The epidemiology of undifferentiated connective tissue disease in women: Assessment of risks of reproductive history and exogenous estrogens, medical devices, and environmental chemicals.

Abstract

Classification criteria for the systemic rheumatic conditions such as systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have improved the precision of clinical diagnoses and the validity of inferences based on clinical research, but some non-specific rheumatic conditions do not satisfy current classification criteria. The term undifferentiated connective tissue disease (UCTD) has been proposed for patients who do not meet criteria for any other rheumatic disease but who have signs, symptoms, and laboratory abnormalities that suggest a connective tissue disease. UCTD and other atypical connective tissue disorders have been reported in association with silicone breast implants and other environmental exposures. A case-control study of 205 women with UCTD in Michigan and Ohio and 2,095 healthy population-based controls was conducted to investigate multiple potential risk factors. Case status was determined by medical record review, and occupational, reproductive, and lifestyle data were obtained through a telephone questionnaire administered to all cases and controls. Odds ratios (OR) and 95 percent confidence intervals (CI) were calculated using conditional logistic regression, adjusting for age and year of birth, for all risk factors. The odds of exposure to silicone-containing medical devices (OR = 2.81, 95% CI 1.34-5.89) and to non-silicone-containing devices (OR = 1.93, 95% CI 1.15- 3.22) were significantly higher in cases than in controls, but breast implants were not significantly associated with UCTD (0R = 2.22, 95% CI 0.65-7.57). Women with UCTD were more likely to have used oral contraceptives (OR = 1.68, 95% CI 1.18-2.39) and estrogen replacement therapy (OR = 2.09, 95% CI 1.38-3.17) than controls. Self-reported occupational exposures to silicones and solvents were confirmed by expert review, blinded to case or control status. Expert-reviewed exposures to paint thinners and removers (OR = 2.73.95% CI 1.80-4.16) were significantly more likely in cases than controls. As the first epidemiologic investigation of risk factors for UCTD, this study suggests that certain silicones, estrogen during the menopausal transition, and petroleum distillates increase the risk of UCTD in women. The etiology of UCTD is unknown, but these environmental triggers may directly influence the pathogenesis of or induce an autoimmune response in UCTD or other connective tissue diseases.