The classic full presentation includes the acute onset of fever, palpable purpura on the lower extremities (Figure 39–1) and buttocks, abdominal pain, arthritis, and hematuria. All components of this presentation are not required for the diagnosis, however. Conversely, even classic presentations are not diagnostic of this disorder. In adults, the diagnosis should be confirmed in most cases by biopsy (direct immunofluorescence as well as conventional hematoxylin and eosin staining). Pediatricians are more likely to rely on clinical diagnoses in the setting of classic presentations, which is reasonable given the relatively high incidence of HSP in children compared to adults.
Palpable purpura with some superficial ulcerations in a patient with Henoch-Schönlein purpura. Note also the presence of right ankle swelling due to arthritis.
The cutaneous findings of HSP include purpura (usually palpable, although sometimes not), urticarial papules, and plaques. Among adults, 60% of the patients have bullous or necrotic lesions (Figure 39–2), but these are uncommon in children. Lesions are concentrated over the buttocks and lower extremities and tend to involve the small blood vessels in the superficial dermis. Medium-sized vessels are rarely involved in HSP except in the rare cases of HSP associated with IgA paraproteinemia. Localized edematous swelling of the subcutaneous tissues of the lower extremities is frequently observed and does not correlate with the presence or degree of proteinuria. Persistent rash over a period longer than 1 month is a significant predictor of disease relapse and renal sequelae in children with HSP.
A bullous lesion with a purpuric component in a patient with Henoch-Schönlein purpura.
Joint disease, which occurs in more than 80% of patients with HSP, manifests itself as arthralgias or arthritis in large joints, especially the knees and ankles and, to a lesser degree, the wrists and elbows. Migratory patterns of joint involvement are common. Lower extremity involvement among patients with HSP and arthritis is nearly universal; up to one third of patients have upper extremity involvement as well. The pain associated with HSP arthritis may be incapacitating. The arthritis is nondeforming in nature.
Approximately 60% of patients with HSP have abdominal pain and 33% have evidence of gastrointestinal bleeding. Abdominal symptoms result from edema of the bowel wall as well as hemorrhage induced by mesenteric vasculitis. Abdominal pain may precede the appearance of purpura by up to 2 weeks, leading often to diagnostic confusion and occasionally to invasive testing or even laparotomy. The abdominal pain is typically colicky and may worsen after eating (ie, intestinal angina). Some patients experience nausea, vomiting, and upper or lower gastrointestinal bleeding. Mesenteric ischemia in HSP rarely leads to gut perforation. Massive gastrointestinal hemorrhage occurs in only 2% or so of patients. Purpuric lesions may be seen on endoscopy, commonly in the descending duodenum, stomach, and colon.
Gastrointestinal involvement in children with HSP can cause intussusception, a rare complication in adults. In contrast to idiopathic intussusception, which typically is ileocolic, HSP-associated intussusception is usually ileoileal. Other rare complications include pancreatitis, cholecystitis, and a protein-losing enteropathy.
Renal involvement is the most potentially debilitating complication of HSP. Forty percent of patients with HSP have renal disease. In general, renal involvement is more frequent and tends to be persistent in adults, who have a higher risk of developing end-stage renal disease than children. In a retrospective study of 134 children with HSP, age greater than 4 years, persistent purpura, and severe abdominal symptoms increased the likelihood of renal involvement.
In contrast to gastrointestinal disease and arthritis, both of which occasionally precede the onset of purpura, glomerulonephritis almost always appears after the development of skin manifestations. The occurrence of glomerulonephritis may be delayed by several weeks in up to 25% of all patients with this complication. The clinical hallmark of nephritis in HSP is hematuria, often macroscopic, but more typically microscopic. The hematuria can be transient, persistent, or recurrent. Proteinuria never occurs in the absence of hematuria in the acute setting. Even in cases in which the renal disease resolves spontaneously, many patients have persistent urinary abnormalities (eg, proteinuria).
The most common renal lesion (60% of cases) is a focal, proliferative endocapillary glomerulonephritis. Crescents are present in up to 40% of biopsies. Direct immunofluorescence studies characteristically demonstrate IgA deposition in the mesangium. Regardless of age, the degree of proteinuria, the presence of renal dysfunction at presentation, the number of crescents, and the degree of interstitial fibrosis on biopsy correlate with outcome. Histologic recurrences of HSP nephritis in renal allografts occur in 50% of patients who undergo renal transplantation. Allograft recurrences are associated with clinically significant disease in 20%, allograft failure in 12%, and allograft loss in 9% of cases.
Pulmonary and central nervous system (CNS) complications of HSP have been described, but these are very rare. When present, the usual lung manifestation of the disease is alveolar hemorrhage. Seizures are the usual CNS manifestation of HSP; the precise mechanism is obscure. Testicular involvement occurs in up to 10% of boys with this disease and may mimic torsion.
The results of routine laboratory tests and more specialized assays in HSP are shown in Table 39–2. All of these tests are appropriate at the initial evaluation of a patient with possible HSP. The exclusion of other forms of vasculitis that may mimic HSP in presentation is essential. Sixty percent of patients have an elevated serum IgA. Although there are two subclasses of IgA, HSP is associated with serum elevations and tissue deposits of IgA1 only. The reason for the preferential elevation of IgA1 is not clear.
Table 39–2. The Laboratory Evaluation in Henoch-Schönlein Purpura (HSP). ||Download (.pdf)
Table 39–2. The Laboratory Evaluation in Henoch-Schönlein Purpura (HSP).
|Complete blood cell count, with differential||Mild to moderate leukocytosis common, but otherwise the complete blood count is usually normal.|
|Electrolytes||Hyperkalemia in the setting of advanced renal dysfunction.|
|Liver function tests||Hypoalbuminemia can occur with nephrotic proteinuria. Otherwise, the liver function tests are normal.|
|Urinalysis with microscopy|
Hematuria (ranging from mild to too numerous to count red blood cells).
Red blood cell casts.
Proteinuria (nephrotic range proteinuria in a small minority).
|Erythrocyte sedimentation rate/C-reactive protein||Modestly elevated acute phase reactants may be observed. Approximately one-third of patients have abnormal erythrocyte sedimentation rates.|
|Serum IgA level||60% of patients have an elevated serum IgA. Although there are two subclasses of IgA, HSP is associated with increases only in IgA1.|
|C3, C4||Even though immune complexes containing IgA are essential to the pathophysiology of HSP, serum complement levels are usually normal.|
|ANCA||Negative (both IgG and IgA ANCA)|
Chest radiography should be performed to rule out pulmonary lesions. The presence of pulmonary involvement, unusual in HSP, raises the possibility of other diagnoses that may require other treatment approaches (see Differential Diagnosis).
Direct immunofluorescence studies of skin biopsies can only be performed on fresh samples, and therefore must be planned at the time the biopsy is performed. The usual procedure is to biopsy one skin lesion for hematoxylin and eosin staining and another for immunofluorescence. Alternatively, a single biopsy sample can be split into different portions for the two types of studies.