Urticaria, otherwise known as hives, is an itchy red blotchy rash resulting from swelling of the superficial part of the skin. It can be localised or more widespread. Angio-oedema occurs when the deeper tissues, the lower dermis and subcutaneous tissues, are involved and become swollen.
The typical lesion is a central itchy white papule or plaque due to swelling of the surface of the skin (weal or wheal). 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 are typically transient. They come and go within a few minutes to hours and precise questioning may be needed to establish this. If there is uncertainty about how long each lesion lasts, a line drawn around one lesion will demonstrate any change when inspected the following day. Individual weals may join to form large patches.
In terms of timescale, urticaria can be classified into:
- Acute urticaria - where symptoms develop quickly but resolve speedily, often within 48 hours.
- Chronic urticaria - where the rash persists for more than six weeks.
Approximately 15% of people experience urticaria at some time in their lives. Acute urticaria is much more common than chronic urticaria. (Estimated lifetime incidence is 1 in 6 people compared to 1 in 1,000.) The prevalence rate for chronic urticaria has been estimated as 1-5 per 1,000. Acute urticaria is most common in children and is more common in women than in men, particularly in the 30-60 age range. It is more common in individuals who have atopy.
Urticaria is due to activation of mast cells in the skin, resulting in the release of histamine and other mediators. These chemicals cause capillary leakage, which causes the swelling of the skin, and vasodilation causing the erythematous reaction. There may be a trigger identified which causes this release but often the cause is not identifiable, particularly in chronic urticaria. An autoimmune reaction is thought to be involved in many such cases.
Some of the triggers are listed below within the classification section.
There are some differences in terminology and classification internationally.
British guidelines classify urticaria as follows:
In acute urticaria, a cause is identified in only about half of cases. Possible triggers include:
- Allergies: foods, bites, stings, medication.
- Viral infections.
- Skin contact with chemicals, nettles, latex, etc.
- Physical stimuli: firm rubbing (dermatographism), pressure, cold, heat.
Subtypes of chronic urticaria are:
- Chronic spontaneous urticaria. Triggers include medication, stress and infection. This was previously called idiopathic urticaria.
- Autoimmune urticaria (in the European guidelines this would come under the chronic spontaneous urticaria subtype above). This may account for half of all cases of chronic urticaria in adults and older children. There may be an association with other autoimmune conditions.
- Inducible urticaria. Triggers include:
- Contact with hot or cold water (aquagenic).
- Exercise or emotion (cholinergic).
- Exposure to cold or heat.
- Firm rubbing, minor trauma (dermatographism).
- Pressure (delayed pressure).
- Sun exposure (solar).
The British guideline refers to chronic urticaria/angio-oedema; it also lists angio-oedema without weals as a subtype and refers to urticarial vasculitis as a differential diagnosis. Urticarial vasculitis is vasculitis of the skin characterised by inflammation of the small blood vessels rather than urticaria. Causes include infection (hepatitis B/C, glandular fever or streptococcal infection), medication (penicillins, fluoxetine, thiazides, allopurinol, quinolones or carbamazepine), autoimmune disease, paraproteinaemia and malignancy.
- Erythema multiforme.
- Dermatitis herpetiformis.
- Urticaria pigmentosa.
- Chronic pruritus.
- Polymorphic eruption of pregnancy.
- Urticarial vasculitis (as above).
The diagnosis is usually made clinically and on history - particularly in acute ordinary urticaria - and no investigations are needed. It can be established once it has been shown that individual lesions only last a few hours. A detailed history may point to a trigger in some cases.
In chronic or recurring cases where investigations are needed, these will be guided by history.
Tests may include:
- ESR or CRP.
- Physical challenge. Cold provocation testing (ice cube), heat provocation test (warm water), pressure testing, UV light testing, exercise or hot bath provocation for cholinergic urticaria.
- Elicit dermatographism.
- Patch testing/prick testing for contact urticarias.
- IgE tests for specific allergens.
- Thyroid autoantibodies if autoimmune mechanism is suspected.
- Exclusion of suspected medication or food.
- Tests for infectious diseases
- Skin biopsy (urticarial vasculitis).
Where possible, identify and treat the cause. Nonspecific aggravating factors should be minimised, such as overheating, stress, alcohol, caffeine and medication likely to cause urticaria (eg, non-steroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme (ACE) inhibitors). Topical anti-pruritic agents such as calamine lotion or topical menthol 1% in aqueous cream may help ease symptoms.
Non-sedating H1 antihistamines are the mainstay of treatment. Cetirizine, loratadine and fexofenadine are usual choices. Studies comparing antihistamines are limited and so far no single antihistamine has shown itself to be superior for chronic spontaneous urticaria. Once symptom control has been achieved, the antihistamine should be continued for 3-6 months.
Where a standard dose of a non-sedating H1 antihistamine is ineffective, doses of up to four times the standard dose may be used, or another antihistamine added. Evidence for up-titrating the dose varies. An additional sedating antihistamine such as chlorphenamine may be useful if itch is interfering with sleep. Avoid hydroxyzine if the person has a prolonged QT interval or risk factors for QT interval prolongation in line with recent guidance from the Medicines and Healthcare products Regulatory Agency (MHRA).
Antihistamines should be avoided where possible in pregnancy. There are no systematic studies of safety in pregnancy, and chlorphenamine is often the first choice if an antihistamine is required in this situation. Loratadine or cetirizine are preferred in women who are breast-feeding.
Where symptoms are severe, a short course of oral steroids may be appropriate - for example, prednisolone 40 mg daily for seven days.
Second-line options which may be considered in secondary care for refractory chronic urticaria include:
- Antileukotrienes (eg, montelukast), which may provide additional benefit in some selected patients when combined with an H1 antihistamine; there is little evidence that they are effective as monotherapy.
- Omalizumab, an anti-IgE antibody. It is effective in 80% but requires monthly injections and relapse is common when it is stopped. The National Institute for Health and Care Excellence (NICE) recommends omalizumab as an add-on treatment for refractory severe chronic spontaneous urticaria.
- Ciclosporin for its immunosuppressive effect.
Evidence to help guide choice in second-line treatment is of variable quality.
When to refer
- If symptoms are not well controlled.
- If antihistamines are needed continuously to control symptoms for more than six weeks.
- If urticaria is painful and persistent, suspect vasculitic urticaria and refer for biopsy and histological diagnosis.
- Urgent hospital admission is indicated if acute urticaria rapidly develops into angio-oedema or anaphylactic shock.
This is variable. Most cases of idiopathic urticaria resolve over a period of six months but a minority can persist for many years. Some remit and then relapse. 50% of cases of chronic urticaria have resolved within 3-5 years. At least 20% of chronic urticaria patients requiring referral to secondary care are still symptomatic 10 years after first presentation. Factors associated with lasting duration include severe symptoms, associated angio-oedema and positive antithyroid antibodies.
Complications of chronic urticaria can include insomnia, depression and poorer quality of life. Anaphylaxis may occur in association with acute urticaria.
Further reading and references
; Primary Care Dermatology Society
; DermNet NZ
; The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014 May133(5):1270-7. doi: 10.1016/j.jaci.2014.02.036.
; NICE CKS, May 2016 (UK access only)
; British Society for Allergy and Clinical Immunology (Feb 2015)
; Urticaria Guidelines: Consensus and Controversies in the European and American Guidelines. Curr Allergy Asthma Rep. 2015 Jun15(6):30. doi: 10.1007/s11882-015-0535-z.
; The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014 Jul69(7):868-87. doi: 10.1111/all.12313. Epub 2014 Apr 30.
; DermNet NZ
; H1-antihistamines for chronic spontaneous urticaria. Cochrane Database Syst Rev. 2014 Nov 14(11):CD006137. doi: 10.1002/14651858.CD006137.pub2.
; Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. Br J Dermatol. 2016 May 30. doi: 10.1111/bjd.14768.
; Medicines and Healthcare products Regulatory Agency (MHRA), April 2015
; Omalizumab: a review of its use in patients with chronic spontaneous urticaria. Drugs. 2014 Sep74(14):1693-9. doi: 10.1007/s40265-014-0290-9.
; NICE Technology Appraisal Guidance, June 2015
; Systematic review of treatments for chronic spontaneous urticaria with inadequate response to licensed first-line treatments. Int J Dermatol. 2015 Sep54(9):1088-104. doi: 10.1111/ijd.12727. Epub 2014 Dec 16.