Effect of long-term colchicine therapy on jejunal mucosa

Colchicine is recommended as daily prophylactic therapy in patients with familial Mediterranean fever (FMF) to prevent febrile paroxysms. The drug is known to be a potent inhibitor of mitotic activity and might therefore be expected to have a significant adverse effect on tissues that undergo rapid turnover. We studied small bowel biopsies from nine patients with FMF who were receiving daily low-dose oral colchicine therapy. In each patient the lengths of 20 crypts and villi were measured and the number of mitotic figures in 20 crypts were counted. The data were compared with similar measurements from histologically normal-appearing biopsies obtained from 14 patients with a variety of mild gastrointestinal complaints. The mean crypt length was found to be significantly greater (0.197 mm vs 0.186 mm, P < 0.0001) and the mean villous length significantly smaller (0.369 mm vs. 0.442 mm, P < 0.0001) in the FMF patients than in the control population. In addition, the mean number of mitotic figures per crypt was significantly higher in the FMF patients (2.58 vs 1.00, P < 0.001). The data reveal a pattern of mucosal injury in the colchicine-treated FMF patients characterized by a hyperplastic crypt-villous atrophy pattern with increased mitotic rate, which is indicative of an increase in cell turnover and opposite to what we anticipated based on colchicine's known effect on mitotic activity.