Differentiating IBS from Crohn's Disease

Initial Non-Invasive Testing

The European Crohn’s and Colitis Organisation recommends using fecal calprotectin as the initial screening test to differentiate IBS from Crohn's disease, with a level above 100-250 μg/g stool warranting ileocolonoscopy with biopsies, while a normal level (<50 μg/g) effectively rules out inflammatory bowel disease 1, 2
Fecal calprotectin is the cornerstone of differentiation between IBS and Crohn's disease, with pooled sensitivity of 93% and specificity of 96% for diagnosing IBD in adults, according to the American Gastroenterological Association 1, 3
Setting the threshold at 100-250 μg/g stool improves positive predictive value with minimal reduction in negative predictive value, as suggested by the European Society of Gastrointestinal Endoscopy 2
Fecal lactoferrin serves as an alternative biomarker with similar utility for differentiating IBD from functional disease, as stated by the American College of Gastroenterology 1, 3
Fecal calprotectin will be elevated in acute infectious gastroenteritis, so stool culture must be performed first to exclude infection before interpreting results, according to the Infectious Diseases Society of America 2

Ileocolonoscopy with biopsies of both affected and normal-appearing areas is mandatory when fecal calprotectin exceeds the local threshold or when clinical suspicion remains high despite normal biomarkers, as recommended by the American Society for Gastrointestinal Endoscopy 1, 3, 4
Discontinuous "skip" lesions with segments of normal mucosa between inflamed areas are characteristic of Crohn's disease, according to the European Crohn’s and Colitis Organisation 5
Cobblestoning, strictures, and fistulas are highly suggestive of Crohn's disease, as stated by the American Gastroenterological Association 5
Perianal disease strongly indicates Crohn's rather than IBS, according to the European Society of Gastrointestinal Endoscopy 5, 6

A complete blood count should be obtained to assess for anemia, which is common in Crohn's but not IBS, as recommended by the American College of Gastroenterology 3, 4
CRP level should be measured, recognizing that approximately 20% of patients with active Crohn's disease may have normal CRP, according to the European Crohn’s and Colitis Organisation 1, 3, 4
Albumin, liver profile, iron studies, renal function, and vitamin B12 should be assessed to establish baseline nutritional status, as suggested by the American Gastroenterological Association 3, 4, 7

MR enterography (or CT enterography if MRI unavailable) should be performed in all patients at diagnosis to assess small bowel involvement, disease extent, and complications, as recommended by the European Society of Gastrointestinal Endoscopy 3, 4, 7
Small bowel involvement occurs in approximately one-third of Crohn's patients and cannot be adequately assessed by colonoscopy alone, according to the American College of Gastroenterology 6
Imaging detects transmural inflammation, abscesses, and penetrating disease characteristic of Crohn's but absent in IBS, as stated by the European Crohn’s and Colitis Organisation 4, 6

Upper endoscopy with biopsies should be performed in pediatric patients and adults with upper GI symptoms, as upper tract involvement suggests Crohn's disease, according to the American Society for Gastrointestinal Endoscopy 4, 7
Small bowel capsule endoscopy may aid diagnosis when ileocolonoscopy, gastroscopy, and cross-sectional imaging are inconclusive but clinical suspicion for Crohn's remains high, as suggested by the European Society of Gastrointestinal Endoscopy 3, 7

Serial calprotectin monitoring should be considered to detect emerging inflammation, as 53% of patients with initially elevated levels show reduction on repeat testing, according to the American Gastroenterological Association 2
Alternative mechanisms such as small intestinal bacterial overgrowth, bile acid diarrhea, and carbohydrate intolerance should be considered based on symptom patterns, as stated by the American College of Gastroenterology 8, 9
Functional symptom management with a low FODMAP diet, psychological therapies, antispasmodics, and avoidance of opiates should be considered, according to the European Crohn’s and Colitis Organisation 8, 9, 10