title: Topical tacrolimus therapy for vitiligo: therapeutic responses and skin messenger RNA expression of proinflammatory cytokines.
abstract: BACKGROUND
  Previous studies have documented humoral and cell-mediated immunologic defects in patients with vitiligo.
  
  
  OBJECTIVE
  This 24-week study assessed the efficacy and safety of tacrolimus 0.1% ointment in patients with generalized vitiligo as well as the pretreatment and post-treatment expression of cytokines in the depigmented and normal skin of patients compared with controls.
  
  
  METHODS
  Twenty-three patients were enrolled in this investigation, and 19 patients completed the study; 8 were male and 11 were female. Fifteen age-, race-, and sex-matched control subjects were also included. Patients were treated with tacrolimus 0.1% ointment applied twice daily. Repeat evaluations were performed at 4, 8, 12, 16, 20, and 24 weeks. Three-millimeter punch biopsy specimens were taken from the depigmented, non-sun-exposed skin and adjacent normal skin of patients at baseline and 24 weeks, and from normal, non-sun-exposed skin of controls. Cellular messenger RNA expression for interleukin 2 (IL-2), IL-4, IL-10, tumor necrosis factor alfa (TFN-alpha), and interferon gamma (IFN-gamma) were determined by real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  At 24 weeks, 17 of 19 patients (89%) achieved varying levels of repigmentation. There was a statistically significant decrease in overall disease severity scores at 24 weeks. Thirteen patients (68%) had greater than 75% repigmentation of face and/or neck lesions. Signs and symptoms of irritation were minimal. At baseline, compared with healthy controls, vitiligo patients demonstrated a statistically significant increase in the expression of IFN-gamma in involved and adjacent uninvolved skin (P=.05 and P=.02, respectively); significantly increased TNF-alpha expression in involved and uninvolved skin (P=.01 and P=0.02, respectively); and significantly increased IL-10 expression in involved and uninvolved skin (P=.01 and P=.04, respectively). Posttreatment, TNF-alpha expression decreased in the depigmented and adjacent uninvolved skin (P <.001). There was no statistically significant change in IL-10 or IFN-gamma posttreatment. These data suggest that tacrolimus 0.1% ointment is a safe and effective therapy for patients with vitiligo. It further suggests that an imbalance in local cytokine expression may play a role in the pathogenesis of vitiligo. Suppression of TNF-alpha after topical tacrolimus application may be associated with repigmentation of vitiligo.
authors.affiliation: Vitiligo and Pigmentation Institute of Southern California, and the Division of Dermatology, David Geffen School of Medicine, University of California, Los Angeles, USA. pegrimesmd@earthlink.net
authors.forename: Pearl E
authors.initials: PE
authors.lastname: Grimes
authors.forename: Robert
authors.initials: R
authors.lastname: Morris
authors.forename: Erik
authors.initials: E
authors.lastname: Avaniss-Aghajani
authors.forename: Teresa
authors.initials: T
authors.lastname: Soriano
authors.forename: Maria
authors.initials: M
authors.lastname: Meraz
authors.forename: Allan
authors.initials: A
authors.lastname: Metzger
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism; D016559:Tacrolimus / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014820:Vitiligo / Q000188:drug therapy*
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D016559:Tacrolimus