title: A mild topical steroid leads to progressive anti-inflammatory effects in the skin of patients with moderate-to-severe atopic dermatitis.
abstract: Topical glucocorticosteroids are considered an efficient treatment option for atopic dermatitis (AD), but a global assessment of glucocorticosteroid responses on key disease circuits upon weeks to months of treatment is currently lacking.
  
  
  
  We sought to assess short (4 weeks) and long-term (16 weeks) application of topical glucocorticosteroids on AD skin and define response biomarkers.
  
  
  
  The effects of triamcinolone acetonide cream 0.025% were assessed based on gene expression and immunohistochemistry studies at baseline, 4 weeks, and 16 weeks in biopsy specimens from 15 patients with moderate-to-severe AD.
  
  
  
  At 16 weeks, only 3 patients were clinical responders (by using SCORAD50 criteria), but 6 patients qualified as responders based on histologic criteria. Baseline characteristics indicated more severe disease in nonresponders. While 3 of 15 patients experienced only transient benefit after 4 weeks, others showed progressive improvements toward 16 weeks. Topical glucocorticosteroid use in patients with AD resulted in improvements of the AD genomic signature of 25.6% at 4 weeks and 71.8% at 16 weeks, respectively, and even 123.9% in the histologic responder group. Cytokines (IL-12p40, IL-13, IL-22, CCL17, CCL18, peptidase inhibitor 3 [PI3]/elafin, and S100As) showed consistent decreases from baseline toward 16 weeks with corresponding improvements in epidermal disease hallmarks (keratin 16 and loricrin) in lesional skin from responders (P < .05). Nonresponders largely showed lesser/nonsignificant reductions in key inflammatory and barrier markers (keratin 16, IL-13, IL-22, CCL17, CCL18, PI3/elafin, S100As, and loricrin). The combination of IL-21 and IFN-γ baseline expression closely predicted individual clinical glucocorticosteroid responses at 16 weeks of treatment.
  
  
  
  Our study indicates that even low-potency glucocorticosteroids can broadly affect immune and barrier responses in patients with moderate-to-severe AD, associating higher baseline severity with increased steroid resistance in patients with AD.
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Brunner
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Saakshi
authors.initials: S
authors.lastname: Khattri
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Sandra
authors.initials: S
authors.lastname: Garcet
authors.affiliation: Department of Dermatology, Jefferson Medical College, Philadelphia, Pa.
authors.forename: Robert
authors.initials: R
authors.lastname: Finney
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Margeaux
authors.initials: M
authors.lastname: Oliva
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Riana
authors.initials: R
authors.lastname: Dutt
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Xiuzhong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Bonifacio
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Norma
authors.initials: N
authors.lastname: Kunjravia
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Israel
authors.initials: I
authors.lastname: Coats
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Inna
authors.initials: I
authors.lastname: Cueto
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY; Icahn Institute for Genomics and Multiscale Biology at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001706:Biopsy; D016000:Cluster Analysis; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013256:Steroids / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D013256:Steroids
keywords: Atopic dermatitis; epidermal; immune; topical glucocorticosteroids; triamcinolone acetonide