What is the recommended treatment for a patient presenting with urticaria?

Treatment of Urticaria

Start all patients with urticaria on a second-generation H1-antihistamine (cetirizine, fexofenadine, loratadine, desloratadine, or levocetirizine) at standard dosing, and if inadequate control after 2-4 weeks, increase the dose up to 4 times the standard dose before considering additional therapies. 1, 2

First-Line Treatment Approach

• Begin with second-generation H1-antihistamines as monotherapy, offering patients a choice of at least two different options since individual responses vary significantly 3, 1
• Standard dosing should be maintained for 2-4 weeks before assessing response 1, 2
• Second-generation agents are strongly preferred over first-generation antihistamines due to superior safety profiles and reduced sedation 1
• Over 40% of patients with urticaria show good response to antihistamines alone 3

Dose Escalation Strategy

If symptoms remain inadequately controlled after 2-4 weeks on standard dosing:

• Increase the second-generation H1-antihistamine dose up to 4-fold above the manufacturer's recommended dose 3, 1, 2
• This practice has become standard despite being off-label, as potential benefits outweigh risks in most patients 3, 4
• Continue updosed antihistamines for an adequate trial period before advancing therapy 1

Adjunctive Therapies for Resistant Cases

Add the following sequentially if updosed antihistamines fail:

• H2-antihistamines (ranitidine or famotidine) can be added to H1-antihistamines for additional benefit 3, 1, 4
• Leukotriene receptor antagonists (montelukast) provide benefit particularly in aspirin-sensitive and autoimmune urticaria 1, 4
• First-generation antihistamines at bedtime (hydroxyzine) can help with nocturnal symptoms and sleep disturbance 3, 4

Corticosteroid Use: Strict Limitations

• Restrict oral corticosteroids to short courses only for severe acute urticaria or life-threatening angioedema affecting the airway 3, 4
• Avoid prolonged corticosteroid therapy due to cumulative toxicity including hypertension, hyperglycemia, osteoporosis, and gastric complications 4
• Exceptions include delayed pressure urticaria or urticarial vasculitis, which may require more prolonged courses 3

Second-Line Treatment for Refractory Disease

For patients failing high-dose antihistamines with or without adjunctive therapy:

• Omalizumab 300 mg subcutaneously every 4 weeks is the preferred second-line agent for chronic spontaneous urticaria 1, 4, 2, 5
• Allow up to 6 months for full response assessment 4
• In clinical trials, 36% of patients achieved complete symptom resolution (no itch, no hives) at week 12 with omalizumab 300 mg versus 9% with placebo 5
• Omalizumab is FDA-approved for chronic spontaneous urticaria in patients ≥12 years of age 5

Third-Line Treatment

For patients unresponsive to omalizumab after 6 months:

• Cyclosporine 2.5-5 mg/kg/day divided twice daily (or 4 mg/kg daily for up to 2 months) is effective in approximately 65-70% of severe autoimmune urticaria cases 4, 2
• This should be restricted to patients with disabling disease who have failed all conventional treatments 3
• Regular monitoring for hepatic and renal function is essential 3

General Measures and Trigger Avoidance

All patients should be counseled to:

• Avoid nonspecific aggravating factors including overheating, stress, and alcohol 3, 4
• Avoid aspirin and NSAIDs, which inhibit cyclooxygenase and can exacerbate urticaria in susceptible patients 4
• Avoid codeine and other opiates that can trigger non-immunologic histamine release 3
• Avoid ACE inhibitors if angioedema is present, and use cautiously when angioedema accompanies urticaria 4
• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 1

Special Considerations by Urticaria Type

Physical urticarias:

• Wheals typically resolve within 1 hour (except delayed pressure urticaria, which lasts up to 48 hours) 1
• Treatment follows the same antihistamine-based algorithm, but focus on trigger avoidance specific to the physical stimulus 1
• For cholinergic urticaria specifically, avoid core temperature increases 1

Urticarial vasculitis:

• Suspect when individual wheals persist >24 hours and leave bruising or hyperpigmentation 2
• Obtain skin biopsy for definitive diagnosis as management differs significantly from ordinary urticaria 3, 2

Monitoring and Treatment Adjustment

• Use the Urticaria Control Test (UCT) for patients with wheals ± angioedema; scores <12 indicate poor control requiring treatment escalation 2
• Use the Angioedema Control Test (AECT) for patients with angioedema ± wheals; scores <10 indicate poor control 2
• After achieving complete symptom control for ≥3 consecutive months, consider stepping down therapy gradually, reducing by no more than 1 tablet per month 1
• If symptoms recur during step-down, return to the last effective dose that provided complete control 1

Emergency Management

For severe urticaria with anaphylaxis or airway-threatening angioedema:

• Administer intramuscular epinephrine 0.5 mL of 1:1000 immediately 4
• Follow with antihistamines, corticosteroids, and supportive care as needed 4

Prognosis

• Approximately 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 3, 4
• Patients with both wheals and angioedema have a poorer prognosis, with >50% still having active disease after 5 years 3
• More than half of patients with chronic urticaria will experience resolution or significant improvement within one year 6