What is the best approach to treat patients with urticaria?

Treatment of Urticaria

Start all patients with urticaria on second-generation H1 antihistamines as first-line therapy, and escalate doses up to 4 times the standard dose if symptoms persist after 2-4 weeks. 1

Initial Management Approach

First-Line Treatment

• Begin with a single second-generation H1 antihistamine at standard dosing (cetirizine, fexofenadine, loratadine, or desloratadine) for 2-4 weeks 2
• Over 40% of patients show good response to antihistamines, which remain the mainstay of therapy 1
• If the first antihistamine is ineffective, trial at least two different non-sedating antihistamines, as individual responses vary significantly 2

Dose Escalation Strategy

• When standard dosing provides inadequate control after 2-4 weeks, increase the antihistamine dose up to 4 times the standard dose 1, 2
• This practice has become common when potential benefits outweigh risks, even above manufacturer's licensed recommendations 1

Adjunctive Therapies for Resistant Cases

Second-Line Additions

• Add H2 antihistamines (ranitidine or famotidine) for patients not responding to high-dose H1 antihistamines alone 1, 2
• Add leukotriene receptor antagonists (montelukast), particularly beneficial for aspirin-sensitive and autoimmune urticaria 1, 2
• Add first-generation antihistamines (hydroxyzine) at night for additional symptom control and sleep improvement 2

Corticosteroid Use

• Restrict oral corticosteroids to short courses only for severe acute urticaria or life-threatening angioedema affecting the airway 1, 2
• Avoid long-term corticosteroid use except under specialist supervision due to cumulative toxicity including hypertension, hyperglycemia, osteoporosis, and gastric complications 2
• More prolonged treatment may be necessary for delayed pressure urticaria or urticarial vasculitis 1

Advanced Therapies for Refractory Disease

Third-Line Options

• Omalizumab 300 mg subcutaneously every 4 weeks is recommended for chronic spontaneous urticaria unresponsive to high-dose antihistamines 3, 2
• Allow up to 6 months for response to omalizumab 3, 2
• Cyclosporine 4 mg/kg daily for up to 2 months is effective in approximately 65-70% of patients with severe autoimmune urticaria who fail omalizumab 2
• Mandatory monitoring of blood pressure and renal function every 6 weeks when using cyclosporine 3

Restriction of Immunomodulating Therapies

• Reserve immunomodulating therapies for chronic autoimmune urticaria only in patients with disabling disease who have not responded to optimal conventional treatments 1

Trigger Avoidance and General Measures

Critical Avoidance Strategies

• Avoid aspirin and NSAIDs in all urticaria patients, as they inhibit cyclooxygenase and can exacerbate symptoms through leukotriene formation 3, 2
• Avoid ACE inhibitors if angioedema is present without wheals, and use cautiously when angioedema accompanies urticaria 2
• Identify and minimize aggravating factors including overheating, stress, and alcohol 2
• Provide advice on general measures and information, especially if an avoidable physical or dietary trigger can be identified 1

Emergency Management

Anaphylaxis Protocol

• Administer intramuscular epinephrine 0.5 mL of 1:1000 immediately for severe urticaria with anaphylaxis or angioedema affecting the airway 2

Monitoring and Treatment Duration

Follow-Up Strategy

• Reassess disease activity at every visit using validated patient-reported outcome measures to guide treatment decisions 3
• Continue treatment until complete symptom control is maintained for at least 3-6 months before considering dose reduction 3
• For patients with cytopenia, repeat complete blood count every 4-6 weeks until cytopenias resolve or underlying cause is identified 3

Clinical Pearls and Pitfalls

Duration Assessment

• Ordinary urticaria wheals typically last 2-24 hours, while physical urticaria resolves in less than 1 hour 2
• If individual lesions persist beyond 24 hours, consider urticarial vasculitis and obtain a skin biopsy 1, 2

Prognosis Considerations

• About 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 2
• Patients with both wheals and angioedema have a poorer prognosis, with over 50% still having active disease after 5 years 2
• More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within one year 4