157.1 Henoch-Schönlein Purpura
HSP, also known as anaphylactoid purpura, is a vasculitis of small vessels. It is the most common cause of nonthrombocytopenic purpura in children.
The etiology of HSP is unknown, but HSP typically follows an upper respiratory tract infection. The incidence and prevalence of HSP are probably underestimated because cases are not reported to public health agencies. However, of 31,333 new patients seen at 54 pediatric rheumatology centers in the United States, 1,120 had some form of vasculitis and 558 were classified as HSP. Although HSP accounted for 1% of hospital admissions in the past, changes in medical practice have reduced the frequency of admissions; 0.06% of admissions (62/9,083 in 1997) were for HSP at one large Midwestern pediatric center. This illness is more frequent in children than adults, with most cases occurring between 2–8 yr of age, most frequently in the winter months. Males are affected twice as frequently as females. The overall incidence is estimated to be 9/100,000 population.
The specific pathogenesis of HSP is not known, although in specific populations, patients with HSP have an significantly higher frequency of HLA-DRB1*07 than geographic controls. Increased serum concentrations of the cytokines tumor necrosis factor-a (TNFa) and interleukin (IL)-6 have been identified in active disease. In one study, almost half of the
Figure 157.1-1 Histopathology of a skin biopsy from a patient with Henoch-Schönlein purpura showing leukocytoclastic vasculitis with nuclear degeneration (“nuclear dust”).
patients had elevated antistreptolysin O (ASO) antibodies, implicating group A Streptococcus. This illness is considered by histopathology to be an IgA-mediated vasculitis of small vessels. Immunofluorescence techniques show deposition of IgA and C3 in the small vessels of the skin and the renal glomeruli, but the role of complement activation is controversial.
The disease onset may be acute, with the appearance of several manifestations simultaneously, or insidious, with sequential occurrence of symptoms over a period of weeks or months. Low-grade fever and fatigue occur in more than half of affected children. The typical rash and the clinical symptoms of HSP are a consequence of the usual location of the acute small vessel damage primarily in the skin, gastrointestinal tract, and kidneys.
The hallmark of the disease is the rash, beginning as pinkish maculopapules that initially blanch on pressure and progress to petechiae or purpura, which are characterized clinically as palpable purpura that evolve from red to purple to rusty brown before they eventually fade ( Fig. 157–2 ). The lesions tend to occur in crops, last from 3–10 days, and may appear at intervals that vary from a few days to as long as 3–4 mo. In fewer than 10% of children, recurrence of the rash may not end until as late as a year, and rarely several years, after the initial episode. Damage to cutaneous vessels also results in local angioedema, which may precede the palpable purpura. Edema occurs primarily in dependent areas—for example, below the waist, over the buttocks (or on the back and posterior scalp in the infant), or in areas of greater tissue distensibility, such as the eyelids, lips, scrotum, or dorsum of the hands and feet.
Arthritis, present in more than two thirds of children with HSP, is usually localized to the knees and ankles and appears to be concomitant with edema. The effusions are serous, not hemorrhagic, in nature and resolve after a few days without residual deformity or articular damage. They may recur during a subsequent reactive phase of the disease.
Edema and damage to the vasculature of the gastrointestinal tract may also lead to intermittent abdominal pain that is often colicky in nature. More than half of patients have occult heme-positive stools, diarrhea (with or without visible blood), or hematemesis. The recognition of peritoneal exudate, enlarged mesenteric lymph nodes, segmental edema, and hemorrhage into the bowel may prevent unnecessary laparotomy for acute abdominal pain. Intussusception may occur, which is suggested by an empty right lower abdominal quadrant on physical examination or by currant jelly stools, which may be followed by complete obstruction or infarction with bowel perforation.
Figure 157.1-2 Henoch-Schönlein purpura. (From Korting GW: Hautkrankheiten bei Kindern und Jugendlichen, 3rd ed. Stuttgart, FK SchattauerVerlag, 1982.)
Several other organ systems may be involved during the acute phase of disease. Renal involvement occurs in 25–50% of children, and hepatosplenomegaly and lymphadenopathy may also be present during active disease. A rare but potentially serious outcome of central nervous system (CNS) involvement is the development of seizures, paresis, or coma. Other rare complications include rheumatoid-like nodules, cardiac and eye involvement, mononeuropathies, pancreatitis, and pulmonary or intramuscular hemorrhage.
The pattern of crops of palpable purpuric lesions of similar hue in dependent areas of the body is characteristic of HSP. Diagnostic uncertainty arises when the symptom complex of edema, rash, arthritis with abdominal complaints, and renal findings occurs for a prolonged period. HSP can occur with other forms of vasculitis or autoimmune disease such as familial Mediterranean fever or inflammatory bowel disease. In polyarteritis nodosa, the cutaneous lesions are different, and peripheral neurologic and cardiac manifestations are more common. Palpable purpura can occur in meningococcemia, if there are pre-existing coagulation abnormalities such as factor V Leiden, protein S, or protein C deficiency. The presentation of unremitting fever, a maculopapular rash that does not reappear in crops but is prominent on the lower extremities, and peripheral arthritis suggests Kawasaki disease. HSP must be distinguished from systemic-onset juvenile rheumatoid arthritis, in which the salmon-pink rash is evanescent and maculopapular, with swelling that does not extend beyond the joint.
Routine laboratory tests are neither specific nor diagnostic. Affected children often have a moderate thrombocytosis and leukocytosis. The erythrocyte sedimentation rate (ESR) may be elevated. Anemia may result from chronic or acute gastrointestinal blood loss. Immune complexes are often present, and 50% of patients have elevated concentrations of IgA as well as IgM but are usually negative for antinuclear antibodies (ANAs), antibodies to nuclear cytoplasmic antigens (ANCAs), and rheumatoid factor (even in the presence of rheumatoid nodules). Anticardiolipin or antiphospholipid antibodies may be present and contribute to the intravascular coagulopathy. Intussusception is usually ileoileal in location; barium enema may be used for both identification and nonsurgical reduction. Renal involvement is manifested by red blood cells, white blood cells, casts, or albumin in the urine.
Definitive diagnosis of vasculitis, confirmed by biopsy of an involved cutaneous site, shows leukocytoclastic angiitis. Renal biopsy may show IgA mesangial deposition and occasionally IgM, C3, and fibrin. Patients with IgA nephropathy may have elevated plasma antibody titers against H. parainfluenzae.
Symptomatic treatment, including adequate hydration, bland diet, and pain control with acetaminophen, is provided for self-limited complaints of arthritis, edema, fever, and malaise. Avoidance of competitive activities and of maintaining the lower extremities in persistent dependence may decrease local edema. If edema involves the scrotum, elevation of the scrotum and local cooling, as tolerated, may decrease discomfort.
Intestinal complications (e.g., hemorrhage, obstruction, and intussusception) may be life threatening and managed with corticosteroids and, when necessary, reduction (by air or barium) or resection of the intussusception. Therapy with oral or intravenous corticosteroids (1–2?mg/kg/24?hr) is often associated with dramatic improvement of both gastrointestinal and CNS complications, which may recur for as long as 3 yr.
Management of renal involvement is the same as for other forms of acute glomerulonephritis (see Chapter 504 ). If anticardiolipin or antiphospholipid antibodies are identified and thrombotic events have occurred, aspirin (81?mg; a “baby” aspirin) given once may decrease the risks associated with a
hypercoagulable state. Rheumatoid nodules may respond to alternate-day colchicine (0.6?mg/24?hr every other day).
The major complications of HSP are renal involvement, including nephrotic syndrome, and bowel perforation. An infrequent complication of scrotal edema is testicular torsion, which is quite painful and must be treated promptly.
HSP is a self-limited vasculitic disease with an excellent overall prognosis. Chronic renal disease may result in morbidity: a population-based study indicated that fewer than 1% of patients with HSP develop persistent renal disease and fewer than 0.1% develop serious renal disease. Rarely, death may occur during the acute phase of the disease as a result of bowel infarction, CNS involvement, or renal disease. Occasionally, children who present with an HSP-like syndrome acquire characteristics of other connective tissue diseases.