Full Papers
Geographic variation in calcinosis cutis among patients with systemic sclerosis: a preliminary ecological analysis of water chemistry exposure in two U.S. cohorts
K. Myers1, A. Major2, T.M. Frech3
- Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN; and Department of Medicine, Tennessee Valley Healthcare System, Veterans Affairs, Nashville, TN, USA.
- Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN; and Department of Medicine, Tennessee Valley Healthcare System, Veterans Affairs, Nashville, TN, USA. tracy.frech@vumc.org
CER29
Full Papers
Received: 10/06/2026
Accepted : 29/06/2026
In Press: 21/07/2026
Abstract
OBJECTIVES:
Calcinosis cutis is a debilitating complication of systemic sclerosis (SSc) with poorly understood pathogenesis and no effective therapies. Environmental exposures, including drinking water mineral composition, have not been systematically evaluated as contributors to calcinosis risk. We report a preliminary ecological comparison of calcinosis prevalence in two geographically distinct SSc cohorts and examine differences in municipal water fluoridation coverage and water hardness as possible environmental variables.
METHODS:
We compared calcinosis prevalence in 84 SSc patients from Davidson County, Tennessee (Nashville metropolitan area) with 121 SSc patients from Salt Lake County, Utah (Salt Lake City metropolitan area) in a cross-sectional analysis. Water fluoridation status and fluoride concentration data were obtained from the CDC Water Fluoridation Reporting System whereas water hardness data were obtained from the USGS Water Quality Portal. Between-group differences in calcinosis prevalence were assessed using Fisher’s exact test and unadjusted odds ratios with 95% confidence intervals.
RESULTS:
Calcinosis was present in 20 of 84 patients (23.8%) in the Davidson County cohort and 6 of 121 patients (5.0%) in the Salt Lake County cohort (OR 5.93, 95% CI 2.27–15.49, p<0.001). Davidson County municipal water systems provide near-universal fluoridation at the EPA-optimal level of 0.70 mg/L (~96% of population on community water systems), with moderate water hardness (mean ~158 mg/L CaCO3). Salt Lake County has partial fluoridation coverage (~52% of population), with substantially higher water hardness (mean ~327 mg/L CaCO3).
CONCLUSIONS:
These data identify a significant difference in calcinosis prevalence between two SSc cohorts that co-vary with differences in municipal water fluoridation coverage. The inverse relationship with water hardness suggests that fluoride exposure, rather than calcium substrate alone, may contribute to the environmental risk for calcinosis in SSc. Prospective patient-level studies incorporating individual water source characterisation and comprehensive clinical covariate adjustment are warranted.
