Pitfalls in the Diagnosis and Classification of Crohn's Disease: Misdiagnosis, Overdiagnosis, and Misclassification

Crohn's disease (CD) remains challenging to diagnose and classify accurately despite advances in endoscopy, cross-sectional imaging, intestinal ultrasound, and inflammatory biomarkers. Earlier diagnosis and treat-to-target strategies have improved outcomes but have also increased the risk of misdiagnosis, overdiagnosis, and misclassification of disease activity or severity. Misdiagnosis may expose patients without CD to unnecessary immunosuppressive therapy while delaying recognition and treatment of the true underlying condition, including drug-induced enteropathy, bile acid malabsorption, irritable bowel syndrome, and other disorders of gut-brain interaction. This is particularly relevant in tuberculosis (TB)-endemic regions, where intestinal TB remains one of the most challenging mimics of CD. Overdiagnosis commonly results from overinterpretation of nonspecific symptoms, incidental terminal ileitis, or isolated endoscopic and histological abnormalities. Elevated fecal calprotectin lacks specificity, whereas a low value provides stronger evidence against CD, although it does not reliably exclude isolated small-bowel disease. Misclassification most often reflects underestimation of disease severity, particularly when standard ileocolonoscopy fails to detect proximal small bowel or transmural disease or when discordant endoscopic and cross-sectional imaging findings are not appropriately reconciled. This review examines the major diagnostic and classification pitfalls in CD and proposes a practical, multidisciplinary approach based on integrating complementary investigations, longitudinal reassessment, and diagnostic reconsideration when uncertainty persists.