title: Successful treatment of TAFRO syndrome, a variant type of multicentric Castleman disease with thrombotic microangiopathy, with anti-IL-6 receptor antibody and steroids.
abstract: 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.
authors.affiliation: Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Tyuou-ku, Kumamoto, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Tyuou-ku, Kumamoto, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mochinaga
authors.affiliation: Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Tyuou-ku, Kumamoto, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Nakata
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Blood Transfusion and Cell Therapy, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Uchiba
authors.affiliation: Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mikami
authors.affiliation: Division of Informative Clinical Sciences, Faculty of Medical Sciences, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hata
authors.affiliation: Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Tyuou-ku, Kumamoto, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Tyuou-ku, Kumamoto, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
authors.affiliation: Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Tyuou-ku, Kumamoto, Japan. knosaka95@gmail.com.|Cancer Center of Kumamoto Medical School of Medicine, Kumamoto, Japan. knosaka95@gmail.com.
authors.forename: Kisato
authors.initials: K
authors.lastname: Nosaka
mesh_terms: D000071120:ADAMTS13 Protein; D000906:Antibodies / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D005871:Castleman Disease / Q000175:diagnosis*; D003937:Diagnosis, Differential; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D013256:Steroids / Q000627:therapeutic use; D057049:Thrombotic Microangiopathies / Q000209:etiology*; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; C508600:IL6 protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D013256:Steroids; D000071120:ADAMTS13 Protein; C502936:tocilizumab
keywords: ADAMTS13; Castleman disease; TAFRO syndrome; Tocilizumab