Adverse effects of dupilumab have been noted to include pathologies of the ocular surface, including conjunctivitis, blepharitis, keratitis, eye pruritus, dry eye, nasopharyngitis, upper respiratory tract infection, herpes simplex virus, exacerbation of AD, injection-site infection, facial redness, alopecia, and arthralgia [8, 9]. Biologic therapies such as dupilumab inhibit certain cytokines and suppress inflammation of the target organs, but often paradoxically induce or enhance inflammation in other organs. These phenomena are called “paradoxical reactions”[10]. Head and neck erythema have been reported as paradoxical reactions after dupilumab therapy for AD [11]. Histological examination of skin biopsies of such erythema have revealed a psoriasiform reaction pattern suggestive of a drug-induced skin reaction [11]. The frequency of conjunctivitis in clinical trials of dupilumab and in real-world data from a systematic review and meta-analysis have been reported as 8.6–22.1% and 26.1%, respectively [8, 9]. This report presents a case of allergic conjunctivitis associated with eosinophilia as paradoxical reactions induced by dupilumab therapy for AD.

Case report A 46-year-old woman was referred to the ocular inflammation service at Nippon Medical School Tama-Nagayama Hospital, for bilateral red eyes and itchiness. She was undergoing a sixth cycle of dupilumab in 10 weeks for AD. Slit lamp examination revealed bilateral conjunctive hyperemia, papillary hyperplasia, and bilateral blepharitis (Fig. 1 a). No intraocular inflammation was evident in either eye. She had no past ocular history. Blood tests revealed a high eosinophil count (1400 cells/μL) and a high concentration of IgE (8520 IU/mL) at her first visit to our ocular inflammation service. Atopic dermatitis was improved after dupilumab administration, with the Investigator Global Assessment scale for Atopic Dermatitis (IGA) score improved from 4 before dupilumab administration to 2 at 10weeks after starting dupilumab therapy. However, at the same time as improvement of dermatitis, allergic conjunctivitis paradoxically occurred. When the conjunctivitis appeared (ie, after 10 weeks of dupilumab administration), serum IgE levels were lower than before dupilumab administration (Fig. 2 a). If the allergic conjunctivitis had been a response to pollen or other antigens, serum IgE levels should have been increased, as serum IgE levels in patients with allergic conjunctivitis have been reported as high [12]. In addition, the patient had no nasal symptoms suggestive of allergic rhinitis, such as runny nose