Drawing attention to a neglected injecting-related harm: A systematic review of AA-amyloidosis among people who inject drugs.

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 synthesise 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 (I2: 86%); 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. Proportions of PWID with AA amyloidosis at post-mortem range from 1.6% (Germany) to 22.5% (Serbia). Biopsy studies report 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 (32.8%). Treatment difficulties, end-stage renal failure (40%), and premature death from sepsis (33%) 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%) appear 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