【临床指南】中国荨麻疹诊疗指南(_2014版)

中国荨麻疹诊疗指南荨麻疹是一种常见的皮肤病，也叫做风疹、风团病等。

它的主要表现为皮肤上出现红色、瘙痒、大小不一的风团或斑块，有些会伴随着皮肤红肿、水肿、脱屑、表面积水囊等症状。

此外，荨麻疹还可能会影响到呼吸系统、消化系统、泌尿系统等，导致相应的症状，使患者的生活质量受到很大的影响。

荨麻疹的病因和诊断荨麻疹是由身体对某些过敏源（包括药物、食物、化学物质、寄生虫等）发生过敏反应而引起的皮肤病。

另外，荨麻疹可能与自身免疫、感染、体内激素以及心理因素等有关。

因此，荨麻疹的患者需要在医生的指导下，对可能引起过敏反应的物质进行测试和鉴定，从而找出可能的病因并采取相应的治疗措施。

荨麻疹有时也会因为病史不清、诊断错误、误诊等原因而延误治疗。

因此，为避免这种情况的发生，最好选择具有丰富临床经验和专业知识的医生进行诊断和治疗。

常规检查包括皮肤病理学检查、过敏试验、血液检查等，并需要针对患者的症状和严重程度来制定个性化的治疗方案。

荨麻疹的治疗原则荨麻疹的治疗原则是清除过敏源、缓解皮肤症状、预防复发，同时也应根据患者的情况进行相应的辅助治疗。

清除过敏源首先要清除过敏源，例如避免接触或食用可能引起过敏的食品或药物，清除体内的激素水平，避免过于紧张或焦虑等。

此外，平时也要注意改善生活习惯，增强免疫力，提高身体的抵抗力。

缓解皮肤症状治疗荨麻疹的主要手段是使用药物。

常用的药物有抗组胺药、肾上腺素能药、口服激素及其类似物等。

其中，抗组胺药是缓解症状最快，用量较小，且不易产生副作用。

因此，抗组胺药是治疗荨麻疹的首选。

对于激素类药物，建议在医生指导下使用，避免不当使用导致副作用。

同时，还需要注意药物的跟踪监测，早期发现并处理可能的不良反应。

此外，患者在接受治疗时也应注意注重个人卫生，保持皮肤的干燥清洁，避免使用含磨砂颗粒的沐浴露或洗涤剂等。

预防复发除了药物治疗外，预防荨麻疹的复发也非常重要。

对于过敏性荨麻疹的患者，在发病期间应避免接触过敏源，同时也要避免轻易地改变药物或化妆品使用。

中国荨麻疹诊疗指南引言：荨麻疹是一种常见的皮肤病，主要特征是皮肤出现红色、瘙痒、隆起的疱疹，通常会消失和重新出现。

荨麻疹的发病机制及诊治方法一直在不断研究和发展，中国荨麻疹诊疗指南(2024版)是根据最新的临床实践及研究成果制定的指南，旨在提供给临床医生最新的诊疗方法。

第一部分：定义与病因一、定义荨麻疹是一种以瘙痒为主要症状的皮肤病，特征为皮肤隆起的红色疱疹，可持续数分钟至数小时。

二、病因1.免疫介导荨麻疹：由于过敏反应引起的免疫系统异常，包括IgE介导的变态反应、药物过敏等。

2.非免疫介导荨麻疹：与体温变化、运动、应激等因素有关。

3.特发性荨麻疹：病因未知。

第二部分：临床表现一、急性荨麻疹1.全身性瘙痒2.皮肤出现红色、隆起的疱疹3.结局良好，一般数小时至数天会自行消退二、慢性荨麻疹1.持续或反复出现荨麻疹疱疹，持续超过6周2.结局不一，有的会痊愈，有的会持续数年第三部分：诊断一、根据病史和症状1.病史：详细询问发作时间、消失时间、出现诱因等。

2.症状：红色、隆起的疱疹，伴有瘙痒。

二、实验室检查1.皮肤划痕试验：用尖锐器轻轻划破皮肤后观察是否出现红色、隆起的疱疹。

2.血清IgE水平测定：可用于判断是否过敏反应引起的。

第四部分：治疗方案一、避免诱因1.避免与过敏源接触2.避免剧烈运动、高温等刺激二、药物治疗1.抗组胺药物：适用于急性荨麻疹，如非那根、氯雷他定等。

2.变应原免疫治疗：适用于过敏引起的荨麻疹，如单克隆抗体药物。

3.免疫抑制剂：适用于慢性荨麻疹，如环孢素A等。

三、中医中药治疗中医中药可以作为辅助治疗荨麻疹的方法，具体的药方根据病情和体质进行个性化调整。

四、其他治疗1.冷敷或温水浸泡：可以缓解瘙痒、减轻红肿。

2.心理辅导和应激管理：对于因精神压力引起的荨麻疹可进行心理辅导和应激管理。

结语：中国荨麻疹诊疗指南(2024版)是根据最新的临床实践及研究成果制定的指南，为临床医生提供了最新的诊疗方法。

生冒医垣盘查鲨！！生！旦笠！！鲞笙！塑显！翌生笪垒垒！！堕堕逝！ｉ塑：壁！翌！翌垫！！：∑生：！！，№：！中国荨麻疹诊疗指南（２０１４版）解读梁云生于碧慧陆前进４１００１ｌ长沙，中南大学湘雅二医院皮肤科通信作者：陆前进，Ｅｍａｉｌ：ｑｉａｎｌｕ５８６０＠ｇｍａｉｌ．ｃｏｍＤＯＩ：１０．３７６０／ｃｍａ．ｊ．ｉｓｓｎ．１００８—１３７２．２０１６．０２．００３【关键词】荨麻疹／诊断／治疗；指南本着服务临床、着重诊疗的宗旨，２０１４版中国荨麻疹诊疗指南（以下简称２０１４版指南）是在２００７版中国荨麻疹诊疗指南（以下简称２００７版指南）基础上，结合近年来国内外研究进展，主要由中华医学会皮肤性病学分会免疫学组成员反复讨论修改，由郝飞教授、陆前进教授、宋志强教授执笔完成。

２０１４版指南相比较２００７版指南作了如下修改。

１定义荨麻疹是由于皮肤、黏膜小血管扩张及渗透性增加出现的一种局限性水肿反应。

临床上特征性表现为大小不等的风团伴瘙痒，２０１４版指南在定义方面增加并强调血管性水肿在荨麻疹的诊断的重要性，因为临床上出现瘙痒性风团如果伴有血管性水肿就可以明确诊断为荨麻疹，不要其它检查排除遗传性血管性水肿以及自身炎症病，而且荨麻疹患者出现风团伴有血管性水肿常常提示常规治疗效果欠佳。

２０１４版指南将慢性荨麻疹的定义由２００７版风团伴瘙痒几乎每天发生，改为风团每周至少发作２次，持续时间１＞６周不变¨引。

２病因学２０１４版指南将荨麻疹的常见病因归纳分为：外源性与内源性。

外源性因素多为暂时性，与２００７版指南相比较，增加了植入物（人工关节、吻合器、心脏瓣膜、骨科的钢板、钢钉及妇科的节育器）以及运动等这一发病因素；内源性因素多为持续性，内源性因素强调肥大细胞对ＩｇＥ高敏感性，并在病因上特别强调了ＩｇＥ介导的食物变应原在荨麻疹（特别是慢性荨麻疹）发病中的作用是有限的，对变应原检测结果应该正确分析，有条件的单位可酌情开展双盲、安慰剂对照的食物激发试验验证。

【诊疗指南】中国荨麻疹诊疗指南（2014版）2015-08-26中国荨麻疹诊疗指南（2014版）中华医学会皮肤性病学分会免疫学组定 义荨麻疹是由于皮肤、黏膜小血管扩张及渗透性增加出现的一种局限性水肿反应。

临床上特征性表现为大小不等的风团伴瘙痒，可伴有血管性水肿。

慢性荨麻疹是指风团每周至少发作2次，持续≥ 6周者［2］。

少数慢性荨麻疹患者也可表现为间歇性发作。

病 因急性荨麻疹常可找到病因，但慢性荨麻疹的病因多难以明确。

通常将病因分为外源性和内源性［2-3］。

外源性因素多为暂时性，包括物理刺激（摩擦、压力、冷、热、日光照射等）、食物（动物蛋白如鱼、虾、蟹、贝壳类、蛋类等，植物或水果类如柠檬、芒果、李子、杏子、草莓、胡桃、可可、大蒜、西红柿等，腐败食物和食品添加剂）、药物（免疫介导的如青霉素、磺胺类药、血清制剂、各种疫苗等，或非免疫介导的肥大细胞释放剂如吗啡、可待因、阿司匹林等）、植入物（人工关节、吻合器、心脏瓣膜、骨科的钢板、钢钉及妇科的节育器等）以及运动等。

内源性因素多为持续性，包括肥大细胞对IgE高敏感性、慢性隐匿性感染（细菌、真菌、病毒、寄生虫等感染，如幽门螺杆菌感染在少数患者可能是重要的因素）、劳累或精神紧张、针对IgE或高亲和力IgE受体的自身免疫以及慢性疾病如风湿热、系统性红斑狼疮、甲状腺疾病、淋巴瘤、白血病、炎症性肠病等。

特别指出，慢性荨麻疹很少由变应原介导所致［2-3］。

发病机制荨麻疹的发病机制至今尚不十分清楚，可能涉及感染、变态反应、假变态反应和自身反应性等。

肥大细胞在发病中起中心作用，其活化并脱颗粒，导致组胺、白三烯、前列腺素等释放，是影响荨麻疹发生、发展、预后和治疗反应的关键［3］。

诱导肥大细胞活化并脱颗粒的机制包括免疫性、非免疫性和特发性。

免疫性机制包括针对IgE或高亲和力IgE 受体的自身免疫、IgE依赖的以及抗原抗体复合物和补体系统介导等途径；非免疫性机制包括肥大细胞释放剂直接诱导，食物中小分子化合物诱导的假变应原反应，或非甾体抗炎药改变花生烯酸代谢等；还有少数荨麻疹患者目前尚无法阐明其发病机制，甚至可能不依赖于肥大细胞活化［2-4］。

荨麻疹诊疗指南【定义】该病是某些具有过敏体质的人由于食物、药物、各种感染、内脏疾患、昆虫叮咬等很多原因引起的变态反应和非变态反应，表现为皮肤黏膜血管扩张、通透性增高、血清渗出而形成局部水肿(即风团)。

【病因】1、食物：鱼虾，蟹，贝壳类，蛋类，柠檬，芒果，李子，杏子，草莓，胡桃，可可，大蒜，西红柿等奶类食物腐败食品添加剂。

2、药物：青霉素，磺胺，呋喃唑酮，血清制剂，各种疫苗，咖啡，可待因，可卡因，奎宁，阿司匹林等。

3、感染：细菌，真菌，病毒，寄生虫，幽门螺旋杆菌。

4、吸入物。

花粉，动物羽毛及皮屑，粉尘，烟，气雾剂，挥发性化学品5、物理因素：摩擦，压力，冷，热，日光照射，运动等。

6、系统性疾病：风湿热，系统性红斑狼疮，甲状腺疾病，淋巴瘤，白血病，传染性单核细胞增多症。

【发病机制】荨麻疹发病机制复杂，至今尚未完全清楚。

皮肤发生风团有免疫和非免疫介导两种方式。

在临床工作中，多数荨麻疹为原因不明的特发性荨麻疹。

【分类】1、特发性荨麻疹：分为急性荨麻疹和慢性荨麻疹。

2、物理性：分为冷性荨麻疹、迟发压力性荨麻疹、热性荨麻疹、日光性荨麻疹、人工荨麻疹/皮肤划痕征、振动性荨麻疹/血管性水肿、运动诱导的荨麻疹。

3、自身免疫性荨麻疹；感染性荨麻疹。

4、其他：水源性荨麻疹、胆碱能性荨麻疹、接触性荨麻疹。

【诊断】皮疹主要表现是风团，为大小不等、形状不一、红色或瓷白色的水肿性隆起损害。

风团全身均可发生，有的局限于某些部位，如寒冷性荨麻疹，多由冷水或冷风接触而致，好发于面颈或四肢，压力性荨麻疹主要发生在受压部位。

常突然发作，持续数分钟至数小时消退，退后不留痕迹，但新疹又不断发生，此起彼伏，病程6周以上称慢性荨麻疹。

自觉剧痒，少数有疼痛和触痛。

少数可累及黏膜出现腹痛、腹泻或胸闷、气紧。

若喉头水肿，可出现呼吸困难，甚至窒息。

【荨麻疹的治疗】荨麻疹治疗应遵循以下原则：1、病因治疗：消除刺激因素或可疑因素在荨麻疹治疗中最为重要。

因为消除刺激因素或可疑因素后荨麻疹可能自然消退；反之，重新暴露相关因素后荨麻疹复发，可为确定致病原因提供证据。

P O S I T I O N P A P E RThe EAACI/GA2LEN/EDF/WAO Guideline for the definition, classification,diagnosis,and management of urticaria:the2013revision and updateT.Zuberbier1,W.Aberer2,R.Asero3,C.Bindslev-Jensen4,Z.Brzoza5,G.W.Canonica6,M.K.Church1,L.F.Ensina7,A.Gim e nez-Arnau8,K.Godse9,M.Goncßalo10,C.Grattan11,J.Hebert12,M.Hide13,A.Kaplan14,A.Kapp15,A.H.Abdul Latiff16,P.Mathelier-Fusade17,M.Metz1,A.Nast1,S.S.Saini18,M.S a nchez-Borges19,P.Schmid-Grendelmeier20,F.E.R.Simons21,P.Staubach22,G.Sussman23,E.Toubi24,G.A.Vena25,B.Wedi15,X.J.Zhu26& M.Maurer11Department of Dermatology and Allergy,Allergy-Centre-Charit e,Charit e–University Hospital Berlin,Berlin,Germany;2Department of Dermatology,Medical University of Graz,Graz,Austria;3Allergy Clinic,Clinica San Carlo,Paderno Dugnano,MI,Italy;4Department of Dermatology and Allergy Centre,Odense University Hospital,University of Southern Denmark,Odense,Denmark;5Department of Internal Diseases,Allergology and Clinical Immunology in Katowice,Medical University of Silesia,Zabrze,Poland;6Respiratory Diseases&Allergy, University of Genoa,IRCCS AOU SanMartino,Genoa,Italy;7Department of Clinical Immunology and Allergy,Federal University of Sao Paulo, Sao Paulo,Brazil;8Hospital del Mar.Parc de Salut Mar,Universitat Aut o noma Barcelona,Barcelona,Spain;9Department of Dermatology,Dr.D.Y.Patil Medical College&Hospital,Nerul,Navi Mumbai,India;10Clinic of Dermatology,Faculty of Medicine and University Hospital, Coimbra,Portugal;11St John’s Institute of Dermatology,Guy’s and St Thomas’Hospitals NHS Foundation Trust,London,UK;12Center for Applied Research on Allergy Qu e bec,Qu e bec,QC,Canada;13Department of Dermatology,Institute of Biomedical and Health Sciences, Hiroshima University,Hiroshima,Japan;14Division of Pulmonary and Critical Care Medicine,Allergy and Clinical Immunology,Department of Medicine,Medical University of South Carolina,Charleston,SC,USA;15Department of Dermatology and Allergy,Hannover Medical School, Hannover,Germany;16Department of Paediatrics,Pantai Hospital Kuala Lumpur,Bangsar,Kuala Lumpur,Malaysia;17Department of Dermatology and Allergy,University Hospital of Tenon,Paris,France;18Johns Hopkins Asthma and Allergy Center,Baltimore,MD,USA;19Allergy and Clinical Immunology Department Centro M e dico-Docente La Trinidad,Caracas,Venezuela;20Allergy Unit,Department of Dermatology,University Hospital,Z€u rich,Switzerland;21Departments of Pediatrics&Child Health,Immunology,University of Manitoba, Winnipeg,MB,Canada;22Department of Dermatology,University Medical Center Mainz,Mainz,Germany;23Division of Allergy and Clinical Immunology,University of Toronto,Toronto,ON,Canada;24Bnai-Zion Medical Center,Faculty of Medicine,Technion,Haifa,Israel;25Unit of Dermatology and Venereology,Department of Biomedical Sciences and Human Oncology,University of Bari,Bari,Italy;26Department of Dermatology,Peking University First Hospital,Beijing,ChinaTo cite this article:Zuberbier T,Aberer W,Asero R,Bindslev-Jensen C,Brzoza Z,Canonica GW,Church MK,Ensina LF,Gim e nez-Arnau A,Godse K,Goncßalo M, Grattan C,Hebert J,Hide M,Kaplan A,Kapp A,Abdul Latiff AH,Mathelier-Fusade P,Metz M,Nast A,Saini SS,S a nchez-Borges M,Schmid-Grendelmeier P, Simons FER,Staubach P,Sussman G,Toubi E,Vena GA,Wedi B,Zhu XJ,Maurer M.The EAACI/GA2LEN/EDF/WAO Guideline for the definition,classification, diagnosis,and management of urticaria:the2013revision and update.Allergy2014;69:868–887.Keywordsangioedema;consensus;hives;urticaria; wheal.CorrespondenceTorsten Zuberbier,Department of Dermatology and Allergy,Allergy Centre Charit e,Charit e University Hospital Berlin, Charit e platz1,D-10117Berlin,Germany. Tel.:+49-30-450-518135Fax:+49-30-450-518919E-mail:torsten.zuberbier@charite.de*Endorsing societies are listed in Appendix1.Accepted for publication30September 2013AbstractThis guideline is the result of a systematic literature review using the‘Grading of Recommendations Assessment,Development and Evaluation’(GRADE)method-ology and a structured consensus conference held on28and29November2012, in Berlin.It is a joint initiative of the Dermatology Section of the European Aca-demy of Allergy and Clinical Immunology(EAACI),the EU-funded network of excellence,the Global Allergy and Asthma European Network(GA2LEN),the European Dermatology Forum(EDF),and the World Allergy Organization (WAO)with the participation of delegates of21national and international socie-ties.Urticaria is a frequent,mast cell-driven disease,presenting with wheals,an-gioedema,or both.The life-time prevalence for acute urticaria is approximately 20%.Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life,but also affect performance at work and school and,as such,are members of the group of severe allergic diseases.This guideline covers the definition and classification of urticaria,taking into account the recent progress in identifying its causes,eliciting factors and pathomecha-DOI:10.1111/all.12313 Edited by:Thomas Bieber nisms.In addition,it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.This guideline was acknowl-edged and accepted by the European Union of Medical Specialists(UEMS).This guideline is the result of a systematic literature review using the‘Grading of Recommendations Assessment,Develop-ment and Evaluation’(GRADE)methodology and a structured consensus conference held on28and29November2012,in Berlin.It is a joint initiative of the European Academy of Allergy and Clinical Immunology(EAACI)Dermatology Sec-tion,GA2LEN,the European Dermatology Forum(EDF), and the World Allergy Organization(WAO)with the participa-tion of delegates of21national and international societies.The American Academy of Allergy,Asthma&Immunology (AAAAI)participated in the process of developing these guide-lines,but is not an endorsing founder society(see Acknowledg-ments).It is an update and revision of the previous EAACI/ GA2LEN/EDF/WAO guidelines on urticaria(1,2).The wide diversity and number of different urticaria subtypes that have been identified reflect,at least in part,our increasing understanding of the causes and eliciting factors of urticaria and the molecular and cellular mechanisms involved in its pathogenesis.The aim of this guideline is to provide an updated definition and classification of urticaria,thereby facilitating the interpretation of divergent data from different centers regard-ing underlying causes,eliciting factors,and therapeutic respon-siveness of subtypes of urticaria.Furthermore,this guideline provides recommendations for diagnostic and therapeutic approaches in common subtypes of urticaria.This guideline has involved societies and experts from all areas of the world and as a global guideline thus also takes into consideration that causative factors in patients,medical systems,and access to diagnosis and treatment vary in different countries.MethodsThe detailed methods used in the development of this guide-line2013revision and update,including all evaluations of the literature,are published in a separate paper for the sake of brevity and readability.A brief summary is provided here as Appendix2.In short,as members of the panel and delegates of their soci-eties,the authors had prepared in advance their suggestions regarding the definition,classification,diagnosis,and treat-ment of urticaria.The resulting draft of the guideline took into account all available evidence in the literature(including Med-line and Embase searches as well as manual search of abstracts at international allergy congresses between2004and2012)and was based on the existing consensus papers of thefirst three symposia in2000,2004,and2008(1–6).These suggestions were then discussed in detail between the panel and the partici-pants of the meeting.A consensus wasfinally achieved during a structured consensus conference using a TED voting system. The participation of urticaria specialists from39countries ensured that this consensus includes regional differences worldwide in viewpoint and provides a basis for improved comparison of future studies in thefield of urticaria.In the previous version of the guideline,studies were already partly evaluated using the GRADE approach.The key principle of the GRADE approach is to provide trans-parency and clear,explicit criteria for assessing the quality of evidence(see Table1)and grading the strength of recommen-dations(7–11)based on risk vs benefits.The following translation to the GRADE quality of evi-dence was used acknowledging that a more detailed assess-ment will possibly change the quality of evidence and that additional quality criteria are considered in GRADE.SIGN level of evidence GRADE quality of evidence1++High1+Moderate1ÀLow2++Low2+Low2ÀVery low3Very low4Very lowFor this2013revision and update,a modified version of GRADE was applied throughout the guideline.The questions addressed were developed by the panel members and selected with respect to their relevance by all the panel members in a Delphi voting.The selection and wording process used as well as other methodological details are described in a separate Table1Levels of evidence for identified literature sourcesThe quality of the evidence was assessed using the Methodology Checklist2:RCTs of the Scottish Intercollegiate Guidelines Network(SIGN;compare for(2))1++High-quality meta-analyses,systematic reviews of RCTs,or RCTs with a very low risk of bias1+Well-conducted meta-analyses,systematic reviews of RCTs, or RCTs with a low risk of bias1ÀMeta-analyses,systematic reviews of RCTs,or RCTs with a high risk of bias2++High-quality systematic reviews of case-controlled or cohort or studies.High-quality case-controlled or cohort studieswith a very low risk of confounding,bias,or chance and ahigh probability that the relationship is causal2+Well-conducted case-controlled or cohort studies with a low risk of confounding,bias,or chance and a moderateprobability that the relationship is causal2ÀCase-controlled or cohort studies with a high risk ofconfounding,bias,or chance and a significant risk that therelationship is not causal3Nonanalytic studies,for example case reports,case series 4Expert opinionRCT,randomized controlled trials.Zuberbier et al.EAACI/GA2LEN/EDF/WAO urticaria guidelinereport on methods used for the generation of this revision and update of the guideline.Briefly,the strength of a recommendation and the quality of supporting evidence were assessed indepen-dently by two assessors for each recommendation.They took into consideration as negative/risk:side-effects(graded on severity)and costs;and as benefits:reduction in urticaria symptoms(e.g.,UAS7[UAS,Urticaria Activity Score;UAS7, Average Urticaria Activity Score for7days]in newer studies) and improvement in quality of life(QoL).Importantly,the GRADE system permits strong recommendations supported by low-or(very rarely)very-low-quality evidence from down-graded RCTs or observational studies.On the other hand,weak recommendations may be based on high-quality evidence if other factors are important,for example the price of a treatment option.The expression‘we recommend’was used for strong rec-ommendations and‘we suggest’for weak recommendations in order to adhere to the same methodology used for the Allergic Rhinitis and its Impact on Asthma guideline2008 update(10).This same terminology has also been adhered to in those parts of the guideline where the assessment of the evidence was not done in full.Participants of the consensus conference were presented with a draft version of this document and were asked to dis-cuss and vote whether they agreed with recommendations and other specific parts of the text.It was only allowed to vote yes or no,to ensure clear majority decisions.In state-ments not receiving votes>90%during thefirst voting,the recommendation was re-discussed,rephrased,and re-voted and passed in the following votings if a minimum of>75% agreement was achieved.Conflicts of interest of all group members were collected prior to the consensus conferences.They were assessed by the steering committee.All declarations of conflicts of inter-est are presented as online Supporting Information to this guideline and in detail in the methods report.DefinitionUrticaria is a disease characterized by the development of wheals(hives),angioedema,or both.Urticaria needs to be differentiated from other medical conditions where wheals, angioedema,or both can occur as a symptom,for example skin prick test,anaphylaxis,auto-inflammatory syndromes, or hereditary angioedema(bradykinin-mediated angioedema). Clinical appearanceUrticaria is characterized by the sudden appearance of wheals,angioedema,or both.A wheal consists of three typical features:1It is characterized by a central swelling of variable size, almost invariably surrounded by a reflex erythema.2It is associated with itching or sometimes a burning sen-sation.3It has afleeting nature,with the skin returning to its nor-mal appearance,usually within1–24h.Sometimes wheals resolve even more quickly.Angioedema is characterized by 1A sudden,pronounced erythematous or skin-colored swelling of the lower dermis and subcutis with frequent involvement below mucous membranes and2Sometimes pain rather than itching and frequent involve-ment below mucous membranes.Its resolution is slower than that for wheals and can take up to72h. Pathophysiological aspectsUrticaria is a mast-cell-driven disease.Histamine and other mediators,such as platelet-activating factor(PAF)and cyto-kines released from activated mast cells,result in sensory nerve activation,vasodilatation,and plasma extravasation as well as cell recruitment to urticarial lesions.The mast-cell-activating signals in urticaria are ill-defined and likely to be heterogeneous and diverse.Histologically,wheals are character-ized by edema of the upper and mid-dermis,with dilatation of the postcapillary venules and lymphatic vessels of the upper dermis.In angioedema,similar changes occur primarily in the lower dermis and the subcutis.Skin affected by wheals virtually always exhibits upregulation of endothelial cell adhesion mole-cules and a mixed inflammatory perivascular infiltrate of vari-able intensity,consisting of neutrophils and/or eosinophils, macrophages,and T cells,but without vessel-wall necrosis, which is a hallmark at urticaria vasculitis(12–14).A mild-to-moderate increase of mast cell numbers has also been reported by some authors.In delayed pressure urticaria,the infiltrate is typically located in the mid-to lower dermis.In some subtypes of urticaria,up-regulation of adhesion molecules(15)and altered cytokine expression are also seen in uninvolved skin (16).Thesefindings underline the complex nature of the patho-genesis of urticaria,which has many features in addition to the release of histamine from dermal mast cells(17,18).These changes are also seen in a wide variety of inflamma-tory reactions and are thus not specific or of diagnostic value.A search for more specific histological biomarkers for different subtypes of urticaria is desirable.Considerations about patient-related outcomes in patients with urticariaQuality of lifePatient-related outcomes are important to be looked at in the treatment for urticaria(19).The available data indicate that urticaria has a detrimental effect on both objective function-ing and subjective well-being.For example,O’Donnell et al.(20)showed that health status scores in patients with chronic spontaneous urticaria(CSU)are comparable to those reported by patients with coronary artery disease.Further-more,both health status and subjective satisfaction in patients with CSU are lower than in healthy subjects and in patients with respiratory allergy(21).A study of Poon et al.(22)focused on the extent and nature of disability in different types of urticaria,showing a large variation in Health-Related Quality of Life(HR-QoL)scores within different urticarial subsets.In this study,the assessment of HR-QoL was performed using generic tools.A QoL Questionnaire specifically developed for CSU was validated,including physical,emotional,social,and practicalEAACI/GA2LEN/EDF/WAO urticaria guideline Zuberbier et al.aspects characteristic of this condition (23).This new tool named Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL)was originally generated and tested in the Italian language following well-established procedures.The CU-Q2oL meets the standards for validity with good construct validity,internal consistency,reliability,and responsiveness.These psychometric characteristics make it suitable for the assessment of the health burden of CSU.It has now been translated and validated in German,Spanish,Polish,Turk-ish,Greek,Bulgarian,Brazilian-Portuguese,and other ver-sions are currently being validated (24–28).In addition,another questionnaire covers patients with angioedema (29).The Angioedema Quality of Life Questionnaire (AE-QoL),a symptom-specific Qol instrument,has been developed in Ger-man (29)and has been translated in various languages,including English (USA),Spanish,French,Azeri,Swedish,Hungarian,Romanian,Greek,and Polish.Classification of urticaria on the basis of its duration,frequency,and causesThe spectrum of clinical manifestations of different urticaria subtypes is very wide.Additionally,two or more different subtypes of urticaria can coexist in any given patient.Acute urticaria is defined as the occurrence of spontaneous wheals,angioedema,or both for <6weeks.Table 2presents a classification for clinical use of chronic urticaria subtypes.This revised classification deals with previous inconsistencies,for example physical urticarias may also be chronicconditions,but they were grouped separately due to the special nature of their eliciting physical factors.Urticaria pigmentosa (cutaneous mastocytosis),urticaria vasculitis ,auto-inflammatory syndromes (e.g.,cryopyrin-associated periodic syndromes or Schnitzler’s syndrome),and nonmast cell mediators mediated/induced angioedema (e.g.,bradyki-nin-mediated angioedema)are not considered to be subtypes of urticaria,due to their distinctly different pathomecha-nisms,but are listed in Table 3for reference.Wheals are also features of several syndromes (Table 3).Assessment of disease activity and impactDisease activity in spontaneous urticaria should be assessed both in clinical care and in trials with the UAS7(Table 4),a unified and simple scoring system that was proposed in the last version of the guidelines and has been validated (30).The signs and symptoms are evaluated by the patient making this score especially valuable.The use of the UAS facilitates com-Table 2Classification of chronic urticaria subtypes (presenting with wheals,angioedema,or both)Chronic urticaria subtypes Chronic spontaneous urticaria Inducible urticariaSpontaneous appearance of wheals,angioedema,orboth ≥6weeks due to known or unknown causesSymptomatic dermographism *Cold urticaria †Delayed pressure urticaria ‡Solar urticaria Heat urticaria §Vibratory angioedema Cholinergic urticaria Contact urticaria Aquagenic urticaria*also called urticaria factitia ,dermographic urticaria;†also called cold contact urticaria;‡also called pressure urticaria;§also called heat contact urticaria.Table 3Diseases related to urticaria for historical reasons and syndromes that present with hives and/or angioedema Maculopapular cutaneous mastocytosis (urticaria pigmentosa) Urticarial vasculitisBradykinin-mediated angioedema (e.g.,HAE) Exercise-induced anaphylaxisCryopyrin-associated periodic syndromes (CAPS;urticarial rash,recurrent fever attacks,arthralgia or arthritis,eye inflammation,fatigue and headaches),that is,familial cold autoinflammatory syndrome (FCAS),Muckle –Wells syndrome (MWS),or neonatal onset multisystem inflammatory disease (NOMID).Schnitzler’s syndrome (recurrent urticarial rash and monoclonal gammopathy,recurrent fever attacks,bone and muscle pain,arthralgia or arthritis and lymphadenopathyGleich’s syndrome (episodic angioedema with eosinophilia) Well’s syndrome (Granulomatous dermatitis with eosinophilia)These diseases and syndromes are related to urticaria (i)because they present with wheals,angioedema,or both and/or (ii)because of historical reasons.Table 4The UAS7for assessing disease activity in CSU ScoreWhealsPruritus0NoneNone1Mild (<20wheals/24h)Mild (present but notannoying or troublesome)2Moderate (20–50wheals/24h)Moderate (troublesome but does not interfere with normal daily activity or sleep)3Intense (>50wheals/24h or large confluent areas of wheals)Intense (severe pruritus,which is sufficientlytroublesome to interfere with normal daily activity or sleep)Sum of score:0–6for each day is summarized over one week (maximum 42).Zuberbier et al.EAACI/GA 2LEN/EDF/WAO urticaria guidelineparison of study results from different centers.The UAS is based on the assessment of key urticaria symptoms (wheals and pruritus).It is suitable for the evaluation of disease activ-ity by urticaria patients and their treating physicians.Further-more,this scoring system has been widely used in trials and should thus be maintained for future comparison.As urticaria symptoms change frequently in intensity,the overall disease activity is best measured by advising patients to document 24-h self-evaluation scores once daily for several days.A modifi-cation of the UAS7assessing signs and symptoms two times per day was also validated (31),but voting preferred to use the classical UAS because (i)measuring only once daily for the last 24h does give a bias in patients with primarily noc-turnal symptoms only and (ii)it has been more widely used and it is important to use the same tool worldwide in trials to allow comparison.The UAS7,that is,the sum score of seven consecutive days,should be used in routine clinical practice to determine disease activity and response to treatment of patients with CSU,as well as in some cases of patients with inducible or physical urticaria as well.For patients with an-gioedema,a novel activity score,the Angioedema Activity Score has been developed and validated (29).In addition to disease activity,it is important to assess the impact of disease on QoL both in clinical practice and in trials.In physical urticaria and in cholinergic urticaria,the threshold of the eliciting factor(s)should be determined to assess severity,for example critical temperature and stimula-tion time thresholds for cold provocation in cold urticaria.These thresholds allow both patients and treating physicians to evaluate disease activity and response to treatment.Diagnosis of urticariaIn the last two decades,many advances have been made in identifying causes of different types and subtypes of urticaria,for example,in CSU reviewed in Refs (32–33).Among oth-ers,autoreactivity including autoimmunity mediated by func-tional autoantibodies directed against the IgE receptor,pseudo-allergy (nonallergic hypersensitivity reactions)to foods and drugs,and acute or chronic infections (e.g.,Heli-cobacter pylori or Anisakis simplex )have been described (34–44)(Table 5).However,there are considerable variations in the frequency of underlying causes in the different studies.This also reflects regional differences in the world,forexample,different traditional diets and different prevalence of infections.Thus,it is important to remember that not all possible causative factors need to be investigated in all patients and the first step in diagnosis is a thorough history,taking the following questions into consideration:1Time of onset of disease2Frequency/duration of and provoking factors for wheals 3Diurnal variation4Occurrence in relation to weekends,holidays,and for-eign travel5Shape,size,and distribution of wheals 6Associated angioedema7Associated subjective symptoms of lesions,for exampleitch,pain8Family and personal history regarding urticaria,atopy 9Previous or current allergies,infections,internal diseases,or other possible causes10Psychosomatic and psychiatric diseases11Surgical implantations and events during surgery,forexample after local anesthesia 12Gastric/intestinal problems13Induction by physical agents or exercise14Use of drugs (e.g.,non-steroidal anti-inflammatorydrugs (NSAIDs),injections,immunizations,hormones,laxatives,suppositories,ear and eye drops,and alterna-tive remedies)15Observed correlation to food16Relationship to the menstrual cycle17Smoking habits (especially use of perfumed tobaccoproducts or cannabis)18Type of work 19Hobbies20Stress (eustress and distress)21Quality of life related to urticaria and emotional impact 22Previous therapy and response to therapy 23Previous diagnostic procedures/resultsThe second step of the diagnosis is the physical examina-tion of the patient.This should include a diagnostic provoca-tion test including drug,food,and physical tests where it is indicated by history.All subsequent diagnostic steps will depend very much on patient history and on the nature of the urticaria subtype,as summarized in Fig.1and Table 5.EAACI/GA 2LEN/EDF/WAO urticaria guidelineZuberbier et al.Intensive and costly general screening programs for causesof urticaria are strongly advised against.The following fac-tors should only be investigated based on patient history.Type I allergy is a rare cause of CSU in patients who presentwith daily or almost daily symptoms,but may be consideredin CSU patients with intermittent symptoms.In contrast,pseudo-allergic(non-allergic hypersensitivity reactions)toNSAIDs food or food additives may be more relevant forCSU with daily symptoms.Diagnosis should be based on aneasy-to-follow diet protocol(see patient information page indifferent languages under /).Bacterial,viral,parasitic,or fungal infections,for example,with H.pylori,Streptococci,Staphylococci,Versinia,Giardialamblia,Mycoplasma pneumonia,Hepatitis virus,Norovirus,Parvovirus B19,Anisakis simplex,Entamoeba ssp.,Blastocystis Table5Recommended diagnostic tests in frequent urticaria subtypesTypes SubtypesRoutine diagnostic tests(recommended)Extended diagnostic program*(suggested based onhistory only)For identification of underlying causes or elicitingfactors and for ruling out possible differential diagnosesif indicatedSpontaneousurticariaAcute spontaneous urticaria None None†Chronic spontaneousurticariaDifferential blood count.ESR or CRPOmission of suspecteddrugs(e.g.,NSAID)Test for(in no preferred order):(i)infectious diseases(e.g.,Helicobacter pylori),(ii)type I allergy,(iii)functional autoantibodies,(iv)thyroid hormonesand autoantibodies,(v)skin tests including physicaltests,(vi)pseudoallergen-free diet for3weeks,(vii)tryptase‡,(viii)autologous serum skin test,and(ix)lesional skin biopsyInducibleurticariaCold urticaria Cold provocation andthreshold test(ice cube,cold water,cold wind)Differential blood count and ESR or CRP cryoproteinsrule out other diseases,especially infections Delayed pressure urticaria Pressure test andthreshold testNoneHeat urticaria Heat provocation andthreshold testNoneSolar urticaria UV and visible light ofdifferent wavelengthsand threshold testRule out other light-induced dermatosesSymptomaticdermographismVibratory AngioedemaElicit dermographismand thresholdtest(dermographometer)Test with,for example,vortexDifferential blood count,ESR or CRPNoneAquagenic urticaria Wet cloths at bodytemperatureapplied for20minNoneCholinergic urticaria Exercise and hot bath provocation NoneContact urticaria Cutaneous provocationtest.Skin tests withimmediate readings,for example prick testNoneESR,erythrocyte sedimentation rate;CRP,C-reactive protein.*Depending on suspected cause.†Unless strongly suggested by patient history,for example allergy.‡As indication of severe systemic disease.Zuberbier et al.EAACI/GA2LEN/EDF/WAO urticaria guideline。