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Urticaria (Hives)

Urticaria is a distressing but generally benign and self-limiting condition. Transient symptoms occur in around 1 in 30 children and up to 1 in 5 people during life. Most patients respond to explanation, symptomatic treatment and clinical follow-up.

Up to 1 in 1000 adults suffer from chronic or recurrent disease, which has a significant effect on quality of life. Investigation and specialist referral is indicated in the presence of prolonged, refractory or atypical symptoms, or when underlying disease is suspected.

Clinical features

Urticarial lesions may be flat or raised, itchy or asymptomatic, of variable size and last minutes to hours. Diagnostic confusion may arise when patients present with long-lasting secondary dermatitis from scratching. Urticarial vasculitis should be suspected when lesions last longer than 24 hours, particularly if painful, purpuric or accompanied by bruising or systemic symptoms. Disorders mimicking urticaria need to be considered in the differential diagnosis (Table 1).

Angioedema occurs in the dermis and subcutaneous tissue, either alone or in association with urticaria. Swellings are less demarcated, may burn or hurt, and often last longer than 24 hours. The face and larynx is most often involved. Swelling elsewhere may cause diagnostic confusion. Extensive limb involvement, for example, may be mistaken for arthritis or cellulitis. Visceral angioedema is most commonly associated with hereditary angioedema (HAE; C1 esterase deficiency), but is observed occasionally in patients prescribed ACE (kininase) inhibitors and in idiopathic disease.

Classification of urticaria

Urticaria is best considered a "syndrome"of many potential causes (Table 2), traditionally classified into acute ( 6 weeks) duration. When considering aetiology, it is useful conceptually to add a third group of patients presenting with short-lived and isolated "episodic" symptoms lasting less than 12 hours, where investigation for an allergic cause may be fruitful.

Episodic and acute urticaria

Severe and dramatic symptoms that resolve within 12 hours (extensive swelling may take longer) should prompt consideration of an allergic cause, particularly if associated with systemic symptoms suggestive of anaphylaxis. Common triggers include food, medication (particularly NSAIDS or antibiotics) and venomous insect stings. Reactions to envenomation in most cases occurs within 30 minutes of being stung, although delayed reactions have occasionally been described. Allergic reactions to food and medication almost always occur within 6 hours. Symptoms consistent with anaphylaxis should prompt referral to a specialist in Allergy.

Antibiotic reactions usually follow a similar time course, although delayed reactions lasting several weeks occur from time to time. Penicillins, cephalosporins and sulphonamides (and occasionally insect stings or transfusions) can also trigger serum sickness, presenting with atypical urticaria, arthritis, lymphadenopathy and fever. Infection is such a common trigger of urticaria in children (up to 90 % of hospitalised cases in 1 study) that one is often left with uncertainty whether infection or its treatment was the cause.

Contact urticaria (e.g. food, animal saliva) is usually transient and localised. Inhalant allergy (e.g. animal dander) is almost always associated with symptoms of rhinoconjunctivitis. Food additives rarely trigger urticaria.

Urticaria occurring on a daily basis, whether it is for 2 weeks or 2 years, is rarely allergic.

Chronic urticaria & angioedema

The physical urticarias are a common explanation for chronic symptoms, yet are often overlooked. They may occur alone or accompany spontaneous urticaria. Recognition of symptoms triggered by rubbing (dermographism), sweating (cholinergic urticaria) or less commonly by cold, heat, sunlight, vibration, pressure or water may obviate the need for extensive investigation.

Once physical urticaria and allergic triggers are excluded, an explanation for chronic symptoms is rarely found. There is little convincing evidence that chronic infection causes uncomplicated urticaria.

Atypical clinical features or the presence of systemic symptoms should prompt examination for underlying disease, notwithstanding the fact that most associated disorders (e.g. SLE, rheumatoid arthritis) are clinically obvious by the time urticaria appears. Of particular interest is recent evidence of an autoimmune pathogenesis in a subset of patients with chronic urticaria, providing an explanation for an increased incidence of thyroid autoimmunity in this group.

Hereditary angioedema (HAE) should be considered in patients presenting with isolated angioedema, even in the absence of a positive family history. Since urticaria is not a characteristic of HAE, patients with mixed urticaria/angioedema are unlikely to suffer this malady. Symptoms in patients taking ACE inhibitors should be attributed to this medication until proven otherwise, even if the drug has been taken for many months or even years. With the exception of acquired C1 esterase deficiency in some patients with lymphoma, malignancy is an exceedingly rare cause of urticaria / angioedema. Other conditions can mimic urticaria / angioedema and should be considered in the differential diagnosis (Table 1).

Patient evaluation

The three prime factors in evaluating patients presenting with urticaria are the:

  • clinical assessment;
  • provocation testing; and
  • laboratory investigation.

History

A structured interview should be undertaken to determine the:

  • Duration of symptoms
  • Characteristics of individual lesions
  • Presence or absence of systemic symptoms
  • Circumstances surrounding the onset of symptoms
  • Aggravating and relieving factors

Allergy testing

An allergic cause should be considered in patients with short-lived "episodic" symptoms. Exposure to potential allergens in the previous 12 hours should be recorded. By contrast, routine skin testing or measurement of total or allergen-specific IgE ('RAST' blood tests) often results in misleading or irrelevant results.

Provocation testing

Provocation testing is used to confirm the diagnosis of a physical urticaria, where skin testing or laboratory testing is not diagnostic. Since facilities for resuscitation and close supervision are required, challenges should be restricted to specialist allergy centres.

Laboratory investigation

The yield from routine laboratory investigations is low. In the absence of unusual clinical features or historical evidence of underlying disease, short-lived episodes are best evaluated clinically (with or without allergy testing), 'acute' episodes treated and observed, and 'chronic' or atypical urticaria referred for specialist evaluation and further testing (Table 3). Perhaps the most useful (but underutilised) investigation is a punch biopsy of several atypical lesions, which may confirm the presence of urticarial vasculitis or indicate an alternative diagnosis.

Management

Patients generally present with the dual concerns of distressing physical symptoms and concern about the cause. Most patients respond to an explanation that they have a self-limiting condition that is unlikely to indicate a dangerous systemic process. Management principles are summarised in Table 4.

Further reading

  • Greaves MW. Chronic Urticaria (Current Concepts). New Engl J Med 1995; 332: 1767-72.
  • Juhlin L. Recurrent urticaria: clinical investigation of 330 patients. Brit J Dermatol 1981; 104: 369-380.
  • Mortureux P et al. Acute urticaria in infancy and early childhood. A prospective study. Arch Dermatol 1998; 134: 319-323.
  • Mullins RJ. Anaphylaxis in Australia's Capital - II: Clinical Features. Allergy Clin Immunol International 2000 (Supplement 2); 98.
  • Joint Task Force on Practice Parameters. The Diagnosis and Management of Urticaria: a Practice Parameter. Ann Allergy, Asthma, Immunol 2000; 85 (Part 2): 521-44. 

Table 1. Differential diagnosis  

Urticaria

Common

Scabies
Urticarial vasculitis
Erythema multiforme
Papular urticaria (due to insect bites)

Uncommon

Bullous skin diseases (early stages)
Urticaria pigmentosa (cutaneous mastocytosis)
Pruritis of other cause (dry skin, cholestasis, malignancy etc)
Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)

Angioedema

Common

Cellulitis
Laryngospasm
Globus hystericus
Orofacial granulomatosis (Melkersson-Rosenthal syndrome)

Uncommon

Angiosarcoma
Blepharochalasia
Lymphoedema
Aschers syndrome
SVC Obstruction


© ASCIA 2010

The Australasian Society of Clinical Immunology and Allergy (ASCIA) is the peak professional body of Clinical Immunologists and Allergists in Australia and New Zealand.

Website: www.allergy.org.au

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Disclaimer

ASCIA Education Resources (AER) information is reviewed by ASCIA members and represents the available published literature at the time of review. Information contained in this document is not intended to replace professional medical advice and any questions regarding a medical diagnosis or treatment should be directed to a medical practitioner.

Content last updated January 2010

Table 2. Potential Causes of Urticaria

Acute

Post-Infective
Allergy (food, medications, stings, aeroallergens, contact allergens)
Serum sickness
Food additives (MSG, tartrazine, benzoates, antioxidants, sulphites)
Radiographic contrast dyes

Chronic/Recurrent

Physical urticarias
Chronic infection
Systemic disease (autoimmune thyroid disease, connective tissue disease, systemic or cutaneous vasculitis, malignancy)
Urticaria pigmentosa (cutaneous mastocytosis)


Table 3. Laboratory Investigation

Investigation Result Interpretation
Urinalysis Blood, protein UTI, renal involvement in systemic disease
ASOT elevated Recent Streptococal infection
FBC eosinophilia Parasitic infection, vasculitis, hypereosinophilia syndromes
ESR elevated Systemic disorder, vasculitis, delayed pressure urticaria
LFT elevated Vasculitis, chronic hepatitis
Electrolytes, Urea, Creatinine abnormal renal involvement in systemic disease
TSH, thyroid antibodies abnormal Thyroid disease associated with urticaria
ANA Rheumatoid Factor Detected SLE, Rheumatoid arthritis, vasculitis
C3, C4 depressed Vasculitis, hereditary angioedema
Serum EPG Monoclonal bands Acquired angioedema
Stool examination Parasites detected Chronic infestation as cause of urticaria
Chest xray abnormal vasculitis
Hepatitis B/C serology positive Vasculitis, cold urticaria

 Table 4. Management Principles

TIME - the majority of patients will settle over a period of weeks to months.

AVOID IDENTIFIED AGGRAVANTS such as excessive heat, tight clothing, aspirin or alcohol. A food diary may also assist in the management of patients with suspected dietary triggers.

MEDICATION

  • Long-acting and non-sedating antihistamines are first line therapy.
  • Patients should be instructed that medications are palliative (not curative) and need regular administration for optimal symptomatic control.
  • Judicious use of H2 antagonists, corticosteroids or other immunomodulatory agents may be indicated but should never be used as monotherapy.
  • Avoid corticosteroids in patients with chronic symptoms where possible.
  • Inhaled or injected adrenalin may be required in patients experiencing upper airway angioedema.

ELIMINATION DIETS are useful in selected patients but should be temporary, closely supervised and followed by challenge procedures if successful.


Practice Points

  • Most cases of urticaria resolve with symptomatic treatment and do not require extensive investigation.
  • Allergic urticaria is generally severe, of rapid and dramatic onset and resolves within 12 to 24 hours.
  • Urticaria occurring on a daily basis, whether it be for 2 weeks or 2 years, is rarely allergic.
  • Isolated angioedema in a patient taking ACE inhibitors should be attributed to the medication until proven otherwise.
  • Measurements of total IgE and RAST testing with panels of foods or inhalants often leads to misleading or irrelevant results.
  • Specialist referral is indicated in the presence of prolonged, refractory or atypical symptoms or when underlying disease such as vasculitis is suspected.

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