The British Society for Allergy and Clinical Immunology guideline alleviates the diagnostic and therapeutic challenge of urticaria, say Dr Imran Rafi (left) and Dr Shuaib Nasser

TThe Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) has produced a comprehensive guideline for the management of chronic urticaria and angio-oedema in both adults and children.1 It is intended for use by physicians involved in the care of patients affected by these conditions and is therefore relevant to members of the primary healthcare team, including GPs and practice nurses.

The guideline highlights the need to improve primary care-based expertise in the management of these conditions, which can impact on quality of life and schooling. It also emphasises the need for accessible and responsive referral pathways to specialist allergy services.

The recommendations from BSACI were developed after consultation between experts of the SOCC and other members of the society using evidence-based grading. The guideline provides practical advice on questions to ask patients and useful investigations. It also discusses in considerable detail the pharmacological management of urticaria and angio-oedema.

What are urticaria and angio-oedema?

Urticaria, otherwise known colloquially as ‘hives’ or ‘nettle rash’, manifests as a red, raised, itchy rash. Weals may vary in number, size and longevity, and can cause intense itching and impact considerably on the quality of life of affected patients. Angio-oedema can occur concurrently or independently of urticaria. It is characterised by swelling of the skin, mucosa, or submucosal tissues.

The prevalence of chronic urticaria in adults was found to be 0.6% in a Spanish population study.2 In the UK, 0.1% to 3% of children may be affected by chronic urticaria, with about half of them also being affected by angio-oedema.

The guideline is intended to help in the management of patients with chronic urticaria and/or angio-oedema, which is defined as daily symptoms lasting more than 6 weeks. Guidance is also included for patients with episodic, acute intermittent urticaria and/or angio-oedema lasting for hours or days and recurring over months or years.1

In urticaria, the underlying vasodilation and increased vascular permeability occur as a result of mast cell activation, which leads to the release of histamine, and typically affects the superficial skin layers.1 Patients are often non-atopic and usually have a non-allergic cause, although many of them believe the symptoms to have an allergic basis. Angio-oedema typically involves the subcutaneous tissues around the mouth, eyes, and the submucosa, and swelling can persist for days, whereas in urticaria the lesions peak between 8 and 12 hours and resolve within 24 hours.

As many as 20% of patients with chronic urticaria may have symptoms lasting for longer than 10 years,3 and between them urticaria and angio-oedema constitute a common reason for referral for consultation with allergy specialists. The clinical classification of chronic urticaria and angio-oedema is given in Box 1.

Physical urticaria (e.g. pressure or cold) accounts for the most common causes of chronic urticaria in children; approximately 25% of them will go into remission within the first 3 years. Henoch–Schönlein purpura is the commonest cause of acute vasculitic urticaria.1

Box 1: Aetiological classification of chronic urticaria and angio-oedema11

Breakdown of cases:

  • urticaria alone=50%
  • combination of urticaria and angio-oedema=40%
  • angio-oedema alone=10%

Idiopathic—accounts for 40–50% of cases; mechanism of action is unknown but typical triggers include stress and viral infections

Autoimmune—occurs as a result of immunoglobulin G auto-antibody reacting to mast cell receptors; may be associated with autoimmune thyroiditis

Physical stimuli—can lead to direct mast cell mediator release; common triggers include exercise, cold, heat, pressure, vibration, water, and dermatographism

Drug induced—can be associated with reduced kinin metabolism commonly associated with ACE inhibitors where angio-oedema alone is present or there may be elevated leukotriene levels associated with NSAIDs; antidepressants and statins have also been implicated

Infection—associated with immune complex formation; can occur as a result of infection with Epstein–Barr virus, and hepatitis B and C; can be triggered by parasites and viral exanthems

Allergic-mediated urticaria and/or angio-oedema (IgE mediated)—has been associated with latex, animals, certain foods, and grass

C1 inhibitor deficiency—usually genetic, in the form of hereditary angio-oedema type 1 and 2, or acquired associated with a paraproteinaemia

Mast cell degranulation (non-allergic)—can be triggered by opiates

Vasculitis—particularly in small vessels can lead to urticaria

Lymphoproliferative disorders—associated with paraproteinaemia; these have been associated with B-cell lymphoma

Foods—some, with constituents such as salicylates, have been implicated, although the mechanism of action is unknown

Coeliac disease—there are case reports of an association between coeliac disease and urticaria

ACE= angiotensin-converting enzyme; NSAID=non-steroidal anti-inflammatory drug; IgE=immunoglobulin E

Reaching a diagnosis

A good clinical history and examination are essential to making the diagnosis, and symptom diaries are often helpful. A key question to consider from the history is whether there is an underlying allergic, vasculitic, or pharmacological cause (see Box 1 and Figure 1).

Further investigations may not be required, as the diagnosis is based primarily on clinical history.1 However, tests that may be used to identify the underlying aetiology are listed in Table 1.

Figure 1: Algorithm for diagnosis of chronic urticaria and/or angio-oedema*

Algorithm for diagnosis of chronic urticaria and/or andio-oedema
*Idiopathic urticaria ± angio-oedema: accounts for 40–50% of cases
Other individuals who may need referral include those patients who are pregnant or lactating, children where there is parental anxiety, or if school or work is being affected (see Box 3)

Table 1: Investigations to be undertaken in primary or secondary care,

when it is important to exclude known potential causes

Primary care

Secondary care

Full blood count Skin prick tests
Erythrocyte sedimentation rate Skin biopsy to exclude a vasculitis
Urinalysis Challenge testing with relevant stimuli, e.g. ice cube for suspected cold urticari
Thyroid function and thyroid autoantibodies  
Anti-streptolysin O  
Liver function, hepatitis B and C serology, and viral serology  
Immunoglobulin electrophoresis  
Serum-specific IgE to potential allergen  

Urticaria with or without angio-oedema

It is important to take a good history, including a drug and family history. When presenting in primary care, patients frequently consider food allergies as a cause for either urticaria or angio-oedema. However, food allergy usually becomes evident within 1 hour of the intake of the allergen, although, rarely, wheat allergy only becomes clinically evident following exercise up to 4 hours later. If the symptoms come on overnight or present first thing in the morning or several hours after ingestion, food allergy is unlikely to be the cause.

Immunoglobulin E-mediated food allergy usually exhibits other symptoms, such as lip, mouth, or pharyngeal itching and swelling, wheeze, abdominal pain, or vomiting, and rarely presents as chronic urticaria or angio-oedema.1 Life-threatening reactions may occur. Common triggers include eggs, milk, and peanuts, and referral to a specialist allergy department is indicated.

Urticarial vasculitis is usually characterised by lesions that last longer than 24 hours, and are possibly associated with systemic features such as fever or malaise. Lesions may be tender and painful and there may be evidence of petechial or purpuric haemorrhage or bruising.1 Referral to a specialist is recommended.

Taking a good drug history is important to consider whether the patient has symptoms that are caused by a medicine they are taking, such as aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors, antidepressants, or other medication.

Angio-oedema alone

Two primary causes to consider are whether this is drug-related, such as when an ACE inhibitor is being used, or whether there is a defect in the complement pathway—either hereditary angio-oedema or an acquired C1 inhibitor deficiency resulting from autoantibody binding of C1 inhibitor, or its depletion due to C1 activation by paraprotein.

The use of ACE inhibitors has been associated with swelling of the tongue, lips, pharynx, and larynx. The angio-oedema, can start many years after commencement of therapy and sometimes persists for a few weeks, even after stopping the ACE inhibitor.1 If the patient’s condition does not improve within 1–2 months of stopping treatment, then the underlying cause should be re-investigated.


There are several elements of treatment. These include:

  • providing reassurance
  • treating underlying conditions, such as autoimmune hypothyroidism
  • avoiding triggers, such as drugs like NSAIDs
  • controlling symptoms to help improve the patient’s quality of life
  • managing stress, which may help in the case of idiopathic urticaria.

Good sources of information include patient information leaflets from the British Association of Dermatologists (

Pharmacological therapy

In adults, a long-acting, non-sedating, second generation antihistamine (e.g. loratadine, fexofenadine, cetirizine), at the standard dose, is the mainstay of treatment in those with continuing symptoms where avoidable or treatable causes have been excluded. Patients with a long history of urticaria at presentation or urticaria with angio-oedema are advised to continue on treatment for 6 months or more, although patients with intermittent symptoms may be treated on an ‘as required’ basis or prophylactically (e.g. prior to a stressful life event). Most cases will respond to such measures, however, the guideline recommends that specialists consider the use of above-licensed doses of non-sedating H1-antihistamines in severe cases (e.g. 20 mg cetirizine o.d.) or add a second non-sedating antihistamine.

To aid sleep at night, adding a first-generation, sedating antihistamine, such as hydroxyzine or chlorphenamine, which are also licensed for use in patients under 2 years of age, can be helpful, although neither is recommended for long-term use. In very severe exacerbations, short courses of corticosteroids may be helpful; for example 1 mg/kg of prednisolone in children for up to 3 days, and 30–40 mg per day for 7 days in adults.1 If symptoms are persistent or refractory to standard therapy, referral to a specialist is indicated for further investigation and possible addition of second-line drugs, such as leukotriene receptor antagonists, low-dose corticosteroids, tranexamic acid, ciclosporin, and tacrolimus.

Referral to a specialist may also be indicated in women who are pregnant or during lactation, when antihistamines should only be used if the benefits outweigh the risks and after the patient has been informed about possible adverse effects. Chlorphenamine or loratadine, at the lowest possible dose, can be considered in pregnancy, although manufacturers advise avoidance of all antihistamines during pregnancy. During breast feeding there is significant excretion of most antihistamines into breast milk, although loratadine and cetirizine are found at relatively low levels in breast milk.1

Implications for primary care

Workload implications include having the time to take a detailed and relevant clinical history, the use of basic laboratory investigations, and accessing local referral pathways and expertise. Most GPs should feel confident in initiating relevant blood and urine tests, although most of these tests are likely to be negative. Skin prick testing is not widely used in primary care as a means of determining sensitivity to specific allergens. Employing the skills of local practitioners with a specialist interest in allergy, dermatology, or paediatrics may assist with diagnosis.

Future developments

Specialist allergy services throughout the UK are poorly resourced.4 The Government,5 in its response to the House of Common’s Health Select Committee report on allergy services,6 agreed that a national primary care allergy network should be created, and responsibility for this should fall to strategic health authorities (SHAs) and primary care trusts, which must consider local needs.

The House of Lords Science and Technology Committee 2007 report on allergy recommends the establishment in each SHA of at least one allergy centre, led by a full time allergy specialist.7 It suggests that each centre should be able to call upon other disciplines with an interest in allergy, including a chest physician; dermatologist; surgeon specialising in ear, nose, and throat; immunologist; gastroenterologist; occupational health practitioner; and paediatrician. Once established, the centre would act as the ‘hub’ of a ‘hub and spokes’ model. The centre would be responsible for:7

  • coordinating allergy training of local GPs and other healthcare workers
  • acting as the focal point of expertise with outreach clinical services
  • providing education and training for primary care.

The role of practice-based commissioning

Practice-based commissioning could act as a lever to drive appropriate local services for the treatment of urticaria (see Box 2). Referral guidelines with local ownership may reassure patients that less common causes of chronic urticaria and angio-oedema have been considered. The algorithm (see Figure 1) provides a pathway to guide the practitioner when faced with a worried patient, and Box 3 summarises the indications for referral.

Box 2: How practice-based commissioning can help to implement the

guideline recommendations

Implementation of the guideline can be facilitated by ensuring:

  • community practitioners with a relevant special interest meet clinical governance standards through education, training, and the necessary competence in the management of this condition
  • referral pathways are established, clearly defined, and have capacity to manage demand to satisfy access waiting targets, particularly in cases as outlined in Box 3 (below)
  • primary care matches the aims of the ‘hub and spoke’ model of care, incorporating a multidisciplinary approach

Box 3: Indications for referral to a specialist allergy department

Diagnostic or therapeutic challenges where specialist referral should be considered include:
  • cases of diagnostic uncertainty
  • urticaria and/or angio-oedema where it is important to exclude an allergic cause
  • severe angio-oedema
  • abnormal C4 or C1 inhibitor deficiency in the presence of angio-oedema or paraproteinaemia
  • lymphoproliferative disease
  • possibility of vasculitic urticaria
  • a pregnant or breast-feeding woman who requires treatment
  • a patient who is symptomatic despite treatment with regular antihistamines
  • children, with anxious parents or if schooling is affected


Chronic urticaria, with or without angio-oedema, is distressing for those affected and a diagnostic and therapeutic challenge for the physician looking after these patients. The BSACI guideline has been adapted for use across disciplines and highlights the need for close collaboration between primary and secondary services.

  • These are common conditions affecting approximately 0.1–3% of children and 0.6% of adults
  • The House of Lords Science and Technology Committee 2007 report on allergy recommends the establishment of at least one allergy centre per SHA area, to coordinate allergy care pathway development1
  • Tariff prices:2
      • allergy clinic = £152 (new), £115 (follow-up) (includes skin testing where required)
      • dermatology outpatient for adults = £118 (new), £58 (follow-up)
      • dermatology outpatient for children = £129 (new), £71 (follow-up)
      • clinical immunology = £244 (new), £180 (follow-up)
  1. Powell R, Du Toit G, Siddique N et al. BSACI guidelines for the management of chronic urticaria and angio-oedema.Clin Exp Allergy 2007; 37 (5): 631–650.
  2. Gaig P, Olona M, Munoz Lejarazu D et al. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol 2004; 14 (3): 214–220.
  3. Humphreys F, Hunter J. The characteristics of urticaria in 390 patients. Br J Dermatol 1998; 138 (4): 635–638.
  4. Royal College of Physicians. Allergy: the unmet need—a blueprint for better patient care. London: RCP, 2003.
  5. Department of Health. Government response to the House of Commons Health Committee Report on the provision of allergy services. Sixth report of session 2003–04. Norwich: The Stationery Office, 2005.
  6. House of Commons Health Committee. Report on the provision of allergy services. Sixth report of session 2003–04. House of Commons, 2004. (accessed 29th September 2007).
  7. House of Lords Science and Technology Committee. Sixth report of Session 2006–7, Allergy Volume 1: report. London: The Stationery Office, 2007.G