Urticaria And Angioedema

Dr Michael Radcliffe explains the difference.

 

I work in a busy NHS allergy clinic in central London and in a full day of seeing patients in the out-patient clinic, I will typically see 10 new referrals.  The commonest reason for being referred is a condition called urticaria.  Amongst 10 new referrals I will expect to make this diagnosis 3 or 4 times.

But what is it and what causes it?  Some peoples call it hives, or welts or stinging nettle rash.  The last name is closest to the truth.  The Latin word for the stinging nettle is Urtica and so Urticaria is Latin for the itchy rash that occurs when someone brushes against stinging nettle leaves, the hairs of which are rich in plant histamine, whereas urticaria occurs when human histamine is released without good reason from immune system cells called mast cells in the skin and mucous membranes.

Urticaria causes transient, itchy skin blotches that are called wheals.  Urticarial wheals may appear singly, or a rash may form when wheals are constantly coming and going.  By comparison, angioedema causes non-itchy, pale or pink swellings that are more deep-seated and arise around the eyes, lips, face or anywhere on the body.  Urticaria and angioedema are common conditions, affecting 1 in 5 people at some time in their lives. Urticaria may occur alone (50% of cases), with angioedema (40% of cases), or angioedema may occur alone (10% of cases).  There is a common misunderstanding that the most likely cause of these conditions is a hidden allergy.   Surprisingly this is very rarely found to be true.  Whilst an allergic reaction to a food (e.g. nuts), a sting venom (e.g. a wasp sting) or a drug (e.g. penicillin) can lead to urticaria, it typically arises in combination with other allergic symptoms or, in extreme cases, as one part of the life-threatening condition known as anaphylaxis.  Moreover, in cases where urticaria occurs due to food, insect sting venom or a drug or medicine, the relationship is usually obvious and not in doubt.

Urticaria

Wheals (hives) may be numerous and can vary in size from a 5p coin to a dinner plate.  They have an irregular outline and may look like stinging nettle rash.  They are often pale pink, usually raised, and can be surrounded by a red flare.  Wheals come and go, with each one lasting from a few minutes to a few hours.

      Acute spontaneous urticaria is a single attack or a cluster of attacks lasting from a few hours to a few weeks. An overactive immune reaction to a trivial viral infection is the most likely cause.  When doctors use the word acute, they are referring to an isolated and self-limiting attack.

      Chronic spontaneous urticaria lasts from several months (most cases) to many years (occasional cases).  It consists of recurring attacks of wheals, each of which can last from several minutes to several hours.  It may be persistent, with one or more attacks each day, or it may be intermittent, with symptom-free weeks or months.  When doctors use the word chronic, they are referring to a continuing and persistent condition.  By convention, urticaria is called acute when it lasts for less than six weeks.

      Chronic inducible urticaria is less common (cold urticaria, heat urticaria, dermatographism, pressure urticaria, exertion-induced urticaria) and some patients may suffer from more than one type.

Angioedema

Angioedema accompanies urticaria in a sub-group of patients, but it can also occur alone as acute spontaneous angioedema (an isolated attack or cluster of attacks) or as chronic spontaneous angioedema when it may last from several months (most cases) to many years (occasional cases).  Attacks can affect the lips, eyelids and face and in some cases the tongue or throat may swell.

Sufferers need to be reassured that in these conditions it is very unlikely that throat swelling would progress rapidly or become life-threatening and that an adrenaline auto-injector (for example Emerade®) is not usually recommended.  But urgent medical help should be sought if tongue or throat swelling affects speaking or threatens to cause breathing difficulty.

Angioedema without urticaria can also be caused in other ways.  A rare cause is the disease hereditary angioedema.  It is diagnosed by blood test and there is often a family history.  Antihistamine and adrenaline auto-injector treatment is not suitable for these patients although other effective treatments are available.

But the commonest cause of angioedema without urticaria amongst patients seen in the allergy clinic is a blood pressure treatment, the group of drugs called ACE (angiotensin converting enzyme) inhibitors.  But this is not drug allergy, it is a side effect.  ACE inhibition causes an alteration in blood chemistry in predisposed individuals (approximately one in three hundred patients who are taking the treatment) that is sufficient to precipitate occasional attacks of angioedema.  This consequence may not become apparent until months or years of ACE inhibitor treatment.

Patients who suffer from food allergy (for example allergy to nuts) drug allergy or bee/wasp venom allergy are at risk from the life-threatening condition known as anaphylaxis.  Although the symptoms are similar, it is a different condition and precautionary adrenaline auto-injector treatment is usually prescribed for these patients.

Quality of Life

In view of its harmless nature, many people regard urticaria as a trivial condition with the main inconvenience being the need to carry antihistamines for use when needed.  Even amongst general practitioners there are some who consider urticaria to be a condition that can be managed by the patient, and they advise their patients to buy over-the-counter antihistamines to manage the symptoms.  Worse still, first generation sedating antihistamines are often advised.  First introduced in the 1950s, first generation antihistamines such as chlorphenamine (trade names such as Piriton®) cause significant side effects such as constipation and somnolence.  Although these effects may appear to wear off with regular treatment, the drugs can also impair co-ordination and increase reaction times in the same way that alcohol can.  It is the opinion of many specialists that second generation antihistamines (drugs such as cetirizine, fexofenadine and loratadine) are preferable.

Urticaria is certainly not regarded as a trivial condition by the patient.  Studies that have measured (by means of validate questionnaires) the quality of life of hospital out-patients suffering from chronic spontaneous urticaria have shown high levels of disability, social and emotional handicap.  By using the same quality of life questionnaire, it is possible make comparisons between groups of patients who suffer from different diseases and the results can be surprising.  For example, one study compared quality of life impairment between two groups of patients, one of which suffered from chronic spontaneous urticaria whilst the other group suffered from heart disease with angina.  There was no difference between the two diseases.

Causes

Attacks of urticaria with or without angioedema occur when histamine is released without good reason from immune system cells called mast cells in the skin and mucous membranes.  The reason why histamine is released is uncertain.  In some cases it may be due to autoimmunity and the inappropriate action of a rogue antibody that may have been formed when the body was fighting a minor infection just before the condition started, although other theories exist.  People who suffer from these conditions sometimes notice that their worst attacks occur shortly after taking a non-steroidal anti-inflammatory painkillers (NSAID) such as aspirin (Anadin®), ibuprofen (Nurofen®) or diclofenac (Voltarol®).

There is also a condition that closely mimics chronic spontaneous urticaria, although the cause is different.  It is a variant of the condition known as food dependent exercise induced anaphylaxis.  In this condition food allergy causes anaphylaxis, but the food allergy is hidden.  Symptoms only occur when exercise is undertaken an hour or two after a meal containing a moderate amount of the causative food.  Exercise when the food has not been eaten causes no symptoms and neither does eating the food when no exercise follows.  Although full-blown anaphylaxis is the usual consequence, allergists are beginning to realise that there may be rare cases amongst patients who diagnosed as suffering from chronic spontaneous urticaria. Surprisingly wheat is the commonest causative food in this condition and it was the arrival of a new wheat allergy blood test that made it possible to spot which patients may be suffering from this condition.

Treatment

Urticaria and angioedema cause stress and the symptoms interfere with everyday life.  But whilst sufferers are often afraid of a life-threatening attack this is unlikely and adrenaline auto-injector treatment is not normally prescribed.  For frequent attacks, doctors prescribe non-sedating antihistamine tablets to be taken every day without a break.  However, the standard dose fails in more than 50% of sufferers and, if this happens, doctors are advised to consult up-to-date urticaria guidelines about the safe prescribing of above-standard doses.                        In this way, the number whose urticaria attacks can be completely prevented can be increased to about 75%.  Other effective treatments are available for resistant cases and almost all patients can be helped.

What else can help?

It may help to avoid provoking factors such as stress, heat, tight clothes, aspirin and NSAID painkillers such as aspirin (Anadin®), ibuprofen (Nurofen®) or diclofenac (Voltarol®).  Whilst not all people who suffer from chronic urticaria are affected by NSAIDs, those who are aware of this problem may find that certain food dyes may also cause attacks, although usually less severe.  However the suggestion that naturally occurring aspirin-like compounds called salicylates may also contribute to the severity of chronic urticaria remains unproven and sufferers are warned that adherence to a low salicylate diet may cause a greater impairment of quality of life than the condition it is intended to help.

It is not only nettle leaves that are rich in naturally occurring histamine.  Foods such as mature cheeses, pickles, shellfish and pulses contain high levels.  It has been suggested that following a low histamine diet might help some chronic urticaria sufferers.  Although I have suggested this to occasional patients with treatment-resistant urticaria, I have not been impressed with the results and a recent study from Berlin reached the same conclusion.

Dr Michael Radcliffe is Consultant in Allergy Medicine at University College London Hospitals, London.

 

This article first appeared in Allergy Newsletter No. 118. Winter 2016.

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