Describing the Clinical Phenotypes of Crohn’s Disease: Lessons from the Past

Abstract

Although there remains some confusion regarding the original description of the clinical entity that is currently termed Crohn’s disease, medical historians have cited clinical portrayals of what is likely the disease in the works of Hippocrates, Giovanni Batista Morgagni (1682–1771), John Abercrombie (1780–1844), Charles Combe (1743–1817), and William Saunders (1743–1817) [1–3]. In 1912, T.K. Dalziel of Glasgow described a disease of the intestine termed ‘‘chronic interstitial enteritis’’ in which chronic inflammatory changes associated with characteristic episodes of abdominal pain simulating intestinal obstruction were present [4]. Preceding its seminal description in the Journal of the American Medical Association (JAMA) [5], and references therein, a heterogeneous group of tumor-like inflammatory masses were documented by Tietze in an encyclopedic article in 1920 [6]. By 1923, Moschowitz and Wilenski from Mount Sinai Hospital in New York had described four cases of benign intestinal granuloma, with one having similarity to the original report of regional ileitis [7]. In the first of two presentations in May 1932, Leon Ginzburg presented, before a meeting of the American Gastro-Enterological Association and later published in an expanded form, a description of 52 cases of a granulomatous disease of the intestines without evidence of recognized diseases, including tuberculosis, syphilis, or actinomycosis [7]. A second presentation by Burrill Crohn entitled ‘‘Terminal Ileitis: Its Clinical Manifestations,’’ was delivered to the Section on Gastro-Enterology and Proctology of the American Medical Association in New Orleans, describing 14 patients, predominantly young adults, with stenosis of the distal ileum and fistulous disease to the large intestine or abdominal wall. Clinical symptoms resembled the known entity ulcerative colitis, while pathology demonstrated subacute or chronic necrotizing inflammation beginning abruptly at the ileocecal valve and extending orally for 8–12 inches (c. 20–30 cm), involving the distal ileum alone. In short order, the presentation, entitled ‘‘Regional Ileitis,’’ was published by Crohn, Ginzburg, and Oppenheimer to a wide audience in JAMA on October 15, 1932 [3, 5]. The original description of regional ileitis was timely and accepted by the medical community with immediate additions to the 14 original cases. J.A. Bargen from the Mayo Clinic offered the term ‘‘regional’’ as opposed to ‘‘terminal’’ ileitis, recalling similar cases and recognizing the ‘‘agonal’’ connotation of the descriptor ‘‘terminal’’ [5]. Julius Friedenwald of Baltimore and Louis Hirschman of Detroit added anecdotal cases similar to the descriptions of Crohn, with the addition of a relationship between a previous diagnosis of ulcerative colitis and granulomatous pathology of the terminal [5]. In Volume 1 of the American Journal of Digestive Diseases and Nutrition (and reprinted in part in this issue), Crohn describes in detail three cases of regional ileitis in his publication ‘‘The Broadening Conception of Regional Ileitis,’’ in an attempt to revise and expand the initial concepts of the diagnosis in the face of growing clinical experience [8]. The original article The broadening conception of regional ileitis by Burrill B. Crohn published in American Journal of Digestive Diseases and Nutrition, April 1934, Volume 1, Issue 2, pp. 97–99. Springer.