TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca including pleural effusion and ascites, fever, renal insufficiency, and organomegaly including hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology is undetermined. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of multicentric Castleman disease (MCD), other specific features can differentiate between them. Some TAFRO syndrome patients have been successfully treated with glucocorticoids and/or immunosuppressants, including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, and eventually succumb to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The present article reports the 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams. These criteria and classification have been applied and retrospectively validated on clinicopathologic data of 28 patients with this and similar conditions (e.g. MCD with serositis and thrombocytopenia).

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This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity.

Castleman disease was initially described as a lymphoproliferative disorder causing mediastinal masses characterized by abnormal histopathology. 1 Castleman disease has since been subclassified clinically into unicentric (UCD) and multicentric Castleman disease (MCD), 2 and subclassified histopathologically into the hyaline-vascular type (HV), plasma-cell type (PC), mixed type, plasmablastic type, and hypervascular type. 3 MCD was recently subclassified into human herpes virus-8 (HHV-8)-associated, HHV-8unassociated (idiopathic MCD [iMCD]), POEMS syndromeassociated, and others. 3 A new clinical entity, TAFRO syndrome, characterized by thrombocytopenia, anasarca (edema, pleural effusion, and ascites), fever, reticulin myelofibrosis (or renal insufficiency), and organomegaly (hepatosplenomegaly and lymphadenopathy), was recently described. 4 Its diagnostic criteria and disease severity criteria, determined by the All Japan TAFRO Syndrome Research Group in the Research Program for Intractable Diseases of the Ministry of Health, Labour and Welfare (MHLW) of Japan, 5 were recently updated (https:// www.facebook.com/CastlemanTAFRO). As the lymph nodes of individuals with TAFRO syndrome were characterized histopathologically as Castleman disease, 6 TAFRO syndrome has been categorized as part of iMCD. Recently, clinical and basic studies on Castleman disease and TAFRO syndrome were started in Japan and the USA. We collected and analyzed data from more than 200 patients with iMCD, TAFRO syndrome, or conditions mimicking these disorders. Most patients with iMCD exhibit a chronic/ indolent clinical course, characterized by polyclonal hypergammopathy, multiple lymphadenopathy, and thrombocytosis. In contrast, most patients with TAFRO syndrome have an acute or sub-acute onset and progressive clinical course, characterized by normal to reduced gammaglobulin levels, thrombocytopenia, small or unnoticeable lymph nodes, and severe pleural effusion, ascites, and anasarca. Lymph node

To identify prognostic factors for TAFRO syndrome, a rare inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Data of patients with TAFRO syndrome were extracted from a Japanese patient registry. Patients were divided into groups according to the clinical and laboratory parameters at initial presentation. Cut-off values for the laboratory parameters were determined using receiver operating characteristic curve analysis and by clinical relevance. Patient survival was analyzed by the Kaplan-Meier method. Univariable analysis was performed using log-rank tests. Multivariable analyses were performed with the logistic regression model and the Cox-proportional hazards model. We extracted the data of 83 patients with TAFRO syndrome from the registry. Univariable analysis identified several potential prognostic factors. Of these factors, age ≥ 60 years and D-dimer ≥ 18 μg/dL remained significant predictors of poor overall survival in the multivariable Cox-proportional hazards model. Based on these results, we developed a simple prognostic scoring system for TAFRO syndrome (TS-PSS). Patients in our cohort were stratified into low, intermediate, and high-risk groups by the TS-PSS. This system should be verified with independent patient cohorts in future studies.

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