AL amyloidosis is a rare condition that affects individuals from ages 50 to 80. In their 2006 update to the Veterans and Agent Orange publication, the Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides from the Institute of Medicine determined that the previous studies of Agent Orange and AL amyloidosis satisfied the criteria for “limited or suggestive evidence of association,” primarily on the basis of its close biologic relationship with multiple myeloma. Because of this determination by the Institute of Medicine, the VA added AL amyloidosis to the list of conditions that are presumed to be caused by exposure to Agent Orange in 2006.
What is AL amyloidosis?
AL amyloidosis is the most common of the amyloid diseases, with approximately 4,500 new cases diagnosed each year. AL amyloidosis is caused by a bone marrow disorder. The bone marrow produces plasma cells that make antibodies to fight infections, as part of the immune system. These plasma cells contain protein chains, called immunoglobulin, which function as antibodies. The immunoglobulins are composed of four protein chains: two light chains, and two heavy chains. AL amyloidosis concerns abnormalities in the light immunoglobulin chains, hence the name (“A” for amyloid and “L” for light chain). These abnormalities take the shape of a misfolded chain.
The abnormal, misfolded proteins are deposited in and around tissues, nerves and organs. As the cells build up in an organ, nerve or tissue, it gradually causes damage and affects their function. Often it affects more than one organ. While not considered a cancer (strictly speaking), AL amyloidosis is treated like a cancerous condition, often with chemotherapy.
What are the symptoms of AL amyloidosis?
The signs and symptoms of amyloidosis depend on the location and size of the amyloid deposits. AL may affect any tissue. Signs and symptoms may be vague and can include the following:
- Heart disease and irregular heart beat—the heart is involved in about 50% of patients with AL
- Kidney disorders, including kidney failure
- Gastrointestinal (GI) disorders, such as perforation (hole), bleeding, slow movement of matter through the GI tract, and blockage
- Enlarged liver
- Diminished function of the spleen
- Diminished function of the adrenal and other endocrine glands
- Skin conditions, such as growths, color changes, purpura (bleeding into the skin) around the eyes, and easy bruising
- Enlarged tongue, sometimes with swelling under the jaw, breathing difficulties, and sleep apnea
- Lung problems
- Swelling of the shoulder joints (may look like shoulder pads under the skin)
- Bleeding problems
- Weight loss
AL amyloidosis is often overlooked because the signs and symptoms can mimic those of more common diseases. Diagnosis as early as possible can help prevent further organ damage.
The Institute of Medicine’s Findings
Originally, the Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides had included AL amyloidosis in the group of non-neoplastic health conditions which were not related to Agent Orange. Because this disease is so rare, it was inherently difficult to conduct studies to determine whether or not AL amyloidosis is caused by Agent Orange. However, the 2006 update noted that AL amyloidosis has characteristics that are similar to multiple myeloma and some types of B-cell lymphoma (both of which conditions have been presumed to be related to Agent Orange in the original Agent Orange Act of 1994). These conditions share several biologic similarities, most notably the over-cloning of B-cell-derived plasma cells and production of abnormal amounts of immunoglobulins.
According to the Institute of Medicine, the observation of common chromosomal abnormalities in AL amyloidosis and multiple myeloma and of “progression” from AL amyloidosis to multiple myeloma supports the biologic plausibility of linking AL amyloidosis with multiple myeloma.
It is also known that AL amyloidosis is associated with B-cell diseases. Roughly 15–20% of the time it occurs with multiple myeloma. Other diagnoses associated with AL amyloidosis include B-cell lymphomas, such as Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Thus, AL amyloidosis can result from such medical conditions as multiple myeloma and B-cell lymphomas for which there is evidence of association with exposure to Agent Orange.
The VA apparently recognizes how debilitating AL amyloidosis can be because it has assigned an automatic 100% evaluation for this condition under the VA rating schedule (#7717). This is a significant benefit to veterans with AL amyloidosis because, once assigned, it cannot be reduced to a lower rating.