Vinceneux P, Pouchot J
Service de Médicine interne 5, Hôpital Louis Mourier, AP-HP, Colombes.
Presse Med. 2005 Jul 23;34(13):947-57. doi: 10.1016/s0755-4982(05)84086-2.
During the first attacks of familial Mediterranean fever, each of the disease symptoms can suggest a series of disorders. When the disease is older, the recurrence of symptoms may simulate some systemic diseases, but mainly suggests familial Mediterranean fever, one of a group of hereditary autoinflammatory diseases. Before the gene for familial Mediterranean fever was identified, various sets of criteria were used for diagnosis. The presence of MEFV mutations confirms the diagnosis, but the clinical criteria still determine who should undergo this genetic testing. The genotype-phenotype correlations add a prognostic dimension to the mutations identified. Genotyping can also lead to the diagnosis of the other autoinflammatory diseases, which constitute the basis of the differential diagnosis of familial Mediterranean fever. The hyperimmunoglobulinemia D syndrome (HIDS) is very similar to familial Mediterranean fever in its recessive transmission and abdominal and articular symptoms. It can be distinguished by the European origin of the patients, the presence of cervical lymph nodes and the increased IgD levels. Of the diseases with dominant transmission, the TNF receptor-associated periodic syndromes (TRAPS) are suggested by periorbital edema and migrating inflammatory cellulitis. Muckle and Wells syndrome is revealed by episodes of fever with urticaria and arthralgia, complicated by deafness and amyloidosis. Mutations in the same gene are responsible for two disorders, both appearing in childhood: familial cold urticaria syndrome (FCUS) and chronic infantile neurocutaneous articular syndrome (CINC). The pathogenesis of familial Mediterranean fever is still unclear. Pyrin/marenostrin, the protein produced by the MEFV gene, appears to hae a physiological antiinflammatory effect that inhibits proinflammatory cytokines. Mutation of the gene may eliminate this feedback mechanism and expose the patient to flares from any inflammatory stimulus, even minimal. Amyloid is produced by the serum amyloid A protein (SAA), and its occurrence is influenced by the type of MEFV mutation, but also the genotype of the gene producing SAA.
在家族性地中海热的首次发作期间，每种疾病症状都可能提示一系列病症。当病程较长时，症状的复发可能类似某些全身性疾病，但主要提示家族性地中海热，它是一组遗传性自身炎症性疾病之一。在家族性地中海热的基因被鉴定出来之前，曾使用过各种诊断标准。MEFV突变的存在可确诊，但临床标准仍决定谁应接受这种基因检测。基因型与表型的相关性为所鉴定的突变增加了预后方面的考量。基因分型还可导致对其他自身炎症性疾病的诊断，这些疾病构成了家族性地中海热鉴别诊断的基础。高免疫球蛋白D综合征（HIDS）在隐性遗传以及腹部和关节症状方面与家族性地中海热非常相似。它可通过患者的欧洲血统、颈部淋巴结的存在以及IgD水平升高来区分。在显性遗传疾病中，眼眶周围水肿和迁移性炎症性蜂窝织炎提示肿瘤坏死因子受体相关周期性综合征（TRAPS）。荨麻疹和关节痛伴发热发作，并发耳聋和淀粉样变性提示穆克勒-韦尔斯综合征。同一基因的突变导致两种均在儿童期出现的疾病：家族性冷荨麻疹综合征（FCUS）和慢性婴儿神经皮肤关节综合征（CINC）。家族性地中海热的发病机制仍不清楚。由MEFV基因产生的蛋白吡啉/海滨蛋白似乎具有生理抗炎作用，可抑制促炎细胞因子。该基因的突变可能消除这种反馈机制，使患者即使受到任何轻微的炎症刺激也会发作病情。淀粉样蛋白由血清淀粉样蛋白A（SAA）产生，其发生受MEFV突变类型的影响，但也受产生SAA的基因的基因型影响。
