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Voriconazole has been increasingly used in the treatment of invasive aspergillosis and for antifungal prophylaxis after allogeneic BMT. The incidence of drug-induced skin reactions is estimated to be 7%. There is a growing awareness of the higher risk of acute and cumulative phototoxicity, and the risk of chronic photo-damage and non-melanoma sun-related skin cancers in immunocompromised patients.
Between August 2009 and June 2012, 40 of 43 consecutive allo-BMT recipients (mean age 9.8 y; 83% Caucasian) received voriconazole prophylaxis [7 mg/kg/dose BID (≤12 yrs age); 200 mg BID (>12yrs); adjusted to target trough ≥1.0 mg/mL]. Nine of forty (22.5%) patients, all Caucasian, developed skin rashes in sun-exposed distributions during spring-summer season. The average prior voriconazole exposure was 6 months (1.8 –12.5 mo). Dermatologic findings included 1) diffuse sunburn-like erythema over the face, outer aspects of forearm, and hands 2) linear papulovesicular lesions 3) severe bullous cheilitis (Image) 4) dermatoheliosis and 5) lentigines. Voriconazole was continued in four, substituted with fluconazole in four and with posaconazole in one patient. Patients were treated with sun avoidance, high-potency sun-screens, and topical steroids with significant improvement in all cases.
While trough voriconazole plasma concentrations do not appear to be different, N-oxide metabolite concentrations were higher in photosensitive patients.
| All (40)
| No Phototoxic rash (31)
| Phototoxic rash (9) |
Mean Vori- level (mg/ml) | 1.3
| 1.2
| 1.5
|
Mean -N oxide (mg/ml )
| 3.5
| 3.2
| 4.8
|
Significant higher incidence of photosensitivity occurs in voriconazole-treated children, especially Caucasians, during prolonged drug use and intense sunshine. Voriconazole N-oxide may act as a chromophore for phototoxicity, and its potential role in individual susceptibility should be explored. Voriconazole may be continued, although change to other azoles may be necessary in some patients. Prolonged voriconazole use requires close monitoring for chronic skin toxicities. Long-term risks including the risk of skin cancer need to be investigated.
