The pharmacologic basis of treatment with colchicine in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is the prototype of auto-inflammatory disorders and is ethnically restricted to people living in the Mediterranean basin and Middle-East. Pyrin, the protein product of the FMF gene, expressed in myeloid cells and fibroblasts, interacts with the cytoskeletal machinery and may modulate leukocyte effector functions. At present colchicine, an alkaloid with antimitotic activity interfering with microtubule formation, which has been used to alleviate acute gout, is the only available drug for patients with FMF to prevent both acute attacks and long-term complications such as amyloidosis. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules, but also through changes at the transcriptional level influencing cell cycle regulation and leukocyte migration. Gastrointestinal side effects may occur early and are the most frequent manifestations of colchicine toxicity in children, whilst multiple organ failure is very rarely reported as overdosage expression.