Facial flush reaction after alcohol ingestion during topical pimecrolimus and tacrolimus treatment.

tion of small quantities of beer or wine. The patients reported the sudden onset of an itching-burning sensation quickly followed by flushing. The facial reaction occurred within 5 and 10 min after the alcohol ingestion and between 2 and 4 weeks after the start of the treatment. The erythema was confined not only to the treated facial areas, but it also extended to the healthy skin, and its total extension varied among the patients. No other systemic symptoms or signs were recorded during the development of the flush reaction. The facial flushing disappeared after 20–30 min from its beginning. After the end of the treatment, the flush reaction of the face did not reappear even after alcohol intake. None of the patients had experienced such symptoms before, had ever noted intolerance to topical products containing ethanol or was suffering from rosacea. The association between a flush reaction of the face and alcohol consumption has already been described, occurring in 6–7% of the topical-tacrolimus-treated patients [1, 5] ; to our knowledge, no similar associations for pimecrolimus-treated patients have been observed up to date. Furthermore, alcohol intolerance has usually been reported in patients with atopic dermatitis. This is the first report in patients with vitiligo. The exact pathophysiological mechanism is still unknown, but 3 hypotheses can be formulated. Either ethanol or calcineurin inhibitors have been shown to induce the release of neuropeptides, and probably their combination could lead to an extreme vasodilatation [6] . The second hypothesis is linked to the aldehyde-dehydrogenase-inhibiting function of the calcineurin inhibitors in the areas where they are applied; in this way, the subsequent accumulation of acetaldehyde could lead to vasodilatation following alcohol consumption as described for disulfiram-treated patients after alcohol ingestion [7] . The third hypothesis is linked to a possible interaction of the two drugs on the calcineurin-calmodulin-calcium complex where both alcohol and tacrolimus/pimecrolimus are known to act [8] . Moreover, an abundant presence of Demodex mites has been observed in patients with flares of rosacea occurring during topical tacrolimus and pimecrolimus treatment [2, 9] . It is possible that the treatments with calcineurin inhibitors lead to an incipient rosacea with flares that appear after alcohol consumption. Despite its difficult pathogenesis and the absence of predictive factors, the flush reaction of the face should be recognized as a new side effect of the treatment with topical calcineurin inhibitors, both pimecrolimus and tacrolimus, independently from the skin disease.