Henoch-Schönlein purpura (HSP) is also known as anaphylactoid purpura or purpura rheumatica. It is a leukocytoclastic vasculitis affecting small blood vessels in virtually any organ system, but predominantly the skin, joints, and kidneys. HSP is the most common type of childhood systemic vasculitis, with an annual incidence of 10 to 20 per 100,000 children less than 17 years of age and a slight male predominance.1 Most patients are between the ages of 3 and 10 years, with the peak age of onset 4 to 6 years. The clinical course is usually benign and self-limited, although a small proportion of patients may have significant long-term sequelae, mainly as a result of renal involvement.
Immunoglobulin A (IgA) levels are characteristically elevated in HSP, but the pathophysiologic process leading to leukocytoclasis is incompletely understood. Environmental and genetic factors also play a role. HSP often follows infections, most commonly streptococcal upper respiratory tract infections, explaining the preponderance of HSP cases in in the fall, winter, and spring. Other triggering factors include immunizations, medications, or insect bites. The rate of HSP is higher in patients with certain complement deficiencies and those with a mutation in the gene associated with familial Mediterranean fever, the MEFV gene.2
Biopsy of affected organs is not often undertaken unless the diagnosis is in question or the severity of renal involvement requires additional information to direct therapy (see Diagnostic Evaluation, below). Pathologic examination of involved tissue early in the process reveals evidence of immune-complex-mediated leukocytoclastic vasculitis. There is a perivascular infiltrate of neutrophils and mononuclear cells around necrotic small blood vessels. Immunofluorescence and electron microscopy may reveal deposits of IgA, C3, and fibrin. If the biopsy is delayed, findings will be nonspecific, as prolonged compromise of vascular integrity allows leakage of all plasma elements.
HSP is marked by the classic triad of nonthrombocytopenic palpable purpura, arthritis, and abdominal pain. Renal involvement may be reflected by the presence of hematuria or proteinuria, which is often mild. In rare cases, renal involvement may progress to chronic renal failure.
The typical history is of an otherwise well child presenting with a constellation of symptoms of rash, arthralgia, and colicky abdominal pain 1 to 3 weeks after an upper respiratory infection. Malaise or a low-grade fever may precede the classic symptoms by a few days. The three symptoms may occur concurrently or develop within days, and occasionally weeks, of each other. The classic rash and joint pain alone, or rash and abdominal pain, may be sufficient to make the diagnosis.
In three-quarters of affected children, a rash is the initial presenting feature of HSP. It is characteristically a symmetric, dark red or purple, non-blanching palpable exanthem. The lesions are usually not painful but occasionally may be pruritic (Figure 148-1). They begin as urticarial wheals or petechiae, evolving later to form the typical purpura or ecchymoses. Sometimes the rash may take the appearance of deep bruises or even bullous or hemorrhagic lesions. The rash is most extensive in pressure-dependent areas. In nonambulatory children, this corresponds to the face, trunk, and upper limbs, whereas the extensor surfaces of the legs and buttocks are involved in older patients. This pattern of distribution is thought to be from deposition of large IgA-immune complexes that activate the alternative complement pathway in gravity-dependent areas, disrupting vascular integrity and leading to extravasation of red blood cells. Cutaneous involvement may take the form of tender, localized subcutaneous edema affecting the forehead, periorbital region, or dorsum of the hands and feet.
FIGURE 148-1.
Characteristic palpable purpuric rash on the lower extremities, especially along the sock line of the left leg, on a child with HSP. (Reproduced with permission from Shah SS, Ludwig S eds. Symptom-based Diagnosis in Pediatrics. New York: McGraw-Hill Education; 2014:242. With permission of BMJ Publishing Group Ltd.)
Resolution of these skin findings usually occurs in a week, with the rash fading to a yellow or purple brown, as is characteristic of bruises. Scarring is not typical. Successive crops of lesions may develop over the course of the illness, leading to a polymorphous appearance. A recurrent rash is seen in about one-third of patients, usually within the first month of onset. Rarely recurrences may be seen for up to 2 years, although they tend to become milder over time.
Joint inflammation is the second most common manifestation of HSP, affecting 50% to 90% of children. It is the presenting symptom in one-sixth of patients,3 generally presenting as obvious periarticular swelling and tenderness without erythema, warmth, or joint effusion. Knees and ankles are most frequently affected, while elbows, wrists, and hands may be involved as well. Usually, one to three joints are affected, with the small joints usually spared, although edema of the hands and feet may give the appearance of synovitis in these extremities. Patients complain of significant pain and discomfort, with corresponding limitation of motion and avoidance of usual activities.
Colicky abdominal pain affects 50% to 75% of patients with HSP. Gastrointestinal (GI) symptoms usually occur within a week of the rash, but may present up to 4 weeks later or precede the dermatologic manifestations. When the abdominal pain precedes the rash, it may be challenging to differentiate it from other causes of an acute abdomen, particularly appendicitis.
The abdominal pain in HSP is caused by submucosal hemorrhage and edema stemming from vasculitis of the GI tract, similar to the vasculitis observed in the skin. The pain has a characteristic waxing and waning nature. Exacerbations may cause affected children to cry or curl up in pain, followed by a completely pain-free interval minutes later. Usually, the pain is self-limiting, though in some cases it may be severe enough to prevent sufficient oral intake. Complications such as intussusception, bowel infarction, or perforation may occur, and urgent evaluation for such events should be undertaken should the nature or intensity of the pain change.
Intussusception occurs in 1% to 5% of patients and is ileo-ileal in up to 60% of cases, thus distinguishing it from the typical ileocolic lesions related to mesenteric adenitis or viral infections in young children.4 Hemorrhage and edema in a portion of the GI tract provides a lead point for the intussusception. When this is suspected, an ultrasound should be the initial screening investigation.
GI bleeding may be evidenced by melena, guaiac-positive stools, or hematemesis. Massive GI hemorrhage is rare. Vomiting and paralytic ileus may be seen. Less common GI manifestations are acute pancreatitis, cholecystitis, hydrops of the gall bladder, or protein-losing enteropathy.5
Nephritis is seen in 20% to 54% of children6 and is the fourth classical manifestation of HSP. This usually takes the form of asymptomatic hematuria or proteinuria detected on urinalysis within the first 6 weeks of disease.7 Most (97%) patients will have some evidence of renal involvement within the first 6 months of disease, though it is often mild, and evident on urinalysis only.8 In such cases, the risk of progression to chronic renal failure is less than 1%, with the risk increasing to 15% if the child has nephritic or nephrotic features and as much as 40% with evidence of both hematuria and high-grade proteinuria. The progression to renal failure is higher in older patients, and up to 30% in adults. Renal biopsies reveal histological features similar to IgA nephropathy. Other parts of the genitourinary system may be involved as well as the kidneys. For example, scrotal swelling and tenderness, usually from epididymo-orchitis, occurs in up to 5%.6
HSP is a systemic vasculitis and thus may involve virtually any organ system. Rarely, interstitial pneumonia and diffuse alveolar hemorrhage (DAH) may occur, usually in male adolescents or in adults. DAH may present as hemoptysis, anemia, or chest infiltrates on radiographs. As with other involved organs, lung biopsy reveals leukocytoclastic vasculitis with alveolar hemorrhage, or alveolar hemorrhage alone, with variable IgA staining by immunofluorescence.
Clinical neurologic involvement is uncommon and usually affects patients with significant nephritis. Mental status changes, headaches, ataxia, focal neurologic deficits, and peripheral neuropathies have all been described.9 It is important to remember that in a systemic inflammatory disorder such as HSP, neurologic disturbances may arise from a variety of causes other than cerebral vasculitis, including severe hypertension, electrolyte abnormalities due to renal or GI involvement, stroke, or intracranial hemorrhage.
