Amyloidosis is a group of rare disorders caused by the buildup of abnormal proteins in organs and tissues. These misfolded proteins form deposits known as amyloid fibrils, which interfere with normal organ function. This article focuses on Amyloidosis Type AA, or secondary amyloidosis. The “AA” signifies the deposits are from a blood protein called Serum Amyloid A (SAA), and the condition arises as a complication of a long-standing disease causing persistent inflammation or infection.
Underlying Causes and Risk Factors
The development of AA amyloidosis is directly linked to chronic inflammation. In response to a persistent infection or inflammatory disease, the liver produces a protein called Serum Amyloid A (SAA). When an underlying condition causes inflammation to continue for months or years, SAA protein levels remain excessively high. Over time, a fragment of the SAA protein can misfold, becoming insoluble and depositing in tissues as amyloid fibrils.
The risk of developing AA amyloidosis is highest for individuals with diseases that cause sustained, systemic inflammation. Among the most common underlying causes are:
- Chronic inflammatory arthritis conditions, such as rheumatoid arthritis and ankylosing spondylitis.
- Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis.
- Chronic infections that the body struggles to clear, like tuberculosis.
- The bone infection osteomyelitis.
Symptoms and Organ Involvement
The signs of AA amyloidosis can be subtle and initially mistaken for symptoms of the primary underlying disease. General symptoms often include unexplained weight loss, weakness, and a feeling of bloating or nausea. The location of these protein deposits determines the specific symptoms a person will experience.
The kidneys are the most frequently and severely affected organs. The initial sign of kidney involvement is often the presence of protein in the urine (proteinuria), which can make urine appear foamy. As protein loss from the blood becomes more severe, it can lead to nephrotic syndrome, which includes significant swelling (edema) in the legs, ankles, and feet. This progressive damage can lead to chronic kidney disease and end-stage renal failure.
While the kidneys are the primary target, other organs can also be affected. The gastrointestinal tract may accumulate amyloid deposits, causing issues like chronic diarrhea and poor nutrient absorption. The liver and spleen can also become sites of deposition, leading to their enlargement and impaired function. Heart involvement is extremely rare in AA amyloidosis, distinguishing it from some other forms of the disease.
The Diagnostic Process
Diagnosing AA amyloidosis involves a multi-step process that begins with laboratory tests. Blood tests can reveal elevated markers of inflammation and check kidney function by measuring creatinine levels. A urinalysis is performed to detect proteinuria, which is often the first indicator of kidney damage. While these tests can suggest the disease, they are not sufficient for a definitive diagnosis.
Confirmation of amyloidosis requires a tissue biopsy to directly visualize the protein deposits. A common and minimally invasive procedure is a biopsy of the abdominal fat pad, though a sample may be taken from an affected organ, such as the kidney, to assess the extent of the damage.
The diagnostic test involves staining the tissue sample with a dye called Congo red. When viewed under a microscope with polarized light, amyloid deposits stained with Congo red exhibit a characteristic “apple-green” color. This finding confirms the presence of amyloid, and mass spectrometry is then used to identify the protein as Type AA to guide treatment.
Treatment and Management
The main treatment for AA amyloidosis is to manage the underlying chronic inflammatory or infectious disease. The objective is to lower the production of the SAA protein to stop new amyloid deposits from forming. For inflammatory conditions like rheumatoid arthritis, biologic drugs that target specific inflammatory pathways are highly effective. For cases caused by chronic infections, treating the infection with appropriate antibiotics is the focus.
Alongside treating the root cause, management also involves supportive care to address the organ damage that has already occurred. Medications are often prescribed to control high blood pressure and to manage fluid retention and swelling through the use of diuretics. Regular monitoring of kidney function through blood and urine tests is a standard part of patient care.
In situations where the disease has progressed to cause severe organ damage, more intensive interventions become necessary. For patients who develop end-stage renal disease, treatment options include dialysis to perform the functions of the failed kidneys. In some cases, a kidney transplant may be considered as a potential treatment to restore kidney function.