Joshua Chang1, Nandita Mitra2, Ole Hoffstad2, David J Margolis3. 1. Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 2. Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 3. Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania2Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Abstract
Importance: Atopic dermatitis (AD) is a common illness of childhood. Objective: To determine whether variations in FLG and TSLP genotype corresponded to differences in treatment use over time. Design, Setting, and Participants: This prospective cohort study recruited and followed a volunteer sample of 842 children enrolled in the Pediatric Eczema Elective Registry who provided saliva samples for DNA extraction for 10 years. Eligibility criteria included age 2 to 17 years, AD diagnosis without cancer, and prior pimecrolimus use. Participants were followed for an average of 7.6 years (approximately 6396 person-years); 138 patients (16.4%) had no missing data over 10 years of follow-up. Exposures: Evaluation of FLG and TSLP genotypes. Main Outcomes and Measures: Self-reported outcomes of whether a child's AD required the use of topical steroids, topical calcineurin inhibitors, or other medications within the past 6 months at 6-month intervals. Results: Overall, 842 children (mean [SD] age, 1.9 [2.7] years; 438 girls) were included in this study. Treatment use among patients with 0, 1, or 2 FLG loss of function (LOF) alleles was compared as well as those that were wildtype, heterozygous, or homozygous for the TSLPrs1898671 single-nucleotide polymorphism. Patients with 2 FLG LOF alleles were less likely to report skin clearance (odds ratio [OR], 0.20; 95% CI, 0.07-0.55) and more likely to use steroids (OR, 5.04; 95% CI, 1.91-13.31). TSLPrs1898671 homozygotes were less likely to report topical calcineurin inhibitor use (OR, 0.16; 95% CI, 0.06-0.42), and among all patients that had discontinued topical calcineurin inhibitors, those with the rs1898671 single-nucleotide polymorphism were more likely to have stopped all other treatment as well (OR, 0.45; 95% CI, 0.26-0.76). In all but 1 of our comparisons, no significant difference between wildtype and heterozygous patients were found. Conclusions and Relevance: Treatment use and likely effectiveness was associated with genetic variation. Variation was limited to children with 2 FLG LOF alleles or TSLPrs1898671 homozygotes, with no significant difference observed between wildtype and heterozygous patients in the majority of the outcomes studied. Therefore, the key differentiating factor in our analyses was the number of FLG LOF alleles or TSLP SNPs rather than the absolute presence or absence of these variants. This may be an important consideration for future studies.
Importance: Atopic dermatitis (AD) is a common illness of childhood. Objective: To determine whether variations in FLG and TSLP genotype corresponded to differences in treatment use over time. Design, Setting, and Participants: This prospective cohort study recruited and followed a volunteer sample of 842 children enrolled in the Pediatric Eczema Elective Registry who provided saliva samples for DNA extraction for 10 years. Eligibility criteria included age 2 to 17 years, AD diagnosis without cancer, and prior pimecrolimus use. Participants were followed for an average of 7.6 years (approximately 6396 person-years); 138 patients (16.4%) had no missing data over 10 years of follow-up. Exposures: Evaluation of FLG and TSLP genotypes. Main Outcomes and Measures: Self-reported outcomes of whether a child's AD required the use of topical steroids, topical calcineurin inhibitors, or other medications within the past 6 months at 6-month intervals. Results: Overall, 842 children (mean [SD] age, 1.9 [2.7] years; 438 girls) were included in this study. Treatment use among patients with 0, 1, or 2 FLG loss of function (LOF) alleles was compared as well as those that were wildtype, heterozygous, or homozygous for the TSLPrs1898671 single-nucleotide polymorphism. Patients with 2 FLG LOF alleles were less likely to report skin clearance (odds ratio [OR], 0.20; 95% CI, 0.07-0.55) and more likely to use steroids (OR, 5.04; 95% CI, 1.91-13.31). TSLPrs1898671 homozygotes were less likely to report topical calcineurin inhibitor use (OR, 0.16; 95% CI, 0.06-0.42), and among all patients that had discontinued topical calcineurin inhibitors, those with the rs1898671 single-nucleotide polymorphism were more likely to have stopped all other treatment as well (OR, 0.45; 95% CI, 0.26-0.76). In all but 1 of our comparisons, no significant difference between wildtype and heterozygous patients were found. Conclusions and Relevance: Treatment use and likely effectiveness was associated with genetic variation. Variation was limited to children with 2 FLG LOF alleles or TSLPrs1898671 homozygotes, with no significant difference observed between wildtype and heterozygous patients in the majority of the outcomes studied. Therefore, the key differentiating factor in our analyses was the number of FLG LOF alleles or TSLP SNPs rather than the absolute presence or absence of these variants. This may be an important consideration for future studies.
Authors: David J Margolis; Nandita Mitra; Ole J Hoffstad; Brian S Kim; Dimitri S Monos; Elizabeth J Phillips Journal: J Immunol Date: 2021-08-18 Impact factor: 5.426
Authors: Carolyn Lou; Nandita Mitra; Bradley Wubbenhorst; Kurt D'Andrea; Ole Hoffstad; Brian S Kim; Albert Yan; Andrea L Zaenglein; Zelma Chiesa Fuxench; Katherine L Nathanson; David J Margolis Journal: Ann Allergy Asthma Immunol Date: 2019-09-04 Impact factor: 6.347
Authors: David J Margolis; Nandita Mitra; Brian S Kim; Jamie L Duke; Ron A Berna; Ole J Hoffstad; Jenna R Wasserman; Deborah A Ferriola; Tim L Mosbruger; Bradley S Wubbenhorst; Kathrine L Nathanson; Dimitri S Monos Journal: J Immunol Date: 2021-04-16 Impact factor: 5.422