What is the recommended oral management for urticaria?

Oral Management of Urticaria

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

Step 1: Initial Treatment with Second-Generation Antihistamines

• Begin with standard-dose second-generation H1 antihistamines as definitive first-line therapy 1, 2
• Offer patients at least two different non-sedating antihistamines to trial, as individual responses and tolerance vary significantly between agents 2, 3
• Preferred options include cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine 2, 3
• Cetirizine reaches maximum concentration fastest, making it advantageous when rapid symptom relief is needed 2

Step 2: Dose Escalation for Inadequate Control

If symptoms remain inadequately controlled after 2-4 weeks (or earlier if symptoms are intolerable), increase the antihistamine dose up to 4-fold the standard dose. 1, 2

• This dose escalation is now common practice when potential benefits outweigh risks 1
• Bilastine, fexofenadine, levocetirizine, and cetirizine have Grade A evidence supporting up-dosing 4
• Desloratadine and ebastine have Grade B evidence for up-dosing 4
• Higher-than-fourfold dosing (up to 8-12 times standard dose) has been shown effective in 49% of patients who fail fourfold dosing, with minimal increase in side effects 5
• The most common side effect is somnolence (17% of patients), with cetirizine having the highest risk of dose-related sedation 5, 4

Step 3: Add Omalizumab for Chronic Spontaneous Urticaria

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

• Allow up to 6 months for patients to respond before declaring treatment failure 1, 2
• If insufficient response at standard dosing, increase to 600 mg every 2 weeks 1, 2
• Approximately 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 2

Step 4: Add Cyclosporine as Third-Line Therapy

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

• Cyclosporine is effective in approximately 54-73% of patients, particularly those with autoimmune chronic spontaneous urticaria 2
• Mandatory monitoring: Check blood pressure and renal function regularly due to potential nephrotoxicity and hypertension 2, 3

Adjunctive Therapies for Resistant Cases

• Consider adding H2 antihistamines, sedating antihistamines at night, or antileukotrienes for resistant cases 1
• First-generation antihistamines (like hydroxyzine) can be added at night for additional symptom control and to help patients sleep 1, 3

Role of Oral Corticosteroids: Severe Acute Cases Only

Restrict oral corticosteroids to short courses (3-10 days) for severe acute urticaria or angioedema affecting the mouth—never use chronically. 1, 2, 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
• More prolonged treatment may be necessary only for delayed pressure urticaria or urticarial vasculitis 1

Step-Down Protocol for Disease Control

When patients achieve complete disease control (UCT score >16), consider stepping down treatment to reduce burden and assess for spontaneous remission. 1

• Do not step down higher-than-standard-dosed antihistamines before completing at least 3 consecutive months of complete control 1
• Reduce the daily dose by no more than 1 tablet per month 1
• If control is lost during step-down, return to the last dose that provided complete control 1

Trigger Identification and Avoidance

• Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine 2, 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 Pitfall to Avoid

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

Prognosis

• 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