Castleman disease (CD) is a rare disorder of the lymphatic system involving an abnormal overgrowth of lymph tissue. Whether CD is fatal depends entirely on the specific form a person is diagnosed with, as it is best understood as a spectrum of disorders. Understanding this distinction, the underlying pathology, and the available treatments is necessary to grasp the true risks.
Defining Castleman Disease
Castleman disease is an uncommon lymphoproliferative disorder defined by the overgrowth of immune cells within lymph nodes (lymphadenopathy). This lymph node enlargement is not cancer, but a severe inflammatory disorder that can mimic malignancy. The core pathology involves a dysregulation of the immune system, leading to an overproduction of inflammatory signaling proteins called cytokines.
This cytokine overproduction can escalate into a state of hyperinflammation, sometimes referred to as a cytokine storm, which drives the systemic features of the disease. The chronic activation of the immune system and the resulting inflammatory cascade cause the characteristic tissue changes. The systemic effects of the immune dysregulation are what pose a serious health risk.
The Critical Distinction in Disease Types
The clinical course and potential for fatality hinge upon whether the condition is localized or systemic. Physicians broadly categorize the disorder into two main types: Unicentric Castleman Disease (UCD) and Multicentric Castleman Disease (MCD). UCD is the less severe form, confined to a single lymph node or group of lymph nodes in one region of the body.
The systemic form, MCD, involves multiple lymph node regions throughout the body and is driven by chronic, widespread inflammation. This systemic nature makes MCD the form associated with severe illness and a significantly higher mortality risk.
MCD is further classified based on its cause, most notably into Human Herpesvirus 8 (HHV-8)-associated MCD and idiopathic MCD (iMCD). The HHV-8 virus infects plasma cells and drives cytokine dysregulation, while iMCD has no known cause and is considered a heterogeneous group of disorders.
Understanding Prognosis and Mortality Risk
The prognosis for Castleman disease is directly tied to the type of disease, showing a clear separation in potential outcomes. For Unicentric Castleman Disease, the prognosis is generally excellent, and the condition is rarely fatal. Life expectancy for UCD patients is typically not changed by the diagnosis, especially when successfully treated.
In stark contrast, Multicentric Castleman Disease carries a substantial mortality risk due to the systemic nature of the illness. Death in MCD results from severe complications of chronic, uncontrolled systemic inflammation and cytokine overdrive. These complications include multi-organ failure, severe and opportunistic infections due to immune dysfunction, or the development of associated malignancies like lymphoma.
Survival statistics highlight the severity of MCD. Studies show that the 5-year overall survival rate for patients with the idiopathic form of the disease (iMCD) can be around 75%, though older data reported rates as low as 65% before modern therapies became common. The difference in outcome is dramatic, as the 5-year overall survival rate for UCD patients is typically over 90%.
Current Management and Treatment Approaches
Treatment strategies for Castleman disease are tailored to the type and severity of the condition. For Unicentric Castleman Disease, management is straightforward: surgical excision of the affected lymph node is the primary approach. This surgical removal is often curative, requiring little or no further treatment.
For Multicentric Castleman Disease, treatment involves medical management designed to suppress the overly active immune system and halt the inflammatory cytokine cascade. Targeted immunotherapies are frequently employed, such as anti-interleukin-6 (IL-6) therapy, which blocks a key inflammatory cytokine. Siltuximab, for instance, is a preferred first-line therapy for iMCD, aiming to manage symptoms and prevent complications.
HHV-8-associated MCD is typically treated with the monoclonal antibody rituximab, which targets B-cells and controls the HHV-8 infected plasma cells. In cases of severe or refractory MCD, stronger treatments like systemic corticosteroids and conventional chemotherapy are often necessary to bring the hyperinflammation under control. These systemic interventions are necessary to mitigate the high mortality risk by managing the underlying immune dysfunction.