2019 Updated diagnostic criteria and disease severity classification for TAFRO syndrome

Abstract

TAFRO syndrome, first reported in 2010, is a systemic inflammatory disorder manifesting as thrombocytopenia; anasarca, including pleural effusion and ascites; fever; reticulin myelofibrosis and/or renal insufficiency; and organomegaly, including hepatosplenomegaly and lymphadenopathy. The annual incidence rate of TAFRO syndrome in Japan has been estimated to be 0.9–4.9 per million individuals, and the nationwide prevalence to be 860–7240 cases [1], numbers which are larger than previously expected. Most patients with TAFRO syndrome manifest modest-to-mild systemic lymphadenopathy with characteristic histopathological features resembling those of Castleman disease. Some researchers, therefore, consider that TAFRO syndrome to be a subtype of idiopathic multicentric Castleman disease (iMCD) [2]. However, clinical features of TAFRO syndrome are quite different from those of classical Castleman disease [3], and we consider TAFRO syndrome to be a distinct clinical entity, although several pathological findings of lymph nodes resemble those in iMCD. In 2015, we proposed diagnostic criteria and a disease severity classification for TAFRO syndrome [4], which have been widely accepted and cited. Almost simultaneously, another research group proposed diagnostic criteria for TAFRO syndrome with iMCD histology (TAFRO-iMCD) [2]. In the latter criteria, characteristic histopathological findings of lymph nodes are essential for diagnosis. We are aware that histological findings from lymph nodes are important for diagnosis, but lymph node biopsy from patients with TAFRO syndrome is sometimes difficult or nearly impossible, due to anasarca, bleeding tendency, and/ or the smallness or unclear of the target lymph node. In addition, prompt diagnosis and initiation of treatment without delay are required to rescue such patients. Therefore, our diagnostic criteria include patients without histological confirmation of lymph nodes. After our proposal of the diagnostic criteria and disease severity classification in 2015, we gained some additional insights and experiences that prompted us to update these criteria and classification. Recently, we retrospectively analyzed data from 220 patients stored in the database of the Multicenter Collaborative Retrospective Study for establishing the concept of TAFRO syndrome [3]. In that study, we compared clinical features of patients with iMCD, not otherwise specified (iMCD-NOS), TAFRO-iMCD, and TAFRO-withoutproven-iMCD (TAFRO-w/op-iMCD). Our analysis clearly demonstrated that iMCD-NOS and TAFRO-iMCD are different clinical entities, whereas TAFRO-iMCD and TAFRO-w/ op-iMCD, which were diagnosed without lymph node biopsy, could be considered the same clinical entity, requiring prompt diagnosis and intensive care [3]. In this retrospective study, we also found that patients with various diseases, including * Yasufumi Masaki [email protected]