What is the appropriate workup and treatment for a patient with chronic urticaria (hives)?

Chronic Urticaria Workup and Treatment

The diagnostic workup for chronic urticaria should include a thorough history, physical examination, and basic laboratory tests including differential blood count, C-reactive protein/ESR, total IgE, and IgG-anti-thyroid peroxidase (TPO) levels, followed by a stepwise treatment approach starting with second-generation H1 antihistamines, escalating to omalizumab, and then cyclosporine for refractory cases. 1

Diagnostic Workup

Initial Assessment (The 7 Cs Approach)

1. Confirmation: Rule out differential diagnoses

   • Document duration of symptoms (chronic urticaria defined as >6 weeks)
   • Review photos of wheals/angioedema
   • Assess for characteristic features: pruritic wheals that resolve within 24 hours

2. Causes: Basic laboratory tests should include:

   • Complete blood count with differential
   • C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR)
   • Total IgE levels
   • IgG-anti-thyroid peroxidase (TPO) antibodies 1

3. Cofactors: Identify triggers and aggravating factors

   • NSAIDs, aspirin
   • Food additives/pseudoallergens
   • Physical stimuli (pressure, cold, heat)

4. Comorbidities: Check for associated conditions

   • Thyroid autoimmunity (present in 14% of chronic urticaria vs. 6% in general population) 1
   • Consider screening for other autoimmune diseases in refractory cases

5. Consequences: Assess impact on quality of life

   • Use validated tools like Urticaria Control Test (UCT) and/or Angioedema Control Test (AECT) 1

Additional Testing (Only When Indicated)

• For suspected physical urticarias: Specific provocation testing
• For angioedema without wheals: Serum C4 (screening for C1 inhibitor deficiency)
• For suspected urticarial vasculitis: Skin biopsy
• For antihistamine-resistant cases: Consider CU index to detect antibodies against IgE or FcεRI 1

Pitfall to Avoid: Extensive laboratory testing is unnecessary for most patients with chronic urticaria and leads to increased costs without improving outcomes. The diagnosis is primarily clinical. 1

Treatment Algorithm

Step 1: First-Line Treatment

• Second-generation H1 antihistamines at standard doses
  • Options include desloratadine, fexofenadine, levocetirizine, or mizolastine 2
  • Avoid sedating antihistamines as first-line due to cognitive impairment

Step 2: If Inadequate Response After 2-4 Weeks

• Increase second-generation H1 antihistamine up to 4× the standard dose
• Consider adding:
  • H2 antihistamines
  • Leukotriene receptor antagonists (montelukast)
  • First-generation H1 antihistamines at bedtime if sleep disturbance is significant

Step 3: If Inadequate Response After 2-4 Weeks

• Omalizumab 300 mg subcutaneously every 4 weeks 1, 3
  • Allow up to 6 months for response
  • If insufficient response, consider:
    • Shortening the interval between doses
    • Increasing the dose (up to 600 mg every 14 days)
  • Clinical trials show significant reduction in itch severity and hive count compared to placebo 3

Step 4: If Inadequate Response to High-Dose Omalizumab

• Cyclosporine (effective in approximately 75% of patients) 1, 2
  • Monitor blood pressure and renal function every 6 weeks
  • Use lowest effective dose for maintenance

Important Caveat: The risk-benefit profile of high-dose omalizumab is superior to that of cyclosporine, which carries risks of hypertension, renal failure, and other side effects. 1

Monitoring and Follow-up

• Use validated tools to assess disease control:

  • Urticaria Control Test (UCT): Score ≥12 indicates well-controlled disease
  • Angioedema Control Test (AECT): Score ≥10 indicates well-controlled disease
  • 7-Day Urticaria Activity Score: To monitor disease activity 1

• Adjust treatment based on control scores:

  • If well-controlled for 3-6 months, consider step-down therapy
  • If poorly controlled, move to next step in algorithm

Prognosis

• Chronic urticaria resolves spontaneously in 30-55% of patients within 5 years 2
• More than half of patients will have resolution or improvement within one year 4
• Treatment should follow the "as much as needed and as little as possible" approach, stepping up and down as required 1

Remember that the primary goal of treatment is complete control of symptoms to improve quality of life, which often requires adjustments to therapy based on individual response.