Treatment of Autoimmune Urticaria
Start with second-generation H1 antihistamines at standard doses, escalate up to 4 times the standard dose if inadequate response after 2-4 weeks, then add omalizumab 300 mg subcutaneously every 4 weeks for antihistamine-refractory disease, followed by cyclosporine if omalizumab fails after 6 months. 1, 2
First-Line: Second-Generation H1 Antihistamines
- Begin with a second-generation non-sedating H1 antihistamine (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine) at standard dosing 1
- Offer at least two different non-sedating antihistamines to each patient, as individual responses and tolerance vary significantly between agents 1, 2
- If symptoms remain inadequately controlled after 2-4 weeks, increase the dose up to 4 times the standard dose before adding other therapies 1, 2
- More than 40% of patients with urticaria respond to antihistamines alone, making dose escalation critical before advancing therapy 3, 4
Key point: It has become common practice to increase second-generation H1 antihistamines above the manufacturer's licensed recommendation when potential benefits outweigh risks 3
Second-Line: Omalizumab
- For urticaria unresponsive to high-dose antihistamines (at least 50% of patients), add omalizumab at 300 mg subcutaneously every 4 weeks 1, 5
- Allow up to 6 months for patients to respond to omalizumab before considering it a treatment failure 1, 2
- Omalizumab is effective in approximately 70% of antihistamine-refractory patients 5
- If insufficient response at standard dosing, increase to 600 mg every 2 weeks as the maximum recommended dose 1
Important caveat: At least 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 2
Third-Line: Cyclosporine
- For patients who do not respond to high-dose antihistamines and omalizumab within 6 months, add cyclosporine to the antihistamine regimen at a dose of up to 5 mg/kg body weight 1
- Cyclosporine is effective in approximately 65-70% of patients with severe autoimmune urticaria 1, 5
- A treatment duration of 16 weeks with cyclosporine is superior to 8 weeks for reducing therapeutic failures 1
- Monitor blood pressure and renal function every 6 weeks due to potential nephrotoxicity and hypertension 1, 5
This is particularly relevant for autoimmune urticaria: At least 30% of patients with chronic urticaria have an autoimmune etiology with histamine-releasing autoantibodies, making them candidates for immunomodulating therapies like cyclosporine 3
Role of Corticosteroids (Critical Pitfall)
- Restrict oral corticosteroids to short courses (3-10 days) for severe acute exacerbations only—never use chronically due to cumulative toxicity 1, 4, 5
- Prednisolone 50 mg daily for 3 days is the guideline-recommended regimen for severe acute urticaria in adults 4
- Long-term oral corticosteroids should not be used in chronic urticaria except in very selected cases under regular specialist supervision 1, 4
Most critical error to avoid: Using chronic corticosteroids for chronic spontaneous urticaria leads to cumulative toxicity without sustained benefit 4
Adjunctive Measures
- Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 1, 2
- Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief 1
- Combinations of nonsedating H1 antihistamines with H2 antihistamines or sedating antihistamines at night can be useful for resistant cases, though evidence is limited 3
When to Consider Immunomodulating Therapies
- Immunomodulating therapies for chronic autoimmune urticaria should be restricted to patients with disabling disease who have not responded to optimal conventional treatments 3
- Refractoriness to both omalizumab and cyclosporine is expected in less than 5% of patients 6