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Teaching and Research Department, Fundao Alfredo da Matta, Manaus, Amazonas, Brazil
Amazon State University, Manaus, Amazonas, Brazil
c
Department of Dermatology, Universidade Nilton Lins, Manaus, Amazonas, Brazil
d
Tropical Medicine Centre, University of Braslia, Asa Norte, Brazil
b
Abstract Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It mainly affects the
peripheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bones
and joints, mucous membranes, eyes, testes, muscles, and adrenals. Leprosy clinical presentation varies
from few to widespread lesions. In most patients, early leprosy presents as macular and hypopigmented
lesions. This initial clinical presentation is known as indeterminate leprosy and occurs in individuals
who have not developed cell-mediated immunity against M leprae yet. The number of lesions depends
on the genetically determined cellular immunity of the patient. Individuals presenting a vigorous cellular
immune response and limited humoral immune responses to M leprae, usually present few skin lesions.
Without treatment, those patients tend to evolve into the polar tuberculoid or borderline tuberculoid form of
leprosy. Due to the inability to mount an effective cellular-mediated response to M leprae and the consequent
hematogenous spread of the bacilli, some patients may present with numerous and symmetrically distributed
hypochromic lesions. Without treatment these patients evolve to a nonresistant form of leprosy,
polar lepromatous.
2015 Elsevier Inc. All rights reserved.
Clinical leprosy
Leprosy is a chronic, infectious disease caused by
Mycobacterium leprae. It mainly affects the peripheral
nervous system, skin, and certain other tissues such as the
reticulo-endothelial system, bones and joints, mucous
membranes, eyes, testes, muscles, and adrenals. The clinical
presentation of leprosy clinical presentation varies from few
to widespread lesions.1 Similarly, histopathology of skin
lesions varies from compact granulomas to diffuse infiltration of dermis, which largely depend upon the immune status
of the patient and may not be in agreement with the clinical
diagnosis.24 Leprosy classification has been a matter of
Corresponding author.
E-mail address: gpenna@gpenna.net (G.O. Penna).
http://dx.doi.org/10.1016/j.clindermatol.2014.07.002
0738-081X/ 2015 Elsevier Inc. All rights reserved.
I leprosy
In most patients, early leprosy presents as macular and
hypopigmented lesions. This initial clinical presentation
is known as I leprosy and occurs in individuals who have
not developed cell-mediated immunity against M leprae
yet. 1,10 The single (Figure 1) or multiple macules have no
more than 34 cm wide, present with a smooth surface and
are not scaling or pruriginous (Figure 2). The lesions may
also be red in light-skinned patients or coppery in darkskinned patients. There is normal sweating and body hairs
are present. 1114
A very important characteristic of leprosy lesions is the
impaired sensation (anesthesia). On I leprosy lesions the
patient commonly presents with loss of thermal sensation,
not being able to distinguish between a cold and a hot tub
of water. Hyperalgesia often precede the detection of skin
lesions.12,13
The number of lesions depends on the genetically
determined cellular immunity of the patient. Individuals
presenting a vigorous cellular immune response and limited
humoral immune responses to M leprae, usually present few
skin lesions.12 Without treatment, those patients tend to
evolve into the polar T or BT form of leprosy. Individuals
within the tuberculoid pole may present a tendency towards
spontaneous healing. Patients presenting with numerous or
countless number of hypochromic lesions, without treatment,
tend to evolve into BB, BL, or LL forms.13,14
27
28
C. Talhari et al.
Tuberculoid leprosy
Tuberculoid leprosy (TT) is characterized by the presence
of unique or few small-sized lesions showing well-defined
and elevated borders (papules and plaques) (Figure 6).18 The
elevated border indicates either central healing or peripheral
spread.13 Typical TT lesions have decreased sweating,
rarefied body hair, and are anesthetic: first thermal, then
tactile, and pain sensitivity is lost. There are patients with
tuberculoid leprosy that presents anesthetic areas without
changes in the skin color or peripheral trunk nerve
enlargement, with or without skin lesions.19 It is very
important to remember that lesions on the face may present
normal sensitivity, in this area the rich sensory innervations
compensates for the damaged nerves.1,11
In early cases of TT, macules may be observed; in lightskinned patients these lesions are erythematous or coppery in
dark-skinned individuals; it may also be homogeneously
hypopigmented. These macules show a dry surface and due
to anhidrosis are rough to the touch. Due to the intense
cellular-mediated immunity, papules can appear on the edges
of the macule (Figure 7).10,13
Fig. 5
29
Seborrhoeic dermatitis, lobomycosis, chromomycosis, psoriasis, parapsoriasis, sarcoidosis, mycosis fungoides, morphea,
necrobiosis lipoidica, Kaposis sarcoma, cutaneous tuberculosis
and leishmaniasis are other diseases that may mimic T leprosy.
Borderline leprosy
According to the Ridley and Jopling classification, the
vast majority of patients fit in this group.2,3 Usually there is
30
C. Talhari et al.
Borderline tuberculoid leprosy (BT)
The skin lesions (up to 10 or 20 or more) are similar to
those observed in tuberculoid leprosy. Usually the lesions are
larger than those observed in TT. It is frequent to observe
satellite lesions near the larger lesions or finger-like which
extends from the edges of the plaques or macules (Figure 12)
into the normal skin, and the color varies from hypochromic
to reddish. Lesions may vary in size, shape and color in the
same patient. Reactions (type 1) are frequent and swollen/
ulceration of the cutaneous lesions may occur.1,10,11 Nerves
are severely involved during reactions in BT leprosy
(Figure 13).24 Nerve function may deteriorate rapidly, and
urgent treatment to prevent permanent deformity and
disability is necessary.
Some patients may present only anesthetic macules and
nerve enlargement. They are called maculoanesthetic
borderline.1,10,11
The bacilloscopy varies from negative to positive (2+).22
Borderline leprosy (BB) or mid-borderline leprosy
BB leprosy is characterized by the presence of infiltrated
plaques of variable sizes, with a central apparently spared skin
(usually it is hypochromic), well defined inner edge and vague
defined outer edges, invading the normal skin in some areas
(Figure 14).1 The combination of these lesions gives the
Swiss cheese like aspect (Figure 15). Macules, plaques,
papules, and nodules are usually found in combination with the
typical lesions. In BB leprosy there are disseminated reddish
coppery lesions, usually symmetrically distributed.10,11
BB leprosy is rare and considered the most unstable part
of the spectrum. It moves rapidly towards one of the polar
forms (TT or LL). Nerve involvement is variable in these
patients. It may be severe during the frequent type 1 reaction
or up/downgrading evolution.23
The bacilloscopy is usually strongly positive (2+ to 4+).22
Borderline lepromatous leprosy (BL)
As in other types of leprosy, BL starts as hypopigmented
macular lesions. In these patients, the lesions are disseminated,
symmetrically distributed. With time the macula increase in
31
32
C. Talhari et al.
33
damage 38 and gynecomastia 39 are also associated with
lepromatous leprosy. Bones of the face, hands, feet, and
others may also be affected and contribute to disabilities.40
In LL patients the bacilloscopy is strongly positive with
globi and a bacterial index of 6 + (the maximum of this
logarithmic scale as mentioned above).22
The following diseases should be differentiated from LL
and BL leprosy 1,10,16,17:
34
C. Talhari et al.
Fig. 24 Ulnar claw. Fourth and fifth fingers flexion due to ulnar
nerve damage in a leprosy patient.
Coinfection HIV/AIDS/leprosy
HIV prevalence rates are still increasing in many countries
where leprosy is endemic. According to the Joint United Nations
Programme on HIV/AIDS (UNAIDS), in 2011, the number of
people living with HIV worldwide continued to grow, reaching
an estimated 34 million (31.4-35.9 million).48
In such scenario, it would be expected that the
geographical overlap of these two diseases would result in
an increasing number of co-infected individuals.49 Global
data indicates that, contrary to the early expectations, there
seems to be no significant increase in leprosy and HIV coinfection.50 Most of the larger studies on the subject were
done in the early to mid-1990s, examining the rate of HIV
serum positivity among leprosy patients.5157
An interesting aspect of the pathogenesis of leprosy in Aids
patients with low T-CD4 + cell count is what has been called
the granuloma paradox: an apparent preservation of the ability
to form granuloma among these patients, in clear contrast with
what is observed in M tuberculosis and HIV co-infected
patients. It has been shown that histopathologic features of
leprosy appear to be maintained in co-infected patients.49
Recent findings demonstrate a possible impact of HIVinfection, HAART, and MDT over leprosy granuloma
formation, contrasting with the granuloma paradox initially
proposed and reinforce the need of careful follow-up of coinfected patients.58
The most often observed clinical form of leprosy in coinfected patients is BT (Figure 25). The large majority of
35
these cases have been reported in association with an
immunopathological phenomenon called Immune Reconstitution Inflammatory Syndrome (IRIS).5864 IRIS occurs in a
subgroup of AIDS patients with apparent clinical deterioration
despite the T-CD4 + cell count improvement induced by
highly active antiretroviral therapy (HAART).59
One particularly challenging aspect of leprosy-HIV/AIDS
co-infection is the diagnosis of patients with peripheral
neurological manifestations. It may be confounded by
neuropathy associated with HIV itself or with stavudine
and other nucleoside-analogue reverse-transcriptase inhibitors. The clinical findings such as nerve enlargement,
sensory loss, muscle force impairment, and electromyoneuromyography results are important for the diagnosis.58
Recently, it was suggested that even though leprosyHIV/AIDS co-infection does not manifest homogenously
across affected populations, immunological features seem
to be shared by certain sub-groups. In this context, a clinical
classification of M leprae and HIV/AIDS co-infected
patients was proposed and include the following: 1
M leprae-HIV true co-infection: this group is composed
by HIV-positive individuals that do not fulfill AIDS
criteria, therefore, not under HAART; behaving similarly
to immunocompetent subjects; 2 opportunistic leprosy
disease: composed by AIDS patients not receiving
HAART, presenting usually multibacillary leprosy; this
group would be composed by individuals manifesting
leprosy as an opportunistic mycobacteriosis, as expected in
immunosuppressed individuals; and 3 HAART related
leprosy: including AIDS patients presenting all clinical
forms of leprosy related or not to IRIS. Combined HAART
and multidrug therapy might cause upgrading shift
within the leprosy clinical spectrum, as may be revealed
by long-term follow-up. 58
Finally, there is still a lot to learn about this ancient
disease that, despite intense research efforts throughout the
past centuries 65,66, is yet not fully understood. Although
important progress has been made concerning the treatment
36
of leprosy, as published by WHO in 2010 67, a major effort
is still necessary to seek an uniform and shorter multidrug
therapy with potent bactericidal drugs.68
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