Division of Medicine, Rheumatology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Rheumatology (Oxford). 2024 Feb 1;63(2):309-318. doi: 10.1093/rheumatology/kead439.
Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent attacks of fever and polyserositis. Its first description as a new entity was published by Siegal in 1945. Colchicine has been the treatment of choice for this disease since 1972. Significant progress has been made over the years in understanding FMF's clinical features, diagnosis, mode of inheritance, pathogenesis and therapeutic approach. However, many old paradigms related to FMF have proven inaccurate, leading to the emergence of new concepts that provide more precise insights. The term 'FMF' is no longer appropriate as the disease is found beyond the Mediterranean basin. The concept of diagnosis based only upon clinical ground proved to be wrong. The paradigm that MEFV mutations in FMF lead to loss of function of the encoded peptide pyrin turned out to be a gain of function mutation. Finally, the concept that as a genetic disease FMF should be treated for life was found to be inaccurate for the subpopulation of the heterozygote patients. Thus, the breakthroughs of identifying the gene associated with the disease (MEFV) and the deciphering of its pathogenesis revolutionized our old paradigms and replaced them with new and more precise insights.
家族性地中海热（FMF）是一种遗传性自身炎症性疾病，其特征为反复发作的发热和多浆膜炎。1945 年，Siegal 首次将其描述为一种新的疾病实体。自 1972 年以来，秋水仙碱一直是该病的首选治疗方法。多年来，人们在了解 FMF 的临床特征、诊断、遗传模式、发病机制和治疗方法方面取得了重大进展。然而，许多与 FMF 相关的旧观念已被证明是不准确的，从而出现了提供更准确见解的新概念。“FMF”一词不再适用，因为这种疾病不仅在地中海盆地发现。仅基于临床依据诊断的概念被证明是错误的。MEFV 突变导致编码肽 pyrin 失去功能的概念原来是一种获得功能的突变。最后，FMF 作为一种遗传病应终身治疗的概念被发现对杂合子患者的亚群并不准确。因此，与疾病相关的基因（MEFV）的鉴定及其发病机制的阐明彻底改变了我们的旧观念，取而代之的是更准确的新观念。
