AA amyloidosis

AA amyloidosis is a form of

AA amyloidosis is a complication of a number of inflammatory diseases and infections,[2] although only a small portion of patients with these conditions will go on to develop AA amyloidosis. The most common presentation of AA amyloidosis is renal in nature, including proteinuria, nephrotic syndrome and progressive development of chronic kidney disease leading to end stage kidney disease (ESKD) and need for renal replacement therapy (e.g. dialysis or kidney transplantation).^[3] A natural history study of AA amyloidosis patients reported a number of conditions associated with AA amyloidosis:^[1]

• Autoimmune diseases
  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Crohn disease and ulcerative colitis
• Chronic infections
  • Tuberculosis
  • Bronchiectasis
  • Chronic osteomyelitis
• Autoinflammatory diseases
  • Familial Mediterranean fever (FMF)
  • Muckle–Wells syndrome (MWS)
• Cancer
  • Hodgkin's lymphoma
  • Renal cell carcinoma
• Chronic foreign body reaction
• HIV/AIDS^[4]
• Silicone-induced granulomatous reaction^[5][6][7]

Signs and symptoms of amyloidosis can vary depending on the affected organ. AA amyloidosis is commonly found in organs like the kidneys, liver, and stomach. If the kidneys are affected, an individual may see swelling in the legs, reduced urination, and at times excessive bubbles in the urine. Amyloid proteins in the kidneys can also lead to high cholesterol.[8] Other organs like the stomach may result in bleeding, constipation, etc.^[9]

Pathology

In a healthy individual, the median plasma concentration of SAA is 3 mg per liter.^[10] This can increase to over 2000 mg per liter during an acute phase response and a sustained overproduction of SAA is required for the creation of the AA deposits that define AA amyloidosis.^[11] High levels of SAA, however, is not a sufficient condition for the development of systemic AA amyloidosis and it remains unclear what triggers the accumulation of AA.^[12]

The AA protein is mainly deposited in the liver, spleen and kidney, and AA amyloidosis can lead to nephrotic syndrome and ESRD.^[13][14] Natural history studies show, however, that it is the kidney involvement that drives the progression of the disease. In general, old age, reduced serum albumin concentration, end stage kidney failure, and sustained elevated SAA concentration are all associated with poor prognosis.^[15]

Diagnosis

Tissue biopsy using subcutaneous abdominal fat tissue aspiration is typically used as it is safe and sensitive. It is also possible to biopsy the rectal mucosa or minor salivary glands. Amyloidosis is confirmed by histological identification of amyloid deposits. At this point, amyloid typing with immunochemical staining is necessary, as the differential diagnosis includes AA amyloidosis,

There is evidence that eating amyloid fibers may lead to amyloidosis. This evidence is based on studies in cattle, chickens, mice, and cheetahs.[18] Thus, in a sense, SAA amyloidosis may be considered a contagious disease, although whether this occurs or is important in the development of naturally occurring amyloidosis remains unknown. Nevertheless, because amyloid fibers can be detected in muscle in low amounts, it raises some concern about whether people could develop amyloidosis as a result of ingesting meat from an animal with the disease.^[18]

References