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Need to know - urticaria

Dermatologist Dr Olivia Stevenson answers questions from GP Dr Sonia Barros D’Sa on combining antihistamines, using steroids and managing patient expectations

Dermatologist Dr Olivia Stevenson answers questions from GP Dr Sonia Barros D'Sa on combining antihistamines, using steroids and managing patient expectations

1. Are we any nearer knowing why ‘idiopathic' urticaria occurs and why it stops?

In a word, no. Common triggers for episodes of chronic urticaria are intercurrent viral infections and possibly stress but there is little evidence for any other more specific triggers for truly idiopathic urticaria. The other forms of urticaria may present similarly but are usually easy to distinguish and are listed in table 1.

If the clinical history and examination are typical of chronic idiopathic urticaria (CIU) then further investigation is rarely useful – see table 2 overleaf.41163694

2. What can I tell a patient with chronic urticaria – say over six weeks – about the likely course?

Chronic idiopathic urticaria (CIU) may last a few months or many years but duration tends to correlate with severity and most patients will have symptoms for ‘a few' years. More than 20% of patients with symptoms severe enough to warrant hospital intervention remained symptomatic 10 years on1.

The presence of angioedema and/or anti-thyroid antibodies is also associated with longer disease duration and physical urticarias tend to have a more protracted course.

3. We know viruses can precipitate urticaria but is there anything different about the management and outlook in children?

Acute urticaria is relatively common in children often with an obvious trigger – acute infection or allergen ingestion – and rapid remission.

CIU is thought to affect between 0.1% and 3% of children in the UK, commonly with accompanying angioedema. Children with urticaria are frequently overinvestigated, and in general the causes tend to be the same as in adults and investigations remain rarely helpful. Often the main challenge is to persuade the parents against food allergy.

However, it's important to consider urticarial vasculitis and possible underlying connective tissue disease if there is:
• fever
• arthralgia
• painful lesions
• raised ESR
• lesions lasting more than 24 hours.

The most common cause of acute vasculitic urticaria in children is Henoch-Schönlein purpura.

Also, continuing TFTs are suggested if thyroid autoantibodies are detected.

The natural history for chronic urticaria in childhood is remission. About 25% will remit within three years.

4. Is any one antihistamine better than another?

All antihistamines are licensed for the treatment of CIU, but avoid long-term use of first generation antihistamines due to sedation and psychomotor retardation.

There is little evidence to suggest one is better than another although a recent randomised double-blind study comparing cetirizine 10mg with fexofenadine 180mg demonstrated a significantly higher clearance rate in the cetirizine group after one month of treatment.

Patients with more intermittent symptoms may benefit from a rapid response and cetirizine will reach maximum effects in 30 to 60 minutes, making it the fastest onset of the second generation antihistamines.

Acrivastine also works fairly rapidly but has a very short duration of action making it less useful for regular control.

Even second-generation antihistamines may produce some sedation and this will vary from patient to patient. Every patient will respond slightly differently – both in clinical effect and side-effect profile – and so I cannot endorse any particular antihistamine. Finding the right one for each patient is often trial and error.

Higher than recommended antihistamine doses are frequently required in order to control symptoms adequately. This has been shown to be safe and is common practice in resistant disease and forms part of the guidance from the British Society for Allergy and Clinical Immunology2.

5. What is the rationale for combining more than one and how would you do that?

Combining antihistamines is also common practice but there is no real rationale or method and little evidence. If an antihistamine has given some, but not complete, relief and increasing the dose is unhelpful then there may be a case for adding in an alternative similar antihistamine.

Common combinations include fexofenadine plus cetirizine or loratadine. Remember that both of these can then be used at double dose to achieve control quite safely.

6. How long would you continue antihistamine treatment?

Treatment should be continued for at least three to six months before weaning off. If symptoms recur, restart and continue for a further six months before trying without.

Many patients will continue to have some breakthrough urticaria and therefore trials without therapy are not necessary.

There is no limit to the length of time antihistamines can be safely taken but always warn patients about sedation, driving and operating heavy machinery.

7. Is there any real benefit in adding an H2 blocker such as cimetidine?

There is little evidence that adding an H2 blocker will be any more effective than increasing the dose of monotherapy and this is recommended first. Some patients will benefit from them in addition to their antihistamine in a similar way to adding a second antihistamine.

8. What other drugs are worth trying and for how long to assess an effect? Can you explain the rationale as I find patients on a lot of treatments for urticaria get pretty fed up?

You should always start by explaining that the aim of treatment may not be complete control of symptoms but adequate control. Also reiterate that the same drug can work differently in different people and that it may be a matter of trial and error to find the right combination for them. Each treatment should be given at least a one-month trial.

After you have exhausted the usual antihistamines alone and in combination there are a few alternatives worth considering prior to referral.

• Leukotriene receptor antagonists – montelukast and zafirlukast – may be helpful, especially in patients with positive autoantibodies, or with positive challenge tests suggesting food, food additive or salicylate sensitivity. They are also useful in delayed pressure and may be more helpful in atopic patients but are usually used in combination with antihistamines.

• Tranexamic acid seems to be helpful in patients with angio-oedema – with or without urticaria.

• Other drugs such as ciclosporin should not be initiated in primary care.

• Occasionally patients will have symptoms of angioedema serious enough to warrant intramuscular adrenaline but these should not be used to control urticarial symptoms.

• Cooling creams such as 1%-4% menthol in aqueous cream can be useful for symptomatic relief of heat and itching.

9. When should one suspect vasculitic urticaria and how is it diagnosed?

Vasculitic urticaria tends to present rather differently from normal urticaria. There are several clues that should point you towards urticarial vasculitis:

• typically, true urticaria tends to last at most a few hours – if there for longer than 24 hours, be suspicious

• urticaria fades away to leave no sequelae whereas urticarial vasculitis will often fade after several days to leave a bruised area

• the symptoms with urticarial vasculitis will be more tenderness and less itch and may be associated with fever and/or arthralgia.

Although often no cause is identified for urticarial vasculitis, investigation for underlying causes should be performed and referral is usually warranted. Diagnosis can be simply made on punch biopsy through the lesion. For other investigations see table 2 above.

10. Is there anything a dermatologist might do that we can't and if so which patients should we refer?

Much of what I do is reassurance that a patient is doing everything they can and they may have to put up with a certain amount of residual urticaria. Many patients will take a lot of persuasion that there is neither a cause that we can identify nor any cure.

Sometimes prick testing can be helpful, but mostly to disprove a food allergy.

Some patients will need to consider ciclosporin if symptoms are sufficiently severe.

I would suggest referring any patient in whom there is diagnostic concern, or in whom urticarial vasculitis is suspected as well as any patient whose symptoms are not adequately controlled with the above measures or who requires further reassurance.

11. Is there anything else new? Are there any management pitfalls not covered by the questions above?

There is not much new in urticaria except for montelukast and zafirlukast. The main management pitfall is lack of adequate explanation. Many of the patients we see in secondary care have never received a good explanation of their condition and so continue to seek the allergen or expect a cure.

Dr Olivia Stevenson is a consultant dermatologist at Kettering General Hospital in Northamptonshire

Competing interests None declared


Useful website

www.bad.org.uk/public/leaflets

The British Association of Dermatologists has excellent patient information leaflets for this and many other dermatological diseases.

References

1 Humphreys F, Hunter JA. The characteristics of urticaria in 390 patients. Br J Dermatol 1998;138:635-8

2 Powell RJ, Du Toit GL, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy, 2007 May;37(5):631-50

What I will do now

Dr Barros D'Sa reflects on the answers to her questions
• I will try combinations of antihistamines as well as unlicensed ‘higher than recommended' doses of single antihistamines
• I will also consider other drugs in combination with antihistamines, such as leukotriene receptor antagonists or tranexamic acid
• Patients might well benefit from a cooling cream and menthol in aqueous cream sounds ideal
• I'll keep the differential diagnoses of vasculitis and connective tissue disease in mind and investigate atypical urticaria in children
• I'll refer patients to secondary care when there is diagnostic uncertainty or a suspicion of vasculitis
• It's important to make time to explain to patients about the likely course of idiopathic urticaria, and make sure they go away with information
Dr Sonia Barros D'Sa is a freelance GP in Basingstoke and north Hampshire

What triggers urticaria? Table 2: Investigations Take home points It is safe to double the dose of antihistamine if control is not achieved Urticaria

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