Chapter 56 - Drug-induced lupus

Abstract

Drug-induced lupus (DIL) is a side effect of long-term use of up to 100 medications. Rheumatologic symptoms including fever, malaise, weight loss, polyarticular arthralgias, and symmetric myalgias develop in less than 1% of treated patients for some and less than 0.1% for most of the drugs with propensity to induce lupus-like symptoms. However, autoantibody induction by some drugs is considerably more common, and autoantibody serology can be indistinguishable from that of systemic lupus erythematosus. The defining, although retrospective, feature of DIL is resolution of symptoms after discontinuation of the suspected medication, usually without the need for immunosuppressive agents. Several genetic factors predispose to DIL, but dose and duration of therapy are the predominate risks. It is unlikely that the ingested, parent compound mediates DIL, and reactive metabolites of multiple pharmacological classes of lupus-inducing drugs are candidate initiators. Experimental studies support several possible mechanisms to account for autoimmunity in DIL, including specific and nonspecific activation of immune cells, cytotoxicity-mediated release of autoantigens, and the disruption of immune tolerance machinery. From the basic science perspective, DIL is a fascinating window into how the immune system normally acquires self-tolerance and how these mechanisms can fail, resulting in the development of autoimmunity and lupus-like disease.