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Basic mechanisms of itch and advances in clinical management 瘙痒的基本机制及临床治疗进展。
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.09.014
Giulia Coscarella MD , Elise Edwards BA , Gil Yosipovitch MD
Chronic pruritus requires comprehensive assessment and management due to its profound impact on quality of life. The etiologies of pruritus are diverse, encompassing dermatologic, neuropathic, systemic, psychogenic, and mixed causes. Pruritogens activate C and Aδ fibers through histaminergic and non-histaminergic pathways. Increasing evidence highlights the role of TH2 cytokines, particularly interleukin (IL)-4, IL-13, and IL-31, which directly stimulate sensory neurons and perpetuate the itch-scratch cycle. Itch perception arises from dynamic interactions between the immune system and the peripheral and central nervous systems. Signals transmitted by sensory fibers are processed in the dorsal horn and relayed to thalamic and cortical centers, reinforcing chronicity. Diagnostic evaluation begins with detailed history and examination, complemented by laboratory testing such as complete blood cell count, kidney, liver, glucose, and thyroid function tests to uncover systemic or neurologic contributors. For dermatologic conditions, topical immunomodulators, including corticosteroids, calcineurin inhibitors, and PDE4 (phosphodiesterase-4) inhibitors, are first-line options for localized itch. Extensive itch may require systemic immunosuppressants or phototherapy. Biologic agents targeting IL-4/IL-13 and IL-31 pathways have revolutionized treatment for atopic dermatitis and prurigo nodularis, whereas Janus kinase signal transducer and activator of transcription inhibitors also offer significant antipruritic effect in atopic dermatitis and beyond. Neuropathic itch may respond to topical anesthetics, menthol, pramoxine, capsaicin, or compounded ketamine-amitriptyline-lidocaine formulations, and systemic gabapentinoids and antidepressants. Systemic or intractable pruritus may benefit from kappa opioid receptor agonists. New drugs targeting the mast cell such as Bruton’s tyrosine kinase inhibitors, c-KIT inhibitors, and MRGPRX2 antagonists have robust anti-pruritic effects in mast cell–mediated diseases. Supportive measures, including psychosocial interventions, remain integral to long-term management.
由于慢性瘙痒对生活质量的深刻影响,需要全面的评估和管理。瘙痒的病因是多种多样的,包括皮肤病、神经性、全身性、心因性和混合病因。搔痒原通过组胺能和非组胺能途径激活C和Aδ纤维。越来越多的证据强调了Th2细胞因子的作用,特别是白细胞介素(IL)-4、IL-13和IL-31,它们直接刺激感觉神经元并使瘙痒-抓痒循环持续下去。瘙痒感产生于免疫系统与外周和中枢神经系统之间的动态相互作用。由感觉纤维传递的信号在背角被处理并传递到丘脑和皮层中心,从而加强了慢性。诊断评估从详细的病史和检查开始,辅以实验室检查,如全血细胞计数、肾、肝、葡萄糖和甲状腺功能检查,以发现全身性或神经系统疾病。对于皮肤病,局部免疫调节剂——包括皮质类固醇、钙调磷酸酶抑制剂和PDE4抑制剂——是局部瘙痒的一线选择。广泛的瘙痒可能需要全身免疫抑制剂或光疗。靶向IL-4/IL-13和IL-31途径的生物制剂已经彻底改变了特应性皮炎和结节性痒疹的治疗,而JAK-STAT抑制剂也在特应性皮炎及其他疾病中具有显著的止痒作用。神经性瘙痒可能对局部麻醉剂有反应:薄荷醇、普拉莫辛、辣椒素或复合氯胺酮-阿米替林-利多卡因制剂,以及全身加巴喷丁类药物和抗抑郁药。系统性或难治性瘙痒可能受益于阿片受体激动剂。针对肥大细胞的新药物,如BTK抑制剂、c-KIT抑制剂和MRGPRX2拮抗剂,在肥大细胞介导的疾病中具有强大的抗瘙痒作用。支持性措施,包括社会心理干预,仍然是长期管理的组成部分。
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引用次数: 0
Lessons from the American College of Allergy, Asthma and Immunology inborn errors of immunity survey 来自ACAAI IEI调查的经验教训:为执业过敏症专家-免疫学家推进诊断和治疗策略。
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.09.026
Barbara Ariue MD , Niraj C. Patel MD , Joseph A. Bellanti MD

Background

Inborn errors of immunity (IEIs) have been increasingly well characterized on the molecular and genetic levels. Their clinical recognition and management among practicing allergist-immunologists remain challenging.

Objective

To evaluate the consultative practices of allergist-immunologists in diagnosing and managing IEIs by identifying subtypes encountered, current approaches, multidisciplinary collaboration, barriers, and educational needs.

Methods

The American College of Allergy, Asthma and Immunology distributed a 30-question web-based survey assessing IEI experience through SurveyMonkey to US-based members in a 4-week period during the spring of 2024.

Results

Most IEI consultations originated from outpatient primary care settings (82%), with 56% of respondents providing both outpatient and inpatient consultations. Frequently encountered IEIs included common variable immunodeficiency (100%), specific antibody deficiency (99%), selective IgA deficiency (97%), and C1 esterase inhibitor deficiency (90%). Less frequently encountered were Chediak-Higashi syndrome (40.5%) and type I interferonopathies (41%). The greatest need for subspecialty input was from hematology/oncology for quantitative phagocyte cell defects (89%) and autoimmune lymphoproliferative syndrome caused by a mutation in the FAS gene (74%). Severe combined immunodeficiency and defects of cytotoxicity (50%) most often required expert immunology consultation. The top educational priorities were genetic testing (61%) and gene therapy (60%). The major barriers were complexity and wide range of IEIs (39%) and low referral volume (36%). Comfort levels and need for knowledge varied significantly by practice type and clinician age. A major limitation of this study was the overrepresentation of academic practitioners.

Conclusion

This American College of Allergy, Asthma and Immunology study provides insight into the current consultative practices and management of allergist-immunologists engaging in IEI care. These findings highlight the critical need for enhanced training, improved access to multidisciplinary support, and targeted continuing education to optimize care for patients with these complex disorders.
背景:先天性免疫错误(IEI)在分子和遗传水平上的特征越来越明显。他们的临床识别和管理执业过敏症-免疫学家仍然具有挑战性。目的:通过识别遇到的亚型、目前的方法、多学科合作、障碍和教育需求,评估过敏科-免疫学家在诊断和管理iei方面的咨询实践。方法:美国过敏、哮喘和免疫学学院在2024年春季的四周时间里,通过SurveyMonkey向美国会员分发了一份30个问题的网络调查,评估IEI的体验。结果:大多数IEI咨询来自门诊初级保健机构(82%),56%的受访者同时提供门诊和住院咨询。常见的iei包括常见可变免疫缺陷(CVID)(100%)、特异性抗体缺乏症(99%)、选择性IgA缺乏症(97%)和C1酯酶抑制剂缺乏症(90%)。较少出现的是Chediak-Higashi综合征(40.5%)和I型干扰素病变(41%)。对亚专科输入需求最大的是血液学/肿瘤学的定量吞噬细胞缺陷(89%)和ALPS-FAS(74%)。严重的联合免疫缺陷(SCID)和细胞毒性缺陷(50%)最常需要专家免疫学咨询。最受教育的是基因检测(61%)和基因治疗(60%)。主要障碍是iei的复杂性和范围广(39%)和转诊量低(36%)。舒适程度和知识需求因实践类型和临床医生年龄的不同而有显著差异。本研究的一个主要限制是学术实践者的过度代表性。结论:这项ACAAI研究为目前从事IEI护理的过敏症-免疫学家的咨询实践和管理提供了见解。这些发现强调了加强培训、改善获得多学科支持的机会和有针对性的继续教育的迫切需要,以优化对这些复杂疾病患者的护理。
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引用次数: 0
Characterization of food protein-induced enterocolitis syndrome among Asian American children 亚裔美国儿童食物蛋白诱导的小肠结肠炎综合征的特征。
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.11.002
Charles Feng MD , Priscilla Wong MD , Satish Mudiganti MS , Xiaowei Yan MS, PhD, MPH , Diamonne Mitchell MPH , Ngoc Tran MD , Latha Palaniappan MD, MS , Anna Chen Arroyo MD, MPH

Background

Limited data currently exist regarding the clinical characteristics of food protein-induced enterocolitis syndrome (FPIES) among Asian American (AsA) children.

Objective

To evaluate a cohort of AsA children with FPIES in a Northern California health care system.

Methods

We performed a retrospective analysis of children below 18 years of age with more than or equal to 1 outpatient clinical encounter with FPIES (International Classification of Diseases, 10th Revision, Clinical Modification, K52.21) diagnosed between October 1, 2015, and December 31, 2022. Patient/parent self-reported race/ethnicity was used. Two board-certified allergists reviewed the charts of all AsA children diagnosed with having FPIES. Market basket analysis was performed to identify correlations among FPIES food categories.

Results

Of 129,989 AsA children, 146 (0.11%) had acute FPIES, most of which were male (52%) and had atopic dermatitis (55.5%). Median age at diagnosis was 7 months. Among 21 children (14%) who underwent oral food challenges, 66.6% (14/21) passed the challenge. Multi-food FPIES was observed in 23.9% (35/146) and atypical FPIES was observed in 14.4% (21/146) of the cohort. Approximately 28% of Asian Indian and 10% of Filipino children had more than 1 trigger food. The most common culprit foods included egg (36.3%), oats (24%), milk (16.4%), avocado (9.6%), rice (6.8%), and peanut (5.5%). Market basket analysis revealed that having an egg-related trigger was associated with not having an avocado-related trigger, with a confidence level of 88% and a lift value of 1.33.

Conclusion

This large pediatric AsA FPIES cohort demonstrates distinguishing features, including a high proportion of egg FPIES and lack of common food co-associations. Understanding these clinical differences may significantly enhance clinicians’ ability to diagnosis and manage FPIES among the rapidly growing heterogeneous AsA population.
背景:目前关于亚裔美国人(AsA)儿童食物蛋白性小肠结肠炎综合征(FPIES)临床特征的数据有限。目的:我们评估北加州医疗保健系统中AsA儿童的FPIES队列。结果:129989例AsA患儿中,146例(0.11%)有急性FPIES,其中多数为男性(52%),并有特应性皮炎(55.5%)。诊断时的中位年龄为7个月。在21名(14%)接受口腔食物挑战的儿童中,66.6%(14/21)通过了挑战。23.9%(35/146)的患者出现多种食物FPIES, 14.4%(21/146)的患者出现非典型FPIES。大约28%的亚洲印度儿童和10%的菲律宾儿童食用了bbb1触发食物。最常见的罪魁祸首食物包括鸡蛋(36.3%)、燕麦(24%)、牛奶(16.4%)、鳄梨(9.6%)、大米(6.8%)和花生(5.5%)。MBA表明,有鸡蛋相关的触发因素与没有鳄梨相关的触发因素相关,置信水平为88%,提升值为1.33。结论:这个大型儿童AsA FPIES队列显示出明显的特征,包括鸡蛋FPIES比例高和缺乏常见的食物联合关联。了解这些临床差异可以显著提高临床医生在快速增长的异质AsA人群中诊断和管理FPIES的能力。
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引用次数: 0
Cellular endotypes and nasal cytology 细胞内型和鼻细胞学
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.09.030
Matteo Gelardi MD , Massimo Landi MD , Michele Cassano MD
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引用次数: 0
Basophils in atopic dermatitis 嗜碱性粒细胞在特应性皮炎中的免疫学作用和临床意义。
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.11.005
Mrinmoy Das PhD , Raif S. Geha MD
Atopic dermatitis (AD) or eczema is a chronic inflammatory skin disease, characterized by dysfunction of the epidermal skin barrier causing increased sensitization to environmental allergens. The resulting type 2-dominated local and systemic immune responses cause epidermal hyperplasia, dermal infiltration by T cells and eosinophilia, and elevated levels of total and allergen‐specific IgE. In addition, the skin of patients with AD is often colonized with Staphylococcus aureus which correlates with diseases severity. Recent emerging studies highlight a significant role for basophils in both local and systemic responses of AD pathogenesis. Although rare in the circulation, basophils rapidly infiltrate inflamed skin, and on activation, they release IL-4 and IL-13, which are key players in the development of AD. They also secrete mediators such as histamine, leukotrienes, and IL-31 which contribute to inflammation and pruritus. Basophils also influence through their production of IL-4 T-cell polarization and B-cell class switching, supporting systemic sensitization and the development of atopic march. Basophils are gaining recognition as clinically actionable contributors to AD. The basophil activation test, which measures the activation of basophils in the blood in response to specific allergens, offers promising tools for assessing AD pathogenesis and response to treatment. In addition, therapies such as dupilumab, tralokinumab, and nemolizumab which target IL-4, IL-13, and IL-31, respectively, likely exert part of their effect by modulating basophil activity. In this review, we summarize the immunologic functions of basophils in AD pathogenesis, discuss their relevance as biomarkers and therapeutic targets, and outline future directions for integrating basophil-focused strategies in the management of patients with AD.
特应性皮炎(AD)或湿疹是一种慢性炎症性皮肤病,其特征是表皮皮肤屏障功能障碍,导致对环境过敏原的敏感性增加。由此产生的2型主导的局部和全身免疫反应导致表皮增生,T细胞和嗜酸性粒细胞的真皮浸润,总IgE和过敏原特异性IgE水平升高。此外,AD患者的皮肤常定植金黄色葡萄球菌,这与疾病的严重程度有关。最近新出现的研究强调了嗜碱性细胞在AD发病机制的局部和全身反应中的重要作用。虽然在循环中很少见,但嗜碱性细胞迅速浸润炎症皮肤,并在激活后释放IL-4和IL-13,这是AD发展的关键因素。它们还会分泌组胺、白三烯和IL-31等导致炎症和瘙痒的介质。嗜碱性粒细胞还通过产生IL-4 T细胞极化和B细胞类别转换来影响,支持全身致敏和特应性进行的发展。嗜碱性粒细胞被认为是阿尔茨海默病的临床可操作的贡献者。嗜碱性粒细胞激活试验,测量血液中嗜碱性粒细胞对特定过敏原的激活,为评估AD的发病机制和治疗反应提供了有希望的工具。此外,dupilumab、tralokinumab和nemolizumab等分别靶向IL-4、IL-13和IL-31的疗法可能通过调节嗜碱性粒细胞活性来发挥部分作用。在这篇综述中,我们总结了嗜碱性粒细胞在阿尔茨海默病发病机制中的免疫功能,讨论了它们作为生物标志物和治疗靶点的相关性,并概述了在阿尔茨海默病患者管理中整合以嗜碱性粒细胞为重点的策略的未来方向。
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引用次数: 0
New advances in our understanding of itch 我们对瘙痒理解的新进展
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.11.016
Francesca Levi-Schaffer PharmD, PhD , Donald Y.M. Leung MD, PhD
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引用次数: 0
Who actually has asthma? The challenge of defining and diagnosing asthma 谁真的患有哮喘?定义和诊断哮喘的挑战
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.11.014
Meera R. Gupta MD , Theresa A. Bingemann MD
{"title":"Who actually has asthma? The challenge of defining and diagnosing asthma","authors":"Meera R. Gupta MD ,&nbsp;Theresa A. Bingemann MD","doi":"10.1016/j.anai.2025.11.014","DOIUrl":"10.1016/j.anai.2025.11.014","url":null,"abstract":"","PeriodicalId":50773,"journal":{"name":"Annals of Allergy Asthma & Immunology","volume":"136 2","pages":"Pages 125-126"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reflective listening and response strategies to support families with food allergy–related mental health burden 支持有食物过敏相关心理健康负担家庭的反思性倾听和反应策略。
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.11.010
Brinda Prasanna Kumar MBBS , Alexandria Brunkow PhD , Dominic Candido PhD , Karen S. Hsu Blatman MD, MBA , Marcus Shaker MD, MS
{"title":"Reflective listening and response strategies to support families with food allergy–related mental health burden","authors":"Brinda Prasanna Kumar MBBS ,&nbsp;Alexandria Brunkow PhD ,&nbsp;Dominic Candido PhD ,&nbsp;Karen S. Hsu Blatman MD, MBA ,&nbsp;Marcus Shaker MD, MS","doi":"10.1016/j.anai.2025.11.010","DOIUrl":"10.1016/j.anai.2025.11.010","url":null,"abstract":"","PeriodicalId":50773,"journal":{"name":"Annals of Allergy Asthma & Immunology","volume":"136 2","pages":"Pages 233-235"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical and genetic findings of individuals tested using the navigateAPDS genetic testing program 通过navigateAPDS基因检测计划测试的个体的临床和遗传发现。
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.07.015
Emily Campbell MD , Jenny Garkaby MD , Julia Upton MD , Nami Park PharmD , Mike Samad MD , Michelle Hogue MS , Joseph R. Harper PharmD , Anurag Relan MD , Heather McLaughlin PhD , Kelli W. Williams MD, MPH

Background

Inborn errors of immunity (IEIs), including activated phosphoinositide-3-kinase delta syndrome (APDS), are underdiagnosed due to factors including heterogenous clinical manifestations, lack of awareness, and limited genetic testing access. Genetic testing may establish the molecular diagnosis (MolDx) of numerous IEIs, which may result in management changes.

Objective

To investigate the clinical utility of the navigateAPDS sponsored program established to increase MolDx of APDS through broad genetic testing.

Methods

The eligibility criteria to receive sponsored testing included APDS clinical features.

Results

Between March 2021 and September 2024, a total of 7811 patients across the United States and Canada underwent genetic testing. The median age at time of testing was 33 (range, 0-89) years, and the most selected eligibility criterion was severe, recurrent sinopulmonary infections. Of the 630 patients who received a positive MolDx, 377 (60%) had disorder-associated clinical actionability; 73 (12%) had Food and Drug Administration–approved treatments available. The most identified IEIs included genetically defined common variable immune deficiency and APDS. Of the patients with variants in PIK3CD or PIK3R1, 35 received an APDS MolDx and 131 received a variant of uncertain significance (VUS). Patients with APDS had a median age at time of symptom onset of 3 (range, 0-44) years and a median diagnostic delay of 13 (range, 0-50) years. Of the 13 APDS-causing variants identified, 5 were novel for APDS.

Conclusion

These findings demonstrate that broad genetic testing for IEIs is useful and may contribute to disease management changes and improved health outcomes. Variant identification and VUS resolution are crucial in elucidating the genetic contribution to the clinical spectrum of IEIs and APDS.
背景:先天性免疫错误(IEI),包括活化PI3Kδ综合征(APDS),由于临床表现异质性、缺乏认识和基因检测途径有限等因素,未被充分诊断。基因检测可以建立许多iei的分子诊断(MolDx),这可能导致管理的改变。目的:建立导航APDS赞助计划,通过广泛的基因检测提高APDS的MolDx;在这里,我们研究了它的临床应用。方法:接受赞助检测的资格标准包括APDS临床特征。结果:在2021年3月至2024年9月期间,美国和加拿大的7811名患者接受了基因检测。检测时的中位年龄为33岁(范围0-89岁),大多数选择的合格标准是严重的复发性肺感染。在接受MolDx阳性的630例患者中,377例(60%)具有与疾病相关的临床可操作性;73例(12%)有fda批准的治疗方法。最确定的iei包括遗传定义的常见可变免疫缺陷和APDS。在PIK3CD或PIK3R1变异的患者中,35人接受了APDS MolDx, 129人接受了不确定意义变异(VUS)。APDS患者出现症状时的中位年龄为3岁(范围0-44岁),诊断延迟的中位年龄为13年(范围0-50年)。在鉴定出的13种引起APDS的变异中,有5种是APDS的新变异。结论:这些发现表明,对iei进行广泛的基因检测是有用的,可能有助于改变疾病管理和改善健康结果。变异鉴定和VUS分辨率对于阐明iei和APDS临床谱的遗传贡献至关重要。
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引用次数: 0
Interleukin-31 targeting and other novel drugs in itch 靶向il -31及其他治疗瘙痒的新药。
IF 4.7 2区 医学 Q1 ALLERGY Pub Date : 2026-02-01 DOI: 10.1016/j.anai.2025.11.007
Peter Olah PhD , Ulrike Raap MD , Bernhard Homey MD
Chronic pruritus is a debilitating symptom of several inflammatory skin conditions, presenting severe quality-of-life decreasing effects and major clinical challenges in terms of disease management. In the past decade, novel biological therapies have offered increasingly effective targeted interventions for the treatment of chronic pruritus, in which traditional approaches were often lacking or presented suboptimal safety profiles. However, recent advancements in the molecular characterization of sensory neuronal subsets helped to shed light on specific mechanisms of pruriception and thus have furthered our understanding of the peripheral nervous system and disease-relevant neuroimmune crosstalk. These developments have highlighted the targeting of interleukin-31, a major pruritus-associated cytokine, as a highly promising therapeutic target for chronic pruritus in inflammatory skin conditions. In this review, we therefore provide a focused overview of inflammatory conditions in which pruritus represents the major burden, the fundamental immune pathways, and sensory circuits involved, alongside the efficacies and safety profiles of novel therapies addressing chronic pruritus.
慢性瘙痒是几种炎症性皮肤病的衰弱症状,在疾病管理方面表现出严重的生活质量下降效应和主要的临床挑战。在过去的十年中,新型生物疗法为治疗慢性瘙痒症提供了越来越有效的靶向干预措施,而传统方法往往缺乏或呈现出次优的安全性。另一方面,最近在感觉神经元亚群分子表征方面的进展有助于阐明瘙痒感觉的特定机制,从而进一步加深了我们对周围神经系统和疾病相关的神经免疫串扰的理解。这些进展突出了靶向白介素-31,一种主要的瘙痒相关细胞因子,作为炎症性皮肤条件下慢性瘙痒的极有希望的治疗靶点。因此,在这篇综述中,我们提供了炎症条件的重点概述,其中瘙痒是主要的负担,基本的免疫途径和感觉回路,以及治疗慢性瘙痒的新疗法的有效性和安全性。
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引用次数: 0
期刊
Annals of Allergy Asthma & Immunology
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