The CDCN works hard to compile useful resources for physicians treating Castleman disease patients and researchers interested in Castleman disease.

This resource section contains:

• Clinical guidance via CD pages on UpToDate, authored by Dr. David Fajgenbaum, a leading CD researcher in the USA. These pages provide extensive details for all subtypes of CD.
• Full text of the diagnostic criteria for idiopathic multicentric Castleman disease, published in Blood, 2017
• Full text of the treatment guidelines for idiopathic multicentric Castleman disease, published in Blood, 2018
• Full texts of recent and significant CD publications
• Compiled evidence for idiopathic multicentric Castleman disease treatment target
• Pathology toolkit describing pathologic features of CD

UpToDate Guidance

Dr. David Fajgenbaum, the leading Castleman disease researcher in the USA, authors all three CD pages on UpToDate. Each page provides extensive information about CD written primarily for physicians treating CD patients. Links to these pages are provided here.

• Unicentric Castleman disease – This UpToDate clinical reference (authored by David C. Fajgenbaum, MD) covers Unicentric Castleman Disease (UCD), one of at least three subtypes of Castleman disease, a group of lymphoproliferative disorders sharing common lymph-node histopathology. UCD is defined by enlarged lymph node(s) confined to a single region of the body, with pathology falling along a spectrum from the more common hyaline-vascular subtype to the plasma-cell subtype. It is distinguished from HHV-8/HIV-associated and idiopathic multicentric Castleman disease (MCD), which involve multiple nodal regions and more severe systemic illness. Many UCD patients are asymptomatic and discovered incidentally, though a subset develop systemic inflammatory symptoms; diagnosis requires excisional lymph-node biopsy to confirm the histopathology and exclude malignancy and other causes of lymphadenopathy. Because the disease is localized, complete surgical resection of the involved node(s) is the mainstay of treatment and is typically curative, with adjunctive options (such as embolization, rituximab, or the anti-IL-6 agent siltuximab) reserved for unresectable disease or persistent symptoms. Overall prognosis is excellent, with high long-term survival after complete excision.
• HHV-8-associated multicentric Castleman disease – This UpToDate clinical reference (authored by David C. Fajgenbaum, MD) covers HHV-8-associated multicentric Castleman disease, the form of Castleman disease caused by uncontrolled infection with human herpesvirus-8 (HHV-8, also called Kaposi sarcoma–associated herpesvirus). Unlike the localized unicentric form, multicentric CD involves enlarged lymph nodes in multiple regions of the body and produces systemic inflammatory illness—generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and organ dysfunction—driven by excessive pro-inflammatory cytokines, particularly interleukin-6 (both human IL-6 and a viral IL-6 homolog encoded by HHV-8). It accounts for roughly half of MCD cases and occurs almost exclusively in immunocompromised patients, most often those with HIV infection, in whom weakened immune control allows HHV-8 to replicate in lymph-node plasmablasts. Diagnosis rests on lymph-node biopsy demonstrating characteristic histopathology together with confirmation of HHV-8. Because B cells play a central role, B-cell depletion with rituximab is the mainstay of treatment—given alone or combined with chemotherapy (such as pegylated liposomal doxorubicin or etoposide) in more aggressive disease—alongside antiretroviral therapy for HIV-positive patients and, in selected cases, antiviral agents targeting HHV-8. Outcomes have improved substantially in the rituximab era, though the disease can relapse and requires ongoing clinical monitoring.
• HHV-8-negative (idiopathic) multicentric Castleman disease – This UpToDate clinical reference (authored by David C. Fajgenbaum, MD) covers HHV-8-negative, or idiopathic, multicentric Castleman disease (iMCD), which accounts for roughly half of MCD cases and shares nearly identical clinical and histopathologic features with the HHV-8-associated form but has an unknown cause. Like other multicentric disease, iMCD presents with lymphadenopathy across multiple regions plus systemic inflammatory symptoms—hepatosplenomegaly, cytopenias, organ dysfunction, and abnormal labs (elevated CRP, ferritin, fibrinogen, VEGF, and often IL-6)—resulting from immune dysregulation and a cytokine storm. Interleukin-6 is a key driver in many patients, and the article reviews proposed etiologic mechanisms and the TAFRO clinical subtype. Diagnosis is one of exclusion, ruling out infections, malignancies, and autoimmune disorders that can mimic it. First-line treatment is the anti-IL-6 monoclonal antibody siltuximab (supported by a randomized controlled trial), with or without glucocorticoids; patients with severe or rapidly progressive disease may need accelerated siltuximab plus high-dose steroids, and those refractory to anti-IL-6 therapy may require additional immunosuppressants or combination chemotherapy. A practical caveat noted is that IL-6 lab measurements become uninterpretable for 18–24 months after siltuximab or tocilizumab dosing. Prognosis is more variable than the unicentric form, ranging from mild relapsing-remitting disease to life-threatening flares.

Diagnostic Criteria and Treatment Guidelines

The diagnostic criteria for idiopathic (HHV-8-negative) multicentric Castleman disease–the first-ever diagnostic criteria for CD–was published in the journal Blood in 2017. The full text is available here.

Treatment guidelines for idiopathic (HHV-8-negative) multicentric Castleman disease–the first-ever treatment guidelines for CD–was published in the journal Blood in 2018. The full text is available here.

Research is underway for diagnostic criteria and treatment guidelines for unicentric Castleman disease. This research is being led by Dr. Frits van Rhee at the University of Arkansas for Medical Sciences with significant contributions from Dr. David Fajgenbaum and the CDCN Scientific Advisory Board.