Mima Yoshihito, Yamamoto Masako, Iozumi Ken
Department of Dermatology, Tokyo Metropolitan Police Hospital, Tokyo 164-8541, Japan.
J Clin Med. 2025 Apr 27;14(9):3026. doi: 10.3390/jcm14093026.
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, with interleukin (IL)-4, IL-13, and IL-31 recognized as key mediators. Prurigo nodularis (PN) is another chronic inflammatory disorder driven by T helper type 2-mediated inflammation and neural dysregulation, leading to severe pruritus. Nemolizumab, a humanized monoclonal antibody targeting IL-31 receptor A, has been approved for use in the treatment of AD and PN. Clinical trials have demonstrated significant reductions in pruritus and cutaneous symptoms associated with its use. In clinical practice, acute eczema and edematous erythema frequently occur, occasionally necessitating the discontinuation of treatment. Despite these observations, no comprehensive review has examined nemolizumab-associated cutaneous adverse events. This review aimed to examine various cutaneous reactions associated with nemolizumab therapy, including psoriasiform eruptions, AD exacerbation, bullous pemphigoid, drug-induced eruptions, and fungal infections. Potential mechanisms underlying these reactions include T-cell activation due to drug sensitization, immune responses triggered by nemolizumab acting as a hapten, and a relative increase in IL-4 and IL-13 levels following IL-31 inhibition. However, the precise pathophysiological mechanism and risk factors remain unclear, and standardized clinical management guidelines are lacking. Further accumulation of clinical data and immunological research are essential for developing evidence-based strategies to manage these adverse events, ensuring treatment continuity and optimizing patient outcomes.
特应性皮炎（AD）是一种慢性炎症性皮肤病，其特征为表皮屏障功能障碍和免疫失调，白细胞介素（IL）-4、IL-13和IL-31被认为是关键介质。结节性痒疹（PN）是另一种由2型辅助性T细胞介导的炎症和神经失调驱动的慢性炎症性疾病，可导致严重瘙痒。奈莫利珠单抗是一种靶向IL-31受体A的人源化单克隆抗体，已被批准用于治疗AD和PN。临床试验表明，使用该药物后瘙痒和皮肤症状显著减轻。在临床实践中，急性湿疹和水肿性红斑经常发生，偶尔需要停药。尽管有这些观察结果，但尚未有全面的综述研究奈莫利珠单抗相关的皮肤不良事件。本综述旨在研究与奈莫利珠单抗治疗相关的各种皮肤反应，包括银屑病样皮疹、AD加重、大疱性类天疱疮、药物性皮疹和真菌感染。这些反应的潜在机制包括药物致敏导致的T细胞活化、奈莫利珠单抗作为半抗原引发的免疫反应，以及IL-31抑制后IL-4和IL-13水平的相对升高。然而，确切的病理生理机制和危险因素仍不清楚，且缺乏标准化的临床管理指南。进一步积累临床数据和开展免疫学研究对于制定基于证据的策略来管理这些不良事件、确保治疗的连续性以及优化患者预后至关重要。
