AA amyloidosis

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AA amyloidosis
Classification and external resources
ICD-10 E85
ICD-9-CM 277.3
DiseasesDB 16
eMedicine med/3388

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]

Causes[edit]

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. A natural history study of AA amyloidosis patients published in the New England Journal of Medicine reported a number of conditions associated with AA amyloidosis.[1] The most common presentation of AA amyloidosis is renal in nature, including proteinuria, nephrotic syndrome and progressive development of renal insufficiency leading to End Stage Renal Disease (ESRD) and need for renal replacement therapy (e.g. dialysis or renal transplantation).[3]

Pathology[edit]

In a healthy individual, the median plasma concentration of SAA is 3 mg per liter.[7] 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.[8] 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.[9]

The AA protein is mainly deposited in the liver, spleen and kidney, and AA amyloidosis can lead to nephrotic syndrome and ESRD.[10][11] Natural history studies show, however, that it is the renal involvement that drives the progression of the disease. In general, old age, reduced serum albumin concentration, end stage renal failure, and sustained elevated SAA concentration are all associated with poor prognosis.[12]

There are currently no approved treatments for systemic AA amyloidosis.[10] 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 treaments to slow down the decline of their renal function, such as angiotensin II receptor blockers or angiotensin converting enzyme inhibitors.[13]

Current Clinical Research[edit]

Kiacta - (eprodisate disodium) is currently being evaluated as a protector of renal function in AA amyloidosis. Kiacta, inhibits the formation and deposition of the amyloid A fibrils into the tissues.[14]

Transmission of amyloidosis[edit]

There is evidence that eating amyloid fibers may lead to amyloidosis. This evidence is based on studies in cattle, chickens, mice, and cheetahs.[15] 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.[15]

References[edit]

  1. ^ a b Lachmann HJ, Goodman HJ, Gilbertson JA et al. (June 2007). "Natural history and outcome in systemic AA amyloidosis" (PDF). New England Journal of Medicine 356 (23): 2361–71. doi:10.1056/NEJMoa070265. PMID 17554117. 
  2. ^ Chapter 5 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.
  3. ^ Richa Dhawan, MD; Mohammed Mubashir Ahmed MD; Eisha Mubashir, MD; Joel N Buxbaum, MD; Ratinder J Kaur MD. "AA (Inflammatory) Amyloidosis Clinical Presentation". 
  4. ^ d'Ythurbide, G; Kerrou, K; Brocheriou, I; Hertig, A (2012). "Reactive amyloidosis complicated by end-stage renal disease 28 years after liquid silicone injection in the buttocks". Case Reports 2012: bcr2012006803. doi:10.1136/bcr-2012-006803. PMID 23035166.  edit
  5. ^ Emekli, U; Tümerdem, B; Demiryont, M (2002). "Rupture of a silicone gel mammary prosthesis and amyloidosis: A case report". Aesthetic Plastic Surgery 26 (5): 383–7. doi:10.1007/s00266-002-2022-x. PMID 12432480.  edit
  6. ^ Goldman, A. B.; Bansal, M (1996). "Amyloidosis and silicone synovitis: Updated classification, updated pathophysiology, and synovial articular abnormalities". Radiologic clinics of North America 34 (2): 375–94, xi. PMID 8633122.  edit
  7. ^ Biasucci LM, Liuzzo G, Grillo RL, Caligiuri G, Rebuzzi AG, Buffon A, Summaria F, Ginnetti F, Fadda G, Maseri A. (February 1999). "Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability.". Institute of Cardiology, Catholic University of the Sacred Heart. PMID 10027805. 
  8. ^ Familial Mediterranean Fever. Springer. ISBN 3319146157. 
  9. ^ Diego Real de Asúa, Ramón Costa, Jose María Galván, María Teresa Filigheddu, Davinia Trujillo, Julen Cadiñanos (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clinical Epidemiology. doi:10.2147/CLEP.S39981. 
  10. ^ a b "AA (Inflammatory) Amyloidosis". Medscape Reference. 
  11. ^ "AA Amyloidosis". BU Amyloid Treatment & Research Program. 
  12. ^ Daisuke Katagiri, Eisei Noiri, and Fumihiko Hinoshita (2013). "Multiple Myeloma and Kidney Disease". The Scientific World Journal. 
  13. ^ Fernández-Nebro A. "Treatment of rheumatic inflammatory disease in 25 patients with secondary amyloidosis using tumor necrosis factor alpha antagonists.". AM J Med. p. 118(5): 552-6. Retrieved 12 June 2015. 
  14. ^ "Efficacy and Safety Study of KIACTA in Preventing Renal Function Decline in AA Amyloidosis". Clinicaltrials.gov. May 15, 2015. Retrieved 12 June 2015. 
  15. ^ a b 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. 

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