Tegafur-induced photosensitivity : evaluation of provocation by UVB irradiation

Dermatology, A 75-year-old Japanese man with photodistributed erythematous lichen planus 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 1994, he was exposed to the sun for 2 h and the following day noticed an itchy rash in the areas exposed to the sun. He consulted his surgeon and stopped i taking the tegafur In October. Thereafter his eruption gradually improved. A biopsy J specimen taken on the initial visit to our hospital, 22 days after the cessation of tegafur, revealed perivascular collections of mononuclear cells in the upper dermis and slight liquefaction degeneration of the epidermal basal cells with some civatte bodies. Immunofluorescent staining showed no deposits of immunoglobulins or complements. Photosensitivity studies were performed with a bank of 7 fluorescent sunlamps (Toshiba FL20SE) emitting 280–370 nm (nnainly UVB energy, peaKing at 305 nm) and a bank ot 14 fluorescent black lights (Toshiba FL32SBL) emitting 300–420 nm (mainly UVA energy peaking at 365 nm). His minimal erythema doses (MEDs) of 58.5 mJ/cm2 in UVB and of large dose of UVA over 12.6 J/cm2 were in the normal range. Patch tests and two sets of photopatch tests were made with 5% tegafur and 5-fluorouracil (5-FU) in white petrolatum using Finn chambers. One set was exposed to 6.3 J/cm2 of UVA, and a second set to a suberythemal dose of UVB, 40 mJ/cm2, 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 abnormal reactions in patch and photopatch tests were detected. Tegafur was 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 (6–120 mJ/cm2) and UVA (2–12.6 J/cm2) two hours after the last oral intake of tegafur. No decrease in MED or any abnormal reaction was observed. 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 4200 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 (day 8), 3 MED and 5 MED of UVB was again irradiated on the same sites that were irradiated on the previous day, and 10 MED UVB and 21 J/cm2 UVA were irradiated at new individual sites. Eight days after the last irradiation (day 16, after 9600 mg of drug intake) the 10 MED UVB irradiated site revealed miliar-sized papules with a faint red hue after sunburn reaction. Simultaneously, an edematous erythema recurred on the face, neck, upper back, and hands, where the rash had previously been, without exposure to UVB or UVA. These tests were conducted while the patient was hospitalized and he was very careful not to be exposed to the sun, even through glass. The biopsy specimens of 10 MED irradiated sites and the flare-up lesion of his upper back revealed liquefaction degeneration of the epidermal basal cells with civatte bodies. Immunofluorescent staining study showed IgM, IgA, and C4 deposition of the civatte bodies in the flare-up lesion which had not been exposed to any UV irradiation.