title: Association of Filaggrin Loss of Function and Thymic Stromal Lymphopoietin Variation With Treatment Use in Pediatric Atopic Dermatitis.
abstract: Atopic dermatitis (AD) is a common illness of childhood.
  
  
  
  To determine whether variations in FLG and TSLP genotype corresponded to differences in treatment use over time.
  
  
  
  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.
  
  
  
  Evaluation of FLG and TSLP genotypes.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Joshua
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Ole
authors.initials: O
authors.lastname: Hoffstad
authors.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Margolis
mesh_terms: D000483:Alleles; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D000091344:Filaggrin Proteins; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013256:Steroids / Q000627:therapeutic use*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D065095:Calcineurin Inhibitors; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D013256:Steroids; D000094632:Thymic Stromal Lymphopoietin