AA amyloidosis

AA amyloidosis is a form of amyloidosis, a disease characterized by the abnormal deposition of fibers of insoluble protein in the extracellular space of various tissues and organs. In AA amyloidosis, the deposited protein is serum amyloid A protein (SAA), an acute-phase protein which is normally soluble and whose plasma concentration is highest during inflammation.^[1]

AA amyloidosis
Specialty	Rheumatology

Causes

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]

Symptoms

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, 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.^[16]

Treatment

There are currently no approved treatments for systemic AA amyloidosis.^[13] 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.^[17]

Transmission of 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

1. Lachmann HJ, Goodman HJ, Gilbertson JA, Gallimore JR, Sabin CA, Gillmore JD, Hawkins PN (June 2007). (PDF). The New England Journal of Medicine. 356 (23): 2361–2371. doi:10.1056/NEJMoa070265. PMID 17554117. S2CID 18801734. Archived from the original (PDF) on 2014-01-09.
2. Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). "Chapter 5". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1.
3. Roberts JR, Mank VM, Wolf RE, Buxbaum JN, Mubashir D, Dhawan R, Ahmed MM, Kaur RJ (19 December 2022). Talavera F, Goldberg E (eds.). "AA (Inflammatory) Amyloidosis Clinical Presentation". MedScape.
4. Jung O, Haack HS, Buettner M, Betz C, Stephan C, Gruetzmacher P, et al. (November 2012). "Renal AA-amyloidosis in intravenous drug users--a role for HIV-infection?". BMC Nephrology. 13: 151. doi:10.1186/1471-2369-13-151. PMC 3519698. PMID 23171281.
5. d'Ythurbide G, Kerrou K, Brocheriou I, Hertig A (September 2012). "Reactive amyloidosis complicated by end-stage renal disease 28 years after liquid silicone injection in the buttocks". BMJ Case Reports. 2012: bcr2012006803. doi:10.1136/bcr-2012-006803. PMC 4543521. PMID 23035166.
6. Emekli U, Tümerdem B, Demiryont M (2002). "Rupture of a silicone gel mammary prosthesis and amyloidosis: a case report". Aesthetic Plastic Surgery. 26 (5): 383–387. doi:10.1007/s00266-002-2022-x. PMID 12432480. S2CID 6865930.
7. Goldman AB, Bansal M (March 1996). "Amyloidosis and silicone synovitis: updated classification, updated pathophysiology, and synovial articular abnormalities". Radiologic Clinics of North America. 34 (2): 375–94, xi. doi:10.1016/S0033-8389(22)00474-2. PMID 8633122. S2CID 251523786.
8. "AA Amyloidosis". Amyloidosis Foundation. Retrieved 9 January 2022.
9. "Amyloidosis: AA". Cleveland Clinic. Retrieved 9 January 2022.
10. Biasucci LM, Liuzzo G, Grillo RL, Caligiuri G, Rebuzzi AG, Buffon A, et al. (February 1999). "Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability". Circulation. 99 (7): 855–860. doi:10.1161/01.cir.99.7.855. PMID 10027805.
11. Lachmannn HJ (2015-03-19). "Long-Term Complications of Familial Mediterranean Fever". Familial Mediterranean Fever. Springer. ISBN 978-3319146157.
12. Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clinical Epidemiology. 6: 369–377. doi:10.2147/CLEP.S39981. PMC 4218891. PMID 25378951.
13. Roberts JR, Mank VM, Wolf RE, Buxbaum JN, Mubashir D, Dhawan R, Ahmed MM, Kaur RJ (2019-02-02). Talavera F, Goldberg E (eds.). "AA (Inflammatory) Amyloidosis". Medscape Reference.
14. "AA Amyloidosis". Amyloidosis Center. Boston University School of Medicin e.
15. Katagiri D, Noiri E, Hinoshita F (2013). "Multiple myeloma and kidney disease". TheScientificWorldJournal. 2013: 487285. doi:10.1155/2013/487285. PMC 3826468. PMID 24288486.
16. Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clinical Epidemiology. 6: 369–377. doi:10.2147/CLEP.S39981. PMC 4218891. PMID 25378951.
17. Fernández-Nebro A, Tomero E, Ortiz-Santamaría V, Castro MC, Olivé A, de Haro M, et al. (May 2005). "Treatment of rheumatic inflammatory disease in 25 patients with secondary amyloidosis using tumor necrosis factor alpha antagonists". The American Journal of Medicine. 118 (5): 552–556. doi:10.1016/j.amjmed.2005.01.028. PMID 15866260.
18. Murakami T, Ishiguro N, Higuchi K (March 2014). "Transmission of systemic AA amyloidosis in animals". Veterinary Pathology. 51 (2): 363–371. doi:10.1177/0300985813511128. PMID 24280941.

External links

• Booklet and explanatory video explaining the difference between the types of amyloidosis. Written by doctors at Mayo Clinic, Boston University, Indiana University and others
• UK NHS National Amyloidosis Centre Patient Information Site: information on AA amyloidosis