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Chronic urticaria

Author and DermNet NZ Editor-in-Chief: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, January 2015.

Chronic urticaria — codes and concepts

What is urticaria?

Urticaria is a skin condition characterised by weals (hives) or angioedema (swellings, in 10%) or both (in 40%). There are several types of urticaria.

  • The name urticaria is derived from the common European stinging nettle Urtica dioica.
  • A weal (or wheal) is a superficial skin-coloured or pale skin swelling, usually surrounded by erythema (redness) that lasts anything from a few minutes to 24 hours. Usually very itchy, it may have a burning sensation.
  • Angioedema is deeper swelling within the skin or mucous membranes and can be skin-coloured or red. It resolves within 72 hours. Angioedema may be itchy or painful but is often asymptomatic.

What is chronic urticaria?

Chronic urticaria is urticaria in which there are daily or episodic weals or angioedema that is present for more than six weeks. Chronic urticaria may be spontaneous or inducible. Both types may co-exist.

Inducible or physical urticaria is classified according to the stimulus that provokes wealing.

Chronic urticaria

See more images of urticaria.

Who gets chronic urticaria?

Chronic spontaneous urticaria affects 0.5–2% of the population; in some series, two-thirds are women. Inducible urticaria is more common than spontaneous chronic urticaria. There are genetic and autoimmune associations.

What are the clinical features of chronic urticaria?

Urticaria is characterised by weals.

  • Weals can affect any site of the body and tend to be distributed widely. 
  • Weals can be a few millimetres or several centimetres in diameter.
  • They can be coloured white or red, with or without a red flare.
  • Each weal may last a few minutes or several hours and may change shape before resolving.
  • Weals may be round, or form rings, a map-like pattern or giant patches.

Angioedema is more often localised.

  • It commonly affects the face (especially presenting as swollen eyelids and lips), hands, feet and genitalia.
  • It may involve tongue, uvula, soft palate and larynx.

In chronic inducible urticaria, weals appear about 5 minutes after the stimulus and last a few minutes or up to one hour. Characteristically, weals are:

The weals are more persistent in chronic spontaneous urticaria, but each has gone or has altered in shape within 24 hours. They may occur at certain times of the day.

Urticaria severity assessment

Visual analogue scales can be used to record and compare the degree of itch.

The activity of chronic urticaria can be assessed using the UAS7 scoring system. The daily weal/itch scores are added up for seven days; the maximum score is 42.

Score 0

  • No weals for 24 hours
  • No itch

Score 1

  • < 20 weals during 24 hours
  • Mild itch

Score 2

  • 20–50 weals during 24 hours
  • Moderate itch

Score 3

  • > 50 weals during 24 hours
  • Intense itch

The emotional impact of urticaria and its effect on the quality of life should also be assessed. The Dermatology Life Quality Index (DLQI) and CU-Q2oL, a specific questionnaire for chronic urticaria, have been validated for chronic urticaria, where sleep disruption is a particular problem.

Systemic symptoms in chronic spontaneous urticaria

Some patients with chronic spontaneous urticaria report various associated systemic symptoms. These include:

  • A headache and fatigue
  • Joint pain or swelling
  • Wheezing, flushing and palpitations
  • Gastrointestinal symptoms. 

What causes chronic urticaria?

Weals are due to release of chemical mediators from tissue mast cells and circulating basophils. These chemical mediators include histamine, platelet-activating factor and cytokines. The mediators activate sensory nerves and cause dilation of blood vessels and leakage of fluid into surrounding tissues. Bradykinin release causes angioedema.

Several hypotheses have been proposed to explain urticaria. The immune, arachidonic acid and coagulation systems are involved, and genetic mutations are under investigation.

Chronic spontaneous urticaria is mainly idiopathic (cause unknown). An autoimmune cause is likely. About half of investigated patients carry functional IgG autoantibodies to immunoglobulin IgE or high-affinity receptor FcεRIα.

Chronic spontaneous urticaria has also been associated with:

Weals in chronic spontaneous urticaria may be aggravated by:

Inducible urticaria is a response to a physical stimulus.

Symptomatic dermographism

  • Stroking or scratching the skin
  • Tight clothing
  • Towel drying after a hot shower

Cold urticaria

  • Cold air on exposed skin
  • Cold water
  • Ice block
  • Cryotherapy

Cholinergic urticaria

  • Sweat induced by exercise
  • Sweat induced by emotional upset
  • Hot shower

Contact urticaria

  • Eliciting substance absorbed through the skin or mucous membrane
  • Allergens (IgE-mediated): white flour, cosmetics, textiles, latex, saliva, meat, fish, vegetables
  • Pseudoallergens or irritants: stinging nettle, hairy caterpillar, medicines

Delayed pressure urticaria

  • Pressure on affected skin several hours earlier
  • Carrying heavy bag
  • Pressure from a seat belt
  • Standing on a ladder rung
  • Sitting on a horse

Solar urticaria

  • Sun exposure to non-habituated body sites
  • Often does not affect the face, neck, or hands
  • May involve long-wavelength UV or visible light

Heat urticaria

  • Hot water bottle
  • Hot drink

Vibratory urticaria

  • Jackhammer

Aquagenic urticaria

  • Hot or cold water
  • Fresh, salt or chlorinated water

Recurrent angioedema without urticaria can be due to inherited or acquired complement C1 esterase deficiency, or to the longterm use of an anticholinesterase inhibitor drug.

How is chronic urticaria diagnosed?

Chronic urticaria is diagnosed in people with a long history of daily or episodic weals that last less than 24 hours, with or without angioedema. A family history should be elicited. A thorough physical examination should be undertaken to evaluate the cause. Inducible urticaria is often confirmed by inducing the reaction, such as scratching the skin in dermographism or applying an ice cube in suspected cold urticaria.

There are no routine diagnostic tests in chronic spontaneous urticaria apart from blood count and C-reactive protein (CBC, CRP), but investigations may be undertaken if an underlying disorder is suspected.

  • The autologous serum skin test is sometimes carried out in chronic spontaneous urticaria, but its value is uncertain. It is positive if an injection of the patient's serum under the skin causes a red weal.
  • Investigations for a systemic condition or autoinflammatory disease should be undertaken in urticaria patients with fever, joint or bone pain, and malaise.
  • Patients with angioedema without weals should be asked if they take ACE–inhibitor drugs and should be tested for complement C4; C1-INH levels, function and antibodies; and C1q.
  • Biopsy of urticaria can be non-specific and difficult to interpret. The pathology shows oedema in the dermis and dilated blood vessels, with a variable mixed inflammatory infiltrate. Vessel-wall damage indicates urticarial vasculitis

What is the treatment for chronic urticaria?

The main treatment for chronic urticaria in adults and children is with an oral second-generation H1antihistamine chosen from the list below. If the standard dose (eg, 10 mg for cetirizine) is not effective, the dose can be increased fourfold (eg, 40 mg cetirizine daily). There is not thought to be any benefit from adding a second antihistamine.

  • Cetirizine
  • Loratadine
  • Fexofenadine
  • Desloratadine
  • Levocetirizine
  • Rupatadine
  • Bilastine

Terfenadine and astemizole should not be used as they are cardiotoxic in combination with ketoconazole or erythromycin. They are no longer available in New Zealand.

Although systemic treatment is best avoided during pregnancy and breastfeeding, there have been no reports that second-generation antihistamines cause birth defects. If treatment is required, loratadine and cetirizine are currently preferred.

Conventional first-generation antihistamines such as promethazine or chlorpheniramine are no longer recommended for chronic urticaria:

  • They are short-lasting.
  • They have sedative and anticholinergic side effects.
  • They impair sleep, learning and performance.
  • They cause drowsiness in nursing infants if taken by the mother.
  • They interact with alcohol and other medications.
  • Lethal overdoses are reported.

Avoidance of trigger factors

In addition to antihistamines, the triggers for urticaria should be avoided where possible. For example:

  • Treat identified chronic infections such as H pylori.
  • Avoid aspirin, opiates and nonsteroidal anti-inflammatory drugs (paracetamol is generally safe).
  • Minimise dietary pseudoallergens for a trial period of at least three weeks.
  • Avoid known allergies that have been confirmed by positive specific IgE/skin prick tests if these have clinical relevance for urticaria.
  • Cool the affected area with a fan, cold flannel, ice pack or soothing moisturising lotion.

The physical triggers for inducible urticaria should be minimised; see examples below. However, symptoms often persist.

Some patients with inducible urticaria benefit from daily induction of symptoms to induce tolerance. Phototherapy may be of benefit for symptomatic dermographism.

Treatment of chronic refractory urticaria

Patients with chronic urticaria that has failed to respond to maximum-dose second-generation oral antihistamines taken for four weeks should be referred to a dermatologist, immunologist or medical allergy specialist.

There is good evidence to support treatment with omalizumab or ciclosporin, which each have a 65% response rate in antihistamine-resistant patients.

  • Omalizumab is a monoclonal antibody directed against IgE, with low toxicity. Omalizumab is not funded by PHARMAC in New Zealand for urticaria (2015).
  • Ciclosporin is a calcineurin inhibitor, with potentially serious side effects (it may increase blood pressure and reduce renal function).

Other treatments that are sometimes used off-label in chronic urticaria include:

Long-term systemic corticosteroids are not generally recommended, as high doses are often required to reduce symptoms of urticaria and they have inevitable adverse effects that can be serious. However, a study published in 2018 has reported effective clearance and the long-lasting response of chronic spontaneous urticaria to oral prednisolone.

What is the outlook for chronic urticaria?

Although chronic urticaria clears up in most cases, 15% continue to have wealing at least twice weekly after two years.

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