THE BENEFITS AND RISKS OF LONG-TERM PUVA PHOTOCHEMOTHERAPY

Psoralen (methoxsalen, 8-methoxypsoralen or 8-MOP) and UVA/PUVA therapy is widely accepted and approved by the U.S. Food and Drug Administration as one of the standard treatment modalities for severe forms of psoriasis . PUVA photochemotherapy is the use of oral psoralens , methoxsalen (8-methoxy-psoralen), or bergapten (5-methoxypsoralen) followed by exposure to UVA (320–400 nm) or narrow-band UVB (311 nm). Repeated exposures are given two, three, or four times weekly until clearing in psoriasis is obtained in 12 to 22 exposures. This is followed by maintenance with a gradual reduction: once weekly for 1 month, once biweekly for 1 month, and then once per month for 2 months. Treatments are then stopped, and there are varying periods of remission from 6 months to years; treatments are resumed with recurrences of the psoriasis. The most commonly reported side effects of PUVA therapy are nausea and pruritus, which occur in approximately 15% of patients. 46 Rarely, the use of oral methoxsalen in PUVA therapy is limited by drug intolerance , manifested as severe nausea 78 ; bergapten is better tolerated with less or no nausea. In some individuals, PUVA therapy is more difficult because of skin phototoxicity reactions in the form of severe erythema, edema, and even blistering; therefore, cautious UVA dosimetry and delivery are required to clear psoriasis, especially in light-sensitive individuals (skin phototypes I and II). In the more than two decades since PUVA was introduced for the treatment of psoriasis vulgaris , 56 there has been substantial progress in modifying and optimizing the therapy. Evidence to date suggests that the incidence of short-term risks, primarily the signs and symptoms of inflammation, 1 , 74 and long-term hazards such as skin cancer, 18 , 23 , 38 , 44 , 47 , 59 , 60 , 68 , 72 actinic degeneration, 15 , 28 , 30 , 62 , 73 and immunologic 34 , 36 , 48 , 49 , 51 and ophthalmologic 8 , 10 , 12 , 32 , 39 , 40 , 41 , 55 , 71 effects of UV radiation, are related to the total number of treatments and the degree of inflammation induced by each treatment. Skin cancer and actinic degeneration are known to result from the accumulated effects of sun exposure, but the exact relationship to the number of exposures, the degree of sunburn, or the total cumulative dose is not known.