Primary Care Dermatology Society
The leading primary care society for dermatology and skin surgery

Urticaria and Angioedema

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Latest update 23/04/10

This chapter is set out as follows:

Overview

Definitions

  • Urticaria is a transient eruption of erythematous or oedematous swellings of the dermis and is usually associated with itching
  • Angioedema causes transient swellings of deeper dermal, subcutaneous and submucosal tissues, often affecting the face (lips, tongue and eyelids) or other areas such as the genitalia

Key diagnostic features

  • History – itchy lesions lasting 30 minutes to 4 hours that change and move daily
  • Morphology – oedematous, raised pink plaques without scale. Annular lesions result from central clearing and white halos. Lesions vary in size, some can be very large
  • Other presentations
    • Cholinergic urticaria – lesions are a lot smaller (see later under physical urticaria)
    • Individual lesions lasting over 24 hours – can represent delayed pressure urticaria or urticarial vasculitis (both discussed later)
  • Urticaria and angioedema often occur together and should be considered as a similar process. If angioedema occurs without urticaria it is important to look for other causes such as drugs e.g. ACEI and the much rarer C1 esterase inhibitor deficiency (see later)

Figure 1 – Chronic ordinary urticaria

Figure 2 – Acute urticaria caused by food allergy

Acute and intermittent urticaria

  • Symptoms tend to last for a few days at a time
  • Causative agents include:
    • Drugs – antibiotics, aspirin, NSAIDs. ACEI can cause angioedema without urticaria
    • Food – the majority of food allergies causing urticaria are caused by nuts (especially peanuts and tree nuts), white fish (e.g. cod), shellfish (e.g. prawns), hen eggs, milk, some fruits (especially strawberries, kiwis and citrus fruits). Many other foods can be responsible
    • Bee and wasp stings
  • Investigations: most of the time the patient will be able to identify the cause. Food specific IgE or RAST tests (blood tests) can be performed for suspected allergens but the results are not always easy to interpret and a negative result does not always exclude the relevant food from being the cause. A more reliable test is a skin prick test, which should only be done in a specialist setting, but it still has its limitations in that for both RAST and skin prick tests a positive result does not necessarily indicate that the food is responsible for the urticaria. Given the difficulties with such tests it is often preferable to simply avoid the food for a period of at least 4-6 weeks and see if symptoms improve. Urticaria is a type I immediate hypersensitivity reaction and patch tests are of no value - patch tests are used for type IV delayed hypersensitivity reactions such as contact allergic dermatitis
  • Treatment
    • Avoid triggers
    • Non-sedating antihistamines PRN

Contact urticaria

  • Symptoms - an immediate but transient localised swelling and redness that occurs on the skin after direct contact with an offending substance
  • Aetiology - it can be both non-immunological e.g. nettle rash, and immunological e.g. food, latex, plants or animal hair/fur
    • Latex allergy – for more information please click here
    • Contact food allergy - symptoms include a tingling sensation, peri-oral flare and swelling of the lips, tongue and soft palate. The offending food is normally obvious as symptoms often occur within a few minutes of contact with the food, if this is not the case it may be worth keeping a food diary. If the cause of the symptoms is less clear and the symptoms persist it is worth referring to a dermatologist to rule out other causes such as a contact allergic dermatitis to toothpaste or amalgam in fillings (the later can cause facial swelling in some cases)

Physical urticaria

Physical urticaria's are a distinct subgroup of urticaria in which a specific physical stimulus induces the symptoms. For such a diagnosis to be made the physical stimulus must be the main cause of symptoms, as patients with chronic ordinary urticaria can also have features of physical urticaria

The different types are as follows:

  • Dermographism – is the commonest form of urticaria. It affects 5% of the population and tends to present in young adults. Many people develop a white line, then a red line with slight swelling of the skin when it is firmly stroked. In dermographism this response is exaggerated with symptoms occurring at sites of trauma or friction
  • Delayed pressure urticaria – in its predominant form is uncommon, but it is found frequently in patients with chronic ordinary urticaria. Symptoms occur at sites of sustained pressure, tending to arise several hours after contact and lasting between 12-72 hours. Examples include at sites of tight clothing and the buttocks after sitting
  • Cholinergic urticaria – small (1-4mm) papules erupt in relationship to sweating, they are most commonly found on the trunk
  • Solar urticaria – a sore, itchy rash develops within minutes of sun exposure. For more information refer to the chapter on photodermatoses
  • Aquagenic urticaria – small wheals develop within 30 minutes of exposure to water, hot or cold
  • Cold urticaria - symptoms develop after exposure to the cold such as going outside into a cold wind, or fullness of the throat / swelling of the lips after drinking cold liquids. Due to massive histamine release patients can drown if they swim in cold water and so patients should be advised to avoid bathing in cold water. Up to 96% of cases are idiopathic but a few are secondary to underlying disorders such as cryoglobulinaemia. Patients should be referred to a dermatologist for further assessment and advice on management. Patients should carry two epipens and know how/when to use them

For guidance on management please refer to the section on chronic ordinary urticaria

Figure 3 – Dermographism

Figure 4 – Dermographism in a 3 year old child

Figure 5 – Delayed pressure urticaria  



(copied with kind permission of Dermatoweb)

Figure 6 – Cholinergic urticaria 



(copied with kind permission of Dermatoweb)
Figure 7 – Cholinergic urticaria



(copied with kind permission of Dermatoweb)

Figure 8 – Solar urticaria



(copied with kind permission of Dermatoweb)

Chronic ordinary urticaria (syn. chronic idiopathic urticaria)

Aetiology

  • 90% of patients with chronic urticaria have no known cause, and in the absence of a predominantly physical urticaria they are defined as having chronic ordinary urticaria (COU)
  • It is believed that some cases result from an autoimmune process, and such patients may have anti-thyroid antibodies present

Natural history

  • Fifty percent of patients with COU can be expected to be clear in 6 months, but some go on for years

Investigations
The following investigations are recommended for patients whose symptoms persist despite of standard doses of non-sedating antihistamines:

  • FBC - identify eosinophilia caused by parasitic infestation, and low white cell count from systemic lupus erythematosus
  • PV / ESR – if raised suggest the possibility of an underlying systemic disease e.g. lupus or urticarial vasculitis
  • TFT and thyroid antibodies
  • COU is rarely (if at all) caused by allergy and so referral for allergy testing is seldom indicated

Management

  • Step 1 – General measures
    • Lifestyle - keep the skin cool, reduce stress
    • Avoid any obvious physical / other triggers
    • Medications – drugs such as aspirin, NSAIDs and in some cases codeine may aggravate symptoms. ACEI can cause angioedema without urticaria. It is important to check both presribed and over the counter medications
    • Provide a patient information leaflet on urticaria
  • Step 2 – Non-sedating oral antihistamines
    • Start with a standard dose of one a day – patients not responding to one formulation may respond to a different antihistamine
    • If response is inadequate the dose can be increased – it is belived to be safe for adults to take up to four times the recommended dose
    • Antihistamines tend to work best if taken OD but if patients feel tired on higher doses they can be taken BD
    • At higher doses it is impotant to consider co-existent morbidities such that fexofenadine (Telfast ®) 180mg and cetirizine are excreted by the kidneys and loratadine and desloratadine (Neoclarityn ®) are metabolised by the liver
    • It is safe for patients to take antihistamines for as long as is needed
  • Step 3 - Sedating anithistamines
    • These can be added in at night for patients who have symptoms interefering with sleep e.g. Hydroxyzine (Atarax ®) tablets in adults 25-50mg nocte
    • Warn that patients could feel drowsy in the morning
  • Step 4 – H2 antagonists
    • Patients not responding adequatly to the above can be given a trial of either ranitidine (Zantac ®) 300mg OD or cimetidine 400mg BD
    • They should be added into the antihistamines
    • If there is no response after 4-6 weeks the H2 antagonists should be withdrawn
  • Step 5 – other considerations
    • Aspirin / NSAID sensitive – add in an LRA e.g. montelukast (Singulair ®) tablets 10mg OD
    • Associated anxiety / depression – add in doxepin 75mg nocte if no contraindication (doxepin has antihistaminic properties)
    • Again trial for 4-6 weeks
  • Step 6 - referral to secondary care
    • Patients not responding to treatment can be referred for consideration of other treatments such as ciclosporin (can be very useful for patients thought to have an autoimmune basis for their urticiaria), methotrexate and systemic steroids (the latter is used more so in the US)

Managing acute flares

  • Patients who develop a more acute episode, especially if associated with troublesome angioedema and not responding to antihistamines are best managed with systemic prednisolone (adult 30-40mg) OD for 1-3 days
  • Patients with a history of developing life-threatening symptoms of severe angioedema (e.g. swelling of the mouth or throat) / anaphlaxis need to be trained in the use of epipens and may benefit from being referred to an immunologist

Pregnancy, young children

  • Pregnancy – chlorpheniramine is the main antihistamine used in preganancy and tends to be used from the end of the 1st trimester
  • Young children - Desloratadine (Neoclarityn ®) is licensed for use from the age of one year, loratadine from two years

Urticarial vasculitis

  • History - lesions persist for more than 24 hours and may burn as well as itch. They can be painful or tender
  • Clinical findings - rather angulated patches of urticaria that are most prominent on the extremities. Lesions can resolve with residual bruising or staining
  • Systemic upset is common, 50% of patients have arthralgia
  • Patients are best referred to secondary care for further management as urticarial vasculitis can be associated with hypocomplementaemia (with or without lupus) and a number of other conditions. Histology often shows a small-vessel vasculitis
  • For most the condition runs a relatively benign course and lasts for about three years. Patients with associated hypocomplementaemia tend to be more problematic

Figure 9 – Urticarial vasculitis

Angioedema without urticaria

Angioedema is found quite frequently in patients with urticaria but when this is not the case it is important to look for a cause:

  • ACEI – angioedema tends to start within three weeks of the drug being introduced, although in some patients the time lag can be a lot longer. Black African patients tend to develop the most serious adverse reactions. Other ACEI should be avoided although some patients may tolerate Angiotensin-II receptor antagnoists (ARBs) - the benefits of the drug need to be weighed up against the risks of introducing an ARB
  • C1 esterase inhibitor deficiency – the vast majority are hereditary (HAE), approximately 10% are acquired (AAE) and can be secondary to lymphoproliferative disease or autoimmune disorders. 50% of cases of HAE start before puberty but onset can be in adult life. AAE starts in adult life. Patients with C1 esterase inhibitor deficiency often have associated respiratory and abdominal symptoms. Attacks may be spontaneous or triggered by dental work, infections and oestrogens. Blood tests for complement C4 offer a good screening tool, if low a sample should be sent for C1 esterase inhibitor level and function. Patients found to have abnormal results should be referred to a dermatologist for further management
  • Patients not on ACEI and who do not have C1 esterase inhibitor deficiency are classified as having ordinary angioedema, and such patients are managed in a similar way to that described above for chronic ordinary urticaria

Figure 10 - Ordinary angioedema of the lips

Who to refer

  • Dermatology
    • Cold and solar urtciaria
    • Latex allergy
    • Chronic ordinary urticaria not responding to steps 1 to 5 in the management section
    • Suspected cases of vasculitic urticaria
    • C1 esterase inhibitor deficiency
  • Immunology
    • Certain food allergies – patients with moderate/severe reactions to eggs. Patients with nut allergies often have multiple allergies and may require further investigations
    • Patients with life-threatening symptoms such as severe angioedema (e.g. with swelling of the mouth or throat) and anaphylaxis sometimes require further investigations, and may benefit from advice on how to manage symptoms including the proper use epipens