Institute of Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Hindenburgdamm 27, 12203, Berlin, Germany.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
Clin Exp Med. 2023 Dec;23(8):4177-4197. doi: 10.1007/s10238-023-01141-x. Epub 2023 Aug 9.
Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by clonal accumulation of neoplastic T-lymphocytes in the skin. Severe pruritus, one of the most common and distressing symptoms in primary CTCL, can significantly impair emotional well-being, physical functioning, and interpersonal relationships, thus greatly reducing quality of life. Unfortunately, effectively managing pruritus remains challenging in CTCL patients as the underlying mechanisms are, as of yet, not fully understood. Previous studies investigating the mechanisms of itch in CTCL have identified several mediators and their corresponding antagonists used for treatment. However, a comprehensive overview of the mediators and receptors contributing to pruritus in primary CTCL is lacking in the current literature. Here, we summarize and review the mediators and receptors that may contribute to pruritus in primary CTCL to explore the mechanisms of CTCL pruritus and identify effective therapeutic targets using the PubMed and Web of Science databases. Studies were included if they described itch mediators and receptors in MF and SS. Overall, the available data suggest that proteases (mainly tryptase), and neuropeptides (particularly Substance P) may be of greatest interest. At the receptor level, cytokine receptors, MRGPRs, and TRP channels are most likely important. Future drug development efforts should concentrate on targeting these mediators and receptors for the treatment of CTCL pruritus.
原发性皮肤 T 细胞淋巴瘤（CTCL）包括蕈样肉芽肿（MF）和赛泽里综合征（SS），是一组以皮肤克隆性聚集的肿瘤性 T 淋巴细胞为特征的淋巴增生性疾病。瘙痒是原发性 CTCL 中最常见和最令人痛苦的症状之一，它会显著损害情绪健康、身体功能和人际关系，从而大大降低生活质量。不幸的是，由于目前尚未完全了解其潜在机制，有效地管理 CTCL 患者的瘙痒仍然具有挑战性。先前研究 CTCL 瘙痒机制的研究已经确定了几种用于治疗的介质及其相应的拮抗剂。然而，目前的文献中缺乏对原发性 CTCL 瘙痒的介质和受体的全面概述。在这里，我们总结和回顾了可能导致原发性 CTCL 瘙痒的介质和受体，以探索 CTCL 瘙痒的机制，并使用 PubMed 和 Web of Science 数据库确定有效的治疗靶点。如果研究描述了 MF 和 SS 中的瘙痒介质和受体，则将其纳入研究。总的来说，现有数据表明蛋白酶（主要是胰蛋白酶）和神经肽（特别是 P 物质）可能最受关注。在受体水平上，细胞因子受体、MRGPRs 和 TRP 通道可能最为重要。未来的药物开发工作应集中于针对这些介质和受体来治疗 CTCL 瘙痒。
