Treatment of Chronic Urticaria
Start with a second-generation H1 antihistamine at standard dose, and if symptoms remain inadequately controlled after 2-4 weeks, increase the dose up to 4 times the standard dose before considering other therapies. 1
First-Line Treatment: Second-Generation H1 Antihistamines
Begin with standard-dose second-generation H1 antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine) as these are the mainstay of therapy with superior safety profiles compared to first-generation agents 1, 2
Offer at least two different non-sedating antihistamines to each patient, as individual responses and tolerance vary significantly between agents 3, 2
If inadequate control after 2-4 weeks, up-dose to 4 times the standard dose before moving to second-line therapy 3, 1, 2
Avoid first-generation sedating antihistamines (diphenhydramine, hydroxyzine) as first-line therapy due to significant sedation, cognitive impairment, and altered REM sleep patterns without superior efficacy 2, 6
Second-Line Treatment: Omalizumab
For urticaria unresponsive to high-dose antihistamines, add omalizumab 300 mg subcutaneously every 4 weeks 3, 1, 7
Allow up to 6 months for response before considering treatment failure 3, 1, 2
- At least 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 8
If insufficient response at standard dosing, increase to 600 mg every 2 weeks as the maximum recommended dose 3
Critical safety warning: Omalizumab carries a black box warning for anaphylaxis, which can occur after the first dose or beyond 1 year of treatment; initiate therapy in a healthcare setting with appropriate observation period 7
Third-Line Treatment: Cyclosporine
For patients who fail both high-dose antihistamines and omalizumab within 6 months, add cyclosporine at up to 5 mg/kg body weight to the antihistamine regimen 3, 1, 2
Cyclosporine is effective in approximately 54-73% of patients with severe urticaria, particularly those with autoimmune chronic spontaneous urticaria 9, 8
Monitor blood pressure and renal function every 6 weeks due to potential nephrotoxicity and hypertension 3, 1, 2
Treatment duration of 16 weeks is superior to 8 weeks for reducing therapeutic failures 3
Role of Corticosteroids
- Restrict oral corticosteroids to short courses (3-10 days) for severe acute exacerbations only—never use as maintenance therapy due to cumulative toxicity including adrenal suppression, osteoporosis, diabetes, hypertension, and Cushing syndrome 4, 3, 2
Adjunctive Therapies (Limited Evidence)
Consider adding H2-antihistamines (cimetidine) in combination with H1-antihistamines for resistant cases, though evidence is limited 4, 2
Antileukotrienes (montelukast) can be useful for resistant cases as add-on therapy 4
Low-dose doxepin is effective and especially suitable for patients with associated depression 9
Treatment Monitoring and Step-Down
Use the Urticaria Control Test (UCT) to assess disease control 1
Once complete symptom control is achieved, maintain the effective dose for at least 3 consecutive months before considering step-down 1
When stepping down, reduce the daily dose 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
Trigger Avoidance
Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 3, 2
Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief 3, 2
Important Diagnostic Considerations
Distinguish chronic spontaneous urticaria (lesions lasting 2-24 hours) from urticarial vasculitis (lesions lasting >24 hours), as the latter requires skin biopsy for confirmation and different management 4, 1
In patients with angioedema without wheals, test serum C4 to screen for hereditary or acquired C1 inhibitor deficiency, and avoid ACE inhibitors 2