Clofazimine enteropathy: possible relation to Peyer's patches.

Clofazimine administered orally to rats and mice caused pigmentation of the intestines, draining lymph nodes, fat, and other tissues and organs. Peyer's patches were always more deeply colored than the remainder of the intestine. A microscopic study revealed crystal-containing epithelioid cell granulomas in the patches and in the draining mesenteric lymph nodes but not in the remainder of the gut. During the evolution of the granulomas, some of the epithelioid cells were capable of phagocytosing an iron complex, a circumstance which made it possible to get detailed views of the clofazimine crystals in paraffin sections by negative contrast in histochemical stains for iron. The granulomas appeared after three oral treatments during 1 week, but were better developed after six or more treatments during 2 or more weeks. Similar observations were made in three strains of rats and in mice. We hypothesize that the greater pigmentation of Peyer's patches and their granulomatous response to clofazimine might indicate a special susceptibility to toxic effects of the drug. Whether or not this susceptibility is the starting point for an enteropathy can only be determined by examination of affected human tissues and by further animal experimentation.