Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research.

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in "omics" technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN's collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.

Castleman disease.

Castleman disease (CD), a heterogeneous group of disorders that share morphological features, is divided into unicentric CD and multicentric CD (MCD) according to the clinical presentation and disease course. Unicentric CD involves a solitary enlarged lymph node and mild symptoms and excision surgery is often curative. MCD includes a form associated with Kaposi sarcoma herpesvirus (KSHV) (also known as human herpesvirus 8) and a KSHV-negative idiopathic form (iMCD). iMCD can present in association with severe syndromes such as TAFRO (thrombocytopenia, ascites, fever, reticulin fibrosis and organomegaly) or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes). KSHV-MCD often occurs in the setting of HIV infection or another cause of immune deficiency. The interplay between KSHV and HIV elevates the risk for the development of KSHV-induced disorders, including KSHV-MCD, KSHV-lymphoproliferation, KSHV inflammatory cytokine syndrome, primary effusion lymphoma and Kaposi sarcoma. A CD diagnosis requires a multidimensional approach, including clinical presentation and imaging, pathological features, and molecular virology. B cell-directed monoclonal antibody therapy is the standard of care in KSHV-MCD, and anti-IL-6 therapy is the recommended first-line therapy and only treatment of iMCD approved by the US FDA and EMA.