Henoch-Schönlein purpura is a nonthrombocytopenic, purpuric and systemic vasculitis of childhood¹ that occurs twice as often in males as in females. It has an incidence of 14 cases per 100,000 people and occurs most frequently in the spring and fall.² Henoch-Schönlein purpura may present as a triad of symptoms: a palpable purpuric rash on the lower extremities, abdominal pain or renal involvement, and arthritis. It can masquerade as many different conditions, depending on the symptoms. Purpura may be defined as visible, unblanching hemorrhages in the skin or mucous membranes that are 5 to 10 mm in diameter and often palpable. Knowledge of the classifications of purpura may be helpful to the physician in constructing a differential diagnosis of purpura.³

Henoch-Schönlein purpura is an inflammatory disorder of unknown cause characterized by IgA-dominant immune complexes in smaller venules, capillaries and arterioles. It represents a diffuse vasculitis that is secondary to hypersensitivity. The disorder appears to represent a variety of leukocytoclastic angiitis initiated by deposition of immune complexes and can occur in response to infectious agents such as group A streptococci, Mycoplasma, Epstein-Barr virus and Varicella virus. Parvovirus B19 and Campylobacter enteritis have also been associated with Henoch-Schönlein purpura.^4,5 Cases have been reported following vaccinations for typhoid, measles, cholera and yellow fever.⁶ In addition, exposure to allergens in drugs or food, exposure to cold, and insect bites have been linked to the development of Henoch-Schönlein purpura.⁶ However, the precise etiology of the disorder is unknown. It is thought to be an IgA-mediated vasculitis, with renal lesions that are histopathologically indistinguishable from IgA nephropathy (Berger's disease). Both diseases can progress to renal insufficiency.⁷

Clinical Presentation

Rash

Henoch-Schönlein purpura is a disease of children and young adults, with 75 percent of cases occurring between two and 11 years of age^1,8; peak incidence is five years of age. Children younger than two years of age tend to have a milder course. A rash of erythematous papules is typically followed by purpura, abdominal pain, arthritis and nephritis. The rash occurs in 100 percent of cases. Lesions typically appear on the lower extremities and buttocks, but may also involve the upper extremities, face and trunk, and are accentuated in areas of pressure (such as sock lines and the waistline). Classic lesions consist of urticarial wheals, erythematous maculopapules and larger, palpable ecchymosis-like lesions. Petechiae and target lesions may be present as well. These lesions may initially blanch on pressure but later lose this feature. The purpuric areas evolve from red to purple, become rust-colored with a brownish hue and then fade.⁹ In more severe cases, hemorrhagic, purpuric or necrotic lesions may be prominent. It is mandatory to differentiate these lesions from those of meningococcal septicemia or other septic emboli or toxic vasculitides, such as those seen with drug reactions, iodides and arsenicals.¹⁰

Abdominal Pain

The second most frequent symptom of Henoch-Schönlein purpura is abdominal pain, which occurs in up to 65 percent of cases. The most common complaint is colicky abdominal pain, which may be severe and associated with vomiting. Stools may show gross or occult blood; hematemesis may also occur. The pain may mimic that of an acute abdomen. Severe cases may proceed to intussusception, hemorrhage and shock. Younger children are less likely to exhibit gastrointestinal symptoms.¹¹ Endoscopic evaluation often shows mucosal erosions and swelling.³

Joint Involvement

The third symptom of the triad is arthritis characterized by warmth, tenderness and swelling of the joints, particularly the large joints. The ankles and knees are most frequently affected; however, the elbows, hands and feet may also be involved. Joint symptoms occur in 70 percent of cases, are transient and leave no permanent deformity.¹² Joint symptoms may precede the rash in 25 percent of cases.³

Renal Disease

The most serious sequela of Henoch-Schönlein purpura is renal involvement. This complication occurs in 50 percent of older children but in only 25 percent of children younger than two years. Fewer than 1 percent of cases progress to end-stage renal disease.¹³ Patients who develop renal involvement generally do so within three months of the onset of rash. The most common manifestation of renal disease is hematuria. Apparently, development of bloody stools with Henoch-Schönlein purpura is also a risk factor for renal disease.¹³ Rash persistence is also associated with nephropathy. The presence of proteinuria and hematuria is also associated with progression to renal insufficiency. In 50 percent of patients who display a combination of nephritis-nephrotic symptoms, end-stage disease develops after 10 years. On renal biopsy, those with glomerular crescents have a 100 percent chance of developing end-stage disease.¹³ Renal histopathology may include minimal change to severe glomerulonephritis that is indistinguishable from IgA nephropathy.

Other Clinical Manifestations

Other rare systemic manifestations of Henoch-Schönlein purpura are listed in Table 1 and may include hepatosplenomegaly, myocardial infarction, pulmonary hemorrhage and pleural effusion. Central nervous system involvement may manifest as behavioral changes, seizures, headaches and focal deficit. Peripheral nervous system lesions may appear as mononeuropathies. Extrarenal genital involvement such as scrotal swelling and testicular torsion has also been reported. An illustration of Henoch-Schönlein purpura can be seen in Figure 1.

Diagnosis

Diagnosis is not difficult if the classic triad of rash, gastrointestinal complaints or hematuria, and arthritis is present. The American College of Rheumatology¹² provided criteria for differentiating Henoch-Schönlein purpura from hypersensitivity vasculitis, with the major differences being the presence of elevated blood urea nitrogen and creatinine levels and—more importantly—global organ involvement in hypersensitivity vasculitis. Ultrasound is probably the imaging modality of choice for patients with gastrointestinal-related Henoch-Schönlein purpura.¹⁴ However, when symptoms are not typical, the differential diagnosis can become extensive (Table 2). Abdominal pain alone can mimic an acute abdomen, and children have occasionally undergone laparotomy with negative findings. Joint involvement raises the question of many rheumatic illnesses of childhood such as rheumatic fever, rheumatoid arthritis or systemic lupus erythematosus. The rash alone may be mistaken for child abuse, trauma, drug reactions, hemorrhagic diathesis or a septicemia such as meningococcemia. Other conditions that present with palpable purpura include subacute bacterial endocarditis and Rocky Mountain spotted fever.¹⁵

The diagnosis of Henoch-Schönlein purpura depends on clinical findings and history. There is not a specific laboratory test for the disorder, although an elevated serum IgA level is suggestive. The complete blood count may reveal a normal or elevated white blood cell count and possible eosinophilia. Sedimentation rate and platelet count may be elevated. Electrolytes may be affected secondary to gastrointestinal involvement. Urinalysis may show hematuria. Renal manifestations may follow the development of the rash by up to three months; therefore, urinalysis should be performed monthly, as well as measurements of blood urea nitrogen and creatinine levels in the presence of continued hematuria. A stool guaiac test may be positive. An underlying infectious etiologic agent should be excluded when clinically indicated. A normal platelet count differentiates Henoch-Schönlein purpura from thrombocytopenic purpura. Skin biopsy may show a leukocytoclastic vasculitis.

Treatment

There is no specific treatment for Henoch-Schönlein purpura. Bed rest and supportive care, such as assuring adequate hydration, are helpful. Nonsteroidal anti-inflammatory drugs can relieve joint and soft tissue discomfort. Corticosteroids have some use in patients with severe abdominal pain. However, corticosteroids are not recommended for treatment of rash, joint pain or renal disease alone.

Treatment with cyclophosphamide (Cytoxan, Neosar), plasmapheresis, cyclosporine (Neoral) and azathioprine (Imuran) is controversial. In the absence of renal disease and central nervous system involvement, the prognosis for patients with Henoch-Schönlein purpura is excellent. The illness lasts four to six weeks in most patients. One half of patients have a reccurrence. Long-term follow-up is necessary for patients with renal disease. The renal disease may not arise for several years. Renal biopsy may be performed to establish the diagnosis and determine the prognosis. Prognosis overall is excellent. The primary long-term complication is renal disease, which develops in 5 percent of patients. One study suggests that corticosteroids and azathioprine may be helpful in treating renal disease once it develops.¹⁶

Final Comment

In summary, Henoch-Schönlein purpura is generally a benign, self-limited condition but bears close follow-up with repeated urinalysis as a small percentage of patients progress to renal failure. Pharmacologic treatments are controversial, and more research needs to be done to clarify therapeutic regimens.