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PhD Candidate, Hospital Pharmacy Resident Pharmacy Department Hospital del Mar Institut Municipal d'Assistència Sanitària (IMAS) Barcelona, Spain
Clinical Pharmacist Pharmacy Department Hospital del Mar–IMAS Passeig Marítim, 25-29 08003 Barcelona, Spain fax 34 93 248 32 56 FMateu{at}imas.imim.es
Clinical Pharmacist Pharmacy Department Hospital del Mar–IMAS
PhD Candidate, Hospital Pharmacy Resident Pharmacy Department Hospital del Mar–IMAS
Published Online, March 8, 2005. www.theannals.com, DOI 10.1345/aph.1E529
Case Report. A 27-year-old white woman had been diagnosed with atopic dermatitis in childhood. Nine years ago, she had presented with vitiligo on the face, hands, and elbows. She was treated with topical corticosteroids without good results. In July 2004, she began treatment with topical tacrolimus 0.1% once daily on the affected areas while discontinuing corticosteroids and taking no other medication. After one month of tacrolimus use, she ingested 40 mL of wine, equivalent to 5 mL of alcohol. Five minutes later, she presented with facial flushing, periocular edema, intense itching, and skin irritation on the area of facial tacrolimus application. The episode resolved in 30 minutes. On rechallenge with 10 mL of wine, equivalent to 1.2 mL of alcohol, she did not present with periocular edema, and the other symptoms were less intense. This episode resolved in 10 minutes. At this time, the tacrolimus blood concentration was undetectable as determined by IMx (Version 4.0, Abbott Scientific Diagnostics, Madrid, Spain). She was advised to avoid alcoholic beverages and since then has remained free of adverse reactions. The Naranjo probability scale indicated a highly probable association between the alcohol intake and topical tacrolimus therapy.2
Discussion. This adverse event has been described as alcohol intolerance in clinical trials, but this description may lead one to misinterpret it as a systemic disulfiram-like reaction (DLR).1 DLR presents as flushing of the face and hands, headache, vomiting, hypotension, palpitations, and respiratory difficulties in patients taking certain drugs and exposed to alcohol.3 If tacrolimus interacted with alcohol as disulfiram does, the amount of alcohol ingested by our patient would have been enough to trigger a mild DLR. Since this did not happen, a systemic DLR was unlikely in this case. In our patient, the adverse event was not related to the tacrolimus blood concentration, although its intensity was correlated with the amount of alcohol ingested.
Two mechanisms could explain this interaction. Alcohol prevents the formation of the calcineurin–calmodulin–calcium complex.4 Tacrolimus also acts on this biochemical pathway, and an interaction could be supposed. Alternatively, facial erythema had been related to the cutaneous aldehyde dehydrogenase inhibition in areas where tacrolimus was applied. The subsequent accumulation of acetaldehyde through prostaglandins as mediators could lead to vasodilation following alcoholic consumption. It could be called a local DLR. Aspirin could inhibit this reaction.5 However, none of these mechanisms explained why alcohol intolerance has not been reported with oral tacrolimus or why it was only present on the face and not on other areas of tacrolimus application.
In conclusion, this adverse event was confined to the face, its intensity was related to the ingested alcohol amount, and it seemed to be a local DLR. Clinicians should advise patients to avoid alcoholic beverages while being treated with topical tacrolimus.
References
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