Causes of AA amyloidosis: a systematic review

From a clinical perspective, there is a need for a reliable and comprehensive list of diseases causing AA amyloidosis. This list could guide clinicians in the evaluation of patients with AA amyloidosis in whom an obvious cause is lacking. In this systematic review, a PubMed, Embase and Web of Science literature search were performed on causes of AA amyloidosis published in the last four decades. Initially, 4066 unique titles were identified, but only 795 full-text articles and letters were finally selected for analysis. Titles were excluded because of non-AA type of amyloidosis, language, no full-text publication or irrelevance. Hundred and fifty diseases were initially reported to be associated with the development of AA amyloidosis. The presence of AA amyloid was proven in 208 articles (26% of all) of which 140 (67%) showed a strong association with an underlying disease process. Disease associations were categorized and 48 were listed as strong, 19 as weak, 23 as unclear, and 60 as unlikely. Most newly described diseases are not really unexpected because they often cause longstanding inflammation. Based on the spectrum of identified causes, a pragmatic diagnostic approach is proposed for the AA amyloidosis patient in whom an obvious underlying disease is lacking.