ABSTRACT
Exposure to a wide variety of synthetic compounds has been causally related to the induction of autoimmunity. The vast majority of implicated agents are deliberately ingested medications, and these are associated most often with development of lupus-like signs and/or symptoms. However, it is useful to split these phenomena into distinctive categories of xenobiotic-induced autoimmune diseases as follows (Table 1):
Drug exposure that is temporally related to syndromes which resemble systemic lupus erythematosus (SLE), a spontaneous, idiopathic autoimmune disease. From a clinical perspective this category encompasses both drug-induced lupus and drug-associated exacerbation of SLE or initiation of SLE flares. The latter group involves cases of pre-existing SLE which remain or recur after withdrawal of the implicated medication, while bonafide drug-induced lupus usually occurs in the setting of a previously normal immune system and disappears after discontinuation of the medication. These are mechanistically separate phenomena as discussed below.
Drugs or environmental agents associated with distinct autoimmune diseases, including symptoms or signs sometimes occurring in SLE. This category encompasses drug-induced hemolytic anemia, eosinophilia-myalgia syndrome associated with L-tryptophan ingestion, toxic oil syndrome associated with ingestion of aniline-adulterated cooking oil, silicosis associated with inhaled silica or asbestos dust and autoimmunity associated with vinyl chloride exposure. A so-called “adjuvant disease” associated with silicone breast implants is of dubious validity.
Environmental agents suspected of causing lupus-like disease based solely on studies in experimental animals. The principal examples in this category are the lupus-like syndrome associated with alfalfa sprouts (L-canavanine) in monkeys and scleroderma-like autoimmunity associated with heavy metals in rats and mice.
Drugs known to be immune modulating that produce autoimmune features in a minority of treated patients. Cyclosporine A has been reported to precipitate graft-vs-host disease (GVHD) after withdrawal from patients receiving autologous bone marrow transplants. Gold therapeutics might be included in this heterogeneous category. Therapeutic biologics such as interleukin-2, interferon-α,-β, and -γ, and anti-tumor necrosis factor-α have been occasionally associated with a variety of musculoskeletal manifestations and serological features of autoimmunity.
