Seeing what is not there: negative evidence, diagnostic inertia, and the tuberculosis legacy

Abstract In the early 20th century, tuberculosis (TB) reigned as the prototypical granulomatous disease, deeply embedded in the diagnostic mindset and reasoning of Western medicine. This article traces the diagnostic inertia that delayed recognition of Crohn’s disease by examining how the TB framework suppressed emerging patterns of negative evidence. While gastrointestinal tuberculosis (GITB) and Crohn’s disease are distinct entities, although they can closely mimic one another in clinical and histopathological presentation. We draw from the unpublished 1893 student notebook of Albert A. Berg – later a pioneering surgeon at Mount Sinai Hospital – and analyze its detailed descriptions of TB pathology, including identification of caseous necrosis, phthisis, and giant cell formation. These types of observations were foundational to medical education at the time and shaped generations of clinicians trained to see chronic intestinal inflammation as a variant of TB. The misclassification of Crohn’s disease persisted even into the 1930s, despite mounting clinical and surgical evidence suggesting a distinct entity. By anchoring our analysis in historical sources, including Berg’s personal records and published surgical literature, we show how TB’s diagnostic dominance represents a case study in medical paradigm entrenchment. We argue that the underemphasis of negative evidence – findings that failed to support the TB diagnosis – contributed to the decades-long lag in recognizing Crohn’s disease. While the article draws lessons from history that are relevant to modern paradigms, we note that in certain contemporary high-TB-burden settings such as India, where Crohn’s incidence is rising while GITB remains prevalent, diagnostic decisions may be shaped by a deliberate preference to treat presumptively for TB in order to avoid the potentially catastrophic consequences of inappropriate immunosuppression. (Choudhury A, Dhillon J, Sekar A, Gupta P, Singh H, Sharma V. Differentiating gastrointestinal tuberculosis and Crohn’s disease: challenges and clinical importance. BMC Gastroenterol 2023;23:123; Makharia GK, Srivastava S, Das P, Goswami P, Singh U, Tripathi M, et al. Clinical, endoscopic, and histological differentiations between Crohn’s disease and intestinal tuberculosis. Gut 2006;55:1413–9). Notwithstanding, the historical narrative carries contemporary relevance, illuminating how medical education, cognitive framing, and clinical culture continue to struggle with ambiguity and diagnostic alternatives. We conclude with implications for today’s clinical training: educators must explicitly teach the recognition and integration of negative evidence, challenge entrenched diagnostic heuristics, and highlight the possibility that what is absent may be just as diagnostic as what is present. These goals align with established competency frameworks that emphasize clinical reasoning, diagnostic accuracy, and cognitive flexibility.