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Management of chronic urticaria and angioedema

Terms used in this guideline

  • C1 inhibitor deficiency: low serum levels of the complement C1 inhibitor protein, which is associated with angioedema, due to a rare inherited or acquired deficiency of the C1 inhibitor
  • Non-IgE mediated mast cell degranulation: acute reaction due to the activation of mast cells by non-IgE mediated stimuli (e.g. such as opiates)

Definition

  • Chronic urticaria/angioedema has traditionally been defined as weals, angioedema or both with daily or almost daily symptoms lasting for more than 6 weeks. This guideline includes patients with episodic acute intermittent urticaria/angioedema lasting for hours or days and recurring over months or years
  • Weals and angioedema commonly occur together, but may also occur separately
  • Chronic urticaria affects 2–3% of individuals (lifetime prevalence) and significantly reduces quality of life (QoL)

Aetiology

  • Urticaria may occur alone in about 50% of cases, urticaria with angioedema in 40%, and angioedema without weals in 10%
  • Aetiological classification of chronic urticaria/angioedema:
    • spontaneous (previously called idiopathic) (40–50% cases)
    • autoimmune
    • physical stimuli (triggers include exercise, exposure to cold or heat)
    • drug induced
    • infection (e.g. parasites, Epstein–Barr virus, hepatitis B and C)
    • allergy to latex, grass, animals, food can sometimes produce intermittent urticaria/angioedema
    • C1 inhibitor deficiency:
      • genetic
      • acquired
    • non-IgE mediated mast cell degranulation (can be triggered by opiates)
    • vasculitis
    • food constituent (rare; triggers include salicylates/benzoates)
  • Autoimmune urticaria/angioedema accounts for about 50% of chronic urticaria and may be associated with other autoimmune conditions such as thyroiditis
  • Angioedema without weals is the hallmark of hereditary angioedema (HAE) and typically involves subcutaneous sites, gut, and larynx. In HAE, levels of C4 and C1 inhibitor (functional or antigenic) are low
  • There are important differences in aetiology and management in children compared with adults

Diagnosis

  • The diagnosis is based primarily on the clinical history
  • Investigations are determined by the clinical history and presentation and may not be required
  • Investigations may include:
    • full blood count
    • urinalysis
    • erythrocyte sedimentation rate and/or C-reactive protein
    • thyroid function and thyroid autoantibodies
    • challenge testing
    • skin prick tests
    • occasionally skin biopsy (to exclude vasculitis)
  • Food can usually be excluded as a cause of urticaria/angioedema if there is no temporal relationship to a particular food trigger, either by ingestion or contact. Food additives rarely cause chronic urticaria and angioedema
  • Certain drugs (e.g. aspirin and non-steroidal anti-inflammatory drugs) can cause chronic intermittent urticaria and/or angioedema and hence a detailed drug history is mandatory
  • Angiotensin-converting enzyme (ACE) inhibitors can cause angioedema without weals occurring on the face and in the oropharynx. They should be stopped in individuals with any history of angioedema and are contraindicated in individuals with a history of angioedema with or without weals
  • Management must include the identification and/or exclusion of possible triggers, patient education, and a personalised management plan

Treatment

  • Pharmacological treatment should be started with a standard dose of a non-sedating H1 antihistamine. Higher doses may be appropriate to gain full control of symptoms
  • The treatment regimen should be modified according to treatment response and the development of side-effects
  • Increasing evidence suggests that a psychological approach may be useful
  • Autoimmune and some inducible weals (physical urticarias) are more resistant to anti-histamines and can follow a protracted course
  • Additional pharmacotherapy can be considered after consultation with a specialist:
    • tranexamic acid: useful in the treatment of spontaneous angioedema (off-licence) alongside antihistamines
    • leukotriene receptor antagonists (e.g. montelukast, zafirlukast)
    • omalizumab: used for chronic urticaria when higher dose antihistamines have failed to control symptoms
    • ciclosporin: may be considered in severe unremitting disease uncontrolled by antihistamines; requires close patient monitoring

Algorithm for diagnosis of chronic urticaria and/or angioedema*

Algorithm for diagnosis of chronic urticaria and/or angioedema

Reasons for referral to specialist

  • These include:
    • cases of diagnostic uncertainty
    • urticaria and/or angioedema where it is important to exclude an allergic cause
    • a patient who is symptomatic despite treatment with regular antihistamines
    • angioedema that is persistent, recurrent, or affecting the airway
    • abnormal C4 ± C1 inhibitor deficiency in the presence of angioedema alone without urticaria
    • possibility of vasculitic urticaria
    • a pregnant or breast-feeding woman who requires treatment
    • children, if schooling is affected

full guideline available from...

Standards of Care Committee, British Society for Allergy and Clinical Immunology

www.bsaci.org

Powell RJ, Leech SC, Till S et al. BSACI guideline for the management of chronic urticaria and angioedema. Clinical and Experimental Allergy 2015; 45: 547–565.
First included: April 2016. Updated July 2017.