New Onset of Alcohol Flushing in an Atopic Dermatitis Patient Treated with Dupilumab

Dear Editor:

Dupilumab is a monoclonal antibody that targets the alpha subunit of the interleukin-4 receptor. It has been used as an effective treatment for moderate to severe atopic dermatitis (AD) patients¹. The adverse events include conjunctivitis, herpes simplex virus infection, and injection site reaction in varying proportions¹. A 20-year-old male patient visited our hospital with pruritic erythematous plaques on the entire body from childhood. Based on the clinical findings, AD was diagnosed, and treatment with cyclosporine 100~200 mg was prescribed for more than one year. Because the cyclosporine treatment had not been effective, dupilumab administration was initiated. Subsequently, the patient’s clinical symptoms improved rapidly; however, after several months, he complained of facial flushing within a few minutes of consuming small amounts of alcohol (Fig. 1). He complained that this symptom lasted for less than one hour and had never occurred before treatment with dupilumab. No medications or topical agents were being taken concurrently. We considered the flushing in this patient as a rare adverse event that could occur after treatment with dupilumab, and the patient was educated to avoid alcohol consumption during the post-treatment period.

Fig. 1. (A, B) Clinical photography of cutaneous manifestations showing diffuse erythematous patches distributed from the face to the neck after alcohol consumption (we received the patient’s consent form about publishing all photographic materials).

Flushing is a transient erythema that most commonly occurs in the face because of an increase in cutaneous blood flow following vasodilation. One of the causes is the use of vasoactive substances, which include medication, food, and alcohol². Alcohol flushing is caused by an increase in the acetaldehyde level due to deficiency or inactivity of aldehyde dehydrogenase 2 (ALDH2), which plays a major role in alcohol metabolism²,³. Igelman et al.⁴ suggested that alcohol flushing caused by dupilumab could be due to a change in cytochrome P450 2E1 (CYP2E1) activity rather than the change in ALDH2 activity because dupilumab is known to affect the formation of the cytochrome P450 enzyme. Because the mechanism of alcohol metabolism is described as being associated with the CYP2E1 pathway, which is considered to be a minor pathway³, it may be explained that alcohol flushing caused by dupilumab rarely occurs. However, the possibility that other mechanisms may be involved cannot be ruled out, and further studies may be needed to determine whether dupilumab actually affects the activity of CYP2E1. Although it has been reported that facial erythema may occur after dupilumab¹, alcohol flushing is different in that it occurs only after alcohol intake, and is transient because it disappears within one hour when the intake is stopped.

There have been two cases reported in the literature for the new onset of alcohol flushing related to dupilumab⁴,⁵. Both patients in the reported cases were Caucasian, and as in this case, the flushing lasted less than one hour, and no topical agents were being used concurrently. To the best of our knowledge, new-onset alcohol flushing caused by dupilumab has not yet been reported in Asians. As alcohol flushing is prevalent in Asians because of a genetic polymorphism², it would be important to determine whether it is a new symptom after dupilumab treatment, which will help patient education and the continued use of dupilumab as a treatment.