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.

Diagnosis of Castleman disease can be challenging due to its various clinical presentations and similarity with other clinical conditions, including infectious diseases; blood disorders, like certain lymphomas; and autoimmune conditions.

Certain blood tests may be performed to support the diagnosis of Castleman disease, like IL-6 levels and a polymerase chain reaction, or PCR, for human herpesvirus-8 DNA.

Imaging techniques, such as a CT scan, may be useful to detect how many lymph nodes are affected and distinguish between unicentric and multicentric disease.

Additionally, a PET scan, which uses a radiotracer to detect increased cell activity, may be done to identify small collections of fast-growing cells that might not be visible with other imaging studies.

Confirmation of the diagnosis can only be achieved through a lymph node biopsy showing features of Castleman disease. First-line treatment of unicentric Castleman disease is surgical removal of the affected lymph node.

If surgery is not possible, medications like rituximab may be given to attempt to shrink the lymph node. On the other hand, treatment of multicentric Castleman disease involves anti-IL-6 therapy with siltuximab, which is the only FDA-approved treatment for idiopathic multicentric Castleman disease.

In individuals where siltuximab is not effective, rituximab, corticosteroids, or chemotherapy regimens may be used.Alright, as a quick recap, Castleman disease describes a rare group of related disorders characterized by lymph node enlargement and inflammatory signs and symptoms.

Diagnosis is confirmed through lymph node biopsy. Treatments can include surgery; medications like rituximab,