Secondary, AA, Amyloidosis

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Key points

  • Secondary, AA, amyloidosis can complicate any long-term inflammatory disorder.

  • Extracellular deposition of serum amyloid A (SAA) protein as amyloid primarily affects kidney function, with proteinuria as first clinical manifestation.

  • Biopsy is the diagnostic gold standard and serum amyloid P component scintigraphy can help to define amyloid type and distribution.

  • Targeted anti-inflammatory treatment promotes normalization of circulating SAA levels, preventing further amyloid deposition and renal

Formation of AA Amyloid

Amyloid is an amorphous and insoluble proteolytic resistant material derived from the spontaneous aggregation of fibrils composed of twisted protofilaments.1, 2, 3 Protofilaments derive from misfolded proteins, called amyloid precursors, and share a common X-ray diffraction fingerprint of a β-sheet structure in cross-β conformation.4 At least 30 different proteins can be deposited as amyloid in humans. In addition to the fibrillary protein a number of other proteins are also present in all

Epidemiology

AA amyloidosis has almost certainly been underdiagnosed; the estimated incidence varies from 1 to 2 cases per million person-years, but is now clearly decreasing.49, 50, 51, 52, 53, 54 Prevalence in chronic inflammatory diseases is 5% to 10% or substantially higher if asymptomatic patients are considered.31, 55, 56, 57 A recently reported rise in the median age of diagnosis, from 50 to 70 years, probably reflects changes in the underlying diseases and improved access to effective therapies.58

General Management

Widespread availability of effective agents to control chronic inflammatory conditions, such as antibiotics and biologics, are likely to continue to reduce the incidence of AA amyloidosis in the future (Table 1).98, 99, 100, 101, 102 Once AA amyloid is present, long-term suppression of the circulating SAA level is pivotal to improving patient and renal outcomes,59, 96, 103, 104 and must be achieved by aggressively treating the underlying disease with the aim of persistent normalization of the

Summary

AA amyloidosis can complicate any chronic inflammatory disorders. Despite its rarity, physicians from many specialities may encounter affected patients due to variety of possible underlying causes. Proteinuria is the typical presentation and progression to renal insufficiency occurs if the diagnosis is missed. A routine urine dipstick in patients with inflammatory conditions is an inexpensive screening test. Histology is required for the final diagnosis and positive immunohistochemistry for AA

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