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AA amyloidosis
Etiology:
1) chronic suppuration or tissue breakdown
a) rheumatoid arthritis (50%)
b) ankylosing spondylitis
c) Crohn's Disease
d) chronic infection
1] tuberculosis
2] osteomyelitis
3] infection in paraplegic patients
e) bronchietasis
2) familial Mediterranean fever
3) Castleman disease
4) lymphoma
6) vasculitis
Pathology:
1) amyloid contains protein A, a fragment of serum acute phase protein (SAA)
2) amyloid fibrils in AA amyloidosis mostly deposit in liver, spleen & kidneys
3) end-stage renal disease is major cause of death (40-60%)
Clinical manifestations:
1) renal failure (nephrotic syndrome) is most common presentation
2) gastrointestinal* (image) [5]
a) chronic diarrhea
b) GI bleeding
c) abdominal pain
d) malabsorption
3) hepatosplenomegaly
4) heart failure [1]
Laboratory:
- serum protein electrophoresis: polyclonal gammopathy
- urinalysis: hematuria & pyuria minimal or absent
Special laboratory:
- electrocardiogram: low voltage
- renal biopsy
- yellow-green birefringence in polarized light
- Congo red stain
- thioflavin-T stain
Differential diagnosis:
- AL-amyloidosis
- serum protein electrophoresis: monoclonal gammopathy (M spike)
- post-infectious glomerulonephritis
- serum complement low
- active urine sediment: hematuria, erythrocyte casts
- lupus nephritis:
- low serum complement C3, serum complement C4 & CH50
- anti-dsDNA Ab in serum present in high titer
- hematuria, erythrocyte casts in urine
- IgA nephropathy
- microscopic hematuria
- nephrotic syndrome is an unusual presentation
- interstitial nephritis
- pyuria
- proteinuria generally not nephrotic range unless NSAID-induced
Management:
1) tocilizumab has been used in patients with rheumatoid arthritis [1,5]
2) Fibrillex (Neurochem Inc, Phase II/III clinical trials in 2003) <orphan drug status in the U.S. and in Europe>
3) poor prognosis: 5 year survival 50%
General
amyloidosis
References
- Medical Knowledge Self Assessment Program (MKSAP) 11, 18.
American College of Physicians, Philadelphia 1998, 2018.
- http://www.neurochem.com/ResearchActivities.htm
- Bodin K et al.
Antibodies to human serum amyloid P component eliminate
visceral amyloid deposits.
Nature 2010 Nov 4; 468:93.
- Obici L, Raimondi S, Lavatelli F, Bellotti V, Merlini G.
Susceptibility to AA amyloidosis in rheumatic diseases:
a critical overview.
Arthritis Rheum. 2009 Oct 15;61(10):1435-40.
PMID: 19790131 Free Article
- Izuka S, Yamashita H
Images in Clinical Medicine. Gastrointestinal Amyloidosis.
N Engl J Med 2021; 384:2144
PMID: 34077646
https://www.nejm.org/doi/full/10.1056/NEJMicm2034179
- NEJM Knowlege+
- Lane T, Pinney JH, Gilbertson JA et al
Changing epidemiology of AA amyloidosis: clinical observations over 25 years at
a single national referral centre.
Amyloid. 2017 Sep;24(3):162-166.
PMID: 28686088 Clinical Trial.
- Lachmann HJ, Goodman HJ, Gilbertson JA et al
Natural history and outcome in systemic AA amyloidosis.
N Engl J Med. 2007 Jun 7;356(23):2361-71.
PMID: 17554117 Free article.
https://www.nejm.org/doi/pdf/10.1056/NEJMoa070265