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Granulocytopenia Due to Nifuroxazide followed by a G-CSF- Induced Leukemoid Reaction

had no familial history of vitiligo nor personal or familial history of autoimmune diseases. He experienced occupational exposure to trichloroethylene and cyanides until 1993. Due to the worsening of his condition, bilateral pallidotomy was performed in July 1998; however, drug therapy was continued. In the months following pallidotomy, his skin lesions continued to enlarge and reached the elbow, and new achromic lesions appeared on both knees. Discussion. While the pathogenesis of vitiligo is unknown, hypotheses concerning its etiology have focused on autoimmune, autocytotoxic, and neural mechanisms.4 The autocytotoxic theory suggests that melanocytes are damaged by precursors of melanin, such as tyrosine and levodopa. Tyrosinase hydroxylase catalyzes the hydroxylation of tyrosine to levodopa, followed by the dehydrogenation of levodopa to dopaquinone. The results of biochemical and cytologic investigations suggest that substances that block tyrosinase directly or indirectly (e.g., tyrosine, levodopa, other amino acids, phenolic, catechol compounds) exert a cytotoxic effect (cytotoxic inhibition) on melanocytes. Small amounts of levodopa are necessary to activate tyrosinase, but excessive tyrosine or levodopa concentrations block this enzyme, resulting in cellular damage. Moreover, the presence of levodopa in melanocyte cultures decreases protein and cellular DNA synthesis.5 The concomitant administration of levodopa/carbidopa and tolcapone increases levodopa plasma concentrations by inhibiting dopa-decarboxylase and COMT-mediated levodopa metabolism.2 The resulting increase in levodopa concentration potentially affected melanin synthesis, leading to vitiligo. To date, no published cases of vitiligo or skin discoloration have been associated with tolcapone, levodopa, pergolide, trichloroethylene, or cyanides. Any contribution of the patient’s occupational exposure to trichloroethylene and cyanides is therefore unlikely. Although the use of tolcapone will probably be restricted due to its hepatotoxicity, the significance of this case report lies in its relation to the possible etiology of certain cases of vitiligo. Special attention should be paid to additional case reports of vitiligo associated with other COMT inhibitors.