Henoch-Schönlein purpura (HSP) is a syndrome characterized by cutaneous purpura, arthritis, nephritis, abdominal pain, and gastrointestinal bleeding. The clinical features of HSP are a consequence of widespread leukocytoclastic vasculitis owing to immunoglobulin (Ig)A deposition in vessel walls (1). Gastrointestinal involvement occurs in 50% to 75% of children with HSP. The dominant clinical features are colicky abdominal pain, vomiting, and bleeding (1,2). In 15% to 20% of patients, the gastrointestinal symptoms precede the diagnostic rash by a number of days (1,2). In such patients, inflammatory bowel disease is often a diagnostic consideration. Nevertheless, the coexistence of HSP and inflammatory bowel disease has not been reported. In this report, we describe a child with HSP as the presenting feature of Crohn's disease.
A 14-year-old girl had a 6-week history of intermittent purpuric rash on her lower extremities and painful, swollen ankles. One month before the onset of symptoms, she was evaluated for symptoms of decreased energy and pallor. Evaluation revealed low serum iron and ferritin concentrations. The patient was treated with iron replacement therapy, but she discontinued therapy after 2 weeks. The patient denied any history of weight loss, abdominal pain, diarrhea, or melena, but she reported the infrequent appearance of a small amount of blood on the toilet paper after bowel movements.
Physical examination revealed a thin but healthy-appearing adolescent girl. Her weight was 44.5 kg (10th to 25th percentile) and her height was 162 cm (50th percentile). There were multiple palpable purpuric lesions on her legs and feet (Fig. 1). Findings in the remainder of the physical examination were normal.
Laboratory studies revealed a leukocyte count of 13,000/μl with 70% neutrophils, 20% lymphocytes, and 8% monocytes. Hemoglobin was 8.3 g/dl, the platelet count was 584,000/μl, the reticulocyte count was 0.9%, and the erythrocyte sedimentation rate was 37 mm/hr. The red blood cells were hypochromic and microcytic. Results of urinalysis were normal. Serum concentrations of IgG, IgA, and IgM were normal. Tests for antinuclear antibody, rheumatoid factor, and antineutrophil cytoplasmic antibody (ANCA) were negative. A biopsy specimen of one of the purpuric skin lesions showed leukocytoclastic vasculitis involving the small vessels of the dermis. Direct immunofluorescence studies of the biopsy specimen revealed IgA, IgM, and C3 staining of the vessel walls. The diagnoses of HSP and iron-deficiency anemia were made, and iron was prescribed for treatment of the anemia.
Two weeks later, a more pronounced vasculitic rash developed with painful swelling of the feet and ankles. The patient received 40 mg/day prednisone for 10 days, and the rash and arthritis resolved within several days. Two days after the prednisone was discontinued, the rash and arthritis recurred. She was again treated with 40 mg/day prednisone for 7 days, and the rash and arthritis quickly resolved. She had another recurrence of rash and arthritis soon after the prednisone was discontinued. Because of persistent symptoms of vasculitis, she was treated with dapsone in a dosage of 75 mg/day for 10 days and 50 mg/day thereafter. The rash and joint pain resolved promptly. Nevertheless, while taking dapsone, she reported intermittent abdominal pain and hematochezia. Dapsone therapy was discontinued after 4 weeks.
One week after dapsone was discontinued, the patient experienced increased abdominal pain and hematochezia. She reported myalgia and joint pain, but there was no joint swelling. The purpuric rash had not recurred since dapsone treatment had begun. Laboratory study results revealed hemoglobin of 8.7 g/dl, a reticulocyte count of 9%, serum ferritin concentration of 41 ng/ml, and serum albumin of 2.0 g/dl. An upper gastrointestinal series with small bowel follow-through showed edematous duodenal folds and substantial nodularity of the terminal ileum. Endoscopic examination of the upper gastrointestinal tract revealed chronic active gastritis and duodenitis. Endoscopic examination of the colon revealed severe colitis, with relative sparing of the rectum. Biopsy specimens from the colon showed the formation of macrophage and histiocyte aggregations, but there were no well-formed granulomas. There was no histologic evidence of vasculitis. A repeat test for ANCA was positive with perinuclear staining on immunofluorescence. A test for antibody to Saccharomyces cerevisiae was negative. A diagnosis of Crohn's disease was made, and the patient was treated with prednisone, 5-aminosalicylic acid, and 6-mercaptopurine. The gastrointestinal symptoms quickly abated. There has been no recurrence of abdominal pain, bleeding, rash or arthritis in the 6 months since therapy was instituted. The prednisone was subsequently tapered and discontinued.
The patient in this report had many typical clinical and histologic features of HSP (1,2). Nevertheless, there were other features that were somewhat unusual and in retrospect may have served as clues to the presence of concomitant Crohn's disease. First, the patient in this report was an adolescent girl. Although HSP may occur in adults, it is primarily a disease of young children. The mean age of patients with HSP is 4 to 7 years, with 75% of children less than 8 years of age and 90% less than 10 years of age (1,2). Second, on several occasions, the patient reported hematochezia in the absence of concomitant abdominal pain. Gastrointestinal bleeding occurs in approximately 33% of patients with HSP, but it is important to note that gastrointestinal bleeding in HSP rarely, if ever, occurs in the absence of abdominal pain (1,2).
Crohn's disease was diagnosed four months after the onset of vasculitic symptoms. The endoscopic findings, histologic changes, and serologic results were all consistent with the diagnosis of Crohn's disease.
Histologically, Crohn's disease is characterized by a transmural inflammatory infiltrate composed predominantly of lymphocytes and macrophages. Macrophage aggregates are often seen in biopsy specimens, but well-developed granulomas are present in only approximately 50% of resected specimens (3). Although no granulomas were seen in the bowel biopsy specimens in our patient, there were aggregates of macrophages and histiocytes suggesting impending granuloma formation. There was no evidence of vasculitis on the bowel biopsy specimens. By contrast, the bowel histology in patients with HSP is characterized by neutrophilic vasculitis of the submucosal vessels with prominent IgA deposition in the vessel walls (4,5). These findings are virtually identical with the histologic findings on skin biopsy, and suggest that vasculitis plays a major role in the pathogenesis of the gastrointestinal involvement in HSP (4).
A test for ANCAs was negative when the patient was having symptoms of HSP, but a second test for ANCAs produced positive results with a perinuclear staining pattern at the time of diagnosis of Crohn's disease. Test results for ANCAs are routinely negative in children with HSP (1). By contrast, a substantial proportion of children with inflammatory bowel disease have positive results for ANCA with a perinuclear staining pattern. Perinuclear ANCA is present in 40% and 80% of patients with ulcerative colitis and in 10% and 40% of patients with Crohn's disease (6,7). Colitis was a prominent feature of Crohn's disease in our patient. In that regard, Vasiliauskas et al. (8) reported that ANCA-positive Crohn's disease is often associated with prominent clinical and histologic features of colitis.
Vasculitis is an uncommon complication of Crohn's disease. Cutaneous polyarteritis nodosa has been reported in a few patients with Crohn's disease (9), but small vessel leukocytoclastic vasculitis is very rare (10). Moreover, in the few patients reported, the Crohn's disease preceded the onset of cutaneous leukocytoclastic vasculitis by months to years (11–13). To date, HSP has not been reported in association with Crohn's disease.
The causes of HSP and Crohn's disease are unknown. It is clear, however that IgA plays a central role in the immunopathogenesis of HSP (1). The clinical features of HSP are a consequence of widespread leukocytoclastic vasculitis owing to IgA deposition in vessel walls. Crohn's disease appears to be a T-cell–mediated disease, and there is little if any evidence that IgA or circulating immune complexes play any role in the pathogenesis of Crohn's disease (3). We conclude therefore that the patient in this report had both HSP and Crohn's disease. In patients with HSP who experience prolonged or atypical gastrointestinal symptoms, a search for concomitant Crohn's disease deserves consideration.
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