IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis

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IgA vasculitis (Henoch-Schönlein purpura): Clinical

manifestations and diagnosis
Authors: Fatma Dedeoglu, MD, Susan Kim, MD, MMSc
Section Editors: Robert Sundel, MD, Suzanne C Li, MD, PhD
Deputy Editor: Elizabeth TePas, MD, MS

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2023. | This topic last updated: Feb 22, 2023.

INTRODUCTION

Immunoglobulin A vasculitis (IgAV; formerly called Henoch-Schönlein purpura [HSP]) [1,2],

is the most common form of systemic vasculitis in children, with an incidence range of 3 to
27 per 100,000 [3]. Ninety percent of cases occur in the pediatric age group. In contrast to
many other forms of systemic vasculitis, IgAV is typically self-limited. The disease is
characterized by a tetrad of clinical manifestations:

● Palpable purpura in patients with neither thrombocytopenia nor coagulopathy

● Arthritis/arthralgia
● Abdominal pain
● Kidney disease

The clinical manifestations, pathogenesis, diagnosis, and differential diagnosis of IgAV are
presented here. The management of IgAV and a more complete discussion of the kidney
manifestations of IgAV are found elsewhere. (See "IgA vasculitis (Henoch-Schönlein
purpura): Management" and "IgA vasculitis (Henoch-Schönlein purpura): Kidney
manifestations".)

EPIDEMIOLOGY

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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis

IgAV is primarily a childhood disease that occurs between the ages of 3 and 15 years [3,4].
In a population-based study from the United Kingdom, the annual incidence was
approximately 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 [5]. 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 [6,7]. A subsequent population-
based study from France showed an incidence relatively similar to previously reported
numbers (approximately 19 per 100,000 children), suggesting general stability of the
incidence [8]. A higher incidence has been reported in several Asian studies, including a
South Korean study that found an incidence of approximately 56 per 100,000 children [9].
Another South Korean observational study comparing two time periods (1987 to 1996
versus 2006 to 2015) found that the peak incidence was five years of age and also reported
longer hospitalization and higher rate of proteinuria and recurrence in the earlier time
period [10].

IgAV is less common in adults [11], with an estimated annual incidence of 5 per 100,000
adults in Slovenia [12]. In several retrospective studies, 20 to 30 percent of patients with
IgAV were adults. In these cohorts, adults had significantly worse kidney outcomes
compared with children [13-15].

Most studies show a male predominance, with reported male-to-female ratios of 1.2:1 to
1.8:1 [3,5,6,12,16,17], although two Korean studies have shown a slight female
predominance [9,18]. IgAV is seen less frequently in Black British children compared with
White or South Asian British children [2,5].

IgAV occurs primarily in the fall, winter, and spring but rarely in the summer months
[2,8,16-19], possibly explained by the association of IgAV with infections. Approximately
one-half of the cases of IgAV are preceded by an upper respiratory tract infection [20],
especially those caused by Streptococcus [21]. Other infectious agents, vaccinations, and
insect bites also have been implicated as possible triggers for IgAV [20]. A large
epidemiologic study of 16,000 children from South Korea demonstrated a temporal
relationship with respiratory syncytial virus (RSV), influenza, and norovirus [18]. In a
systematic literature review, it was noted that a majority of the studies had failed to show
causal association between vaccinations and vasculitides including IgAV [22-24]. The rate
of IgAV is significantly higher (approximately 5 percent) in patients with familial
Mediterranean fever [25,26]. In addition, MEFV innate immunity regular, pyrin (MEFV)
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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis

pathogenic variants may affect clinical presentation of IgAV. Abdominal pain and
intussusception were more common in patients with MEFV pathogenic variants [27].

CLASSIFICATION CRITERIA

A variety of classification criteria for IgAV 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, a committee of the American College of Rheumatology (ACR) established criteria

to classify seven types of vasculitides including IgAV [28,29]. The ACR criteria for the
diagnosis of IgAV are as follows:

● Palpable purpura
● Age at onset ≤20 years
● Acute abdominal pain
● Biopsy showing granulocytes in the walls of small arterioles and/or venules

These criteria were based upon a comparison between 85 patients with IgAV 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 IgAV from those
with other causes of vasculitis.

In 2005, pediatric consensus criteria were developed by the European Alliance of

Associations for Rheumatology (EULAR; formerly known as European League Against
Rheumatism) and the Paediatric Rheumatology European Society (PRES) [30] and were
subsequently validated in conjunction with the Paediatric Rheumatology International
Trials Organisation (PRINTO) [31]. These criteria, which have a 93 percent sensitivity and 89
percent specificity, are more appropriate for pediatric settings in which a clinician is most
likely seeking features to distinguish IgAV from gastroenteritis or appendicitis rather than
from granulomatosis with polyangiitis. 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:

● Abdominal pain (usually diffuse, with acute onset)

● Arthritis or arthralgia (acute onset)

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● Kidney involvement (proteinuria, hematuria)
● Leukocytoclastic vasculitis or proliferative glomerulonephritis, with predominant IgA
deposition

However, IgAV is not the only disease that may have these manifestations. (See 'Differential
diagnosis' below.)

PATHOGENESIS

IgAV is an immune-mediated vasculitis associated with IgA deposition accompanied with

complement deposition and neutrophil recruitment. Although a variety of infectious and
chemical triggers are recognized, the underlying cause of IgAV remains unknown.
Immunologic, genetic, and environmental factors all seem to play a role [32-34]. The
human leukocyte antigen (HLA) region as well as polymorphisms in other immune-related
genes are associated with IgAV, sometimes with conflicting results, which could be due to
differences in ethnic and environmental factors [35,36]. Susceptibility polymorphisms in
genes that are associated with vascular response, such as the genes encoding endothelial
nitric oxide synthase (eNOS), interleukin (IL) 18, and angiotensin-converting enzyme (ACE),
have also been shown [2,37]. There are numerous case reports of IgAV occurring after
vaccination, and a case-control study found an increased risk of IgAV within 12 weeks after
vaccination with the measles-mumps-rubella (MMR) vaccine (odds ratio [OR] 3.4, 95% CI
1.2–10.0) but not with other vaccines [38]. The absolute risk was low, though (2.8 percent of
cases had MMR within 12 weeks of developing IgAV compared with 1 percent of controls).
A case-crossover study of 167 children found no increased risk of IgAV within three months
of receiving a vaccine compared with the three months prior to that (OR 1.6, 95% CI 0.8-
3.0) [24]. Similar results were seen for IgAV risk within 1, 1.5, or 2 months of vaccination.
These results suggest that vaccinations are not a major etiologic factor in IgAV and
therefore should not be avoided. A temporal relationship of IgAV with administration of
many classes of drugs including biologics has been reported [39,40].

The characteristic finding of IgAV is leukocytoclastic vasculitis accompanied by IgA immune

complexes within affected organs ( image 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. (See 'Biopsy' below.)
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Immunofluorescence studies show IgA, complement component 3 (C3), and fibrin

deposition within the walls of involved vessels. IgA, C3, fibrin, immunoglobulin G (IgG),
and, less commonly, immunoglobulin M (IgM) also are deposited within the endothelial
and mesangial cells of the kidney ( picture 1).

Attention has focused on the potential role of increased serum levels of IgA and IgA
immune complexes in the pathogenesis of IgAV, which contributed the current name
change. In addition, several studies report alterations in the glycosylation of IgA, elevated
levels of IgA anticardiolipin antibodies, and increased levels of transforming growth factor
(TGF) beta in patients with IgAV [17,41-45]. The fact that only one of the two IgA subtypes
(galactose-deficient IgA1, but not IgA2) is found in the inflammatory infiltrates of this
disease remains unexplained [46,47]. Galactose-deficient IgA1 containing immune
complexes may deposit more easily [3]. Similarly, the precise role of IgA and the specific
involvement of IgA1 in the pathogenesis of IgAV remain unclear. Some research suggests
that IgA anticardiolipin antibodies may play a role [41,48,49]. Results from one study
suggest that beta-2-glycoprotein I (beta-2GPI) is an antigenic target for IgA [50]. Despite
the increased presence of these antibodies, there are few reports of thrombosis. Activated
neutrophils and increased production of IL-8, as well as activated cytotoxic T cells and
natural killer (NK) cells, may also play a role [51,52].

CLINICAL MANIFESTATIONS IN CHILDREN

The classic tetrad of IgAV includes:

● Palpable purpura without thrombocytopenia and coagulopathy

● Arthritis/arthralgia
● Abdominal pain
● Kidney 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
IgAV 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. (See 'Differential diagnosis' below.)

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The mean age of onset of IgAV is between six and seven years. Based upon retrospective
reviews from several different countries, the major clinical manifestations develop with the
following frequencies [5,6,13,14,16,17,53-57]:

● Purpura – Purpura is the presenting symptom in approximately three-quarters of

patients, preceding other symptoms by a mean of four days in one series [58].

● Arthralgia/arthritis – In most of the series, joint symptoms were the second most
common manifestation, occurring in slightly over one-half to three-quarters of the
patients.

● Abdominal pain – Colicky pain occurred in approximately one-half of patients and

gastrointestinal bleeding in approximately 20 to 30 percent of patients.

● Kidney disease – The frequency of kidney involvement ranged from 21 to 54 percent.

Skin manifestations — Rash is the presenting sign in approximately three-quarters of

patients. The rash often begins with erythematous, macular, or urticarial wheals but also
can have less typical presentations including targetoid lesions. The rash may be itchy but is
rarely painful. The initial rash may coalesce and evolve into the typical ecchymoses,
petechiae, and palpable purpura ( picture 2A-E). 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 [2,3].

Localized subcutaneous edema is a common feature that may be found in dependent and
periorbital areas, especially in younger children (less than three years of age) ( picture 3
and picture 4). Even adult patients, however, may also have this manifestation of IgAV,
particularly involving the dorsal aspect of the hands. Blistering eruptions may also occur
[59].

Arthritis/arthralgia — Arthritis/arthralgia occur in up to 84 percent of patients [16,56].

However, joint complaints are uncommon as the sole symptom at presentation and are the
presenting symptom in approximately 15 percent of patients.

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) [2,3,16,17,53].
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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, though usually by no more than one or two days.

Gastrointestinal symptoms — Gastrointestinal symptoms occur in approximately one-

half of children with IgAV 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 [60].
The frequent presence of fecal occult blood, increased stool alpha-1-antitrypsin, and
hypoalbuminemia without proteinuria, even in patients without gastrointestinal
symptoms, suggests that gastrointestinal involvement and mucosal injury are more
common than the clinical history indicates [58].

Gastrointestinal symptoms typically develop within eight days of the appearance of the
rash, although much longer intervals (weeks to months) have been described [61].
Gastrointestinal complaints precede the rash in approximately 15 to 35 percent of cases. In
such patients, the diagnosis of IgAV is significantly more difficult. Gastrointestinal
symptoms without the appearance of cutaneous purpura at any time also have been
described in case reports [62-64]. In one small, retrospective review of children who had
skin biopsies, edema and rash above the waist were most common in patients who
presented with gastrointestinal involvement [65]. The reason for such a putative
association is not clear, since the rash of IgAV is typically found in gravity/pressure-
dependent areas. This finding will require confirmation in a larger cohort before it can be
relied upon. In a meta-analysis, high neutrophil-to-lymphocyte ratio (NLR) and low mean
platelet volume (MPV) were predictors of severe gastrointestinal involvement, though
there was significant heterogeneity among studies that were from only a few regions
(China, Turkey, and South Korea), limiting the generalizability of these findings [66].

Gastrointestinal pain associated with IgAV 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 "Overview of gastrointestinal manifestations of vasculitis".)
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Intussusception is the most common gastrointestinal complication of IgAV. Rarer

gastrointestinal manifestations include acute pancreatitis, gall bladder involvement, bowel
perforation, and, in children, protein-losing enteropathy [60,67-72].

Edema and hemorrhage can act as a pathologic lead point, contributing to the
development of intussusception. Intussusception is limited to the small bowel in
approximately 60 percent of cases, in contrast to idiopathic intussusception, which is
typically ileocolic [73]. Intussusception in IgAV has a reported overall incidence of 2.3 to 3.5
percent, although some retrospective series reported an incidence of only 0.4 to 0.6
percent [16,53,60]. 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 IgAV from two centers in
Chicago, 63 patients (42 percent) presented with severe abdominal pain [74]. Four patients
were diagnosed with intussusception, two of which were ileoileal intussusceptions. All four
patients required surgical correction. Intussusception is discussed in greater detail
separately. (See "Intussusception in children".)

Kidney disease — The kidney manifestations of IgAV, including prognosis and treatment,
are discussed in detail elsewhere. (See "IgA vasculitis (Henoch-Schönlein purpura): Kidney
manifestations".)

Kidney involvement has been reported in 20 to 54 percent of children with IgAV. It is more
prevalent in older children and adults [53,55]. The most common presentation is
hematuria with or without red blood cell casts and mild or no proteinuria. Nephrotic-range
proteinuria, an elevated serum creatinine, and/or hypertension are present in a minority of
patients. These findings, as well as the coexistence of hematuria and proteinuria, are
associated with an increased risk of progressive disease, which occurs more frequently in
adults. The findings on kidney biopsy are identical to those in IgA nephropathy. The
presence of microscopic papillary dermal edema and perivascular deposition of C3 on
direct immunofluorescence of skin biopsy samples may be associated with development of
kidney involvement [65].

Risk factors predicting kidney involvement are not well known, but several clinical and
laboratory features have been reported as kidney disease risk factors. In one meta-
analysis, older age at onset; gastrointestinal symptoms; relapse; elevated white blood cell
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count, platelet count, and antistreptolysin O (ASLO) titer; and low C3 were reported as
kidney disease risk factors, and a scoring system for risk of kidney disease development
was suggested [75]. Other findings associated with development of severe kidney disease
include delay in diagnosis, angioedema, central nervous system (CNS) involvement, and
persistent purpura [76,77]. Long-term follow-up of these patients is important to
determine which patients go on to develop end-stage kidney disease (ESKD), thus
identifying which of the kidney risk factors are actually associated with ESKD.

Other organ involvement — Other organ systems occasionally are involved in IgAV.

Urologic — Urologic involvement, most commonly of the scrotum, but also the ureter,
bladder, prostate, testicle, and penis, is reported [78]. The rate of scrotal involvement in
boys with IgAV ranges from 2 to 38 percent [79-82]. Rarely, scrotal pain may be the
presenting symptom. Clinical findings include pain, tenderness, and swelling of the
involved testicle and/or scrotum.

The presentation may mimic testicular torsion [83]. 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 IgAV.

The clinical presentation of scrotal involvement in IgAV was reviewed in a retrospective

study of 120 Korean boys diagnosed with IgAV between 1992 and 2004 [84]. Twenty-six
patients (22 percent) had scrotal involvement, which presented as scrotal swelling (23
patients) or scrotal pain or tenderness (18 patients). Unilateral involvement was more
common, with seven patients demonstrating inflammation of the scrotum bilaterally (27
percent). Scrotal pain was the initial manifestation of IgAV in two of the patients. Imaging
(ultrasonography and/or radionuclide scan) was performed in 15 patients and
demonstrated epididymitis in 13 and orchitis in 2 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 in children with IgAV including headaches, seizures,
encephalopathy (both hypertensive encephalopathy and posterior reversible
encephalopathy syndrome [PRES]), focal neurologic deficits, ataxia, intracerebral
hemorrhage, and central and peripheral neuropathy [85-88]. Most of the CNS findings are
transient except for occasional permanent sequelae associated with hemorrhagic stroke.
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Respiratory tract — In a cohort of French patients hospitalized for IgAV, 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 [89]. Similarly, another study found impaired lung diffusion capacity
in IgAV patients who did not have clinical or radiologic evidence of lung involvement
compared with age-matched control patients [90]. On the other hand, severe lung
involvement, such as pulmonary hemorrhage, is rare in patients with IgAV and is primarily
reported in adults and adolescents [91-94]. A comprehensive, 40-year review of lung
involvement in IgAV found diffuse alveolar hemorrhage was the most frequent
presentation [95].

Eyes — Keratitis and uveitis are rare sequelae of IgAV and usually suggest other diseases
[96]. (See "The red eye: Evaluation and management" and "Uveitis: Etiology, clinical
manifestations, and diagnosis".)

CLINICAL MANIFESTATIONS IN ADULTS

Adult patients with IgAV present with clinical manifestations similar to those that occur in
children [97]. There are two main differences between adults and children with IgAV:

● Intussusception is rare in adults.

● Adults are at increased risk for developing significant kidney involvement including
end-stage kidney disease (ESKD) [11,14,98-102]. (See 'Kidney disease' above.)

These characteristics of IgAV in adults were best illustrated in a retrospective review of 250
French patients whose median age was 50 years. At presentation, clinical findings included
palpable purpura (96 percent), arthritis (61 percent), and gastrointestinal symptoms (48
percent) [98]. Almost one-third of patients had kidney insufficiency (creatinine clearance
<50 mL/minute per m2) within four months of presentation. At a median follow-up of 14.8
years, persistent kidney impairment was seen in 80 patients (32 percent of the original
cohort), including ESKD in 27 patients and severe kidney impairment (creatinine clearance
<30 mL/minute) in another 32 patients. Potential explanations for the high prevalence of
substantial kidney impairment in this study include the possibility of selection bias (all
patients in the study had kidney disease severe enough to require kidney biopsy), the long

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period of follow-up compared with other studies, and the possible role of comorbidities
(eg, hypertension) contributing to the progression of kidney disease. An updated report on
this cohort that included an additional 10 patients revealed similar results [99]. However, a
smaller case series of adult patients from Northern India showed greater rates of arthritis
(90 percent) and abdominal pain in only 10 percent of adults at presentation [103], which
may suggest differences related to genetic and environmental exposures between these
countries. Reported outcomes are worse in adult patients >65 years of age compared with
other adults: Older patients achieved clinical remission less often (23.9 versus 46.2 percent)
and developed a 50 percent increase in their serum creatinine more often during the
period of observation (21.7 versus 4.7 percent) [101]. Another retrospective cohort study
comparing 35 adults to 159 children with IgAV also found kidney involvement to be more
common in adults. Upper respiratory infections were a frequent trigger for both groups.
Nonsteroidal antiinflammatory drugs (NSAIDs) were used more often in children, while
adults were typically treated with glucocorticoids and azathioprine. Persistent hematuria
was found to be independent risk factor for relapse in both groups and was more common
in adults [15].

Another retrospective series reviewed 68 adults with IgAV who had a skin biopsy with
leukocytoclastic vasculitis on histopathologic evaluation and IgA on direct
immunofluorescence. Notable findings in this patient group included a higher rate of
kidney involvement in patients older than 40 years whose skin biopsies showed an
absence of eosinophils and a higher rate of gastrointestinal involvement in patients whose
biopsies showed an absence of histiocytes [104].

Adults with no known trigger for the development of IgAV should have additional
evaluation for solid-organ cancers, especially if the disease is prolonged or recalcitrant to
treatment [105].

A more complete discussion of the kidney manifestations and the management of kidney
disease in patients with IgAV is found separately. (See "IgA vasculitis (Henoch-Schönlein
purpura): Kidney manifestations".)

LABORATORY FINDINGS

Serum IgA levels have been reported to be elevated in 50 to 70 percent of patients with

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IgAV, and higher levels are associated with kidney involvement [17,42,106].

Findings on routine blood tests (eg, complete blood cell count, serum chemistries, and
urinalysis) are nonspecific. Patients may have a normochromic anemia because of occult or
overt gastrointestinal bleeding. Other results, such as markers of inflammation, generally
reflect the triggering condition. IgAV following bacterial infections is more likely to be
characterized by leukocytosis (white blood cell count >20,000 cells/mm3) and an elevated
erythrocyte sedimentation rate (ESR). IgAV after viral illnesses, on the other hand, often
fails to demonstrate elevation of acute-phase reactants. Nevertheless, IgAV generally does
not cause systemic inflammation; as such, when present, other etiologies mimicking IgAV
should be considered (see 'Differential diagnosis' below). Prothrombin time (PT), partial
thromboplastin time (PTT), bleeding time, and platelet count are usually all normal. The
initial urinalysis is also typically normal, although proteinuria and/or hematuria may
develop over time.

Hypocomplementemia is reported in a significant percentage of children with IgAV, and

these patients are more likely to have evidence of a recent streptococcal infection [107]. A
case series of 338 children hospitalized at one center in China during a six-month period in
2010 to 2011 found that 53 children (15.7 percent) had decreased levels of complement
component 3 (C3) and/or complement component 4 (C4). Complement levels normalized
within three months in all patients, and they did not correlate with disease severity or
presence of nephritis in this cohort. As noted previously, several reports and a meta-
analysis suggest neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV)
may be predictors of severe gastrointestinal involvement [66]. Additional studies with
larger cohorts are needed to confirm these findings.

DIAGNOSIS

The diagnosis of IgAV is typically based upon clinical manifestations of the disease
(palpable purpura without thrombocytopenia or coagulopathy and two or three of the
remaining clinical features: arthritis/arthralgia, abdominal pain, and kidney disease)
[2,3,108,109]. The diagnosis is straightforward when patients present with the classic signs
and symptoms (palpable purpura of the lower extremities and buttocks in combination
with two or more of the other typical disease manifestations). However, the classic rash of
IgAV is not the initial presenting sign in approximately one-quarter of affected persons. It
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may be difficult to make the diagnosis of IgAV prior to the appearance of a rash in patients
who present with other clinical manifestations, such as abdominal pain or arthritis,
particularly in isolation. In patients with incomplete or unusual presentations, a biopsy of
an affected organ (eg, skin or kidney) that demonstrates leukocytoclastic vasculitis with a
predominance of IgA deposition confirms the diagnosis of IgAV. The diagnostic approach is
reviewed in the algorithm ( algorithm 1).

Biopsy — In pediatric patients, biopsy is reserved for patients with an unusual

presentation of IgAV (ie, no rash, or an atypical rash) or those with significant kidney
disease.

Confirmation of the diagnosis by biopsy is more important in adult patients because of the
lower incidence of IgAV beyond the pediatric age group and the comparatively higher
incidence of other forms of vasculitis that may be clinically similar to IgAV.

Skin — Biopsies of the skin, which sample the small blood vessels of the superficial
dermis, are usually adequate to make the diagnosis of IgAV. Light microscopy studies
(hematoxylin and eosin stains) demonstrate the classical leukocytoclastic vasculitis in
postcapillary venules with IgA deposition that is pathognomonic of IgAV ( image 1A-B)
[110]. The biopsy should contain skin lesions that are less than 24 hours old because, in
more chronic lesions, vessel damage leads to nonspecific leakage of all isotypes of
immunoglobulin. Immunofluorescence studies, essential to confirming the diagnosis of
IgAV, generally require biopsy of a second skin site.

Kidney — Kidney biopsy is reserved for patients in whom the diagnosis is uncertain or if
there is clinical evidence of severe kidney involvement. IgAV is characterized by IgA
deposition in the mesangium on immunofluorescence microscopy that is identical to that
in IgA nephropathy ( picture 1). Light microscopy changes range from isolated mesangial
proliferation to severe crescentic glomerulonephritis. (See "IgA vasculitis (Henoch-
Schönlein purpura): Kidney manifestations".)

Laboratory tests — No laboratory test is diagnostic for IgAV. However, confirmation of a

normal platelet count and coagulation studies (prothrombin time [PT], partial
thromboplastin time [PTT], and bleeding time) are necessary when clinical features do not
allow conclusive distinction of IgAV from other diseases that present with purpura due to
thrombocytopenia or coagulopathy. Other studies may be performed as part of the
evaluation for disorders in the differential diagnosis. Some laboratory studies, such as
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urinalysis, are obtained once the diagnosis of IgAV is made but are not required for
diagnosis. (See 'Differential diagnosis' below and "Purpuric skin lesions (petechiae,
purpura, and ecchymoses) in children: Evaluation" and 'Additional evaluation' below.)

In patients who have an atypical presentation, such as abdominal pain before or without
the rash, endoscopy (EGD) or video capsule endoscopy (VCE) may be needed to confirm the
diagnosis. One study of 30 children in whom the diagnosis was still under question even
after standard EGD described VCE findings of IgAV (eg, mucosal erosion, erythema, and/or
petechia) in most patients [111].

DIFFERENTIAL DIAGNOSIS

In children presenting with the classic signs of palpable purpura plus some combination of
abdominal pain, arthritis/arthralgia, and/or kidney involvement, the diagnosis of IgAV is
generally straightforward [30]. However, the diagnosis is more difficult if there is an
incomplete presentation of IgAV, particularly if the skin manifestations are initially absent.
In these circumstances, other causes for purpura, arthritis, abdominal pain, and kidney
disease need to be considered [2].

Purpura — Petechiae and purpuric rashes may be associated with septicemia, immune
thrombocytopenia (ITP), hemolytic uremic syndrome, leukemia, and coagulopathies (eg,
hemophilia). Normal platelet count and coagulation studies differentiate IgAV from these
entities.

However, there are several other conditions that may present with purpura with normal
platelet counts and coagulation studies:

● Acute hemorrhagic edema of infancy (AHEI) – AHEI (also known as Finkelstein or

Seidlmayer disease) is a leukocytoclastic vasculitis described in children between the
ages of four months to two years [112-116]. It is a self-limited disease that presents
with fever, purpura, ecchymosis, and inflammatory edema of the limbs and resolves
in one to three weeks ( picture 5). Involvement of the kidney and the
gastrointestinal tract is uncommon, but, when it occurs, it is very similar to that seen
in IgAV [117,118]. Biopsy of the skin demonstrates a leukocytoclastic vasculitis with
occasional IgA deposition. It is unclear whether this condition is truly a separate
entity from IgAV or actually overlaps with it.
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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis
● Hypersensitivity vasculitis – Hypersensitivity vasculitis is an inflammation of the
small vessels that occurs after exposure to drugs or infection or without an
identifiable trigger [29]. Patients present with fever, urticaria, lymphadenopathy, and
arthralgias but not usually glomerulonephritis. Histopathology shows a
leukocytoclastic vasculitis primarily of the postcapillary venules, but IgA deposition is
absent. (See "Hypersensitivity vasculitis in children".)

● Other small vessel vasculitides – There are a number of causes of small vessel
vasculitis (including IgAV) that may present with asymmetric polyneuropathy,
palpable purpura, and/or pulmonary or kidney involvement. These diseases include
primary vasculitides (eg, granulomatosis with polyangiitis), microscopic polyangiitis,
eosinophilic granulomatosis with 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 are uncommon in children. (See "Overview of and approach to the
vasculitides in adults" and "Vasculitis in children: Incidence and classification".)

Laboratory evaluation of autoantibodies, including antinuclear antibodies, anti-double-

stranded DNA (anti-dsDNA), and antineutrophil cytoplasmic antibodies (ANCAs), is typically
negative in IgAV. Abnormal results for any of these studies may differentiate IgAV from the
other causes of small vessel vasculitis. The majority of patients have normal complement
levels, but hypocomplementemia has been reported both in IgAV and in AHEI [117]. Light
microscopic examination of a purpuric lesion demonstrates leukocytoclasis in many small
vessel vasculitides, but it is the predominance of IgA deposition that distinctively
characterizes IgAV. (See "Vasculitis in children: Incidence and classification" and "Overview
of and approach to the vasculitides in adults", section on 'Small-vessel vasculitis'.)

Arthritis and arthralgia — In approximately 15 percent of patients with IgAV, arthritis or

arthralgia may be the presenting manifestation, usually preceding the skin manifestations
by only one day. Until a patient develops the classical purpura of IgAV, other causes of joint
complaints must be considered including autoimmune diseases, septic or reactive arthritis,
and toxic synovitis (also called transient synovitis).

Autoimmune diseases, such as SLE, juvenile idiopathic arthritis (JIA), and rheumatic fever,
may present with joint symptoms similar to IgAV. Assays for serum complement,
antinuclear and anti-dsDNA antibodies, and rheumatoid factor are typically normal in

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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis

patients with IgAV. Abnormal results for any of these studies may help to differentiate IgAV
from SLE and JIA, although at least 15 percent of patients with IgAV may also have
transient hypocomplementemia [107].

Evidence of a recent group A beta-hemolytic streptococci infection (eg, positive throat

culture, positive rapid streptococcal antigen test, or elevated anti-streptolysin O [ASLO]
titers) and the clinical course distinguish acute rheumatic fever from IgAV, with the caveat
that a significant proportion of cases of IgAV are triggered by streptococcal infections.
Reactive arthritis may be triggered by a variety of genitourinary and gastrointestinal
pathogens including beta-hemolytic streptococcal infections. Reactive arthritis may cause a
painful polyarthritis and high fevers, but the characteristic rash of IgAV should allow
distinction between these conditions. Similarly, when considering toxic synovitis, another
self-limited disease with transient joint findings that resolve without long-term sequelae,
evolution of the other manifestations of IgAV will help differentiate the two conditions.
(See "Childhood-onset systemic lupus erythematosus (SLE): Clinical manifestations and
diagnosis" and "Polyarticular juvenile idiopathic arthritis: Clinical manifestations, diagnosis,
and complications" and "Oligoarticular juvenile idiopathic arthritis" and "Acute rheumatic
fever: Clinical manifestations and diagnosis".)

Septic arthritis and toxic synovitis also may present with joint symptoms similar to those
seen in patients with IgAV. Septic arthritis and toxic synovitis also may present with joint
symptoms similar to those seen in patients with IgAV. These typically involve only one joint,
unlike the oligoarthritis involving several joints seen in IgAV. Additionally, affected joints
are warm and erythematous in septic arthritis, unlike those in IgAV. In most circumstances,
these conditions are easily distinguished from IgAV by an experienced clinician. However,
joint aspiration may be needed to differentiate the two. (See "Bacterial arthritis: Clinical
features and diagnosis in infants and children", section on 'Clinical features' and "Approach
to hip pain in childhood", section on 'Common causes of hip pain in children' and
"Overview of the causes of limp in children".)

Abdominal pain — Distinguishing acute abdominal emergencies, such as appendicitis,

from IgAV may be difficult before purpura develops. Although the rash of IgAV usually
precedes gastrointestinal manifestations and seldom lags by more than a few days,
evaluation for potential acute abdomen cannot be delayed. In addition, the IgAV rash may
be a nonspecific erythematous or urticarial exanthem or limited to lesions on the buttocks
or lower extremities early in the disease course. Thus, careful serial examinations of the
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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis

entire child are essential when considering the diagnosis. Radiologic studies used to
screen for surgical causes of abdominal pain are also used in patients with IgAV who
develop gastrointestinal complications, such as intussusception, bowel infarction, or
perforation. (See "Causes of acute abdominal pain in children and adolescents" and
'Imaging studies' below.)

Kidney disease — Patients with IgA nephropathy present with immunologic and
histopathologic findings similar to those of patients with IgAV. As is true of patients with
IgAV, manifestations of IgA nephropathy vary from microscopic hematuria to acute kidney
injury. Although patients with IgA nephropathy do not have the other clinical
characteristics of IgAV, these two entities may share a similar pathogenesis. (See "IgA
nephropathy: Clinical features and diagnosis".)

ADDITIONAL EVALUATION

Additional studies that are frequently performed upon diagnosis as part of the initial
evaluation include urinalysis in all patients and imaging studies in those with significant
gastrointestinal symptoms.

Kidney studies — Urinalysis should be performed in all patients with IgAV to screen for
evidence of kidney involvement. In general, findings on urinalysis reflect the degree of
kidney injury and may include the presence of red or white blood cells, cellular casts, and
proteinuria. Serum creatinine should be obtained in all adult patients with IgAV because of
the increased risk of significant kidney disease. Kidney disease is less prevalent in children,
so serum creatinine need not be obtained unless the patient is hypertensive or has
abnormalities on the urinalysis. Kidney involvement often becomes detectable after other
manifestations of IgAV, so urinary screening should be continued beyond the acute
presentation. (See "IgA vasculitis (Henoch-Schönlein purpura): Kidney manifestations".)

Imaging studies — Imaging studies generally are performed in patients with significant
abdominal symptoms. Plain abdominal radiography may demonstrate dilated loops of
bowel consistent with decreased intestinal motility. Abdominal ultrasonography can detect
increased bowel wall thickness, hematomas, peritoneal fluid, and intussusception
[17,73,74].

If intussusception is considered, ultrasonography rather than contrast enemas should be

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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis

the initial screening test. Ileoileal intussusception is seen in more than one-half of the
cases of intussusception in patients with IgAV. Contrast enemas, usually indicated in
children with signs of an intussusception, neither detect nor help reduce ileoileal
intussusception. (See "Intussusception in children".)

In males who present with scrotal symptoms, Doppler flow studies and/or radionuclide
scans can distinguish scrotal pain caused by IgAV from testicular torsion. These studies
demonstrate decreased blood flow to the testicle in testicular torsion, but testicular blood
flow is normal or increased in males with IgAV. (See 'Urologic' above and "Causes of scrotal
pain in children and adolescents", section on 'Testicular torsion'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Vasculitis".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th 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 the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the 10th to
12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

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.)

● Basics topic (see "Patient education: IgA vasculitis (Henoch-Schönlein purpura) (The
Basics)")

● Beyond the Basics topic (see "Patient education: Vasculitis (Beyond the Basics)")

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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis

SUMMARY AND RECOMMENDATIONS

● Epidemiology – Immunoglobulin A vasculitis (IgAV), formerly called Henoch-

Schönlein purpura (HSP), is the most common systemic vasculitis of childhood. IgAV
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 IgAV cases occur in adults. (See
'Epidemiology' above.)

● Pathogenesis – The underlying cause of IgAV is unknown. It is thought that IgAV

represents an immune-mediated vasculitis that may be triggered by a variety of
antigens, which may include various infections or other environmental exposures.
(See 'Pathogenesis' above.)

● Clinical manifestations – IgAV is a self-limited disease and is characterized by a

tetrad of clinical manifestations that vary in their occurrence and order of
presentation (see 'Clinical manifestations in children' above):

• Palpable purpura without thrombocytopenia and coagulopathy ( picture 2A-E)

• Arthralgia and/or arthritis
• Abdominal pain
• Kidney disease

● Diagnosis – The diagnosis of IgAV is usually based upon clinical manifestations of the
disease ( algorithm 1). There are no diagnostic laboratory tests for IgAV. 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 IgAV.
(See 'Diagnosis' above.)

● Differential diagnosis – The diagnosis is more difficult if there is an incomplete

presentation of IgAV or if the skin manifestations are absent at disease onset. In
these circumstances, other causes for purpura, arthritis, abdominal pain, and kidney
disease must be considered. Patients in whom the diagnosis is at all in doubt should
have a complete blood count, prothrombin time (PT), and urinalysis. The presence of
thrombocytopenia or a coagulopathy largely excludes the diagnosis of IgAV. (See
'Differential diagnosis' above and 'Laboratory tests' above.)

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IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis
● Additional evaluation – A urinalysis is performed in all patients diagnosed with IgAV.
A serum creatinine level should be obtained in children with hypertension or an
abnormal urinalysis. Serum creatinine should be assayed in all adult patients with
IgAV because of the increased risk of significant kidney disease. Imaging studies are
performed in those with significant gastrointestinal symptoms. Abdominal
ultrasonography is indicated in patients with severe abdominal pain. It can detect
increased bowel wall thickness, hematomas, peritoneal fluid, and intussusception.
Contrast studies may miss intussusception in patients with IgAV. (See 'Additional
evaluation' above.)

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