What is the likely diagnosis and management for a young to middle-aged adult presenting with mucosal enhancement and submucosal edema/fatty infiltration confined to the terminal ileum, particularly in the very distal aspects?

Crohn's Disease of the Terminal Ileum

The imaging findings of mucosal enhancement and submucosal edema/fatty infiltration confined to the distal terminal ileum are highly characteristic of active Crohn's disease, and you should proceed with ileocolonoscopy with biopsies to confirm the diagnosis, followed by initiation of immunosuppressive therapy based on disease severity. 1, 2

Diagnostic Interpretation

The imaging pattern described represents classic features of active inflammatory Crohn's disease:

• Segmental mural hyperenhancement with wall thickening confined to the terminal ileum has moderately high sensitivity and specificity for small bowel Crohn's disease, particularly when combined with submucosal changes 1, 2

• Submucosal edema indicates active inflammation and correlates with moderate to severe endoscopic disease activity 1

• Fatty infiltration (intramural fat deposition) indicates chronicity but does not determine whether active inflammation is present or absent 1

• The distal terminal ileum is the most common location for Crohn's disease, as this condition characteristically affects the terminal ileum and colon with transmural inflammation 1, 3

Key Imaging Features Supporting Crohn's Disease

• Wall thickness ≥10 mm indicates severe inflammation, while 5-9 mm represents moderate inflammation 1, 2

• Stratified (bi- or tri-laminar) enhancement pattern with submucosal edema is typical of active Crohn's disease 1

• Asymmetric thickening, particularly affecting the mesenteric border more than the antimesenteric border, is highly specific for Crohn's disease 1, 2

Differential Diagnosis Considerations

While Crohn's disease is most likely, other conditions must be excluded:

• Infectious enteritis (Yersinia, Salmonella, Campylobacter, Cytomegalovirus) can cause terminal ileal inflammation but typically presents acutely 3, 4

• Intestinal tuberculosis is the primary differential in endemic regions, characterized by circumferential ulcers and strictures 4

• Backwash ileitis from ulcerative colitis affects the terminal ileum in up to 20% of patients with extensive colitis, but shows continuous inflammation extending from the colon rather than isolated terminal ileal disease 3, 4

• NSAID enteropathy, radiation enteritis, and ischemia can cause similar imaging findings but have distinct clinical contexts 1

Diagnostic Workup Algorithm

Step 1: Endoscopic Evaluation

• Perform ileocolonoscopy with multiple biopsies from both visible lesions and normal-appearing mucosa to establish histologic diagnosis 1, 3

• Endoscopic features suggesting Crohn's disease include aphthous ulcers, longitudinal ulcers, and cobblestone appearance 4, 5

• Histopathologic features of Crohn's disease include focal (discontinuous) chronic inflammation, transmural involvement, and non-caseating granulomas 3, 4, 6

Step 2: Exclude Infectious Causes

• Obtain stool cultures for bacterial pathogens (Yersinia, Salmonella, Shigella, Campylobacter) and test for Clostridium difficile toxin 1, 4

• Consider testing for tuberculosis in endemic regions or high-risk patients, as intestinal TB characteristically affects the ileocecal region 4

Step 3: Assess Disease Extent

• MR enterography with oral and IV contrast is the preferred modality for evaluating the full extent of small bowel involvement, with sensitivity of 66-95% and specificity of 64-97% 2

• Small bowel follow-through or enteroclysis can define the extent and location of disease if MR enterography is unavailable 1

Step 4: Laboratory Assessment

• Obtain complete blood count, erythrocyte sedimentation rate or C-reactive protein, liver function tests, and renal function 1

• Consider TPMT and NUDT15 testing before initiating thiopurine therapy, as deficiency increases risk of severe myelotoxicity 7

Management Strategy

Initial Treatment Based on Disease Severity

For moderate to severe active Crohn's disease:

• Initiate induction therapy with infliximab 5 mg/kg IV at weeks 0,2, and 6, followed by maintenance dosing every 8 weeks 8

• Conventional immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate) are alternatives for patients with less severe disease or as maintenance therapy 1

• Anti-TNF biologics (infliximab, adalimumab) are first-line biologics due to good effectiveness/safety profile and lower cost with biosimilars 1

For inadequate response to anti-TNF therapy:

• Next-line biologics include vedolizumab (anti-integrin) or ustekinumab (IL-12/23 inhibitor) 1

Monitoring Treatment Response

• Focus on transmural remission (normalization of all imaging features) rather than endoscopic response alone, as transmural remission is associated with better long-term outcomes 1

• Responsive imaging features include bowel wall thickness, vascularization, stratification, ulcers, and perienteric inflammatory changes 1

• Reassess with cross-sectional imaging to evaluate for transmural response, stable disease, or progression 1

Critical Pitfalls to Avoid

• Do not delay endoscopic evaluation - imaging alone cannot provide histologic confirmation or exclude other diagnoses 1, 3

• Residual mural thickness or fatty deposition may persist after mucosal healing, potentially causing false-positive findings of active disease on imaging 1

• Screen for latent tuberculosis before initiating anti-TNF therapy, as these patients are at increased risk for reactivation 8

• Monitor for serious infections and malignancy during immunosuppressive therapy, particularly hepatosplenic T-cell lymphoma in young males receiving combination therapy with azathioprine and anti-TNF agents 8, 7

• Patients with TPMT or NUDT15 deficiency require dose reduction or alternative therapy to avoid life-threatening myelotoxicity 7