Jurnal Internasional Wawasan baru dan pendekatan terapeutik pada penyakit Castleman multisentrik idiopatik
Castleman's disease (CD) describes a group of heterogeneous hematological disorders that have a distinctive lymph node histopathology. Patients of all ages present with either a single enlarged lymph node (unicentric CD) or multicentric lymphadenopathy (MCD) with systemic inflammation, cytopenias, and life-threatening multiple organ dysfunction resulting from storm cytokines often driven by interleukin 6 (IL-6) . Uncontrolled human herpesvirus-8 infection (HHV-8) causes about 50% of cases of MCD, whereas etiology is unknown in the remaining cases of HHV-8-negative / idiopathic MCD (iMCD). A limited understanding of the etiology, cell type, and signaling pathways involved in iMCD has slowed the progress of treatment and contributed to historically poor patient outcomes. Here, the latest developments to diagnose iMCD, ethio-pathogenesis characterization, and follow-up care are reviewed. Some clinicopathological analyzes provide an evidence base for the first diagnostic criteria and reveal different clinical subtypes: thrombocytopenia, anasarca, fever, reticulin fibrosis / renal dysfunction, organomegaly (iMCD-TAFRO) or iMCD-not determined (iMCD-NOS), both of which are observed in the whole world. In 2014, siltuximab anti-IL-6 therapy became the first iMCD treatment approved by the US Food and Drug Administration, based on a 34% long-lasting response rate; consensus guidelines recommend it as front-line therapy. Recent cytokines and proteomic profiles show normal IL-6 levels in many patients with iMCD and potential alternative driving cytokines. Changes in the candidate's new genome, unregulated cell types, and signaling pathways have also been identified as candidate therapeutic targets. RNA sequencing for viral transcripts does not reveal new viruses, HHV-8, or other viruses that are pathologically related to iMCD. Despite progress, the iMCD is still poorly understood. Further efforts to explain the etiology, pathogenesis, and treatment approach, especially for siltuximab refractory patients, are needed.