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Abstract: Background and Aims: Chronic skin and soft tissue infections (SSTI) among people who inject drugs (PWID) can lead to AA amyloidosis: a serious, yet neglected, multi‐organ disease. We aim to synthesize findings on the epidemiology, risk factors, clinical outcomes, screening recommendations and challenges to treatment for AA amyloidosis among PWID. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). We searched the following bibliographic databases in July 2017: CINAHL Plus, Embase, Global Health, MEDLINE, PsycEXTRA, PsycINFO and SCOPUS. Studies were included if they investigated AA amyloidosis in PWID. Studies were not restricted to location, study type, year or language of publication. Study heterogeneity precluded meta‐analysis; we present a narrative review of the literature. Results: Thirty‐seven papers from eight countries met inclusion criteria. A total of 781 PWID are reported on, of whom 177 had AA amyloidosis. Where disease causality is established, it is attributed to chronic inflammation caused by injecting‐related SSTIs. Most (88.7%) PWID with AA amyloidosis had SSTIs. The proportion of PWID with AA amyloidosis at post‐mortem ranged from 1.6% (Germany) to 22.5% (Serbia). Biopsy studies reported from 5.26% (Portugal) to 50% (Germany) of AA amyloidosis in PWID with suspected or known kidney disease. Following diagnosis, the typical trajectory for PWID with AA amyloidosis was rapid deterioration of renal function requiring haemodialysis. Treatment difficulties, end‐stage renal failure and premature death from sepsis were observed. Good outcomes, including reversibility of AA amyloidosis, are attributed to rapid treatment of the underlining inflammation and injecting cessation. Notably, given the population in question, no studies were published in addiction or harm reduction journals; most (92%) appeared in specialist nephrology and medical journals. Conclusion: There is strong evidence of an association between skin and soft tissue infections (SSTIs) and AA amyloidosis. Among people who inject drugs, injecting‐related SSTIs are a significant cause of morbidity and premature mortality and there is evidence of increasing SSTI prevalence. Limitations in the literature make it difficult to estimate AA amyloidosis prevalence among people who inject drugs. [ABSTRACT FROM AUTHOR]