Appearance

The typical lesion is a central itchy white papule or plaque due to dermal oedema (weal).^[1] This is surrounded by an erythematous flare. The lesions are variable in size and shape and may be associated with swelling of the soft tissues of the eyelids, lips and tongue (angio-oedema).

Individual lesions come and go within a few hours and the patient may need to be questioned carefully to establish this. If they are unsure how long each lesion lasts, a line drawn around one lesion will demonstrate any change when inspected the following day.

Epidemiology

Approximately 15% of people experience urticaria at some time in their lives.The prevalence rate has been assessed as 1-5 per 1,000.^[2]

The most common age range for chronic urticaria is the fourth and fifth decades.^[3]

Causes^[2][4]

Urticaria is thought to be due to release of histamine and other mediators from mast cells in the skin; why this occurs is not always understood. In a sample of patients with chronic urticaria, approximately 30% have been demonstrated to have autoantibodies which act on mast cells and basophils.The autoantibodies have a high affinity for IgE receptors or the IgE bound to these cells, causing them to degranulate with a consequent release of histamine.

The British Association of Dermatologists (BAD) has recently released updated guidelines which classify the aetiology of urticaria into idiopathic, immune or nonimmune, as follows:^[5]

• Idiopathic
• Immunological:
  • Autoimmune (autoantibodies against Fc epsilon 5RI or IgE).
  • Allergic (IgE-mediated type I hypersensitivity reactions).
  • Immune complex (urticarial vasculitis).
  • Complement-dependent (C1 esterase inhibitor deficiency).
• Nonimmunological:
  • Direct mast cell-releasing agents (eg opiates).
  • Aspirin, nonsteroidal anti-inflammatories and dietary.
  • Pseudoallergens.
  • Angiotensin-converting enzyme inhibitors.

Presentation

The BAD guidelines identify a number of subtypes, depending on clinical features and possible causes:^[5]

• Ordinary urticaria:
  • Acute (up to 6 weeks of continuous activity).
  • Chronic (6 weeks or more of continuous activity).
  • Episodic (acute intermittent or recurrent activity).
• Physical urticarias (reproducibly induced by the same physical stimulus).
• Mechanical:
  • Delayed pressure urticaria.
  • Symptomatic dermographism.
  • Vibratory angio-oedema.
• Thermal:
  • Cholinergic urticaria.
  • Cold contact urticaria.
  • Localised heat urticaria.
• Other:
  • Aquagenic urticaria.
  • Solar urticaria.
  • Exercise-induced anaphylaxis.
• Angio-oedema without weals:
  • Idiopathic.
  • Drug-induced.
  • C1 esterase inhibitor deficiency.
• Contact urticaria (contact with allergens or chemicals).
• Urticarial vasculitis (defined by vasculitis on skin biopsy).
• Autoinflammatory syndromes:
  • Hereditary:
    • Cryopyrin-associated periodic syndromes - CIAS1 mutations.
• Acquired:
  • Schnitzler's syndrome (chronic, nonpruritic urticaria in association with recurrent fever, bone pain, arthralgia or arthritis and a monoclonal IgM gammopathy).

Diagnosis

This is established once it has been shown that individual lesions only last a few hours. Sometimes an eczema may be difficult to distinguish if the history is vague.

Physical urticarias occur in relation to local heat (cholinergic), scratching (dermographism), pressure, cold and ultraviolet light (solar).

Differential diagnosis^[2][3]

• Erythema multiforme
• Dermatitis herpetiformis
• Urticarial vasculitis
• Pemphigoid
• Erysipelas
• Eczema

Investigation

Investigations are rarely necessary in mild cases but in patients who fail to respond to treatment or who have severe recurrent symptoms investigations are appropriate, depending on subtype:

• Ordinary urticaria - acute/episodic - IgE.
• Chronic urticaria - full blood count (FBC), erythrocyte sedimentation rate (ESR), thyroid antibodies.
• Physical urticaria- physical challenge.
• Angio-oedema without weals - C4 (component of complement as a marker for C1 esterase inhibitor deficiency and in hypocomplementaemic urticarial vasculitis).
• Contact urticaria - IgE
• Urticarial vasculitis - FBC, ESR, C4, skin biopsy.^[2]
• Autoinflammatory syndrome - FBC, ESR.

Primary care management^[5]

Urgent hospital admission is indicated if acute urticaria rapidly develops into angioneurotic oedema or anaphylactic shock.

Nonspecific aggravating factors should be minimised, such as overheating, stress and drugs likely to cause urticaria (eg aspirin, codeine).

• Antihistamines:
  • Non-sedating H1 antihistamines are the mainstay of treatment. There are no meta-analyses comparing the different antihistamines for the treatment of acute urticaria, so choice is a matter of personal preference. It is common practice to offer the patient at least two choices of non-sedating H1 antihistamine in view of differences in tolerability and response. Alternatives include:^[5]
    • Acrivastine
    • Cetirizine hydrochloride
    • Desloratadine
    • Fexofenadine hydrochloride
    • Levocetirizine hydrochloride
    • Loratadine
    • Mizolastine
    • Rupatidine
    H1 antihistamines may be increased beyond their licensed dose but this approach is usually initiated by a specialist.
    
    Urticarial reactions to H1 antihistamines have occasionally been reported and this should be borne in mind when a patient treated with these drugs gets worse.^[6]
    
    
  • Sedating antihistamines such as chlorphenamine may be helpful in patients whose itching causes sleep disturbance but they are otherwise to be avoided due to their increased adverse effects (eg headache, psychomotor impairment and antimuscarinic effects).^[5]
  • The addition of an H2 antihistamine (egcimetidine) may provide additional benefit in some cases.^[7]
• Menthol 1% in aqueous cream helps to soothe itch, although the residue can cause itching in some patients.^[2]
• Oral steroids may help to shorten the duration of acute urticaria. 50 mg of prednisolone for 3 days is recommended, although lower doses may be effective. Long-term oral steroids are not indicated in chronic urticaria.^[5]
• Antileukotrienes (eg montelukast) may provide additional benefit in some patients when combined with an H1 antihistamine; there is little evidence that they are effective as monotherapy.^[5]

When to refer

Acute urticaria which fails to respond to treatment may require intravenous hydrocortisone. Chronic urticaria which fails to respond to general measures and medication may require detailed investigation to exclude an autoimmune cause and treatment with immunosuppressive therapy.^[5] Ciclosporin is the best studied but further evaluation is required as to dosage, duration of treatment and selection of patients likely to respond.^[5] Anticoagulant drugs have also occasionally been used because chronic urticaria is thought to be linked to the coagulation system.

Prognosis

This is variable. Most cases of idiopathic urticaria resolve over a period of 6 months but a minority can persist for many years. Chronic urticaria patients with angio-oedema and weals seem to have a worse prognosis than those presenting with weals alone.^[5]