What is the recommended workup and treatment for chronic urticaria?

Workup and Treatment for Chronic Urticaria

The recommended workup for chronic urticaria should be limited to clinical classification based on presentation, with minimal laboratory testing, followed by a stepwise treatment approach starting with second-generation H1 antihistamines at standard doses and up-titrating to 4x the standard dose if needed. 1, 2

Diagnostic Workup

Clinical Classification

• Determine duration of wheals:
  • Physical urticaria: wheals typically last <1 hour (except delayed pressure urticaria)
  • Ordinary chronic urticaria: wheals last 2-24 hours
  • Urticarial vasculitis: consider if wheals last >24 hours (confirm with skin biopsy)

Laboratory Testing

• Minimal laboratory testing is recommended for most cases of chronic urticaria 1
• Consider only targeted testing based on history and physical findings:
  • Anti-thyroid peroxidase antibodies (30% of chronic urticaria patients have autoimmune etiology) 1
  • Autologous serum skin test (ASST) may identify patients with autoimmune urticaria 1
  • Skin biopsy only if urticarial vasculitis is suspected (wheals lasting >24 hours)

Treatment Algorithm

First-Line Treatment

1. Start with standard dose second-generation H1 antihistamine:

   • Cetirizine 10 mg daily
   • Loratadine 10 mg daily
   • Fexofenadine 180 mg daily
   • Levocetirizine 5 mg daily
   • Desloratadine 5 mg daily

2. If inadequate control after 2-4 weeks:

   • Increase second-generation H1 antihistamine dose up to 4x standard dose 1, 2
   • Example: Cetirizine 10 mg QID or Fexofenadine 180 mg QID

Second-Line Treatment

1. If inadequate control despite up-dosing antihistamines:
   • Add omalizumab 300 mg subcutaneously every 4 weeks 1, 3
   • Can increase to 600 mg every 2 weeks if needed 1

Third-Line Treatment

1. If inadequate control with omalizumab:
   • Add cyclosporine up to 5 mg/kg body weight 1, 2
   • Monitor blood pressure and renal function every 6 weeks

Additional Treatment Strategies

Adjunctive Therapies

• H2 antihistamines may provide additional benefit when added to H1 antihistamines 1, 2
• Consider adding sedating antihistamine at night (e.g., hydroxyzine 10-50 mg) for sleep disturbance 1, 2
• Short courses of oral corticosteroids only for severe acute urticaria or angioedema affecting the mouth 1, 2

Treatment Step-Down

• Do not attempt step-down before completing at least 3 consecutive months of complete control 1
• When stepping down, reduce dose by no more than 1 tablet per month 1
• If symptoms recur during step-down, return to the last effective dose 1, 2

Important Considerations

Safety of Up-Dosing Antihistamines

• Up-dosing second-generation antihistamines to 4x standard dose is safe and effective 4, 5
• Cetirizine may cause dose-related sedation; fexofenadine and bilastine have minimal sedative effects at higher doses 5
• No reports of cardiotoxicity with up-dosing of modern second-generation antihistamines 5

Treatment Duration

• Chronic urticaria resolves spontaneously in 30-55% of patients within 5 years 6
• More than half of patients will have resolution or improvement within one year 7
• Continue treatment as long as symptoms persist, periodically reassessing need for continued therapy 1, 2

Common Pitfalls to Avoid

• Avoid first-generation antihistamines as monotherapy due to sedation and anticholinergic effects 7, 8
• Avoid long-term oral corticosteroids for chronic urticaria due to adverse effects 1, 2
• Avoid premature treatment changes; allow 2-4 weeks to assess response before escalating therapy 2
• Do not rely solely on antihistamines for anaphylaxis or severe angioedema with respiratory/cardiovascular involvement 2

By following this evidence-based approach to diagnosis and treatment, most patients with chronic urticaria can achieve adequate symptom control and improved quality of life.