SKIN July 2023 Volume 7 Issue 4 (c) 2023 THE AUTHORS. Published by the National Society for Cutaneous Medicine. 876 RESEARCH LETTER Cutaneous Fungal Infections Associated with Pediatric-Onset Diabetes: A Case-Control Study in the All of Us Research Program Emily Strouphauer, BSA1, Rajani Katta, MD2 1 School of Medicine, Baylor College of Medicine, Houston, TX 2 Department of Dermatology, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, TX With the rapidly increasing incidence of pediatric diabetes mellitus (DM) in the United States,1 an understanding of the risk of long- term cutaneous consequences, particularly the risk of cutaneous fungal infections, is important. Here, we evaluate the association between pediatric-onset Type 1 diabetes (T1D) and Type 2 diabetes (T2D) with the later development of cutaneous fungal infections in the All of Us research program. This is a National Institutes of Health ABSTRACT Introduction: With the rapidly increasing incidence of pediatric diabetes mellitus (DM) in the United States, an understanding of the risk of long-term cutaneous consequences, particularly the risk of cutaneous fungal infections, is important. In this study, we evaluate the association between pediatric-onset Type 1 diabetes (T1D) and Type 2 diabetes (T2D) with the later development of cutaneous fungal infections. Methods: Through the All of Us electronic health record database, 300 de-identified participants with a diagnosis of T1D or T2D before the age of 18 were selected at random. These 300 participants, composing our pediatric-onset diabetes cohort, were diagnosed with T1D and/or T2D before the age of 18 and developed cutaneous fungal infections between less than 1 and 24 years later. Each case was age-, race-, and sex-matched to four control participants without T1D or T2D diagnoses, and we compared cutaneous fungal infections between pediatric-onset diabetic cases and controls. Results: Compared to the control cohort, participants with pediatric-onset diabetes were significantly more likely to present in adulthood with candidiasis of the mouth, onychomycosis, pityriasis versicolor, candidiasis of urogenital sites, and unspecified superficial mycosis, as well as dermatophytosis of the body, feet, and perianal regions than their non-diabetic counterparts. Conclusion: With the increasing incidence of pediatric DM, it will be important for clinicians to monitor the long-term cutaneous complications, including the risk of fungal infections, to improve dermatology patient outcomes. Further research is warranted to investigate the role of childhood diabetes intervention and glycemic control in mitigating dermatologic fungal complications through adulthood. INTRODUCTION SKIN July 2023 Volume 7 Issue 4 (c) 2023 THE AUTHORS. Published by the National Society for Cutaneous Medicine. 877 database presenting health information on Americans who are historically underrepresented in research. Through the All of Us electronic health record database, we randomly selected 300 de- identified participants with a diagnosis of T1D or T2D before the age of 18. These 300 participants, composing our pediatric-onset diabetes cohort, were diagnosed with T1D and/or T2D before the age of 18 and developed cutaneous fungal infections between less than 1 and 24 years later. Each case was age-, race-, and sex-matched to four control participants without T1D or T2D diagnoses. Participant demographics are displayed in Table 1. We compared cutaneous fungal infections between pediatric-onset diabetic cases and controls. All analyses were performed using R Statistical Software,2 and the results are depicted as odds ratios (OR) with 95% confidence intervals (CI) in Table 2. Compared to the control cohort, participants with pediatric-onset diabetes were significantly more likely to present with candidiasis of the mouth (OR 8.34, 3.34- 20.86 CI), onychomycosis (OR 34.70, 10.37- 116.05 CI), pityriasis versicolor (OR 3.56, 1.28-9.90 CI), and unspecified superficial mycosis (OR 16.20, 1.80-145.51 CI) which encompasses dermatophytosis, onychomycosis, and dermal mycosis diagnoses. Additionally, pediatric-onset diabetes participants were significantly more likely to experience localized dermatophytosis of the body (tinea corporis; OR 6.49, 3.00-14.02 CI), feet (tinea pedis; OR 9.01, 3.40-23.92 CI), and perianal region (OR 28.25, 1.46-548.37 CI) than their non- diabetic counterparts. Tinea cruris, a dermatophyte infection localized to the groin, was not clearly increased in the pediatric- onset diabetes cohort (OR 20.12, 0.96- 419.99 CI). Consistent with the findings of a separate study,3 we observed a significant association between pediatric-onset diabetes and candidiasis of urogenital sites (OR 12.77, 8.16-19.98 CI). Notably, literature suggests that the relationship between pediatric diabetes and vulvovaginal candidiasis may be isolated to postpubescent teenagers, as low estrogen levels during early childhood create a rich, anaerobic flora that inhibits Candida sp. growth.4 Although participants were randomly selected, our case cohort exhibited female predominance (74%). One potential explanation is that puberty generally begins earlier in females, and physiological insulin resistance during this time gives rise to a higher incidence of T2D in adolescent females over males.5 Due to the retrospective nature of this study, a causal relationship between pediatric-onset diabetes and cutaneous fungal infection prevalence cannot be determined. Additionally, this study does not investigate glycemic control and correlation to cutaneous fungal infections. However, the findings do suggest that certain cutaneous fungal infections are more likely to occur in adulthood in those with pediatric-onset DM, including in underrepresented research populations. With the increasing incidence of pediatric DM, it will be important for clinicians to monitor the long-term cutaneous complications, including the risk of fungal infections, to improve dermatology patient outcomes. Further research is warranted to investigate the role of childhood diabetes intervention and glycemic control in mitigating dermatologic fungal complications through adulthood. Conflict of Interest Disclosures: Dr. Rajani Katta serves on an advisory board for Vichy Laboratories. Emily Strouphauer has no conflicts of interest to disclose. SKIN July 2023 Volume 7 Issue 4 (c) 2023 THE AUTHORS. Published by the National Society for Cutaneous Medicine. 878 Table 1. Demographics of pediatric-onset diabetes cases and corresponding controls in All of Us SD, standard deviation Characteristic Cases Controls n 300 1200 Average age (SD) 30.0 (7.69) 30.0 (7.69) Race/Ethnicity (%) Asian 1 (0.33) 4 (0.33) Black or African American 79 (26.33) 316 (26.33) More than one population 13 (4.33) 52 (4.33) Other 92 (30.66) 368 (30.66) White 115 (38.33) 460 (38.33) Ethnicity (%) Hispanic or Latino 94 (31.33) 376 (31.33) Not Hispanic or Latino 195 (65.0) 780 (65.0) Other 11 (3.66) 44 (3.66) Sex (%) Female 222 (74.0) 888 (74.0) Male 78 (26.0) 312 (26.0) SKIN July 2023 Volume 7 Issue 4 (c) 2023 THE AUTHORS. Published by the National Society for Cutaneous Medicine. 879 Table 2. Cutaneous fungal comorbidities of pediatric-onset diabetes cases and corresponding controls in All of Us CI, confidence interval; OR, odds ratio *Denotes significance Diagnostic count of fungal infections Cases Controls OR (95% CI) P value Candidal intertrigo 0 1 1.331 (0.0541-32.745) 0.8613 Candidiasis of urogenital site 74 30 12.770 (8.163-19.977) <0.0001 * Candidiasis of mouth 14 7 8.3427 (3.337-20.860) <0.0001 * Dermal mycosis 0 1 1.331 (0.0541-32.745) 0.8613 Dermatophytosis 48 19 11.840 (6.842-20.488) <0.0001 * Dermatophytosis of unspecified region 13 2 27.132 (6.089- 120.907) <0.0001 * Tinea corporis 17 11 6.493 (3.008-14.016) <0.0001 * Tinea cruris 2 0 20.1089 (0.963- 419.988) 0.0529 Tinea pedis 13 6 9.014 (3.397-23.919) <0.0001 * Tinea of perianal region 3 0 28.2471 (1.455- 548.369) 0.0273 * Onychomycosis due to dermatophyte 24 3 34.696 (10.374- 116.045) <0.0001 * Pityriasis versicolor 7 8 3.560 (1.281-9.896) 0.0149 * Superficial mycosis (unspecified) 4 1 16.203 (1.804- 145.506) 0.0129 * Individuals with more than one fungal diagnosis Cases Controls OR (95% CI) P value Number of participants (%) 102 (34%) 63 (5.25%) 9.297 (6.562-13.173) <0.0001 * SKIN July 2023 Volume 7 Issue 4 (c) 2023 THE AUTHORS. Published by the National Society for Cutaneous Medicine. 880 Funding: None Corresponding Author: Emily Strouphauer, BSA 1 Moursund St Houston, TX, 77030 Phone: (512)-925-6838 Email: emily.strouphauer@bcm.edu References: 1. Divers J. Trends in Incidence of Type 1 and Type 2 Diabetes Among Youths — Selected Counties and Indian Reservations, United States, 2002–2015. MMWR Morb Mortal Wkly Rep. 2020;69. doi:10.15585/mmwr.mm6906a3 2. Aragon TJ. epitools: Epidemiology Tools. Published online 2020. https://CRAN.R- project.org/package=epitools 3. Atabek ME, Akyürek N, Eklioglu BS. Frequency of Vagınal Candida Colonization and Relationship between Metabolic Parameters in Children with Type 1 Diabetes Mellitus. J Pediatr Adolesc Gynecol. 2013;26(5):257-260. doi:10.1016/j.jpag.2013.03.016 4. Banerjee K, Curtis E, de San Lazaro C, Graham JC. Low prevalence of genital candidiasis in children. Eur J Clin Microbiol Infect Dis. 2004;23(9):696-698. doi:10.1007/s10096-004-1189-2 5. Temneanu O, Trandafir L, Purcarea M. Type 2 diabetes mellitus in children and adolescents: a relatively new clinical problem within pediatric practice. J Med Life. 2016;9(3):235-239.