What are the causes of terminal ileal ulcers?

Causes of Terminal Ileal Ulcers

Terminal ileal ulcers can be caused by several conditions, with Crohn's disease being the most common etiology, accounting for approximately 25.7% of cases. 1

Common Causes

Inflammatory Bowel Disease

• Crohn's disease is the most frequent cause of terminal ileal ulcers, characterized by transmural inflammation that can occur throughout the gastrointestinal tract but commonly affects the terminal ileum 2
• Ulcerative colitis may present with "backwash ileitis," which is continuous extension of inflammation from the cecum into the terminal ileum, seen in up to 20% of patients with extensive colitis 3
• Microscopic colitis (collagenous or lymphocytic colitis) can occasionally involve the terminal ileum with increased intraepithelial lymphocyte count and subepithelial collagen deposition 4

Medication-Induced

• Non-steroidal anti-inflammatory drugs (NSAIDs) are a significant cause, accounting for approximately 14.9% of terminal ileal ulcers 1
• Various medications can cause drug-induced ulceration that mimics Crohn's disease 5

Infectious Causes

• Intestinal tuberculosis accounts for about 12.2% of terminal ileal ulcers 1
• Other infectious agents include:
  • Yersinia species 6
  • Salmonella species 6
  • Shigella species 6
  • Campylobacter species 6
  • Cytomegalovirus, particularly in immunocompromised patients 6
  • Clostridium difficile as a superimposed infection 6

Other Inflammatory Conditions

• Eosinophilic enteritis is responsible for approximately 6.8% of cases 1
• Nonspecific terminal ileal ulcers account for about 40.5% of cases, which may resolve with symptomatic treatment 1
• Behçet's disease can present with terminal ileal ulceration 7
• Spondyloarthropathies may have associated intestinal inflammation 8
• Vasculitides affecting the intestinal vasculature 8, 7

Less Common Causes

Neoplastic Conditions

• Primary small bowel lymphomas 7
• Other primary intestinal cancers 7
• Metastatic lesions from distant organs 7

Miscellaneous Causes

• Ischemic conditions affecting the terminal ileum 7
• Sarcoidosis with gastrointestinal involvement 8
• Amyloidosis with intestinal deposition 8
• Endometriosis involving the terminal ileum 7
• Lymphoid hyperplasia 5

Diagnostic Approach

Endoscopic Evaluation

• Ileocolonoscopy with biopsies is essential for diagnosis 4
• Severe inflammation is characterized by wall thickening of 3-5 mm, presence of ulcerations, or high T2 intramural signal on imaging 9
• Multiple biopsies should be taken from both visible lesions and normal-appearing mucosa 4

Imaging

• Cross-sectional enterography (CT or MRI) can help assess the extent and severity of terminal ileal inflammation 9
• Findings of severe inflammation include marked wall thickening, intramural edema, and small ulcerations 9
• Restricted diffusion on MRI, when present with other signs of inflammation, supports the diagnosis of severe inflammation 9

Histopathological Features

• Crohn's disease: Focal (discontinuous) chronic inflammation, transmural involvement, granulomas (non-crypt related) 4
• Ulcerative colitis with backwash ileitis: Continuous inflammation extending from colon to terminal ileum 3
• Infectious causes: May show specific histological features depending on the pathogen 6
• NSAID-induced: Typically shows nonspecific inflammation 1

Clinical Significance and Management

• Proper identification of the underlying cause is crucial as treatment approaches differ significantly 8
• Misdiagnosis of Crohn's disease may lead to inappropriate therapy and potentially unnecessary surgery 5
• For nonspecific terminal ileal ulcers, symptomatic treatment may be sufficient, but close monitoring is recommended if symptoms persist 1
• Most patients with nonspecific terminal ileal ulcers show clinical improvement (91.7%) and endoscopic resolution (77.8%) with appropriate treatment 1

Important Considerations

• Terminal ileal ulcers found during colonoscopy should never be automatically attributed to Crohn's disease without thorough evaluation 7, 5
• In patients with gastrointestinal symptoms and terminal ileal ulcers, more than half have specific etiologies that can be identified with appropriate testing 1
• Follow-up endoscopy may be necessary in cases where the initial diagnosis is unclear or symptoms persist despite treatment 1