Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study

N Engl J Med. 1997 Apr 10;336(15):1041-5. doi: 10.1056/NEJM199704103361501.


Background: Photochemotherapy with oral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is an effective treatment for psoriasis. However, PUVA is mutagenic, increases the risk of squamous-cell skin cancer, and can cause irregular, pigmented skin lesions. We studied the occurrence of melanoma among patients treated with PUVA.

Methods: We prospectively identified cases of melanoma and documented the extent of exposure to PUVA among 1380 patients with psoriasis who were first treated with PUVA in 1975 or 1976. Using incidence data, we calculated the expected incidence of melanoma in this cohort and compared it with the observed incidence. Using regression models, we assessed the risks of melanoma associated with a long time (> or = 15 years) since the first treatment and with a large number of PUVA treatments (> or = 250).

Results: From 1975 through 1990, we detected four malignant melanomas, about the number expected in the overall population (relative risk, 1.1). From 1991 through 1996, we detected seven malignant melanomas (relative risk, 5.4; 95 percent confidence interval, 2.2 to 11.1). The risk of melanoma was higher in the later period than in the earlier one (incidence-rate ratio, 3.8) and higher among patients who received at least 250 PUVA treatments than among those who received fewer treatments (incidence-rate ratio, 3.1).

Conclusions: About 15 years after the first treatment with PUVA, the risk of malignant melanoma increases, especially among patients who receive 250 treatments or more.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Male
  • Melanoma / etiology*
  • Methoxsalen / therapeutic use
  • Middle Aged
  • Odds Ratio
  • PUVA Therapy / adverse effects*
  • Prospective Studies
  • Psoriasis / complications
  • Psoriasis / drug therapy*
  • Regression Analysis
  • Risk
  • Risk Factors
  • Skin Neoplasms / etiology*
  • Time Factors


  • Methoxsalen