What is the first‑line treatment for a patient presenting with urticaria (hives)?

First-Line Treatment for Urticaria

Start with a second-generation non-sedating H1 antihistamine at standard dosing—cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine are all appropriate first-line options. 1

Initial Treatment Approach

• Begin with standard dosing of any second-generation H1 antihistamine, as these are definitively superior to first-generation sedating antihistamines in terms of both efficacy and side effect profile 1, 2
• Offer patients at least two different non-sedating antihistamines to trial, since individual responses and tolerance vary significantly between patients 1, 3
• Choose cetirizine if rapid symptom relief is the priority, as it reaches maximum concentration fastest among the available options 1, 3

The evidence strongly supports second-generation antihistamines over first-generation agents. Patients consistently report that second-generation drugs are more effective and cause significantly fewer unwanted effects, particularly less sedation 2. First-generation antihistamines like diphenhydramine and hydroxyzine cause significant sedation and cognitive impairment without superior efficacy and should be avoided as first-line therapy 4.

Dose Escalation Strategy

• If symptoms persist after 2-4 weeks on standard dosing, increase the dose up to 4 times the standard dose before adding other therapies 1, 3, 4
• Approximately 40-54% of patients report significant added benefit from taking 2-4 tablets daily 2
• Up-dosing does not significantly increase unwanted effects or sedation compared to standard doses 2

Critical Pitfall to Avoid

Do not use on-demand dosing strategies—continuous daily treatment is essential. On-demand H1-antihistamines show minimal beneficial effects on existing wheals, with no improvement in wheal area or volume compared to no treatment 5. A preventive treatment strategy with daily dosing should always be preferred 5.

When First-Line Treatment Fails

If high-dose antihistamines (up to 4x standard dose) fail after 2-4 weeks, add omalizumab 300 mg subcutaneously every 4 weeks 1, 3, 4

• Allow up to 6 months for patients to respond to omalizumab before declaring treatment failure 1, 3, 4
• The dose can be increased to 600 mg every 2 weeks in patients with insufficient response 1, 3

If both high-dose antihistamines and omalizumab fail within 6 months, add cyclosporine at 4-5 mg/kg daily 1, 3, 4

• Cyclosporine is effective in approximately 54-73% of patients 1
• Treatment duration is typically up to 2 months 1
• Mandatory monitoring: check blood pressure and renal function regularly due to potential nephrotoxicity and hypertension 1, 3, 4

Role of Corticosteroids

Restrict oral corticosteroids to short courses (3-10 days) for severe acute urticaria or angioedema only—never use for chronic management 1, 4

• Corticosteroids have slow onset of action and are ineffective for acute symptom relief 1
• Chronic use leads to cumulative toxicity including adrenal suppression, growth interference in children, dermal thinning, hypertension, diabetes, Cushing syndrome, cataracts, muscle weakness, and impaired immune function 4

Adjunctive Measures

• Identify and minimize aggravating factors: overheating, stress, alcohol, aspirin, NSAIDs, and codeine 1, 3, 4
• Avoid NSAIDs in aspirin-sensitive patients with urticaria 1, 3, 4
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief 3, 4

Special Population Adjustments

• Avoid acrivastine in moderate renal impairment 1
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 1
• Avoid mizolastine in significant hepatic impairment 1
• Avoid antihistamines if possible during first trimester of pregnancy; if necessary, choose chlorphenamine due to its long safety record 1