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Original Investigation
November 30, 2016

Association of Filaggrin Loss of Function and Thymic Stromal Lymphopoietin Variation With Treatment Use in Pediatric Atopic Dermatitis

Author Affiliations
  • 1Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
  • 2Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
JAMA Dermatol. Published online November 30, 2016. doi:10.1001/jamadermatol.2016.4467
Key Points

Question  In atopic dermatitis, do variations in FLG and TSLP genotype correspond to differences in treatment use over time?

Findings  In this cohort study of 842 children with atopic dermatitis, those with 2 FLG LOF alleles were less likely to experience skin clearance and more likely to use steroids, and TSLPrs1898671 homozygotes were less likely to use topical calcineurin inhibitors. 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.

Meaning  Treatment use and likely effectiveness was associated with genetic variation.

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.

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