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Drug Safety

, Volume 8, Issue 5, pp 340–349 | Cite as

Minimising the Risks of PUVA Treatment

  • Marinus C. G. van Praag
  • Larissa N. L. Tseng
  • A. Mieke Mommaas
  • Bart W. Boom
  • Bert Jan Vermeer
Commentary

Summary

Psoralen photochemotherapy (PUVA) is a combination of orally administered psoralen and long wave ultraviolet-A radiation (UVA), and is one of the most effective forms of therapy for psoriasis. The unwanted effects of PUVA therapy can be divided into short and long term adverse effects. The short term adverse effects include erythema, pruritus, nausea and headache. While short term adverse effects are limited and reversible after discontinuation of treatment, potential long term adverse effects such as chronic actinic skin damage, dyskeratotic and precancerous skin conditions, nonmelanoma skin cancer, immunological alterations and cataract formation are of greater concern.

Long term risks associated with PUVA therapy can be minimised by several measures. Careful patient selection is mandatory; for example, patients with chronic actinic damage and a history of skin cancer may bear a higher risk for the development of new cancers, and previous arsenic intake and ionising radiation also increase the risk of nonmelanoma skin cancers. Certain drug combinations make it possible to lower the UVA dose, which is important because of the dose-dependent increase in the incidence of squamous cell carcinomas in patients treated with PUVA. It has been demonstrated that 200 treatments or a total UVA dose of 1200 J/cm2 seems to be the threshold for development of nonmelanoma skin cancer. Shielding male genitalia during PUVA treatment is essential because of the increased risk of genital squamous cell carcinomas. Yearly dermatological examination to detect skin cancer at an early stage is highly advisable. Sunscreen use, protective clothing and avoidance of sun exposure reduce the uncontrolled dose of solar UV radiation. Other psoralens with a less carcinogenic potential can be used. UVA-opaque sunglasses during the entire period of increased photosensitivity after psoralen ingestion help avoid cataract formation.

Assignment to PUVA ought to be based on the risk-benefit ratio for the individual patient and should be limited to those who can be monitored and controlled by informed, competent and conscientious physicians.

Keywords

Psoriasis Vitiligo Psoralen Nonmelanoma Skin Cancer PUVA Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abramowicz M. Drugs that can cause photosensitivity. Medical Letter on Drugs and Therapeutics 28: 51–52, 1986Google Scholar
  2. Bjellerup M, Bruze M, Forsgren A, Krook G, Ljunggren B. Antinuclear antibodies during PUVA therapy. Acta Dermato-Venereologica (Stockholm) 59: 73–75, 1979Google Scholar
  3. Bruynzeel I, Bergman W, Hartevelt HM, Kenter CCA, van de Velde EA et al. ‘High single-dose’ European PUVA regimen also causes an excess of non-melanoma skin cancer. British Journal of Dermatology 124: 49–55, 1991CrossRefPubMedGoogle Scholar
  4. Deleu H, Roelandts R. Protecting the eye from ultraviolet A radiation during photochemotherapy. Photodermatology, Photoimmunology and Photomedicine 7: 233–236, 1990PubMedGoogle Scholar
  5. El Mofty AM. Vitiligo and psoralens, pp. 147–195, Pergamon Press, Oxford, 1968Google Scholar
  6. Eskelinen A, Halme K, Lassus A, Idanpaan-Heikkila J. Risk of cutaneous carcinoma in psoriatic patients treated with PUVA. Photodermatology 2: 10–14, 1985PubMedGoogle Scholar
  7. Farber EM, Epstein JH and other contributors. Current status of oral PUVA therapy for psoriasis. Journal of the American Academy of Dermatology 6: 851–855, 1982CrossRefGoogle Scholar
  8. Forman AM, Roenigk HH, Caro WA, Magid ML. Long-term follow-up of skin cancer in the PUVA 48 cooperative study. Archives of Dermatology 125: 515–519, 1989CrossRefPubMedGoogle Scholar
  9. Frenk E. Malignant melanoma in a patient with severe psoriasis treated by oral methoxalen photochemotherapy. Dermatologica 167: 152–154, 1983CrossRefPubMedGoogle Scholar
  10. Friedmann PS. Disappearance of epidermal Langerhans cells during PUVA therapy. British Journal of Dermatology 105: 219–221, 1981CrossRefPubMedGoogle Scholar
  11. Gibbs NK, Hönigsmann H, Young AR. PUVA treatment strategies and cancer risk. Lancet 1: 150–151, 1986CrossRefPubMedGoogle Scholar
  12. Griffm AC. Methoxalen in ultraviolet carcinogenesis in the mouse. Journal of Investigative Dermatology 32: 367–372, 1959CrossRefGoogle Scholar
  13. Gschnait F, Wolff K, Hönigsmann H, Stingl G, Brenner W, et al. Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients. British Journal of Dermatology 103: 11–22, 1980CrossRefPubMedGoogle Scholar
  14. Gupta AK, Anderson TF. Psoralen photochemotherapy. Journal of the American Academy of Dermatology 17: 703–734, 1987CrossRefPubMedGoogle Scholar
  15. Gupta AK, Stem RS, Swanson NA, Anderson TF. Cutaneous melanoma in patients treated with psoralens plus ultraviolet A. Journal of the American Academy of Dermatology 19: 67–76, 1988CrossRefPubMedGoogle Scholar
  16. Henseler T, Christophers E, Hönigsmann H, Wolff K, et al. Skin tumors in the European PUVA study: eight-year follow-up in 1,643 patients treated with PUVA for psoriasis. Journal of the American Academy of Dermatology 16: 108–116, 1987CrossRefPubMedGoogle Scholar
  17. Henseler T, Wolff K, Hönigsmann H, Christophers E. The European PUVA study (EPS): oral 8-methoxypsoralen photochemotherapy of psoriasis. A cooperative study among 18 European centres. Lancet 1: 853–857, 1981CrossRefPubMedGoogle Scholar
  18. Hofmann C, Plewig G, Braun-Falco O. Bowenoid lesions, Bowen’s disease and keratoacanthomas in long-term PUVA treated patients. British Journal of Dermatology 101: 685–692, 1979CrossRefPubMedGoogle Scholar
  19. Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, et al. Prevention of second primary tumors with isotretinoin in squamous cell carcinoma of the head and neck. New England Journal of Medicine 323: 795–801, 1990CrossRefPubMedGoogle Scholar
  20. Hönigsmann H, Wolff K, Gschnait F, Brenner W, Jaschke E. Keratoses and nonmelanoma skin tumors in long-term photochemotherapy (PUVA). Journal of the American Academy of Dermatology 3: 406–414, 1980CrossRefPubMedGoogle Scholar
  21. Horio T, Okamoto H. The mechanisms of inhibitory effect of 8-methoxypsoralen and long-wave ultraviolet light on experimental contact sensitization. Journal of Investigative Dermatology 78: 402–405, 1982CrossRefPubMedGoogle Scholar
  22. Langner A, Wolska H, Marzulli FN, Jablonska S, Jarzabek-Chorzelska M, et al. Dermal toxicity of 8-methoxypsoralen administered (by gavage) to hairless mice irradiated with long-wave ultraviolet light. Journal of Investigative Dermatology 69: 451–457, 1977CrossRefPubMedGoogle Scholar
  23. Lerman S. Ocular phototoxicity and psoralen plus ultraviolet radiation (320-400 nm) therapy: an experimental and clinical evaluation. Journal of the National Cancer Institute 69: 287–302, 1982PubMedGoogle Scholar
  24. Lerman S, Megaw J, Willis I. Potential ocular complications from PUVA therapy and their prevention. Journal of Investigative Dermatology 74: 197–199, 1980CrossRefPubMedGoogle Scholar
  25. Levin DL, Roenigk Jr HH, Caro WA, Lyons M. Histologic, immunofluorescent, and antinuclear antibody findings in PUVA-treated patients. Journal of the American Academy of Dermatology 6: 328–333, 1982CrossRefPubMedGoogle Scholar
  26. Lindelof B, Sigurgeirsson B, Tegner E, Larko O, Johannesson A, et al. PUVA and cancer: a large-scale epidemiological study. Lancet 338: 91–93, 1991CrossRefPubMedGoogle Scholar
  27. Melski JW, Tanenbaum L, Parrish JA, Fitzpatrick TB, Bleich HL, et al. Oral methoxalen photochemotherapy for the treatment of psoriasis: a cooperative clinical trial. Journal of Investigative Dermatology 68: 328–335, 1977CrossRefPubMedGoogle Scholar
  28. Morison WL. PUVA combination therapy (a review). Photodermatology 2: 229–236, 1985PubMedGoogle Scholar
  29. Morison WL. Risks of therapy. In Morison WL (Ed.) Phototherapy and photochemotherapy of skin diseases, pp. 197–213, Raven Press, New York, 1991Google Scholar
  30. Morison WL, Parrish JA, Bloch KJ, Krugler JI. In vivo effects of PUVA on lymphocyte function. British Journal of Dermatology 104: 405–413, 1981aCrossRefPubMedGoogle Scholar
  31. Morison WL, Parrish JA, Woehler ME, Bloch KJ. The influence of PUVA and UVB radiation on skin-graft survival in rabbits. Journal of Investigative Dermatology 75: 331–333, 1980CrossRefPubMedGoogle Scholar
  32. Morison WL, Parrish JA, Woehler ME, Krugler Jl, Bloch KJ. The influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig. Journal of Investigative Dermatology 76: 484–488, 1981bCrossRefPubMedGoogle Scholar
  33. Morison WL, Strickland PT. Environmental UVA radiation and eye protection during PUVA therapy. Journal of the American Academy of Dermatology 9: 522–525, 1983CrossRefPubMedGoogle Scholar
  34. Okamoto H, Horio T, Maeda M. Alteration of lymphocyte function by 8-methoxypsoralen and long-wave ultraviolet light radiation II. The effect of in vivo PUVA on IL-2 production. Journal of Investigative Dermatology 89: 24–26, 1987CrossRefPubMedGoogle Scholar
  35. Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxalen and long-wave ultraviolet light. New England Journal of Medicine 291: 1207–1211, 1974CrossRefPubMedGoogle Scholar
  36. Pathak MA, Daniels Jr F, Hopkins CE, Fitzpatrick TB. Ultraviolet carcinogenesis in albino and pigmented mice receiving furocoumarins: psoralen and 8-methoxypsoralen. Nature 183: 728–730, 1959CrossRefPubMedGoogle Scholar
  37. Schenley RL, Hsie AW. Interaction of 8-methoxypsoralen and near-UV light causes mutation and cytotoxicity in mammalian cells. Photochemistry and Photobiology 33: 179–185, 1981CrossRefPubMedGoogle Scholar
  38. Sina B, Adrian RM. Multiple keratoacanthomas possibly induced by psoralens and ultraviolet A photochemotherapy. Journal of the American Academy of Dermatology 9: 686–688, 1983CrossRefPubMedGoogle Scholar
  39. Stem RS and members of the photochemotherapy follow-up study. Genital tumors among men with psoriasis exposed to psoralens and ultraviolet A radiation A (PUVA) and ultraviolet B radiation. New England Journal of Medicine 322: 1093–1097, 1990CrossRefGoogle Scholar
  40. Stern RS, Lange R. Non-melanoma skin cancer occurring in patients treated with PUVA five and ten years after first treatment. Journal of Investigative Dermatology 91: 120–124, 1988CrossRefPubMedGoogle Scholar
  41. Stern RS, Morison WL, Thibodeau LA, Kleinerman RA, Parrish JA, et al. Antinuclear antibodies and oral methoxalen photochemotherapy (PUVA) for psoriasis. Archives of Dermatology 115: 1320–1324, 1979aCrossRefPubMedGoogle Scholar
  42. Stern RS, Scotto J, Fears TR. Psoriasis and susceptibility to non-melanoma skin cancer. Journal of the American Academy of Dermatology 12: 67–73, 1985CrossRefPubMedGoogle Scholar
  43. Stern RS, Thibodeau LA, Kleinerman RA, Parrish JA, Fitzpatrick TB, et al. Risk of cutaneous carcinoma in patients9 treated with oral methoxalen photochemotherapy for psoriasis. New England Journal of Medicine 300: 809–813, 1979bCrossRefPubMedGoogle Scholar
  44. Stingl G, Aberer W, Romani N, Elbe A, Tschachler E. Effects of short-wave UV and PUVA treatment on structure and phenotype of bone marrow-derived dendritic cells of the mouse epidermis. Current Problems in Dermatology 15: 195–204, 1986PubMedGoogle Scholar
  45. Strauss GH, Bridges BA, Greaves M, Hall-Smith P, Price M. Inhibition of delayed hypersensitivity reaction in skin (DNCB test) by 8-methoxypsoralen photochemotherapy: possible basis for pseudopromoting action of skin carcinogenesis? Lancet 2: 556–559, 1980CrossRefPubMedGoogle Scholar
  46. Stuttgen G. The risk of photochemotherapy. International Journal of Dermatology 21: 198–202, 1982CrossRefPubMedGoogle Scholar
  47. Swanbeck G, Thyresson M. Induction of respiration-deficient mutants in yeasts by psoralen and light. Journal of Investigative Dermatology 63: 242–244, 1974CrossRefPubMedGoogle Scholar
  48. Swart R, Kenter CCA, Suurmond D. The incidence of PUVA-induced freckles. Dermatologica 168: 304–305, 1984CrossRefPubMedGoogle Scholar
  49. Tanew A, Hönigsmann H, Ortel B, Zussner C, Wolff K. Nonmelanoma skin tumors in long-term photochemotherapy treatment of psoriasis: an 8-year follow-up study. Journal of the American Academy of Dermatology 15: 960–965, 1986CrossRefPubMedGoogle Scholar
  50. Tanew A, Ortel B, Rappersberger K, Hönigsmann H. 5-meth-oxypsoralen (Berghapten) for photochemotherapy. Journal of the American Academy of Dermatology 18: 333–339, 1988CrossRefPubMedGoogle Scholar
  51. Van Praag MCG, Bouwes Bavinck JN, Bergman W, Mommaas AM, Bruynzeel I, et al. PUVA keratosis; A new clinical and histopathological entity associated with an increased risk of non-melanoma skin cancer. Journal of the American Academy of Dermatology, in press, 1993Google Scholar
  52. Van Praag MCG, Out-Luyting C, Claas FHJ, Vermeer BJ, Mommaas AM. Effect of topical sunscreens on the UV-radiation-induced suppression of the alloactivating capacity in human skin in vivo. Journal of Investigative Dermatology 97: 629–633, 1991CrossRefPubMedGoogle Scholar
  53. Warin AP. The ultraviolet erythemas in man. British Journal of Dermatology 98: 473–477, 1978CrossRefPubMedGoogle Scholar
  54. Wolff K. Side-effects of psoralen photochemotherapy (PUVA). British Journal of Dermatology 122(Suppl. 36): 117–125, 1990CrossRefPubMedGoogle Scholar
  55. Wolff K, Gschnait F, Hönigsmann H, Konrad K, Parrish JA, et al. Phototesting and dosimetry for photochemotherapy. British Journal of Dermatology 96: 1–10, 1977CrossRefPubMedGoogle Scholar
  56. Wolff K, Hönigsmann H. Clinical aspects of photochemotherapy. Pharmacological Therapy 12: 381–418, 1981CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • Marinus C. G. van Praag
    • 1
    • 2
  • Larissa N. L. Tseng
    • 1
  • A. Mieke Mommaas
    • 2
  • Bart W. Boom
    • 2
  • Bert Jan Vermeer
    • 2
  1. 1.Department of DermatologySint Franciscus GasthuisRotterdamThe Netherlands
  2. 2.Department of DermatologyUniversity HospitalLeidenThe Netherlands

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