Fujiwara Shiho, Mochinaga Hiromi, Nakata Hirotomo, Ohshima Koichi, Matsumoto Masanori, Uchiba Mitsuhiro, Mikami Yoshiki, Hata Hiroyuki, Okuno Yutaka, Mitsuya Hiroaki, Nosaka Kisato
Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Tyuou-ku, Kumamoto, Japan.
Department of Pathology, Kurume University School of Medicine, Fukuoka, Japan.
Int J Hematol. 2016 Jun;103(6):718-23. doi: 10.1007/s12185-016-1978-2. Epub 2016 Mar 15.
TAFRO syndrome is a rare variant type of multicentric Castleman disease, which is characterized by thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly. Here, we report a case of TAFRO syndrome that was successfully treated with tocilizumab. A 50-year-old man, who presented with fever, epigastric pain, abdominal fullness, and massive edema of the extremities, was admitted to our hospital. Computed tomography revealed bilateral pleural effusions, ascites, and lymphadenopathy. Laboratory data showed renal dysfunction, anemia, and thrombocytopenia. Examination of bone marrow and cervical lymph nodes led to a diagnosis of hyaline vascular-type Castleman disease. The level of serum interleukin (IL)-6 was extremely high. TAFRO syndrome was finally diagnosed. The patient was treated weekly with tocilizumab, an anti-IL-6 receptor antibody and steroids. In 4 weeks, all symptoms disappeared and serum IL-6 level returned to normal. Activity of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), which was significantly decreased (9.9 %) prior to treatment, increased after treatment with tocilizumab. The present case suggests that tocilizumab is an effective therapeutic agent for TAFRO syndrome. We suggest that hypercytokinemia in TAFRO syndrome inhibits ADAMTS13 activity, thereby inducing thrombotic microangiopathy.
TAFRO综合征是多中心Castleman病的一种罕见变异类型,其特征为血小板减少、全身水肿、骨髓网状纤维增生、肾功能不全和器官肿大。在此,我们报告1例用托珠单抗成功治疗的TAFRO综合征病例。一名50岁男性,因发热、上腹部疼痛、腹部胀满和四肢重度水肿入院。计算机断层扫描显示双侧胸腔积液、腹水和淋巴结病。实验室检查显示肾功能不全、贫血和血小板减少。骨髓和颈部淋巴结检查诊断为透明血管型Castleman病。血清白细胞介素(IL)-6水平极高。最终诊断为TAFRO综合征。患者每周接受抗IL-6受体抗体托珠单抗和类固醇治疗。4周内,所有症状消失,血清IL-6水平恢复正常。治疗前显著降低(9.9%)的ADAMTS13(含Ⅰ型血小板反应蛋白基序的解聚素和金属蛋白酶13)活性在接受托珠单抗治疗后升高。本病例提示托珠单抗是治疗TAFRO综合征的有效药物。我们认为TAFRO综合征中的高细胞因子血症抑制ADAMTS13活性,从而诱发血栓性微血管病。