Pharma, and Unilever. The other authors have no conflict of interest to declare. ACKNOWLEDGMENTS The content in this manuscript has not been published or submitted for publication elsewhere. All authors have contributed significantly and are in agreement with the content of the manuscript. AUTHOR CONTRIBUTIONS Conceptualization: SGK, SPP; Data Curation: SPP; Formal Analysis: SPP; Methodology: SGK, SK, SPP; Supervision: SGK, SK; Visualization: SPP, RK, MB; Writing - Original Draft Preparation: SPP, RK, MB; Writing - Review and Editing: SPP, RK, MB, SK, SGK. Sagar P. Patel 1 , Raveena Khanna 1 , Micah Belzberg 1 , Sewon Kang 1 and Shawn G. Kwatra 1,* 1 Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA * Corresponding author e-mail: skwatra1@jhmi. edu REFERENCES Araviiskaia E, Berardesca E, Bieber T, Gontijo G, Sanchez Viera M, Marrot L, et al. The impact of airborne pollution on skin. 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Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium and arsenic. Toxicol Appl Pharmacol 2008;233:92e9. Wei J, Zhang JJ, Ji JS. Association of environmental exposure to heavy metals and eczema in US population: Analysis of blood cadmium, lead, and mercury. Arch Environ Occup Health 2018:1e13. Weng CH, Hsu CW, Hu CC, Yen TH, Chan MJ, Huang WH. Blood lead level is a positive predictor of uremic pruritus in patients undergoing hemo- dialysis. Ther Clin Risk Manag 2017;13:717e23. Pediatric to Adult Shift in Vitiligo Onset Suggests Altered Environmental Triggering Journal of Investigative Dermatology (2020) 140, 241e243; doi:10.1016/j.jid.2019.06.131 TO THE EDITOR Vitiligo is a common autoimmune disease in which the destruction of melanocytes results in patches of depigmented skin, sometimes in asso- ciation with other concomitant auto- immune diseases (Picardo and Taı ¨eb, 2019). Vitiligo heritability is 46% e 72%, underscoring the importance of both genetic and environmental con- tributions. However, although genome- wide association studies have identified 50 vitiligo risk loci, no environmental triggers are known with certainty (Roberts and Spritz, 2018). Epidemiologic studies have shown that a number of autoimmune diseases are increasing in incidence and prevalence in industrialized countries (Lerner et al., 2016; Wang et al., 2015; Bach, 2018), sometimes paralleled by earlier disease onset (Karvonen et al., 1999; Wang et al., 2015). Hypotheses to explain these trends include altered timing and increasing frequency of exposures to in- fectious agents (Bach, 2018) and a wide variety of other possible environmental triggers (Cojocaru et al., 2008). There are no reported longitudinal prevalence or incidence data for vitiligo, so to detect clues to possible environmental triggers we analyzed historical trends in vitiligo age-of-onset. Vitiligo consists of two major age-of- onset subgroups: early-onset (mean 10.3  5.6 years; 38.4% of cases) and late-onset (mean 34.0  14.5 years; 61.6% of cases) (Jin et al., 2019). The principal underlying genetic dif- ference is the specific association of early-onset vitiligo with a major histo- compatibility complex class II regula- tory haplotype, rs145954018del- rs9271597A, that increases HLA gene expression and may accelerate the loss of immune tolerance. Here, we analyzed self-reported vitiligo age-of- onset in a cohort of 4,406 unrelated North American and European Cauca- sian cases incident from 1951-2013. As shown in Figure 1, over the study period vitiligo age-of-onset exhibited remarkable change, with mean age-of- onset more than doubling, from 14.7  9.3 years in 1951 to 31.8  20.2 years in 2013. The pattern of age-of- onset increase appeared generally similar in vitiligo cases from both North America and Europe (Supplementary Figure S1a and b). Segmented linear regression indi- cated that almost all the change in vitiligo age-of-onset occurred over the period from 1970 to 2004, from a mean 14.6  9.4 years in 1970 to 30.2  17.3 years in 2004, an increase rate of Abbreviation: GWAS, genome-wide association study Accepted manuscript published online 28 June 2019; corrected proof published online 6 September 2019 ª 2019 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. Y Jin et al. Pediatric to Adult Shift in Vitiligo Onset www.jidonline.org 241