Robert S. Peters

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 colchicines known effect on mitotic activity.

Long-term colchicine therapy of familial mediterranean fever+

Familial Mediterranean fever is a disorder characterized by recurrent fever and polyserositis. Continuous prophylactic colchicine therapy has been effective in suppressing attacks in affected adults. From 30 children with FMF, 14 were selected for colchicine therapy. Eight children continued prophylactic colchicine therapy for 29 months (mean) and experienced a marked decrease in the frequency of attacks. Six other children did not comply with the treatment regimen. Although no deleterious side effects were noted, the safety of long-term colchicine administration in childhood is unknown.

Microtubules in PMNs from Patients with Familial Mediterranean Fever

Polymorphonuclear (PMN) cells derived from patients with Familial Mediterranean Fever (FMF) were evaluated in vitro for the function and concentration of their microtubules. Using the time-decay colchicine binding assay to determine the tubulin concentration in PMN cells, no difference was found in PMN cells derived from FMF patients in comparison with those from normal healthy subjects. Colchicine treatment had no effect on the detectable tubulin concentration in the cells. The mobility of fluorescent con A(F-con A)-receptor complexes on PMN membranes was used to test the function of the microtubules. PMNs from untreated FMF patients showed the same pattern of con A cap formation as seen in normal cells. PMNs derived from colchicine treated patients, however, showed 22–32% spontaneous cap formation. These cells also showed 10–30% more capping in comparison with normal or untreated FMF cells, for any given in vitro colchicine concentration, suggesting that at therapeutic doses, the colchicine does accumulate in the PMNs in vivo. We were unable to demonstrate a microtubule defect in the neutrophils from FMF patients in these studies. [Am J Med Sci 1982; 284(2):2–7.]