Urticaria and Angioedema

Urticaria is the medical term used to describe an episode of spontaneous skin weal's, also known as hives. They may or may not occur in association with tissue swelling known as Angioedema. These conditions are not trivial and chronic cases can have a profound impact on sleep, school, work and social interactions.

Acute Urticaria (+/- Angioedema) lasts less than 6 weeks while Chronic Urticaria (+/- Angioedema) is present daily or almost daily for more than 6 weeks.

  • Urticaria primarily affects the superficial layers of the skin and consists of a red, raised, itchy rash which can vary in size from a few millimetres to several centimetres. These hives may be single or numerous.
  • Angioedema affects the deeper layers of skin and subcutaneous tissues which become swollen. It most often affects the eyelids, lips, hands, feet and genitalia but can also affect the throat and larynx.

Prevalence

The lifetime prevalence of Acute Urticaria is almost 9% while Chronic Urticaria affects 2% of the population at some point during their life. Urticaria is almost twice as common in women than men. Peak incidence occurs between 20 and 40 years of age.

Adults suffering from Chronic Urticaria have significantly higher rates of allergic rhinitis, eczema and asthma. Interestingly, this is not the case in children where the prevalence of atopic conditions is similar in those with chronic urticaria to other children.

Pathophysiology

Urticaria and Angioedema occur primarily due to mast cell activation resulting in the release of cytokines, histamine, leukotrienes, prostaglandins and other inflammatory mediators. This causes vasodilation, increased blood flow and increased vascular permeability which produces the characteristic raised urticarial rash. Histamine is known to be the most significant mediator of Urticaria while Bradykinin is an important mediator of Angioedema. 

Aetiology

A wide number of factors can potentiate Urticaria and Angioedema and the trigger is often multifactorial. However, statistically no obvious cause is found in up to 50% of cases. In order to guide treatment in cases of chronic urticaria and angioedema it is important to exclude causes such as: 

  • Autoimmune (Thyroid, Coeliac, SLE, Inflammatory Bowel Disease)
  • Chronic Inflammatory processes (allergic rhinitis, gastritis, reflux oesophagitis)
  • Acute and Chronic Infection
  • Drug Induced (NSAID's, ACE Inhibitors, Aspirin)
  • Stress
  • Coagulation Disorder (Complement system)
  • Malignancy (lymphoma)

Aggravating Factors in Chronic Urticaria

  • Physical Stimuli
    • Exercise, Heat, Cold, Pressure, Sunlight
  • Viral Infection
  • Drug Pseudoallergy: NSAIDs, aspirin, opiates
  • Food Pseudoallergy: Salicylates, histamine rich foods, food preservatives and colouring agents 

Treatment

Eliminate underlying causes

It is very important to identify any possible triggers or aggravating factors so that further exposure can be minimised.

  • Identify and treat chronic infections or chronic inflammatory conditions.
  • Ensure all allergically driven inflammatory conditions such allergic rhinitis, eczema and asthma are well controlled. Minimise further exposure to any identified allergic sensitivities such as house dust mite, pollen, animal dander, feathers and mould. 
  • Avoid Aspirin, NSAID's and opiates.
  • Minimise pseudoallergen junk foods which contain additives such as preservatives, artificial colours and flavours.
  • Foods which are rich in histamine should be restricted during exacerbations of urticaria. e.g. tomato, strawberry
  • Smoking and alcohol should be avoided. 
  • Limit any obvious physical aggravating factors. e.g. heat, cold, pressure, sunlight.

Medication

Second generation oral anti-histamines are the mainstay of treatment in Chronic Urticaria. These include cetirizine, levocetirizine, loratadine, desloratadine, fexofenadine and bilastine. First generation anti-histamines such as chlorphenamine (Piriton) and promethazine (Phenergan) are no longer recommended. Although all medications are best avoided in pregnancy, cetirizine and loratadine are preferred if treatment is required. 

All cases which have persisted beyond 4 weeks despite treatment with a second generation anti-histamine should be referred for treatment by an allergy specialist, immunologist or dermatologist.

Additional Options

Leukotriene receptor antagonists (montelukast) can be considered as an adjunct to antihistamines when urticaria has been refractory to treatment. There is a lack of evidence to support general use in Chronic Urticaria but they may be of particular useful to urticarial patients with underlying allergic rhinitis and lower airway irritability.

Tranexamic acid may reduce the frequency of attacks of angioedema.

Corticosteroids are generally not recommended as a long term option but may be required initially to get symptoms under control. High doses are often required for long term control of urticaria which increases the risk of side effects.  

Monoclonal antibody subcutaneous injections (omalizumab) against IgE have emerged as an additional option for cases which are refractory to the treatments above. Randomised controlled trials have not yet been carried out so the safety profile is not clear. It is currently only prescribed in hospital settings. 

Prognosis

Initially about 33% of adults will continue to suffer from symptoms despite maximal tolerated doses of antihistamines. Despite this, Chronic Spontaneous Urticaria has a high rate of remission of up to 80% within 12 months. In 10% of cases symptoms may persist beyond 5 years.

In children with Chronic Spontaneous Urticaria, while just 25% are symptom free within 3 years, this rises to 96% after 7 years. Children with Chronic Inducible Urticaria who try to avoid their physical triggers (heat, cold, pressure, exercise etc) usually reach remission within 3 years.