Castleman disease (CD) describes a group of rare lymphoproliferative disorders that involve enlarged lymph nodes, and a broad range of inflammatory symptoms and laboratory abnormalities. Whether Castleman disease should be considered an autoimmune disease, cancer, or infectious disease is currently unknown. Castleman disease includes at least three distinct subtypes: unicentric Castleman disease (UCD), human herpesvirus 8 associated multicentric Castleman disease (HHV-8-associated MCD), and idiopathic multicentric Castleman disease (iMCD). These are differentiated by the number and location of affected lymph nodes and the presence of human herpesvirus 8, a known causative agent in a portion of cases. Correctly classifying the Castleman disease subtype is important, as the three subtypes vary significantly in symptoms, clinical findings, disease mechanism, treatment approach, and prognosis. All forms involve overproduction of cytokines and other inflammatory proteins by the bodys immune system as well as characteristic abnormal lymph node features that can be observed under the microscope. In the United States, approximately 4,300 to 5,200 new cases are diagnosed each year.Castleman disease is named after Benjamin Castleman, who first described the disease in 1956. The Castleman Disease Collaborative Network is the largest organization dedicated to accelerating research and treatment for Castleman disease as well as improving patient care. Classification
Castleman disease (CD) can involve one or more enlarged lymph nodes  in a single region of the body (unicentric CD, UCD) or it can involve multiple enlarged lymph node regions (multi centric CD, MCD).
Multicentric Castleman disease (MCD)
In this form, patients have multiple regions of enlarged lymph nodes with characteristic microscopic features, flu-like symptoms, and organ dysfunction due to excessive cytokines or inflammatory proteins. MCD is further classified into three categories based on underlying cause: POEMS-associated MCD, HHV-8-associated MCD, and idiopathic MCD (iMCD). POEMS-associated MCD
A cancerous cell population found in patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) can cause MCD in a fraction of patients by producing cytokines that initiate a cytokine storm. In patients who have both POEMS-associated MCD, treatment should be directed at the POEMS syndrome. HHV-8-associated multicentric Castleman disease (HHV-8-MCD)
HHV-8-associated MCD patients have multiple regions of enlarged lymph nodes and episodic inflammatory symptoms due to uncontrolled infection with HHV-8. HHV-8-associated MCD is most commonly diagnosed in HIV infected or otherwise immunocompromised individuals that are not able to control HHV-8 infection. Thus, HHV-8-associated MCD patients may experience additional symptoms related to their HIV infection or other conditions. First-line treatment of HHV-8-associated MCD is rituximab, a drug used to eliminate a type of immune cell called the B lymphocyte. It is highly effective for HHV-8-associated MCD, but occasionally antivirals and/or cytotoxic chemotherapies are needed. Idiopathic multicentric Castleman disease (iMCD)
Idiopathic multicentric Castleman disease (iMCD), which is the most common form of MCD, occurs for an unknown cause. There is no evidence of POEMS syndrome, HHV-8, or any other cancer or infectious disease.