What is the management of persistent urticaria?

Emergency Department Management of Persistent Urticaria

Start with a second-generation non-sedating H1 antihistamine at standard dosing, and if symptoms persist after 2-4 weeks, escalate the dose up to four times the standard dose before considering additional therapies. 1

Immediate ED Assessment and Initial Treatment

First-Line Therapy

• Initiate a second-generation non-sedating H1 antihistamine immediately as the definitive first-line treatment 1, 2
• Preferred agents include: cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine 1
• Choose cetirizine if rapid symptom relief is needed, as it reaches maximum concentration fastest 1, 3
• Offer the patient at least two different non-sedating antihistamines to trial, as individual responses vary significantly 1, 2

Critical Safety Considerations

• Never use antihistamines or corticosteroids in place of epinephrine for anaphylaxis 1
• Antihistamines take 30-120 minutes to reach peak plasma concentrations and lack the vasoconstrictive, bronchodilatory, and mast cell stabilization properties of epinephrine 1
• If angioedema affects the airway or anaphylaxis is present, administer intramuscular epinephrine 0.5 mL of 1:1000 (500 µg) immediately 2

Dose Escalation Strategy for Persistent Symptoms

When Standard Dosing Fails

• If symptoms persist after 2-4 weeks on standard dosing, increase the antihistamine dose up to four times the standard dose before adding other therapies 1, 2
• Bilastine, fexofenadine, levocetirizine, and cetirizine have Grade A evidence for up-dosing 4
• Desloratadine and ebastine have Grade B evidence for up-dosing 4
• Cetirizine up-dosing may increase risk of dose-related sedation, while other agents show no dose-dependent increase in adverse effects 4
• First-generation antihistamines may be added at night for additional symptom control if needed 2

Second-Line Treatment for Refractory Cases

Omalizumab Therapy

• For chronic spontaneous urticaria unresponsive to high-dose antihistamines, add omalizumab 300 mg subcutaneously every 4 weeks 1, 2, 5
• This is FDA-approved for adults and adolescents 12 years and older who remain symptomatic despite H1 antihistamine treatment 5
• The dose can be increased to 600 mg every 2 weeks in patients with insufficient response 1
• Allow up to 6 months for patients to respond before declaring treatment failure 1, 2
• Approximately 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 1

Important Omalizumab Safety Warning

• Anaphylaxis can occur after omalizumab administration, even after the first dose or beyond 1 year of treatment 5
• Initiate therapy in a healthcare setting and observe patients for an appropriate period after administration 5

Third-Line Treatment

Cyclosporine for Severe Refractory Disease

• For patients who fail to respond to high-dose antihistamines and omalizumab within 6 months, add cyclosporine at 4-5 mg/kg daily 1, 2
• Cyclosporine is effective in approximately 54-73% of patients, particularly those with autoimmune chronic spontaneous urticaria 1
• Treatment duration is typically up to 2 months 1, 2
• Regular blood pressure and renal function monitoring is mandatory due to potential nephrotoxicity and hypertension 1, 2

Role of Corticosteroids: Use Sparingly

When to Use Steroids

• Oral corticosteroids should be restricted to short courses for severe acute urticaria or angioedema only—never for chronic management 1, 2
• Corticosteroids have slow onset of action, work by inhibiting gene expression, and are ineffective for acute symptom relief 1
• Chronic use leads to cumulative toxicity that outweighs any benefit 1

Trigger Identification and Avoidance

Key Aggravating Factors to Address

• Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 1, 2, 3
• Avoid NSAIDs in aspirin-sensitive patients with urticaria 1, 2, 3
• Avoid ACE inhibitors in patients with angioedema without wheals 1, 2, 3

Special Population Adjustments

Renal Impairment

• Avoid acrivastine in moderate renal impairment 1, 2
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 1, 2

Hepatic Impairment

• Avoid mizolastine in significant hepatic impairment 1, 2
• Avoid hydroxyzine in severe liver disease 1, 2

Pregnancy

• Avoid antihistamines if possible, especially during the first trimester 1, 2
• If necessary, choose chlorphenamine due to its long safety record 1, 2

Prognosis and Disposition Planning

Expected Disease Course

• Approximately 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 1, 2
• Patients with both wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 1, 2

ED Discharge Instructions

• Prescribe a second-generation antihistamine at standard dosing initially 1
• Arrange follow-up within 2-4 weeks to assess response and consider dose escalation if needed 1
• Provide clear instructions on trigger avoidance 1, 2, 3
• Educate patients on signs of anaphylaxis and when to return to the ED 1