Talmon Aviv, Elias Shlomo, Rubin Limor, Ribak Yaarit, Ben Dori Eyal, Shamriz Oded, Lotem Michal, Adini Irit, Tal Yuval
Allergy and Clinical Immunology Unit, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
J Allergy Clin Immunol Glob. 2023 Jun 23;2(3):100128. doi: 10.1016/j.jacig.2023.100128. eCollection 2023 Aug.
Pruritus can be an intolerable symptom in patients with cancer. Type 2 inflammation, and specifically, the cytokines IL-4, IL-13, and IL-31, play major roles in the itching process. Dupilumab is an antibody against IL-4Rα, which is a common IL-4 and IL-13 receptor subunit. Blocking IL-4 and IL-13 activity reduces the synthesis of IL-31, the "itch cytokine," and receptors for these 3 cytokines are expressed on itch nerves. Dupilumab is approved for treating moderate-to-severe atopic dermatitis, of which itching is a significant symptom.
The objective of this case study was to present the initial evidence of the safety and efficacy of dupilumab as a treatment for intractable malignancy-associated pruritus in 3 patients, thereby providing a basis for further investigation in a larger cohort.
As a proof of concept, we used dupilumab in our center to treat 3 patients with intractable malignancy-associated pruritus. The first patient was a 73-year-old male with a history of prostate cancer, the second patient was a 75-year-old female with cutaneous T-cell lymphoma, and the third patient was a 32-year-old male with metastatic melanoma. All 3 patients experienced debilitating itching, which started at some stage after the malignancy had been diagnosed. Moreover, none of the 3 patients showed clinical evidence of atopic dermatitis or other causes of itching (eg, uremia or liver failure), and none of the 3 patients responded to conventional treatments for pruritus.
Biweekly treatment with dupilumab led to an immediate improvement in itching, which subsided entirely after a few doses without any significant adverse effects.
We propose that dupilumab is a safe and effective treatment for intractable malignancy-associated pruritus, and we are currently testing it in a large cohort.
瘙痒可能是癌症患者难以忍受的症状。2型炎症，尤其是细胞因子白细胞介素-4（IL-4）、白细胞介素-13（IL-13）和白细胞介素-31（IL-31），在瘙痒过程中起主要作用。度普利尤单抗是一种抗IL-4Rα的抗体，IL-4Rα是常见的IL-4和IL-13受体亚基。阻断IL-4和IL-13的活性可减少“瘙痒细胞因子”IL-31的合成，并且这三种细胞因子的受体在瘙痒神经上表达。度普利尤单抗被批准用于治疗中度至重度特应性皮炎，瘙痒是其显著症状。
本病例研究的目的是展示度普利尤单抗治疗3例顽固性恶性肿瘤相关性瘙痒安全性和有效性的初步证据，从而为在更大队列中进行进一步研究提供依据。
作为概念验证，我们在本中心使用度普利尤单抗治疗3例顽固性恶性肿瘤相关性瘙痒患者。首例患者为一名73岁男性，有前列腺癌病史；第二例患者为一名75岁女性，患有皮肤T细胞淋巴瘤；第三例患者为一名32岁男性，患有转移性黑色素瘤。所有3例患者均经历了使人衰弱的瘙痒，瘙痒在恶性肿瘤被诊断后的某个阶段开始。此外，这3例患者均未表现出特应性皮炎或其他瘙痒原因（如尿毒症或肝功能衰竭）的临床证据，并且这3例患者对瘙痒的传统治疗均无反应。
每两周使用度普利尤单抗治疗可使瘙痒立即改善，在使用几剂后瘙痒完全消退，且无任何显著不良反应。
我们提出度普利尤单抗是治疗顽固性恶性肿瘤相关性瘙痒的一种安全有效的方法，我们目前正在一个大型队列中对其进行测试。
