of lupus
patients.” Dr. Carr stressed that his interest in the possibility
that food contains immune complexes came about accidentally.
“We actually were studying DNA: anti-DNA complexes, by
looking for precipitates in an agar gel (much like Jello).” And
he said, “We found an extra line of precipitation when certain
sera were tested against each other. This line did not seem to
relate to either DNA antibody or DNA, and we decided to try
and figure out what it could be. After months of work, we
suddenly realized that one group of the sera which gave this line
had something in common. They were all derived from blood
which had been anti-coagulated (kept from clotting) when
drawn, and they had subsequently caused coagulation after the

addition of thrombin, a clotting protein from cow (bovine) se¬
rum. We tested sera which reacted with the first group against
thrombin and, sure enough, a precipitate formed in every case.
Since the thrombin was isolated from bovine serum, we then
tested these sera against bovine serum, and again got the precipi¬
tate. Finally, we discovered that the sera were reacting with
BGG, and they also reacted very well with milk and beef ex¬
tract, both of which contained BGG. Since these two foods are
staples in the diet, and thus are consumed daily in some form or
another, we got very excited and began our comprehensive study
of the possibility that food can play a role in immune complex
formation.
This fortuitous finding exhibits, in a way, one of our favorite
quotations about research, which is from Albert Szyent-Georgy,
“To see what everyone has seen, and think what no one else has
thought.”
For a number of years, we have known that people who have
an IgA deficiency (a decrease or lack of the main antibody found
in the digestive tract and other mucosal areas) have increased
levels of antibodies to milk proteins. (As mentioned earlier, mu¬
cosa lines the digestive tract, the bronchial tree, and other inter¬
nal areas of the body which come in contact with the environ¬
ment.) Of considerable interest is the fact that people with IgA
deficiency also have an increased frequency of auto-immune
diseases. We also know that IgA tends to inhibit absorption of
immunologically active food from the digestive tract. This infor¬
mation led to the suggestion that the higher incidence of autoim¬
munity in IgA-deficient people might be explained by the in¬
creased amount of absorbed food antigens (which might cross-
react with the individual’s own tissue components) stimulated an
auto-immune response. (A cross-reaction means that two differ¬
ent substances have certain similar features, and an antibody
against one will react with the other because of the similar fea¬
tures.) Since food is clearly loaded with animal or vegetable
tissues and tissue components, we felt that absorption of these
‘foreign’ materials might trigger an auto-immune response. Fur¬
thermore the prevalence of IgA deficiency is increased from the
general population frequency of about 1:700, to 1:25 in lupus.

Although this is a relatively small proportion of SLE patients
(4%), it may be a clue in the search for factors that are important
in the development of some cases of lupus.
Another very closely related area of Dr. Carr’s work stems
from a recent discovery in basic immunology. This discovery is
that certain T-lymphocytes (one of the cell types in the immune
system) play a major role in the regulation of antibody forma¬
tion. One subset of these T cells are called T suppressor cells
because they can turn down the immune response. Current evi¬
dence indicates that one of the basic problems in SLE is a defect
in the function of these T suppressor cells. Recently, Dr. Carr
and others have found that the normal immune response to food
is stimulation of the local production of IgA antibodies, and a
specific suppression of the systemic response of IgG (and IgM)
antibodies to the food substance, a suppression which often ap¬
pears to be due to T suppressor cells.
An exciting new development in this area is Dr. Carr’s find¬
ing that NZB/W mice (a strain of mice which develop a disease
very much like human SLE) fail to show this normal suppressive
sequence when fed BGG, and actually show an eight fold in¬
crease in antibody to BGG when subsequently immunized.
“This finding,’’ said Dr. Carr, “has potentially great signifi¬
cance in helping us to understand SLE. We already know that
foreign proteins which cross-react with self proteins, when in¬
jected can cause disease if an immune response occurs. For
example,’’ he said, “if foreign thyroglobulin (one of the
proteins of. the thyroid gland) is injected into rabbits, an auto¬
immune inflammation of the thyroid gland can develop, because
the rabbit makes antibodies to the foreign thyroglobulin which
results in the formation of cross-reacting autoantibodies. Oral
tolerance induction (the term used to denote the suppressive
sequence described above) might be a protective mechanism in
normal animals, which helps to prevent auto-immune phenom¬
ena analogous to the rabbit thyroiditis (thyroid inflammation)
phenomena triggered by food antigen exposure. The develop¬
ment of oral tolerance would help to prevent the animal from
mounting massive immune responses against such food anti-
gens, many of which would clearly be similar to many self

antigens. The failure of oral tolerance in NZB/W mice might
therefore lead to some of the autoimmune problems seen in these
animals. By inference, a similar failure in SLE could account for
the high levels of antibodies to BGG and casein which we have
found,” Dr. Carr continued.
“This failure might be contributing to the disease develop¬
ment, either by food antigen containing immune complexes, or
the development of autoantibodies secondary to the cross-react¬
ing food stimulus. Furthermore,” he said, “suppressor T cells
are apparently activated by exposure to immune complexes
which contain antibodies of specific classes, and the suppressor
cells which decrease the specific systemic immune response af¬
ter ingestion of food apparently come from the region of the
intestinal tract where IgA is the predominant antibody. One can
therefore concoct a vbry intriguing story with respect to IgA
deficiency, food reactivity, and autoimmune diseases like
SLE.”
Dr. Carr explained that in IgA deficient individuals, the sup¬
pressor cells which are normally activated in the region of the
intestine by immune complexes containing IgA antibodies (the
intestinal antibodies) and the food, are never triggered, because
there is little or no IgA. Thus, no suppression of the systemic
immune system occurs. In addition, absorption of the food into
the bloodstream occurs more rapidly because of the lack of IgA.
(Other workers have shown that IgA decreases absorption of
immunologically active food.) This combination of failure of
suppression and increased circulating antigen may lead to an
increased systemic immune response which could result in the
formation of damaging immune complexes and/or auto-antibo¬
dies.
Dr. Carr cautioned that this is purely a hypothesis. That is,
although it is based on observations of immune system function
and regulation, it is entirely speculative at the moment. Dr. Carr
and his colleagues are intensively examining various aspects of
this story, because it will help them understand the integration of
immune regulation in the different systems of the body, and it
may directly point at certain pathogenic factors in at least some
Ingested Antigens May Play a Role in the Pathogenesis of SLE 117
patients with SLE. Dr. Carr also pointed out that, as with many
things, the IgA story has two sides. Some patients with SLE and
other diseases have IgA deposits in their kidneys. “We are also
attempting to determine if these deposits contain food anti¬
gens,” Dr. Carr said. “In this case, rather than failing to pro¬
duce systemic suppression, the cell defects may actually result in
an increase in IgA antibody to food, and immune complexes
(containing the food in question and the specific IgA antibody)
may deposit, leading to tissue damage. We suspect such a mech¬
anism in some cases of a disease called Anaphylactoid-Purpura,
especially in children. In this disease, symptoms often include
nephritis, a rash, and digestive tract disturbances. IgA deposits,
which look like immune complex deposits, are often found in
the kidney and the skin, and we have found a very high preva¬
lence of antibodies to both casein and BGG, as well as circulat¬
ing antigen and immune complexes in the sera of these patients.
We are now working to show whether or not food antigens and
antibodies are in the immune deposits in their tissues.”
I told Dr. Carr that many lupus patients claim that they have a
lower concentration of some vitamins in their bodies than other
people, or lower vitamin activity. I asked Dr. Carr for a com¬
ment.
“The role of vitamin therapy in various diseases is a major
problem,” Dr. Carr said. He pointed out that in vitamin defi¬
ciency states vitamin therapy was the appropriate treatment. He
stressed that in response to a variety of diseases, ranging from
the common cold to SLE, vitamin therapy and/or hyper-vitamin
prophylaxis is being pushed by some individuals. “When and if
it is all sorted out,” he said, “I would not be surprised to find
that vitamins are beneficial in certain conditions which, as of
now, are not associated with vitamin deficiencies.”
Dr. Carr continued, “As to the use of vitamin therapy in
SLE, a number of lupus patients (and probably some physicians
as well), feel that taking vitamin supplements (sometimes in
large quantities) has resulted in a marked improvement in their
state of well being.” He said that he could not discount the
changes they describe, but pointed out that a number of factors
must be considered before everyone jumps on the “vitamin
bandwagon.” First, lupus is a disease which frequently has

spontaneous remissions, which may last for long periods, and
drug-induced remissions may last just as long in some individu¬
als. If a remission occurs during the time vitamin therapy is
being assessed by the patients, they will probably attribute their
getting better to the vitamins, which, in fact, may have abso¬
lutely nothing to do with the improvement. Secondly, some of
the manifestations of SLE which are an obvious problem to the
patient, like fatigue and the feeling of weakness, often have a
psychological component as well as the real physical problem.
Clearly if one does not feel “well”, one has a tendency to “self-
debilitate,” and this can be a major problem in any chronic
illness. If this psychological component is effected by an indi¬
vidual’s faith in vitamins, an increase in well-being may cer¬
tainly occur, and it may be attributed by the person to a
“biochemical” effect of the vitamins.
Dr. Carr continued, “A number of years ago, physicians
thought vitamin BI2, pantothenic acid, and vitamin E, might
have an effect on SLE, but careful studies have failed to support
these observations. One of the keys to scientific progress is the
examination of ‘impressions’ in a hard and coldly analytical
fashion. It is often amazing how incorrect even the most obvious
impressions can turn out to be!” After a few moments. Dr. Carr
said, “I will tell you a story that has nothing to do with lupus
but is worth describing. A central nervous system disease called
Kuru only occurs among natives in a New Guinea highland. It
occurred in natives who left and went to live in other places, but
it never occurred in missionaries or other foreign settlers, lead¬
ing to an assumption that Kuru was an inherited disease. How¬
ever, careful scientific studies revealed an incredible fact. The
disease is not inherited at all! It is an infection, caused by what
is now called a slow virus, a virus which, after transmission,
takes years to produce disease.” Dr. Carr smiled.
“But how does this explain why foreigners never get the in¬
fection? In the words of Sherlock Holmes, ‘Very simple, my
dear Watson.’ ” He explained that the disease appears to be
transmitted in only one way. Because of a tradition in that area
of New Guinea (based on the idea that by ingesting the brains of
people who died, some of their wisdom would be gained) the

natives ate and fed their children the brains and other organs of
people who died of Kuru. “In other words,” he said, “they
were cannibals! The foreign visitors, of course, would not par¬
ticipate in this tradition, and thus were never exposed, and be¬
cause the virus takes a long time to manifest itself in disease,
those who left as children but had been exposed, still developed
Kuru even years after they left New Guinea. With recent
changes in populations and institution of more modem thought,
cannibalism is slowly being eliminated, and the number of cases
of Kum has progressively decreased since 1960.”
Dr. Carr certainly made his point! I could see how important
it is either to confirm or refute impressions with sound objective
investigation before reaching a conclusion. But, as he pointed
out, some individuals swear by vitamin therapy, even though no
scientific evidence supports their impressions. Most physicians
feel, at least as of now, that vitamins should be used in people
who have vitamin deficiency diseases, but not as a shotgun
therapeutic approach to SLE. So much for vitamin therapy.
I asked Dr. Carr to elaborate about several of his studies of
SLE patients who are being given alternate day steroids. I
thought that such a regimen previously was felt to be relatively
ineffective in SLE, although presumably safer than daily therapy
because it would produce fewer side effects.
Dr. Carr explained that physicians have been interested in the
possibility that, at least in some patients with SLE, alternate day
steroids might be effective. The general feeling however, has
been that this is inadequate therapy for lupus. Researchers have
now found that in certain patients, whose dosage is followed by
frequent visits and laboratory testing, alternate day steroid
therapy can be effective. These studies are still very much in a
research stage, and the long-term effects of such a treatment
regimen are now being assessed. It cannot yet be advised as a
routine approach to treatment, but preliminary studies do look
promising. Eventually Dr. Carr hopes, carefully selected pa¬
tients with lupus can be treated in this way.
“Are you involved in other lupus research?” I asked.
“My colleagues and I are investigating the possibility of lupus

being infectious, although not infectious in the usual sense,” he
said. “Something transmissible may be involved. While study¬
ing DNA antibodies in SLE patients, we found a number of
normal individuals who have significant elevations of antibodies
to single-stranded DNA.” (DNA occurs in two forms, one in
which two strands are intertwined, so called double-stranded, or
native DNA; and another in which the strands are separated, so
called single-strand or denatured DNA.) Lupus patients can have
antibodies to either of these DNA types, but antibodies to single¬
strand DNA are much more common. Research showed that
most of the normals with elevated antibodies to single-strand
DNA were people who worked in laboratories studying SLE. In
fact, about one third of the people working in SLE labs have this
increase. Dr. Carr’s colleagues wondered if this was due to a
transmissible stimulus, and why it afflicted only one third of the
SLE lab workers, since they could not relate it to age, sex,
duration of working in the laboratory, or any of a number of
other factors. Studies done by a host of others in mice and, more
recently, in humans, reveal that certain genetic factors play a
major role in immune regulation, and also appear to play a role
in human diseases associated with the immune system. For ex¬
ample, over 90% of patients with ankylosing spondylitis, a rheu¬
matic disease, have a genetic factor called HLA-B27. Towards
the end of 1978, two groups, one at NIH and one at the Rocke¬
feller University in New York, found that in SLE, two genetic
antigens, one called DWR2 and another called DWR3, had a
combined incidence of 70-80%. Of special interest to him is the
fact that this combination occurs in almost one-third of the gen¬
eral population, the same proportion he found among laboratory
people who showed an increase in anti single-stranded DNA.
Their next step is to examine the genetic types of the laboratory
people, especially since another research team has recently
found that DWR3 appears to be associated with anti-DNA in
SLE and other diseases. If they find that the one third who are
reacting have a very high frequency of DWR2 and DWR3, that
will strongly support the concept that regulation of the ability to
form significantly elevated levels of antibodies to DNA might be
associated with these or closely related genetic factors. It might

also support the idea that, in humans, certain genetic factors
involved in the control of immune regulation play a major role
in the development of auto antibodies, and thus perhaps in the
onset of autoimmune diseases. If true, this hypothesis should
contribute to our understanding of the factors involved in the
development of SLE.
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Unravelling Some of the Mysteries of Lupus 123
Unravelling Some of The
Mysteries of Lupus
‘‘The lupus patient needs an imaginative

and understanding doctor and an affec¬
tionate spouse or friend.”
— DR. CHARLES STEINMAN
I have not had the pleasure of meeting Dr. Charles Steinman

in person, but I have heard him lecture in Boston and in New
York. Dr. Steinman is an Associate Professor of Medicine
at Mount Sinai School of Medicine of the City University of
New York, and Director of Rheumatology Research.
I called Dr. Steinman in New York and expressed my concern
that the present criteria for the diagnosis of systemic lupus
erythematosus are inadequate and outdated. I knew that he had
been working on this for a considerable length of time, and that
his findings could help in devising a more sensitive and accurate
test for lupus. I had read some of his papers on antibodies to
double-stranded DNA ( anti-ds DNA), in which he explained
that the distinction between the two forms of DNA, double- and
single-stranded, is important because antibodies to the former
appears to occur only in SLE patients, while antibody to single-
stranded DNA (anti-ss DNA) is found, not only in SLE, but also
in other diseases. I asked Dr. Steinman if he believes that detec¬
tion of anti-ds DNA in a patient was a good diagnostic indica¬
tion of SLE. And, if it is, why is this fact not widely recog¬
nized?
Dr. Steinman said: “This observation, which was made and
confirmed in a number of laboratories some time ago, seemed to
have gotten lost for awhile because some later investigators
unwittingly confused mixtures of ds-DNA and ss-DNA, thinking
it was pure ds-DNA. This led to a number of possibly erroneous
reports of ‘anti-ds DNA’ in diseases other than SLE. The task of
purifying ds-DNA, and of being sure it was free of ss-DNA, so
that the antibody that was detected by it was directed only to ds-
DNA, proved to be much more difficult than many anticipated.”
“What approach have you used to facilitate this task?” I
asked.
“Our approach was to use a synthetic variety of DNA (poly
dAT) which, unlike natural DNA, is made in such a way that,
because of basic biochemical considerations, it cannot be con¬
verted to ss-DNA under the conditions used for the antibody
test. Hence, its use appears to detect only anti-ds DNA and not
anti-ss DNA. I should also point out that other approaches to
this problem are available and, in general, they seem to lead to

similar conclusions. ’ ’
“What can you show by using this test?”
“By using this test, we are able to show that (1) antibody to
ds-DNA (or at least to dAT) does in fact occur only in SLE
patients, contrary to the reports I just described, and (2) anti-ds
DNA, at least in patients not yet receiving much prednisone
therapy, appears to correlate roughly in amount with one of the
currently available prognostic indicators of lupus nephritis
(which is the amount, and perhaps location, of immune com¬
plexes in the basement membrane of the glomerulus of the kid¬
ney, as determined by electron microscopy). In addition, the use
of dAT rather than natural DNA has given us an approach to
purifying anti-ds DNA which we hope will allow us to examine
the general mechanism of autoimmunity in more detail.”
“Will this or any other test you know of be helpful in diag¬
nosing all patients?”
Dr. Steinman answered that he knows of no substitute for an
acute physician. “Suspicion of SLE was obviously needed be¬
fore any specifically relevant tests could be done. Further¬
more,” he said, “rarely, if ever, is a test for anti-ds DNA
positive without the antinuclear antibody test also being posi¬
tive. Hence, since the latter is much more easily done, the anti-
ds DNA test probably is not a good test for initially screening
patients for lupus.” Dr. Steinman noted that its greatest diagnos¬
tic use was likely to be among patients known to have some sort
of collagen disease that requires more specific identification. He
emphasized that the findings of anti-ds DNA in such a patient
might be very useful diagnostically, since a positive antinuclear
antibody test may be found in a number of diseases other than
lupus. “However,” he said, “the diagnosis of SLE must still be
considered to rest primarily on clinical grounds, so even a highly
specific laboratory test must be interpreted in the clinical context
using good medical Judgment. ’ ’
Dr. Steinman continued, “The ideal diagnostic test for lupus
would be one that is invariably positive in patients who have the
disease, and invariably negative in those who do not. Very few,
if any, diseases in medicine have such tests. Those few that
come close generally are the ones in which we are able to iden¬
tify a basic abnormality (such as biochemical or genetic defect,
or an infecting micro-organism such as a virus) that is directly or
indirectly responsible for causing the symptoms we recognize as
the disease. Although much progress has been made in under¬
standing the cause(s) of lupus, we still have not clearly identi¬
fied it (them) at a sufficiently basic level to have such a test.
Another important consideration that is relevant here is the likely
possibility that the disease we call lupus today may ultimately
prove to be more than one disorder, with different (and possibly
related) causes. Here again, the greater our understanding of the
disease mechanism(s), the more likely we are to be able to dis¬
tinguish among similar but different diseases and the closer we
will be to having an ‘ideal’ diagnostic test.”
Dr. Steinman pointed out that once medical researchers un¬
derstand a disease at a sufficiently basic level, they may also be
able to treat or prevent it by directing their efforts at thwarting
the specific mechanism causing it. In this way, improved basic
understanding, more precise diagnosis, disease prevention, and
more specific, effective treatment tend to be very closely con¬
nected. “Incidentally, it is interesting to note that, historically,
the sequence does not always proceed from first understanding
the cause of a disease to the discovery of a treatment. For exam¬
ple, in diabetes mellitus, the recognition that patients had sugar
in the urine (which served as a fairly specific test for the disease)
came first, followed later by recognition that this was related to
a variety of more basic metabolic abnormalities, which led even¬
tually to the discovery of insulin for treatment.”
I asked if the criteria for the diagnosis of lupus will ever be
perfect.
“The use of diagnostic criteria in lupus is, first of all, the
result of our present state of ignorance about SLE,” Dr. Stein¬
man answered. “For example, if we knew of an ‘ideal’ test for
lupus, as I explained, we might not need such criteria.
Secondly, these criteria should probably be used only for inves¬
tigative purposes, because their intended function is to identify
patients whose diagnosis is unequivocal. In this way, investiga¬
tors studying lupus in different areas can be sure they are, in
fact, studying patients with the same disease. Prior to the defini¬
tion of these criteria, different investigators defined lupus some¬
what differently; so that observations regarding one such group
of patients were not necessarily relevant to another group of
lupus patients. Although we all recognize that the criteria have
many shortcomings, their use, perhaps in an updated form, is
critical for studies of lupus. However, they do not, in my view,
have any role in the diagnosis of an individual lupus patient,
where many other considerations are involved, and where we
hope to recognize patients at an earlier stage of the disease, or at
least have a high index of suspicion, even if we can’t be abso¬
lutely sure of the diagnosis. Here is where individual medical
judgment and experience are critical in suspecting the possibility
of lupus before it becomes so full blown that a computer could
make the diagnosis.”
“You have conducted a separate series of experiments to ex¬
plore the significance of DNA in the human circulation,” I said,
and I asked if he could explain this some more.
“Our present understanding of lupus nephritis is based
largely on the pioneering studies of Dr. Henry KunkeP and his
co-workers. This and subsequent work have led most of us to
believe that, in SLE patients, circulating immune complexes,
some of which contain DNA combined with anti-DNA, are de¬
posited in the kidneys, and there incite inflammation which may
result in renal failure. Because of this, we thought we should try
to find out the circumstances under which free DNA appears in
the human circulation. When we started, several years ago, a
great deal of work had already been done by a number of inves¬
tigators, so we had the benefit of their findings. One difficulty,
however, was an important disagreement in the literature having
to do with the very basic question of whether or not free DNA
was normally present in the circulation. Clearly, this had to be
looked into before we could explore the meaning of circulating
DNA in lupus patients.”
“How did you get around this confusion?” I asked.
“We had to deal with two major problems,” Dr. Steinman
said. “The first resulted from the discovery by Dr. John Davis^
and his co-workers that DNA was released during the clotting of
blood in the test tube. Therefore, in order to get a true picture of

what was going on in patients rather than in test tubes, we had to
avoid this artifact by using blood which was prevented from
clotting (the liquid portion of which is called plasma). The sec¬
ond difficulty was the sensitivity of the tests used, most of
which could detect only relatively large amounts of DNA in
serum (the liquid portion after the blood is clotted) or plasma. A
newly-reported technique seemed to hold promise for improving
the sensitivity, and, by modifying it, we were able to detect
DNA in plasma in amounts as small as 50 billionths of a gram
per ml. Using this and other methods, we then examined plasma
specimens from normal volunteers, to reexamine the question of
whether DNA in fact occurred in normal individuals, and found
that it did not. ’ ’
Dr. Steinman continued: “When we examined plasma from
lupus patients we found that most of them also had no DNA
circulating (confirming an earlier report by Dr. John Davis), a
result that raised some question about the role circulating DNA
might play in causing lupus nephritis. However, in the course of
these studies a few lupus patients did appear to have circulating
DNA and, as we subsequently found, these patients generally
had either of two manifestations of lupus, namely, central ner¬
vous system involvement, or severe inflammation of the blood
vessels (vasculitis).”
“Is this now a confirmed fact?” I asked.
Dr. Steinman said, “We have tried to confirm it by looking,
not only at isolated plasma specimens of patients with lupus who
had these manifestations of the disease, but also at multiple
specimens taken from individual patients over prolonged periods
of time. In this way. We were able to show that the appearance
of DNA was not an isolated event, but that it usually persisted
for a prolonged period of time, at least while active involvement
of these systems was present. Still,” Dr. Steinman said, “noth¬
ing is considered ‘confirmed’ until other investigators have been
able to reproduce the results. Since this has not yet been done,
the answer to your question is ‘no.’ ”
“Central nervous system involvement seems to be a common
problem in SLE, with psychiatric and organic central nervous
system dysfunction,” I said. “The clinical symptoms have been

described in several recent studies, but many aspects of the
problem remain nebulous. The symptoms of the patient with
CNS involvement are often unclear to the physician, and the
patient may be sent home with the wrong medication, wrong
diagnosis, or wrong prognosis.” I asked if his research will
facilitate the diagnosis of CNS involvement.
“This work could lead to a useful diagnostic test for CNS
lupus, but that still requires more work,” Dr. Steinman said,
and explained that another, and perhaps even more exciting
question, is whether the circulating DNA might provide a clue to
a viral or another infectious agent which could be an underlying
cause of the disease.
I mentioned that prior to my diagnosis of lupus, my physician
suspected that I had a chronic viral infection. I asked Dr. Stein¬
man if he saw a connection between chronic viral infections and
lupus.
“We know that lupus can mimic almost any disease,” Dr.
Steinman said. “Chronic viral infection has long been one of the
hypothesized causes of many of the connective tissue group of
diseases. In view of reports in the literature connecting a known
viral infection, namely chronic viral hepatitis, both with circu¬
lating viral DNA and also with another of the connective tissue
diseases, polyarteritis nodosa (which itself may be similar to the
vasculitis that sometimes occurs in SLE and which is associated
with circulating DNA), we thought we should examine the cir¬
culating DNA to determine whether it had the characteristics that
would identify it as human DNA or not. If it proved not to be
human, then it could be viral. We therefore developed and mod-
ifed existing methods that allowed us to purify very small
amounts of DNA found in the plasma of some SLE patients.
Because the amounts were so small, we used a technique called
‘nick translation’ to makeThe DNA radioactive without chang¬
ing the properties we wanted to study. Having done this, we
proceeded to analyze the DNA for the characteristics that would
identify it as human, and, in preliminary experiments, have
demonstrated that most of such DNA appears to be derived from
the patient with lupus (i.e., is human DNA) and hence is not of
viral origin. However, the possibility remains that a small pro¬

portion of this DNA could still be non-human and therefore of
viral or other microbial origin. This work is still in progress and,
of course, these conclusions are still tentative.”
I asked Dr. Steinman to tell me something about one of the
newer methods of treatment called plasmapheresis.
Dr. Steinman said, “This rationale for this treatment is that, if
SLE is caused by circulating immune complexes, we should try
to diminish the amount of such complexes in the circulation, a
result that can be achieved by this technique. Exactly how much
clinical benefit, if any, actually results from this procedure is
currently being investigated and therefore remains unclear. As
always, medicine remains largely an art, and the efficacy of
plasmaphoresis has yet to be established. Perhaps, in another
year or two, this sort of hard data will be available. ”
^Henry Kunkel, M.D., Abby Rockefeller Manze Professor, Rockefeller University,

Department of Immunology, New York, N.Y.
^John Staige Davis, IV M.D., Professor of Medicine, University of Virginia School
of Medicine, Division of Rheumatology, Charlottesville, Virginia 22901
The Kidneys and Other Aspects of SLE 131
The Kidneys and
Other Aspects of SLE
In a universe suddenly divested of illu¬

sions and lights man feels an alien, a
stranger.
— ALBERT CAMUS
I had a gratifying visit with Dr. Naomi Rothfield, Director,

Division of Rheumatic Diseases and Professor of Medicine at
the University of Connecticut Health Center in Farmington,
Connecticut. Dr. Rothfield came to the University of Connecti¬
cut Health Center after twelve years at New York University
Medical School, where she worked with many lupus patients.
There Dr. Rothfield laid the foundation for a study which
showed that the prognosis for black lupus patients was worse
than for whites.
I found Dr. Rothfield outgoing, charming, and determined.
Her face lit up when she explained advances in medical re¬
search. Dr. Rothfield and her associates are trying to study the
metabolism of the proteins of the complement system in patients
with lupus, in order to determine how they become deposited in
the kidney and skin, and lead to renal and skin disease. Dr.
Rothfield was the first to show that one of the proteins (proper¬
din) is present in the kidney and skin, and further studies are
under way to determine the significance of the presence of this
protein in lupus kidney and skin. “We hope that more can be
learned about how the kidney becomes inflamed, and therefore
how this inflammation can be stopped in the patient,” Dr. Roth-
field said. She carried out a study, while on sabbatical at the
Necker Hospital in Paris, to determine the clinical significance
of deposits in the skin of SUE patients who had nephritis. “We
were able to study a large group of SEE patients with renal
disease, who had skin biopsies and kidney biopsies taken at the
same time,” she said, “and found that the deposits were present
in the normal skin of SEE patients who had different forms of
nephritis, as well as in the skin of those without nephritis.”
They noted that the presence of one of the proteins of the com¬
plement system (Clq), in the skin occurred in patients who had
more extensive proliferation (inflammation) in the kidney, and
that the patients with this protein in their skin also had higher
levels of anti-DNA antibodies, lower serum levels of C3 and
C4, and more severe illness than the patients without this protein
in their skin. “Thus, we appear to have found a marker for
severe generalized SEE, which can be found in a biopsy of
normal skin using immunofluorescent technique,”. Dr. Rothfield
The Kidneys and Other Aspects of SLE 133
said. “We are now analyzing serial (multiple) biopsies, taken

over periods of disease activity and remission in 31 SLE pa¬
tients, and we are finding that the presence of the proteins, and
the number of proteins present in the skin, depends on the sero¬
logic and clinical evidence of activity in the patients at the time
the biopsy was taken. Patients who had multiple proteins in the
skin at the time of diagnosis when they were very sick were
rebiopsied after treatment, while in clinical remission. The sec¬
ond biopsies were either negative (no proteins present) or had
only one protein present, usually IgM.
I asked Dr. Rothfield if lupus is as prevalent in France as it is
in the United States.
“Nobody knows about the prevalence there,” Dr. Rothfield
said. “The majority of the lupus patients seen in Paris were
from the Mediterranean area: Spain, Portugal or Algeria. I was
very intrigued by this finding, and I would like to go back and
do a scientific survey of the incidence of lupus in the French-
bom versus the Mediterranean people.”
“You have also been to Russia,” I interjected.
“Yes,” smiled Dr. Rothfield. “At a formal medical banquet
in Moscow, I held up one t-shirt which said ‘Lupus Awareness’
in bright yellow colors. I carried a pile of such t-shirts around
this long banquet table which was loaded with vodka, cognac,
hors d’houvres, and lots of caviar. I put the t-shirt in front of Dr.
Nasonova, who is the head of rheumatology in the whole Soviet
Union. She could not believe it when I told her how lupus
patients in America have taken it upon themselves to spread
awareness of lupus, help one another, and raise funds for lupus
research. Dr. Nasonova and the people in her institute are doing
a large series of collaborative research projects in lupus, with the
people in the United States. Results from the collaboration are
now being published.” Dr. Rothfield paused. “It’s encouraging
to know that so much attention is given to lupus in Russia and in
other parts of the world,” she said.
“Patients and doctors are worried about necrosis of the bones,
caused by steroids when taken over a long period of time to keep
the lupus under control. The steroids have saved many lives, and
patients have to live with them and their side effects because no
Other drug of choice is available,” I said and asked if anything is

being done about that.
“We are trying,” Dr. Rothfield said, and she explained that
she and her colleagues are presently doing a computer analysis
of the course of the disease in 356 patients with lupus. “Most of
the patients have been followed for a long time,” she said, “and
our recent survival studies show a marked improvement in our
patients with SLE. Survival rates for two groups of cortico¬
steroid treated SLE patients have been compared using life-table
analysis. Group I consists of 209 lupus patients, studied in New
York City between 1957 and 1968; Group II consists of 156
SLE patients, studied in Connecticut between 1968 and 1976.
We have studied the role of corticosteroid treatment (predni¬
sone-cortisone) in the development of some side effects in long¬
term treated patients. Damage of the bone of the hip joint or
knee (aseptic necrosis) occurs in about 10% of lupus patients.
The relationship of corticosteroid therapy to the development of
aseptic necrosis (AN) was investigated in 365 patients with SLE.
Seventeen patients (4.7%) were identified as having AN. The
dosage of corticosteroids ingested during the initial period of
therapy in patients with AN was tabulated and compared with
that of 25 SLE control patients. A substantially greater dose of
corticosteroids was ingested in the first three months of therapy
for the patients with AN, than was ingested by the control SLE
group. Severity of disease and duration of therapy were not
found to correlate with AN. Total corticosteroid dose was virtu¬
ally identical in both groups. Thus, high initial corticosteroid
dosages in patients with SLE seem to be associated with the
development of AN,” Dr. Rothfield said, and she explained that
a percentage of patients in each group were followed closely.
The five-year survival rate was 70% for Group I, compared with
93% for Group IT The improved survival could not be explained
by differences in racial composition, incidence of CNS manifes¬
tations, or incidence of severe renal disease. The markedly im¬
proved survival may be due to several factors, including a gener¬
ally better understanding of the disease, and the recent use of
newer antibiotics. The management of the two groups was simi¬
lar, except that Group II patients’ conditions were managed not
The Kidneys and Some Other Aspects ofSLE 135
only on the basis of clinical evidence of disease activity, but also

on the basis of the serum complement (C3) level, and on the
basis of the level of antibody to native DNA. “These data sug¬
gest that the use of such serologic values to help manage patients
may lead to improved survival,” Dr. Rothfield said. “More¬
over, we are trying to identify those manifestations of the dis¬
ease which indicate poor survival. We have already shown that
patients with discoid lesions have a better survival than those
with lesions of systemic disease.”
After a pause. Dr. Rothfield continued, “We would like to
have funds for ongoing computer analysis. For this we would
need a full-time programmer, and a computer console in the lab,
hooked up to the Health Center computer. We would then be
able to put laboratory values and patients’ symptoms into the
computer at every clinic visit. Retrieval could be done at any
time. Our data are unique. They have been accumulated over a
long period of time and on a large number of patients. ”
While I was saying goodbye to Dr. Rothfield, she suddenly
remembered something. “We have a very sick patient,” she
said. “The woman is very depressed. Nothing will make her
smile. Let’s go and see if we can cheer her up.”
Until Dr. Rothfield gets her computer, she will carry the labo¬
ratory values of her patients in her mind, but she will always
carry their problems in her heart.
Henrietta Aladjem and Dr. Naomi Rothfield in Hartford, Conn.

Prostaglandin Offers Hope in Lupus 137
Prostaglandin Offers
Hope in Lupus
“Everything that makes men work and

get excited utilizes hoped’
— ALBERT CAMUS
O ne hot summer morning, I went to interview Dr. Robert

Zurier at the University of Connecticut School of Medi¬
cine where he was an Associate Professor of Medicine.
(Robert Zurier, M.D., currently holds the title of Professor and
Chairman of the Department of Rheumatology at the University
of Pennsylvania School of Medicine in Philadelphia.)
I asked Dr. Zurier to tell me something about his research. He
showed me an adult female “lupus” mouse (NZB/NZW fi hy¬
brid mouse), the offspring of a breeding between a New Zealand
black mouse and a New Zealand white mouse. It had a disease
which was remarkably similar to human lupus. In mice, as in
humans, abnormal functioning of the immune system appears to
be responsible for tissue damage and death. The effect of a
given therapeutic agent in the mouse model often is similar to
that seen in patients. Drugs used to treat human lupus are usu¬
ally studied intensively in the NZB/NZW mice. Dr. Zurier has
been treating the “lupus” mice with prostoglandin Ei (called
PGEi), a potent biological compound found in nearly every cell
of the body. He added, parenthetically, that the name prosta¬
glandin is a misnomer, chosen because these fatty acids were
first found in seminal fluid and were, therefore, thought to be
produced by the prostate gland. Scientists later found that the
compounds in semen are actually produced by the seminal vesi¬
cles. An effort was made to change their name to vesiglandins,
but to no avail because, by then, the inappropriate name had
become entrenched in the literature.
“At any rate, PGEi appears to help regulate cell function,”
Dr. Zurier said. He and his colleagues found that its effect on
mouse lupus was dramatic: 18 of 19 female mice treated with
PGEi, injected under the skin, were alive at 58 weeks of age,
whereas only two of 19 untreated control mice survived. He
went on to say that they now have similar data for male mice.
With PGEi, Dr. Zurier explained, the kidney function of the
mice remains normal, and microscopic examination reveals nor¬
mal kidney tissue. Untreated mice die of kidney failure, and the
kidneys are inflamed and scarred. Perhaps more importantly,
these studies showed that PGEi retards progression of disease.
Prostaglandin Ojfers Hope in Lupus 139
and prevents death when treatment is begun after the mice al¬
ready have moderately severe disease with kidney damage.
Such results are similar to what has been seen in human stud¬
ies. Researchers have recently developed an analog of prosta¬
glandin El, a similar but synthetic compound (made in the labo¬
ratories of The Upjohn Company) that is more resistant than
natural PGEi to breakdown in the body. Using the analog, they
have been able to prevent kidney damage with one-fiftieth of the
natural PGEi dose. The next step will be to test whether this
analog or a similar compound is effective when given by mouth.
Dr. Zurier said: “The prostaglandins are quite remarkable
compounds, and their use for a wide variety of disorders is just
beginning to be explored. They have already proved to be life¬
saving in some forms of neonatal heart disease, and their use in
inducing labor is well established.” Dr. Zurier continued, “The
prostaglandins also appear to be potentially helpful in treatment
of bronchial asthma and peptic ulcer disease, in regulation of
blood pressure, and in management of peripheral vascular dis¬
ease.” He explained that the prostaglandins are able to induce
inflammation as well as suppress it, and can increase or decrease
immune responses. These observations led scientists to the con¬
clusion that prostaglandins might be used therapeutically.
“However,“ he said, “whether they will prove clinically valu¬
able in treatment of diseases, such as SEE, characterized by
disordered immune responses and chronic inflammation, is not
entirely clear.” Dr. Zurier pointed out that several prostaglan¬
dins and prostaglandin-like compounds are made by the body,
and an appropriate balance of these is apparently necessary for
optimal regulation of cell function (including those cells which
take part in immune and inflammatory responses). A drug that
selectively inhibits one or another of the prostaglandins may
prove more useful clinically than a prostaglandin itself. “In ei¬
ther case,” he said, “these studies may help develop therapy
that does not have the adverse effects of steroids and the cyto¬
toxic drugs.”
Dr. Zurier emphasized that these experiments are only the
first steps down what will surely be a long and twisting path.
New Zealand Black and White mice from Dr. Yves Borel’s laboratory.
See Chapter 4.
This lupus mouse is on steroid

therapy. Its fur is rough and thin
and its body is bloated with fluid.
The Genetics of Lupus 141
The Genetics of Lupus
In a mans attachment to life there is

something stronger than all the ills in the
world.
— ALBERT CAMUS
The Myth of Sisyphus
Antigen-Antibody or
Antigen Antibody Immune Complex
+
ff
Figure 1. Immune Complex Formation
Excess Antibody Secretion

Antigen Excess Antibody Secretion
Antigen
Normal T-Cell Arm Over-Reactive B Cell YYYY
YYYY
Figure 4. Under-Reactive Suppressor T Cells Leading to Excess
Figure 3. Over-Reactive B Cells Leading to Excess Antibody Antibody Secretion
Secretion
These diagrams were given to me by the National Institute of Allergy and Infectious
Diseases at the National Institute of Health, Bethesda, Maryland, to help understand the
immune response (Figs. 1 to 6)
I n another conversation with Dr. Chester Alper, I told him

that the opportunity to participate in the endeavors of the
National Institute of Allergy and Infectious Diseases
(NIAID) as a member of the institute’s advisory council brought
me in contact with distinguished scientists working in the areas
relevant to SLE. I have become aware that medical genetics is
the fastest growing and perhaps the most commonly misunder¬
stood area of medicine. I also stressed that it may be the most
critical problem to the lupus patient. I asked him what is meant
by genetics.
Dr. Alper answered that genetics is the study of inherited
traits. The earliest genetic studies involved examining the inheri¬
tance of visible characteristics such as flower color in garden
peas or wing shape in fruit flies. An important early concept was
that inheritance of such traits occurs in two main forms, domi¬
nant and recessive. In traits that are inherited recessively, ex¬
pression only occurs if the individual has inherited the trait from
both parents, as, for example, blue eyes in humans. Brown eye
color, on the other hand, is expressed if the trait is inherited
from only one parent (or both, of course). Considerations such
as these gave rise to the concept of the gene as the hereditary
unit controlling visible traits. We now know that the hereditary
material in man is DNA or deoxyribonucleic acid. DNA con¬
tains four chemical compounds called nucleotides, arranged in a
precise sequence, and the DNA is organized into structures
called chromosomes. Humans possess 23 pairs of chromosomes,
one set from each parent, for a total of 46. Genes are strung out
in chromosomes in a specific order.
At the Institute, I heard a good deal about molecular biology.
I asked Dr. Alper if this related to genetics.
Dr. Alper assured me that the connection was a very close
one. He explained that the field of molecular biology was
founded some 25 or 30 years ago, as scientists working with
bacteria and certain viruses made enormous progress in our un¬
derstanding of how DNA directs the production of specific
proteins. Parts of DNA, researchers discovered, served as a tem¬
plate for the production of messenger RNA. RNA is similar to
DNA and consists of nucleotides that correspond precisely to
those in DNA. Thus, the nucleotide sequence of DNA could be

transcribed to a specific sequence in RNA. The messenger RNA
could then be used to direct the synthesis of a protein (the gene
product). It turned out that specific sequences of three nucleo¬
tides coded for specific amino acids and amino acids (some 20
of them) are what proteins are made of. This made clear how the
information in DNA was transcribed into RNA and then trans¬
lated into proteins. We now know that some of the DNA in man
does not code for proteins. Taking this into account, estimates
have been made that there are around half a million human
genes.
I questioned whether birth defects are caused by mistakes in
our genetic code and the way those mistakes occur.
Dr. Alper answered, “Some defects detected at birth are not
inherited, cerebral palsy, for example, or certain congenital
heart defects. Inherited disorders may or may not be detectable
at birth or even while the baby is still in the mother’s womb.
The first disease shown to be the result of a mistake in the DNA
coding for hemoglobin was sickle cell anemia, which affects
blacks almost exclusively and is associated with episodes of
severe abdominal and bone pain, severe anemia, infections, and
a shortened life span. Red blood cells from people with the
disease become markedly deformed when oxygen is extracted
from the blood, and this deformation leads to all the manifesta¬
tions of the disease. The deformed red cells plug small blood
vessels leading to local lack of oxygen, pain, and death of tis¬
sue, and to increased destruction of the red cells, leading to
anemia. The same deformation of the red cells on removal of
oxygen can be shown with solutions of pure hemoglobin (the red
protein that carries oxygen) from sickle cell patients. The differ¬
ence between normal and sickle hemoglobin consists of a single
amino acid difference in the 300 amino acid sequence of human
hemoglobin. This represents a change of one nucleotide in the
nearly 1000 that code for this protein. Sickle hemoglobin is
thought to have arisen by a spontaneous substitution of one
DNA nucleotide for another, called a mutation, and the gene is
believed to have spread because carriers (people with one nor¬
mal and one sickle hemoglobin gene, also called heterozygotes)
were better able to resist malaria than people with only normal
hemoglobin. Individuals with two sickle genes are much less
common than carriers, even in populations in which the gene is
common. One can detect carriers because some of their hemo¬
globin is normal, and some is sickle hemoglobin (the variation
can be distinguished chemically), but only those with two sickle
genes (only sickle hemoglobin present) get the severe disease.
Therefore, at the molecular level, expression is co-dominant
(normal and abnormal genes both expressed), but the disease is
recesssive. As with all recessive diseases, one quarter of the
children of two carriers will have the disease, one half will be
carriers, and one quarter will be normal.” Dr. Alper continued.
“Because some red cells in affected fetuses make sickle hemo¬
globin, diagnosis before birth can be accomplished by obtaining
small amounts of fetal blood from the placenta. Very recently,
methods have been developed for determining whether the un¬
born baby has sickle cell anemia by examining the fluid around
the baby. The DNA of fetal cells is tested for markers of the
sickle gene. Obtaining such fluid, amniocentesis, is a simple and
safe procedure, particularly today when ultrasound and other
techniques can be used to define precisely the position of the
fetus and placenta in the womb.
I asked Dr. Alper about the question of genetic screening.
He explained that this was usually applied to tests of the
baby’s blood or urine at or shortly after birth. A case in point is
the mandatory screening in Massachusetts for phenylketonuria.
This disease occurs once in about 50,000 Caucasian births. The
justification for screening is that, if unrecognized and untreated
early in life, the disease leads to mental retardation. A strict diet
can apparently help avoid this.
In order to tie some of these ideas to an understanding of
lupus, I asked about the connection between genetics and immu¬
nology.
Dr. Alper said with considerable conviction that one cannot
explain normal or abnormal immune responses without involv¬
ing genetics, and lupus clearly involves abnormal immune re¬
sponses. “We are just beginning to understand the ways in
which genes control immunologic responses, just as we have
only recently come to understand more fully how certain cells

interact to produce these responses,” Dr. Alper said. “Much of
this knowledge has come from study of animals, and details in
humans are not yet worked out.” Dr. Alper continued. “The
immune responses consist of either the production of specific
antibody to the inducing substance, the antigen, or the growth of
certain kinds of lymphocytes, some of which are able to interact
directly with antigen. Antibodies are protein molecules called
immunoglobulins. Part of these immunoglobulin molecules have
relatively constant structures, which allow them to interact with
certain cells of the body, including scavengers called phago¬
cytes, and other proteins in the blood such as the complement
system. By this means, the removal and/or killing of foreign
particles, such as microorganisms, is effected. Just as with hem¬
oglobin, the normal population contains some inherited variation
in the amino acid sequence of the constant regions of immuno¬
globulins. The antibody activity of immunoglobulin molecules,
that is the ability to combine with antigen, resides in a part of
the molecules where the structure is variable from molecule to
molecule. Despite this variability, structures common to antibo¬
dies may be directed against the same antigen. These common
structures are called idiotypes and are also genetically deter¬
mined. Thus, antibody molecules are under complex genetic
control we are only now beginning to understand. Whether or
not an animal will mount an immune response to specific anti¬
gens and the magnitude of that response are to some extent
under the control of genes in a chromosomal region called the
major histocompatibility complex (MHC). Genes in this region
code for cell surface structures that determine tissue graft accept¬
ance or rejection. These structures are detected by antibodies
produced by individuals of the same species. In man, these anti¬
gens are called HLA-A, B, C and D (for human leukocyte anti¬
gens) and appear to occur on all body cells except for red blood
cells. The antibodies are usually obtained from women who
have had many children. Since HLA markers vary greatly
among people, babies usually have HLA genes from their fa¬
thers not present on their mothers’ chromosomes.” Dr. Alper
paused. “During pregnancy, some of the babies’ cells leak into
the mother’s circulation, and these HLA antigens stimulate anti¬

body production. In the same region as HLA (the short arm of
chromosome number 6 in man) are genes coding for three com¬
plement proteins, C2, C4, and factor B. Other genes in this
region control cell-cell interactions during the immune response,
and produce proteins found on certain lymphocytes but not on
others. Lymphocytes, which may look similar under the micro¬
scope, are now known to differ enormously in function.” Dr.
Alper explained that lymphocytes which produce anitbodies are
derived from the bone marrow and are called B-cells. Other
lymphocytes are derived from the thymus (the thymus is a gland
in the neck that is largest during early childhood) and are called
T-cells. These T cells play a profound part in modulating anti¬
body production, either as helper or suppressor T cells, and by
producing molecules that serve as signals modifying other cells
involved in the immune response. Such cells are other lympho¬
cytes and macrophages (one kind of phagocyte essential in the
presenting of antigen to lymphocytes). Some of these signals
carry MHC products and idiotypes as found on antibody molec¬
ules. Other T-cells, called cytotoxic lymphocytes, can kill cells
which are foreign. “Very recently,” he said, “special kinds of
antibodies have been produced which react with suppressor but
not helper T cells and vice versa. They can be used to determine
the number of each kind of T lymphocyte in the blood of pa¬
tients.
My response to all of that was that it sounded very intricate,
and complicated, but I needed help in relating these things to
lupus. First of all, I could understand why lupus was thought to
be a disease with altered immune response. I also knew about all
the antibodies that appear in the blood of lupus patients: antibo¬
dies against their own body cells and constituents such as nu¬
cleic acids. I also was aware that these antibodies are often
found in combination with antigens as immune complexes and
that, in severe lupus, complement levels in serum may be low.
But I asked what evidence suggests that lupus is a genetically
determined disease.
Dr. Alper answered that the evidence is largely circumstan¬
tial. Lupus is clearly not inherited in the straightforward way
that eye color or blood groups or hemoglobin structure are inher¬

ited. The incidence of lupus, or some of the laboratory abnor¬
malities that occur in lupus appears to be increased in family
members of lupus patients. “More convincing is the recent dem¬
onstration that one of the HLA genes (Dw2) is present in a
significantly higher percentage of patients with lupus than
among healthy people,” Dr. Alper said. “This might make
lupus similar to a number of other diseases with significant HLA
associations, such as juvenile onset insulin-dependent diabetes
mellitus, multiple sclerosis, and rheumatoid arthritis. The causes
of these diseases are no better known than the cause of lupus,
but all have been thought to involve unusual responses to viral
infections. The HLA associations may be the result of specific
HLA genes being “stuck” to abnormal immune response genes
in a phenomenon called linkage disequilibrium. In linkage dise¬
quilibrium, two genes are inherited together more often than
expected by chance. One reason for this is that the genes are so
close to one another on the chromosome that they are less af¬
fected by the normal scrambling process of crossing over of
chromosomes at the time of generation of sperm and egg. In this
sense, the HLA type found with increased frequency in lupus
patients is a marker for the abnormal hypothetical immune re¬
sponse gene. In the same way, the increased incidence of lupus
in patients with C2 deficiency and C4 deficiency (two compo¬
nents of the complement system) may be explained by these
deficiency genes being in linkage disequilibrium with similar
abnormal immune response genes.” After another pause Dr.
Alper said, “To carry the analogy even further, studies of juve¬
nile diabetes in genetically identical twins has revealed that
probably no more than 20% of genetically susceptible persons
come down with the disease. This is called partial penetrance
and probably applies to lupus as well. It implies that, although
one must be genetically susceptible to have a disease like lupus,
the actual triggering event in the disease is some environmental
factor, such as a viral infection. To carry the analogy further, a
very recent discovery has been that among multiple sclerosis
patients, a profound shift in the proportions of helper to suppres-
sor T-cells occurs prior to a clinical relapse. It is obviously

worthwhile to look for the same phenomenon in lupus patients.”
Since I had been hearing so much recently about recombinant
DNA and genetic engineering, in possible bold new approaches
to genetic disorders, I could not refrain from asking about them
as a means of preventing lupus.
Dr. Alper smiled and suggested we discuss these things over
another cup of coffee — in about five years.
“This chapter demystifies science of its pretentious claims
that only the highly trained experts can follow what transpires in
medicine today. The delight of revealing for once to the layman
what the scientists are discovering about the human body is
great! I can’t claim to understand all the ins and outs of the
concepts that you have tried to explain, but I certainly come
away with a sense of excitement and a deep desire to look fur¬
ther into the thrilling mysteries about myself and my body. I
must confess, however, I got exasperated with the medical lan¬
guage.”
Dr. Alper’s smile broadened. “It can’t hurt anybody to learn
how to understand and use some of the scientific jargon,” he
said. “Besides, lupus has always congregated under an awk¬
ward barrage of medical terminology.”
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Dogs as Well as People Suffer From Lupus (Part One) 151
Dogs As Well As People
Suffer From Lupus
(Part One)
Ce chien parloit tres - apropos.

Son raisonnement pouvoit estre
Fort bon dans la bouche d’ un
Maistre;
Mais n’eslant que d' un simple
chien,
On trouva qu’il ne valoit rien.
— JEAN DE LA FONTAINE*
^Fables de Jean De La Fontaine; Jean Landru, Editeur; Chaminix, Mont Blanc.

T 1 he remarkable research of Dr. Robert S. Schwartz with

his lupus dogs is known all over the world. I wanted to
learn more about these dogs, and when I telephoned Dr.
Schwartz and asked him to tell me about them, he invited me to
come see for myself.
Dr. Schwartz is Professor of Medicine at Tufts University
Medical School, and Director of Cancer Research, Chief of
Hematology, New England Medical Center. Dr. Schwartz is just
as friendly in person as he sounds over the telephone. He told
me that once he came across a lupus patient with every single
symptom of the disease — a female white poodle. Dr. Robert
M. Lewis^ from Angell Memorial Hospital in Boston was puz¬
zled by the dog’s symptoms, and had brought her to Dr.
Schwartz’s attention. Together they made a diagnosis of lupus.
Since they diagnosed that first dog. Dr. Schwartz and Dr.
Lewis have seen many more dogs with lupus, and have found
that the canine lupus erythematosus is strikingly similar to
human systemic lupus erythematosus. It includes positive lupus
erythematosus cell tests, antibodies to nuclear antigens, purpura,
polyarthritis, and so on. The disease usually affects young
female dogs, and often terminates in renal failure. No particular
breed seems to have a predilection for developing canine SEE;
all could develop the disease. The doctors have treated German
shepherds, French poodles, Laborador retrievers, mongrel pup¬
pies, and others.
Dr. Schwartz explained that the dogs provide an opportunity
to study the etiology (cause) and pathogenesis (origin) of sys¬
temic lupus erythematosus, in a large non-human species. Blood
samples from the dogs are taken at monthly intervals. The serum
is analyzed for antibodies to nuclear antigens, using the LE cell
tests, the fluorescent ANA test, and a radioactive assay for na¬
tive and denatured DNA.
These dogs help the scientists follow genetic and environmen¬
tal factors related to SEE. Dr. Schwartz and his associates are
working on several problems: 1) is SEE a genetically transmit-
table disease; 2) do viruses initiate the development of SEE; and
3) is SEE communicable through infection?
Dogs as Well as People Suffer From Lupus 153
To determine if lupus is contagious, they have injected infant

mice with extracts of tissue from dogs with lupus. These mice
have developed antinuclear and anti-DNA antibodies. They pos¬
tulate that a virus is involved, and it is transmitted from one
animal to another in the extract. Based on the results, they are
now pursuing similar work with human patients. They hope to
uncover evidence in them of a similar lupus-associated virus.
I asked Dr. Schwartz if this could lead to a vaccine.
“Perhaps,” Dr. Schwartz smiled.
Then Dr. Robert Lewis entered the room. I asked him what
made him suspect that the white poodle had lupus. “When the
dog was brought to my attention,” Dr. Lewis said, “she had a
severe case of hemolytic anemia. She also had idiopathic throm¬
bocytopenic purpura. The simultaneous combination of bleeding
and severe anemia in a dog was very unusual. In humans, it’s
known as Evans Syndrome, a condition associated with systemic
lupus erythematosus. Shortly, the white poodle began to pass
protein in the urine. This is an indication of glomerulonephritis.
The occurrence of all three abnormalities was highly unusual.”
“I took a liking to the poodle,” Dr. Lewis said, “and I
wanted to help her, but I couldn’t do it alone. I needed the
assistance of a blood specialist. So, I called to consult Dr.
Schwartz and told him about the multiple problems of my dog.
T think your dog has lupus,’ Dr. Schwartz said, and half an hour
later he came to examine the dog himself. The poodle died on
Christmas Eve in 1962. I performed an autopsy the same eve¬
ning, to determine if the pathology of the dog’s lesion was simi¬
lar to the human disease. It was equivalent in every way to
human lupus.”
“After the dog died, we looked for other dogs with lupus.
One we found is a black poodle by the name of Eifi. This dog is
still alive and we have some of her puppies. ”
The following day, I went to the Harvard University Animal
Research Center in Southborough, Massachusetts. This is where
the lupus dogs are housed. The Center is a large, modem build¬
ing surrounded by 170 acres of lush meadows and a variety of
trees and rhododendrons. The units where the dogs live have
fenced-in playgrounds, and every corner is sparkling clean.
I found Miss Brushwin, the dogs’ nurse, bleeding a dog for

testing. Miss Brushwin spends two days a week bleeding, test¬
ing, and caring for twenty-seven sick dogs. In the past she cared
for 130 dogs, but the number was reduced because of lack of
funds. Today the Center has only nineteen females and eight
males. Four generations of dogs have been bred. However, be¬
cause fertility was not good, only two litters have been bom in
the past two years.
Miss Brushwin explained that most of the sick dogs had
weight loss, retention of fluids, fever, and arthritis. They also
had liver, thymus and renal involvement. She pointed to a lively
German shepherd named Kasper, saying that he was a very im¬
portant dog.
“Kasper was delivered by caesarean section and raised in a
germ-free colony in Ohio,” she said. Kapser was shipped by
plane to Boston, where he was checked for lupus. At the time,
all tests on Kasper were negative. Now the dog shares an enclo¬
sure with a shepherd that has lupus. “If Kasper’s tests should
become positive,” Miss Brushwin said, “this would indicate
that lupus might be communicable through infection.” I glanced
at Kasper’s companion. The shepherd was lying in a comer,
almost motionless. Miss Brushwin followed my gaze. “The
shepherd never touches Kasper or plays with him,” she said. “I
seldom see her stretch.”
In another enclosure, several lively poodles were barking and
jumping all over the place. “Fifi’s puppies,” Miss Bmshwin’s
face brightened in a smile. “They don’t have lupus,” she said.
“They only have a predisposition to the disease, and physicians
are searching for the triggering factors.”
We took a few lupus dogs outdoors to have their picture
taken. A scrawny black poodle ambled by my side, sniffing the
air. I sat on a large stone that made a convenient seat. The
poodle sat next to me on the grass. She nosed the fresh grass and
gazed at me dolefully. I had read^ that when an animal is sick, it
seeks a particular type of weed for itself, and this weed is better
medicine than any that the doctors will prescribe for it. The dog
looked very skinny and weary in the bright sunshine. “It’s a
dog’s life, even for people,” I whispered to the dog. I had a
Dogs as Well as People Suffer From Lupus 155
sense that the dog understood my words. When the time came to
leave, I shook the dog’s paw. I could not help feeling sad. I had
known lupus long enough not to wish it on any living creature.
Photograph by Martha Aladjem Climo

Nurse Mary Brashwin, Henrietta Aladjem and dog with lupus-like disease.
The offspring of these two dogs with a positive A.N. A. developed S.L.E.
^Robert M. Lewis, O.V.M., currently holds the position of Chairman of the Depart¬
ment of Pathology at New York State College of Veterinarian Medicine in Ithaca, New
York.
^Letters of Nikolai Gogol, selected and edited by Carl R. Proffer; University of
Michigan, 1967, p. 147.
Dr. Robert Lewis with one of Fifi’s offspring.

Update on the Lupus Dogs 157
Update On The
Lupus Dogs
(Part Two)
‘‘Systemic Lupus Erythematosus is a dif¬

ficult name to pronounce, but it is even
more difficult to live with/’
— Marjorie Gordon, a patient*
*Marjorie Gordon was the first President of the Lupus Erythematosus Foundation of
Massachusetts.
M y visits to Dr. Schwartz’s lupus dog colony were made

several years ago. Recently, I called Dr. Schwartz to
ask him if he found any new developments. Dr.
Schwartz suggested that I talk with Dr. Fred Quimby,^ who was
helping him with the research on lupus in dogs.
Like Dr. Robert Lewis, Dr. Quimby is a veterinarian and an
immunologist. When he first started this work in 1974, he had
been associated with Dr. Lewis for one year.
“As you recall,” Dr. Quimby said, “the dog colony was
originally developed to study, among other things, whether sys¬
temic lupus can be inherited. Our most recent findings indicate
that the disease could be genetically transmissible. But we
know, from looking at the way these animals develop the dis¬
ease, that the mechanism of inheritance is extremely complex
and at the present time still unpredictable.” He explained that
the incidence of clinical SLE was greater in animals with posi¬
tive ANA and LE cell tests, than in the progeny of dogs with
SLE. This implies that, if the disease is inherited, parents who
do not have clinically active disease may play a role in the
development of the disease in their offspring.
The same results were demonstrated also in New Zealand
black mice.
Another interesting phenomenon is that other, non-SLE, auto¬
immune diseases frequently develop in the offspring of parents
with SLE. This implies that the tendency to develop any autoim¬
mune disease is inherited by a mechanism separate from that
which dictates the precise disease. Dr. Quimby believes that
multiple genes must be involved in the production of SLE in
both dogs and humans.
Scientists have also observed that most dogs who have devel¬
oped autoimmune disease have a defect in lymphocyte function.
In these animals, the production of antibody is abnormally high.
Dr. Quimby notes that this is also seen in both humans and mice
with lupus.
“Are you pursuing the latent virus theory?” I asked.
Update on the Lupus Dogs (Part Two) 159
“Yes, we are,” Dr. Quimby said. “Our interest in the subject

was stimulated by a test conducted in our own lab. In this test
we examined lymphocytes from both humans and dogs with
SLE. To our amazement, the lymphocytes taken from patients
with lupus had on their surface a substance similar to that found
in certain viruses. Lymphocytes from normal people and dogs
did not contain such a substance. In addition, tissues collected
from cadavers of dogs with either SLE or another non-autoim-
mune disease were examined using an entirely different method,
and were found to contain large amounts of viral protein.”
“Though you found a viral protein, how do you know that a
virus caused the disease?” I asked.
“At present, we don’t know,” Dr. Quimby answered. “One
possible way to clarify this issue would be to recover a virus
from dogs with lupus, and show that this virus will cause lupus
in a normal dog.”
After a moment. Dr. Quimby said: “We have documentation
that, in certain instances, microbes found in the environment
may infect an individual, and that individual will subsequently
develop an autoimmune disease. A strep throat may lead to
rheumatic heart disease. This occurs when the patient makes
antibodies against the streptococcus. These antibodies fail to
recognize the difference between streptococcus and heart mus¬
cle. So, in that particular instance, the patient’s body is making
an immune attack against an infectious agent and, at the same
time, making an attack against his or her own body. A certain
number of people who contract the virus responsible for infec¬
tious mononucleosis apparently also develop positive ANA. In
dogs, and in some humans, bacterial infections may lead to the
formation of circulating immune complexes which are subse¬
quently deposited in the kidneys. This renal lesion would mimic
lupus nephritis.
“The latent virus theory, however, is completely different,”
he said. “In this theory, the infectious agent may well be part of
the individual’s body from birth. The virus is not found in the
environment, but, rather, transferred from the parents to their
offspring through genetic mechanisms.”
Dr. Quimby showed me a few slides of lupus dogs. One slide

was of a Shetland sheep dog called Lady. Lady had various
systemic manifestations including central nervous system in¬
volvement (CNS) with personality changes. Three months be¬
fore Dr. Quimby saw this dog, she was extremely friendly, and
would often jump and cuddle up in a stranger’s lap. Then, over a
period of several months. Lady became extremely shy and
would often run to axomer and shake when anyone approached
her. The dog became withdrawn and began experiencing mild
seizures. She also developed a temporary hearing and visual
impairment.
Until recently, no confirmed cases were known of canine
lupus with central nervous system involvement; but scientists
now know that it exists. Even more recently, they have seen
dogs who have developed the classic butterfly rash. These dogs
develop the rash if they are exposed to the sun. Researchers
have observed this in Shetland sheep dogs with clinical and
serological evidence of systemic lupus erythematosus. “Once
you let these dogs roam in the sunshine, they develop a rash and
also hair loss,” Dr. Quimby said. He observed that the dog’s
rashes get better if they are kept indoors.
Another slide was of a Shetland dog with discoid lupus. The
dog had a lesion under its right eye. Dr. Quimby commented
that the Shetland sheep dog appears to be a breed at risk for both
SLE and discoid lupus. Also, some Shetlands with discoid lupus
have subsequently developed systemic disease.
Interestingly, studies of dogs admitted to Angell Memorial
Animal Hospital with SLE indicate that 90% of the female cases
occurred in non-spayed females, although the total clinical pop¬
ulation of female dogs includes 50% spayed dogs. Dr. Quimby
said this may indicate that ovarectomy may have some protec¬
tive effect on the development of the disease in dogs. Literature
indicating a similar effect in humans is scant.
Dr. Quimby has come across several dogs in which the major
symptom was fatigue. Eurther observation of these animals un¬
covered a wide range of other symptoms, including dogs with
simple muscular weakness, and others with profound depres-
sion. Dr. Quimby and his colleagues identified at least three

factors which may contribute to fatigue in dogs with SLE.
One, which has also been described in humans, is anemia.
Many dogs with SLE are diagnosed initially with hemolytic
anemia. The deficiency of circulating red cells leads to poor
oxygenation of skeletal muscle, resulting in fatigue.
Another factor involves malnutrition. Dr. Quimby has seen
several SLE dogs who have stopped eating. This led to malnutri¬
tion and, thus, to fatigue. Dr. Quimby explained that some dogs
may stop eating because they develop ulcers in their mouths and
along their intestinal tracts. Some dogs have had ulcerative col¬
itis; rectal bleeding is common in these animals. In other in¬
stances, dogs have stopped eating with no evidence of ulcera¬
tion. Some of these animals undergo a behavioral change that
influences their eating habits. Some of Dr. Quimby’s dogs who
have stopped eating, began eating again if their standard diet
was modified. Dr. Quimby explained that sometimes these dogs
need a little coaching and tempting to get started again.”
Along these same lines. Dr. Quimby has observed dogs with a
loss of appetite because the lack of normal secretions from their
salivary glands has led to a dry mouth and extensive dental
cavities. The incidence of cavities in dogs normally is extremely
low, unless some condition like this occurs. These dogs, with
lupus and a reduction in salivary flow, might have a problem
called Sjogren’s syndrome.
A third factor which contributes to fatigue in a few dogs with
SLE is polymyositis, inflammation of skeletal muscle. In dogs
with this disease any movement elicits pain. Dr. Quimby also
showed me a slide made from biopsies taken from a lupus dog
who has developed thyroiditis. This animal had an immune
mediated inflammation of the thyroid gland. In addition. Dr.
Quimby said that the lack of thyroxine produced severe depres¬
sion in the dog. “Speaking of fatigue,” Dr. Quimby said, “this
dog was like a rug on the floor; he could not move.” Once Dr.
Quimby realized what was the matter with the dog, he gave him
Synthyroid (a synthetic thyroxine) and the dog became active
again.
Dr. Quimby postulated that the most important factor contrib¬

uting to fatigue in dogs was inflammation of the joints. Similar
to rheumatoid arthritis, this is the most common site of inflam¬
mation in dogs with SLE; 50% of lupus dogs have it. Using a
slide showing the inflammation in a dog’s joint capsule, Dr.
Quimby pointed out how much it looked like the inflammation
in both the thyroid gland and muscle. He explained that inflam¬
mation processes in all organs are virtually the same.
Approximately 5% of dogs with SLE have thrombocytopenia
(a deficiency of platelets). Dr. Quimby explained that these dogs
bruise very easily. He showed me another slide of a dog they
had examined. During the examination, they palpitated the
dog’s abdomen to see if they could detect an enlarged spleen.
Where they pressed the belly, the animal developed bruises.
“This has taught us to be more gentle when we examine dogs
with SLE,” Dr. Quimby said.
I asked Dr. Quimby why fertility was low at the dogs’ colony.
Dr. Quimby said, “In our dog colony we have observed two
phenomena that may account for that. First, lupus dogs that have
not been inbred display a certain incidence of spontaneous abor¬
tion and stillborn deliveries. I have noticed from breeding rec¬
ords of our Shetland sheep dogs that the average litter size ap¬
pears abnormally low in families that have SLE. In our inbred
colony we have observed major problems in reproduction. Many
females remain unresponsive for years. When we studied this
problem, we realized that many of these dogs had abnormalities
in estrogen and progesterone production. These abnormalities
will prevent estrus in female dogs, and also prevent proper im¬
plantation of the embryo in the uterus, leading to early abortion.
In addition, several female dogs had Sjogren’s syndrome, a con¬
dition we discussed earlier. These dogs have extremely dry
mucus membranes, including those of the vagina. This leads to
inflammation and may make intercourse more uncomfortable. In
my opinion,” Dr. Quimby said, “the abnormalities in progest¬
erone secretion observed in some of these dogs certainly contrib¬
ute to decreased sexual responsiveness. I say this because I feel
if the canine estrus cycle is interrupted, sexual drive is also
interrupted.”
Dr. Quimby did not know whether the same phenomenon

aplies to women. He pointed out that one male dog in the lupus
colony developed an immune-mediated inflammation of the
testes, and became sterile. He also mentioned that some male
dogs with thrombocytopenia develop bleeding from the penis,
because of hemorrhaging in the urinary bladder.
On my way home I reflected upon the long talk I had with Dr.
Quimby, and I hoped that more research with these dogs would
provide further understanding of human lupus.
^Dr. Fred Quimby is now Director of Laboratory Animal Resources, Cornell Uni¬
versity School of Medicine, Ithaca, New York.
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Pulse Therapy 165
Pulse Therapy
Extreme remedies are appropriate for ex¬

treme maladies.
— HIPPOCRATES
I welcomed the opportunity to meet with Dr. Edgar Cathcart

and to learn from him about the exciting new method of
treating lupus nephritis called Pulse Therapy.
Dr. Edgar Cathcart is a Professor of Medicine, Boston Uni¬
versity School of Medicine, and Chief of the Arthritis Gerontol¬
ogy Center, Bedford Veterans Hospital, Bedford, Massachu¬
setts. Dr. Cathcart is a tall, fine looking man in his late forties,
with an easy, precise manner of speaking, and a natural gift for
the English language. Dr. Cathcart was kind enough to come to
my house, to explain to me the pulse treatment and the new
concepts in management of lupus nephritis. Dr. Cathcart
stressed that before one can understand rational management of
the renal lesion, or make statements about its prognosis, one
must first determine exactly which of several types is at hand.
He noted that in recent years researchers have learned that, for
prognostic purposes, patients with active lupus nephritis can be
separated into at least three categories: mild (focal) proliferative
glomerulonephritis, severe (diffuse) proliferative glomerulone¬
phritis, and membranous glomerulonephropathy. Medicine, Dr.
Cathcart believes, appears to be entering a new era, in which
therapeutic intervention in patients with SEE may prevent some
or all of the steps leading to the disposition of immune com¬
plexes in renal tissues. One of Dr. Cathcart’s consuming inter¬
ests today is the way coritsone and its derivatives can be used to
best advantage.
Dr. Cathcart pointed out that Boston University Medical Cen¬
ter is probably best known for research on a very rare and often
fatal disease called amyloidosis. His interest in systemic lupus
erythematosus began when a fourteen-year-old boy was referred
to him at University Hospital with a kidney biopsy, demonstrat¬
ing diffuse proliferative glomerulonephritis and a moderate in¬
terstitial lesion. All signs pointed to a rapid downhill course, and
he decided to try a form of steroid therapy that had brought some
favorable results in the management of kidney transplant rejec¬
tion — an intravenous Pulse of methylprednisone. (The intersti¬
tial lesion in lupus nephritis is characterized by changes similar
to those seen in acutely rejecting kidney transplants.) Dr. Cath¬
cart explained that the pulse was given as a 1 gm. bolus on each
Pulse Therapy 167
of three consecutive days, after which low-dose therapy (less

than 40 mg/day) would be withheld as long as ethically possible
in order to assess the effects of pulse therapy.
He explained that the first few days and weeks after the pulse
was marked by fluctuations in serum creatinine levels and pro¬
teinuria. Low-dose prednisone was begun two weeks after the
pulse. After four weeks, serum C3 levels and DNA binding had
returned to normal, as had other vital measurements. In other
words, the boy’s renal function at that time was back to normal.
It continued so until 18 months later, when he was readmitted to
the hospital with evidence of renewed immune complex renal
disease. Another pulse was administered, and renal function
again rapidly improved. Then, months after the second pulse,
serum creatinine levels, and urinary protein excretion, were
within normal limits. The patient is now being maintained on
5mg/day of prednisone.
I thought Dr. Cathcart’s story was very exciting and hopeful,
and I asked him if he has treated any other lupus patients with
pulse therapy.
“We have,” Dr. Cathcart said, “and, because of the favor¬
able response with the initial patient, six others have been tried.
The total study group of seven has survived, symptom-free, for
periods ranging from two to three years,” Dr. Cathcart said.
“All the patients are doing very well, and I hope they will
continue to do well for many years.”
“This treatment has been used by physicians in the United
States and in other parts of the world. And similar beneficial
results have been reported.” Dr. Cathcart emphasized that these
were preliminary, uncontrolled findings in a handful of patients,
and one would want more data before forming definite conclu¬
sions. “This was a chance discovery, but it may lead to new
avenues of research in the field of lupus,” Dr. Cathcart said,
and he stressed that ten clinics from different parts of the United
States are now cooperating in this research. These clinics are
being funded by the National Institute of Arthritis Metabolic and
Digestive Diseases, to test new drugs in rheumatic diseases. A
protocol has just been developed to test, in a double blind fash-
ion, whether pulse therapy is as good or better than the more

conventional modes of therapy for lupus nephritis.
Dr. Cathcart emphasized that, ten years ago, the prognosis of
SLE with renal involvement was not as hopeful as it is today. He
explained that much of the prognostic improvement represents
advances in diagnosis rather than therapy or basic etiologic un¬
derstanding. He explained that lupus nephritis still accounts for
about half the deaths'that occur in SLE, and he pointed out that
more and more mild cases of SLE are being recognized, includ¬
ing many with mild kidney involvement that might have been
missed in an earlier period.
Before Dr. Cathcart left my house, he expressed hope that in
the next few years significant advances will be achieved in ef¬
forts to manage lupus nephritis.
Of NIAID-NIH, In Search of a Cure for Lupus 169
Of NIAID-NIH,
In Search of a
Cure for Lupus
The family doctor, the private in our

great army, should be carefully nurtured
by the schools and carefully guarded by
the public.
— SIR WILLIAM OSLER, M.D.
Acquanimitas
T 1 he National Institute of Allergy and Infectious Diseases at

the National Institute of Health in Bethesda, Maryland con¬
ducts and supports research designed to contribute to a
better understanding of the causes of allergic, immunologic, and
infectious diseases, and to the development of improved meth¬
ods for prevention, diagnosis, and treatment of these illnesses.
At a meeting of the Institute’s National Advisory Allergy and
Infectious Diseases Council, I had the opportunity to talk with
Dr. Sheldon G. Cohen, Director of the Immunology, Allergic,
and Infectious Diseases program at the Institute.
Dr. Cohen is a charming, scholarly-looking man in his fifties,
soft-spoken, with a sense of humor. The walls of his office are
hung with watercolors and sketches, the works of artists from
many countries. Some are the work of Dr. Cohen’s talented
patients, and some are his own sketches.
Dr. Cohen is doing missionary work by trying to make the
efforts and achievements of the National Institute of Allergy and
Infectious Diseases more public, more visible. As one of his co¬
workers said, “he is a leader, and knows just about everybody
who does medical research in the areas where we have interest
and responsibility.” Dr. Cohen’s efforts thus complement those
of Dr. Richard M. Krause, NIAID Director, who has labored to
acquaint both physicians and the public with Institute programs
aimed at improving the outlook for patients with immunologic,
as well as allergic and infectious diseases.
Dr. Cohen explained that the National Institute of Arthritis,
Diabetes, Digestive and Kidney Diseases (NIADDK), has been
assigned chief responsibility for the study of systemic lupus
erythematosus as a disease entity. At the NIADDK, Drs. John
Decker, Chief of the Arthritis and Rheumatism Branch and NI¬
ADDK’s Clinical Director, and Alfred Steinberg, Senior Investi¬
gator, Arthritis and Rheumatism Branch, are conducting import¬
ant studies in that Institute’s Intramural Research Program at the
NIH Clinical Center. Also, Dr. Lawrence E. Shulman, as the
NIADDK’s Associate Director for Arthritis, Bone and Skin Dis¬
eases, is responsible for the administration of a large Extramural
Program, supporting research studies on SLE at universities and
medical centers throughout the country.
OfNIAID-NlH, In Search of a Cure for Lupus 171
“However,” Dr. Cohen said, “because research data points

to immunologic mechanisms and inflammatory sequelae in the
pathogensis of many manifestations of lupus, the interests and
activities of the Program for which I have responsibility at NI-
ADDK’s involve a variety of studies, all of which can relate to
diagnosis, treatment, and prevention of this autoimmune disor¬
der. Our ultimate objective, of course, is to place in the hands of
the practicing physician the tools and information necessary for
early detection and successful management of the patient af¬
fected by SLE. However, this cannot be fully accomplished until
we develop, through in-depth research, a complete understand¬
ing of the basic biology of the immune system in health and
disease. To reach this goal, we also must establish the influence
of individual genetic factors, viral infection, and their interac¬
tions on the cell involved, in and by the immune response. We
are very much interested in lupus research,” Dr. Cohen added in
a reflective tone. “The immune mechanisms in lupus are so
clearly demonstrable that understanding this disease will provide
important information for other disorders that also may be re¬
lated to autoimmune dysfunction. Thus, we recognize the need
to remain alert to the rapid and exciting developments coming
out of current research in such basic sciences as immunology,
microbiology, pharmacology, biochemistry, and genetics, and to
identify and seize upon opportunities where pertinent new
knowledge can be applied expeditiously to clinical areas.
Among the allergic and immunologic diseases, SLE certainly
merits and receives our priority attention.”
I asked Dr. Cohen if NIAID concentrates on research related
to kidney involvement.
Dr. Cohen said: “Since the pathologic mechanisms responsi¬
ble for the development of SLE arise from a disordered regula¬
tion of the immune system, many organs and tissues of the body
influenced by immune processes are affected. Thus, kidney,
skin, brain, lung, joints, heart, and blood vessels can all be
involved in a harmful way when they become targets of the
products of antigen-antibody reactions, immune complexes, and
chemical mediators of inflammation. In physiologic states of
health, immune complexes otherwise would be effectively dis-
posed of during the course of normal body functions of immu¬

nity. To the immunopathologist and clinical immunologist who
understand kidney structure and function, as well as mechanisms
of immune disorders, study of this organ can provide one of
many opportunities, and a particularly good model, to unravel
and define the workings of SLE inducing factors and agents of
disease. While NIAID does not ‘concentrate’ on research related
to kidney disease per se, many of our supported studies and
programmatic concerns do involve the affected kidney along
with other organs and tissues in this multisystem disorder. At the
NIH Clinical Center, patients with SLE are being studied by
both Dr. Alfred Steinberg at NIADDK and Dr. Anthony Fauci at
NIAID. While the types of patients handled by each are differ¬
ent, protocols under Dr. Fauci’s direction do provide for the
study and management of those with kidney involvement. Addi¬
tionally, our interests and activities at NIAID include the direc¬
tion and coordination of a nationwide kidney transplantation his¬
tocompatibility study pertinent to problems of those patients
with loss of kidney function due to SLE pathologic effects.”
“Does lupus return in lupus patients who have had kidney
transplants?”
“We simply do not have enough data to be able to answer this
question definitively,” Dr. Cohen said. “To the best of our
knowledge, only 20-30 SLE patients with kidney dysfunctions
resulting from the SLE process have received organ transplants.
While results could be considered encouraging, treatment of
SLE has always been continued after completion of transplanta¬
tion surgery. Immunosuppressive drugs are required, simulta¬
neously, to both prevent rejection of the transplanted kidney,
and to control or minimize the pathologic inflammatory effects
of the SLE mechanism. While a transplanted kidney provides a
new organ for effective urinary function, it also furnishes a new
target, as long as the SLE immunologically related process ex¬
ists. Bear in mind that the previously damaged and singularly
malfunctioning kidney was the result of the disorder, not the
primary cause. Experience thus far suggests that the chance of
recurrence in a transplanted kidney is minimal, but the possibil¬
ity exists, especially if the drug treatment is discontinued.”
OfNIAID-NIH, In Search of a Cure for Lupus 173
“Respiratory infections are still a major cause of acute illness

in lupus,” I said. “Such infections may be a real threat to life.
I’ve learned NIAID is trying to identify the many viruses that
cause respiratory illnesses, and develop anti-viral compounds
and vaccines, two of the more promising therapeutic ap¬
proaches. Can lupus patients be vaccinated, and do they then
develop immunity?” I asked.
Dr. Cohen answered that, in all probability, the reason for
unusual susceptibility to infection in SLE patients is not the
disease itself, but rather the effects of the drugs that can control
the disease process by suppressing the causative process which,
of course, involves immune function. While treated patients
may be more susceptible to infection than normal individuals,
untreated patients with SLE are not. SLE patients can expect to
achieve the same degree of protective immunity as do normal
individuals, as a result of immunizations with killed vaccines,
(e.g., influenza and typhoid vaccines) or with inactivated micro¬
bial products (e.g., diptheria and tetanus toxoids). However,
because SLE patients under active drug treatment are likely to be
in a state of control only when coincidentally immunosup-
pressed, they should not receive live attenuated vaccines (e.g.,
measles, mumps, smallpox). In the case of poliomyelitis, the
Salk vaccine, because it is a killed virus immunizing agent, can
be given. Dr. Cohen explained that the Sabin oral vaccine con¬
tains attenuated live viruses, and therefore presents potential
dangers to SLE patients who are receiving immunosuppressive
agents. Another important point to be clarified by investigation
is whether the immunizing stimulus of a vaccine can activate a
broad spectrum of immune responses that includes undesired
SLE autoantibodies as well as the intended protective antimicro¬
bial antibodies.
I had asked Dr. Elizabeth Cole if insect bites can trigger
lupus, but I wanted to find out more about this subject and asked
Dr. Cohen the same question.
Dr. Cohen explained that the venoms of stinging insects and
the saliva of biting insects contain foreign materials that in every
way can act as any antigenic (antibody-inducing) agent injected
into the body. For the very same reasons that foreign biological
products (e.g., horse serum antitoxins) or therapeutic agents

(e.g., penicillin) can produce a spectrum of immune and sensi¬
tizing effects, so can and do these insect-derived materials. He
stressed that the allergic state resulting from insect exposure
varies, depending upon an individual’s ability to respond to such
stimuli. Accordingly, insect stings and bites can vary from local¬
ized inflammatory swellings, itching, and hives, to serious gen¬
eralized reactions, with shock and collapse. Since a variety of
causative agents may trigger the immune response leading to
production of antibodies involved in the lupus process, a constit¬
uent of insect venom or saliva, theoretically, might trigger or
exacerbate an SLE mechanism. However, we do not now have
research evidence that might suggest this to be the case. Addi¬
tionally, he said, one important differentiating point must be
kept in mind. In the case of virus infections, chemicals, and the
ultraviolet rays of sunlight, as presumptive causative agents of
SLE, the patient is subject to repetitious if not continuous expo¬
sure. Unless insect stings and bites are multiple and repetitious,
the incident is only single and limited, and the amount of anti¬
genic (antibody-inducing) material received is small and quickly
dissipated so that the stimulus is over in a very short period of time.
Dr. Cohen explained that allergy to drugs and untoward ef¬
fects of therapeutic agents are of special interest and concern to
NIAID. He mentioned that Dr. Robert Goldstein, Chief of the
Allergy and clinical Immunology Branch of the Immunology
Allergic and Immunologic Diseases Program, is heading up a
major project to design and encourage research in this area.
“Since all reactions to drugs are not based on the same mecha¬
nism,” Dr. Cohen said, “we need to understand and define
those which result from immune processes, hypersensitivity phe¬
nomena, abnormalities of handling and disposition of metabolic
products, or lowered tolerance to normal pharmacologic effects.
Perhaps one day we will be able to translate such information
into a classification that will help the practicing physician pre¬
scribe appropriate drugs against the background of a patient’s
individual physiologic makeup, as well as the disease for which
drug treatment is indicated. Additionally, for a variety of proto¬
type drugs, understanding the biochemical, immunologic, phar-
Of NIAID-NIH, In Search of a Cure for Lupus 175
macologic, and pathophysiologic mechanisms and their interac¬

tions in the body, will enable us to give the pharmaceutical
chemist the information needed to design specific drugs for spe¬
cific diseases — perhaps without untoward side effects.”
“Nutrition is a popular field,” I said. “It sparks an interest in
lupus patients. Some become fanatical about it.” I asked if any
studies had been conducted on the effects of nutrition on the
immune system.
“Whether certain foods contain and actually supply critical
types of chemical components to serve as antigens (antibody-
inducing substances) or have the potential for reacting with SLE
antibodies in the body is just not known at this time,” Dr.
Cohen said. “The manner in which some foods do cause classi¬
cal allergic type reactions (e.g., asthma, gastrointestinal upsets,
hives) appears to stem from a different immunologic mechanism
than from that responsible for manifestations of SLE. Thus, the
selection and omission of specific foods in the diet of the SLE
patient, on the basis of what we know now, depends upon clini¬
cal experience and impressions. However, that hypersensitivity
to foods, just as to drugs, may be responsible for SLE mecha¬
nisms and SLE-like disorders, cannot be ruled out, and investi¬
gation in this particular area is being encouraged.”
Dr. Cohen continued, “As for the possible exact role of nutri¬
tion in the immune response, NIAID does indeed have both
interest and meaningful activity. We are fortunate to have as a
staff member of the Institute’s Microbiology and Infectious Dis¬
eases Program, Dr. Robert Edelman as Chief of its Clinical
Trials and Epidemiology Branch. As a medical officer in the
U.S. Army, Dr. Edelman was responsible for conducting critical
and in-depth studies on the relationship of malnutrition to immu¬
nity in Thailand. Upon his return to the U.S., and taking up
duties at NIAID, he has actively expanded his scope of interest
in the problem. In addition to his own activities on nutrition and
immune responses. Dr. Edelman serves as the NIAID represent¬
ative to a trans-NIH Committee on Nutrition and Digestive Dis¬
eases. NIH is keenly aware that many questions remain
unanswered concerning the relationship of diet to health and
chronic disease, and that rewarding investigation could come
about through the interaction of various basic science disciplines

and clinical medical specialties. We are in agreement with a
recent report of the National Commission on Digestive Diseases
that points to the important place of immunology along with
biochemistry, molecular biology, and genetics in such an en¬
deavor.”
Many lupus patients are plagued by minor or more serious
fungal diseases. I asked if NIAID supported research aimed at
prevention and treatment of fungal diseases.
Dr. Cohen explained that the nature of fungal infections in the
SLE patient can, to a very large extent, be explained by the
same factors we discussed in my earlier question on the role of
infection in general. “The serious fungus infections are those
attributed to opportunistic invading agents. That is, fungal or¬
ganisms that are not successful in tissue invasion, as a result of
the action of normal immune defenses, seize the opportunity to
gain a foothold in humans when the physiologic processes that
result in good health are impaired. Thus, the pathology of SLE
in itself is not responsible for serious fungus infections, but,
rather, these infections follow the relative immuno-suppression
that results from the corticosteroid drugs and other therapeutic
agents harmful to white blood cells, but necessary in the treat¬
ment of this disorder.” Dr. Cohen paused briefly. “Because
NIAID’s research mission is targeted upon infection, as well as
allergic and immunologic processes, fungus micro-organisms
and their role in the pathogenesis of disease receive this Insti¬
tute’s attention. We recognize that more investigators need to be
trained in this area if fungal diseases are to get the amount of
research direction and attention they merit. Accordingly, the
Institute wants to support and expand this endeavor. Our own
NIAID Laboratory of Clinical Investigation is at the fore of
fungus disease research, because of the expertise and unique
activities of Dr. John E. Bennett, Chief of the Clinical Mycol¬
ogy Section.”
“Inflammation poses a serious problem in lupus,” I said. “It
affects almost every patient, and it contributes to our debilitating
fatigue.” I asked if NIAID is supporting research dealing with
inflammatory disorders.
OfNIAlD-NIH, In Search of a Cure for Lupus 111
“Inflammation can be a by-product of the body’s immune

defense against challenging agents, and therefore a prominent
feature of many immunologic disorders,” Dr. Cohen said.
“Symptoms of discomfort and fatiguability probably result from
inflammatory events, rather than serving as inciting factors,”
Dr. Cohen paused. “In hypersensitivity disorders two especial
types of inflammation contribute to the patients’ illnesses and
symptom patterns. One is an immediate reaction, after exposure
to causative agents in such allergic diseases as asthma, hay fe¬
ver, and hives. The mediators of allergic inflammation can thus
cause swellings of the skin and membranes of the nose, mucous
formation, and bronchial muscle spasms resulting in cough and
wheezing, experienced by the asthmatic patient.” Dr. Cohen
continued, “A second type of inflammation that results from a
sequence of chemical events due to antigen-antibody interactions
is more delayed in onset, and more persistent. Inflammatory
cells responding to the formation of immune complexes infiltrate
into many organs and tissues of the body. This is the type of
inflammatory manifestation to which you probably refer. As a
consequence of the formation and action of abnormal com¬
plexes, the SLE patient thus can experience involvement of
joints, skin, kidney, heart, and nervous system.” After a
moment or so. Dr. Cohen continued. “Because the programs of
NIAID are so heavily involved in the study of immune mecha¬
nisms and their consequences, we are very much concerned with
accompanying inflammatory reactions. Certainly much of our
work focuses upon the chemical properties and actions of serum
complement, and the potentially injurious enzymes of white
blood cells involved in immunopathology. Thus, we look upon
the study of inflammatory problems in SLE as a natural accom¬
paniment of our primary interest in the immune system and its
disorders.”
“In a report called ‘Sure Foundation,’ written in 1976, Dr.
Richard Krause stressed that lupus erythematosus appears to be a
strange amalgam of infection and immunity. This makes one
wonder if the 14-point criteria for the classification and diagnosis
of lupus diseases by the American Rheumatism Association could
be improved upon or expanded. Do you have any thoughts on that?’ ’
“Any criteria or classification can be established only within

the framework supplied by the state of knowledge at the time it
was developed,” Dr. Cohen said. “lam certain that members of
the panel of experts who drew up the original 14-point criteria
for the classification and diagnosis of lupus established by the
ARA were, and continue to be, aware of the limitations under
which they worked to produce this contribution to clinical medi¬
cine. As with any consensus, the classification can and should
be modified as our base of fundamentally relevant knowledge
expands. Much of the exciting developments emerging from to¬
day’s research data are offering productive and rewarding leads,
not only for extending investigation, but also for application to
clinical practice. Certainly this seems to be so in the case of
factors of infection and immunity. Though the time is not yet
right, we have reason to believe that advancement in these
fields, by properly controlled studies, will ultimately offer evi¬
dence that can be incorporated in an improved or expanded set
of diagnostic criteria.”
I asked Dr. Cohen what is being done, if anything, to bring
awareness of lupus to physicians and nurses, and to help with
programs that will improve the quality of life of the patients.
Dr. Cohen said: “I share your concern that information
should be disseminated to physicians and such paramedical per¬
sonnel as nurses and physicians’ assistants, and to specially
trained social workers who are and will be increasingly called
upon to deal with the SLE patient. Educational efforts in medi¬
cal school curricula, medical specialty fellowships, and post¬
graduate courses giving increased attention to immunologic dis¬
eases, and SLE in particular, are a direct reflection of increasing
knowledge and understanding of the fields of immunopathology
and clinical immunology. As a result of the increasing aware¬
ness among physicians, of lupus and its symptoms as a disease
entity, the diagnosis is being made with increasing frequency. I
would agree that we need to expand all possible efforts, on a
widespread geographic basis, and to make educational opportu¬
nities available in areas where today they may be only minimal.
University and medical centers are contributing considerably to
this endeavor, by serving as points of referral for diagnostic
OfNIAID-NIH, In Search of a Cure for Lupus 179
problems, and encouraging their professional staffs not only to

serve as responsible physicians in patient care, but also to pro¬
vide consultative services, to publish, and to develop post-grad¬
uate courses of instruction within the regions they serve. Since
so little of SLE was known during the day when many of today’s
senior physicians were in medical school, increasing awareness
of this disease is a tribute to the effectiveness of continuing
medical education. The needs of the job ahead can be clearly
visualized, and the objectives met, only by joint efforts of medi¬
cal educators, researchers in the basic sciences, clinical investi¬
gators, and the concerned and informed laity, as represented by
the untiring efforts of your own Lupus Foundation. NIH’s man¬
dated role is that of research and research training. Accordingly,
we at NIAID are exerting our maximal influence to design, de¬
velop, and encourage research in the areas of immunology al¬
lergy, inflammation, and infection that focus upon mechanisms
of multi-system connective tissue disorders represented by SLE.
Through the mechanism of grant awards for fellowships, we are
endeavoring to assure the development and placement of ap¬
propriately trained medical scientists in academic and research
institutions. Additionally, through our Office of Research Re¬
porting and Public Response, the preparation of informational
material, answering of inquiries, and otherwise communicating
with SLE patients is part of the daily routine. In cooperation
with NIADDK, NIAID supports scientific conferences, partici¬
pates in the work of a trans-NIH coordinating committee, and
remains keenly aware of the need to translate promptly, and
transfer pertinent research technology relevant to the practicing
physician.”
“Is it fair to ask you if physicians in the near future will be
able to cope with lupus better than they can today?”
“A loaded question, Mrs. Aladjem, but that’s precisely why
we are here. Otherwise,” said Dr. Cohen, wistfully looking at
the setting of nautical watercolors directly before him, and then
turning to the window in the direction of the Chesapeake Bay,
‘T would be out there sailing.”
*; 9
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Bibliography 181
Bibliography for Additional

Reading and Explanations
Milestones in the History of Systemic Lupus Erythematosus

Gerald Rodnan, M.D.
1. Baehr, G., Klemperer, P., Schifrin, A.: A diffuse disease of the

peripheral circulation (usually associated with lupus erythematosus
and endocarditis). Trans Assoc Amer Phys 50\\2>9-\55, 1935.
2. Klemperer, P., Pollack, A. D., Baehr, G.: Pathology of dissemi¬
nated lupus erythematosus. Arch Path 32:569-631, 1941.
3. Libman, E., Sacks, B.: A hitherto undescribed form of vascular and
mural endocarditis. Arch Intern Med 33:701-737, 1924.
4. Klemperer, P., Pollack, A. D., Baehr, G.: Diffuse collagen disease.
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JAMA 119:331-332, 1942.
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519, 1950.
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bone marrow elements: the “tart” cell and the “L.E.” cell. Proc
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CHAPTER 1
Introductory Chapter
Peter H. Schur, M.D.
10. “And probably no one as much as the patient has managed to give
the disease such insights and profound understandings.” Barbara
Feinberg, President of the Lupus Erythematosus Foundation of
Massachusetts.
11. Tan, E. M., Schur, P. H., Carr, R. I. and Kunkel, H. G.: DNA and
antibodies to DNA in the serum of patients with systemic lupus
erythematosus. J. Clin. Invest. 45:1732-1740, 1966.
12. Kofler, D., Schur, P.H. and Kunkel, H. G.: Immunological studies
concerning the nephritis of systemic lupus erythematosus. J. Exp.
Med. 126:607-623, 1967.
13. Schur, P. H. and Sandson, J.: Immunological factors and clinical
activity in lupus erythematosus. New Eng. J. Med. 278:533-538, 1968.
14. Pincus, P., Schur, P. H., Rose, J. A., Decker, J. L. and Talal, N.:
Measurement of serum DNA-binding activity in systemic lupus
erythematosus. New Eng. J. Med. 281:701-707, 1969.
15. Schur, P. H., Stellar, B. D., Steinberg, A. D. and Talal, N.: Inci¬
dence of antibodies to double-stranded DNA in systemic lupus
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1971.
16. Schur, P. H.: Systemic lupus erythematosus. In Textbook of Medi¬
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19. Raum, D., Glass, D., Carpenter, C. B., Alper, C. A. and Schur, P.
H. The chromosomal order of genes controlling the major histocom¬
patibility complex, properdin factor B, and deficiency of the second
component of complement. J. Clin. Invest. 58:1240-1248, 1976.
20. Schur, Peter H.: Lupus Erythematosus, In Advances in Nephrology,
ed. Hamburger, J., Crosiner, J. and Maxwell, M. H., Yearbook
Medical Publishers, Inc., 1976, pp. 63-11.
21. Schur, Peter H.: Pathophysiology of Rheumatic Diseases. Arthritis
and Rheumatism 20:500-508, 1977.
22. Glass, David and Schur, Peter H.: Autoimmunity and Systemic
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CHAPTER 2
The Physician, The Psychiatrist and The Lupus Patient
23. “To fully understand and know lupus one must feel it’s havoc from
within. Until medicine produces the solutions, we must survive to¬
gether and draw strength from one another.’’ Susan Golick, a patient
and the Founder of the SUE Foundation, Inc. She is also a director of
the Lupus Foundation of America, Inc.
24. “Banishment from Native Eyes’’: The Reason for Emily Dickinson’s
Seclusion Reconsidered by Jerry Ferris Reynolds, The Markham Re¬
view, published by the Horrmann Library of Wagner College.
25. Emily Dickinson; A New Look at Her Life and Poetry Through Her
Physical Illness, by Barbara Jerry Reynolds, a Thesis Submitted in
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26. From a letter written by Emily Heller, physiologist. Board member.
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27. In conversation with Dr. Lucille Carter, psychiatrist, Boston.
28. “The Male Lupus Patient,’’ an excerpt from an article written by
Nancy Hubbord. The article appeared in a Newsletter published by
the Michigan Lupus Foundation.
29. Michael Balint, p. 47 and p. 52. Balint, M., The Doctor, The Pa¬
tient, and His Illness, New York, International Press, 1972.
30. Nicobion; Literature uber die Therapeutische Anwendung der Nikot
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CHAPTER 3
Lupus and Epidemiology
36. “In a sense the epidemiologist is the physician to the community,

whereas the family physician and surgeon are doctors to the individ¬
ual patient.” Richard M. Krause, M.D., Director National Institute
of Allergy and Infectious Diseases, National Institute of Health,
Bethesda, Md. The Restless Tide, p. 61. Published by the National
Foundation For Infectious Diseases, Wash., D.C. 1981.
37. Hoover, R., Fraumeni, J. F. Jr.: Risk of cancer in renal transplant

recipients. Lancet 1973; 2:55-57.
38. Siegel, M., Lee, S. L.: The epidemiology of systemic lupus
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39. Kaslow, R. A., Masi, A. T.: Age, sex, and race effects on mortality
from systemic lupus erythematosus in the United States. Arth Rheum
1978;21:473-479.
40. Reinertsen, J. R.; Kaslow, R. A.; Klippel, J. H., et al: An epidem¬
iologic study of households exposed to canine systemic lupus
erythematosus. Arth Rheum 1980; 24:564-568.
41. Block, S. R.; Winfield, J. B.; Lockshin, M. D.; D’Angelo, W. A.;
Christian, C. L.: Studies of twins with SLE — a review of literature
and presentation of 12 additional sets. Am J Med 1975; 59:533-552.
42. Friedman, G. D.: Primer of Epidemiology. New York, McGraw-
Hill, 1974.
CHAPTER 4
SLE In Children, And Other Lupus Research At Children’s
Hospital Medical Center in Boston
43. “Every patient you see is a lesson in much more than the malady he
suffers.’’ Sir William Osier, M.D., Acquanimitas.
44. Autoimmune Disease: New Evidence About Lupus, Jean L. Marx,
Science, Vol. 192, June 1976.
45. Prevention of Murine Lupus Nephritis by Carrier-Dependent Induc¬
tion of Immunologic Tolerance to Denatured DNA, Science, Vol.
182 (October 5, p. 76, 1973, Yves Borel, Robert M. Lewis and B.
David Stollar.
46. Isologous IgG-Induced Immunologic Tolerance to Haptens: A model
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(1976), p. 3, Vol. 31.
47. Treatment of Lupus Nephritis in Adult (NZB + NZW) F Mice by
Cortisone-Facilitated Tolerance to Nucelic Acid Antigens, Yves
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and Erwin Diener, Journal of Clinical Investigation, Vol. 61, p.
276, 1978.
48. “So safer guess - with must my soul! Upon the window pane -
Where other creatures put their eyes. Unconscious - of the sun.’’
From a poem by Emily Dickinson.
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1253, 1976.
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58. Perry, H. A., Brunsting, L. A.: Pemphigus foliaccus. Arch Derma¬
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CHAPTER 5
Lupus and Photosensitivity
61. From a poem by Emily Dickinson.

62. Dilaiffiy, M.: Lichen planus subtropicus. Arch Dermatol 112:1251-
1253, 1976.
63. Baer, R. L., Harber, L.C.: Photobiology of lupus erythematosus.
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CHAPTER 6
Why Is Lupus More Common in Women?
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CHAPTER 7
Systemic Lupus Erythematosus and Pregnancy, Part One
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CHAPTER 8
Systemic Lupus Erythematosus and Pregnancy, Part Two
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CHAPTER 9
Lupus and Medications
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CHAPTER 10
Ingested Antigens May Play a Role in The Pathogenesis of
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CHAPTER 11
Unravelling Some of the Mysteries of Lupus
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CHAPTER 12
Lupus, the Kidneys and Other Aspects of the Disease
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CHAPTER 13
Prostaglandins Offer Hope In Lupus
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CHAPTER 14
The Genetics of Lupus
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CHAPTER 15
Dogs As Well As People Suffer From Lupus
(Part One and Part Two)
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annual session of Am. Assoc. Lab. Animal Sci., 1978.
193. “Systemic lupus erythematosus is a difficult name to pronounce, but
it is even more difficult to live with.” Marjorie Gordon, the first
President of the Lupus Erythematosus Foundation of Massachusetts.
CHAPTER 17
Pulse Therapy
194. “Extreme remedies are appropriate for extreme maladies. ’ ’ Hippocrates.

195. Baldwin, D. S. et al: The clinical course of the proliferative and
membranous forms of lupus nephritis, Ann. Intern. Med. 73:929,
1970.
196. Epstein, R. H. et al: Case 2-1976 (Case Records of the Massachu¬
setts General Hospital), N. Eng. J. Med. 294:100, 1976.
197. Phillips, P. E.: The virus hypothesis in systemic lupus erythema¬
tosus, Ann. Intern. Med. 83:709, 1975.
198. Decker, J. L. et al: Systerriic lupus erythematosus: contrasts and
comparisons, Ann. Intern. Med. 82:391, 1975.
199. Hahn, B. H., Kantor, O. S., Osterland, C. K.: Azathioprine plus
prednisone compared with prednisone alone in the treatment of sys¬
temic lupus erythematosus, Ann. Intern. Med. 83:597, 1975.
200. Decker, J. L. et al: Cyclophosphamide or azathioprine in lupus
glomerulonephritis, Ann. Intern. Med. 83:606, 1975.
201. Scheinberg, M. A., Cathcart, E. S., Goldstein, A. L.: Thymosin-
induced reduction of “null cells” in peripheral blood lymphocytes of
patients with systemic lupus erythematosus, Lancet 1:424, 1975.
202. Cathcart, E. S. et al: Beneficial effects of methylprednisone “pulse”
therapy in diffuse proliferative lupus nephritis. Lancet 1:162, 1976.
Glossary 197
GLOSSARY
ASPIRIN: In 1763, researchers discovered that an extract of the

willow bark was effective in relieving the pains of rheuma¬
tism. Willow extract owes its therapeutic efficacy to a sub¬
stance that is called salicylic acid — from the Latin name
for willow, salix. A chemically modified form, acetylsali-
cylic acid, is marketed under the name of aspirin. For rea¬
sons still unknown, aspirin proves helpful for relieving
pain.
AUTOGENOUS VACCINES: Vaccines which are made from

the patient’s own bacteria, as opposed to vaccines which
are made from standard bacterial cultures.
AUTOIMMUNE: Sensitive to one’s self; a person’s body

makes antibodies against some of its own cells.
BASAL METABOLISM: Radioactive iodine uptake. The rate

is tested to determine whether the thyroid gland is over or
underactive.
BIOPSY: A sample of tissue for microscopic study.
BLOOD CELL: Three main kinds are recognized: Red blood

cells (erythrocytes) carry oxygen and carbon dioxide; white
blood cells (leukocytes) help fight infection; platelets
(thrombocytes) help prevent bleeding.
BRONCHIA: The tubes formed by the division of the wind¬

pipe, and which convey the air to the lung cells.
BUN: Blood Urea Nitrogen. When the kidneys fail, the BUN
rises, as does the uric acid.
BUTTERFLY RASH: A form of double-wing shaped skin rash

around the nose and cheeks indicative of lupus.
CAPILLARIES: The smallest of the blood vessels that connect

arteries and veins.
CELL BIOLOGIST: One who studies cell architecture and

function.
CHRONIC: Lasting for a long period of time.
CNS: Central Nervous System.
COLLAGEN DISEASE: A group of diseases characterized by

inflammation of connective tissues, especially the skin and
joints — viz. RA, SLE, scleroderma, Sjogren’s, JRA —
also usually synonymous with rheumatic disease.
COMPLEMENT PROTEIN: A regulatory of the immune re¬

sponse.
CONNECTIVE TISSUE: Substance which binds the body to¬

gether, like a body glue. Connective tissue is the most
widespread and abundant tissue in the body.
CORTICOSTEROID: Product of adrenal cortex.
CORTISONE: A potent hormone of the adrenal glands; the pure

compound was first discovered in adrenal secretion simul¬
taneously in 1936 by Dr. Edward C. Kendall of the Mayo
Clinic, and by Dr. Reichstein of Basel, Switzerland. It is
now synthesized as a pure chemical.
COVALENT: A chemical bond formed by the sharing of elec¬

trons.
CUTANEOUS LESIONS: Visible changes in skin which are

abnormal; rashes or “sores” or scars.
D AND C: Abbreviation for “dilation of the cervix and curett-

ment of the uterus.”
DENATURED: To change the nature ... the quality of.

Glossary 199
DEOXYRIBONUCLEIC ACID: The basic constituent of

genes. Genes are the cellular constituents which determine
inheritance.
DERM ATOM YOSITIS: A chronic inflammatory disease of the

skin and muscles.
DIPLOPIA: Double vision.
DIURETIC: A drug that helps to make more urine.
DNA: Deoxyribonucleic acid, a large complex molecule com¬

posed of chemicals called sugars and nucleic acids.
DROPSY: The swelling of the legs and abdomen which most

often is caused by heart failure, but can be due to kidney or
liver disease.
EKG (OR ECG): Electrocardiogram. This is a recording of

electrical forces from the heart.
ENDOCRINOLOGY: The study of the glands of internal secre¬

tion.
ENZYME: A protein substance that catalyzes a biological or

chemical reaction.
ERYSIPELAS: A contagious, infectious disease of skin and

subcutaneous tissue, marked by redness and swelling of
affected areas and with constitutional symptoms.
ERYTHEMA NODOSUM: Painful red bumps on the skin. A

skin manifestation of several diseases, including lupus.
ERYTHROCYTES: The normal non-nucleated red cells of the

circulating blood; the red blood corpuscles.
ESTROGEN: A family hormone produced by the ovaries and

responsible for secondary sexual characteristics in female
and preparation of the uterus for implantation of the ferti¬
lized egg.
ESTRUS: The time period in the female reproductive cycles of

mammals other than man and monkey, when ovulation oc¬
curs and the female will permit intercourse, known also as
the “heat” period.
EXACERBATION: Symptoms reappear; another word for

flare.
FALSE-POSITIVE WASSERMAN: The Wasserman test is just

one of the methods used in testing for syphilis. One of the
common, current tests for syphilis is referred to as the
“RPR”. Some people will have a positive test for syphilis
yet don’t have the disease. Systemic lupus erythematosus
is one of the conditions which may give you a positive test
for syphilis, although syphilis is not present. This is called
a false-positive test for syphilis. Because the immune sys¬
tem in systemic lupus erythematosus is supposedly overac¬
tive, it makes antibodies to a variety of infectious organ¬
isms and proteins. Therefore, a lupus patient could make
antibodies to a protein-like substance that is structurally
similar to the syphilis organism, and consequently, give a
false-positive test for syphilis.
GALACTOSE: One of the sugars in milk, a part of the lactose

molecule.
GASTRIC: Belonging to the stomach.
GASTRIC PARIETAL CELLS: The acid-producing cells of the

stomach.
GENETIC: Pertaining to the genes; the word “genetic” refers

to the property of transmission of parental characteristics to
offspring. See DNA.
GLOMERULONEPHRITIS: A type of kidney inflammation

characterized by involvement of the glomerulus of the kid¬
ney.
Glossary 201
HAPTENS: A chemical which, when coupled to a protein, will

induce a immune response.
HEMATOLOGIC ROUTINE: Tests to count the cells of the

blood. The LE cell is a white cell that has eaten the nucleus
of another white cell; the latter appears as a blue staining
spot inside the first cell.
HEMATOLOGIST: A specialist in the study of blood.
HEMATURIA: Red blood cells in the urine.
HEMIPARESIS: A slight paralysis or weakness of one-half of

the face or body.
HEMOLYTIC ANEMIA: A condition characterized by a reduc¬

tion in circulating red cells due to increased destruction by
the body.
HEPATITIS: Inflammation of the liver.
HISTIOCYTE: A tissue macrophage — scavenger of cell

debris, viruses, bacteria.
HISTOLOGICAL: The magnified tissue as opposed to the gross

clinical examination.
HISTOPATHOLOGY: Change in tissues and cells.
HLA SYSTEM: A genetic system controlling proteins to and on

cell surfaces — often linked to disease.
HORMONE: From the Greek “to excite”; hormones are chem¬

ical messengers which excite a response in other tissue.
HYALENE: Thickening.
HYDROXYCHLOROQUINE: Antimalarial drug that has also

been used as a suppressant for lupus.
HYPERSENSITIVITY; A form of allergy generally mediated

by antibodies, a special group of blood proteins.
HYPOCHONDRIAC: Morbid anxiety about health.
IMMUNE COMPLEXES: The specific combination of anti¬

bodies with their corresponding antigens.
IMMUNE MEDIATED: Being produced by the immune sys¬

tem, i.e. antibodies and lymphocytes.
IMMUNITY: The power to resist infection or an invasion of

bacteria.
IMMUNOFLUORESCENCE: A special histological technique

using a fluorescent dye to mark antibody or immune proc¬
ess taking place at a given site in the tissue.
IMMUNOGEN: Any substance capable of eliciting cellular or

humoral immunity.
IMMUNOLOGIC TOLERANCE: The specific suppression of

immunity to a substance called antigens. Normally, we do
not make antibodies to our own antigens such as our own
cells, tissue proteins or DNA.
LYSED: Nuclear material
MEPACRINE: Quinacrine, Atabrine, the antimalarial drug

which was taken by United States Armed Forces personnel
during World War 11.
METABOLISM: The series of chemical changes in the living

body by which life is maintained.
METHYLPREDNISONE: A synthetic form of corticosteroid.
MIXED CONNECTIVE TISSUE DISEASE Consisting of two

or more of the connective tissue diseases, e.g. lupus, rheu¬
matoid arthritis, scleroderma.
Glossary 203
MORPHOLOGICAL: The grossly visible anatomy of a lesion

as seen by the human eye.
MOTOR APHASIA: Loss of speech due to an immunological

defect affecting the muscles of speech.
MUCOSAL IMMUNITY: Immunity of the GI, GU, or bron¬

chial tracts.
MURINE: Pertaining to a member of the rodent family.
MYASTHENIA GRAVIS: A disease in which nerve impulses

are not properly transmitted to the muscle cells. As a re¬
sult, muscles all over the body become weak.
NEUROSIS: A disorder of the mental constitution.
NICONACID: Swiss-French trademark for a preparation of ni¬

cotinic acid.
NICOTINOMIDE: The acid of pyridine 3 — carboxylic acid

(Niacin) C6H6ON2. Nicotinomide will produce results com¬
parable in every way to those obtained by use of the free
acid (Eli Lilly and Co., Indianapolis, Indiana).
NOXIOUS STIMULI: Unpleasant or damaging substances.
NUCLEOSIDE: One of four types of the building blocks of

DNA.
NYSTAGMUS: Involuntary rapid movement of the eye.
OVARIECTOMY: Removal of the female reproductive organs.
OVULATION: The cyclic ripening and maturation of the

ovum.
OVUM: The female germ cell or egg, which when fertilized by

a single male sperm cell, produces the embryo.
PANTOTHENIC ACID: A constituent of the vitamin B com¬

plex.
PATHOGENIC: Producing something undesirable or unwell.
PATHOLOGIST: One who is well versed in detecting changes

in tissue.
PATHOLOGY: That branch of medicine which treats the nature

and effects of disease.
PELLAGRA: A deficiency of niacin, one of the B vitamins,

which causes diarrhea, dermatitis, and dementia.
PENICILLIN: Antibiotic.
PERIARTERITIS: A particular form of vasculitis (inflamma¬

tion of blood vessels) affecting all types of blood vessels.
May be caused by hepatitis.
PERIPHERAL NEUROPATHY: Neuropathy of arms or legs,

i.e. malfunction of nerves to arms or legs.
PERNICIOUS ANEMIA: A condition characterized by a reduc¬

tion in circulating red cells due to a deficiency in proper
numbers being produced in the bone marrow.
PHAGOCYTOZED NUCLEAR MATERIAL: White cells that

have ingested nuclei from other cells.
PHAGOCYTOSIS: The engulfment by phagocytes of foreign or

other particles, or cells harmful to the body.
PHLEBITIS: Inflammation of a vein.
PHOTOSENSITIVITY: Capacity to overreact to light energy.
PLACEBO: An inactive substance given to a patient either for

its pleasing effect or as a control in experiments with an
active drug.
Glossary 205
PLASMA: The fluid portion of the blood in which the blood

cells are floating.
PLEURITIS: Inflammation of the pleura (lining of the lung).
POLYARTERITIS NODOSA: Inflammation of the large arter¬

ies.
POLYMORPHONUCLEAR LEUKOCYTE: A particular type

of white blood cell.
POLYS (POLYMORPHONUCLEAR): White blood cells.
PREDNISONE: The chemical name for a steroid hormone.
PROGESTERONE: The female hormone produced during preg¬

nancy which is primarily responsible for maintaining preg¬
nancy and development of the mammary glands.
PROPERDIN: One of the compliment proteins.
PROSTAGLANDIN E (PGE): The prostaglandins are a large

family of pharmacologically active lipids widely distrib¬
uted in mammalian tissue. (Lipids = fats)
PROTEINS: Building blocks of body regulators of cell func¬

tion.
PROTEINURIA: Protein in the urine.
PSYCHOSOMATIC: The relationship of the body to the head;

having bodily symptoms to mental rather than physical dis¬
order.
PTOSIS: A drooping, particularly that of the eyelid.
PULMONARY: Connected with lungs.

PUPILLARY REACTION: Constriction of the pupil in re¬

sponse to light which may be painful in inflammatory dis¬
orders of the eye.
PURPURA: A disease that is characterized by the rupture of

blood vessels with leakage of blood into the tissues.
QUANTITATE: Precisely measured amount.
RHEUMATOID ARTHRITIS: A chronic disease of the joints.
SCLERODERMA: “Hard skin,” a chronic connective tissue

disease characterized by leathery thickening of the skin.
The internal organs may also be involved.
SEDIMENTATION: The settling of red blood cells to the lower

portion of a volume of blood which has been treated to
prevent clotting.
SERUM CREATININE LEVELS — CREATININE: A sub¬

stance normally found in blood in low concentration, since
it is eliminated from the serum by the kidneys; high serum
creatinine levels indicate malfunction of the kidneys.
SIDE EFFECT: An adverse effect produced by a drug. One

disorder is being replaced by another.
SJOGREN’S SYNDROME: An autoimmune disease character¬

ized by dryness of the mouth and eyes.
SPONTANEOUS REMISSION: A change in the course and se¬

verity of a disease which occurs without medical interven¬
tion.
STREPTOCOCCUS: The round organism (coccus); a very dan¬

gerous bacterium that may cause sore throats and skin in¬
fections such as nephritis, inflammation of the kidneys,
rheumatic fever, inflammation of the heart and Joints.
Glossary 207
SULFADIAZINE: An anti-infective drug, one of the sulfona¬

mides.
TART CELL: A partial or incomplete LE cell.
TESTIS: Synonym for “testicle,” the male reproductive organ

responsible for production of sperm cells.
TETRACYCLINE: An antibiotic effective against many of the

bacteria which are not affected by penicillin.
THERAPEUTICS: The study of the action of drugs and their

application to the treatment of disease.
THERMAL BURNS: The injury to tissue caused by heat.
THROMBOCYTOPENIA: A reduction of circulating platelets.
THYROID GLAND: A gland which produces thyroxine and is

located in the neck.
THYROIDITIS: Inflammation of the thyroid gland.
THYROXINE: A substance which controls the rate of chemical

reactions in the body.
TITER: The highest dilution of a serum that gives a reaction

with a substance.
TOLERANCE TO NUCLEIC ACID ANTIGENS:Unrespon¬

siveness to nucleic acids which are building blocks of the
genetic code.
ULTRAVIOLET: That portion of the spectrum of sunlight

which tans the skin.
UV-ALTERED NNA: UV energy entering the cell causes suffi¬

cient disruption of the genetic molecules to allow them to
become antigen.
UV RADIATION: Radiation of energy of wave lengths 200-

290 nm (UVC); 290-320 nm (UVB); 320-400 nm (UVA).
UREMIA: Marked kidney insufficiency characterized by

nausea, vomiting, even coma or convulsions, and a urine
odor to the breath.
UTERUS: Synonym for “womb”, the female organ designed

for containment and nourishment of the fertilized egg (em¬
bryo) during pregnancy.
VASOMOTOR: Pertaining to control of the tone of the blood

vessels. Contraction of blood vessels causes blanching
whereas relaxation causes blushing.
VIRAL ETIOLOGY: Caused by a virus.
VIRAL PROTEIN: One of several constituents that make up a

virus particle.
ABOUT THE AUTHOR
Henrietta Aladjem is the author of “The Sun Is My Enemy”
in which she describes her own battle with Systemic Lupus
Erythematosus. She was instrumental in founding a major health
organization, The Lupus Foundation of America, Inc. Henrietta
Aladjem is the editor of Lupus News and a member of the Na¬
tional Allergy and Infectious Disease Council at the National
Institute of Health, Bethesda, Maryland. Mrs. Aladjem is the
mother of three grown children and lives in Waban, Massachu¬
setts with her husband, a wool merchant.
209
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LUPUS-Hope Through Understanding
by Henrietta Aladjem
“A book that can only make wiser, and more understanding, a
public that has known far too little about a terrible and astonishingly
wide-spread disease.”—C. Michael Curtis, Senior Editor; The Atlantic
Monthly, Boston.
“Today, Mrs. Aladjem s book can be read as the story of a myste¬

rious and little-understood disease. Hopefully, heightened public and
scientific awareness of lupus brought about by this publication will
stimulate research needed to better understand the immune system
and to develop more rational approaches to prevent and treat this
and other diseases in which the immune system has gone awry.
Through this research, tomorrow, perhaps, the story of lupus will be
read as but a chapter in the past history of medicine.”—Dorothy D.
Sogn, M.D., Special Assistant to the Director, Immunology, Allergic
and Immunologic Diseases Program, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
“Written by an intelligent, articulate and sensitive woman who

has made herself into a leading expert on the disease and its ramifi¬
cations, “Lupus—Hope 1 Trough Understanding” provides authorita¬
tive, helpful, educational and supportive information for patients,
families, friends, physicians and allied health professionals.
Author Henrietta Aladjem is living proof that hope is justified for
many lupus patient? is a human as well as medically oriented
document, filled with personal observations, its contents reviewed by
medical specialists.”—Herbert Black, Medical Editor, retired; Boston
Globe.
“Lupus—Hope Through Understanding” presents a new adven¬

ture by an accomplished author in presenting information that
would be useful not only for patients with a particular disease but
those various members of the medical and allied health professions
who help take care of them. Mrs. Aladjem has ône many steps
further than her book “The Sun Is My Enemy, ’ which described her
own perso^ ^’‘^^âse. systemic lupus erythemato¬
sus. She h^ I |||j||l Im ’ -êpth in a
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0960866000
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11/15/2017 10:16-2 22
LUPUS FOUNDATION OF AMEKlu/i,
Desif^tied by Kathie Coe/Illustrated by Ron Kyle ISBNO-9608660-0-0

Lupus - Hope Through Understanding - Aladjem, Henrietta, 1917 (Orthomolecular Medicine)

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UJt^

Hope Throu^ Understanding

LUPUS FOUNDATION OF AMERICA, INC.

Books By Henrietta Aladjem

All rights reserved

Library of Congress Cataloging in Publication Data

Printed in the United States of America

Typography and Printing, Acme Printing Company,

Patricia A. Fraser, M.D.

Chester Alper, M.D., Professor of Pediatrics, Harvard University Medi¬

Foreword, Patricia Fraser, M.D. ix

Milestones in the History of Systemic Lupus Erythematosus xv

2 The Physician, The Psychiatrist and 15

3 The Epidemiology of Lupus 41

4 SLE In Children and Other Research 49

5 Lupus and Photosensitivity 59

6 Why is Lupus More Common in Women 73

7 SLE and Pregnancy 79

8 SLE and Pregnancy 83

10 Ingested Antigens May Play a Role in 111

11 Unravelling Some of the Mysteries of Lupus 123

12 The Kidneys and Other Aspects of S.L.E. 131

13 Prostaglandin Offers Hope in Lupus 137

14 The Genetics of Lupus 141

15 Dogs as Well as People Suffer Prom Lupus 151

16 Update on the Lupus Dogs 157

17 Pulse Therapy 165

18 Of NIAID-NIH, In Search of a Cure for Lupus 169

Bibliography for Additional Reading and Explanations 181

Year Author(s) Contribution

‘'And probably no one as much as the

^Barbara Feinberg is the President of the Lupus

The Relationships Between

As the statistics clearly indicate, most lupus patients will not

These lupus rashes fall into two categories: discoid lupus

usually temporary. However, persistent liver enlargement and

casts in the urine, pericarditis and/or pleurisy, psychosis and/or

patients who had a positive ANA test. They found that if a

made when kidney damage is suspected, to determine whether

Others an infection, perhaps a cold or a more serious infection,

*This will be discussed in a later chapter.

These immune complexes can also be deposited in various or¬

To whom should an SLE patient go for treatment? Physicians

5. Cortisone drugs (the most commonly prescribed in predni¬

And The Lupus Patient

'To fully understand and know lupus one

must feel if s havoc from within. Until

I ' n 1953, when I was diagnosed as having systemic lupus

If we try to use such a classification, we must be aware that

a minor manifestation at the bottom of a long and varied list of

disease is in their mind, since they could not possibly have so

A lupus patient who has central nervous system involvement

The woman’s smile broadened. “I am happy that I can still

“The physician should not be ignorant of the fact that the

was depressed and worried, thinking that she had become a

well today,’ that I repeated so often. Yet, I never quite understood

Dr. Nadelson and I were quiet for a moment. “Twenty years

“You outline with great vividness the kind of situation which

Another patient, a professor of literature wrote:

And in another letter the same patient wrote:

had labelled me a neurotic. I began to perceive myself as one. I still

Dr. Nadelson said, “Patients who have absolute manifesta¬

patients are complaining about something that troubles them,

^ .. M ';* -A #TM -1 ‘'■'■ •V i ■ ' *