Epidemiological analysis of multicentric and unicentric Castleman disease and TAFRO syndrome in Japan

Abstract

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

Patient’s age and d-dimer levels predict the prognosis in patients with TAFRO syndrome

“…Fifth, treatment strategies were not standardized; instead, they were chosen by attending physicians in each institute. However, because of the rarity of TAFRO syndrome [31], conducting a largescale prospective study on this syndrome is unrealistic at this moment, unfortunately.…”

Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6–directed therapy

“…This is the first study to our knowledge to report incidence and prevalence estimates of CD and iMCD after the introduction of a CD-specific ICD-10 code and publication of international evidence-based diagnostic criteria for iMCD in 2017. 3 To date, data on the epidemiology of CD come from a variety of sources that include US academic centers, 12 Japan, 13 the Asia-Pacific region, 14 and US administrative claims databases. 3 Each of these studies reported on the incidence and prevalence of CD, UCD, and MCD, but not iMCD, primarily because of the lack of available criteria and specific disease code.…”

Frontline Siltuximab and Rituximab in TAFRO syndrome: A case report

“…Thrombocytopenia, Anasarca, reticulin Fibrosis of the bone marrow, Renal dysfunction and organomegaly (TAFRO) syndrome is a very rare and severe variant of multicenter Castleman's disease firstly reported in Japan in 2010 1,2 . TAFRO syndrome is a hyper‐cytokine disease often caused by an uncontrolled HHV‐8 replication with a severe reduction of T follicular helper cells and atrophic lymphoid follicles; however, histology is not a mandatory diagnostic criterion for TAFRO 3 ; therefore, a prompt start of immunosuppressive and anti‐cytokine therapy is allowed.…”