Heavy chain diseases: Symptoms, diagnosis and treatment

Heavy chain diseases are a group of very rare cancers of B cells, a type of white blood cell. In these cancers, B cells make incomplete antibody proteins. Antibodies, also called immunoglobulins, help the immune system fight germs. A complete antibody has two heavy chains and two light chains. In heavy chain disease, certain B cells make heavy chains without the light chains that typically attach to them.

There are three main types of heavy chain disease:

• Alpha heavy chain disease affects the heavy chain part of an antibody called immunoglobulin A (IgA). It often affects the digestive system. Symptoms may include diarrhea, stomach pain, weight loss and trouble absorbing nutrients from food. It is a type of MALT lymphoma.
• Gamma heavy chain disease affects the heavy chain part of an antibody called immunoglobulin G (IgG). Symptoms may include swollen lymph nodes, tiredness, fever and weight loss. The liver or spleen also may be larger than usual. Some people have no symptoms. Some people with gamma heavy chain disease also have an autoimmune disease or a lymphoma.
• Mu heavy chain disease affects the heavy chain part of an antibody called immunoglobulin M (IgM). Mu heavy chain disease is the rarest type. It can cause an enlarged liver or spleen, changes in blood counts and, less often, swollen lymph nodes. Mu heavy chain disease can resemble other conditions affecting the B cells, including chronic lymphocytic leukemia (CLL).

In heavy chain disease, B cells make heavy-chain proteins without the light chains that typically attach to them. Heavy chain deposition disease is different. In that rare disease, one type of heavy chain builds up in body tissues, especially the kidneys. Light chain deposition disease causes light chains, rather than heavy chains, to build up in tissues.

Healthcare professionals usually use blood and urine tests to diagnose heavy chain disease. These tests look for unusual heavy-chain proteins. Common protein tests may not find the protein if only a small amount is present. A test called immunofixation can help find the unusual heavy-chain proteins made in heavy chain disease. Other tests may include a complete blood count, tests that separate proteins in blood or urine, and tests of bone marrow or other tissue samples.

Treatment depends on the type of heavy chain disease, the symptoms and whether another blood cancer, such as lymphoma, is present. Some people with gamma heavy chain disease have no symptoms. They may have regular checkups instead of starting treatment right away. When treatment is needed, medicines used to treat lymphoma may be used. These may include medicines that treat cancer throughout the body, such as chemotherapy, immunotherapy or targeted therapy. Alpha heavy chain disease that affects the digestive system may be treated with antibiotics and cancer medicines.

The outlook, also called the prognosis, for people with heavy chain disease varies. Some forms may remain stable for years. Other forms can progress more quickly, especially when an aggressive lymphoma is present. Outlook depends on the type of heavy chain disease and whether lymphoma is also present.