Urticaria & Angioedema

Essentials of Diagnosis

• Evanescent wheals or hives

• Intense itching; rarely, pruritus may be absent

• Most episodes are acute and self-limited (1–2 weeks)

• Urticaria is divided into acute and chronic forms

• Chronic urticaria (episodes lasting longer than 6 weeks) may have an autoimmune basis

General Considerations

• Urticaria may be acute (less than 6 weeks' duration) or chronic (more than 6 weeks' duration)

• Urticaria can result from many different stimuli on an immunologic or nonimmunologic basis

  • Most common immunologic mechanism is mediated by IgE, which is seen in the majority of patients with acute urticaria

  • Another involves activation of the complement cascade

• Cholinergic urticaria is triggered by a rise in core body temperature (hot showers, exercise)

• Cold urticaria is acquired or inherited and triggered by exposure to cold and wind

• Chronic urticaria

  • Termed "chronic spontaneous urticaria" when there is no identifiable trigger

  • Called chronic inducible urticaria when can be reproducibly triggered; for example

    • Cholinergic urticaria

    • Solar urticarias

    • Cold urticaria

    • Dermatographism

    • Delayed pressure urticaria

• Some patients with chronic urticaria demonstrate autoantibodies directed against mast cell IgE receptors

• Autoimmune thyroid disease may be associated with autoimmune urticaria

• Acute hepatitis infection may be associated with urticarial vasculitis

Symptoms and Signs

• Lesions are itchy red swellings of a few millimeters to many centimeters

• The morphology of the lesions may vary over a period of minutes to hours

• Individual lesions in true urticaria last less than 24 h, and often only 2–4 h

• Angioedema is involvement of deeper vessels, with swelling of the lips, eyelids, palms, soles, and genitalia

• Angioedema is no more likely than urticaria to be associated with systemic complications such as laryngeal edema or hypotension

• Dermatographism

  • Induced by scratching

  • Can be elicited during the clinic visit by scratching the patient's skin

• In cholinergic urticaria, wheals are 2–3 mm in diameter with a large surrounding red flare

Differential Diagnosis

• Vasculitis

• Erythema multiforme

• Contact dermatitis (eg, poison oak or ivy)

• Cellulitis

Laboratory Tests

• Laboratory studies are not likely to be helpful in the evaluation of acute or chronic urticaria unless there are suggestive findings in the history and physical examination

• A complete blood count with differential, erythrocyte sedimentation rate or C-reactive protein, thyroid-stimulating hormone, and liver chemistries might be appropriate for some patients with chronic urticaria

• Functional ELISA test can detect patients with an autoimmune basis for their chronic urticaria

Diagnostic Procedures

• In patients with individual lesions that persist past 24 h, a skin biopsy may confirm neutrophilic urticaria or urticarial vasculitis

Medications

• H₁-antihistamines

  • Hydroxyzine, 10 mg twice daily orally to 25 mg three times daily or as a single nightly dose of 50–75 mg to reduce daytime sedation, is initial therapy

  • Cyproheptadine, 4 mg four times daily orally, may be useful for cold urticaria

• Second-generation H₁-antihistamines can be added if the generic sedating antihistamines are not effective

  • Fexofenadine in a dosage of 60 mg twice daily orally or 180 mg once daily orally

  • Loratadine or cetirizine in a dosage of 10 mg once daily orally

• Doxepin (a tricyclic antidepressant), 10–75 mg orally at bedtime

  • Can be very effective in chronic urticaria

  • Has anticholinergic side effects and is sedating

• H₂-antihistamines in combination with H₁-blockers may be helpful in patients with symptomatic dermatographism

• Dapsone or colchicine (or both) may be useful if neutrophils are a significant component of the inflammatory infiltrate in chronic urticaria

• Omalizumab

  • Can be highly effective in refractory chronic urticaria

  • Should be considered when severe chronic urticaria fails to respond to high-dose antihistamines

• Ligelizumab has been shown to be effective in early clinical trials

• Adjuvants

  • Systemic corticosteroids, eg, prednisone ~40 mg once daily orally usually suppresses acute and chronic urticaria

  • However, the use of corticosteroids is rarely indicated

  • Cyclosporine (3–5 mg/kg/day) and other immunosuppressive medications may be effective in severe cases of chronic urticaria

  • Topical treatment is rarely rewarding

Therapeutic Procedures

• UVB phototherapy can suppress some cases of chronic urticaria

Prognosis

• Acute urticaria usually lasts only a few days to 6 weeks

• 50% of patients whose urticaria persists for more than 6 weeks will have it for years

• Patients in whom angioedema develops during angiotensin-converting enzyme inhibitor therapy may be switched to an angiotensin receptor blocker with caution (estimated cross reactivity is about 10%)

When to Refer

• There is a question about the diagnosis

• Recommended therapy is ineffective

• Specialized treatment is necessary