title: A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: results from a French nationwide study.
abstract: BACKGROUND
  Voriconazole long-term therapy is suspected to induce cutaneous squamous cell carcinoma (SCC), as suggested by 18 case reports worldwide and 3 retrospective studies.
  
  
  METHODS
  To better characterize the natural history of these potentially voriconazole-associated tumors, a nationwide call for notification of skin cancers and other skin lesions observed between 2002 and 2012 in patients treated by voriconazole was launched in France. A multidisciplinary committee evaluated voriconazole involvement in each case.
  
  
  RESULTS
  Nineteen SCCs were reported. The committee determined the likelihood of voriconazole involvement to be high in 15 cases, intermediate in 2, and low in 2. In the 17 patients with high/intermediate likelihood of voriconazole involvement, the mean time between voriconazole initiation and SCC diagnosis was 39 ± 18 months (range, 28-84 months), and was shorter in transplant recipients (35 vs 45 months, P < .05). Cumulative mean duration of voriconazole therapy at SCC diagnosis was 35 months (range, 7-63 months). A multistep process was noted in 14 of 17 patients: acute phototoxicity during the first year of voriconazole therapy (mean time, 6 months [range, 0-18 months]), actinic keratosis (AK) of the same sun-exposed skin area in the second/third year (mean, 30 months [range, 11-57 months]), followed by SCC during the third year or later. Five cases of AK without SCC and 37 cases of other skin lesions were also reported.
  
  
  CONCLUSIONS
  Our results suggest that long-term voriconazole prescription may be associated with a multistep phototoxic process involving acute skin lesions followed by AK then by SCC. Discontinuation of voriconazole should be strongly considered in patients experiencing chronic phototoxicity.
authors.affiliation: Service des Maladies Infectieuses, Centre Hospitalier Universitaire de Grenoble.
authors.forename: Olivier
authors.initials: O
authors.lastname: Epaulard
authors.forename: Céline
authors.initials: C
authors.lastname: Villier
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.forename: Olivier
authors.initials: O
authors.lastname: Chosidow
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Mamzer-Bruneel
authors.forename: Anne
authors.initials: A
authors.lastname: Thiébaut
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Leccia
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D017484:Dermatitis, Phototoxic / Q000453:epidemiology*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D014230:Triazoles / Q000009:adverse effects*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole
keywords: carcinoma; phototoxicity; skin; voriconazole