Shirai Taiichiro, Onishi Akira, Waki Daisuke, Saegusa Jun, Morinobu Akio
Department of Rheumatology and Clinical Immunology, Kobe University Hospital, Chuo-ku, Kobe, Japan.
Medicine (Baltimore). 2018 Jun;97(23):e11045. doi: 10.1097/MD.0000000000011045.
TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome.
Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly.
In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis.
In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy.
This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.
TAFRO综合征是一种全身性炎症性疾病，其特征为血小板减少、全身性水肿、发热、网状纤维组织增生、肾功能不全和器官肿大。与多中心Castleman病不同，白细胞介素-6靶向治疗策略在某些TAFRO综合征病例中似乎无效；然而，最佳治疗方法仍不明确。在此，我们报告2例TAFRO综合征病例，其中1例患有心肌病，经他克莫司成功治疗。这是TAFRO综合征首例使用他克莫司成功治疗的病例报告。
两名患者（病例1和病例2）均出现发热、全身性水肿、血小板减少、肾功能不全和轻度肝脾肿大。
两名患者的淋巴结病理检查均显示混合型Castleman病样特征，骨髓检查显示网状纤维骨髓纤维化。根据患者的实验室检查、临床和病理结果诊断为TAFRO综合征。在病例2中，我们观察到一种罕见的心肌病并发症，没有应激性心肌病或病毒性心肌炎的证据。
病例1中，托珠单抗联合糖皮质激素治疗无效并导致感染性休克；此外，环孢素A因肝毒性而停用。然而，他克莫司有效缓解了TAFRO综合征，且无任何不良事件。病例2中，他克莫司完全逆转了TAFRO综合征，对心肌病也有效。
本报告表明，他克莫司作为初始治疗药物和糖皮质激素替代药物可能有效且安全。我们的文献综述显示，包括他克莫司在内的钙调神经磷酸酶抑制剂可能对TAFRO综合征有效。由于先前的研究表明Th1炎症在TAFRO综合征发病机制中起作用，因此他克莫司可能对治疗TAFRO综合征有效。
