Prior autoimmune disease and risk of monoclonal gammopathy of undetermined significance and multiple myeloma: A systematic review

Background: Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated.A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma. Methods: A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011. Results: A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-Analysis. "Any autoimmune disorder" was associated with an increased risk of both MGUS [n 1/4 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14-1.75] and multiple myeloma (n>2,530 patients; RR 1.13, 95% CI, 1.04-1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21-2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25-1.80). Conclusions: Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin. Impact: Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma.