Henoch-Schönlein Purpura Presenting as Terminal Ileitis: Case Report and Review of Unusual Causes of Ileitis

Henoch–Schönlein purpura (HSP) is an acute vasculitic syndrome presenting with cutaneous purpura on the lower extremities and buttocks as a hallmark clinical feature.^1,2 Arthritis and gastrointestinal and renal involvement are also frequently associated with HSP. Most often HSP occurs in children, with an annual incidence estimated at 10 per 100,000 children.^3,4 The mean age at diagnosis is 6 years and 90% of affected individuals are less than 10 years of age. HSP is rare in adults but often more severe and more likely to manifest with renal involvement.⁵ Although gastrointestinal manifestations are common in adults, they typically occur with background systemic involvement and, as such, HSP presenting as ileitis is rarely reported in adult populations. We present such a case and discuss the relevant literature pertaining to HSP and other unusual causes of ileitis in adults.

Case Report

An otherwise healthy 21-year-old Asian American woman developed abdominal pain, nausea, vomiting, and diarrhea 2 weeks after experiencing an upper respiratory syndrome. Her only medical condition was a mild anxiety disorder, for which she took paroxetine. She was seen by two physicians within the first 4 weeks of symptom onset because of severe abdominal pain and was diagnosed with gastroenteritis and irritable bowel syndrome (IBS). Four weeks after symptom onset, she was admitted to the hospital due to persistent, severe abdominal pain. A computed tomography (CT) scan of the abdomen revealed inflammation in the mid-ileum. A presumptive diagnosis of Crohn’s disease was made. The patient was started on oral prednisone 40 mg daily and transferred to our institution for further evaluation and treatment.

On admission, the patient was experiencing moderately severe, diffuse abdominal pain. She was afebrile and her pulse and blood pressure were normal. Her abdomen was soft and nondistended and her bowel sounds were normal. There was diffuse tenderness to palpation without peritoneal findings. A violaceous, purpuric rash developed within 12 hours of admission, involving bilateral lower and upper extremities, back, and chest (Figure 1). Her white blood cell count was 18,000/μL and consisted of 69% neutrophils, 25% lymphocytes, 5% monocytes, and 1% eosinophils. Her hemoglobin measured 13.6 g/dL and her platelet count was 361,000/μL. Blood urea nitrogen and serum creatinine levels were within normal limits. Urinalysis was unremarkable. Stool studies done at the transferring facility showed no evidence for parasites, Clostridium difficile toxin, or enteric infection. Serologies for hepatitis B virus, hepatitis C virus, antinuclear antibody, anti–Saccharomyces cerevisiae antibody, perinuclear antineutrophil cytoplasmic antibody, and cytoplasmic antineutrophil cytoplasmic antibody were negative. Total complement, C3, and C4 levels were also normal. Colonoscopy revealed a grossly normal colon throughout but marked confluent ulceration of the ileum (Figure 2). Ileal biopsies showed acute inflammation with ulceration and hemorrhagic necrosis. Random biopsies from the colon were normal. A punch biopsy of a skin lesion revealed neutrophilic dermatitis with karyorrhexis.

Figure 1.

Purpuric rash over the distal aspect of the lower extremities. Similar lesions were present on the upper extremities and trunk.

Figure 2.

Endoscopic appearance of the cecum (left) and terminal ileum (right). The cecum is grossly normal although the ileocecal valve is patulous and erosions can be seen at the orifice. The terminal ileum is diffusely ulcerated. Biopsies of ileal mucosa revealed only ischemic necrosis.

A diagnosis of Crohn’s disease with Sweet syndrome was made and the patient continued on prednisone. Her abdominal pain, diarrhea, and rash resolved, and she was discharged on the fifth day of hospitalization. Reduction of the prednisone dosage as an outpatient led to recurrent abdominal pain and reemergence of the violaceous purpuric rash. She was readmitted, at which time urinalysis revealed greater than 4 grams protein and red blood cell casts. Because of concerns for vasculitis and glomerulonephritis, a renal biopsy was performed. The biopsy demonstrated active nephritis with immunoglobulin A deposition in the mesangium. A (IgA) diagnosis of HSP was made based on renal biopsy findings along with the purpuric rash and ileitis. Intravenous steroids were administered followed by oral prednisone with resolution of symptoms over the next several days. She was discharged on prednisone 40 mg daily. Over the following several weeks, prednisone was gradually tapered without recurrence of symptoms. After 6 months, the patient remains asymptomatic with no evidence of either ileitis or nephritis.

Discussion

This case demonstrates two important clinical points. First, although Crohn’s disease remains the leading cause of ileitis in young adults, evaluation of alternate causes is warranted when associated with extraintestinal symptoms (eg, rash) or when response to therapy is atypical. Further, although HSP most often presents with arthralgias, rash, colicky abdominal pain, and renal involvement in children, it may rarely present as isolated ileitis in young adults.

Vasculitis represents just one of the many uncommon causes of ileitis that are summarized in Table 1.⁶ Yersinia enterocolitica is the most common bacterial infection causing ileitis.^7,8 Less commonly reported infections include cytomegalovirus, salmonella, shigella, Entamoeba histolytica, actinomycosis, and Mycobacterium tuberculosis.^9-15 The latter two entities are capable of causing intestinal fistulization and mimicking Crohn’s disease.^16,17 Malignant involvement of the terminal ileum may mimic ileitis. Lymphomas and carcinomas are the most common tumors in this location, with lymphomas often presenting in patients with longstanding IBS.¹⁸ Adenocarcinoma arising from the ileocecal valve can also give this appearance.^19,20 Medications that cause ileal inflammation include nonsteroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, ergot derivatives, and digoxin.⁶ NSAIDs can also cause thin fibrotic strictures that are easily distinguished from the thick inflammatory strictures of Crohn’s disease.²¹ Ileal involvement is common in patients with spondyloarthropathies but typically goes undetected unless diagnostic colonoscopy is warranted.⁶ Ulcerative ileojejunitis is a rare but potentially severe illness that may occur in association with celiac sprue.²² Eosinophilic gastroenteritis may present with ileal involvement, abdominal pain, and diarrhea associated with full-thickness eosinophilic infiltrates of the bowel.²³

Table 1.

Conditions Associated with Ileitis

Infectious
Yersinia enterocolitica Yersinia pseudotuberculosis Mycobacterium tuberculosis Mycobacterium avium–intracellulare complex Histoplasma capsulatum Salmonella Cryptococcosis Anisakiasis Actinomycosis israelii Entamoeba histolytica Typhlitis
Inflammatory
Appendicitis Appendiceal abscess Torsion of the appendiceal epiploica Cecal diverticulitis
Gynecologic
Pelvic inflammatory disease Tubo-ovarian abscess Ovarian cyst or tumor Ovarian torsion Ectopic pregnancy Endometriosis
Neoplastic
Cecal or small bowel (ileal) adenocarcinoma Lymphoma Lymphosarcoma Carcinoid tumor Metastatic cancer
Drug-related
Nonsteroidal anti-inflammatory drug–related ulcer or stricture Ischemic - Oral contraceptives ergotamine - Digoxin - Diuretics - Antihypertensives
Vascular
Vasculitides - Polyarteritis nodosa - Churg-Strauss syndrome - Takayasu arteritis - Wegener granulomatosis - Lymphomatoid granulomatosis - Giant-cell arteritis - Rheumatoid arthritis vasculitis - Thromboangiitis obliterans Henoch-Schönlein purpura Systemic lupus erythematosus Behçet syndrome Ischemia
Infiltrative and Other
Eosinophilic gastroenteritis Amyloidosis Lymphoid nodular hyperplasia (normal or suggestive of immunoglobulin G deficiency) Ileitis associated with spondyloarthropathy Backwash ileitis arising in ulcerative colitis Radiation enteritis Ulcerative ileojejunitis (celiac sprue)

Ischemia of the terminal ileum also causes ileitis, usually with cecal involvement.^24,25 The most common causes of ischemic ileitis are atherosclerotic vascular disease and “low-flow” states resulting in nonocclusive mesenteric ischemia. Because the ileocolic branches are the longest branches of the superior mesenteric artery, the ileocecal region is most susceptible to ischemia from poor perfusion. Ischemic ileitis has also been reported as a complication of sickle cell disease.²⁶

Vasculitis involving the mesenteric circulation can also result in ischemia. Mesenteric vasculitis is most commonly associated with HSP, polyarteritis nodosa, and systematic lupus erythematosus.²⁷ In general, visceral vasculitis presents with abdominal pain, nausea, vomiting, diarrhea, and gastrointestinal bleeding. Small-vessel or leukocytoclastic vasculitis is characterized by mucosal ischemia whereas vasculitis involving medium-size or larger vessels may more likely result in transmural involvement, leading to peritoneal findings or frank perforation of the digestive tract.

In general, isolated intestinal involvement is unusual in vasculitis as these are systemic conditions typically manifesting signs and symptoms in multiple organ systems. In particular, HSP presenting as ileitis is uncommon and a review of the English-language literature uncovered only eight case reports, including this one.^28-33 In only three of these eight cases did ileitis initially present without associated rash, arthralgias, or renal involvement. Our patient was similar in that she presented with abdominal pain and did not develop rash and nephritis until 1 month later. It is interesting that the syndrome is dominated by involvement of IgA deposits in cutaneous and renal tissue. IgA is predominantly induced in mucosal lymphoid structures (eg, Peyer patches) where it is essential in defending against enteric microbes.³⁴ As Peyer patches abound in the distal ileum, it is possible that induction of IgA at these sites may be involved in the pathogenesis of ileal inflammation in HSP with subsequent spread to other involved tissue (kidney and skin) due to antigen mimicry.

In fact, it was only after the renal biopsy in this case disclosed mesangial immunoglobulin A deposits that the diagnosis of HSP was made. The painful, purpuric rash had raised the possibility of leukocytoclastic vasculitis but the biopsy was nondiagnostic. In fact, the biopsy had actually suggested the possibility of Sweet syndrome. Sweet syndrome is a neutrophilic dermatosis that can occur as an isolated finding or may accompany a variety of conditions, chiefly inflammatory bowel disease, rheumatoid arthritis, and lymphoproliferative disorders.³⁵ Whereas neutrophilic dermatosis is histologically characterized by a dense neutrophilic infiltrate without evidence of vasculitis, Sweet syndrome has been described in association with vasculitis.^36,37 Additionally, biopsies of advanced lesions in leukocytoclastic vasculitis may demonstrate a predominant neutrophilic infiltrate without prominent vasculitic features. Finally, Crohn’s disease is associated with both vasculitis and thromboembolic events.^6,38

In summary, HSP, a disease chiefly affecting children, can occasionally affect adults. The diagnosis can be delayed, particularly when it presents without the classic triad of purpura, colicky abdominal pain, and arthritis. Gastrointestinal involvement in HSP is common, but reports in the literature describing isolated involvement of the terminal ileum are rare. This case highlights both the broad differential diagnosis of ileitis and the importance of this uncommon presentation of HSP as isolated ileitis in an adult.