Eczematous drug eruption in patients with psoriasis under anti‐interleukin‐17A: does interleukin‐22 play a key role?

Background: Eczematous drug eruption (EDE) is a spongiotic skin reaction in response to systemic medications. Up to now, EDE has been described in patients treated with anti-IL17A monoclonal antibodies with a prevalence of 2.2-12.1%. Objectives: To describe the clinical and histologic features, and the skin cytokines milieu in patients with EDE induced by anti-IL-17A, secukinumab and ixekizumab. Methods: A prospective study, enrolling psoriasis patients who developed EDE during treatment with 2 anti-IL17, ixekizumab and secukinumab, from June 2019 to April 2021, was conducted. A 5 mm lesional(Les) and a 3 mm non-lesional(NLes) skin biopsy were taken from all the patients. Les sample was splitted in two parts, one for histological examination and the other for cytokines profile evaluation. Results: 289 patients were treated with anti-IL17A mAb during the study period. Eight (2.8%) patients developed EDE during the treatment. Histopathological evaluation suggested a diagnosis of spongiotic dermatitis in all the patients. Cytokine-gene-expression showed predominance of Th2/Th22 cytokines in EDE-lesions with strong increase of IL-4, IL-22, and S100A7 levels in both Les and Nles skin compared to healthy skin. A significant enhancement of IL-4, IL-22, and S100A7 in Les compared to Nles skin was observed. IL-26 levels were significantly increased compared to healthy skin. Low levels of IL-23A were found both in Les and Nles skin. Conclusion: EDE skin lesions have mainly Th2/Th22 features, with IL-22 playing a major role in the pathogenesis. EDE can be considered as the result of the imbalance towards Th2/Th22 response secondary to the blockade of IL-17A-activity.