What is the recommended treatment for urticaria (hives)?

Treatment for Hives (Urticaria)

Start with a standard-dose second-generation non-sedating H1 antihistamine (cetirizine, loratadine, desloratadine, fexofenadine, or levocetirizine), and if symptoms persist after 2-4 weeks, increase the dose up to 4 times the standard dose before considering additional therapies. 1, 2, 3

First-Line Treatment: Second-Generation Antihistamines

• Begin with standard dosing of a second-generation antihistamine such as cetirizine, loratadine, desloratadine, fexofenadine, or levocetirizine 2, 3, 4
• Offer patients at least two different antihistamines to trial, as individual response and tolerance vary significantly between patients 2, 3, 4
• Cetirizine has the shortest time to maximum concentration, making it the preferred choice when rapid symptom relief is needed 2, 3
• These agents are as effective as first-generation antihistamines like hydroxyzine but without the sedation and anticholinergic side effects 5, 6, 7

Dose Escalation Strategy

• If inadequate control after 2-4 weeks (or earlier if symptoms are intolerable), increase the antihistamine dose up to 4 times the standard dose 1, 2, 3
• This approach is supported by the international urticaria guideline's "as much as needed and as little as possible" philosophy 1
• Up-dosing higher than fourfold (median dosage 8, range 5-12 times standard) has been shown effective in 49% of patients who fail fourfold dosing, with minimal increase in side effects (10% reported adverse effects) 8
• Complete disease control should be maintained for at least 3 consecutive months before attempting step-down, reducing by no more than 1 tablet per month 1

Second-Line Treatment: Omalizumab

• For chronic spontaneous urticaria unresponsive to high-dose antihistamines, add omalizumab 300 mg subcutaneously every 4 weeks 1, 3, 4
• The dose can be increased to 600 mg every 2 weeks in patients with insufficient response 1
• Allow up to 6 months to evaluate response before declaring treatment failure 2, 3, 4
• Approximately 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 3

Third-Line Treatment: Cyclosporine

• For patients who fail both high-dose antihistamines and omalizumab within 6 months, add cyclosporine at 4-5 mg/kg daily 1, 3, 4
• Treatment duration is typically up to 2 months 2, 3, 4
• Cyclosporine is effective in approximately 54-73% of patients, particularly those with autoimmune chronic spontaneous urticaria 3, 4
• Mandatory monitoring of blood pressure and renal function is required due to potential nephrotoxicity and hypertension 3, 4

Role of Corticosteroids: Use Sparingly

• Oral corticosteroids should be restricted to short courses of 3-10 days only for severe acute exacerbations or angioedema involving the mouth 2, 3, 4
• Long-term oral corticosteroids should not be used in chronic urticaria except in highly selected cases under specialist supervision 2
• Corticosteroids have slow onset of action (work by inhibiting gene expression) and are ineffective for acute symptom relief 3
• Chronic use leads to cumulative toxicity that outweighs any benefit 3

Adjunctive Measures and Trigger Avoidance

• Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 2, 3, 4
• Avoid NSAIDs in aspirin-sensitive patients with urticaria 2, 3, 4
• Avoid ACE inhibitors in patients with angioedema without wheals 3, 4
• Cooling lotions can provide additional symptomatic relief 2
• Control environmental temperature to decrease symptoms and reduce the need for antihistamines 2

Critical Management Pitfalls

• Never use antihistamines or corticosteroids in place of epinephrine for anaphylaxis 3
• Antihistamines take 30-120 minutes to reach peak plasma concentrations and lack the vasoconstrictive, bronchodilatory, and mast cell stabilization properties of epinephrine 3
• Avoid first-generation antihistamines in acute infusion reactions, as they can exacerbate hypotension, tachycardia, and shock 3
• Intramuscular epinephrine is life-saving in anaphylaxis and severe laryngeal angioedema: 300 µg for adults/adolescents or 150 µg for children weighing 15-30 kg 2, 4

Special Population Adjustments

Renal Impairment

• Avoid acrivastine in moderate renal impairment 3, 4
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment 3, 4

Hepatic Impairment

• Avoid mizolastine in significant hepatic impairment 3, 4
• Avoid hydroxyzine in severe liver disease 3, 4

Pregnancy

• Avoid antihistamines if possible, especially during the first trimester 3, 4
• If necessary, choose chlorphenamine due to its long safety record 3, 4
• Fexofenadine is Category C: use only if potential benefit justifies potential risk to the fetus 9

Pediatric Patients

• The same stepwise approach applies to children, starting with standard-dose second-generation antihistamines 2
• Safety and effectiveness in children under 6 years of age have not been established 9

Prognosis

• Approximately 50% of patients with chronic urticaria presenting with wheals alone will be symptom-free within 6 months 2, 3, 4
• Patients with both wheals and angioedema have a poorer prognosis, with over 50% still having active disease after 5 years 2, 3, 4