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BSACI Guideline for the Management of Chronic Urticaria and Angioedema R doi: 10.1111/cea.12494 Clinical & Experimental Allergy, 45, 547–565 BSACI GUIDELINE © 2015 John Wiley & Sons Ltd BSACI guideline for the management of chronic urticaria and angioedema R. J. Powell1, S. C. Leech2, S. Till3, P. A. J. Huber4, S. M. Nasser5 and A. T. Clark6 1Department of Clinical Immunology and Allergy, Nottingham University, Nottingham, UK, 2Department of Child Health, Kings College Hospital, London, UK, 3Division of Asthma, Allergy and Lung Biology, Kings College London, London, UK, 4BSACI, British Society for Allergy & Clinical Immunology, London, UK, 5Department of Allergy & Clinical Immunology, Addenbrooke’s NHS Trust, Cambridge, UK and 6Department of Allergy, Addenbrookes NHS Trust, Cambridge, UK Summary Clinical This guidance for the management of patients with chronic urticaria and angioedema has & been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert Experimental opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, Allergy all BSACI members were included in the consultation process using a Web-based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the Correspondence: committee. Included in this management guideline are clinical classification, aetiology, Dr A. T. Clark, Allergy Clinic, diagnosis, investigations, treatment guidance with special sections on children with urti- Cambridge University Hospitals NHS caria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, Foundation Trust, Box 40, Cambridge we have made recommendations for potential areas of future research. CB2 2QQ, UK. E-mail: [email protected] Keywords adult, allergy, angioedema, antihistamine, anti-IgE, auto-antibody, autoimmune, Cite this as: R. J. Powell, S. C. Leech, breastfeeding, BSACI, child, epidemiology, guideline, hypothyroidism, IgE, management, S. Till, P. A. J. Huber, S. M. Nasser and paraprotein, pregnancy, pregnancy, Urticaria A. T. Clark, Clinical & Experimental Allergy, 2015 (45) 547–565. Submitted 6 October 2014; revised 11 December 2014; accepted 9 January 2015 (Appendix Tables B1 and B2). During the development Introduction of these guidelines, all BSACI members were consulted This guidance for the management of patients with using a Web-based system and their comments and chronic urticaria/angioedema is intended for use by suggestions were carefully considered by the Standards physicians treating allergic conditions. It should be rec- of Care Committee (SOCC). Where evidence was ognized that patients referred to an allergy clinic often lacking, a consensus was reached among the experts have a different pattern of presentation (e.g. intermit- on the committee. Conflict of interests were recorded tent acute) from those referred elsewhere and both the by the SOCC. None jeopardized unbiased guideline patient and referring practitioners often wish to deter- development. mine whether allergy is involved. Evidence for the recommendations was collected by Executive summary and recommendations electronic literature searches of MEDLINE and EMBASE (Grades of recommendations are described in Appendix using these primary key words: urticaria, angioedema, Tables B1 and B2) angioneurotic oedema, allergy, allergic, antihistamines, auto-antibody, autoimmune, hypothyroidism, IgE, • Chronic urticaria/angioedema has traditionally been paraprotein, pregnancy, breastfeeding, child, epidemiol- defined as weals, angioedema or both with daily or ogy, management, psychology. In addition, hand almost daily symptoms lasting for more than 6 weeks. searches were performed and the Cochrane library and In these guidelines, we have also included patients with NHS evidence were also searched. Each article was episodic acute intermittent urticaria/angioedema lasting reviewed for suitability by the first and second author for hours or days and recurring over months or years. of this guideline. The recommendations were evidence • Weals and angioedema commonly occur together, graded at the time of preparation of these guidelines but may also occur separately. 548 R. J. Powell et al • Chronic urticaria affects 2–3% of individuals (lifetime Definition prevalence) and significantly reduces quality of life (QoL). • There are important differences in aetiology and Chronic urticaria/angioedema (CU) has traditionally management in children compared to adults. been defined as weals, angioedema or both lasting for • The diagnosis is based primarily on the clinical his- more than 6 weeks [1, 2]. Acute urticaria is an episode < tory. Investigations are determined by the clinical his- of spontaneous weals lasting for 6 weeks and is not tory and presentation, but may not be necessary. considered further in this guideline. However, we have • Management must include the identification and/or included patients with episodic urticaria/angioedema exclusion of possible triggers, patient education and a lasting for hours or days and recurring over months or personalized management plan (grade of recommenda- years. Although rarely life-threatening, chronic urti- tion = D). caria/angioedema leads to both misery and embarrass- • Food allergy can usually be excluded as a cause of urti- ment and has a significant impact on an individual’s – caria/angioedema if there is no temporal relationship to a quality of life [3 5]. Regrettably, this troublesome con- particular food trigger, by either ingestion or contact. Food dition is often trivialized. Box 1 lists the terminology additives rarely cause chronic urticaria and angioedema. pertaining to urticaria referred to in this guideline. • Certain drugs can cause or aggravate chronic urti- Urticaria (‘hives’ or ‘nettle rash’) is characterized by a caria and/or angioedema, and hence, a detailed drug red (initially with a pale centre), raised, itchy rash history is mandatory. resulting from vasodilatation, increased blood flow and • Autoimmune urticaria/angioedema in older children increased vascular permeability. Weals can vary in size and adults is reported to account for up to 50% of from a few millimetres to hand-sized lesions which chronic urticaria and may be associated with other may be single or numerous. The major feature of urti- autoimmune conditions such as thyroiditis. caria is mast cell activation that results in the release of • Autoimmune and some inducible weals can be more histamine (and other inflammatory mediators); that in resistant to treatment and follow a protracted course. turn accounts for the raised, superficial, erythematous • The commonest type of angioedema without weals is weals and accompanying intense pruritus. Angioedema histaminergic. (tissue swelling) is the result of a local increase in vas- • Angioedema without weals is a cardinal feature of cular permeability, often notable in the face, orophar- hereditary angioedema (HAE) and typically involves ynx, genitalia and less frequently in the gastrointestinal subcutaneous sites, gut and larynx. In Types I and II tract. These swellings can be painful rather than itchy. HAE, levels of C4 and C1 inhibitor (functional and/or Weals affect the superficial skin layers (papillary der- antigenic) are low. mis), whereas angioedema can involve the submucosa, • Angiotensin converting enzyme (ACE) inhibitors can the deeper reticular dermis and subcutaneous tissues. cause angioedema without weals resulting in airway Weals and angioedema often coexist, but either can compromise. They should be withdrawn in subjects with occur separately. Characteristically the weals arise a history of angioedema (grade of recommendation = C). spontaneously and each lesion resolves within 24 h. ACE inhibitors are contraindicated in individuals with a This contrasts with angioedematous swellings that can history of angioedema with or without weals. persist for a few days. • Pharmacological treatment should be started with a When functional antibodies are demonstrated, this standard dose of a non-sedating H1-antihistamine suggests an autoimmune basis. In the commonest form (grade of recommendation = A). • The treatment regime should be modified according Box 1. Terminology dependent on how study popula- to treatment response and development of side-effects. tion was characterized • Higher than normal doses of antihistamines may be required to control severe urticaria/angioedema (grade of recommendation = B). Updosing with a single antihista- Term Abbreviation Definition mine is preferable to mixing different antihistamines. Chronic urticaria CU Encompasses CsU and CaU • If an antihistamine is required in pregnancy, the Chronic spontaneous CsU Not associated with lowest dose of chlorphenamine, cetirizine or loratadine urticaria (previously auto-antibodies should be used (grade of recommendation = C). called CiU – chronic • If an antihistamine is required during breastfeeding, idiopathic urticaria) it is recommended that either cetirizine or loratadine Chronic autoimmune CaU Associated with antibodies are taken at the lowest dose. Whenever possible, chlor- urticaria to IgE/IgE receptor Hereditary Angioedema HAE Typically associated with phenamine should be avoided during breastfeeding C1 inhibitor deficiency (grade of recommendation = C). © 2015 John Wiley & Sons Ltd, Clinical & Experimental Allergy, 45 : 547–565
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