Table 2.

Summary of the Strongest Epidemiologic Data and Research Needs Pertaining to Environmental Agents and Autoimmune Diseases^*

Environmental Agent and Autoimmune Disease	Summary of Epidemiologic Data	Research Needs
Agents We Are Confident Contribute to Autoimmune Disease
Solvents and SSc	Multiple studies in different populations with different designs and exposure assessment methods; 2-fold relative risk generally seen with “ever” exposed; publication bias considered; limited evidence of exposure-response gradient	Clarification of role of specific solvent(s), timing of exposure in relation to disease onset, effects of intensity versus duration of exposure, potential contribution of non-occupational sources of exposure; gender differences in exposure or in response to exposures; mechanism studies
Silica and SSc, RA, SLE, and ANCA-related vasculitis	Multiple studies in different populations with different designs and exposure assessment methods; 2-to 4-fold relative risk generally seen with “ever” exposed, evidence of exposure-response gradient	Clarification of timing of exposure in relation to disease onset, effects of intensity versus duration of exposure, potential contribution of non-occupational sources of exposure; gender differences in exposure or in response to exposures; mechanism studies
Cigarette smoke and seropositive RA	Multiple studies in different populations with different designs; 1.5-to 2-fold relative risk generally seen with “ever” exposed and all RA, evidence of exposure-response gradient and higher risks with anti-CCP+ RA; three studies of interaction with human leukocyte antigen genotype	Contribution of tobacco smoke (and other tobacco products) to seronegative RA and other phenotypes; gender differences in exposure or in response to exposures; mechanism studies
Sunlight and MS (higher exposure is protective)	Multiple studies in different populations with different designs and exposure measures; strong inverse associations seen; examination of age periods of effect and genetic interactions	Contribution of various sources of exposure and quantification of exposure, additional studies of exposure and age windows, mechanism studies
Agents We Believe Likely Contribute to Autoimmune Disease
Epstein-Barr virus and MS	Multiple studies showing increased antibody presence or titers in patients with MS; dose effect; one study of interaction with DR15	Additional prospective studies establishing temporal relation between infection and disease onset
Early introduction of complex foods and T1D, GSE	Many studies in different populations, with different designs, but results are quite variable (positive, null, and inverse associations seen)	Clarification of role of specific antigen(s) and timing / order of introduction
Dietary vitamin D and MS (higher exposure is protective)	Supported by two prospective studies in the United States; effects seen among whites	Confirmation in other ethnic groups, examination of exposure-response, relevant periods of exposure, and potential differences in sources of dietary vitamin D
Solvents and MS	Multiple studies in different populations with different designs; 2-fold relative risk generally seen with “ever” exposed; publication bias not considered, exposure assessment more limited than in SSc studies	Examination in newer studies with expanded exposure assessment; clarification of role of specific solvent(s)
Ionizing radiation and Hashimoto thyroiditis, Graves’ disease	Multiple studies establish radiation treatment (i.e., cancer therapy) as a cause of these diseases; studies among atomic bomb survivors, populations exposed after Chernobyl, and occupationally-exposed workers show conflicting results for risk of disease and for development of anti-thyroid antibodies	Clarification of the significance of development of anti-thyroid antibodies in the absence of clinically overt disease; additional studies examining exposure-response patterns
Current cigarette smoke and SLE, MS	Multiple studies; more variability in results compared with RA studies, evidence of exposure-response gradient or genetic interactions not established	Clarification of potential genetic interactions or higher risk subgroups; exposure-response gradients, mechanism studies
Cigarette smoke and Crohn’s disease	Multiple studies showing 1.5-to 2-fold relative risk among current smokers	Clarification of potential genetic interactions or higher risk subgroups; exposure-response gradients, mechanism studies
Cigarette smoke and Hashimoto thyroiditis, Graves’ disease	Multiple studies; 2-to 3-fold relative risk with “ever” exposed; higher risk in patients with ophthalmologic involvement	Clarification of potential genetic interactions or higher risk subgroups; exposure-response gradients, mechanism studies
Cigarette smoke and ulcerative colitis (higher exposure is protective)	Multiple studies showing decreased risk among current smokers (RR 0.6) and increased risk (RR 1.8) among former smokers	Clarification of potential genetic interactions or higher risk subgroups; exposure-response gradients, mechanism studies
Agents We Believe Are Unlikely to Contribute to an Autoimmune Disease
Hair dyes and SLE	Multiple case control studies showing a lack of association and only a single small study suggesting an association	None

^*Abbreviations: anti-neutrophil cytoplasmic antibody (ANCA), anti-cyclic citrullinated peptide antibody (CCP), gluten-sensitive enteropathy (GSE, celiac disease), multiple sclerosis (MS), primary biliary cirrhosis (PBC), rheumatoid arthritis (RA), relative risk (RR), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and type 1 diabetes (T1D).

For italicized agents higher exposures are protective for the development of disease.