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Authors
Fatma
Dedeoglu,
MD
Susan
Kim,
MD,
MMSc
Robert Sundel, MD
Section
Editor
Thomas JA Lehman, MD
Deputy
Editor
Elizabeth TePas, MD, MS
Disclosures
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last
updated: Wed Jun 15 00:00:00 GMT 2011(More)
INTRODUCTION Henoch-Schnlein purpura (HSP) is the most common form of systemic
vasculitis in children. Ninety percent of cases occur in the pediatric age group. In contrast to
many other forms of systemic vasculitis, HSP is self-limited in the great majority of cases.
The disease is characterized by a tetrad of clinical manifestations:
Arthritis/arthralgia
Abdominal pain
Renal disease
The clinical manifestations, pathogenesis, diagnosis, and differential diagnosis of HSP will be
presented here. The management of HSP and a more complete discussion of the renal
manifestations of HSP are found elsewhere. (See "Management of Henoch-Schnlein
purpura" and "Renal manifestations of Henoch-Schnlein purpura".)
EPIDEMIOLOGY HSP is primarily a childhood disease that occurs between the ages of 3
and 15 years. In a population-based study from the United Kingdom, the annual incidence
was about 20 per 100,000 in children <17 years of age with a peak incidence of 70 per
100,000 in children between the ages of four and six years [1]. In reports from Taiwan and
the Czech Republic, there was a lower incidence of 10 per 100,000 in children <17 years of
age with a peak incidence at five to seven years of age [2,3]. Although there are no
comparable epidemiologic data, HSP is less common in adults [4]. The rate of HSP is
significantly higher (approximately 5 percent) in patients with familial Mediterranean fever
[5,6].
There is a male predominance with reported male-to-female ratios of 1.2:1 to 1.8:1
[1,2,7,8]. HSP is seen less frequently in black compared to white or Asian children [1].
HSP occurs primarily in the fall, winter, and spring, but rarely in the summer months [7-9],
possibly explained by the association of HSP with infections. About half of the cases of HSP
are preceded by an upper respiratory infection [10], especially those caused by
streptococcus [11,12]. Other infectious agents, vaccinations, and insect bites also have
been implicated as possible triggers for HSP [10].
PATHOGENESIS HSP is an immune-mediated vasculitis associated with immunoglobulin
A (IgA) deposition. Although a variety of infectious and chemical triggers are recognized,
the underlying cause of HSP remains unknown. Immunologic, genetic, and environmental
factors all seem to play a role.
The characteristic finding of HSP is leukocytoclastic vasculitis accompanied by IgA immune
complexes within affected organs (picture 1A-B). Skin biopsies of purpuric lesions
demonstrate the involvement of small vessels (primarily postcapillary venules) within the
papillary dermis. The predominant cell types within the inflammatory infiltrate are
neutrophils and monocytes.
Immunofluorescence studies show IgA, C3, and fibrin deposition within the walls of involved
vessels. IgA, C3, fibrin, IgG, and less commonly IgM also are deposited within the
endothelial and mesangial cells of the kidney (picture 2).
Attention has focused on the potential role of increased serum levels of IgA and IgA immune
complexes in the pathogenesis of HSP. In addition, several studies report alterations in the
glycosylation of IgA, elevated levels of IgA anticardiolipin antibodies, and increased levels of
transforming growth factor-beta in patients with HSP [8,13-17]. The fact that only IgA1 is
found, out of the two IgA subtypes (IgA1 and IgA2), in the inflammatory infiltrates of this
disease remains unexplained [18,19], and the precise role of IgA and the specific
involvement of IgA1 in the pathogenesis of HSP remain unclear.
Another clue to the pathogenesis of HSP comes from a series of 107 Turkish children with
HSP. Of these, 44 percent had mutations in MEFV, the familial Mediterranean fever (FMF)
gene (eight homozygous, six compound heterozygous, and 33 heterozygous). IgA and
markers of inflammation such as C reactive protein were more likely to be increased in the
patients with MEFV mutations. Fifteen of these patients were also diagnosed with and
treated for FMF. The significance of this overlap remains unclear. (See "Pathophysiology of
familial Mediterranean fever".)
CLINICAL MANIFESTATIONS The classic tetrad of HSP includes:
Arthritis/arthralgia
Abdominal pain
Renal disease
These clinical manifestations may develop over the course of days to weeks and may vary in
their order of presentation. Purpura and joint pain are usually the presenting symptoms, but
this is not always the case. In the absence of the classic purpuric rash, the diagnosis of HSP
may not be obvious. Patients who present with significant joint or abdominal symptoms
without the skin manifestations may be thought to have an infectious or surgical process.
The mean age of onset of HSP is between six and seven years of age [ 1,2,7,8]. Based upon
retrospective reviews from Taiwan, Italy, and the United States, the major clinical
manifestations develop with the following frequencies (table 1) [2,7,18]:
Arthralgia/arthritis In the American and Italian series, joint symptoms were the
second most common manifestation, occurring in three-quarters of the patients. In
the Taiwanese study, joint complaints were present in 43 percent of patients.
Abdominal pain Colicky pain occurred in about half of patients and gastrointestinal
bleeding in approximately 20 to 30 percent of patients.
In the retrospective Italian review of 150 children with HSP, the presenting symptom was
purpura in 74 percent, arthritis in 15 percent, and abdominal pain in 12 percent of patients
[7]. Similar results were seen in a Spanish retrospective review of 78 patients [8]; purpura,
arthritis, and abdominal pain were the initial findings in 70, 12, and 17 percent of patients,
respectively. A Finnish prospective study of 223 HSP patients reported rash as the
presenting symptom in 73 percent, preceding other symptoms by a mean of four days [20].
Skin manifestations The classic rash of HSP is not the initial presenting sign in about
one-quarter of affected children. As a result, it may be difficult to make the diagnosis of HSP
prior to its development in patients who present with other clinical manifestations, such as
abdominal pain or arthritis.
The rash often begins with erythematous, macular, or urticarial wheals. The wheals then
coalesce and evolve into the typical ecchymoses, petechiae, and palpable purpura (picture
3 and picture 4 and picture 5). The rash typically appears in crops, symmetrically
distributed, and located primarily in gravity/pressure-dependent areas such as the lower
extremities. The buttocks are often involved in toddlers, and the face, trunk, and upper
extremities in nonambulatory children.
Localized subcutaneous edema is a common feature that may be found in dependent and
periorbital areas, especially in younger children (<3 years of age). Even adult patients,
however, may also have this manifestation of HSP, particularly involving the dorsal aspect of
the hands.
Arthritis/arthralgia Arthritis/arthralgia, which occur in up to 84 percent of patients
[7] are uncommon as the sole symptom at presentation. As previously noted,
arthritis/arthralgia are the presenting symptom in about 15 percent of patients [7].
The arthritis is usually transient or migratory, typically oligoarticular (one to four joints), and
nondeforming. It usually affects the lower extremity large joints (hips, knees, and ankles),
or less commonly the upper extremities (elbows, wrists, and hands) [7,8]. There is often
prominent periarticular swelling and tenderness, but usually without joint effusion,
erythema, or warmth. Patients may have considerable pain and limitation of motion.
Younger children with lower extremity involvement may refuse to ambulate. The arthritis
does not cause any chronic damage or sequelae. It may precede the appearance of purpura
by one or two days.
Gastrointestinal symptoms Gastrointestinal symptoms occur in about half of children
with HSP and range from mild (nausea, vomiting, abdominal pain, and transient paralytic
ileus) to more significant findings (gastrointestinal hemorrhage, bowel ischemia and
necrosis, intussusception, and bowel perforation). Guaiac-positive stool is found in up to 56
percent of patients, but massive gastrointestinal hemorrhage is rare [21]. The frequent
presence of fecal occult blood, hypoalbuminemia without proteinuria, and positive alpha1antitrypsin tests even in patients without gastrointestinal symptoms suggests that
gastrointestinal involvement and mucosal injury is more common than the clinical history
indicates [20].
Gastrointestinal symptoms typically develop within eight days of the appearance of the rash,
although much longer intervals (weeks to months) have been described [22].
Gastrointestinal complaints precede the rash in about 15 to 35 percent of cases, making the
diagnosis of HSP less apparent in these patients. Gastrointestinal symptoms without the
appearance of cutaneous purpura at any time also have been described in case reports [2325].
Gastrointestinal pain associated with HSP is caused by submucosal hemorrhage and edema.
Purpuric lesions may be seen on endoscopy, commonly in the descending duodenum,
stomach, and colon. The terminal ileum also may be involved. Submucosal edema,
ulceration, and spasm of the ileum and jejunum may be seen in small bowel series.
(See "Gastrointestinal manifestations of vasculitis".)
Intussusception is the most common gastrointestinal complication of HSP. Rarer
gastrointestinal manifestations include acute pancreatitis, gall bladder involvement, bowel
perforation, and, in children, a protein-losing enteropathy [21,26-31].
Intussusception Edema and hemorrhage can act as a pathological lead-point,
contributing to the development of intussusception. Intussusception is limited to the small
bowel in about 60 percent of cases, in contrast to idiopathic intussusception, which is
typically ileocolic [32]. Intussusception in HSP has a reported overall incidence of about 3.5
percent, although some retrospective series reported an incidence of only 0.4 to 0.6 percent
[7,21]. This discrepancy may be due to differences in the population studied. Children
demonstrating severe gastrointestinal pain and/or requiring hospitalization are presumably
at greater risk.
In a retrospective review of 149 hospitalized children with HSP from two centers in Chicago,
63 patients (42 percent) presented with severe abdominal pain [33]. Four patients were
diagnosed with intussusception, two of which were ileoileal intussusceptions. All four
patients required surgical correction.
In patients with HSP, ultrasonography should be the initial screening test in cases of
suspected intussusception. Although contrast enemas are the standard procedure in other
clinical settings to diagnosis intussusception, they cannot detect ileoileal intussusception
typically seen in HSP. (See "Intussusception in children".)
Renal disease Retrospective cohort studies report that 20 to 54 percent of patients with
HSP had some degree of early renal involvement [7,18,34,35]. Manifestations of renal
disease ranged from isolated hematuria and/or proteinuria without any abnormality in renal
function or blood pressure to acute nephropathy with renal insufficiency.
The presentation of renal disease was illustrated in a retrospective review of 261 children
with HSP (<17 years of age) [34]. Renal involvement was detected in 52 patients (20
percent) within four weeks of diagnosis. Specific findings included the following:
In a systematic review of the literature, 12 studies were identified that assessed the course
of renal disease in children with HSP [36]. Of the 1133 patients, one-third had an abnormal
urinalysis during the course of their disease. In 305 patients (27 percent), the abnormality
was either isolated hematuria or proteinuria, and nephritis or nephrosis was seen in only 82
patients (7 percent). At the time of follow-up (range 6 weeks to 36 years), only 21 patients
(1.8 percent) had renal impairment. Patients who had nephritis or nephrosis were at
increased risk for developing renal impairment compared with all patients with HSP (RR
11.8, 95% CI 4.1 to 41.5).
The overall renal prognosis of HSP in children is considered to be excellent. Long-term
follow-up studies demonstrate a small risk of progressive renal disease both in children and
adults, although it does account for much of the chronic morbidity in patients with HSP.
A more complete discussion on the renal manifestations of HSP, including prognosis and
treatment, is found elsewhere. (See "Renal manifestations of Henoch-Schnlein purpura".)
Other organ involvement Other organ systems also may be involved:
scrotum.
The presentation may mimic testicular torsion. Evaluation including ultrasonography
and technetium Tc99m radionuclide scanning can differentiate the two entities. In
testicular torsion, these studies demonstrate decreased blood flow to the testicle, in
contrast to the normal or increased flow seen in boys with HSP.
The clinical presentation of scrotal involvement in HSP was reviewed in a
retrospective study of 120 Korean boys diagnosed with HSP between 1992 and 2004
[40]. Twenty-six patients (22 percent) had scrotal involvement, which presented as
scrotal swelling (23 patients), scrotal pain or tenderness (18 patients), and bilateral
involvement (seven patients). Scrotal pain was the initial finding of HSP in two of the
patients. Imaging (ultrasonography and/or radionuclide scan) was performed in 15
patients and demonstrated epididymitis in 13 and orchitis in two patients. One
patient underwent surgical exploration but there was no evidence of testicular
torsion.
Central and peripheral nervous system Single reports and case series document
neurologic manifestations including headaches, seizures, focal neurologic deficits,
ataxia, intracerebral hemorrhage, and central and peripheral neuropathy in children
with HSP [41-43]. Most of the central nervous system findings are transient except
for occasional permanent sequelae associated with hemorrhagic stroke.
Eyes Keratitis and uveitis, both reported in patients with HSP, are very rare
sequelae of HSP and usually suggest other diseases [44].
Respiratory tract In a cohort of French patients hospitalized for HSP, impaired lung
diffusion capacity and mild interstitial changes on chest radiographs were found in
the majority of patients (97 and 69 percent, respectively), despite the absence of
significant respiratory symptoms [45]. A retrospective review of HSP patients at the
Mayo Clinic, on the other hand, identified only 3 of 124 patients with pulmonary
involvement [46]. There also are case reports of pulmonary hemorrhage in patients
with HSP [47-49].
Adults Adult patients with HSP present with clinical manifestations very similar to those
that occur in children. Two main distinctions exist between adults and children with HSP.
Adults are at increased risk for developing significant renal involvement including
end-stage renal disease [4,50].
This was best illustrated by a retrospective review of 250 French adults with HSP (median
age: 50 years). At presentation, clinical findings included palpable purpura (96 percent),
arthritis (61 percent), and gastrointestinal symptoms (48 percent) [50]. Almost one-third of
patients had renal insufficiency (creatinine clearance <50 ml/min per m2) within four
these studies demonstrate decreased blood flow to the testicle. In boys with HSP, testicular
blood flow is normal or increased. (See 'Other organ involvement' above.)
Classification criteria A variety of classification criteria for HSP have been proposed,
primarily for use in research protocols and outcome studies. They have not been validated
for the diagnosis of individual cases.
In 1990, the American College of Rheumatology (ACR) Classification established criteria to
classify seven types of vasculitides including HSP [56,57]. The ACR criteria for the diagnosis
of HSP are as follows:
Palpable purpura
These criteria were based upon a comparison between 85 patients with HSP and 722 adult
patients with other forms of vasculitis. Two or more of the criteria had a sensitivity and
specificity of approximately 90 percent in separating adult patients with HSP from those with
other causes of vasculitis.
In 2005, pediatric consensus criteria were developed by the European League against
Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PRES) [58], and
were subsequently validated in conjunction with the Paediatric Rheumatology International
Trials Organisation (PRINTO) [59]. These criteria are more appropriate for pediatric settings
in which a clinician is likely seeking features to distinguish HSP from gastroenteritis or
appendicitis rather than from granulomatosis with polyangiitis (Wegener's). The mandatory
criterion is purpura (usually palpable and in clusters) or petechiae, with lower limb
predominance and without thrombocytopenia or coagulopathy. Patients also must have one
or more of the following:
HSP is not the only disease that may have these manifestations (see 'Differential
diagnosis' below). In general, HSP is a clinical diagnosis in children, and biopsies should be
considered only rarely, in atypical or ambiguous cases.
Other small vessel vasculitides There are a number of causes of small vessel
vasculitis (including HSP) that may present with asymmetric polyneuropathy,
palpable purpura, and/or pulmonary-renal involvement. These diseases include
primary vasculitides (eg, granulomatosis with polyangiitis (Wegener's), microscopic
polyangiitis, Churg-Strauss syndrome), and vascular inflammation secondary to a
connective tissue disorder (eg, systemic lupus erythematosus [SLE]) or to an
infectious disease (eg, hepatitis B or C). In general, these diseases, which mimic
HSP, are uncommon in children.
Laboratory evaluation including serum complement levels, antinuclear antibodies, antidouble stranded deoxyribonuclease (anti-dsDNA), and antineutrophil cytoplasmic antibodies
(ANCA), may differentiate HSP from the other causes of small vessel vasculitis. Light
microscopic examination of a purpuric lesion will demonstrate leukocytoclasis in many small
vessel vasculitides, but it is the predominance of IgA deposition that distinctively
characterizes
HSP.
(See "Classification
and
incidence
of
childhood
written in plain language, at the 5 th to 6th grade reading level, and they answer the four or
five key questions a patient might have about a given condition. These articles are best for
patients who want a general overview and who prefer short, easy-to-read materials. Beyond
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Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)
Abdominal pain
Renal disease
HSP occurs primarily between the ages of 3 and 15 years. The annual incidence is 10
to 20 per 100,000 in children <17 years of age with a peak incidence in children
between four to six years of age. Approximately, 10 percent of HSP cases occur in
adults. (See 'Epidemiology' above.)
The diagnosis of HSP is usually based upon clinical manifestations of the disease. In
patients with an incomplete or unusual presentation, biopsy of the affected organ
(eg, skin or kidney) demonstrating predominantly IgA deposition supports the
diagnosis of HSP. (See 'Diagnosis' above.)
There are no diagnostic tests for HSP. Patients in whom the diagnosis is at all in
doubt should have a CBC, prothrombin, and urinalysis. The presence of
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