Journal of the American Academy of Dermatology
Volume 62, Issue 1 , Pages 31-37 , January 2010

Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole

  • Edward W. Cowen, MD, MHSc

      Affiliations

    • Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • Corresponding Author InformationCorrespondence to: Edward W. Cowen, MD, MHSc, Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr, MSC 1908, Bldg 10, Room 12N238, Bethesda, MD 20892.
    • ,
  • Josephine C. Nguyen, MD

      Affiliations

    • Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Daniel D. Miller, MD

      Affiliations

    • Department of Dermatology, University of California, San Francisco, California
    • ,
  • Diana McShane, MD

      Affiliations

    • Department of Dermatology, Duke University Medical Center, Durham, North Carolina
    • ,
  • Sarah T. Arron, MD, PhD

      Affiliations

    • Department of Dermatology, University of California, San Francisco, California
    • ,
  • Neil S. Prose, MD

      Affiliations

    • Department of Dermatology, Duke University Medical Center, Durham, North Carolina
    • ,
  • Maria L. Turner, MD

      Affiliations

    • Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Lindy P. Fox, MD

      Affiliations

    • Department of Dermatology, University of California, San Francisco, California

,Accepted 23 September 2009.

References 

  1. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–415
  2. Patel AR, Turner ML, Baird K, Gea-Banacloche J, Mitchell S, Pavletic SZ, et al. Voriconazole-induced phototoxicity masquerading as chronic graft-versus-host disease of the skin in allogeneic hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2009;15:370–376
  3. Wingard JR, Carter SL, Walsh JT, Kurtzberg J, Small TN, Gersten ID, et al. Results of a randomized, double-blind trial of fluconazole (FLU) vs voriconazole (VORI) for the prevention of invasive fungal infections (IFI) in 600 allogeneic blood and marrow transplant (BMT) patients (abstract). Blood (ASH Annual Meet Abstract). 2007;110:163
  4. Voriconazole (Vfend) product labeling information. New York, NY: Pfizer; 2009;
  5. Denning DW, Griffiths CE. Muco-cutaneous retinoid-effects and facial erythema related to the novel triazole antifungal agent voriconazole. Clin Exp Dermatol. 2001;26:648–653
  6. Dolan CK, Hall MA, Blazes DL, Norwood CW. Pseudoporphyria as a result of voriconazole use: a case report. Int J Dermatol. 2004;43:768–771
  7. Kwong WT, Hsu S. Pseudoporphyria associated with voriconazole. J Drugs Dermatol. 2007;6:1042–1044
  8. Tolland JP, McKeown PP, Corbett JR. Voriconazole-induced pseudoporphyria. Photodermatol Photoimmunol Photomed. 2007;23:29–31
  9. Brunel AS, Fraisse T, Lechiche C, Pinzani V, Mauboussin JM, Sotto A. Multifocal squamous cell carcinomas in an HIV-infected patient with a long-term voriconazole therapy. AIDS. 2008;22:905–906
  10. McCarthy KL, Playford EG, Looke DF, Whitby M. Severe photosensitivity causing multifocal squamous cell carcinomas secondary to prolonged voriconazole therapy. Clin Infect Dis. 2007;44:e55–e56
  11. Vanacker A, Fabre G, Van Dorpe J, Peetermans WE, Maes B. Aggressive cutaneous squamous cell carcinoma associated with prolonged voriconazole therapy in a renal transplant patient. Am J Transplant. 2008;8:877–880
  12. Rubenstein M, Levy ML, Metry D. Voriconazole-induced retinoid-like photosensitivity in children. Pediatr Dermatol. 2004;21:675–678
  13. Racette AJ, Roenigk HH, Hansen R, Mendelson D, Park A. Photoaging and phototoxicity from long-term voriconazole treatment in a 15-year-old girl. J Am Acad Dermatol. 2005;52(Suppl):S81–S85
  14. Feist AA, Osborne SL, Thistlethwaite PA, Madani M, Reed S, Yung G. Voriconazole use increases the incidence of skin cancer in lung transplant recipients. [abstract] J Heart Lung Transplant. 2009;28:S242
  15. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. [comment] N Engl J Med. 2003;348:1681–1691
  16. Murayama N, Imai N, Nakane T, Shimizu M, Yamazaki H. Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol. 2007;73:2020–2026
  17. Bruggemann RJ, Alffenaar JW, Blijlevens NM, Billaud EM, Kosternik JG, Verweij PE, et al. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis. 2009;48:1441–1458
  18. Halliday GM, Lyons JG. Inflammatory doses of UV may not be necessary for skin carcinogenesis. Photochem Photobiol. 2008;84:272–283
  19. Stern RS. Psoralen and ultraviolet a light therapy for psoriasis. N Engl J Med. 2007;357:682–690
  20. Klecak G, Urbach B, Urwyler H. Fluoroquinolone antibacterials enhance UVA-induced skin tumors. J Photochem Photobiol B. 1997;37:174–181
  21. Jensen AO, Thomsen HF, Engebjerg MC, Olesen AB, Sorensen HT, Karagas MR. Use of photosensitizing diuretics and risk of skin cancer: a population-based case-control study. Br J Cancer. 2008;99:1522–1528
  22. Karagas MR, Stukel TA, Umland V, Tsoukas MM, Mott LA, Sorensen HT, et al. Reported use of photosensitizing medications and basal cell and squamous cell carcinoma of the skin: results of a population-based case-control study. J Invest Dermatol. 2007;127:2901–2903
  23. Curtis RE, Metayer C, Rizzo JD, Socié G, Sobocinski KA, Flowers ME, et al. Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood. 2005;105:3802–3811
  24. Leisenring W, Friedman DL, Flowers ME, Schwartz JL, Deeg HJ. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol. 2006;24:1119–1126
  25. Marcil I, Stern RS. Squamous-cell cancer of the skin in patients given PUVA and cyclosporin: nested cohort crossover study. Lancet. 2001;358:1042–1045

 Dr Nguyen is currently a resident in the Department of Dermatology at the University of Pennsylvania, Philadelphia.

 Supported in part by the Intramural Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute.

 Conflicts of interest: None declared.

 Reprints not available from the authors.

PII: S0190-9622(09)01232-8

doi: 10.1016/j.jaad.2009.09.033

Journal of the American Academy of Dermatology
Volume 62, Issue 1 , Pages 31-37 , January 2010

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