What are the causes of terminal ileitis?

Causes of Terminal Ileitis

Terminal ileitis has multiple etiologies with Crohn's disease being the most common cause in Western populations, followed by infectious causes (particularly Yersinia, Salmonella, Campylobacter), ulcerative colitis with backwash ileitis, NSAID-induced enteropathy, and in endemic regions like India, intestinal tuberculosis is the primary cause. 1, 2

Primary Etiologies

Crohn's Disease

• Crohn's disease is the most frequent cause of terminal ileal ulcers in Western populations, characterized by transmural inflammation that commonly affects the terminal ileum 2
• Endoscopic features include aphthous ulcers, longitudinal ulcers, cobblestone appearance, and skip lesions 1
• Histopathology shows focal chronic inflammation, transmural involvement, small non-caseating granulomas, and crypt architectural distortion 1, 2
• Approximately 50% of patients require surgery within 10 years of diagnosis due to complications 1

Infectious Causes

• Yersinia enterocolitica, Salmonella, Shigella, and Campylobacter species cause acute terminal ileitis that typically resolves with appropriate antimicrobial therapy 1, 2
• Yersinia infection in acute terminal ileitis (symptoms ≤1 week) is prognostically favorable—patients with positive Yersinia serology are unlikely to progress to chronic Crohn's disease 3
• Cytomegalovirus can cause terminal ileal ulcers, particularly in immunocompromised patients 2
• Stool cultures should be performed, especially in acute presentations 1

Geographic Variation: Tuberculosis

• In India and other endemic regions, intestinal tuberculosis is the primary etiology of terminal ileal ulcers, followed by Crohn's disease 1
• Tuberculosis typically affects the ileocecal region with circumferential ulcers, strictures, and occasionally perforation 1
• Histopathology shows large granulomas (often multiple and confluent) with caseous necrosis and acid-fast bacilli 1
• Untreated tuberculosis leads to strictures, perforation, and fistula formation 1

Ulcerative Colitis with Backwash Ileitis

• Continuous extension of inflammation from the cecum into terminal ileum occurs in up to 20% of patients with extensive ulcerative colitis 4, 2
• This represents continuous inflammation extending from colon to terminal ileum, not skip lesions 2
• Patients with backwash ileitis are prone to more refractory disease with increased risk of colon neoplasia 4
• Additional small bowel imaging should be considered to differentiate from Crohn's disease 4

NSAID-Induced Enteropathy

• NSAID enteropathy accounts for 12.7% of terminal ileitis cases in diagnostic series 5
• This is typically subclinical and often escapes detection unless symptoms warrant further testing 6
• The inflammation is medication-induced and reversible with drug discontinuation 7, 6

Less Common Causes

Spondyloarthropathies

• Associated ileitis is typically subclinical and may be detected incidentally 6
• Extra-intestinal manifestations such as arthritis may be present 4

Vascular and Systemic Conditions

• Vasculitides can cause terminal ileitis with a chronic and debilitating course complicated by obstructive symptoms and hemorrhage 6
• Ischemic ileitis from mesenteric vascular insufficiency 7, 6
• Sarcoidosis and amyloidosis are rare causes 7, 6

Neoplastic Causes

• In patients with long-standing Crohn's ileitis, recrudescence of symptoms may represent neoplasm involving the ileum 6
• Malignant diseases can present with terminal ileal inflammation 7

Other Inflammatory Conditions

• Eosinophilic enteritis causes terminal ileal inflammation 7, 6
• Microscopic colitis (collagenous or lymphocytic) can occasionally involve the terminal ileum with increased intraepithelial lymphocytes 2

Diagnostic Algorithm

Initial Evaluation

• Ileocolonoscopy with multiple biopsies from both visible lesions and normal-appearing mucosa is the gold standard 1, 2
• Stool cultures for bacterial pathogens and C. difficile toxin 4, 1
• Inflammatory markers (CRP, fecal calprotectin) 4

Advanced Imaging When Needed

• Cross-sectional enterography (CT or MRI) assesses extent and severity, with severe inflammation showing wall thickening of 3-5mm, ulcerations, or high T2 intramural signal 2
• Small bowel capsule endoscopy reveals positive findings in 82.4% of isolated terminal ileitis cases, supporting definite diagnosis in two-thirds of patients 5
• Capsule endoscopy findings predictive of Crohn's disease include proximal small-bowel involvement, diffuse findings, and Lewis score ≥790 5

Critical Pitfalls

• Do not assume all terminal ileitis is Crohn's disease—infectious causes are common and treatable, particularly in acute presentations 1, 3
• In endemic regions, always consider tuberculosis first and obtain appropriate testing including acid-fast bacilli staining 1
• Do not perform appendectomy in the presence of terminal ileitis—this significantly increases risk of intra-abdominal septic complications and fistulas 8
• Obtain detailed medication history for NSAIDs, as this is a reversible cause 5