TEGAFUR-INDUCED PHOTOSENSITIVITY - EVALUATION OF PROVOCATION BY UVB IRRADIATION

A 75-year-old Japanese man with photodistributed erythematous lichen p lanus like eruptions visited the dermatology clinic of Kobe University in November 1994. He had had an operation for gastric cancer in July 1992, and thereafter he had been taking 600 mg/d of tegafur. In July 1 994, he was exposed to the sun for 2 h and the following day noticed a n itchy rash in the areas exposed to the sun. He consulted his surgeon and stopped taking the tegafur in October. Thereafter his eruption gr adually improved. A biopsy specimen taken on the initial visit to our hospital, 22 days after the cessation of tegafur, revealed perivascula r collections of mononuclear cells in the upper dermis and slight liqu efaction degeneration of the epidermal basal cells with some civatte b odies. Immunofluorescent staining showed no deposits of immunoglobulin s or complements. Photosensitivity studies were performed with a bank of 7 fluorescent sunlamps (Toshiba FL20SE) emitting 280-370 nm (mainly UVB energy, peaking at 305 nm) and a bank of 14 fluorescent black lig hts (Toshiba FL32SBL) emitting 300-420 nm (mainly UVA energy peaking a t 365 nm). His minimal erythema doses (MEDs) of 58.5 mJ/cm(2) in UVB a nd of large dose of UVA over 12.6 J/cm(2) were in the normal range. Pa tch tests and two sets of photopatch tests were made with 5% tegafur a nd 5-fluorouracil (5-FU) in white petrolatum using Finn chambers. One set was exposed to 6.3 J/cm(2) of UVA, and a second set to a suberythe mal dose of UVB, 40 mJ/cm(2), after 24 h of closed patch tests. Twenty four hours after UV irradiation for photopatch tests, and 48 h after the initial patch for patch tests, the reaction was evaluated. No abno rmal reactions in patch and photopatch tests were detected. Tegafur wa s readministered at a dose of 200 mg every eight hours. After a total dose of 2400 mg (day 4), the skin of the back was exposed to UVB (6-12 0 mJ/cm(2)) and UVA (2-12.6 J/cm(2)) two hours after the last oral int ake of tegafur. No decrease in MED or any abnormal reaction was observ ed. After a total of 3600 mg (day 6), a new skin site on the back was exposed to 3 MED of UVB. The next day (day 7, after a total dose of 42 00 mg), 3 MED of UVB was irradiated on the same site and 5 MED of UVB was irradiated at a new site. Lastly, after a total dose of 4800 mg (d ay 8), 3 MED and 5 MED of UVB was again irradiated on the same sites t hat were irradiated on the previous day, and 10 MED UVB and 21 J/cm(2) UVA were irradiated at new individual sites. Eight days after the las t irradiation (day 16, after 9600 mg of drug intake) the 10 MED UVB ir radiated site revealed millar-sized papules with a faint red hue after sunburn reaction. Simultaneously, an edematous erythema recurred on t he face, neck, upper back, and hands, where the rash had previously be en, without exposure to UVB or UVA. These tests were conducted while t he patient was hospitalized and he was very careful not to be exposed to the sun, even through glass. The biopsy specimens of 10 MED irradia ted sites and the flare-up lesion of his upper back revealed liquefact ion degeneration of the epidermal basal cells with civatte bodies. Imm unofluorescent staining study showed IgM, IgA, and C-4 deposition of t he civatte bodies in the flare-up lesion which had not been exposed to any UV irradiation.