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Urticaria is one of the most difficult of dermatological problems presenting to the GP ­ Dr Adrian Morris, an allergy specialist,

advises what GPs can do when faced with this problem

Urticaria predominantly affects adult females and up to 20 per cent of the general population sometime during their lifetime. It presents as a diffusely raised, itchy wheal and flare reaction that migrates over the skin surface.

All forms of urticaria may occur in association with deeper skin swelling or angioedema and, equally, angioedema may occur in isolation with no apparent urticaria. When this hereditary angioedema (HAE) is seen, possible deficiency of the C1-esterase inhibitor enzyme should be considered.

Classifying urticaria

Ordinary urticaria

We classify ordinary urticaria as acute when the rash duration appears for less than six weeks, and chronic when it persists for more than six weeks.

The actual cause of acute ordinary urticaria is relatively easy to identify, as the trigger seems immediately apparent and the reaction is reproducible. Examples include: shellfish, penicillin, insect or latex allergy, and the rash associated with a streptococcal or viral hepatitis infection.

This is the only form of urticaria where allergy testing by means of skin-prick or RAST blood tests may be helpful.

Chronic ordinary urticaria

In chronic ordinary urticaria it is far more difficult to identify a specific trigger, and in more than 50 per cent of cases no cause is ever identified: we then label this chronic idiopathic urticaria (CIU). A fraction of chronic ordinary urticaria cases may be triggered by systemic illnesses such as autoimmune thyroid disease, collagen vascular disease, chronic parasitic infections, chronic sinusitis, Helicobacter pylori and chronic dental infections.

One-third of individuals with chronic urticaria display autoantibodies directed against IgE or the mast cell IgE receptor. These autoantibodies trigger mast cell degranulation and histamine release, and make this form of chronic urticaria extremely difficult to control.

Sustained daily intake of food additives (benzoates, sulphites and azo dyes) can lead to chronic urticaria, but true food allergy is unlikely to cause chronic ordinary urticaria, and exhaustive food allergy testing is not helpful.

Physical urticaria

Physical urticaria is due to an external physical trigger and has a familial tendency. In its most benign form it commonly presents as linear dermatographism after firmly stroking the skin. Other reproducible physical stimuli that act as triggers include heat and exercise (cholinergic urticaria), cold, sun exposure (solar urticaria), vibration, deep pressure (delayed pressure urticaria) and water exposure (aquagenic urticaria ­ extremely rare).

The lesions occur within minutes of the stimulus (except delayed pressure) and disappear rapidly within an hour or two.

Just to complicate matters, physical urticaria often occurs in conjunction with chronic ordinary urticaria.

Contact urticaria

In contact urticaria, an immediate IgE-mediated allergy occurs after skin contact with fresh food, pet saliva or latex and settles within a few hours. Children frequently develop discretely grouped itchy papular urticaria following insect bites.

Urticarial vasculitis

This is a rare condition that presents with painful non-migratory lesions that persist for some 24 hours, often with fever, purpura and arthralgia. Skin biopsy and specialist referral are required. It is associated with underlying autoimmune connective tissue diseases and

serum sickness, systemic lupus erythematosus and Sjögren's syndrome should be considered.

Urticaria pigmentosa

This urticaria may occur in children and is a diffuse, dark freckle-like rash that urticates on rubbing the skin and is

due to excess mast cells in the skin (cutaneous mastocytosis).

Exercise-induced urticaria

This may be food allergy related. Hypersensitivity to wheat, celery or shellfish as well as aspirin or alcohol ingestion may manifest with urticaria and even anaphylaxis occurring after exercise (if that food is eaten within four hours before exercise).

If a specific urticaria trigger can be identified, then avoidance is the most desirable action, but very often no underlying cause is ever identified. The main thrust of management should then be to provide support and alleviate symptoms while the urticaria slowly 'burns' itself out and resolves, only to recur again ­ a process that may take many years.

Pharmaceutical management of urticaria

Antihistamines

The second-generation non-sedating antihistamines are the mainstay of current urticaria treatment and doubling the normal recommended dose is often necessary to obtain symptom control (for example, daily cetirizine 10-20mg, loratadine 10-20mg or fexofenadine 180-360mg). Once the urticaria is controlled, the dose can be slowly reduced.

The addition of sedating antihistamines such as chlorpheniramine or hydroxyzine may help if optimal control is not achieved and will

reduce sleep disturbance from itching.

Tolerance to antihistamines can develop and it may help to periodically rotate through different ones.

Ketotifen can be effective in children with its antihistamine and mast-cell stabilising properties.

If it is necessary to use antihistamines in pregnancy, chlorpheniramine, though sedating, is safest. Gastric histamine H2-blockers such as ranitidine 150mg bd offer additional antihistamine effects if used together with conventional antihistamine medication and can be used for long periods of time.

Oral steroids

Although prednisolone (>30mg) is most effective in the short-term for rapid symptom relief, long-term use will lead to undesirable side-effects and

sometimes problematic rebound

urticaria on withdrawal. Occasionally long-term alternate-day regimens may

be necessary to control chronic recalcitrant urticaria.

Steroid-sparing options

The tricyclic antidepressant doxepin

(10-50mg daily) has histamine-blocking properties and is useful as an adjunct, especially if there is co-existent depression with the urticaria. Doxepin cream (Xepin) used topically also has antipruritic properties.

The leukotriene receptor antagonist montelukast (10mg at night) and the

5-lipoxygenase inhibitor zileuton (600mg every six-12 hours) have been used with some success, and are most effective when used in combination with non-sedating antihistamines or doxepin.

Montelukast is particularly useful in aspirin-sensitive individuals (who are prone to urticaria, nasal polyps and asthma), but may cause gastrointestinal disturbances.

Oral sodium cromoglycate may dampen food-related exercise-induced urticaria, while those with exercise-induced anaphylaxis or severe angioedema should carry an EpiPen (adrenaline auto-injector) and avoid vigorous exercise.

Stress (public speaking, examinations, exercise and arguments) may trigger cholinergic urticaria, and propranolol will reduce the symptoms.

Other drugs such as colchicine, warfarin, nifedipine, danazol, dapsone and sulfasalazine have been tried over the years with varying success in chronic urticaria.

Auto-immune thyroid disease with associated urticaria may respond to oral thyroxine supplementation, even if biochemically euthyroid.

Immune suppressive therapy such as ciclosporin or methotrexate is effective, but ciclosporin can cause serious side-effects such as renal impairment and uncontrolled hypertension.

Additional expensive third-line treatments

include intravenous immunoglobulin administration and serum plasmapheresis at a specialist centre.

Iatrogenic triggers

Aspirin-containing flu remedies, and other non-steroidal anti-inflammatory medication such as ibuprofen and diclofenac, as well as codeine and opiate-containing analgesics, should be avoided. If essential, aspirin-sensitive individuals seem to tolerate the newer cyclo-oxygenase-2 selective inhibitors or cox-2 NSAID medications such as rofecoxib and meloxicam.

Paracetamol is the only analgesic and flu treatment that can safely be used in urticaria.

ACE inhibitor antihypertensives are a common trigger for angioedema and urticaria, especially lisinopril, ramipril and enalapril.

ACE inhibitors may suddenly trigger angioedema after prolonged periods of asymptomatic use.

The angiotensin-II receptor antagonists (ACE2) such as valsartan and candesartan are less likely to induce angioedema and urticaria.

Oestrogen replacement therapy (HRT) may trigger angioedema and urticaria and should be used with caution in urticaria.

Advice for patients

The following should be recommended:

·Resist the temptation to rub the itchy and painful lesions

·Try to keep cool at all times and wear loose-fitting clothing

·Avoid all alcoholic drinks, many of which non-specifically trigger urticaria

·Try to reduce stress with relaxation exercises and yoga

·Minor viral illnesses, menstrual periods and oestrogen may aggravate urticaria

·Keep the skin well moisturised with bland emollients

·Avoid non-specific physical triggers such as excess heat, cold, exercise and rapid temperature changes

·All forms of salicylate including toothpaste, wintergreen muscle rubs and peppermints should also be excluded

·There seems to be scant evidence to show that homoeopathy benefits the management of urticaria, although the poor response to conventional treatment and the chronic, disabling nature of urticaria causes dissatisfaction and fuels exploration of alternative medical practices

·Apply calamine, aqueous cream with menthol 1 per cent or 10 per cent crotamiton (Eurax) lotions to soothe the skin

·Avoid topical antihistamine creams (mepyramine, antazoline, diphenhydramine) as these are potent skin-contact sensitisers

·Topical steroid creams are of no value in ordinary urticaria

·Avoid multivitamin preparations containing additives and colourings that may non-specifically aggravate urticaria

Dietary advice

·Patients should avoid food colourings (such as tartrazine) additives (including sodium benzoate and sulphites) and natural salicylate sources (including berry fruits, spices, wine and Ceylon tea)

·Many patients with chronic urticaria benefit from a low vasoactive amine diet ­ see table overleaf for list of food with high histamine that should be avoided

Foods with high

vasoactive amine

(histamine) content

·Fish

mackerel, tuna, smoked salmon, sardines, pickled herring

·Cheese

emmental, parmesan, camembert, cheddar, stilton

·Cured meat

salami, dried ham, smoked sausage, chicken liver

·Fruit and vegetables

aubergine, spinach, red beans, avocado, bananas, dates

·Alcohol

red wine, cider, real ales

·Others

Marmite, soy sauce, tomato ketchup

Useful websites

Allergy and Allergies Agency website www.allergy-network.co.uk/urticaria.htm

www.prodigy.nhs.uk/guidance.asp?gt=

Urticaria

Adrian Morris, clinical assistant, allergy clinic, Royal Brompton Hospital,

London, and Surrey Allergy Clinic ­

he is member-at-large of the World Allergy Organisation and a member of the British Society for Allergy and Clinical Immunology

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