Recurrent Abdominal Pain and Weight Loss After Travel
A 34-year-old woman presents with 8 months of intermittent crampy periumbilical pain, bloating, and non-bloody diarrhea occurring 2–3 times weekly, with 6 kg unintentional weight loss. She traveled to rural South Asia 14 months ago for 3 months. She has iron-deficiency anemia (ferritin 8, Hb 10.9) and a normal colonoscopy with terminal ileal biopsies showing 'mild nonspecific inflammation.' Celiac serology (TTG-IgA) is negative with normal total IgA. Fecal calprotectin is 210 mcg/g. Stool O&P negative x3. CRP 18. CT enterography shows mildly thickened distal ileal loops with no stricture or fistula.
1. Build a differential and explain how you would prioritize testing, including which 'negative' results do not exclude disease.
Read the worked answer
Differential for chronic diarrhea + weight loss + iron deficiency + ileal thickening:
- Crohn's disease - ileal thickening, elevated calprotectin and CRP, anemia. Terminal ileal biopsies can be normal or nonspecific if disease is patchy or deep; a normal colonoscopy does not exclude small-bowel Crohn's.
- Intestinal tuberculosis - critical given South Asia travel. Ileocecal involvement is classic; can mimic Crohn's radiologically and histologically.
- Parasitic/protozoal infection - Giardia (three O&P can miss it), Strongyloides, Cryptosporidium, Cyclospora. Serology and stool antigen/PCR are more sensitive than microscopy.
- Tropical sprue - chronic diarrhea, weight loss, anemia after tropical residence; small-bowel biopsy shows villous blunting with response to antibiotics/tetracycline. Negative TTG does not exclude it.
- Small intestinal bacterial overgrowth - can follow travel/enteric infection.
- Bile acid diarrhea - consider after ileal disease excluded.
- Celiac disease - TTG negative with normal IgA makes it unlikely but not impossible (IgA deficiency excluded; consider duodenal biopsy if suspicion persists).
Testing priorities: stool multiplex PCR (Giardia, Cryptosporidium, Cyclospora), Strongyloides serology, duodenal biopsies at EGD (sprue, Giardia trophozoites, Whipple), small-bowel capsule endoscopy or MR enterography for Crohn's, and IGRA/TB testing plus chest imaging before any immunosuppression. Do not start biologics before excluding TB.
2. How do you distinguish intestinal tuberculosis from Crohn's disease in this patient, and why does the distinction matter practically?
Read the worked answer
Why it matters: giving anti-TNF therapy to a patient with active intestinal TB can cause disseminated/fatal TB. Conversely, treating Crohn's as TB delays effective therapy and exposes the patient to unnecessary antibiotics.
Features favoring intestinal TB:
- Chest radiograph with active or healed TB - obtain in every suspected case.
- IGRA or tuberculin positivity (supportive, not diagnostic - latent TB is common in endemic areas).
- Transverse/annular ulcers, patulous ileocecal valve, less common perianal disease, fewer extraintestinal manifestations.
- Caseating granulomas on biopsy; AFB smear/culture or nucleic acid amplification testing (Xpert MTB/RIF) on tissue.
- Ascites with high ADA, or response to a 4–8 week anti-TB trial.
Features favoring Crohn's:
- Longitudinal ulcers, cobblestoning, skip lesions, perianal fistulae/abscesses, creeping fat, transmural inflammation with non-caseating granulomas.
- Extraintestinal manifestations (erythema nodosum, uveitis, arthralgia).
Practical approach: if TB cannot be excluded, treat empirically for TB first (or run a therapeutic trial) before committing to immunosuppression, and involve infectious disease. A therapeutic trial of anti-TB therapy with reassessment at 4–8 weeks is a legitimate diagnostic strategy in ambiguous cases.
3. If Crohn's disease is ultimately confirmed and she has moderate-to-severe ileal disease, outline induction and maintenance therapy and the monitoring you would build in.
Read the worked answer
Induction (moderate-to-severe ileal Crohn's):
- Anti-TNF (infliximab or adalimumab) is preferred for moderate-to-severe disease, especially with fistulizing or extensive disease. Combination infliximab + thiopurine improves outcomes and reduces immunogenicity, but weigh infection risk.
- Alternatively, ustekinumab (anti-IL-12/23) or vedolizumab (gut-selective, but less effective for small-bowel disease) are options.
- Corticosteroids (oral budesonide for ileocecal disease, or systemic steroids) can induce remission but are not maintenance therapy.
- Ensure TB is excluded and hepatitis B status known before anti-TNF.
Maintenance: continue the biologic; consider immunomodulator for combination therapy. Reassess response at 12–16 weeks with clinical scores, CRP, calprotectin, and endoscopic or cross-sectional healing where feasible.
Monitoring and supportive care:
- Iron repletion (IV iron given malabsorption).
- B12 and folate if terminal ileal disease/resection.
- Bone health (vitamin D, calcium, DXA if steroid exposure).
- Vaccinations before immunosuppression.
- Colon cancer surveillance after 8 years of disease.
- Therapeutic drug monitoring if loss of response.
- Nutrition: dietitian involvement; screen for micronutrient deficiencies.