AL amyloidosis is a serious, systemic disease characterized by the buildup of abnormal protein deposits in various organs and tissues throughout the body. It is the most common type of systemic amyloidosis, a group of rare disorders where misfolded proteins accumulate. Without intervention, these protein deposits can progressively impair organ function, potentially leading to organ failure.
Understanding AL Amyloidosis
The “AL” in AL amyloidosis refers to “amyloid light chain,” indicating the specific type of protein involved. This condition originates from a disorder of plasma cells, which are a type of white blood cell located in the bone marrow.
In AL amyloidosis, abnormal plasma cells produce excessive amounts of misfolded light chain proteins. These misfolded proteins then aggregate into insoluble structures called amyloid fibrils, which deposit in various organs and tissues throughout the body, hindering their normal function.
While AL amyloidosis is not a cancer itself, it is considered a plasma cell disorder and is sometimes associated with multiple myeloma, another plasma cell disorder, in about 10-15% of cases. The damage to organs occurs both from the mechanical effect of the deposits and potentially from a direct toxic effect of the monoclonal light chains.
Recognizing the Signs
The symptoms of AL amyloidosis are diverse and can vary significantly among individuals, depending on which organs are affected and the extent of the damage. Early symptoms are often non-specific, making diagnosis challenging. Common general symptoms include severe fatigue, unexplained weight loss, and generalized weakness.
For instance, if amyloid deposits affect the heart, individuals may experience shortness of breath, swelling in the lower extremities, irregular heartbeats (arrhythmia), or dizziness. Kidney involvement can lead to fluid retention and impaired kidney function, potentially progressing to kidney failure. In the nervous system, deposits can cause numbness, tingling, or pain in the hands and feet (peripheral neuropathy), or affect nerves controlling blood pressure and digestion, leading to dizziness upon standing, nausea, or diarrhea.
Digestive tract involvement can manifest as nausea, diarrhea, constipation, loss of appetite, or feeling full after consuming small amounts of food. Liver enlargement due to amyloid deposits can also occur. Skin changes, such as easy bruising, brittle nails, purplish patches around the eyes, or an enlarged tongue, are also possible signs.
How AL Amyloidosis is Diagnosed
Diagnosis often requires a high level of suspicion due to its varied symptoms. The diagnostic process typically begins with blood and urine tests to detect abnormal proteins and assess organ function. These tests include serum and urine protein electrophoresis with immunofixation and serum free light chain assays, which help identify monoclonal proteins produced by abnormal plasma cells. Cardiac biomarkers such as troponin I, troponin T, and NT-proBNP are also measured to evaluate heart health.
The definitive diagnosis of AL amyloidosis relies on a biopsy to confirm the presence of amyloid deposits. A biopsy of an affected organ or a less invasive site, such as an abdominal fat pad or bone marrow, is commonly performed. The tissue sample is then stained with Congo red. When viewed under a microscope, amyloid proteins stained with Congo red appear apple-green under polarized light, confirming amyloid.
After confirming amyloid, accurate typing of the amyloid protein is essential to distinguish AL amyloidosis from other types. This is typically done using mass spectrometry or immunohistochemistry.
Treatment Approaches
Treatment for AL amyloidosis primarily aims to stop the production of the amyloid-forming light chains by targeting the underlying abnormal plasma cells. This approach helps prevent new amyloid deposits from forming and can potentially improve or reverse organ dysfunction. Various treatment modalities are employed, often in combination, and are tailored to the individual patient’s health, age, and extent of organ damage.
Chemotherapy is a common treatment, with agents such as cyclophosphamide, bortezomib, and dexamethasone frequently used. High-dose chemotherapy followed by autologous stem cell transplantation may be an option for eligible patients whose disease is not advanced and whose heart function is not severely affected. Targeted therapies are also emerging, which work more selectively than traditional chemotherapy by focusing on specific proteins or genes involved in the disease. Immunotherapy, which stimulates the body’s immune system to attack abnormal cells, is another developing area.
Supportive care is also an important aspect of managing AL amyloidosis. This involves treating symptoms and supporting the function of affected organs. For instance, diuretics may be prescribed for fluid retention, and medications can help manage heart rhythm issues. Ongoing research is exploring novel approaches, including therapies specifically designed to clear existing amyloid deposits from organs. These advancements aim to improve outcomes and quality of life for individuals living with AL amyloidosis.