What to do if acute urticaria doesn't settle with antihistamines?

Management of Antihistamine-Resistant Acute Urticaria

For acute urticaria that doesn't respond to standard-dose antihistamines, increase the dose of second-generation H1-antihistamines up to 4 times the standard dose before considering other interventions. 1, 2

Stepwise Treatment Algorithm

Step 1: Optimize Antihistamine Therapy

• Increase the dose of your current second-generation H1-antihistamine (cetirizine, loratadine, fexofenadine, levocetirizine, or desloratadine) up to 4 times the standard dose if symptoms persist after 2-4 weeks at standard dosing 3, 1, 2
• This approach has become common practice when potential benefits outweigh risks, though it exceeds manufacturer's licensed recommendations 3
• If one antihistamine fails at high doses, trial a different second-generation antihistamine, as individual responses vary significantly 1, 4

Step 2: Add Adjunctive Agents for Resistant Cases

• Add an H2-antihistamine (ranitidine or famotidine) to your H1-antihistamine regimen for additional histamine receptor blockade 3, 1
• Consider adding a leukotriene receptor antagonist (montelukast) as combination therapy, particularly useful in resistant cases 3, 1
• Add a first-generation antihistamine (hydroxyzine or chlorpheniramine) at bedtime only if sleep disturbance from pruritus is significant, though avoid as daytime monotherapy due to sedation 2, 5

Step 3: Short-Course Corticosteroids for Severe Cases

• Use oral corticosteroids (prednisolone 50 mg daily for 3 days in adults, adjust for children) ONLY for severe acute urticaria or angioedema affecting the mouth 3, 1, 2
• The evidence for corticosteroid benefit in acute urticaria is questionable, and recent systematic reviews show that adding prednisone to antihistamines did not improve symptoms in 2 out of 3 RCTs 6
• Do NOT continue corticosteroids beyond 3-10 days due to cumulative toxicity that is dose and time dependent 5, 2
• Avoid long-term corticosteroid use except in very selected cases under specialist supervision 2, 4

Critical Diagnostic Considerations

Rule Out Urticarial Vasculitis

• If wheals last longer than 24 hours, perform a skin biopsy to evaluate for urticarial vasculitis, which requires different management 3, 1, 4
• Ordinary acute urticaria wheals typically last 2-24 hours, while physical urticaria wheals last less than 1 hour (except delayed pressure urticaria) 3

Identify and Eliminate Triggers

• Minimize aggravating factors: overheating, stress, alcohol 1, 2, 4
• Avoid medications that worsen urticaria: aspirin, NSAIDs, codeine, ACE inhibitors 1, 2, 4
• Consider food allergy testing only if there is supportive clinical history, particularly in children under 5 years with refractory disease 3

Common Pitfalls to Avoid

• Don't use first-generation antihistamines as first-line monotherapy due to sedating properties that impair school/work performance and have not shown superior efficacy to non-sedating antihistamines in head-to-head trials 2, 7
• Don't perform extensive laboratory workups unless specific underlying conditions are suggested by history or physical examination 8
• Don't use topical antihistamines as they are generally not recommended 3
• Don't continue standard-dose antihistamines for weeks without escalation if inadequate response is evident after 2-4 weeks 1, 2

When to Refer to Specialist

If acute urticaria persists beyond 6 weeks (becoming chronic urticaria by definition), or if the above measures fail to control severe symptoms, refer to allergy/immunology or dermatology for consideration of:

• Omalizumab 300 mg every 4 weeks (effective in 70% of antihistamine-refractory patients) 5, 9, 8
• Cyclosporine (up to 5 mg/kg body weight, effective in 65-70% of resistant cases, requires monitoring of blood pressure and renal function every 6 weeks) 1, 5, 9

Emergency Management

Administer intramuscular epinephrine immediately for anaphylaxis or severe laryngeal angioedema: 150 µg for children 15-30 kg, 300 µg for those over 30 kg and adults 2

Prognosis and Patient Education

Approximately 50% of patients with acute urticaria presenting with wheals alone will be clear by 6 months, though those with wheals and angioedema may have a more prolonged course 3, 2