Eczematous drug eruption in psoriasis patients under anti-IL-17A: does IL-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.