What is the initial workup and treatment for hives (urticaria) of unknown origin?

Initial Workup and Treatment for Hives (Urticaria) of Unknown Origin

The first-line treatment for urticaria of unknown origin is second-generation H1 antihistamines, with dose escalation up to four times the standard dose for inadequate response. 1

Diagnostic Workup

For hives of unknown origin, the diagnostic approach should be targeted and limited:

• Classification by duration:

  • Acute urticaria: < 6 weeks
  • Chronic urticaria: > 6 weeks 1, 2

• Limited laboratory workup is recommended unless specific underlying conditions are suspected 1

  • Extensive testing is unnecessary for most cases of urticaria 1
  • In chronic urticaria, the cause remains unknown in >75% of cases 3

• Key clinical features to assess:

  • Duration of individual wheals (typically <24 hours)
  • Presence of angioedema
  • Potential triggers (foods, medications, physical stimuli)
  • Signs of systemic involvement or anaphylaxis 2, 4

Treatment Algorithm

First-Line Treatment:

• Second-generation (non-sedating) H1 antihistamines 1, 2
  • Examples: fexofenadine 180mg, cetirizine 10mg, loratadine 10mg
  • These are preferred due to minimal sedation and longer duration of action

For Inadequate Response:

1. Increase antihistamine dose up to 4× standard dose 1
2. Add H2 antihistamines as adjunctive therapy 1, 3
   • Examples: ranitidine, cimetidine
   • The combination of H1 and H2 antagonists may be more effective than H1 antagonists alone 5, 3

For Resistant Cases:

• Consider leukotriene receptor antagonists 1
• For chronic urticaria unresponsive to antihistamines:
  • Omalizumab (anti-IgE) 1, 6
  • Cyclosporine (particularly effective in autoimmune urticaria) 1, 6

For Severe Acute Episodes:

• Short courses of systemic corticosteroids may be considered, though evidence is mixed 7
• Note: The addition of corticosteroids to antihistamines did not improve symptoms in two out of three RCTs 7

Special Considerations

• Anaphylaxis: If urticaria is accompanied by signs of anaphylaxis (respiratory distress, hypotension), administer epinephrine 0.3 mg IM in the mid-anterolateral thigh and seek immediate emergency care 1

• Treatment reassessment: Regularly assess treatment response using validated tools like the Urticaria Activity Score (UAS7), with reassessment within 1-2 weeks of initiating or changing therapy 1

• Avoidance of triggers: Identify and avoid potential triggers when possible 2

• Physical urticarias: These require specific evaluation and treatment approaches 3

Important Caveats

• More than 50% of patients with chronic urticaria will have resolution or improvement of symptoms within a year 2

• First-generation antihistamines (like diphenhydramine) should be used cautiously due to sedative effects, but may be useful for nighttime symptoms 5, 2

• Topical treatments have limited evidence in urticaria management; topical doxepin has some evidence but should be limited to 8 days and 10% of body surface area (maximum 12 g daily) due to risk of allergic contact dermatitis 5

• Crotamiton, calamine lotion, and topical capsaicin are not recommended for treatment of generalized pruritus 5