section name header

Information

Author: Alexandra Croom

Urticaria (nettle rash, hives) arises from mast cell degranulation in the skin. Angioedema (tissue swelling) can accompany urticaria and is due to mast cell degranulation in deeper tissues. The clinical features of urticaria and angioedema are described in Box 27.1 and management in Box 27.2.

Urticaria

For diagnostic purposes it is helpful to divide urticaria into two groups:

The underlying causes of each group are different (Table 27.1). No cause is identified (idiopathic) in 50% of acute urticaria and 98% of chronic urticaria; chronic urticaria is rarely IgE mediated (but often perceived as being so).

Priorities

  1. Search for the cause

    Urticaria is a symptom rather than a diagnosis. Although most urticaria is idiopathic, an underlying cause may become apparent on clinical assessment (Table 27.2, Figure 27.1). Some patterns of symptoms are typical, for example the urticaria in an IgE mediated reaction is of rapid onset after exposure (within minutes) and peaks within two hours. Urticaria that evolves over hours or days is not allergic.

    The investigations required for urticaria depend on its type and the suspected underlying cause.

    In acute urticaria investigations are normally unnecessary other than for the identification of allergens in suspected IgE-mediated reactions (e.g. skin prick testing and/or spIgE assays (RASTs)). These are usually deferred until after the acute event and done in specialist clinics. In chronic spontaneous urticaria, testing should be determined by the history and clinical findings, but as a minimum an FBC and ESR/CRP should be performed (as a screen for underlying inflammation as a driver for the urticaria).

    Laboratory testing is not normally required for physical urticaria, with the exception of cold urticaria, which may be associated with the presence of cryoglobulins or cold agglutinins.

    If a trigger is identified or suspected remove it and avoid it in the future. Where there is an underlying condition ‘driving’ the urticaria, treatment of that will be required before there is clinical improvement.

  2. Give treatment

Antihistamines

These are the mainstay of treatment. Where rapid symptom control is required, for example anaphylaxis, use chlorphenamine 10 mg IV. Otherwise chlorphenamine (and other first-generation antihistamines) should, where possible, be avoided as it can cause sedation, and confusion and falls in the elderly. Second-generation antihistamines, for example cetirizine, loratidine and fexofenadine are mostly well tolerated. The onset of action of oral antihistamines is around 20–25 min.

Higher than licensed doses (e.g. cetirizine 10 mg 6–12-hourly) are recommended for chronic urticaria not responding to conventional doses.

Chlorphenamine is the antihistamine of first choice for pregnant women; loratidine is second choice and should be used if excessive sedation is a problem.

Corticosteroids

Corticosteroids may be used, particularly if angioedema dominates the clinical picture or urticaria does not immediately come under control with antihistamines. Short courses should be used (prednisolone 30–40 mg daily for 5–7 days). Avoid protracted courses (>2 weeks) as tachyphylaxis will result in diminishing efficacy and increasing adverse side effects. Specialist referral is required if steroid requirements persist.

There is no role for topical corticosteroids in urticaria.

Isolated Angioedema

Angioedema that occurs without coexistent urticaria (either simultaneously or in the very recent past) is usually not due to mast cell degranulation and consequently responds poorly to antihistamines and corticosteroids. Causes are given in Table 27.3; most cases are idiopathic. Key features from the history are summarized in Table 27.4.

If urticaria is absent, the C1-inhibitor level and functional assay and complement levels should be checked.

Hereditary angioedema (HAE)

This is due to low or dysfunctional C1-inhibitor. Clinical features suggestive of this group of conditions include:

  • Repeated episodes of angioedema developing from childhood/adolescence
  • Triggered by trauma, stress, OCP, menses and infection
  • Non-painful, non-itchy swelling developing over a few hours and lasting 3–5 days
  • Life-threatening laryngeal obstruction (30% mortality rate)
  • Abdominal symptoms – vomiting, abdominal pain, hypotension, ascites; may be confused with acute abdomen

Acute episodes should be treated with plasma derived or recombinant human C1- inhibitor concentrate or icatibant (a bradykinin B2 receptor antagonist); supportive management of the airway may be necessary. FFP should only be used if none of these are available and patients should be counselled about risk of transmission of blood-borne disease. Androgens and antifibrinolytics are used long term for prophylaxis but have no role acutely.

Acquired angioedema (AAE)

This occurs in the context of autoimmune or lymphoproliferative disease. C1 inhibitor production is normal but functional activity is lost either due to increased catabolism of C1 inhibitor (type 1) or due to an autoantibody directed at C1 inhibitor (type 2). In contrast to HAE there is no family history and the onset is from middle age. AAE may improve as the underlying condition is treated. Acute episodes with life-threatening airway obstruction are rare but should be treated as per HAE.

Angiotensin-converting-enzyme inhibitor (ACEi) – associated angioedema

ACEi drugs may be a primary cause of angioedema or make coexisting angioedema worse. In the primary type, swelling is characteristically confined to the head; those of West African descent, women and smokers are at increased risk. The onset of swelling can be from months to years after initiation of treatment and can persist for several months after discontinuation of therapy. A switch to an angiotensin receptor blocking agent is normally well tolerated. Treatment is usually supportive but icatibant can be used if life-threatening airway obstruction occurs.

Further Reading

Powell RJ, Leech SC, Till S, Huber PAJ, Nasser SM, Clark AT. (2015) BSACI guideline for the management of chronic urticaria and angioedema. Clinical & Experimental Allergy 45, 547565. http://onlinelibrary.wiley.com/doi/10.1111/cea.12494/full.