Crohn's disease and the mycobacterioses: a review and comparison of two disease entities

Crohn's disease is a chronic granulomatous ileocolitis, of unknown etiology, which generally affects the patient during the prime of life. Medical treatment is supportive at best, and patients afflicted with this disorder generally live with chronic pain, in and out of hospitals, throughout their lives. The disease bears the name of the investigator who convincingly distinguished this disease from intestinal tuberculosis in 1932. This distinction was not universally accepted, and the notion of a mycobacterial etiology has never been fully dismissed. Nevertheless, it was 46 years after the distinction of Crohn's disease and intestinal tuberculosis before research attempting to reassociate mycobacteria and Crohn's disease was published. Recently, there has been a surge of interest in the possible association of mycobacteria and Crohn's disease due largely to the isolation of genetically identical pathogenic Mycobacterium paratuberculosis from several patients with Crohn's disease in the United States, the Netherlands, Australia, and France. These pathogenic organisms have been isolated from only a few patients, and direct evidence for their involvement in the disease process is not clear; however, M. paratuberculosis is an obligate intracellular organism and strict pathogen, which strongly suggests some etiologic role. Immunologic evidence of a mycobacterial etiology, as assessed by humoral immune determinations, has been conflicting, but evaluation of the more relevant cellular immunity has not been performed. Data from histochemical searches for mycobacteria in Crohn's disease tissues have been equally conflicting, with acid-fast bacilli detected in 0 to 35% of patients. Animal model studies have demonstrated the pathogenic potential of isolates as well as elucidated the complexity of mycobacterial-intestinal interactions. Treatment of Crohn's disease patients with antimycobacterial agent has not been fully assessed, although case reports suggest efficacy. The similarities in the pathology, epidemiology, and chemotherapy of Crohn's disease and the mycobacterioses are discussed. The issue is fraught with controversy, and the data generated on the association of mycobacteria and Crohn's disease are in their infantile stages so that a general conclusion on the legitimacy of this association cannot be made. While no firm evidence clearly implicates mycobacteria as an etiologic agent of Crohn's disease, the notion is supported by suggestive and circumstantial evidence and a remarkable similarity of Crohn's disease to known mycobacterial diseases.