Five things... you may not know about urticaria
In this new series, dermatology experts update your knowledge on various skin conditions
– consultant dermatologist Dr Nuala O'Donoghue kicks off this week with tips on diagnosis and management of urticaria
1. Urticaria is rarely due to allergy
In acute urticaria (up to six weeks' duration), one half of cases are idiopathic in origin, 40 per cent are associated with an upper respiratory tract infection, 9 per cent are due to drugs, and only 1 per cent of cases are thought to be due to food.
The low incidence of associated allergy means that, except where suggested by the history, investigations are not required.
If appropriate, skin prick testing and radioallergosorbant tests (RASTs) can be performed to possible environmental allergens (such as latex or fish) to look for specific
In chronic urticaria (ie lasting more than six weeks), more than one-third of cases are due to auto-immunity, one third are caused by physical stimuli (for example, stroking of the skin in dermagraphism, see picture), and a small proportion are due to urticarial vasculitis and infections. A true allergic cause is exceptional.
There is a small group of patients with urticaria who react to pseudoallergens in food: these are foodstuffs to which patients have a non-allergic response, resulting in a worsening of their urticaria.
Pseudoallergens include food additives and natural salicylates, and excluding them from the diet has been advocated in a number of reports.
Although high success rates with
exclusion diets have been reported by some authors, this may have been partly due to the patients' urticaria resolving spontaneously; when these same patients were
given a double-blind placebo-controlled challenge test with individual additives, less than 20 per cent of them had a disease flare.
2. Urticaria has as much of an impact on a child's quality of life as asthma
The common perspective of physicians is that chronic urticaria is a benign, painless disorder with no threat to function or life. Health-related quality-of-life (QoL) tools, however, have demonstrated that we underestimate the impact of this disorder.
Key concerns of patients and carers include the severity of itch and associated sleep difficulties, the unpredictability of weals (see picture near right) and angioedema, and anxiety related both to the risks of anaphylaxis and the use of epinephrine pens.
Children with chronic urticaria have a worse QoL score than those with epilepsy, enuresis and diabetes, and an equal score to those with asthma. Overall QoL is also markedly reduced in adults with chronic urticaria: social functioning and emotions have been found to be the areas most affected.
Psychiatric co-morbidity (depression, anxiety, somatoform disorders) is associated with a more pronounced reduction of QoL and the severity of psychiatric disease correlates with QoL impairment.
3. Antihistamines are often not used optimally to manage severe chronic idiopathic urticaria
Antihistamines of various types continue to be the keystone of symptomatic treatment for urticaria.
The first generation of H1-receptor blockers, including chlorphenamine and hydroxyzine, are sedating. They are also potent competitive inhibitors of muscarinic receptors and may cause anticholinergic side-effects such as sinus tachycardia, dry skin, dry mucous membranes, dilated pupils, paralytic ileus, urinary retention and even agitated delirium.
Second-generation agents such as cetirizine, loratadine and fexofenadine are more selective for the H1-receptor, and so anticholinergic side-effects are rarely seen. Additionally, as they are less lipophilic they are less likely to cross the blood:brain barrier, and so they cause less sedation. Some second-generation agents have a longer half-life, so can be given once-daily.
Guidelines produced by the British Association of Dermatologists support the use of higher than the licensed doses of antihistamines in refractory urticaria: in particular the addition of a sedating antihistamine, to be taken at night (for example, chlorphenamine 4mg, hydroxyzine 25mg) to a standard dose of a non-sedating antihistamine is recommended.
Although there have been reports of improvement in wheals and itch following the addition of a H2-receptor antagonist (for example, cimetidine 400mg four times daily) to a patient's regime, in practice this can be disappointing.
Leukotriene antagonists such as montelukast, however, are increasingly being shown to be beneficial when given in conjunction with H1-receptor blockers.
4. Tolerance to second-generation antihistamines has not been seen
A common misconception of patients is that antihistamines will stop working adequately if taken regularly over a period of time. This phenomenon, in which a stronger treatment is needed to give the same effect, is known as tachyphylaxis, and is recognised with other drugs (for example, topical steroids used for the long-term management of atopic eczema).
Patients should be reassured, however, that this is not a problem with second-generation antihistamines, and they should be encouraged to use these drugs regularly to minimise urticaria. Patients with chronic ordinary urticaria, for example, should be asked to take a regular dose of antihistamine on a daily basis to keep their urticaria at bay.
They can be informed that every few months they could stop their antihistamines to determine if their urticaria has abated. The majority of patients can be reassured that their urticaria is likely to resolve.
Over 60 per cent of patients with weals alone will undergo spontaneous remission within three years. It is worth noting, however, that patients with angioedema as well as weals have a worse prognosis: half of these patients will still be developing lesions five years after the disease onset.
5. Hereditary angioedema will not respond adequately to antihistamines or steroids
Many patients with chronic urticaria will also develop intermittent angioedema, but angioedema (see picture above) without weals should lead one to consider the diagnosis of hereditary angioedema (HAE). HAE, inherited in an autosomal dominant fashion, is caused by mutations in one copy of the structural gene for C1 esterase inhibitor (C1 INH), resulting in reduced absolute or functional levels of this inhibitor.
Angioedema in this condition is due to activation of kinin formation, and is independent of mast cells, so antihistamines are ineffective.
If a patient (often a young adult or child) has angioedema without weals and is unresponsive to antihistamines, then HAE should be considered.
The screening investigation of choice would be to check the serum C4 which is found to be low in HAE, with 100 per cent sensitivity. The treatment of C1 INH deficiency differs from that of other types of angioedema.
C1 INH concentrate or fresh frozen plasma should be given in an emergency, as it may prove to be lifesaving. C1 INH concentrate may also be given as prophylaxis before surgery, especially when intubation or tooth extraction is necessary. Tranexamic acid and anabolic steroids may help decrease the frequency of attacks.
Nuala O'Donoghue is a locum consultant dermatologist at St John's Institute of Dermatology, St Thomas' Hospital, London, where she sees patients in the specialist
Competing interests None declared