Department of Medicine 1 & Translational Research Center, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Exp Dermatol. 2019 Dec;28(12):1485-1492. doi: 10.1111/exd.14024. Epub 2019 Sep 9.
Chronic pruritus is a relevant symptom burden in various systemic diseases. It is most commonly observed in patients with chronic kidney disease, hepatobiliary and hematological disorders as well as adverse drug reaction. Recent basic research has unravelled novel treatment targets which are currently in preclinical phases, clinical trials or have already been licensed. While µ-opioid receptor antagonists have been used since decades mainly in cholestatic pruritus, the k-opioid receptor agonist nalfurafine has been licensed in Japan for chronic kidney disease-associated pruritus (CKDaP) as well as cholestatic pruritus. Further κ-opioid receptor agonists are currently investigated in various clinical trials including CKDaP. In recent years, the calcium channel blockers gabapentin and pregabalin have also been recognized as effective anti-pruritus therapy in several internal diseases with the best evidence in chronic kidney disease-associated pruritus. Neurokinin-1 receptor antagonists have been investigated with variable benefit in CKDaP, solid tumors and lymphoproliferative disorders such as cutaneous T-cell lymphoma, Sézary syndrome. Inhibitors of the ileal bile acid transporter (IBAT) represent a selective interruption of the enterohepatic circulation and are currently investigated in various hepatobiliary disorders associated with pruritus. The current development and testing of novel drugs in clinical trials offers hope to struggling physicians and suffering patients.
慢性瘙痒是各种系统性疾病的一个重要症状负担。它最常见于慢性肾脏病、肝胆和血液系统疾病以及药物不良反应的患者。最近的基础研究揭示了新的治疗靶点，这些靶点目前处于临床前阶段、临床试验或已获得许可。虽然 μ-阿片受体拮抗剂已被使用了几十年，主要用于胆汁淤积性瘙痒，但 κ-阿片受体激动剂纳呋拉啡已在日本获得许可，用于慢性肾脏病相关瘙痒（CKDaP）和胆汁淤积性瘙痒。此外，目前正在对包括 CKDaP 在内的各种临床试验中研究其他 κ-阿片受体激动剂。近年来，钙通道阻滞剂加巴喷丁和普瑞巴林也被认为是几种内科疾病有效的止痒治疗方法，在慢性肾脏病相关瘙痒中证据最好。神经激肽-1 受体拮抗剂在 CKDaP、实体瘤和淋巴增生性疾病（如皮肤 T 细胞淋巴瘤、塞扎里综合征）中具有不同的获益，已被研究。回肠胆汁酸转运蛋白（IBAT）抑制剂代表了对肠肝循环的选择性中断，目前正在各种与瘙痒相关的肝胆疾病中进行研究。新型药物在临床试验中的开发和测试为苦苦挣扎的医生和痛苦的患者带来了希望。
