Disulfiram
Disulfiram (Antabuse, Wyeth-Ayerst, Philadelphia, PA) is a nonconventional pharmacologic agent used in therapy for nickel contact dermatitis. It is a chelating agent for metals such as nickel and cobalt, but its main use is as supportive therapy for alcohol addiction. After absorption in the gut, disulfiram metabolizes into sodium diethyldithiocarbamate (DDC) in the liver. This metabolite causes the chelation of nickel, with an increasing concentration in blood and major excretion through urine, bile, and perspiration.[19,20] In the last decades, various studies using disulfiram in nickel-sensitized patients affected by chronic relapsing contact dermatitis have had favorable results in regard to the frequency and intensity of flare-ups. Furthermore, various studies have confirmed the benefit of a low-nickel diet in the management of this eczema, even if diet alone cannot clear the condition but only reduce the frequency and intensity of flare-ups.
In 1979, Kaaber and colleagues described 11 patients treated with disulfiram two to four times daily for 4 to 10 weeks. Seven patients completely cleared, two patients improved, and two patients remained stable. Side effects such as fatigue, headache, and dizziness were noted in seven patients. Nickel urine and serum concentrations gradually increased in the first weeks of treatment, then (after the initial 3 weeks of treatment) decreased in the blood, thus suggesting that disulfiram is able to reduce total body nickel.[19]
In 1982, Christensen treated 11 patients with a daily 200 mg dose of disulfiram for 8 weeks. Three patients healed completely, and the other eight improved considerably. The patients' eczema relapsed after 2 to 16 weeks by the end of therapy.[21]
In 1983, Kaaber and colleagues published the results of a double-blind placebo-controlled trial of treatment with disulfiram in 24 patients for 6 weeks. The result was improvement in the dermatitis and decreasing frequency of flares in the disulfiram-treated groups. Two patients showed hepatotoxicity.[22]
In 1987, Hopfer and colleagues observed 61 patients treated with disulfiram for chronic alcoholism for a period of 4 months to 3 years. They demonstrated that serum, blood, and urine nickel concentrations progressively increased during the initial period of treatment. Animal studies have demonstrated cerebral uptake of the lipophilic nickel-DDC complex; thus, nickel may possibly accumulate in brain cells. Physicians should therefore be cautious in administering disulfiram to persons who have nickelcontaining orthopedic prostheses or occupational exposure to nickel.[23]
In 2006, Sharma described a study involving 21 patients: 11 patients on a nickel-free diet took disulfiram for 4 weeks, and 10 patients made up the placebo (control) group. The eczema healed in 10 patients in the first group, as opposed to one patient in the second group. During the 2 to 12 weeks of follow-up, five patients in the treated group experienced a mild relapse. Three patients showed a mild increase of hepatic enzymes.[24]
Dermatitis. 2011;22(05):251-255. © 2011 American Contact Dermatitis Society
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