The first step in any disease is to determine its pathological characteristics. Accordingly, the very first papers characterizing Crohn’s disease (CD) described the histological features of the GI tract of those with CD. Crohn, et.al. observe giant cell granulomas, inflammation in the gastrointestinal tract, destruction of mucosal membranes, thickening of the bowel wall, and a tendency towards perforation in patients with what they call regional iletis (CD). They note necrotizing and cicatrizing inflammation and a condition that is similar to but distinct from ulcerative colitis (Crohn et al., 1932).
Hadfield’s paper is perhaps the second most impactful paper after Crohns’ original report. In this article, he describes in great detail the histological features of the colon inflicted by Crohn’s disease and compares the appearances with other inflammatory diseases, like Boeck’s scarcoidosis. He reports the thickening of submucosa, the development of ulcers and lesions, the impact of the disease on lymphoid tissue, and the absence of acid-fast bacilli, which is notable because a potential cause of CD was thought to be tuberculosis (Hadfield, 1939).
Importantly, several papers worked at distinguishing CD from other diseases, namely ulcerative colitis. In 1948, Warren and Sommers describe the pathological and histological features of cicatrizing enteritis, i.e. regional ileitis/Crohn’s disease, and explain the three phases of the disease: acute, subacute, and chronic. They explain how differentiating between cicatrizing enteritis and other diseases, particularly intestinal tuberculosis, can be quite difficult because the differences often lie at the cellular level, which is not easily seen by the naked eye. The cause of this disease remains unknown at this point, although bacterial infection or involvement is suspected (Warren and Sommers, 1948). Lockhart-Mummery and Morson follow with a meticulous and comprehensive description of the characteristics of CD and work at parsing out differences between ulcerative colitis and CD (Lockhart-Mummery and Morson, 1960). To achieve this and a complete description of CD, characterization at the cellular level was necessary. Researchers identified the presence of components such as giant-cell granulomas and Schaumann body aggregates. A 1976 study by Greenstein, et.al. groups complications of Crohn’s into 3 groups: A, associated with active inflammation, B, associated with disruptions in small bowel function, and C, non-specific issues like osteoporosis and liver disease. Incidence of complications were compared to respective incidences in patients with ulcerative colitis, furthering the distinction between the two IBDs (Greenstein et al., 1976).
Crohn, B.B., Ginzburg, L., Oppenheimer, G.D., 1932. Regional Ileitis: A Pathological and Clinical Entity. JAMA 99, 1323–1329. https://doi.org/10.1001/jama.1932.02740680019005
Greenstein, A.J., Janowitz, H.D., Sachar, D.B., 1976. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine (Baltimore) 55, 401–412.
Hadfield, G., 1939. The Primary Histological Lesion of Regional Ileitis. The Lancet 234, 773–776. https://doi.org/10.1016/S0140-6736(00)62866-0
Lockhart-Mummery, H.E., Morson, B.C., 1960. Crohn’s Disease (Regional Enteritis) of the Large Intestine and its Distinction from Ulcerative Colitis. Gut 1, 87–105.
Warren, S., Sommers, S.C., 1948. Cicatrizing Enteritis (Regional Ileitis) as a Pathologic Entity. Am J Pathol 24, 475–501.