Download Henoch-Schönlein purpura (immunoglobulin A vasculitis): Clinical

Henoch-Schönlein purpura (immunoglobulin A vasculitis): Clinical manifestations and diagnosis
Authors:
Fatma Dedeoglu, MD
Susan Kim, MD, MMSc
Section Editor:
Robert Sundel, MD
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: Sep 2016. | This topic last updated: Dec 15, 2015.
INTRODUCTION — Henoch-Schönlein purpura (HSP), also called immunoglobulin A vasculitis (IgAV) [1], 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 (IgAV) is self-limited in the great majority of cases. The disease is characterized by a
tetrad of clinical manifestations:
●Palpable purpura in patients with neither thrombocytopenia nor coagulopathy
●Arthritis/arthralgia
●Abdominal pain
●Renal disease
The clinical manifestations, pathogenesis, diagnosis, and differential diagnosis of HSP (IgAV) are presented here. The
management of HSP (IgAV) and a more complete discussion of the renal manifestations of HSP (IgAV) are found
elsewhere. (See "Henoch-Schönlein purpura (immunoglobulin A vasculitis): Management" and"Renal manifestations of
Henoch-Schönlein purpura (IgA vasculitis)".)
EPIDEMIOLOGY — HSP (IgAV) is primarily a childhood disease that occurs between the ages of 3 and 15 years [2]. 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 4 and 6 years [3]. 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 5
to 7 years of age [4,5]. HSP (IgAV) is less common in adults [6], with an estimated annual incidence of 5 per 100,000 adults
in Slovenia [7]. In two retrospective studies from Spain and Korea, 25 to 30 percent of patients with HSP (IgAV) were adults.
In both cohorts, adults had significantly worse renal outcomes compared with children [8,9].
There is a male predominance with reported male-to-female ratios of 1.2:1 to 1.8:1 [3,4,7,10,11]. HSP (IgAV) is seen less
frequently in black compared with white or Asian children [3].
HSP (IgAV) occurs primarily in the fall, winter, and spring, but rarely in the summer months [10-12], possibly explained by
the association of HSP (IgAV) with infections. About one-half of the cases of HSP (IgAV) are preceded by an upper
respiratory tract infection [13], especially those caused by streptococcus [14]. Other infectious agents, vaccinations, and
insect bites also have been implicated as possible triggers for HSP (IgAV) [13]. The rate of HSP (IgAV) is significantly higher
(approximately 5 percent) in patients with familial Mediterranean fever [15,16].
CLASSIFICATION CRITERIA — A variety of classification criteria for HSP (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 HSP (IgAV) [17,18]. The ACR criteria for the diagnosis of HSP (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 HSP (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 HSP (IgAV) 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) [19], and were subsequently validated in conjunction with the Paediatric
Rheumatology International Trials Organisation (PRINTO) [20]. These criteria are more appropriate for pediatric settings in
which a clinician is most likely seeking features to distinguish HSP (IgAV) 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:
●Abdominal pain (usually diffuse, with acute-onset)
●Arthritis or arthralgia (acute-onset)
●Renal involvement (proteinuria, hematuria)
●Leukocytoclastic vasculitis or proliferative glomerulonephritis, with predominant immunoglobulin A (IgA) deposition
However, HSP (IgAV) is not the only disease that may have these manifestations. (See 'Differential diagnosis'below.)
PATHOGENESIS — HSP (IgAV) 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 (IgAV) remains unknown.
Immunologic, genetic, and environmental factors all seem to play a role [21-23].
The characteristic finding of HSP (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.)
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 HSP (IgAV). 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 (TGF-beta) in patients with HSP (IgAV) [11,24-28]. The
fact that only one of the two IgA subtypes (IgA1, but not IgA2) is found in the inflammatory infiltrates of this disease remains
unexplained [29,30]. Similarly, the precise role of IgA and the specific involvement of IgA1 in the pathogenesis of HSP
(IgAV) remain unclear. Some research suggests that IgA anticardiolipin antibodies may play a role [24,31,32]. Results from
one study suggest that beta-2-glycoprotein I (beta-2GPI) is an antigenic target for IgA [33]. Despite the increased presence
of these antibodies, there are few reports of thrombosis.
CLINICAL MANIFESTATIONS IN CHILDREN — The classic tetrad of HSP (IgAV) includes:
●Palpable purpura without thrombocytopenia and coagulopathy
●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 (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.)
The mean age of onset of HSP (IgAV) is between six and seven years. Based upon retrospective reviews from several
different countries, the major clinical manifestations develop with the following frequencies [3,4,8-11,34,35]:
●Purpura – All patients developed palpable purpura. This may be an overestimation, since it is most likely that
patients would not be considered for inclusion in these case series without characteristic skin findings.
●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 about one-half of patients and gastrointestinal bleeding in approximately
20 to 30 percent of patients.
●Renal disease – The frequency of renal involvement ranged from 21 to 54 percent.
In the retrospective Italian review of 150 children with HSP (IgAV), the presenting symptom was purpura in 74 percent,
arthritis in 15 percent, and abdominal pain in 12 percent of patients [10]. Similar results were seen in a Spanish retrospective
review of 78 patients [11]. 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 (IgAV) patients reported rash as the presenting symptom in
73 percent, preceding other symptoms by a mean of four days [36]. Similarly, in a retrospective Indonesian study of 128
children with HSP (IgAV), purpura was the first feature in 71 percent of the cases, while abdominal pain was the first feature
in 19 percent and arthritis in 10 percent [34].
Skin manifestations — The classic rash of HSP (IgAV) is not the initial presenting sign in about one-quarter of affected
children. It may be difficult to make the diagnosis of HSP (IgAV) prior to the appearance of a rash 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 2 and picture 3). 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) (picture 4 and picture 5). Even adult patients, however, may also have this manifestation
of HSP (IgAV), particularly involving the dorsal aspect of the hands.
Arthritis/arthralgia — Arthritis/arthralgia occur in up to 84 percent of patients [10]. However, joint complaints are
uncommon as the sole symptom at presentation and are the presenting symptom in about 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) [10,11,34]. 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 about one-half of children with HSP (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 [37]. 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 [36].
Gastrointestinal symptoms typically develop within eight days of the appearance of the rash, although much longer intervals
(weeks to months) have been described [38]. Gastrointestinal complaints precede the rash in about 15 to 35 percent of
cases. In such patients, the diagnosis of HSP (IgAV) is significantly more difficult. Gastrointestinal symptoms without the
appearance of cutaneous purpura at any time also have been described in case reports [39-41]. 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 [42]. The reason for such a putative association is not clear, since the rash of HSP (IgAV)
is typically found ingravity/pressure-dependent areas. This finding will require confirmation in a larger cohort before it can be
relied upon.
Gastrointestinal pain associated with HSP (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 "Gastrointestinal manifestations of vasculitis".)
Intussusception is the most common gastrointestinal complication of HSP (IgAV). Rarer gastrointestinal manifestations
include acute pancreatitis, gall bladder involvement, bowel perforation, and, in children, protein-losing enteropathy [37,4348].
Edema and hemorrhage can act as a pathologic 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 [49]. Intussusception in HSP (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 [10,34,37]. 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 (IgAV) from two centers in Chicago, 63 patients (42 percent)
presented with severe abdominal pain [50]. 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".)
Renal disease — The renal manifestations of HSP (IgAV), including prognosis and treatment, are discussed in detail
elsewhere. (See "Renal manifestations of Henoch-Schönlein purpura (IgA vasculitis)".)
Summarized briefly, renal involvement has been reported in 20 to 54 percent of children with HSP (IgAV). It is apparently
more prevalent in older children and adults [34]. 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 renal
involvement [42]. The most common presentation is hematuria with or without red blood cell casts and no or mild 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 renal biopsy are identical to those in immunoglobulin A
(IgA) nephropathy.
Other organ involvement — Other organ systems occasionally are involved in HSP (IgAV):
Scrotum — Reports of scrotal involvement in boys with HSP (IgAV) range from 2 to 38 percent [51-53]. 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. 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 (IgAV).
The clinical presentation of scrotal involvement in HSP (IgAV) was reviewed in a retrospective study of 120 Korean boys
diagnosed with HSP (IgAV) between 1992 and 2004 [54]. Twenty-six patients (22 percent) had scrotal involvement, which
presented as scrotal swelling (23 patients), scrotal pain or tenderness (18 patients). Unilateral involvement was more
common, with seven patients demonstrating inflammation of both scrotums (27 percent). Scrotal pain was the initial
manifestation of HSP (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 HSP (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 [55-58]. Most of the central nervous system findings are transient except for occasional permanent
sequelae associated with hemorrhagic stroke.
Respiratory tract — In a cohort of French patients hospitalized for HSP (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 [59]. Similarly, another study found impaired lung diffusion capacity in HSP
patients who did not have clinical or radiologic evidence of lung involvement compared with age-matched control patients
[60]. On the other hand, severe lung involvement, such as pulmonary hemorrhage, is rare in patients with HSP (IgAV) and is
primarily reported in adults and adolescents [61-64].
Eyes — Keratitis and uveitis are rare sequelae of HSP (IgAV) and usually suggest other diseases [65]. (See"Evaluation of
the red eye" and "Uveitis: Etiology, clinical manifestations, and diagnosis".)
CLINICAL MANIFESTATIONS IN ADULTS — Adult patients with HSP (IgAV), present with clinical manifestations similar to
those that occur in children. There are two main differences between adults and children with HSP (IgAV):
●Intussusception is rare in adults.
●Adults are at increased risk for developing significant renal involvement including end-stage renal disease [6,9,66].
(See 'Renal disease' above.)
These characteristics of HSP (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) [66]. Almost one-third of patients had renal insufficiency (creatinine clearance
<50 mL/minute per m2) within four months of presentation. At a median follow-up of 14.8 years, persistent renal impairment
was seen in 80 patients (32 percent of the original cohort), including end-stage renal failure in 27 patients and severe renal
impairment (creatinine clearance <30mL/minute) in another 32 patients. Potential explanations for the high prevalence of
substantial renal impairment in this study include the possibility of selection bias (all patients in the study had renal disease
severe enough to require renal biopsy), the long period of follow-up compared with other studies, and the possible role of
comorbidities (eg, hypertension) contributing to the progression of renal disease.
Another retrospective series reviewed 68 adults with HSP (IgAV) who had a skin biopsy with leukocytoclastic vasculitis on
histopathologic evaluation and immunoglobulin A (IgA) on direct immunofluorescence. Notable findings in this patient group
included a higher rate of renal 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
[67].
A more complete discussion of the renal manifestations and the management of renal disease in patients with HSP (IgAV) is
found separately. (See "Renal manifestations of Henoch-Schönlein purpura (IgA vasculitis)".)
LABORATORY FINDINGS — Serum immunoglobulin A (IgA) levels have been reported to be elevated in 50 to 70 percent
of patients with HSP (IgAV), and higher levels are associated with renal involvement [11,25,68].
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. HSP (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). HSP (IgAV) after viral illnesses, on the other hand, often fails to demonstrate elevation of acute-phase reactants.
Hypocomplementemia is reported in a significant percentage of children with HSP (IgAV), and these patients are more likely
to have evidence of a recent streptococcal infection [69]. A case series of 338 children hospitalized at Children's Hospital
Affiliated to Soochow University in South Korea 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/orcomplement component 4 (C4). Complement levels
normalized within three months in all patients, and they did not correlate with disease severity or presence of nephritis.
DIAGNOSIS — The diagnosis of HSP (IgAV) is usually based upon clinical manifestations of the disease [70]. The
diagnosis is straightforward when patients present with the classic signs and symptoms, especially palpable purpura of the
lower extremities and buttocks. 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 immunoglobulin A (IgA) deposition confirms
the diagnosis of HSP (IgAV).
Biopsy — In pediatric patients, biopsy is reserved for patients with an unusual presentation of HSP (IgAV) (ie, no rash, or
an atypical rash) or those with significant renal disease.
Confirmation of the diagnosis by biopsy is more important in adult patients, because of the lower incidence of HSP (IgAV)
beyond the pediatric age group and the comparatively higher incidence of other forms of vasculitis that may be clinically
similar to HSP.
Skin — Biopsies of the skin, which sample the small blood vessels of the superficial dermis, are usually adequate to make
the diagnosis of HSP (IgAV). Light microscopy studies (hematoxylin and eosin stains) demonstrate the classical
leukocytoclastic vasculitis in postcapillary venules with IgA deposition that is pathognomonic of HSP (IgAV) (image 1A-B)
[71]. 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 HSP (IgAV), generally require biopsy of a second skin site.
Kidney — Renal biopsy is reserved for patients in whom the diagnosis is uncertain or if there is clinical evidence of severe
renal involvement. HSP (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 "Renal manifestations of Henoch-Schönlein purpura (IgA vasculitis)".)
Laboratory tests — No laboratory test is diagnostic for HSP (IgAV). However, confirmation of a normal platelet count and
coagulation studies (prothrombin time) are necessary when clinical features do not allow conclusive distinction of HSP
(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. (See 'Differential diagnosis' below
and "Evaluation of purpura in children".)
DIFFERENTIAL DIAGNOSIS — In children presenting with the classic signs of palpable purpura plus some combination of
abdominal pain, arthritis/arthralgia, and/or renal involvement, the diagnosis of HSP (IgAV) is generally straightforward [19].
However, the diagnosis is more difficult if there is an incomplete presentation of HSP (IgAV), particularly if the skin
manifestations are initially absent. In these circumstances, other causes for purpura, arthritis, abdominal pain, and renal
disease need to be considered.
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 HSP (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 is a leukocytoclastic vasculitis described in children between
the ages of four months to two years [72-74]. 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 6). Involvement of the kidney and
the gastrointestinal tract is uncommon, but when it occurs, it is very similar to that seen in HSP (IgAV) [75,76]. Biopsy
of the skin demonstrates a leukocytoclastic vasculitis with occasional immunoglobulin A (IgA) deposition. It is unclear
whether this condition is truly a separate entity from HSP (IgAV), or actually overlaps with it.
●Hypersensitivity vasculitis – Hypersensitivity vasculitis is an inflammation of the small vessels that occurs after
exposure to drugs or infection, or without an identifiable trigger [18]. 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 HSP [IgAV])
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,
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: Classification and incidence".)
Laboratory evaluation of autoantibodies, including antinuclear antibodies, anti-double stranded deoxyribonuclease (antidsDNA), and antineutrophil cytoplasmic antibodies (ANCAs), is typically negative in HSP (IgAV). Abnormal results for any of
these studies may differentiate HSP (IgAV) from the other causes of small vessel vasculitis. The majority of patients have
normal complement levels, but hypocomplementemia has been reported [75]. 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 HSP (IgAV). (See "Vasculitis in children: Classification and incidence" and "Overview of and
approach to the vasculitides in adults", section on 'Small-vessel vasculitis'.)
Arthritis and arthralgia — In about 15 percent of patients with HSP (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
HSP (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 HSP (IgAV). Assays for serum complement, antinuclear and anti-dsDNA antibodies, and rheumatoid factor are
typically normal in patients with HSP (IgAV). Abnormal results for any of these studies may help to differentiate HSP (IgAV)
from SLE and JIA, although at least 15 percent of patients with HSP (IgAV) may also have transient hypocomplementemia
[69].
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 HSP
(IgAV), with the caveat that a significant proportion of cases of HSP (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
HSP (IgAV) should allow distinction between these conditions. Similarly, when considering toxic synovitis, another selflimited disease with transient joint findings that resolve without long-term sequelae, evolution of the other manifestations of
HSP (IgAV) will help differentiate the two conditions. (See "Systemic lupus erythematosus (SLE) in children: 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 HSP (IgAV).
These typically involve only one or two joints, unlike the polyarthritis seen in HSP (IgAV). Additionally, affected joints are
warm and erythematous in septic arthritis, unlike those in HSP (IgAV). In most circumstances, these conditions are easily
distinguished from HSP (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 "Overview
of 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 HSP (IgAV) may be difficult
before purpura develops. Although the rash of HSP (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 HSP (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 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 HSP (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.)
Renal disease — Patients with IgA nephropathy present with immunologic and histopathologic findings similar to those of
patients with HSP (IgAV). As is true of patients with HSP (IgAV), manifestations of IgA nephropathy vary from microscopic
hematuria to acute renal failure. Although patients with IgA nephropathy do not have the other clinical characteristics of HSP
(IgAV), these two entities may share a similar pathogenesis. (See "Clinical presentation and diagnosis of IgA nephropathy".)
ADDITIONAL EVALUATION — Additional studies that are frequently performed as part of the initial evaluation include
urinalysis in all patients and imaging studies in those with significant gastrointestinal symptoms.
Renal studies — Urinalysis should be performed in all patients with HSP (IgAV) to screen for evidence of renal
involvement. In general, findings on urinalysis reflect the degree of renal 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 HSP (IgAV)
because of the increased risk of significant renal disease. Renal disease is less prevalent in children, so serum creatinine
need not be obtained unless the patient is hypertensive or has abnormalities on the urinalysis. Renal involvement often
becomes detectable after other manifestations of HSP (IgAV), so urinary screening should be continued beyond the acute
presentation. (See "Renal manifestations of Henoch-Schönlein purpura (IgA vasculitis)".)
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 [11,49,50].
If intussusception is considered, ultrasonography rather than contrast enemas should be the initial screening test. Ileoileal
intussusception is seen in more than one-half of the cases of intussusception in patients with HSP (IgAV). Contrast enemas,
usually indicated in children with signs of an intussusception, neither detect nor help reduce ileoileal intussusception.
(See "Intussusception in children".)
In boys who present with scrotal symptoms, Doppler flow studies and/or radionuclide scans can distinguish scrotal pain
caused by HSP (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 boys with HSP (IgAV). (See'Scrotum' above and "Causes of
scrotal pain in children and adolescents", section on 'Testicular torsion'.)
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 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 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: Henoch-Schönlein purpura (IgA vasculitis) (The Basics)")
●Beyond the Basics topic (see "Patient education: Vasculitis (Beyond the Basics)")
SUMMARY
●Henoch-Schönlein purpura (HSP), also called immunoglobulin A vasculitis (IgAV), is the most common systemic
vasculitis of childhood. (See 'Introduction' above.)
●HSP (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 4 to 6 years of age. Approximately 10 percent of
HSP (IgAV) cases occur in adults. (See 'Epidemiology' above.)
●The underlying cause of HSP (IgAV) is unknown. It is thought that HSP (IgAV) represents an immune-mediated
vasculitis that may be triggered by a variety of antigens, including various infections and immunizations.
(See 'Pathogenesis' above.)
●HSP (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
•Arthralgia and/or arthritis
•Abdominal pain
•Renal disease
●The diagnosis of HSP (IgAV) 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
immunoglobulin A (IgA) deposition supports the diagnosis of HSP (IgAV). (See 'Diagnosis'above.)
●The diagnosis is more difficult if there is an incomplete presentation of HSP (IgAV) or if the skin manifestations are
absent at disease onset. In these circumstances, other causes for purpura, arthritis, abdominal pain, and renal
disease must be considered. (See 'Differential diagnosis' above.)
●There are no diagnostic tests for HSP (IgAV). Patients in whom the diagnosis is at all in doubt should have a
complete blood count, prothrombin time, and urinalysis. The presence of thrombocytopenia or a coagulopathy largely
excludes the diagnosis of HSP (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 HSP (IgAV) because of the
increased risk of significant renal disease. (See 'Laboratory tests'above and 'Renal studies' above.)
●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 HSP (IgAV). (See 'Imaging studies' above.)
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