title: Voriconazole-induced photosensitivity: photobiological assessment of a case series of 12 patients.
abstract: BACKGROUND
  Voriconazole, a broad-spectrum triazole antifungal agent increasingly used to treat aspergillosis, has been linked with acute photosensitivity and skin carcinogenesis. The action spectrum of the photosensitivity is unknown, while an indirect retinol effect secondary to the antifungal's impact on CYP450 enzymes has been proposed to contribute to the underlying mechanism.
  
  
  OBJECTIVE
  To perform a detailed photobiological assessment of the photosensitivity presenting in a series of 12 patients treated with voriconazole.
  
  
  METHODS
  Minimal erythemal dose thresholds (MED) to narrow wavebands of ultraviolet (UV) A, UVB and visible light were determined. Provocation testing was performed to broadband UVA (310-400 nm) and to solar-simulated radiation (SSR) (290-400 nm). Patients underwent routine photopatch testing and laboratory investigations including serum vitamin A (retinol).
  
  
  RESULTS
  Patients (eight men, four women; median age 54years, range 40-63) experienced moderate-severe cutaneous erythema (n = 12), burning pain (n=5), itching (n=3), scaling (n=5), vesiculation (n=5) and oedema (n=1) following sunlight exposure; increased lentigines (n=4) and actinic cheilitis (n = 4) were also observed. While the majority (n=8) of patients showed normal MED thresholds to monochromator phototesting to UVB, UVA and visible light, a low MED to UVA was observed in four patients. Repeated provocation testing with broadband UVA and SSR provoked an abnormal erythema in eight and 10 patients, respectively. Serum retinol levels were mildly elevated in two patients but normal in the majority.
  
  
  CONCLUSIONS
  UVA sensitivity is the predominant finding in acute voriconazole-induced photosensitivity. We found little evidence of elevated circulating retinol as the causal factor. Patients with voriconazole-induced photosensitivity require education in appropriate UVA protective measures in addition to consideration of skin surveillance for malignant sequelae.
authors.affiliation: Photobiology Unit, Dermatology Centre, University of Manchester, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Stott Lane, Manchester M6 8HD, U.K.
authors.forename: A K
authors.initials: AK
authors.lastname: Haylett
authors.forename: S
authors.initials: S
authors.lastname: Felton
authors.forename: D W
authors.initials: DW
authors.lastname: Denning
authors.forename: L E
authors.initials: LE
authors.lastname: Rhodes
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood / Q000652:urine; D000935:Antifungal Agents / Q000009:adverse effects*; D001228:Aspergillosis / Q000188:drug therapy*; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D008875:Middle Aged; D010328:Patch Tests; D010787:Photosensitivity Disorders / Q000139:chemically induced* / Q000175:diagnosis; D011743:Pyrimidines / Q000009:adverse effects*; D013472:Sunlight / Q000009:adverse effects; D014230:Triazoles / Q000009:adverse effects*; D065819:Voriconazole
chemical_list: D000974:Antibodies, Antinuclear; D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole