Urticaria
Urticaria - Summary
Urticaria is a superficial swelling of the skin (epidermis and mucous membranes) that results in a red, raised, itchy rash. It can be localised or generalised.
Angio-oedema is a deeper form of urticaria with swelling in the dermis and submucosal or subcutaneous tissues.
Urticaria can be classified according to timescale:
Acute urticaria is normally a self-limiting, one-off episode. Symptoms develop suddenly and resolve quickly (most cases last 24–48 hours).
Chronic urticaria may remit and relapse (e.g. triggered by illness, stress, or drugs). Symptoms last for more than 6 weeks (recurrence of acute symptoms or persistent symptoms) and may last for months or years.
Vasculitic urticaria (inflammation of blood vessels due to an autoimmune reaction) should be suspected if urticaria is painful and persistent:
Referral to a dermatologist is indicated for confirmation of diagnosis.
Treatment as for other urticaria should be commenced while awaiting referral.
To manage urticaria, the underlying cause should be identified an managed, where possible.
Acute urticaria may be cause by allergy to certain foods (e.g. eggs and shellfish), insect bites and stings, certain drug (e.g. aspirin and angiotensin-converting enzyme inhibitors), a viral infection, skin contact with irritants (such as chemicals, latex and and cosmetics), and physical stimuli (e.g. change in body temperature and firm rubbing of the skin).
The cause of most cases of chronic urticaria cannot be identified. However, aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate proven chronic urticaria. Chronic urticaria may remit and relapse (e.g. triggered by illness, stress, or drugs) and may disappear in months or last for years.
People with severe urticaria should be given a short course of oral corticosteroids (e.g. prednisolone 40 mg daily for 3–5 days) in addition to a non-sedating oral antihistamine (cetirizine, fexofenadine, or loratadine).
If rebound symptoms occur after a short course of oral corticosteroids, specialist advice should be sought. Oral corticosteroid course should not be repeated.
People with acute, severe urticaria which is thought to be due to a food or latex allergy, should be treated as above and referred to a dermatologist or immunologist.
People with less severe urticaria requiring treatment should be offered a non-sedating antihistamine (cetirizine, fexofenadine, or loratadine) at the standard licensed dose either as required until symptoms settle, or regularly for up to 6 weeks.
If response to treatment is inadequate, the following options should be considered:
In adults, if there are no contra-indications, the standard licensed dose of the first choice antihistamine should be doubled (off-label use).
An alternative non-sedating antihistamine should be tried.
An additional sedative antihistamine (such as chlorphenamine) should be prescribed at night.
A topical antipruritic agent (such as calamine lotion) should be prescribed to relieve itch.
Referral to a dermatologist or immunologist is advised if:
Symptoms are not well controlled on treatment, or
Antihistamines are required continuously for more than 6 weeks to control symptoms.
Have I got the right topic?
This CKS topic covers the management of urticaria.
This CKS topic does not cover the management of angio-oedema, anaphylaxis, or acute drug reactions.
There are separate CKS topics on Angio-oedema and anaphylaxis, Asthma, Dermatitis - contact, Eczema - atopic, and Insect bites and stings.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
November 2011 — revised. A literature search was conducted in October 2011 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. The topic has been restructured to improve clarity and navigation. Recommendations on managing people who have had an inadequate response to the standard licensed dose of antihistamine have been changed to include the option to double the standard licensed dose of the first choice antihistamine, before considering referral to secondary care for further management. Issued in January 2012.
Previous changes
March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.
April 2008 — minor update. Information included from the British Society for Allergy and Clinical Immunology (BSACI) guidelines for the management of chronic urticaria and angio-oedema (2007). Issued in May 2008.
January 2008 — minor update. Updated in line with guidelines for the evaluation and management of urticaria in adults and children from the British Association of Dermatologists (2007). Issued in February 2008.
January to April 2007 — this is a new CKS topic, replacing the CKS guidance on Urticaria and angio-oedema. The evidence base has been reviewed in detail, and recommendations are more clearly justified and more transparently linked to the supporting evidence.
There are no major changes to the recommendations.
January 2006 — minor update. Black triangle removed from desloratadine. Issued in February 2006.
October 2005 — minor technical update. Issued in November 2005.
July 2005 — new CKS patient information leaflet attached. Issued in July 2005.
January 2004 — written. Validated in March 2004 and issued in June 2004.
Update
New evidence
Evidence-based guidelines
No new evidence-based guidelines since 1 October 2011.
HTAs (Health Technology Assessments)
No new HTAs since 1 October 2011.
Economic appraisals
No new economic appraisals relevant to England since 1 October 2011.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of this topic:
Ben-Shoshan, M., Blinderman, I., and Raz, A. (2013) Psychosocial factors and chronic spontaneous urticaria: a systematic review. Allergy 68(2), 131-141. [Abstract]
Caffarelli, C., Cuomo, B., Cardinale, F., et al. (2012) Aetiological factors associated with chronic urticaria in children: a systematic review. Acta Dermato-Venereologica epub ahead of print. [Abstract]
Fedorowicz, Z., van Zuuren, E.J., and Hu, N. (2012) Histamine H2-receptor antagonists for urticaria (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Primary evidence
Randomized controlled trials published since the last revision of this topic:
Maurer, M., Rosen, K., Hsieh, H.J., et al. (2013) Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. New England Journal of Medicine epub ahead of print. [Abstract]
New policies
No new national policies or guidelines since 1 October 2011.
New safety alerts
No new safety alerts since 1 October 2011.
Changes in product availability
No changes in product availability since 1 October 2011.
Goals and outcome measures
Goals
To diagnose the type of urticaria
To determine the cause of urticaria where possible
To relieve the symptoms of urticaria
Background information
Definition
What is it?
Urticaria is a superficial swelling of the skin (epidermis and mucous membranes) that results in a red, raised, itchy rash. It can be localised or generalised.
The mechanism involves local vasodilation of capillaries, and activation of mast cells which release histamine, resulting in plasma leaking from small blood vessels into the skin.
Urticaria is also known as hives, nettle rash, or weals.
Angio-oedema is a deeper form of urticaria with swelling in the dermis and submucosal or subcutaneous tissues. For more information, see the CKS topic on Angio-oedema and anaphylaxis.
Classification of urticaria
How is urticaria classified?
There is no consensus on the classification of urticaria, and categories often overlap. Urticaria can be classified into:
Physical urticaria — follows certain physical stimuli such as exposure to cold or heat.
Contact urticaria — follows skin contact with certain biological or chemical agents such as latex and cosmetics.
Vasculitic urticaria — this is a histopathological diagnosis that is made when skin biopsy findings show inflammation of blood vessels due to an autoimmune reaction. Other features may include joint and kidney involvement. Weals may persist for days rather than hours [Grattan et al, 2007].
Ordinary urticaria — this is the commonest type and diagnosis is made after the exclusion of a physical, contact, or vasculitic cause.
These different types of urticaria can also be classified according to timescale:
Acute urticaria — symptoms develop suddenly and resolve quickly (most cases last 24–48 hours).
Chronic urticaria — symptoms for more than 6 weeks that may be acute and recurrent or persistent.
Previously, chronic urticaria without a cause was known as 'chronic idiopathic urticaria', but the preferred term is now 'chronic urticaria', as a third of cases are thought to have an autoimmune cause.
People may have two or more types of urticaria occurring simultaneously.
Cause
What causes it?
Urticaria can result directly from a type 1 hypersensitivity reaction (e.g. caused by food or bee/wasp sting), an immunological response to a febrile illness or infection, or an adverse drug reaction (which may vary in the mechanism of action).
There is an overlap between the causes of acute and chronic urticaria.
The causative factors in children and adults are the same (except that in children under 6 months there is a higher incidence of allergy to cow's milk) [Kobza-Black and Champion, 1998].
In people with chronic urticaria there may be trigger factors which are not the main cause, but seem to exacerbate the urticarial rash: common trigger factors include medication, stress, exercise, and alcohol [Kozel et al, 2003].
Acute urticaria
In acute urticaria, the literature suggests that a cause may be identified in around 50% of cases. In practice, however, the cause is rarely obvious at the first presentation. Consider:
Allergy to:
Foods such as nuts, strawberries, eggs, additives, spices, and shellfish.
Insect bites and stings — for more information, see the CKS topic on Insect bites and stings.
Drugs such as penicillins, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), vaccinations, and angiotensin-converting enzyme (ACE) inhibitors. A systematic review showed that skin reactions related to drugs are rare (less than 5%), and that NSAIDs cause 5–14% of cases of drug-induced urticaria [Bigby, 2001; Kozel and Sabroe, 2005].
A viral infection, such as an upper respiratory tract infection.
Skin contact with chemicals, latex, cosmetics, plants, ointments, or nettle stings — these cause a localised area of urticaria.
Physical stimuli, including:
Firm rubbing of skin resulting in dermatographism. This is the most common type of physical urticaria affecting 5% of the population.
Pressure applied to the skin resulting in delayed-pressure urticaria, characterized by tender weals (lasting 24–72 hours) that develop between 30 minutes and 12 hours after pressure to the skin.
Increases in core body temperature related to exercise, or a warm environment.
Cold exposure resulting in cold urticaria.
[Kobza-Black and Champion, 1998; Wanderer et al, 2000; Kozel and Sabroe, 2005]
Chronic (recurrent or persistent) urticaria
The cause of most cases of chronic urticaria (62%) cannot be identified [Grattan et al, 2001; Kozel et al, 2003].
An autoimmune reaction is thought to be associated with a high number of chronic urticaria cases without an identifiable cause [Leznoff and Sussman, 1989].
Allergies to food and drugs are uncommon causes of chronic urticaria [Wanderer et al, 2000]. However, aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate proven chronic urticaria.
Chronic infections and infestations such as intestinal parasites, chronic sinusitis, cholecystitis, dental abscesses, Helicobacter pylori infection, and viral hepatitis have all been linked to chronic urticaria [Grattan et al, 2001; Zuberbier, 2003; Powell et al, 2007].
Internal diseases (e.g. connective tissue disorders) are a rare (1.6%) cause of chronic urticaria. There appears to be a link with the presence of thyroid auto-antibodies and chronic urticaria [Leznoff and Sussman, 1989].
Malignancy has been linked with urticaria and may suggest a relapse of the malignancy. Both solid tumours and lymphomas have been associated. A cohort study suggests a possible link with some haematological malignancies but further research is needed [Lindelof et al, 1990; Soderberg et al, 2004].
Physical stimuli, can cause recurrent urticaria. This includes:
Firm rubbing of skin that can result in dermatographism. This is the most common type of physical urticaria affecting 5% of the population.
Pressure applied to the skin that can result in delayed-pressure urticaria, characterized by tender weals (lasting 24–72 hours) that develop between 30 minutes and 12 hours after pressure to the skin.
Increases in core body temperature related to exercise, or a warm environment.
Cold exposure that can result in cold urticaria.
The role of Helicobacter pylori infection in chronic urticaria is unclear and most prospective studies have found no relationship. A systematic review of 10 studies showed that in people with chronic urticaria thought to be caused by H. pylori infection, eradication therapy improved the urticarial rash in approximately a third of cases [Federman et al, 2003]. Nevertheless, the conflicting evidence means the role of H. pylori infection in chronic urticaria remains uncertain.
Prevalence
How common is it?
Acute urticaria is much more common than chronic urticaria. Acute urticaria affects 1 in 6 people at some point in their lives, compared with 1 in 1000 people for chronic urticaria [Humphreys and Hunter, 1998].
Acute urticaria is more common in children, in women (aged 30–60 years), and in people with atopy [Zuberbier, 2003; Kozel and Sabroe, 2005].
The incidence of urticaria in children is estimated to be around 8 per 1000 person-years [Mohammedamin et al, 2006].
Prevalence rates for chronic urticaria vary from 1–5 in every 1000 people [Kobza-Black and Champion, 1998; Kozel et al, 1998].
Angio-oedema can occur concurrently in some cases of acute urticaria, and in up to 50% of cases of chronic urticaria. For more information, see the CKS topic on Angio-oedema and anaphylaxis.
Hospital admissions for urticaria, angio-oedema, and anaphylaxis have increased over the last 10 years, reflecting an overall increase in the incidence of these conditions [Gupta et al, 2003].
Complications and prognosis
Complications
In chronic urticaria:
Daily living can be severely affected by distress, poor sleep (caused by itching), and social isolation (embarrassment) [Greaves and Sabroe, 1998]. One study showed the detrimental effect on quality of life to be comparable to people with coronary heart disease [O'Donnell et al, 1997].
Depression may be present in up to 14% of people with chronic urticaria [Yosipovitch et al, 2002].
Anaphylaxis is a rare complication sometimes seen with acute urticaria and physical urticaria. For more information, see the CKS topic on Angio-oedema and anaphylaxis.
Angio-oedema can occur in up to 50% of people with chronic urticaria, and may lead to airway obstruction.
Prognosis
Acute urticaria is normally a self-limiting, one-off episode, with weals lasting less than 24–48 hours.
Chronic urticaria may remit and relapse (for example triggered by illness, stress, or drugs) and may disappear in months or last for years [Wanderer et al, 2000]:
Fifty percent of cases resolve in 3–5 years [Greaves and Sabroe, 1998; Grattan et al, 2001].
One in five cases persist (relapsing and remitting) for more than 10 years [Grattan et al, 2001].
People with physical urticaria, and those with severe episodes, tend to have a longer duration of urticaria [Kozel and Sabroe, 2005].
Diagnosis
Diagnosis of urticaria
Diagnosis
How do I know my patient has urticaria?
Identify the characteristic features of urticaria:
Weals; small raised areas (1–2 cm) of the skin that develop suddenly.
Weals can be red or white, and are itchy and surrounded by an area of redness (flare).
Usually, weals last less than 24 hours (physical urticaria weals may only last 1–2 hours) and fade before the surrounding flare, making the skin look blotchy.
The rash may disappear completely, but may reappear in hours or days.
Weals may coalesce with others, making the rash look extensive.
If the weals remain for longer than 24 hours and are painful and dark (leaving a residual pigmented lesion such as petechial haemorrhage, purpura, or bruising), consider a diagnosis of vasculitic urticaria, especially if the person also has systemic symptoms such as fever, malaise, and arthralgia.
For pictures, see www.dermnetnz.org/reactions/urticaria.html.
Try to identify the underlying cause for urticaria.
Investigations are not usually helpful. However, when a cause cannot be identified from the history, consider the following investigations to help identify the cause:
Full blood count (FBC)
Erythrocyte sedimentation rate (ESR)
Thyroid function tests (TFTs)
Liver function tests (LFTs)
Helicobacter pylori screening (if gastrointestinal symptoms are present).
Exclude other causes for the rash.
Basis for recommendation
Basis for recommendation
The characteristics of an urticarial rash
The characteristics of an urticarial rash are taken from guidelines from the British Association of Dermatologists and the British Society for Allergy and Clinical Immunology [Grattan et al, 2001; Powell et al, 2007].
Identifying the underlying cause of urticaria
These recommendations are pragmatic advice based on expert opinion from the medical literature [Grattan et al, 2001; Kozel and Sabroe, 2005].
Investigations are not usually helpful for identifying the underlying cause of chronic urticaria. However, there is some evidence to suggest that basic tests in combination with a good history, are just as effective at identifying the cause as an extensive laboratory screen [Leznoff and Sussman, 1989; Kobza-Black and Champion, 1998; Kozel et al, 1998; Wanderer et al, 2000].
Differential diagnosis
What else might it be?
Erythema multiforme minor — the lesions are usually fixed and have a 'target' appearance (often people have a prodromal illness).
Urticaria pigmentosa (a form of mastocytosis) — the skin becomes inflamed and red when stroked (Derier's sign) and has hyperpigmented macules and papules.
Pemphigoid (bullous) and dermatitis herpetiformis — the early lesions are pruritic and have a similar appearance to an urticarial rash.
Chronic pruritus — no weals are present (but can be mistaken if urticarial symptoms occur at night and are not seen).
Polymorphic eruption of pregnancy — urticarial itchy papules mainly occur in the third trimester of pregnancy, often starting on abdominal stretch marks.
Basis for recommendation
Basis for recommendation
This information is based on review articles in the medical literature [Wanderer et al, 2000; Fewell, 2003; Pierson, 2006].
Management
Management
Scenario: Managing urticaria: covers the management of acute and chronic (recurrent or persistent) urticaria.
Scenario: Managing urticaria
Scenario: Managing urticaria
Managing urticaria
How should I manage someone with urticaria?
For people with urticaria and suspected anaphylaxis (features of upper or lower airway obstruction or shock) — see the CKS topic on Angio-oedema and anaphylaxis.
For people with urticaria and angio-oedema — see the CKS topic on Angio-oedema and anaphylaxis.
For people with urticaria that is painful and persistent, suspect vasculitic urticaria and refer to a dermatologist for confirmation of the diagnosis. Treat as for other urticaria while awaiting referral.
Where possible, identify and manage the underlying cause of urticaria.
When a cause cannot be identified for recurrent or persistent urticaria from the history, consider the following investigations; full blood count (FBC), erythrocyte sedimentation rate (ESR), thyroid function tests (TFTs), liver function tests (LFTs), and Helicobacter pylori screening (if gastrointestinal symptoms are present).
Where possible, identify and avoid trigger factors for recurrent or persistent urticaria including:
Stress.
Alcohol, caffeine, and spices.
Overheating. Advise keeping the bedroom cool whilst sleeping and avoid hot baths.
Medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and angiotensin-converting enzyme (ACE) inhibitors.
For people with severe urticaria:
Give a short course of oral corticosteroids (e.g. prednisolone 40 mg daily for 3–5 days) in addition to a non-sedating oral antihistamine (cetirizine, fexofenadine, or loratadine).
If rebound symptoms occur after a short course of oral corticosteroids, seek specialist advice. Do not repeat the course of oral corticosteroids.
For people with acute severe urticaria which is thought to be due to a food or latex allergy, treat as above and refer to a dermatologist or immunologist.
For people with less severe urticaria requiring treatment:
Offer a non-sedating antihistamine (cetirizine, fexofenadine, or loratadine) at the standard licensed dose (see Prescriptions). Based on an assessment of the underlying cause, and the duration of symptoms before treatment, antihistamines may be prescribed either:
As required until symptoms settle, if it is thought that symptoms are likely to be short lived and frequent recurrence is unlikely or
Regularly for up to 6 weeks, if it is thought that symptoms are likely to be persistent or recurrent.
If there is an inadequate response to treatment, consider the following options:
In adults, double the standard licensed dose of the first choice antihistamine (see Prescriptions - double dose). Although off-label, this approach is widely recommended and used by experts. Do not use higher doses in people known to have long QT syndrome, or impaired hepatic or renal function.
Switch to an alternative non-sedating antihistamine.
Prescribe an additional sedative antihistamine (such as chlorphenamine) at night, if itch is interfering with sleep (see Prescriptions - itch at night).
Prescribe a topical antipruritic treatment (such as calamine lotion or topical menthol 1% in aqueous cream) to relieve itch.
For people with mild urticaria with an identifiable and avoidable cause, advise that urticaria is likely to be self-limiting without treatment.
Refer to a dermatologist or immunologist if symptoms are not well controlled on treatment, or antihistamines are required continuously for more than 6 weeks to control symptoms.
Basis for recommendation
Basis for recommendation
Identifying people with urticaria and anaphylaxis or angio-oedema
These recommendations are based on what CKS considers good practice because people with anaphylaxis or angio-oedema require specific management to reduce the risk of harm associated with these conditions.
Identifying the underlying cause of urticaria
These recommendations are pragmatic advice based on expert opinion from the medical literature [Grattan et al, 2001; Kozel and Sabroe, 2005].
Investigations are not usually helpful for identifying the underlying cause of chronic urticaria. However, there is some evidence to suggest that basic tests in combination with a good history, are just as effective at identifying the cause as an extensive laboratory screen [Leznoff and Sussman, 1989; Kobza-Black and Champion, 1998; Kozel et al, 1998; Wanderer et al, 2000].
Trigger factors for chronic urticaria
Stress is an important precipitant of urticaria. In one small non-randomized study, relaxation therapy and hypnosis improved self-reported symptoms, but not the number of observed weals [Shertzer and Lookingbill, 1987].
Alcohol, caffeine, spices, and hot water all cause vasodilation and may precipitate urticaria [Moses, 2003].
Overheating commonly exacerbates itch [Moses, 2003].
Medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and angiotensin-converting enzyme (ACE) inhibitors are all known triggers of urticaria [BAD, 2006].
Oral corticosteroids:
Experts recommend that a short course of high-dose oral corticosteroids should be reserved for severe acute urticaria [Grattan et al, 2001].
Corticosteroids are potent immunosuppressants and can therefore suppress the symptoms of urticaria. However, CKS found only one non-randomized, open study (prednisolone 50 mg daily for 3 days) that examined their use [Zuberbier et al, 1996]. This study found that a 3–day course of oral prednisolone followed by loratadine, shortened the duration of acute urticaria compared with loratadine treatment alone.
In view of the lack of prospective studies of oral corticosteroids for urticaria, CKS recommends a 3–5 day course of oral prednisolone at the same dosage as used for an acute exacerbation of asthma [SIGN and BTS, 2011].
Oral antihistamines:
Antihistamines (H1-receptor blockers) are the only drugs licensed for use in urticaria.
Although the efficacy of antihistamines has only been demonstrated for chronic urticaria, there is a consensus that they are also effective for acute urticaria [Grattan et al, 2001; Zuberbier et al, 2006]:
Histamine is one of the primary mediators of urticaria.
In people with chronic urticaria, randomized controlled trials of non-sedating antihistamines have demonstrated improvements in symptoms of itch, weal formation, frequency of exacerbations, and quality of life [Belaich et al, 1990; Breneman et al, 1995; Kaplan et al, 2005; Zuberbier et al, 2006].
Non-sedating antihistamines should be used initially to control daytime symptoms.
Sedating antihistamines are not recommended for daytime use because the drowsiness they cause can affect a person's ability to drive or perform other skilled tasks [Grattan et al, 2001; Zuberbier et al, 2006]. However, the addition of a sedating antihistamine at night to a non-sedating (daytime) antihistamine may help people who are unable to sleep due to itching, and is considered to be safe [Grattan et al, 2001].
Desloratadine (a metabolite of loratadine) and levocetirizine (an isomer of cetirizine) are more recently marketed products, but there is little evidence to confirm whether they confer any additional benefit over the more established non-sedating antihistamines [MeReC, 2004].
Mizolastine has been implicated in causing an abnormal prolongation of the QT interval and is therefore not recommended as a first-line treatment.
Acrivastine is not recommended as it has a short half-life and needs to be taken three times a day.
Treatment options if there is an inadequate response to treatment with a standard licensed dose of the first choice antihistamine:
These recommendations are based on expert opinion in separate guidelines from the British Association of Dermatologists [Grattan et al, 2001] and the British Society for Allergy and Clinical Immunology [Powell et al, 2007].
Doubling the standard licensed dose of a non-sedating antihistamine is widely recommended by experts because, based on expert opinion, higher doses often control symptoms when standard doses are inadequate.
Higher doses of non-sedating antihistamines are generally well tolerated and serious adverse effects are rare [Micromedex, 2011].
Higher doses are not recommended in people known to have long QT syndrome because there have been case reports of prolongations of the QT interval with fexofenadine and loratadine.
Higher doses of antihistamines are not recommended for people with impaired renal or hepatic function because there is a theoretical risk of toxicity due to impaired drug clearance.
Higher doses of non-sedating antihistamines are not recommended in children because their safety has not been assessed in this age group.
Based on expert opinion individuals vary in their response and tolerance to antihistamines. Therefore switching antihistamine may result in improved control if there is an inadequate response to the initial antihistamine [Grattan et al, 2001].
Calamine lotion generally soothes itch [Grattan et al, 2007], although the residue (when dried) can exacerbate itch in some people [BNF 62, 2011].
Menthol 1% in aqueous cream is cooling and is reported to soothe itch [Greaves and Sabroe, 1998; Grattan et al, 2001]. One small study in 15 healthy volunteers found that a menthol 1% (in ethanol) solution successfully relieved histamine-induced itching [Bromm et al, 1995].
Drugs not recommended:
CKS does not recommend repeat courses of oral corticosteroids for rebound symptoms because of concerns that this will lead to their long term use, and because of the risk of potential adverse effects.
In one small study of highly-selected people with chronic urticaria, the application of a potent topical corticosteroid (clobetasol propionate) followed by plastic occlusion resulted in only a short-term improvement of symptoms [Ellingsen and Thestrup-Pedersen, 1996].
Topical steroids do reduce weal formation, but can lead to adverse effects due to the need for long-term use over a large surface area [Kozel and Sabroe, 2005].
Topical antihistamines have a risk of sensitization and can result in contact dermatitis [Kozel and Sabroe, 2005; BNF 62, 2011].
When to refer:
These recommendations are based on what CKS considers good clinical practice.
Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).
Antihistamines for urticaria
Which antihistamine should I use to treat urticaria?
Cetirizine, fexofenadine, or loratadine (once-daily non-sedating antihistamines) are recommended for the treatment of urticaria.
If the itch is interfering with sleep, consider prescribing an additional sedating antihistamine chlorphenamine or hydroxyzine are recommended.
Basis for recommendation
Antihistamines (H1-receptor blockers) are the only drugs licensed for use in urticaria.
Although the efficacy of antihistamines has only been demonstrated for chronic urticaria, there is a consensus that they are also effective for acute urticaria [Grattan et al, 2001; Zuberbier et al, 2006]:
Histamine is one of the primary mediators of urticaria.
In people with chronic urticaria, randomized controlled trials of non-sedating antihistamines have demonstrated improvements in symptoms of itch, weal formation, frequency of exacerbations, and quality of life [Belaich et al, 1990; Breneman et al, 1995; Kaplan et al, 2005; Zuberbier et al, 2006].
Non-sedating antihistamines should be used initially to control daytime symptoms.
Sedating antihistamines are not recommended for daytime use because the drowsiness they cause can affect a person's ability to drive or perform other skilled tasks [Grattan et al, 2001; Zuberbier et al, 2006]. However, the addition of a sedating antihistamine at night to a non-sedating (daytime) antihistamine may help people who are unable to sleep due to itching, and is considered to be safe [Grattan et al, 2001].
Desloratadine (a metabolite of loratadine) and levocetirizine (an isomer of cetirizine) are more recently marketed products, but there is little evidence to confirm whether they confer any additional benefit over the more established non-sedating antihistamines [MeReC, 2004].
Mizolastine has been implicated in causing an abnormal prolongation of the QT interval and is therefore not recommended as a first-line treatment.
Acrivastine is not recommended as it has a short half-life and needs to be taken three times a day.
Antihistamines in pregnancy/breastfeeding
Which antihistamine can I use during pregnancy and breastfeeding?
Where possible, oral antihistamines should be avoided during pregnancy, especially during the first trimester.
If an oral antihistamine is required to control urticaria or pruritus during pregnancy, chlorphenamine is the antihistamine of choice.
Loratadine and cetirizine are recommended for use during breastfeeding.
Basis for recommendation
Chlorphenamine is not licensed during pregnancy, but there have been several thousand known exposures with no evidence of an increased risk of fetal toxicity.
The safety of other oral antihistamines in pregnancy has not been established. The available evidence does not suggest that other antihistamines (sedating or non-sedating) are associated with a high risk of teratogenic effects, but there are not enough documented exposures to be confident that there is no risk or only a very low risk of fetal malformations.
Loratadine and cetirizine are preferred during breastfeeding as only small amounts are secreted in breast milk and both drugs are non-sedating.
Adverse effects of antihistamines
What are the adverse effects of antihistamines?
Sedating antihistamines cause sedation in 10–50% of people, which can persist into the next day [DTB, 2002].
Most non-sedating antihistamines have the potential to cause sedation, especially at higher doses. Advise people taking non-sedating antihistamines that they may cause sedation, and that the sedative effects are enhanced when combined with alcohol.
Oral corticosteroids
Oral corticosteroids
Adverse effects are uncommon with occasional, short courses of oral corticosteroids used less than 3 or 4 times a year.
If frequent courses of oral corticosteroids are needed, the following monitoring is recommended:
People taking frequent courses of oral corticosteroids require specialist supervision.
Blood pressure: monitor regularly and treat if necessary.
Diabetes mellitus: screen regularly and treat if necessary.
Osteoporosis: see the CKS topic on Osteoporosis - preventing steroid-induced for details about when to prescribe long-acting bisphosphonate therapy.
Growth suppression: record height of children regularly and accurately.
Cataracts: screen children periodically.
Children who are on frequent courses of oral corticosteroids should have regular checks for signs of adrenal suppression, with referral to a paediatrician who can arrange synacthen testing where appropriate.
For more information on oral corticosteroids, see the CKS topic on Corticosteroids - oral.
Basis for recommendation
These recommendations are based on expert opinion on managing adverse effects of oral corticosteroids in people being treated for asthma [SIGN and BTS, 2011].
Evidence
Evidence
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of urticaria.
Search dates
2007 - October 2011
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
exp Urticaria/
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSh subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
University of Michigan Medical School
Michigan Quality Improvement Consortium
Royal Australian College of General Practitioners
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Driver and Vehicle Licensing Agency
NHS Plus (occupational health practice)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
Sources of medicines information
The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.
British National Formulary (BNF)
electronic Medicines Compendium (eMC)
European Medicines Agency (EMEA)
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