What is the recommended management for chronic spontaneous urticaria?

Management of Chronic Spontaneous Urticaria

The recommended first-line treatment for chronic spontaneous urticaria (CSU) is second-generation H1 antihistamines, which should be up-dosed up to 4 times the standard dose if symptoms persist, followed by omalizumab 300mg subcutaneously every 4 weeks for antihistamine-refractory cases. 1

Diagnostic Approach

Before initiating treatment, confirm the diagnosis of CSU by:

• Ensuring wheals and/or angioedema have persisted for >6 weeks
• Ruling out other conditions using the diagnostic algorithm:
  • Average wheal duration <24 hours (wheals lasting >24 hours suggest urticarial vasculitis)
  • No association with fever, joint pain, or systemic symptoms (which suggest autoinflammatory disease)
  • No association with ACE inhibitor use (which can cause angioedema) 2

Treatment Algorithm

Step 1: Second-generation H1 Antihistamines

• Initial treatment: Standard dose of second-generation H1 antihistamines:

  • Cetirizine 10 mg/day
  • Loratadine 10 mg/day
  • Fexofenadine 180 mg/day
  • Desloratadine 5 mg/day 1

• Important: Avoid first-generation antihistamines (e.g., hydroxyzine, diphenhydramine) due to sedating and anticholinergic effects 1, 3

• If inadequate response after 2 weeks: Increase dose up to 4 times the standard dose:

  • Cetirizine up to 40 mg/day
  • Loratadine up to 40 mg/day
  • Fexofenadine up to 720 mg/day 1, 4

• Evidence for up-dosing: Studies show that up-dosing antihistamines to 4 times the standard dose can achieve sufficient response in approximately 23% of patients who failed standard dosing 4

Step 2: Omalizumab

• For patients with inadequate response to high-dose antihistamines, add omalizumab 300 mg subcutaneously every 4 weeks 1, 5
• Omalizumab is effective in approximately 65-87% of antihistamine-refractory patients 1, 6
• FDA-approved specifically for CSU in patients 12 years and older who remain symptomatic despite H1 antihistamine treatment 5
• Duration of therapy: Periodically reassess the need for continued therapy 5

Step 3: Cyclosporine

• For patients unresponsive to both high-dose antihistamines and omalizumab, consider cyclosporine 6
• Dosage: Up to 5 mg/kg body weight 1
• Effective in 65-70% of patients refractory to antihistamines and omalizumab 6
• Caution: Requires monitoring of blood pressure and renal function every 6 weeks 1

Monitoring and Assessment

• Use validated tools to monitor disease activity and treatment response:
  • 7-Day Urticaria Activity Score (UAS7): Scores wheals (0-3) and pruritus (0-3) daily for a week
  • Urticaria Control Test (UCT) 2, 1
• Evaluate response to treatment after 2 weeks before modifying therapy 1

Important Considerations and Caveats

• Corticosteroids: Should not be used chronically due to cumulative toxicity. Reserve for severe exacerbations in short courses (3-10 days) only 1, 6

• Ineffective adjuncts: H2-receptor blockers and leukotriene antagonists are no longer recommended as they add little benefit 6

• Safety of up-dosing: Studies show that up-dosing antihistamines higher than 4-fold can be effective in approximately 49% of patients who failed standard 4-fold dosing, with minimal increase in side effects (10%) 4

• Most common side effects: Somnolence (17%) and headache are the most commonly reported side effects of high-dose antihistamine therapy 4, 7

• Bilastine, fexofenadine, levocetirizine, and cetirizine have Grade A recommendation for up-dosing in non-responsive CSU patients, with bilastine and levocetirizine safely up-dosed to four times the standard dose 8

• Cetirizine may have increased risk of dose-related sedation compared to other second-generation antihistamines when up-dosed 8

By following this stepwise approach, approximately 70-80% of CSU patients can achieve adequate symptom control, significantly improving their quality of life.