Atopic dermatitis exacerbation after Covid‐19 vaccination in Dupilumab‐treated patients

Abstract

Dear Editor, Vaccination is the main weapon against COVID-19 pandemic. Two mRNA vaccines [Comirnaty® (Pfizer/BioNTech; BNT162b2) and Spikevax® (Moderna; mRNA-1273)] and 2 viral vector-based vaccines [Vaxzevira® (AstraZeneca; AZD1222) and COVID-19 vaccine Janssen® (Johnson & Johnson; Ad26.COV2.S)] are currently approved in Italy.1, 2 Atopic dermatitis (AD) is not a contraindication to COVID-19 vaccination and the treatment with dupilumab [a fully human anti-interleukin (IL)-4 receptor alpha monoclonal antibody blocking both IL-4 and IL-13 signalling] seems not to be associated to a reduction in vaccination response.3-6 Few cases of AD flare following vaccines administration were reported.7, 8 The aim of this study was to evaluate the frequency and clinical features of AD flare after COVID-19 vaccine administration in AD patients treated with dupilumab. Therefore, data regarding AD outpatients attending the Dermatology Unit of the University of Naples Federico II from January 2021 to October 2021 were collected. Four-hundred and eighty subjects (256 male; 53.33%; mean age: 58.66 ± 16.71 years) were enrolled. They all were affected with moderate-to-severe AD [mean Eczema Area Severity Index (EASI) before starting dupilumab treatment: 18.61 ± 4.30] and were in treatment with dupilumab at labelled dosage. AD flare was defined as an episode requiring escalation of treatment with a worsening of EASI or needing rescue therapy.9 Four hundred and seven (84.79%) patients had been vaccinated (Table 1): 289 (71%) with Comirnaty®, and 62 (15.23%), 47 (11.54%), and 9 (2.2%) with Spikevax®, Vaxzevira® and COVID-19 vaccine Janssen®, respectively. The general characteristics of study population are reported in Table 1. Eleven (2.7%) subjects (6 male, 54.54%; mean age: 45.18 ± 16.33 years; mean EASI: 9.43 ± 3.97) were admitted to our Department for AD exacerbation (Table 2). The AD flare was reported 7.27 ± 3.20 days after the vaccination. No statistically significant differences between the types of vaccine were assessed, and no significant differences between the first and second doses of vaccine in terms of AD flare have been observed. Rescue treatment with topical corticosteroid or calcineurin inhibitor led to the healing of the flare in all the cases (mean time of treatment 10.25 ± 4.33 days); no patient discontinued dupilumab (Table 2). Flare of some dermatologic diseases (such as psoriasis, urticaria, lichen planus or vitiligo) after COVID-19 vaccine was reported.10 In our experience, AD exacerbation after the vaccine occurred in some patients treated with dupilumab. However, only a small percentage (2.7%) developed the flare. The mechanism of AD flare after COVID-19 vaccination is not clear. The vaccination seems to act as a trigger of the skin disease. However, while the role of T helper (Th) 1 response following the COVID-19 vaccination has been investigated, there are no data on Th2 response.11 Dupilumab did not seem to interfere with AD worsening in our patients. Our experience shows the possible worsening of AD in a small percentage of patients with moderate-to-severe disease treated with dupilumab apparently in correlation with COVID-19 vaccination and regardless of the vaccine administered. Apart from the apparent temporal correlation, it is difficult to establish an obvious cause-effect relationship between vaccination and skin rash, since AD is naturally characterized by exacerbation and flare-up. However, it should be noted that, although in the literature there are reported cases of eczematous eruptions associated with COVID-19 vaccination, to the best of our knowledge in only one patient treated with dupilumab this rash was interpreted as AD flare.7, 8 Furthermore, in our patients the flare appears to be easily controlled with simple topical therapies. Therefore, COVID-19 vaccination should not be discouraged in AD patients, also if under treatment with dupilumab. The patients in this manuscript have given written informed consent to publication of their case details. Luca Potestio: conceptualization, validation, visualization, writing-original draft preparation. Maddalena Napolitano: conceptualization, validation, visualization, writing-original draft preparation, writing – review & editing. Luigi Bennardo: data curation, formal analysis, investigation, visualization, writing-original draft preparation. Gabriella Fabbrocini: conceptualization, validation, visualization, writing-review & editing, supervision. Cataldo Patruno: conceptualization, validation, visualization, writing-original draft preparation, writing – review & editing. M.N. acted as speaker, consultant and advisory board member for Sanofi, Abbvie, Leo Pharma and Novartis, EliLilly; G.F. has been principal investigator in clinical trials sponsored by and/or and has received personal fees from AbbVie, Abiogen, Almirall, Celgene, Eli-Lilly, Leo Pharma, Novartis, Sanofi, and UCB; C.P. acted as investigator, speaker, consultant, and advisory board member for AbbVie, Eli Lilly, Leo Pharma, Novartis, Pfizer, Pierre Fabre and Sanofi. Not required. None. Data are reported in the current study.

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