Descriptions consistent with Crohn’s disease appear in the medical literature from the 18th century onward, including reports by Giovanni Battista Morgagni (1769), Samuel Wilks (1859), Antoni Leśniowski (1903), and Thomas Kennedy Dalziel (1913).^[1][2] The disease was established as a distinct clinicopathologic entity in 1932, when Burrill Bernard Crohn, Leon Ginzburg, and Gordon Oppenheimer described 14 patients with inflammation of the terminal ileum under the title “Regional ileitis: a pathologic and clinical entity.”^[1][3] Over the following decades the concept expanded from an ileal disease to a pan-enteric, transmural inflammatory bowel disease (IBD). It was then stratified by location and behavior, which was later formalized in the Montreal classification. Its etiology has been reframed as a dysregulated mucosal immune response to the gut microbiota in a genetically susceptible host.^[4][5]

• Morgagni is the most frequently cited early observer. His autopsy observations from the 1760s describe a patient with diarrhea, fever, and ileal ulceration with perforation and enlarged mesenteric nodes, features now recognized as compatible with Crohn’s disease.^[1][6]
• In 1859, Samuel Wilks reported a case of non-infectious intestinal inflammation that is now thought to have represented colonic Crohn’s disease rather than ulcerative colitis.^[2][4]
• In 1903, the Polish surgeon Antoni Leśniowski independently described the condition. In Poland it is still termed Leśniowski–Crohn disease.^[1]
• In 1913, the Scottish surgeon Thomas Kennedy Dalziel reported a surgical series of patients with chronic, non-infectious, transmural intestinal inflammation causing obstruction, some with colonic involvement.^[2][7]
• These reports show that the disease was recognized repeatedly before 1932. None of them, however, consolidated it as a reproducible clinicopathologic entity.^[1]

• In May 1932, Crohn, a gastroenterologist at Mount Sinai Hospital, presented 14 cases to the American Medical Association as “terminal ileitis.” The term was changed to “regional ileitis” so that the disease would not be read as fatal. The series was published in JAMA later that year as “Regional ileitis: a pathologic and clinical entity.”^[1][3]
• The original description remains closely aligned with current understanding:^[8]
  • A chronic disease of young adults with fever, diarrhea, right-lower-quadrant pain, anemia, and weight loss.
  • Pathologically, segmental transmural inflammation, granulomas, linear ulcers, and a cobblestone mucosa.
  • Clinical behaviors that anticipate modern phenotyping: inflammatory, stenotic, perforating/abscess-forming, and fistulizing disease.
• The surgeon Albert A. Berg operated on the patients but was not listed as an author. Because authors were listed alphabetically, Crohn appeared first, and the eponym “Crohn’s disease” entered general use soon afterward.^[1][6]
• The appropriateness of the eponym has been debated given the earlier descriptions. Recent historical review concludes that the 1932 paper and Crohn’s later contributions were pivotal, so continued use of the eponym is justified.^[1]

• Between 1930 and 1960, the literature expanded and refined the definition of the disease.^[6] Involvement beyond the ileum, including the upper gastrointestinal tract, made the term “regional ileitis” untenable. Crohn’s disease is now recognized as able to affect any segment of the digestive tract from mouth to anus, often discontinuously.^[8][5]
• In 1960, Lockhart-Mummery and Morson described isolated colonic Crohn’s disease and distinguished it from ulcerative colitis. This formally extended the entity beyond the small bowel.^[4]

• Phenotypic classification evolved to stratify disease by location (isolated ileal, colonic, ileocolonic, and isolated upper gastrointestinal) and by behavior. This approach was formalized in the Montreal classification, which is used for prognosis and treatment selection.^[4] Whether Crohn’s disease should be reclassified as ileum-dominant versus isolated colonic disease remains an open question.^[4]
• Etiologic theories progressed from food allergy, psychogenic causes, and single-pathogen hypotheses toward a multifactorial model: a dysregulated mucosal immune response to the intestinal microbiota in a genetically susceptible host.^[5]
• NOD2/CARD15 was the first susceptibility gene identified for Crohn’s disease. It is associated with Crohn’s disease rather than ulcerative colitis, and more than 200 additional risk loci have since been described.^[9]