Urticaria & Angioedema

Urticaria, commonly known as hives is characterised by transient, itchy, oedematous wheals or red papules. The important thing that distinguishes it from other skin conditions is the transient nature and the intense pruritus. Individual lesions should last no longer than 24 hours and disappear without leaving any marks. Deeper swellings, known as angioedema, are most often found in the mouth, eyelids, or genitalia, but may occur anywhere. Angioedema is associated with urticaria in about 40% of cases or occurs on its own in 10% of cases.

The acute form of urticaria lasts less than 6 weeks, and the chronic form lasts more than 6 weeks, by definition. The list of causes of Urticaria & Angioedema is extensive. When a patient presents within 24 hours of onset, a cause often can be determined. However, in many cases of both acute and chronic urticaria, the cause can be difficult and even impossible to determine. Fortunately, regardless of the underlying cause the management remains straightforward and generally successful.

Prevalence

Urticaria & Angioedema affects 15-20% of the general population at least once in their lifetime.

Causes of Acute Urticaria

  • Idiopathic in up to 50% of cases
  • Foods: fruits (eg, strawberries), milk, eggs, seafood, nuts, and spices
  • Drugs: antibiotics (eg, penicillin & sulfonamides), aspirin and non-steroidal anti-inflammatory drugs, morphine & codeine
  • Viral Infections: This is a common, but poorly recognised cause of acute urticaria, especially in children. Often antibiotics are blamed for this reaction.
  • Wasp or bee sting
  • Blood products
Chronic Urticaria

Chronic urticaria (lasting more than 6 weeks) is much more troublesome than acute urticaria. Recent studies using an internationally recognised quality of life questionnaire, the Nottingham health profile, have highlighted the disability of patients with chronic urticaria, including loss of sleep and energy, social isolation, altered emotional reactions, and difficulties in aspects of daily living. The disability is of the same order as that experienced by patients with sever chronic ischaemic heart disease.

Recently it has become clear from studies done mainly by Malcolm Greaves in the UK, that 27% to 50% of patients with Chronic Urticaria have functional autoantibodies directed against the high-affinity IgE receptor or less commonly against IgE. These antibodies, whose involvement has now been independently confirmed in several centres, are identified by autologous serum skin testing and confirmed by histamine release studies or immunoblotting. Their removal (by intravenous Ig or plasmapheresis) or treatment by cyclosporine has proved highly beneficial in severely affected patients. However, these methods of treatment are not recommended for routine use in chronic autoimmune urticaria.

Clinical features of Chronic Urticaria (CU)

Conventionally, chronic (idiopathic) urticaria is defined as the daily, or almost daily occurrence of urticaria wheals lasting more than 6 weeks. Intermittent urticaria, although a common entity, is less well recognised. It consists of bouts of urticaria lasting days or weeks with intervals of days, weeks, or months in between.

Angioedema occurs with CU in 50% of cases and Delayed pressure urticaria in about 40%. It is important to exclude this and other physical urticarias (as they frequently occur concurrently with CU).

CU is common, occurring in 0.1% of the general population, and 20% will still have the disease after 20 years have elapsed.

There is no increased frequency of atopy with CU.

Compared to physical urticarias, the individual lesions in CU last longer - at least 8 to 12 hours. Systemic symptoms are minimal. Patients frequently feel fatigued, especially during relapses, but respiratory, gastrointestinal, and arthralgic symptoms are rare. Angioedema may affect the oropharynx but is not life threatening. Pruritus is always sever and especially troublesome at nights.

CU is rare in childhood; the average duration of the disease is about 3 to 5 years in adults.

Aetiology of CU

  • Autoantibodies to IgE receptor in about 50% of CU
    That CU is, at least in some patients, autoimmune is not too surprising. An increased frequency of thyroid autoimmune disease in CU has been reported before.
  • Several recent reports of an association with H. Pylori infection - not confirmed as a cause for the urticaria.
Diagnosis of Chronic Autoimmune Urticaria

Patients with autoimmune antibodies have no distinctive diagnostic clinical features. They do tend to have more severe urticaria and histology shows more pronounced eosinophilic degranulation in older lesions compared with nonautoimmune cases, but not enough to be diagnostic. There is no vasculitis.

Currently the clinical diagnosis depends on autologous serum skin testing. Maximum specificity & sensitivity is obtained if serum or plasma, obtained by venisection during a phase of disease activity, is injected, in a volume of 0.05ml intradermally, into clinically uninvolved skin. The reaction at the injected site is examined 30 minutes later. A wheal with a diameter of at least 1.5mm greater than the control saline solution is deemed positive. A positive test is suggestive but not diagnostic of an autoimmune basis. In vitro histamine release tests are required, but these are difficult to calibrate.

Physical Urticaria

It is important to distinguish the physical urticarias from CU. This is to avoid unnecessary investigations, beyond any challenge testing to confirm the diagnosis.

Dermographism is urticaria that develops when the skin is stroked with a firm object.

Cold-induced Urticaria appears after a person is exposed to low temperatures - for example, after a plunge into a swimming pool or when an ice cube is placed against the skin (ice cube test). Characteristically, local whealing and itching occurs within a few minutes after applying the cold stimulus to the skin. The wheal persists for about a half hour or less. This physical urticaria may also occur in the oropharynx after a cold drink. It may occur after a viral infection.

Solar Urticaria arises on parts of the body exposed to the sun; this may occur within a few minutes of exposure.

Cholinergic urticaria, which is associated with exercise, hot showers and/or anxiety, is probably the commonest of all the physical urticarias. Often referred trivially to "heat bumps", it probably occurs in at least 15% of the population at some time.
It occurs predominantly in teenagers and carries a good prognosis. At least 50% are atopic. Wheezing can be associated with cholinergic urticaria. In severe cases attacks of syncope have been known to occur.

Delayed pressure urticaria occurs in at least 40% of patients with CU. It probably does not occur in isolation. Characteristically the wheals occur 2 to 6 hours after application of pressure and last for more than 24 hours. These wheals are itchy or quite painful, especially on the feet. They usually occur under areas of constant local pressure sites (waistband, belts, palms and soles). Delayed pressure urticaria responds poorly to H1 antihistamines.

Treatment of Urticaria

  • The routine treatment of all types of urticaria is the same.
  • General measures including avoidance of alcohol overuse, overtiredness, and overheated surroundings are important.
  • Reassure anxious patients that the urticaria is not a hallmark of any sinister disease.
  • All patients with frequent outbreaks of wheals and itching should be offered non-sedating antihistamine treatment. It is important to impress on patients that regular daily dosage is essential for maximum benefit.
  • In severe cases twice the licensed dose is necessary to control symptoms.
  • Doxipen, a tricyclic antihistamine is useful as a single nocturnal dose. Because anxiety and depression is a feature of patients with severe chronic urticaria & angioedema, this drug, which is also an H2 antihistamine, a powerful sedative, an anxiolytic, and an antidepressant, is appropriate.
  • Oral steroids have a limited role in chronic urticaria. Occasionally, in severe autoimmune chronic urticaria it is the only drug that will offer any relief. In this case a tapering course of alternate day therapy is used.
  • Leukotriene antagonists have received some attention as potential non-steroid therapy for chronic urticaria, but their role if any is limited.
  • Cyclosporine has been tried for the severely affected recalcitrant patients. Most (>75%) show an excellent response.
  • Several researchers in Australia and in Germany claim very high success using low salicylate diets for chronic urticaria.