All cases of UCD and idiopathic MCD have an unknown cause. There are no known risk factors; there is no evidence of any food, lifestyle, or environmental exposure associated with these diseases. There is no known account of a patient contracting Castleman disease directly from another individual.

The HHV-8 positive MCD subtype is known to be associated with HHV-8 virus infection simultaneously with some form of immunosuppression (such as HIV or genetic causes). It is not understood why only a few patients with HHV-8+ infection and immunosuppression develop Castleman disease. Although the HHV-8 virus is contagious, the vast majority of HHV-8+ patients will not develop Castleman disease.


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