AA amyloidosis

Causes

AA amyloidosis is a complication of a number of inflammatory diseases and infections, 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). A natural history study of AA amyloidosis patients reported a number of conditions associated with AA amyloidosis:

• Autoimmune diseases and inflammatory diseases

  • Adult-onset Still's disease
  • Ankylosing spondylitis
  • Behcet's disease
  • Crohn's disease and ulcerative colitis
  • Familial Mediterranean fever (FMF)
  • Giant cell arteritis
  • Gout
  • Hyper-IgD syndrome
  • Juvenile idiopathic arthritis
  • Muckle–Wells syndrome (MWS)
  • Neonatal-onset multisystem inflammatory disease
  • Psoriatic arthritis
  • Polyarteritis nodosa
  • Polymyalgia rheumatica
  • Rheumatoid arthritis
  • Sarcoidosis
  • Takayasu's arteritis
  • TNF receptor associated periodic syndrome

• Chronic infections

  • Bronchiectasis
  • Chronic cutaneous ulcers
  • Chronic osteomyelitis
  • Chronic pyelonephritis
  • Hepatitis B
  • Leprosy
  • Tuberculosis
  • Whipple's disease

• Cancer

  • Acute myeloid leukaemia
  • Adenocarcinoma of the gut
  • Basal cell carcinoma of the skin
  • Castleman's disease
  • Chronic myeloid leukaemia
  • Chronic lymphoid leukaemia
  • Follicular dendritic cell sarcoma
  • Gastrointestinal stromal tumours
  • Hairy cell leukaemia
  • Hepatic adenoma
  • Hodgkin's lymphoma
  • Mesothelioma
  • Non-Hodgkin lymphoma
  • Non-small-cell lung cancer
  • Ovarian carcinoma
  • Papillary bladder carcinoma
  • Pleomorphic splenic sarcoma
  • Renal cell carcinoma
  • Small cell carcinoma of the bladder
  • Uterine leiomyosarcoma
  • Waldenstrom's macroglobulinaemia

• Chronic foreign body reaction

• Silicone-induced granulomatous reaction

• Immunodeficiencies

  • Common variable immunodeficiency
  • Cyclic neutropenia
  • HIV/AIDS
  • Hypogammaglobulinaemia
  • X-linked agammaglobulinaemia

• Other conditions predisposing to chronic infections

  • Cystic fibrosis
  • Epidermolysis bullosa
  • IV drug use
  • Jejuno-ileal bypass
  • Paraplegia

• Obesity

• SAPHO syndrome

• Schnitzler syndrome

Symptoms

Signs and symptoms of amyloidosis can vary depending on the affected organ. AA amyloidosis commonly affects kidneys, liver, and stomach.

Pathology

In a healthy individual, the median plasma concentration of SAA is 3 mg per liter. 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. 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.

The AA protein is mainly deposited in the liver, spleen and kidney, and AA amyloidosis can lead to nephrotic syndrome and ESRD. 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.

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, AL amyloidosis, hereditary amyloidosis, dialysis-related amyloidosis and age-related systemic amyloidosis. Testing of serum and urine for monoclonal immunoglobulins and of serum for free light chains may help rule out immunoglobulin light chain amyloidosis, while genetic testing may be used if hereditary amyloidosis is suspected.

Treatment

There are currently no approved treatments for systemic AA amyloidosis. The current standard of care includes treatments for the underlying inflammatory disease with anti-inflammatory drugs, immunosuppressive agents or biologics. AA amyloidosis patients are also receiving treatments to slow down the decline of their renal function, such as angiotensin II receptor blockers or angiotensin converting enzyme inhibitors.

Transmission

There is evidence that eating amyloid fibers may lead to amyloidosis. This evidence is based on studies in cattle, chickens, mice, and cheetahs.

References

References

1. (June 2007). "Natural history and outcome in systemic AA amyloidosis". The New England Journal of Medicine.
2. (2007). "Robbins Basic Pathology". Saunders.
3. (19 December 2022). "AA (Inflammatory) Amyloidosis Clinical Presentation". MedScape.
4. (2012). "AA amyloidosis: basic knowledge, unmet needs and future treatments.". [[Swiss Medical Weekly]].
5. (May 2010). "[AA amyloidosis complicating sarcoidosis: two cases and literature review].". Revue de Médecine Interne.
6. (31 May 2023). "AA amyloidosis associated with cancers.". Nephrology, Dialysis, Transplantation.
7. (2013). "Nephrotic Syndrome Associated with Lung Cancer: A Rare Case of Malignancy Associated with AA Amyloidosis". Case Reports in Nephrology.
8. (November 2003). "Systemic AA amyloidosis and nephrotic syndrome associated with small cell carcinoma of the bladder.". Nephrology, Dialysis, Transplantation.
9. (September 2012). "Reactive amyloidosis complicated by end-stage renal disease 28 years after liquid silicone injection in the buttocks". BMJ Case Reports.
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12. (November 2012). "Renal AA-amyloidosis in intravenous drug users--a role for HIV-infection?". BMC Nephrology.
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16. (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clinical Epidemiology.
17. (2019-02-02). "AA (Inflammatory) Amyloidosis". Medscape Reference.
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20. (May 2005). "Treatment of rheumatic inflammatory disease in 25 patients with secondary amyloidosis using tumor necrosis factor alpha antagonists". The American Journal of Medicine.
21. (March 2014). "Transmission of systemic AA amyloidosis in animals". Veterinary Pathology.