In a 30‑year‑old adult presenting with intermittent right‑lower‑quadrant abdominal pain, crampy diarrhea, occasional blood or mucus in stool, weight loss, low‑grade fever, mild anemia, elevated C‑reactive protein and hypoalbuminemia, colonoscopy shows patchy inflammation of the terminal ileum; what are the likely etiologies, recommended diagnostic work‑up, and appropriate management?

Patchy Ileitis: Differential Diagnosis, Workup, and Management

In a 30-year-old with patchy terminal ileal inflammation, right lower quadrant pain, bloody diarrhea, weight loss, and elevated inflammatory markers, Crohn's disease is the most likely diagnosis, but you must systematically exclude infectious causes, NSAID-induced enteropathy, and other inflammatory conditions before initiating immunosuppressive therapy. 1

Most Likely Etiologies

Primary Consideration: Crohn's Disease

• Crohn's disease most commonly affects the terminal ileum and right colon, producing right lower quadrant pain with patchy, discontinuous distribution and skip lesions 2
• The clinical presentation—intermittent crampy abdominal pain, diarrhea with blood/mucus, weight loss, fever, anemia, elevated CRP, and hypoalbuminemia—is classic for ileocolonic Crohn's disease 1
• Patchy inflammation is a hallmark endoscopic feature distinguishing Crohn's disease from ulcerative colitis, which shows continuous inflammation 2

Critical Differential Diagnoses to Exclude

Infectious ileitis:

• Bacterial pathogens (Yersinia, Salmonella, Campylobacter, Mycobacterium tuberculosis) can cause acute or chronic terminal ileitis 3, 4
• Stool cultures and C. difficile toxin assay must be performed before initiating any treatment 1

NSAID-induced enteropathy:

• NSAIDs commonly cause patchy ileal inflammation that is typically subclinical but can present with symptoms identical to Crohn's disease 4, 5
• Detailed medication history is essential, as NSAID-induced ileitis resolves with drug cessation 3

Other inflammatory conditions:

• Spondyloarthropathies (ankylosing spondylitis, reactive arthritis) cause subclinical ileitis in up to 60% of cases 4
• Vasculitides (Behçet's disease, Henoch-Schönlein purpura), ischemic ileitis, eosinophilic enteritis, sarcoidosis, and lymphoma must be considered 3, 4

Recommended Diagnostic Work-Up

Immediate Endoscopic Evaluation

Perform complete ileocolonoscopy with systematic biopsies as the cornerstone of diagnosis 1:

• Obtain at least two biopsies from six segments: terminal ileum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum 1
• Biopsy both inflamed AND normal-appearing mucosa to document skip lesions characteristic of Crohn's disease 1
• Use standardized endoscopic scoring (CDEIS or SES-CD) to document severity, though this may not be practical in routine practice 1

Essential Laboratory Testing

Obtain comprehensive baseline laboratory evaluation 1:

• Complete blood count with differential (assess for anemia, leukocytosis, thrombocytosis)
• Comprehensive metabolic panel including albumin (hypoalbuminemia suggests chronic inflammation)
• CRP and ESR (elevated in 80% of active Crohn's disease; note that 20% may have normal CRP despite active disease) 1
• Fecal calprotectin (sensitivity 93%, specificity 96% for IBD vs. functional disease; use cutoff >100 μg/g for better diagnostic precision) 1
• Iron studies, vitamin B12, folate
• Stool cultures, ova and parasites, C. difficile toxin 1

Cross-Sectional Imaging

Obtain CT or MR enterography in all patients at diagnosis to assess disease extent, complications, and small bowel involvement beyond colonoscopic reach 1:

• Approximately one-third of Crohn's disease patients have small bowel disease not detectable by colonoscopy 2
• Presence of stricturing or narrowing on imaging predicts higher likelihood of established Crohn's disease (versus self-limited acute ileitis) 6
• MR enterography is preferred in young patients to avoid radiation exposure

Upper Endoscopy Considerations

Perform upper endoscopy with biopsies if any of the following are present 1:

• Upper GI symptoms (dyspepsia, nausea, vomiting)
• Atypical features suggesting alternative diagnosis
• Focal enhanced gastritis (FEG) on upper endoscopy biopsies is present in 36% of Crohn's disease patients with isolated ileitis versus only 5% of non-Crohn's patients 5

When Diagnosis Remains Uncertain

If initial workup is inconclusive, repeat endoscopic and histologic assessment is appropriate 1:

• Consider capsule endoscopy to evaluate small bowel beyond reach of standard endoscopy (establishes definitive Crohn's diagnosis in 17-70% of IBD-unclassified cases) 7
• Single- or double-balloon enteroscopy if biopsy of abnormal areas is needed beyond standard endoscope reach 1

Key Diagnostic Pitfalls and How to Avoid Them

Distinguishing Crohn's Disease from Ulcerative Colitis with Backwash Ileitis

• Backwash ileitis occurs in 20% of patients with extensive ulcerative colitis and represents continuous extension from cecum into terminal ileum 1, 7
• Critical distinction: Backwash ileitis is continuous from cecum; Crohn's disease shows skip lesions and patchy distribution 7, 2
• If macroscopic and histological rectal sparing or cecal patch is present in newly diagnosed colitis, evaluate small bowel to exclude Crohn's disease 1, 7
• Rectal sparing occurs in ≤3% of ulcerative colitis but is common in Crohn's disease 1, 7

Acute Self-Limited Ileitis vs. Crohn's Disease

• Isolated acute terminal ileitis without chronic histologic features (crypt distortion, plasmacytosis, pyloric metaplasia) rarely progresses to Crohn's disease (only 4.6% over median 54 months) 6
• Presence of stricturing/narrowing on cross-sectional imaging at initial diagnosis significantly predicts eventual Crohn's disease development 6
• Nonspecific terminal ileitis with persistent symptoms and endoscopic findings at follow-up carries 19.6% risk of subsequent Crohn's diagnosis 8

NSAID Use Must Be Explicitly Documented

• Always obtain detailed medication history including over-the-counter NSAIDs, as these are frequently underreported 4, 5
• Consider trial of NSAID cessation before initiating immunosuppression if NSAID use is confirmed

Appropriate Management Strategy

If Crohn's Disease is Confirmed

Initiate treatment based on disease severity, extent, and prognostic factors 1:

• Mild-moderate ileocolonic disease: Consider budesonide or conventional corticosteroids for induction, followed by immunomodulator (thiopurine or methotrexate) for maintenance
• Moderate-severe disease or poor prognostic factors (young age, extensive disease, deep ulcers, stricturing on imaging): Consider early biologic therapy (anti-TNF, vedolizumab, or ustekinumab)
• Establish baseline values for future monitoring: repeat CRP, fecal calprotectin, and consider repeat endoscopy at 6-12 months to assess mucosal healing 1

If Infectious Etiology is Identified

• Treat specific pathogen appropriately (antibiotics for bacterial infections, anti-tuberculous therapy for M. tuberculosis) 3, 4
• Defer immunosuppression until infection is cleared

If NSAID-Induced Ileitis is Suspected

• Discontinue NSAIDs immediately 4
• Consider repeat endoscopy in 8-12 weeks to document resolution
• If inflammation persists despite NSAID cessation, reconsider Crohn's disease diagnosis

If Diagnosis Remains Uncertain After Complete Workup

• In 5-15% of IBD patients, definitive classification between Crohn's colitis and ulcerative colitis is not possible (IBD-unclassified) 7
• Treat empirically based on predominant disease pattern while continuing diagnostic evaluation
• Close follow-up with repeat endoscopy in 3-6 months if symptoms persist 1, 8
• Fecal calprotectin >250 μg/g predicts endoscopic activity with 94% sensitivity and can guide need for repeat endoscopy 1

Monitoring Strategy for Nonspecific Ileitis

For patients with nonspecific terminal ileitis without definitive Crohn's diagnosis 8:

• Clinical follow-up at 3-6 months to assess symptom persistence
• Repeat fecal calprotectin to assess ongoing inflammation
• Patients with persistent symptoms and endoscopic findings are at significantly increased risk for subsequent Crohn's diagnosis (P=0.002 and P=0.038 respectively) 8
• Consider repeat ileocolonoscopy at 6-12 months if symptoms persist or inflammatory markers remain elevated