title: Effects of 1-year intermittent treatment with topical tacrolimus monotherapy on skin collagen synthesis in patients with atopic dermatitis.
abstract: BACKGROUND
  Topical corticosteroids decrease collagen synthesis during short-term treatment and can induce skin atrophy when applied over the long term. In contrast, short-term tacrolimus ointment therapy does not affect collagen synthesis.
  
  
  OBJECTIVE
  Our aim was to evaluate the long-term effects of 0.1% tacrolimus ointment on collagen synthesis and on skin thickness in adults with moderate to severe atopic dermatitis (AD) and to compare the findings with the effects of conventional steroid-based therapy.
  
  
  METHODS
  Fifty-six patients with AD were treated with 0.1% tacrolimus ointment in a 1-year, open-label, prospective clinical trial. Thirty-six patients with AD applied conventional steroid-based therapy and 27 healthy subjects were recruited as controls. The primary endpoint was the change in levels of procollagen propeptides I and III measured by radioimmunoassay between baseline and month 12. Additional endpoints included the change in skin thickness measured by ultrasound between baseline and month 12.
  
  
  RESULTS
  Procollagen propeptide baseline values were significantly lower in the group to be treated with tacrolimus ointment than in healthy controls. One-year treatment with tacrolimus ointment was associated with an increase in collagen synthesis; the median increase in combined procollagen propeptide levels was 272 micro g L-1 (+ 140.9%, P < 0.001) and was accompanied by a significant increase in skin thickness. In three patients with visible skin atrophy, this condition ameliorated. Corticosteroid-based therapy had no significant effect on collagen synthesis; the median increase in combined procollagen propeptide levels was 11 micro g L-1 (+ 3.9%). A significant reduction in skin thickness was demonstrated.
  
  
  CONCLUSIONS
  Long-term tacrolimus ointment therapy in patients with AD is nonatrophogenic and reverses corticosteroid-induced skin atrophy.
authors.affiliation: Department of Dermatology, Hospital for Skin and Allergic Diseases, University of Helsinki, 00250, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Kyllönen
authors.forename: A
authors.initials: A
authors.lastname: Remitz
authors.forename: J M
authors.initials: JM
authors.lastname: Mandelin
authors.forename: P
authors.initials: P
authors.lastname: Elg
authors.forename: S
authors.initials: S
authors.lastname: Reitamo
mesh_terms: D000287:Administration, Topical; D000328:Adult; D016022:Case-Control Studies; D003094:Collagen / Q000096:biosynthesis*; D024042:Collagen Type I / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012867:Skin / Q000000981:diagnostic imaging / Q000378:metabolism*; D018709:Statistics, Nonparametric; D016559:Tacrolimus / Q000627:therapeutic use*; D014463:Ultrasonography
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003094:Collagen; D016559:Tacrolimus