What is the recommended treatment for urticaria?

Urticaria Treatment

Start with a standard-dose second-generation H1 antihistamine (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine), and 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

First-Line Treatment: Second-Generation Antihistamines

• Second-generation non-sedating H1 antihistamines are the definitive first-line treatment for both acute and chronic urticaria 2, 3

• Preferred agents include cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine 1, 2

• Offer patients at least two different non-sedating antihistamines to trial, as individual responses and tolerance vary significantly between agents 2, 3

• Cetirizine reaches maximum concentration fastest, making it advantageous when rapid symptom relief is needed 2

• These agents are equally effective as first-generation antihistamines like hydroxyzine but without the problematic CNS sedation and anticholinergic side effects 4, 5

Dose Escalation Strategy

• If symptoms persist after 2-4 weeks on standard dosing, increase the antihistamine dose up to 4 times the standard dose before considering additional therapies 1, 2

• This updosing approach is critical—do not prematurely add second-line agents 1, 2

• First-generation antihistamines may be added at night for additional symptom control if needed 3

Second-Line Treatment: Omalizumab

• For chronic spontaneous urticaria unresponsive to high-dose antihistamines, add omalizumab 300 mg subcutaneously every 4 weeks 1, 2, 3

• This recommendation is based on robust double-blind placebo-controlled studies demonstrating efficacy 1

• Allow up to 6 months for patients to respond to omalizumab before declaring treatment failure 1, 2

• In patients with insufficient response, updosing should be considered by shortening the interval and/or increasing the dosage 1

• The maximum recommended dose is 600 mg every 2 weeks, particularly beneficial in patients with high body mass index 1, 2

• Approximately 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 2

• The risk-benefit profile of high-dose omalizumab is superior to cyclosporine 1

Third-Line Treatment: Cyclosporine

• For patients who fail to respond to high-dose antihistamines and omalizumab within 6 months, add cyclosporine at 4-5 mg/kg daily 1, 2, 3

• Cyclosporine is effective in approximately 54-73% of patients, particularly those with autoimmune chronic spontaneous urticaria 2, 3

• Treatment duration is typically up to 2 months, though 16 weeks is superior to 8 weeks for reducing therapeutic failures 2, 6

• Monitor blood pressure and renal function (blood urea nitrogen and creatinine) every 6 weeks due to potential nephrotoxicity, hypertension, epilepsy risk in predisposed patients, hirsutism, and gum hypertrophy 1, 2

Role of Corticosteroids: Critical Limitation

• Oral corticosteroids should be restricted to short courses (3-10 days) for severe acute urticaria or angioedema only—never for chronic management 2, 6, 3

• Corticosteroids have slow onset of action, work by inhibiting gene expression, and are ineffective for acute symptom relief 2

• Chronic use leads to cumulative toxicity that outweighs any benefit 2, 6

• Long-term oral corticosteroids should not be used except in very selected cases under regular specialist supervision 6

Treatment Step-Down Protocol

• Use an "as much as needed and as little as possible" approach by stepping up and stepping down treatment based on disease control 1

• Patients should not step down a higher than standard-dosed antihistamine before completing at least 3 consecutive months of complete control 1

• Reduce the daily dose by no more than 1 tablet per month 1

• When control is lost during step-down, return to the last dose that previously provided complete control 1

Trigger Identification and Avoidance

• Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 2, 6, 3

• Avoid NSAIDs in aspirin-sensitive patients with urticaria 2, 3

• Avoid ACE inhibitors in patients with angioedema without wheals 2, 3

Special Population Adjustments

Renal Impairment

• Avoid acrivastine in moderate renal impairment 2, 3
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 2, 3

Hepatic Impairment

• Avoid mizolastine in significant hepatic impairment 2, 3
• Avoid hydroxyzine in severe liver disease 2, 3

Pregnancy

• Avoid antihistamines if possible, especially during the first trimester 2, 3
• If necessary, choose chlorphenamine due to its long safety record 2, 3

Critical Management Pitfalls

• Never use antihistamines or corticosteroids in place of epinephrine for anaphylaxis 2

• Antihistamines take 30-120 minutes to reach peak plasma concentrations and lack the vasoconstrictive, bronchodilatory, and mast cell stabilization properties of epinephrine 2

• Avoid first-generation antihistamines in acute infusion reactions, as they can exacerbate hypotension, tachycardia, and shock 2

• Do not confuse cholinergic urticaria (punctate 1-3 mm wheals after core temperature increase) with exercise-induced anaphylaxis, which requires immediate epinephrine 6

Prognosis and Patient Counseling

• Approximately 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 2, 3

• Patients with both wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 2, 3