PROTOPORPHYRIN PHOTOSENSITIVITY CANNOT BE ATTENUATED BY ORAL N-ACETYLCYSTEINE

The photodermatosis in erythropoietic protoporphyria (EPP) is caused b y the accumulation of photosensitizing protoporphyrin (PP) in the skin , due to a defect in ferrochelatase, the enzyme that inserts ferrous i ron into PP to form heme. Hydroxyl radical (.OH) and singlet oxygen ge neration with subsequent lipid peroxidation are thought to play a majo r role in the pathogenesis of the photodermatosis in EPP. Hydrogen per oxide (H2O2) can generate .OH in the Haber-Weiss as well as the Fenton reaction, and is thus a potentially harmful intermediate in the photo reduction of O-2. The use of oxyradical scavengers, such as beta-carot ene, has been reported to be beneficial in the treatment of EPP photod ermatosis. In this study, N-acetylcysteine (NAC) 1800 mg/day was used for 3 reasons: (i) its -SH groups directly scavenge H2O2; (ii) ferroch elatase can be activated by sulfhydryl groups: (iii) NAC was reported to upregulate the glutathione redox system, which is a major endogenou s anti-oxidant system. However, in a double-blind crossover placebo co ntrolled study on 6 EPP patients, we could neither demonstrate an effe ct through photosensitivity tests, nor on light hypersensitivity as re ported by the patients. This dosage of NAC could not increase reduced glutathione and did not affect the red blood cell PP content nor the e xcretion of PP in the feces. Neither were adverse effects observed. We conclude that the oral administration of NAC, in the relatively low d ose used here, is not effective in the treatment of photodermatosis in EPP.