title: Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation. A double-blind, vehicle-controlled comparison of 0.1% and 0.025% tretinoin creams.
abstract: METHODS
  The efficacy of topical tretinoin (all-trans-retinoic acid) in treating photoaging is well established. Questions that remain are (1) whether irritation causes all or part of the improvement; (2) the concentration of tretinoin that maximizes clinical response with minimal side effects; and (3) the effects of long-term treatment on components of the cutaneous immune system. To address these issues, 99 photoaged patients completed a 48-week study using 0.1% tretinoin cream (n = 32), 0.025% tretinoin (n = 35), or vehicle (n = 32) once daily in a double-blind manner. Before and after treatment, we assessed histologic features, keratinocyte expression of HLA-DR and intercellular adhesion molecule-1, numbers of epidermal Langerhans' cells and epidermal and dermal T lymphocytes, and vascularity as measured by dermal endothelial cell area.
  
  
  RESULTS
  Both 0.1% and 0.025% tretinoin produced statistically significant overall improvement in photoaging of the face compared with vehicle; there were no clinically or statistically significant differences in efficacy between the two concentrations of tretinoin. After 48 weeks, 0.1% and 0.025% tretinoin produced similar statistically significant epidermal thickening (by 30% and 28%, respectively) compared with vehicle (11% decrease) and increased vascularity (by 100% and 89%, respectively) compared with vehicle (9% decrease). By various analyses, irritant side effects (erythema and scaling) were statistically significantly greater with 0.1% tretinoin than with 0.025% tretinoin. No significant changes occurred in any immunologic markers when tretinoin and vehicle treatments were compared.
  
  
  CONCLUSIONS
  Tretinoin 0.1% and 0.025% produce similar clinical and histologic changes in patients with photoaging, despite significantly greater incidence of irritation with the higher concentration. The separation between clinical improvement and irritation suggests that mechanisms other than irritation dominate tretinoin-induced repair of photoaging in humans.
authors.affiliation: Department of Dermatology, University of Michigan Medical Center, Ann Arbor, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Griffiths
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.forename: C N
authors.initials: CN
authors.lastname: Ellis
authors.forename: K J
authors.initials: KJ
authors.lastname: Kim
authors.forename: L J
authors.initials: LJ
authors.lastname: Finkel
authors.forename: L C
authors.initials: LC
authors.lastname: Ortiz-Ferrer
authors.forename: G M
authors.initials: GM
authors.lastname: White
authors.forename: T A
authors.initials: TA
authors.lastname: Hamilton
authors.forename: J J
authors.initials: JJ
authors.lastname: Voorhees
mesh_terms: D000368:Aged; D015815:Cell Adhesion Molecules / Q000032:analysis; D004311:Double-Blind Method; D019040:E-Selectin; D005145:Face; D005260:Female; D005542:Forearm; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009824:Ointments; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015595:Skin Aging / Q000187:drug effects* / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D006684:HLA-DR Antigens; D009824:Ointments; D018799:Intercellular Adhesion Molecule-1; D014212:Tretinoin