De la maladie périodique à l’amylose

Abstract

The progression of familial Mediterranean fever is marked by the recurrence, at varying intervals, of acute flares that regress spontaneously. Prognosis, which depends on the occurrence of amyloidosis, has been transformed by colchicine treatment. Incidence of amyloidosis is higher in certain ethnic groups (Jews from North Africa, Turks) and depends on by the specific MEFV mutation. Amyloid is composed of clusters of protein strands identical to the AA protein of secondary amyloidosis and infiltrates the walls of all arterioles except those of the central nervous system. The earliest and most consistent localization is in the kidney, where it develops over several years and in 4 stages--preclinical (latency), proteinuric, nephrotic and uremic--before concluding in end-state renal failure. Before the advent of colchicine, dialysis and transplantation, only renal amyloidosis caused clinical manifestations and lethal complications; any amyloidosis at any other sites remained latent. Prolonged survival with hemodialysis and kidney transplantation now leaves time for manifestation of these other localizations, such as infiltration into the intestines causing malabsorption, or potentially lethal cardiac lesions. Treatment of familial Mediterranean fever is based on the continuous administration of colchicine, which at the average dose of 1 to 2 mg per day can prevent flares or at least reduce their frequency or intensity. Systematic use of colchicine also prevents the onset of amyloidosis, even in the rare cases where it cannot prevent flares. These data fully justify the systematic use of colchicine for continuous prophylactic treatment from diagnosis and even after kidney transplantation, to prevent recurrence of the grafted kidney or extension to other organs. The curative efficacy of colchicine on flares is debatable, although several studies report positive results against progression of early amyloidosis.