There is no intrinsic difference between drugs and other chemicals, and it has been suggested that some fraction of idiopathic lupus is caused by environmental agents, especially aromatic amines and hydrazines (Reidenberg 1983). Adulteration of rape-seed oil with aniline led to a large number of serious autoimmune reactions in Spain (Kammuller et al. 1988). Aniline is an aromatic amine that, when heated with vegetable oils, forms fatty acid anilides. However, it is still not clear exactly which component of the adulterated oil was responsible for the syndrome or what the mechanism of the syndrome was. Other agents that have been of concern are p-aminobenzoic acid (PABA) (Mackie and Mackie 1999) and paraphenylene diamine hair dyes (Steinberg et al. 1991). Although PABA and aniline-based hair dyes can be sensitizers, there is no clear association with the induction of lupus. Exposure to specific chemicals, such as hydrazine, has also been reported to induce lupus (Reiden-berg et al. 1983). Administration of trichloroethylene led to a significant acceleration in a lupus-like autoimmune syndrome in female MRL+/+ mice, a strain that is predisposed to lupus (Khan et al. 1995). An epidemiologic link between trichloroethylene exposure and lupus-related symptoms has been reported (Kilburn and Warshaw 1992).
Although it is possible that some idiopathic lupus may be due to chemical exposure, it seems unlikely that this represents a significant cause of idiopathic lupus. The observation that large doses of pharmaceutical agents are required to induce a lupuslike syndrome may provide an explanation for this apparent failure of environmental agents to cause a significant incidence of lupus. Specifically, with the exception of natural food constituents, it would be extremely rare to be exposed to the same "dose" of environmental agents that are associated with drug-induced lupus. Ingesting large amounts of alfalfa sprouts, which contain relatively high levels of an unusual amino acid, L-canavanine, causes an autoimmune syndrome in monkeys (Malinow et al.
1982). The amount required is unlikely to be consumed by many humans, but consumption of alfalfa tablets from health food stores is a concern.
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