eMedicine Specialties > Dermatology > Diseases of the Vessels

Henoch-Schonlein Purpura (Anaphylactoid Purpura)

Author: Andrew D Montemarano, DO, Consulting Staff, The Skin Cancer Surgery Center
Coauthor(s): Gina M Forte, Medical Assistant, The Skin Cancer Surgery Center
Contributor Information and Disclosures

Updated: Jan 29, 2010

Introduction

Background

Henoch-Schönlein purpura (HSP, or anaphylactoid purpura) is an immunoglobulin (Ig) A-mediated small-vessel vasculitis that predominantly affects children but also is seen in adults. HSP is a subset of necrotizing vasculitis characterized by fibrinoid destruction of blood vessels and leukocytoclasis. Clinical manifestations primarily include palpable purpura, arthralgia or arthritis, abdominal pain, gastrointestinal (GI) bleeding, and nephritis. The most serious long-term complication from HSP is progressive renal failure, which occurs in 1-2% of patients.

Heberden first described the disease in 1801 in a 5-year-old child with abdominal pain, hematuria, hematochezia, and purpura of the legs. In 1837, Johann Schönlein described a syndrome of purpura associated with joint pain and urinary precipitates in children. Eduard Henoch, a student of Schönlein's, further associated abdominal pain and renal involvement with the syndrome. Frank proposed the term "anaphylactoid purpura" in 1915. This followed from the reasoning that the pathogenesis likely involved a hypersensitivity reaction to an inciting agent.

Two major classification systems are used to make a diagnosis of HSP. The first, from the American College of Rheumatology, requires 2 or more of the following to be present:

• Patient age younger than 20 years
• Palpable purpura
• Abdominal pain or GI bleeding
• Extravascular or perivascular granulocytes on biopsy

• Direct immunofluorescence (DIF) results consistent with vascular IgA deposition
• Patient age younger than 20 years
• GI involvement
• Upper respiratory tract infection tract (URI) prodrome
• Mesangioproliferative glomerulonephritis with or without IgA deposition

• Palpable purpura
• Bowel angina
• GI bleeding
• Hematuria
• Patient age of onset younger than 20 years
• No medications as a precipitating agent

Also see the eMedicine articles Henoch-Schonlein Purpura (emergency medicine) and Henoch-Schonlein Purpura (pediatrics).

Pathophysiology

The etiology of HSP (anaphylactoid purpura) is unknown but involves the vascular deposition of IgA immune complexes. More specifically, the immune complexes are composed of IgA1 and IgA2 and are produced by peripheral B lymphocytes. These complexes likely are formed in response to an inciting factor. The circulating complexes become insoluble, are deposited in the walls of small vessels (arteries, capillaries, venules), and activate complement, most likely by the alternative pathway (based on the presence of C3 and properdin and the absence of the first component of complement in most biopsies).

Polymorphonuclear leukocytes are recruited by chemotactic factors and cause inflammation and necrosis of vessel walls with concomitant thrombosis. This leads to extravasation of erythrocytes from hemorrhage in the affected organs and is manifested histologically as leukocytoclastic vasculitis.

Histology of involved skin reveals polymorphonuclear cells or cell fragments around small dermal blood vessels. Immune complexes containing IgA and C3 have been found in skin, kidneys, intestinal mucosa, and joints, which are the major organ sites involved in HSP.

Clinical manifestations of HSP reflect small-vessel injury. Abdominal pain, present in as many as 65% of patients, is secondary to vasculitis-induced submucosal and subserosal hemorrhage and edema, with thrombosis of the microvasculature in the gut. Hematuria and proteinuria occur in HSP-associated nephritis. Renal manifestations range from minimal change to severe crescentic glomerulonephritis.

Etiology is secondary to the mesangial deposition of IgA predominantly, but IgG, IgM, C3, and properdin deposition also may occur. These deposits also can occur in the subendothelial and subepithelial glomerular spaces. Many believe that both HSP nephritis and IgA nephropathy (Berger disease), which are the most common causes of glomerulonephritis in the world, are different clinical presentations of the same disease process. Dermatologic manifestations occur secondary to immune complex deposition (IgA, C3) in vessels of the papillary dermis, resulting in vessel injury, extravasation of RBCs, and clinically observable palpable purpura. This tends to occur in dependent body regions, such as the lower legs, buttocks, back, and abdomen.

As many as 50% of occurrences in pediatric patients are preceded by a URI, and a recent study in adults demonstrated that 40% of patients had an antecedent URI. Several agents have been implicated, including group A streptococci, varicella, hepatitis B, Epstein-Barr virus, parvovirus B19, Mycoplasma, Campylobacter, and Yersinia. Less commonly, other factors have been associated as inciting agents in the development of HSP. These include drugs, malignancy, foods, pregnancy, familial Mediterranean fever, and exposure to cold. HSP also has been reported following vaccinations for typhoid, measles, yellow fever, and cholera.

Frequency

United States

In the United States, 75% of HSP (anaphylactoid purpura) occurrences are in children aged 2-14 years. The incidence in this age group is 14 cases per 100,000 population.

International

Although no reports cite differences in the incidence of HSP among countries, one source states that the occurrence of glomerulonephritis resulting from HSP varies among countries. HSP accounts for 18-40% of glomerular diseases in Japan, France, Italy, and Australia while responsible for only 2-10% of glomerular lesions in the US, Canada, and the United Kingdom. No explanation for these differences was offered, but they may be secondary to differences in associated provocative or inducing factors among locations.

Mortality/Morbidity

Most morbidity and mortality in HSP (anaphylactoid purpura) results from glomerulonephritis and its associated acute and chronic renal manifestations. At a minimum, transient hematuria occurs in 90% of patients. Renal insufficiency occurs in less than 2% of patients, and end-stage renal failure occurs in less than 1%. HSP accounts for 3-15% of children entering dialysis programs.

Although a rare complication of HSP, pulmonary hemorrhage is often fatal when it does occur.³

Race

HSP (anaphylactoid purpura) is uncommon in black persons, both in the United States and in Africa.

Season: HSP (anaphylactoid purpura) incidence is greatest in the spring, fall, and winter months.

Sex

The male-to-female predominance for HSP (anaphylactoid purpura) ranges from 1.5-2:1.

Age

Most HSP (anaphylactoid purpura) patients (75%) are children aged 2-14 years. The median age of onset is 4-5 years. Although one of the criteria for the diagnosis of HSP as published by the American College of Rheumatology is "age less than 20 years," the disease can occur from infancy to the ninth decade. A study by Allen et al shows that the clinical manifestations of HSP vary with age. Children younger than 2 years have less renal, GI, and joint involvement but more subcutaneous edema.⁴

Clinical

History

The presenting history varies with each patient who has Henoch-Schönlein purpura (HSP, or anaphylactoid purpura). The hallmark of the disease is the characteristic palpable purpura. HSP tends to occur on the buttocks and upper thighs in younger children and on the feet, ankles, and lower legs of older children and adults only. Patients often present with low-grade fever and malaise in addition to more specific symptoms. Purpura may be the presenting sign. As many as 50% of children present with symptoms other than purpura. The eruption often is preceded by arthralgia or arthritis, abdominal pain, or testicular swelling. Although it may be present initially, renal disease often develops up to 3 months after initial presentation.

• Joint symptoms: Arthralgia or arthritis is the presenting complaint in 25% of patients and occurs at some point in 60-75% of patients. Ankles and knees are affected most commonly, although any joint may be involved.
• Abdominal pain: Abdominal pain with concomitant hematochezia is the second most frequent symptom, is observed in 50-65% of patients, and is the presenting complaint in 10-15%. Pain tends to be sharp or colicky, and surgical consultation may be indicated to exclude a surgical abdomen. Indeed, as many as 6% of patients require surgery as a result of complications such as intussusception, bowel wall perforation, or infarction. Gastric hemorrhage with hematemesis, hydrops of the gallbladder, appendicitis, and pancreatitis also has been reported.
• Renal involvement
  • An incidence of renal involvement of 10-60% has been reported, and the extent of glomerular injury mostly determines the long-term morbidity and mortality of HSP. The presence of glomerular crescents on renal biopsy correlates with a poor prognosis. One study of 57 adults with HSP showed that a recent URI, purpura of the upper part of the trunk, fever, and presence of serum markers of inflammation (eg, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]; see Lab Studies) predicted renal involvement.
  • HSP nephritis usually presents as macroscopic hematuria and proteinuria lasting days to weeks. These may be accompanied by increased plasma creatinine and/or hypertension, followed by microscopic hematuria, which may last months to years. Gross hematuria may occur years after the initial illness with relapses of purpura, often following a URI. Of those patients with renal involvement, as many as 10% may develop chronic renal failure and end-stage renal disease. However, less than 1% of patients with HSP have this poor prognosis.
• Disease recurrence: Disease recurrence occurs throughout weeks to months in adults and children. In the large pediatric study by Allen et al, children older than 2 years had a recurrence rate of 50%, while those younger than 2 years had a less than 25% chance of recurrence.⁴ The primary differences between children and adults, according to one study of 57 adults with HSP, are the chronicity and severity of the eruption in the latter population. Bullae and ulcers are more common in adults, and cutaneous exacerbations may be seen for 6 months or longer. 
• Other signs and symptoms: Less common manifestations of HSP include testicular pain and swelling, hepatosplenomegaly, central or peripheral nervous system involvement (seizures or mononeuropathies, respectively), headache, and rarely, myocardial infarction or pulmonary hemorrhage.
• Other pertinent history: Ascertain the history of recent drug ingestion and food consumption, since reports exist of medication-associated and food-associated HSP.

Physical

A full physical examination is indicated, since Henoch-Schönlein purpura (HSP, or anaphylactoid purpura) can affect all organ systems.

• Skin - Primary lesion 
  • The eruption may begin as erythematous macular or urticarial lesions, progressing to blanching papules, and later, to palpable purpura, usually 2-10 mm in diameter.
  • Bullae, vesicles, petechiae, and ecchymotic, necrotic, ulcerative, or targetlike lesions also may occur.
  • Subcutaneous edema is common in children younger than 3 years.
  • See images below.
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    Purpuric papules and plaques of the lower extremity characteristic of Henoch-Schönlein purpura.

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    Purpuric papules and plaques of the lower extremity characteristic of Henoch-Schönlein purpura.

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    Hemorrhagic macules, papules, and patches on the ankle and foot of a child with Henoch-Schönlein purpura.

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    Hemorrhagic macules, papules, and patches on the ankle and foot of a child with Henoch-Schönlein purpura.

• Skin - Distribution 
  • Lesions typically are symmetric and tend to be distributed in dependent body areas, such as the ankles and lower legs in older children and adults (as shown in the image below), and the back, buttocks, upper extremities, and upper thighs in young children, since these regions tend to be dependent in the latter group.
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    Older lesions of Henoch-Schönlein purpura demonstrating increased extravasation with ecchymoses on the dorsal foot and ankle.

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    Older lesions of Henoch-Schönlein purpura demonstrating increased extravasation with ecchymoses on the dorsal foot and ankle.

  • The face, palms, soles, and mucous membranes usually are spared, except in infants, in whom facial involvement may not be uncommon. The subcutaneous edema prominent in young children involves the scalp, periorbital regions, hands, feet, and scrotal area.
  • Lesions usually occur in crops and may fade over several days. Recurrences tend to occur in the same sites as previous lesions.
• Skin: Color as seen in the areas of purpura progresses from red to purple, then becomes rust-colored or brown before fading.
• Heart: Cardiac tamponade and myocardial infarction rarely have been reported with HSP.
• Lungs: Although fortunately rare, pulmonary hemorrhage has been reported. When present, it is a poor prognostic sign with a 50% mortality rate. One pediatric study showed that 95% of patients with active disease had impaired diffusion capacity of carbon monoxide, which was readily reversible once the syndrome resolved.
• Abdomen: Pain secondary to vasculitic involvement of small mesenteric or bowel mucosal vessels is common. Examine the abdomen for a palpable mass, which may indicate intussusception. Pancreatitis, gallbladder hydrops, appendicitis, and massive gastric hemorrhage also have been reported.⁵
• Scrotum/testicles: Testicular involvement has varied in reports from 4-38%. Testicular pain may be so intense that it mimics torsion.
• Extremities: Arthralgia and arthritis are common, primarily affecting the ankles and knees, although any joint may be involved. Periarticular inflammation is common.
• Neurologic: Headaches, seizures, and mononeuropathies rarely have been reported with HSP. Perform a careful neurologic examination for focal deficits.

Causes

Knowledge concerning the exact mechanisms by which the immune complexes implicated in the pathogenesis of Henoch-Schönlein purpura (HSP, or anaphylactoid purpura) are formed is lacking. Similarly, factors that predispose certain patients to development of the disease are poorly understood. The most common associated factor reported is an antecedent URI in approximately 50% of patients. Other reported associated factors are noted as follows:

• Infections
  • Bacteria - Group A beta hemolytic streptococci, Campylobacter jejuni, Yersinia species, Mycoplasma pneumoniae, and Helicobacter pylori (reported in one patient)
  • Viruses - Varicella, hepatitis B, Epstein-Barr virus, and parvovirus B19
• Drugs
  • Drugs associated with HSP are more frequent in adults than children (although reported in both populations)
  • Drugs associated with HSP include: Ampicillin, penicillin, erythromycin, quinines, and chlorpromazine
• Neoplasms
  • Leukemia
  • Lymphoma
• Solid tumors
  • Ductal carcinoma of the breast⁶
  • Bronchogenic carcinoma
  • Adenocarcinoma of the prostate
  • Adenocarcinoma of the colon
  • Renal cell carcinoma
  • Cervical carcinoma
  • Melanoma
• Foods - Sensitivity to foods containing salicylates and azo dyes
• Other - Pregnancy, familial Mediterranean fever, and cryoglobulinemia

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