“癢”是人體防禦的重要機轉之一，但持續的癢感會嚴重影響病人生活品質與身心健康。根據統計，超過三分之一的皮膚科病人為癢所困擾。當癢的症狀超過六週以上，我們定義為慢性搔癢，而此疾患對於病人的影響不亞於慢性疼痛。傳統使用的止癢藥物包括抗組織胺和類固醇。其他有研究證實能改善癢感的藥物，包含選擇性血清素再吸收抑制劑（SSRIs）、三環抗憂鬱劑（TCA）、鴉片類藥物、神經傳遞素如Gabapentin和Pregabalin。然而，這些藥物有時並無法有效的控制病人的症狀，尤其是針對慢性搔癢的患者。
　　近幾年，在異位性皮膚炎（Atopic dermatitis）的研究上發現，反覆搔抓會造成細胞的破壞，並釋放胸腺基質淋巴生成素（Thymic stromal lymphopoietin, TSLP）和介白質33（IL-33）。誘導下游的免疫細胞釋放組織胺、神經?、介白質4(IL-4)、介白質13 (IL-13)與介白質31(IL-31)，刺激周邊神經產生癢感。針對此機轉的藥物包括，抑制介白質4受體（IL-4R）的杜避炎（Dupilumab），使用在異位性皮膚炎（Atopic dermatitis）的病人身上能有顯著的止癢效果，已在台灣使用數年。另外，針對介白質13（IL-13）的抗體藥物如Tralokinumab近期獲得美國食品藥物管理局（FDA）認證用於異位性皮膚炎（Atopic dermatitis）的病人，但尚未在台灣上市，而Lebrikizumab仍在臨床試驗中。針對介白質31（IL-31）的抗體藥物Nemolizumab，對於癢有相當好的療效，在2019年獲得美國食品藥物管理局（FDA）認證用於結節性癢疹（Prurigo nodularis）的病人。
　　往癢的致病機轉的下游走，這些與搔癢相關的細胞激素都隸屬於第二型發炎反應，而且都是藉由JAK-STAT路徑作用。多種抑制JAK的口服小分子藥物包括Baricitinib、Upadacitinib及Abrocitinib，和外用的小分子藥物如Delgocitinib，在臨床試驗和實際病人使用上，已被證實能大幅且快速的改善癢的嚴重程度。其中，針對JAK1的抑制對於癢有較明顯的療效。近年來關於癢的治療正快速的進展中，了解這些藥物並針對癢的特定分子進行阻斷將協助臨床醫師有效的幫助病人脫離癢的惡夢。
　　"Itch" is one of the important mechanisms of human defense, but persistent itching affects the quality of life as well as physical and mental health of patients profoundly. According to statistics, more than one-third of dermatological patients are troubled by itching. When pruritus symptom persist for more than six weeks, it could be define as chronic itching, which influences the patient as much as chronic pain. Traditionally, antihistamines and steroids are used to control pruritus. In addition, some different mechanisms of medicine, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), opiates, and neurotransmitters such as gabapentin and pregabalin are proved to be effective in itching reduction. However, in most of the time the efficacy of these drugs is limited, especially for chronic itching.
　　In recent years, research on atopic dermatitis (AD) found that repeated scratching can cause cell damage and release thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL-33), which induce downstream immune cells to release histamine, neuropeptide, IL-4, IL-13 and IL-31, and stimulate peripheral nerves to produce itching sensation. Based on this scenario of pruritus molecular mechanism, several biologics, including dupilumab, tralokiunumab and lebrikizumab which target IL-4 and IL-13 were developed. In fact, these monoclonal antibodies showed promising pruritus control in AD patients. Except IL-4 and IL-13, nemolizumab, targeting on IL-31, was approved in treating prurigo nodularis, an extremely itching skin disease.
　　Going downstream of the pathogenesis of itching, all the involved cytokines belong to type II inflammation, all of which are activated by the JAK-STAT pathway. A variety of oral small-molecule drugs that inhibit JAKs, including baricitinib, upadacitinib, and abrocitinib, and topical small-molecule drugs such as Delgocitinib, have been approved to be effectively and rapidly improve the severity of itching in clinical trials and real-world patient usage. Understating the signaling pathway involved in pruritus more and targeting the specific molecules identified allow physicians to help patients get rid of the nightmare of itching in the future.