Case Report: A Pediatric Case of Familial Mediterranean Fever Concurrent With Autoimmune Hepatitis.
Case Report: A Pediatric Case of Familial Mediterranean Fever Concurrent With Autoimmune Hepatitis.
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DOI：
10.3389/fimmu.2022.917398
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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家族性地中海热（FMF）是一种遗传性自身炎症性疾病，可引起反复发热、关节炎和浆膜炎。FMF的诊断是基于典型的临床症状和地中海热基因（MEFV）测试。然而，挑战在于诊断非典型病例。在这份报告中，我们描述了一个复杂的FMF儿科患者的诊断需要三个完整的外显子测序（WES）和功能验证的一种罕见的MEFV变异。一个3岁的男孩表现为反复发作的肝酶升高和关节痛。他被诊断患有自身免疫性肝炎（AIH），他的肝酶在类固醇治疗后迅速改善。然而，他表现出复发性关节痛和严重的腹部发作。Trio-WES鉴定了MEFV中的复合杂合突变（V726 A和I692 del）。已用艰难梭菌毒素A（TcdA）和秋水仙碱预处理的患者的单核细胞和巨噬细胞的离体功能测定与典型FMF患者的那些相当，从而证实FMF的诊断。尽管他因肝毒性而对秋水仙碱不耐受，但随后的卡那单抗给药成功改善了他的腹部发作。然而，它对肝损伤无效，在类固醇逐渐减少后复发。因此，在这种情况下，AIH的发病机制可能是白细胞介素-1 β（IL-1β）非依赖性的。事实上，AIH可能是FMF的并发症，而不是其并发症。然而，进一步的研究是必要的，以确定是否FMF诱导的炎性小体激活有助于AIH的发展。此外，我们必须考虑在这些同时呈现不同病理的非典型患者中混合表型的可能性。
Familial Mediterranean fever (FMF) is a hereditary, autoinflammatory disease that causes recurrent fever, arthritis, and serositis. The diagnosis of FMF is based on the presentation of typical clinical symptoms and the Mediterranean fever gene (MEFV) test. However, the challenge lies in diagnosing atypical cases. In this report, we have described a pediatric patient with complex FMF whose diagnosis required trio-whole exome sequencing (WES) and functional validation of a rare MEFV variant. A 3-year-old boy presented with recurrent episodes of elevated liver enzymes and arthralgia. He was diagnosed with autoimmune hepatitis (AIH), and his liver enzymes improved rapidly with steroid treatment. However, he exhibited recurrent arthralgia and severe abdominal attacks. Trio-WES identified compound heterozygous mutations in MEFV (V726A and I692del). Ex vivo functional assays of the patient’s monocytes and macrophages, which had been pre-treated with Clostridium difficile toxin A (TcdA) and colchicine, were comparable to those of typical FMF patients, thereby confirming the diagnosis of FMF. Although he was intolerant to colchicine because of liver toxicity, subsequent administration of canakinumab successfully ameliorated his abdominal attacks. However, it was ineffective against liver injury, which recurred after steroid tapering. Therefore, in this case, the pathogenesis of AIH was probably interleukin-1β (IL-1β)-independent. In fact, AIH might have been a concurrent disease with FMF, rather than being one of its complications. Nevertheless, further studies are necessary to determine whether FMF-induced inflammasome activation contributes to AIH development. Moreover, we must consider the possibility of mixed phenotypes in such atypical patients who present distinct pathologies simultaneously.