Division of Internal Medicine, Clinica Medica "Augusto Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Piazza Giulio Cesare 11, 70124, Bari, Italy.
Section of Medical Genetics, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
Clin Rheumatol. 2020 Feb;39(2):585-594. doi: 10.1007/s10067-019-04741-9. Epub 2019 Aug 10.
An 86-year-old Caucasian man had prior episodes of fever (up to 38 °C), mild abdominal pain, tachycardia, and malaise in the last 3 months, lasting 2-3 days. He never suffered from abdominal or chest pain, rash, or arthralgia. Major causes of fever were excluded (pulmonary, urinary, abdomen, skin infections, neoplasms, and major rheumatologic disorders). The patient was native of Altamura with a family history of familial Mediterranean fever (FMF). The genetic testing confirmed the presence of MEFV gene variants c.442G>C (E148Q) on exon 2 and c.2282G>A (R761H) on exon 10, all in heterozygosity. Mildly elevated serum transaminases suggested an ongoing form of FMF hepatitis on nonalcoholic liver steatosis. The patient started colchicine 1 mg/day that induced symptom control and normalization of inflammatory markers, hyperbilirubinemia, and markers of cholestasis. Symptoms of FMF can appear at any age in life and our patient represents a very late-onset clinical case. The Apulian region has a consistent clustering of MEFV variants and FMF families with affected individuals in multiple consecutive generations. Families show unique clinical features and rare signs of secondary amyloidosis without kidney damage. Genetic and environmental bases of this phenotypic variant are under scrutiny. Colchicine lifetime remains the mainstay of treatment in FMF patients. KEY POINTS: • Familial Mediterranean fever (FMF) is the most frequent hereditary monogenic recurrent fever syndrome, and symptoms can appear at any age in life. • Late-onset FMF approaches 30% in late adulthood, but in general, onset of FMF after the age of 40 (late onset FMF) is rare, usually associated with M694V heterozygosity. • In a local cluster of FMF families (Altamura, Puglia, Southern Italy), we report a very late-onset FMF (variants E148Q, R761H) in an 86-year-old patient with a positive family history of FMF in two generations of descendants. • While lifetime colchicine remains the mainstay of treatment in FMF patients, prospective studies need to identify the characteristics of several phenotypic variants accounting for (very)-late onset FMF.
一位 86 岁的白种人男性在过去 3 个月中出现了发热（高达 38°C）、轻度腹痛、心动过速和全身不适，持续 2-3 天。他从未有过腹痛或胸痛、皮疹或关节痛。发热的主要原因已被排除（肺部、尿路、腹部、皮肤感染、肿瘤和主要风湿性疾病）。该患者来自阿尔塔穆拉，有家族性地中海热（FMF）家族史。基因检测证实存在 MEFV 基因变异 c.442G>C（E148Q）在exon2 和 c.2282G>A（R761H）在 exon10，均为杂合子。血清转氨酶轻度升高提示非酒精性脂肪性肝 steatosis 存在持续形式的 FMF 肝炎。患者开始服用 1 毫克/天的秋水仙碱，诱导症状控制和炎症标志物、高胆红素血症和胆汁淤积标志物的正常化。FMF 的症状可在任何年龄出现，而我们的患者代表了一个非常晚发性的临床病例。阿普利亚地区存在 MEFV 变异和 FMF 家族的一致聚类，这些家族在多个连续代中都有受影响的个体。这些家族表现出独特的临床特征和罕见的继发性淀粉样变性而无肾脏损害的迹象。这种表型变异的遗传和环境基础正在受到审查。秋水仙碱的终身治疗仍然是 FMF 患者的主要治疗方法。关键点： • 家族性地中海热（FMF）是最常见的遗传性单基因复发性发热综合征，症状可在任何年龄出现。 • 晚发性 FMF 在成年后期接近 30%，但一般来说，40 岁以后（晚发性 FMF）发病罕见，通常与 M694V 杂合性有关。 • 在 FMF 家族的一个当地聚类（意大利南部普利亚大区的阿尔塔穆拉）中，我们报告了一例非常晚发性 FMF（变异 E148Q、R761H）在一位 86 岁患者中，该患者在两代后代中有 FMF 的阳性家族史。 • 虽然秋水仙碱的终身治疗仍然是 FMF 患者的主要治疗方法，但前瞻性研究需要确定导致（非常）晚发性 FMF 的几种表型变异的特征。
