What is the recommended treatment for spontaneous urticaria?

Treatment for Spontaneous Urticaria

The first-line treatment for spontaneous urticaria is a second-generation non-sedating H1 antihistamine, which should be started at standard dose and increased up to fourfold if symptoms persist, following a stepwise approach. 1

First-Line Treatment: Second-Generation Antihistamines

Initial Approach

• Start with a standard dose of a second-generation non-sedating H1 antihistamine
• Options include:
  • Cetirizine 10 mg once daily
  • Loratadine 10 mg once daily
  • Desloratadine 5 mg once daily
  • Fexofenadine 180 mg once daily
  • Levocetirizine 5 mg once daily

Step-Up Approach

If symptoms persist after 2-4 weeks (or earlier if symptoms are intolerable):

1. Increase the dose of the second-generation antihistamine up to fourfold (e.g., cetirizine 40 mg daily) 1
2. This higher-than-licensed dosing has shown effectiveness in up to 49% of patients who fail standard dosing, with minimal increase in side effects 2

Second-Line Treatment: Omalizumab

If inadequate control persists despite up to fourfold antihistamine dosing:

• Add omalizumab 300 mg subcutaneously every 4 weeks 1, 3
• If response is insufficient, consider:
  • Increasing to 600 mg every 2 weeks
  • Allow up to 6 months for response assessment

Third-Line Treatment: Cyclosporine

If inadequate control persists despite optimized omalizumab therapy:

• Add cyclosporine up to 5 mg/kg body weight 1
• Monitor blood pressure and renal function every 6 weeks
• Be aware of potential side effects including hypertension, hirsutism, gum hypertrophy, and renal failure

Special Considerations

Patient Monitoring

• Use the Urticaria Control Test (UCT) to assess disease control
• Follow the "as much as needed and as little as possible" approach 1
• Consider step-down after 3 consecutive months of complete control
• When stepping down, reduce by no more than 1 tablet per month

Special Populations

• Renal impairment: 1

  • Avoid acrivastine in moderate renal impairment
  • Halve the dose of cetirizine, levocetirizine and hydroxyzine
  • Avoid cetirizine, levocetirizine and alimemazine in severe renal impairment
  • Use loratadine and desloratadine with caution in severe renal impairment

• Hepatic impairment: 1

  • Avoid mizolastine in significant hepatic impairment
  • Avoid alimemazine, chlorphenamine, and hydroxyzine in severe liver disease

• Pregnancy: 1

  • Avoid antihistamines if possible, especially in first trimester
  • If necessary, chlorphenamine has the longest safety record
  • Loratadine and cetirizine are FDA Pregnancy Category B drugs

Treatment Pitfalls to Avoid

1. Using first-generation antihistamines as monotherapy (causes sedation and reduced performance) 1
2. Failing to try at least two different non-sedating antihistamines (responses vary between individuals) 1
3. Prematurely advancing to second-line therapy before optimizing antihistamine dosing
4. Not allowing sufficient time (up to 6 months) for omalizumab response before moving to cyclosporine
5. Overlooking the potential for H2 antihistamine addition, which may provide better control in some patients 1

Adjunctive Treatments

• For sleep disturbance: Consider adding a sedating antihistamine at night (e.g., chlorphenamine 4-12 mg, hydroxyzine 10-50 mg) 1
• For associated dyspepsia: Consider adding an H2 antihistamine 1
• For urticaria with angioedema: More aggressive antihistamine up-dosing may be needed, as patients with wheals plus angioedema require up-dosing more frequently (80%) than those with angioedema alone (64%) 2

This stepwise approach to spontaneous urticaria treatment optimizes symptom control while minimizing side effects, significantly improving quality of life for patients with this challenging condition.