What is the recommended treatment for urticaria?

Treatment of Urticaria

The recommended first-line treatment for urticaria is second-generation non-sedating H1 antihistamines, which can be up-dosed to 4 times the standard dose if symptoms persist, followed by omalizumab as second-line therapy and cyclosporine as third-line therapy for chronic spontaneous urticaria. 1, 2, 3, 4

First-Line Treatment: Second-Generation H1 Antihistamines

• Start with standard dose of second-generation non-sedating H1 antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, mizolastine) 2, 3
• Offer at least two different non-sedating antihistamines as responses and tolerance vary between individuals 2, 4
• For inadequate symptom control after 2-4 weeks (or earlier if symptoms are intolerable), increase the dose up to 4 times the standard dose 1, 2, 4
• First-generation antihistamines should be avoided due to sedative and anticholinergic effects, except possibly at night for additional symptom control 2, 5

Dose Escalation Protocol

• Do not reduce the antihistamine dose before completing at least 3 consecutive months of complete control 1
• When stepping down, reduce the daily dose by no more than 1 tablet per month 1
• If control is lost during step-down, return to the last dose that provided complete control 1

Second-Line Treatment: Omalizumab

• For patients with chronic spontaneous urticaria unresponsive to high-dose antihistamines, add omalizumab (anti-IgE monoclonal antibody) 1, 2, 4
• Standard starting dose is 300 mg subcutaneously every 4 weeks, with option to increase to 600 mg every 2 weeks in patients with insufficient response 4, 6
• Allow up to 6 months for patients to respond to omalizumab before considering alternative treatments 2, 4
• FDA-approved for chronic spontaneous urticaria in adults and adolescents 12 years and older 6

Third-Line Treatment: Cyclosporine

• For patients who do not respond to high-dose antihistamines and omalizumab, add cyclosporine 1, 2, 4
• Recommended dose is 4-5 mg/kg body weight daily 1, 2, 4
• Regular monitoring of blood pressure and renal function is required due to potential side effects 2, 4
• Effective in about two-thirds of patients with severe autoimmune urticaria 3, 4

Special Considerations

Corticosteroids

• Oral corticosteroids should be restricted to short courses for severe acute urticaria or angioedema affecting the mouth 2
• Not recommended for long-term management due to side effect profile 7

Angioedema

• For hereditary angioedema, C1 inhibitor concentrate should be given for emergency treatment of serious attacks or as prophylaxis before surgery 2
• ACE inhibitors should be avoided in patients with angioedema without wheals 2, 3

General Measures

• Identify and minimize aggravating factors such as overheating, stress, alcohol, and certain medications (aspirin, NSAIDs, codeine) 2, 3, 4
• NSAIDs should be avoided in aspirin-sensitive patients with urticaria 2, 3
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief 3, 4

Treatment Approach Algorithm

1. Start with standard dose second-generation H1 antihistamine 1, 2
2. If inadequate control after 2-4 weeks (or earlier if symptoms intolerable), increase dose up to 4x standard dose 1, 2
3. If still inadequate control, add omalizumab 300 mg every 4 weeks 1, 2, 6
4. If inadequate response to omalizumab within 6 months, add cyclosporine (up to 5 mg/kg body weight) 1, 2

Prognosis

• About 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 2
• Patients with wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 2, 7

Cautions and Pitfalls

• Up-dosing antihistamines higher than fourfold may be considered in refractory cases, with limited increase in side effects 8
• Monitor for sedation with higher doses of antihistamines, which occurs in approximately 17% of patients 8
• Anaphylaxis can occur with omalizumab, particularly early in treatment, so initial doses should be administered in a healthcare setting 6
• Avoid mizolastine in significant hepatic impairment 2, 4
• In renal impairment, avoid acrivastine and halve the dose of cetirizine and levocetirizine 2, 4