Debaryomyces is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

Alterations of the mycobiota composition associated with Crohn's disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that Debaryomyces hansenii preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. D. hansenii cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice. We reisolated D. hansenii from injured areas of these mice, fulfilling Koch's postulates. Mechanistically, D. hansenii impaired mucosal healing through the myeloid cell-specific type 1 interferon-CCL5 axis. Taken together, we have identified a fungus that inhabits inflamed CD tissue and can lead to dysregulated mucosal healing.

Clofazimine-induced crystal-storing histiocytosis producing chronic abdominal pain in a leprosy patient.

Clofazimine-induced crystal-storing histiocytosis is a rare but well-recognized condition in the literature. Besides the common reddish discoloration of the skin, clofazimine produces gastrointestinal disturbances-sometimes severe abdominal pain, prompting exploratory laparotomy, because pathologic and radiologic findings can produce diagnostic difficulties if the pathologic changes caused by clofazimine are not recognized. The authors report such a case in a leprosy patient to emphasize the importance of history taking, the radiologic abnormalities of the small intestine, and the pathologic findings in small intestine and lymph node biopsies. Clofazimine crystals are red in the frozen section and exhibit bright-red birefringence. However, they are clear in routinely processed histologic sections because they dissolve in alcohol and organic solvents. They also appear as clear crystal spaces during electron microscopic study, but some osmiophilic bodies can be observed. Histiocytosis caused by clofazimine crystals produces infiltrative lesions in radiologic studies mimicking malignant lymphoma or other infiltrative disorders. Associated plasmacytosis in the histologic sections can simulate lymphoplasmacytic lymphoma or multiple myeloma with crystal-storing histiocytosis. With the knowledge of this rare condition caused by clofazimine, appropriate management to avoid an unnecessary laparotomy is possible.

On the etiology of Crohn disease.

Crohn disease (CD) is a chronic, panenteric intestinal inflammatory disease. Its etiology is unknown. Analogous to the tuberculoid and lepromatous forms of leprosy, CD may have two clinical manifestations. One is aggressive and fistulizing (perforating), and the other is contained, indolent, and obstructive (nonperforating) [Gi]-berts, E. C. A. M., Greenstein, A. J., Katsel, P., Harpaz, N. & Greenstein, R. J. (1994) Proc. Natl. Acad. Sci. USA 91, 12721-127241. The etiology, if infections, may be due to Mycobacterium paratuberculosis. We employed reverse transcription PCR using M. paratuberculosis subspecies-specific primers (IS 900) on total RNA from 12 ileal mucosal specimens (CD, n = 8; controls, n = 4, 2 with ulcerative colitis and 2 with colonic cancer). As a negative control, we used Myobacterium avium DNA, originally cultured from the drinking water of a major city in the United States. cDNA sequence analysis shows that all eight cases of Crohn's disease and both samples from the patients with ulcerative colitis contained M. paratuberculosis RNA. Additionally, the M. avium control has the DNA sequence of M. paratuberculosis. We demonstrate the DNA sequence of M. paratuberculosis from mucosal specimens from humans with CD. The potable water supply may be a reservoir of infection. Although M. paratuberculosis signal in CD has been previously reported, a cause and effect relationship has not been established. In part, this is due to conflicting data from studies with empirical antimycobacterial therapy. We conclude that clinical trials with anti-M. paratuberculosis therapy are indicated in patients with CD who have been stratified into the aggressive (perforating) and contained (nonperforating) forms.

[Small intestine transit anomalies in a patient with chronic abdominal pain and treated for Hansen's disease]. / Anomalies du transit du grêle chez une patiente présentant des douleurs abdominales chroniques et traitée pour une maladie de Hansen.

This new case of enteropathy due to Clofazimine provided demonstration of the diagnostic value of small bowel follow-through examination in this complication. Various small intestine anomalies have been reported: ileal or partial jejunal lesions; variations in caliber; loss of physiologic folds; irregularly outlined surface and border lacunae and persistence of suppleness of pathologic loops. Knowledge of these anomalies should avoid exploratory laparotomy, Clofazimine-induced enteropathy regressing after discontinuation of treatment. Repeat small bowel follow up examinations can be performed to review course of this regression.

[Enteropathy caused by clofazimine]. / Entéropathie à la clofazimine.

A case of Clofazimine enteropathy is reported, diagnosed on the demonstration of red brown birefringent crystals in the small bowel mucosa and submucosa as well as in the mesenteric lymph nodes whereas the clinical and radiological signs appear to be non specific. After the withdrawal of the drug, a clear improvement of the symptoms was achieved only under a gluten free diet. The possibility of such accidents, sometimes lethal, suggests the restriction of clofazimine to leprosy.

Structure and function of the small bowel in lepromatous leprosy.

The structural and functional status of the small bowel was examined in ten patients with lepromatous leprosy. The absorptive functions were essentially normal in all patients except for minor abnormalities; one patient had mild steatorrhea and two others had derangement of D-xylose absorption. Barium examination did not reveal any abnormality in any patient. Histological study of the small intestinal mucosa showed mild, partial villous atrophy in two patients and normal appearances in the remaining eight. The above abnormalities were mild and were not considered to be of any clinical significance. It is therefore concluded that the small bowel is not commonly involved in lepromatous leprosy.