title: AA amyloidosis complicating the hereditary periodic fever syndromes.
abstract: OBJECTIVE
  AA amyloidosis is a life-threatening complication of the hereditary periodic fever syndromes (HPFS), which are otherwise often compatible with normal life expectancy. This study was undertaken to determine the characteristics, presentation, natural history, and response to treatment in 46 patients who had been referred for evaluation at the UK National Amyloidosis Centre.
  
  
  METHODS
  Disease activity was monitored by serial measurement of serum amyloid A. Renal function was assessed by measurement of serum creatinine and albumin levels, the estimated glomerular filtration rate, and proteinuria from 24-hour urine collections. The amyloid load was measured by serum amyloid P scintigraphy.
  
  
  RESULTS
  Twenty-four patients had familial Mediterranean fever, 12 patients had tumor necrosis factor receptor-associated periodic syndrome, 6 patients had cryopyrin-associated periodic syndromes, and 4 patients had mevalonate kinase deficiency. The median age at onset of HPFS was 5 years; median age at presentation with AA amyloidosis was 38 years. Diagnosis of an HPFS had not been considered prior to presentation with AA amyloidosis in 23 patients (50%). Eleven patients (24%) had end-stage renal failure (ESRF) at presentation; of these, 3 had received transplants prior to referral. A further 13 patients developed ESRF over the followup period, with 10 undergoing renal transplantation. The median time to progression to ESRF from onset of AA amyloidosis was 3.3 years (interquartile range [IQR] 2-8), with a median time to transplant of 4 years (IQR 3-6). Eleven patients (24%) died. The median survival in the entire cohort was 19 years from diagnosis of AA amyloidosis. Of the 37 patients who were treated successfully, or in whom at least partial suppression of the underlying HPFS was achieved, 17 (46%) showed amyloid regression, 14 (38%) showed a stable amyloid load, and 2 (5%) showed increased amyloid deposition over the followup period.
  
  
  CONCLUSIONS
  AA amyloidosis remains a challenging and serious late complication of HPFS; however, outcomes are excellent when HPFS is diagnosed early enough to allow effective treatment, thus preventing or retarding further amyloid deposition and organ damage.
authors.affiliation: National Amyloidosis Centre, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: Thirusha
authors.initials: T
authors.lastname: Lane
authors.forename: Jutta M
authors.initials: JM
authors.lastname: Loeffler
authors.forename: Dorota M
authors.initials: DM
authors.lastname: Rowczenio
authors.forename: Janet A
authors.initials: JA
authors.lastname: Gilbertson
authors.forename: Alison
authors.initials: A
authors.lastname: Bybee
authors.forename: Tonia L
authors.initials: TL
authors.lastname: Russell
authors.forename: Julian D
authors.initials: JD
authors.lastname: Gillmore
authors.forename: Ashutosh D
authors.initials: AD
authors.lastname: Wechalekar
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D002648:Child; D015331:Cohort Studies; D056587:Cryopyrin-Associated Periodic Syndromes / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D018450:Disease Progression; D010505:Familial Mediterranean Fever / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D005260:Female; D056660:Hereditary Autoinflammatory Diseases / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D008875:Middle Aged; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000685:Serum Amyloid A Protein