Castleman disease: Year of the Zebra

Castleman disease describes a group of immune-related disorders characterized by lymph node enlargement resulting from the overactivation of the immune system. There are two main types of Castleman disease: unicentric, or localized, which only affects a single lymph node region; and multicentric, or generalized, where there is lymph node enlargement in multiple regions of the body along with a broad range of inflammatory symptoms.

Castleman disease is linked to the overproduction of a protein called interleukin-6, or IL-6, which plays a key role in regulating immune responses. The exact reason for this abnormal IL-6 production is not entirely understood, but it may result from an exaggerated immune response to certain viral infections, such as human immunodeficiency virus, or HIV, the infection responsible for AIDS.

Individuals with unicentric Castleman disease are often asymptomatic. If they experience symptoms, they are usually mild and related to the compression of surrounding structures by enlarging lymph nodes. Common symptoms include feeling a lump under the skin in the neck, armpit or groin area; and a feeling of fullness or pressure in the chest that can make swallowing or breathing more difficult.

On the other hand, multicentric Castleman disease is a potentially life-threatening condition, where individuals experience a wide range of systemic symptoms in addition to enlargement of the lymph nodes. These can include flu-like symptoms, such as fever, fatigue, night sweats, and unintentional weight loss; as well as enlargement of the liver and spleen.

Although it is unclear why, some individuals with multicentric Castleman disease develop life-threatening organ dysfunction caused by a sudden and massive release of proinflammatory mediators, leading to significant tissue inflammation and organ damage. This may result in liver and kidney dysfunction and symptoms of fluid accumulation in the body, such as edema and ascites, or excess fluid in the abdomen.