Megna Matteo, Caiazzo Giuseppina, Parisi Melania, Ruggiero Angelo, Capasso Gianmarco, Mascolo Massimo, Russo Daniela, Gallo Lucia, Fabbrocini Gabriella, Napolitano Maddalena, Patruno Cataldo
Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy.
Pathology Unit, Department of Advanced Biomedical Sciences, University of Naples Federico II, Napoli, Italy.
Clin Exp Dermatol. 2022 May;47(5):918-925. doi: 10.1111/ced.15052. Epub 2022 Feb 9.
Eczematous drug eruption (EDE) is a spongiotic skin reaction in response to systemic medications. To date, EDE has been described in patients treated with anti-interleukin (IL)-17A monoclonal antibodies with a prevalence of 2.2%-12.1%.
To describe the clinical and histological features and the skin cytokine milieu in patients with EDE induced by anti-IL-17A biologics.
This was a prospective study, enrolling patients with psoriasis who developed EDE during treatment with two anti-IL-17 biologics, ixekizumab and secukinumab, from June 2019 to April 2021. Skin biopsies were taken from all patients: a 5-mm lesional biopsy (LB) and a 3-mm nonlesional biopsy (NLB). The LB sample was split into two parts, one for histological examination and the other for cytokine profile evaluation.
During the study period, treatment with an anti-IL-17A drug was given to 289 patients of whom 8 (2.8%) developed EDE during the treatment. Histopathological evaluation suggested a diagnosis of spongiotic dermatitis in all eight patients. Cytokine gene expression showed a predominance of T helper (Th)2/Th22 cytokines in EDE lesions with a large increase in IL-4, IL-22 and S100A7 levels in both LB and NLB samples compared with healthy skin. IL-4, IL-22 and S100A7 were significantly higher in LB compared with NLB samples. IL-26 levels were also significantly increased in both LB and NLB compared with healthy skin, whereas low levels of IL-23A were found in both LB and NLB.
Eczematous drug eruption skin lesions have mainly Th2/Th22 features, with IL-22 playing a major role in their pathogenesis. EDE seems to be the result of an imbalance towards a Th2/Th22 response, secondary to the blockade of IL-17A activity.
药疹性湿疹（EDE）是一种针对全身性药物的海绵状皮肤反应。迄今为止，已有接受抗白细胞介素（IL）-17A单克隆抗体治疗的患者出现EDE的相关报道，其患病率为2.2%-12.1%。
描述抗IL-17A生物制剂诱导的EDE患者的临床和组织学特征以及皮肤细胞因子环境。
这是一项前瞻性研究，纳入了2019年6月至2021年4月期间在使用两种抗IL-17生物制剂（依奇珠单抗和司库奇尤单抗）治疗银屑病过程中发生EDE的患者。对所有患者进行皮肤活检：取5毫米的皮损活检（LB）和3毫米的非皮损活检（NLB）。LB样本分为两部分，一部分用于组织学检查，另一部分用于细胞因子谱评估。
在研究期间，289例患者接受了抗IL-17A药物治疗，其中8例（2.8%）在治疗期间出现EDE。组织病理学评估显示所有8例患者均诊断为海绵状皮炎。细胞因子基因表达显示EDE皮损中辅助性T（Th）2/Th22细胞因子占主导，与健康皮肤相比，LB和NLB样本中的IL-4、IL-22和S100A7水平大幅升高。与NLB样本相比，LB中的IL-4、IL-22和S100A7显著更高。与健康皮肤相比，LB和NLB中的IL-26水平也显著升高，而LB和NLB中均发现低水平的IL-23A。
药疹性湿疹皮肤病变主要具有Th2/Th22特征，IL-22在其发病机制中起主要作用。EDE似乎是IL-17A活性被阻断后向Th2/Th22反应失衡的结果。
