What is the role and management of the terminal ileum in relation to conditions like Crohn's disease?

Terminal Ileum: Clinical Overview

Anatomical and Functional Significance

The terminal ileum is the distal 10-20 cm of the small intestine, representing a critical site for nutrient absorption and immune surveillance that is disproportionately affected by Crohn's disease due to genetic predisposition and bacterial colonization patterns 1.

Key Absorptive Functions

• Vitamin B12 absorption occurs exclusively in the terminal ileum through intrinsic factor-mediated uptake 2
• Bile acid reabsorption takes place in the terminal ileum, with resection leading to bile acid malabsorption in >80% of patients 3
• Resections <20 cm typically do not cause vitamin B12 deficiency, while resections of 20-60 cm place patients at high risk 2

Disease Distribution in Crohn's Disease

The terminal ileum is the most common site of Crohn's disease involvement, with 25% having isolated ileitis and 50% having ileocolitis 4, 1. This predilection occurs because:

• Genetic polymorphisms (CARD15, CEACAM6, ATG16L1, IRGM) favor colonization by adherent-invasive E. coli specifically in the terminal ileum 1
• Reduced ileal defensin expression in CARD15 mutation carriers allows bacterial adherence 1
• Defective autophagy genes impair macrophage bacterial killing, leading to chronic inflammation 1

Diagnostic Approach to Terminal Ileal Disease

Initial Evaluation

Ileocolonoscopy with biopsies of both the terminal ileum and colon is the first-line investigation for suspected Crohn's disease 3, 5. Key steps include:

• Intubation of the terminal ileum is essential but may fail in up to 20% of cases 3
• Multiple biopsies from both diseased and normal-appearing mucosa are mandatory 3, 5
• Fecal calprotectin >100-250 μg/g warrants endoscopic evaluation with 93% sensitivity and 96% specificity for IBD 6

Endoscopic Scoring

The Simple Endoscopic Score for Crohn's Disease (SES-CD) evaluates the terminal ileum for ulcer size, ulcerated surface area, affected surface area, and presence of strictures 3. The Rutgeerts score (i0-i4) specifically assesses postoperative recurrence at the neoterminal ileum 3:

• i0-i1: Low risk of clinical recurrence
• i2-i4: High risk requiring treatment escalation 3

Cross-Sectional Imaging

MR enterography or CT enterography should be performed in all newly diagnosed patients to assess disease extent beyond the reach of colonoscopy 3, 6. Approximately one-third of Crohn's patients have proximal small bowel disease not visible on ileocolonoscopy 3, 6.

Management of Terminal Ileal Crohn's Disease

Medical Therapy

For localized ileocecal disease with obstructive symptoms but minimal active inflammation, surgery is preferred over medical therapy 3. When medical management is appropriate:

• Corticosteroids and TNF inhibitors are most effective for induction 4
• Thiopurines, methotrexate, and TNF inhibitors maintain remission 4
• High-dose mesalazine is an option for isolated ileal resection 3

Surgical Considerations

Wide-lumen stapled ileocolic side-to-side (functional end-to-end) anastomosis is the preferred surgical technique 3. Key principles include:

• Laparoscopic approach is preferred when expertise is available 3
• Resection margins need not be wide; microscopic involvement at margins does not affect recurrence 3
• Stricturoplasty is appropriate for multiple strictures or when >100 cm of bowel has been previously resected 3
• Terminal ileitis found incidentally at appendectomy should NOT be routinely resected due to high risk of intra-abdominal septic complications 3

Postoperative Management

Endoscopic surveillance at 6 months postoperatively is recommended to assess the neoterminal ileum and guide treatment escalation if Rutgeerts score ≥i2 3. Risk factors for postoperative recurrence include:

• Smoking increases endoscopic recurrence 2.5-fold and clinical recurrence 2-fold 3
• Prior resection, penetrating disease, perianal disease, and extensive resection (>50 cm) 3
• All patients who smoke after resection should be actively encouraged to stop 3

Anti-TNF prophylaxis is the most effective strategy for preventing postoperative recurrence, superior to thiopurines 3. Long-term prophylaxis should be recommended 3.

Complications of Terminal Ileal Resection

Bile Acid Malabsorption

A therapeutic trial of bile acid sequestrants is appropriate for diarrhea following ileal resection, particularly when fecal calprotectin is not significantly elevated 3. Management options:

• Cholestyramine is first-line but may be unpalatable 3
• Colestipol or colesevelam are alternatives 3
• Loperamide can also be used 3
• SeHCAT scanning should only be requested when there is diagnostic uncertainty 3

Small Intestinal Bacterial Overgrowth

SIBO occurs in approximately 30% of patients after Crohn's disease resection and mimics active disease with bloating, diarrhea, and malnutrition 3. It is more common with blind loops, dysmotility, or strictures 3.

Nutritional Deficiencies

• Vitamin B12 deficiency occurs with resections ≥20 cm 2
• Malnutrition can be severe and potentially fatal if untreated 7
• Parenteral nutrition may be required if <100 cm of jejunum remains proximal to a jejunostomy 3

Differential Diagnosis of Terminal Ileal Ulcers

Beyond Crohn's disease, consider 5:

• Backwash ileitis from ulcerative colitis (continuous extension from cecum in up to 20% of extensive colitis)
• Infectious causes: Yersinia, Salmonella, Campylobacter, CMV (especially in immunocompromised patients)
• Microscopic colitis with terminal ileal involvement
• Medication-induced (NSAIDs)

Stool cultures and C. difficile testing are mandatory in all cases of suspected or worsening IBD before escalating immunosuppression 8. Failure to exclude infection can lead to worse outcomes including higher colectomy rates 8.