Vinceneux P, Pouchot J
Service de Médicine interne 5, Hôpital Louis Mourier, AP-HP, Colombes.
Presse Med. 2005 Jul 23;34(13):958-66. doi: 10.1016/s0755-4982(05)84087-4.
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.
家族性地中海热的病程特点是急性发作会不定期复发，且可自行消退。预后取决于淀粉样变性的发生情况，而秋水仙碱治疗已改变了这种疾病的预后。某些种族群体（来自北非的犹太人、土耳其人）中淀粉样变性的发病率较高，且取决于特定的MEFV突变。淀粉样蛋白由与继发性淀粉样变性的AA蛋白相同的蛋白质链簇组成，会浸润除中枢神经系统小动脉壁之外的所有小动脉壁。最早且最常见的定位是在肾脏，淀粉样变性在肾脏中会经过数年发展，并经历四个阶段——临床前期（潜伏期）、蛋白尿期、肾病期和尿毒症期，最终发展为终末期肾衰竭。在秋水仙碱、透析和移植出现之前，只有肾淀粉样变性会引发临床表现和致命并发症；其他任何部位的淀粉样变性都处于潜伏状态。现在，通过血液透析和肾脏移植实现的长期存活，使得这些其他部位的病变有时间表现出来，比如浸润肠道导致吸收不良，或者引发潜在致命的心脏病变。家族性地中海热的治疗基于持续服用秋水仙碱，平均每日剂量为1至2毫克时，秋水仙碱可以预防发作，或者至少降低发作频率或减轻发作强度。系统使用秋水仙碱还可以预防淀粉样变性的发生，即使在极少数无法预防发作的情况下也是如此。这些数据充分证明了从诊断时起，甚至在肾脏移植后，系统使用秋水仙碱进行持续预防性治疗的合理性，以防止移植肾复发或病变扩散至其他器官。秋水仙碱对发作的治疗效果存在争议，不过有几项研究报告称其对早期淀粉样变性的进展有积极作用。
