One of the most important uses of cimetidine in dermatological therapy is to reduce the dapsone induction of methemoglobinemia. Cimetidine reduces the hepatic oxidation of dapsone to the hydroxylamine, thereby limiting methemoglobinemia formation. This strategy allows maintenance of higher daily dosages of dapsone, sometimes even in excess of 200 mg.

In one study, co-administration of cimetidine with dapsone kept methemoglobin levels at 30% below the control values for nearly three months. Eight patients with dermatitis herpetiformis, linear IgA disease, or folliculitis decalvans, who were on long term dapsone therapy, added cimetidine, 1.6 g daily, for three months. Their mean methemoglobin level fell in the third week.

However, there was a significant fall in the visual analogue score for headache. The patients also reported a significant decrease in lethargy. These improvements were not associated with any deterioration in the control of the various skin disorders. Similar findings were obtained in an earlier study in dermatitis herpetiformis patients.

In rats, cimetidine has been shown to be more effective than ranitidine or famotidine in the reversible inhibition of the toxic metabolic pathway which produces dapsone’s hydroxylamine metabolite. Cimetidine also did not appear to inhibit the detoxification pathways of dapsone or cytosolic acetylation because of its greater affinity for cytochrome P-450.

Cimetidine has yet to be proven to be an effective monotherapy for dermatological diseases. It seems that cimetidine is probably most effective when used in conjunction with other medications. Promising uses include treating urticaria in conjunction with other antihistamines, and treating warts in conjunction with levamisole.

Despite its common use, cimetidine has few cutaneous side effects. It has been reported to precipitate erythema multiforme and toxic epidermal necrolysis. Cross-reaction with famotidine to induce erythema multiforme has been reported in cases where cimetidine-related erythema multiforme has already occurred.

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