What are the gastrointestinal manifestations of Behçet disease and how should they be evaluated and managed?

Gastrointestinal Manifestations of Behçet Disease

Gastrointestinal Behçet disease primarily causes deep penetrating ulcers in the terminal ileum and ileocecal region that frequently perforate and require emergency surgical resection, with high rates of recurrence demanding aggressive immunosuppression to prevent mortality. 1

Clinical Manifestations

Location and Ulcer Characteristics

• Deep penetrating ulcers most commonly affect the terminal ileum, ileocecal region, and colon, though any segment of the GI tract can be involved. 1
• The ileocecal area is the typical site of involvement after the oral cavity. 2, 3
• Ulcers can appear as "volcano-type" lesions, which are associated with poor prognosis. 4
• Esophageal, gastric, and duodenal aphthae occur but are less frequent than intestinal involvement. 5

Clinical Presentation

• Patients present with diarrhea, gastrointestinal bleeding, or acute perforation. 1
• Prolonged hemorrhagic diarrhea with marked deterioration in general condition is common. 5
• Acute complications include perforation and massive hemorrhage, both requiring emergency intervention. 5
• Constitutional symptoms such as weight loss, fever, night sweats, and general malaise frequently accompany GI involvement. 1

Complications and Prognosis

• Perforation is a frequent complication necessitating emergency surgical resection (ileocolectomy or hemicolectomy). 1
• Long-term recurrence rates and re-operation rates are high, with ulcerative recurrences commonly developing at anastomotic sites. 1, 5
• Fistulae may develop at anastomoses, sometimes requiring extensive intestinal resections or long-term ileostomies. 5
• GI involvement is associated with significant morbidity and mortality, marking it as a major organ involvement requiring aggressive treatment. 1, 3

Evaluation

Diagnostic Approach

• Diagnosis is based on clinical criteria—there are no pathognomonic laboratory tests. 3
• Look for deep colonic ulcerations frequently situated in otherwise healthy mucosa, distinguishing this from inflammatory bowel disease. 5
• Endoscopic findings show inflammatory lesions that may mimic severe acute colitis, hemorrhagic proctocolitis, or Crohn's disease. 5
• Radiological and endoscopic evaluation should assess the extent and severity of ulceration. 5

Histopathology

• Biopsy reveals non-specific inflammatory infiltrate affecting the entire colonic wall. 5
• Lesions of vasculitis and perivasculitis with leukocytoclasis and fibrinoid necrosis are characteristic. 5

Prognostic Factors

• Young age at diagnosis, higher disease activity, volcano-type ulcers, absence of mucosal healing, elevated C-reactive protein, prior surgery history, and lack of initial response to medical therapy all predict poor outcomes. 4
• Novel disease activity indices have been developed to monitor treatment response. 4

Management

Medical Treatment Strategy

Medical treatment with sulfasalazine, corticosteroids, and azathioprine should be tried before surgery, except in emergencies. 6

First-Line Therapy

• Glucocorticoids are recommended for rapid ulcer healing during acute exacerbations. 7
• High-dose glucocorticoids (prednisolone 1 mg/kg/day) should be initiated for acute flares, followed by gradual taper over 2-3 months. 6
• 5-aminosalicylic acid (5-ASA) agents serve as disease-modifying therapy. 7, 3

Steroid-Sparing Immunosuppression

• Azathioprine is the preferred disease-modifying agent for maintenance therapy. 7
• Immunomodulators should be combined with corticosteroids to minimize long-term steroid exposure. 6

Refractory Disease

• For severe or refractory cases, monoclonal anti-TNF antibodies (infliximab) and/or thalidomide are recommended. 6, 7
• Anti-TNF agents can achieve clinical responses and remission in patients previously nonresponsive to corticosteroids or immunomodulators. 4
• Screen for tuberculosis before initiating anti-TNF therapy, as endemic areas for Behçet disease overlap with TB-endemic regions. 6

Surgical Management

• Surgery is reserved for emergencies (perforation, massive hemorrhage) or medical treatment failure. 6, 3
• Extensive intestinal resections may be necessary given the high incidence of anastomotic recurrences. 5
• Long-term ileostomies or diversions may be required for recurrent fistulae. 5

Critical Clinical Warnings

Immediate Action Required

• GI involvement represents major organ disease requiring immediate aggressive immunosuppression to prevent irreversible damage or death. 1, 7
• Delaying immunosuppression in major organ involvement can result in permanent damage. 7

Common Pitfalls

• Do not mistake GI Behçet disease for inflammatory bowel disease—the diagnosis depends on recognizing the constellation of extraintestinal manifestations (oral/genital ulcers, ocular disease, skin lesions). 5
• Avoid cyclosporine A if any CNS involvement is present or suspected due to neurotoxicity risk. 6, 7
• Recognize that young males with early disease onset have more severe courses and warrant more aggressive treatment from the outset. 1, 7