What is the recommended management for acute urticaria and chronic spontaneous urticaria?

Management of Urticaria

First-Line Treatment: Second-Generation H1-Antihistamines

Start all patients with urticaria on standard-dose second-generation H1-antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine) as first-line therapy. 1

• Second-generation antihistamines are superior to first-generation agents due to reduced sedation, better safety profile, and equivalent or superior efficacy 1, 2, 3
• Offer patients a choice of at least two different non-sedating antihistamines, as individual responses and tolerance vary significantly 4, 2
• Standard dosing achieves adequate control in approximately 40% of patients 5
• Continue treatment for 2-4 weeks before escalating therapy 1, 6

Practical Antihistamine Selection

• Cetirizine has the shortest time to maximum concentration, advantageous when rapid effect is needed 4
• Desloratadine has the longest elimination half-life (27 hours) and requires discontinuation 6 days before skin prick testing 4
• Adjust timing of medication to ensure peak drug levels coincide with anticipated urticaria symptoms 4

Step-Up Approach: High-Dose Antihistamines

If symptoms remain inadequately controlled after 2-4 weeks, increase the second-generation H1-antihistamine dose up to 4 times the standard dose. 1, 2, 5

• Up-dosing achieves sufficient response in approximately 23% of patients who failed standard dosing 1
• Patient surveys demonstrate that 40%, 42%, and 54% report significant added benefit from 2,3, or 4 tablets daily respectively 3
• Up-dosing does not significantly increase unwanted effects or sedation compared to standard doses 3
• This off-label use is common practice when potential benefits outweigh risks 4

Adjunctive Therapies (Limited Evidence)

• Consider adding H2-antihistamines (cimetidine) for resistant cases, though evidence is limited and may be more helpful for accompanying dyspepsia 4, 1
• Antileukotrienes (montelukast) can be added for resistant cases, though efficacy data are limited 4, 1
• Adding sedating antihistamines at night (chlorphenamine 4-12 mg, hydroxyzine 10-50 mg) may help sleep but provides little additional urticaria control if H1 receptors are already saturated 4

Second-Line Treatment: Omalizumab

For patients with inadequate control despite up-dosed antihistamines, add omalizumab 300 mg subcutaneously every 4 weeks. 1, 7, 5

• Omalizumab is effective in approximately 70% of antihistamine-refractory patients 7, 5
• Allow up to 6 months for patients to demonstrate response before considering alternative therapies 1
• At least 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 5
• For insufficient response to standard dosing, consider updosing by shortening the interval and/or increasing dosage to a maximum of 600 mg every 14 days 8

Third-Line Treatment: Cyclosporine

If inadequate control persists with omalizumab, add cyclosporine at doses up to 5 mg/kg body weight to the antihistamine regimen. 1, 8, 7

• Cyclosporine improves symptoms in approximately 54-73% of patients, especially those with autoimmune chronic spontaneous urticaria and omalizumab nonresponse 7, 5
• Monitor blood pressure and renal function every 6 weeks due to risks of kidney dysfunction and hypertension 1, 8
• This is particularly effective for patients with IgG-mediated autoimmune endotypes 5

Corticosteroid Use: Severe Exacerbations Only

Restrict oral corticosteroids to short courses (3-10 days) for severe acute exacerbations only. 1, 7, 6

• Avoid long-term corticosteroids due to cumulative toxicity including adrenal suppression, osteoporosis, diabetes, hypertension, and Cushing syndrome 1
• Brief courses should be an infrequent occurrence 7
• More prolonged treatment may be necessary specifically for urticarial vasculitis, which requires different management 8

Trigger Avoidance and General Measures

• Avoid NSAIDs, aspirin, codeine, alcohol, and stress, which can worsen urticaria 1, 2
• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 2
• Prevent skin drying, avoid hot showers, scrubbing, and excessive sun exposure 6

Monitoring and Step-Down Strategy

Use the Urticaria Control Test (UCT) every 4 weeks to assess disease control. 1

• Once complete symptom control is achieved, maintain the effective dose for at least 3 consecutive months before stepping down 1, 2
• When stepping down, reduce the daily dose by no more than 1 tablet per month 1, 2
• If symptoms recur during step-down, return to the last effective dose that provided complete control 1, 2
• The 7-Day Urticaria Activity Score (UAS7) provides objective measurement of disease activity (range 0-42) 1

Critical Diagnostic Distinctions

Distinguish chronic spontaneous urticaria (wheals lasting 2-24 hours) from urticarial vasculitis (lesions lasting >24 hours), as management differs fundamentally. 1, 8

• Urticarial vasculitis requires lesional skin biopsy for confirmation and may need prolonged corticosteroid therapy 8
• Physical urticarias typically resolve within 1 hour, except delayed pressure urticaria which can last up to 48 hours 2
• Isolated or recurrent angioedema without wheals warrants evaluation for hereditary or acquired angioedema, requiring specialist referral 1

Special Population Considerations

Renal Impairment

• Avoid acrivastine in moderate renal impairment (creatinine clearance 10-20 mL/min) 4
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate impairment 4
• Avoid cetirizine and levocetirizine in severe renal impairment (creatinine clearance <10 mL/min) 4

Hepatic Impairment

• Mizolastine is contraindicated in significant hepatic impairment 4
• Avoid chlorphenamine and hydroxyzine in severe liver disease due to inappropriate sedating effects 4

Pregnancy

• Avoid all antihistamines when possible, especially during first trimester 4
• Chlorphenamine is often chosen when antihistamine therapy is necessary due to long safety record 4
• Loratadine and cetirizine are FDA Pregnancy Category B drugs 4