与先天性白细胞介素 17A 受体阻断有关的脓皮病:两例病例的报告和文献综述。

IF 1.6 4区 医学 Q3 DERMATOLOGY
Cynthia M Magro, Neil Crowson, Taylor Kalomeris, Gerard Nuovo
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引用次数: 0

摘要

坏疽性脓皮病(PG)是一种罕见的坏死性嗜中性皮肤病,由单核细胞和自反应性 T 细胞分别分泌的单核因子和细胞因子驱动。Th1介导的自身免疫性疾病和骨髓增生性疾病可能与此病有关。最近,某些药物,包括 TNF-α 抑制剂、利妥昔单抗和 IL-17A 抑制剂(如 secukinumab)也被认为与此有关,PG 的发生被认为是皮肤免疫不良反应。我们介绍了两名在使用具有 IL-17A 抑制作用的药物治疗时出现类似 PG 的自身炎症综合征的患者。其中一名患者使用的药物是erunumab,另一名患者使用的药物是secukinumab。其中一名患者接受了抗降钙素基因相关肽靶向疗法艾伦单抗来预防偏头痛。虽然这种药物以前并未与 PG 的发病有关,但它会导致 IL-17A 受体阻断。另一名患者正在使用secukinumab,这是一种选择性靶向IL-17A的单克隆抗体。我们记录了一个富含IL-17A的微环境,强调阻断影响的是受体的功能,而不是T细胞产生IL-17A的数量减少。IL-17A的定性功能性阻断可能会导致IL-23的矛盾性增加,而IL-23是一种促炎细胞因子,可能会导致中性粒细胞的大量涌入,这在病理上与PG有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pyoderma Gangrenosum Associated With Iatrogenic Interleukin 17A Blockade: A Report of Two Cases and a Review of the Literature.

Pyoderma gangrenosum (PG) is a rare necrotizing neutrophilic dermatosis driven by monokines and cytokines elaborated by monocytes and autoreactive T cells, respectively. Th1-mediated autoimmune disorders and myeloproliferative disease are among the potential disease associations. More recently, certain medications were implicated, including TNF-alpha inhibitors, rituximab, and IL-17A inhibitors, such as secukinumab, where the development of PG is held to represent a cutaneous immune adverse effect. We present two patients who developed an autoinflammatory syndrome resembling PG in the setting of drug therapy with agents exhibiting an IL-17A inhibitory effect. The drugs were erunumab in one and secukinumab in the other. One patient received the anti-calcitonin gene-related peptide targeted therapy, erenumab, for migraine prophylaxis. While this drug has not been previously implicated in the development of PG, it can cause IL-17A blockade. The other patient was on secukinumab, a monoclonal antibody that selectively targets IL-17A. We documented a microenvironment enriched in IL-17A, emphasizing that the blockade impacts the functionality of the receptor as opposed to a quantitative reduction in IL-17A production by T cells. Qualitative functional IL-17A blockade could result in a paradoxical increase in IL-23, a pro-inflammatory cytokine that may contribute to the influx of neutrophils pathogenetically implicated in PG.

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来源期刊
CiteScore
3.20
自引率
5.90%
发文量
174
审稿时长
3-8 weeks
期刊介绍: Journal of Cutaneous Pathology publishes manuscripts broadly relevant to diseases of the skin and mucosae, with the aims of advancing scientific knowledge regarding dermatopathology and enhancing the communication between clinical practitioners and research scientists. Original scientific manuscripts on diagnostic and experimental cutaneous pathology are especially desirable. Timely, pertinent review articles also will be given high priority. Manuscripts based on light, fluorescence, and electron microscopy, histochemistry, immunology, molecular biology, and genetics, as well as allied sciences, are all welcome, provided their principal focus is on cutaneous pathology. Publication time will be kept as short as possible, ensuring that articles will be quickly available to all interested in this speciality.
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