Laboratory Testing for Urticaria (Hives)
For most patients with acute urticaria or mild chronic urticaria responding to antihistamines, no laboratory tests are necessary. 1
Diagnostic Approach Based on Clinical Presentation
Acute Urticaria (< 6 weeks duration)
- No routine laboratory testing is recommended unless suggested by specific history 1
- Consider targeted testing only when history suggests:
- IgE-mediated allergic reactions: Skin-prick testing or specific IgE blood tests for suspected allergens (foods, latex, etc.)
- Drug reactions: Detailed medication history
- Suspected infection: Targeted testing based on symptoms
Chronic Urticaria (≥ 6 weeks duration)
For patients with severe or antihistamine-resistant chronic urticaria, a limited screening panel is recommended:
Basic screening tests:
- Complete blood count with differential (to detect eosinophilia or leukopenia)
- Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
- Thyroid function tests and thyroid autoantibodies (especially if autoimmune etiology suspected)
Additional tests based on clinical suspicion:
- Autologous serum skin test (ASST) to screen for autoimmune urticaria (in specialized centers)
- Complement C4 level (if angioedema without wheals is present)
- Skin biopsy (if urticarial vasculitis suspected - lesions lasting >24 hours with purpura)
Special Clinical Scenarios
Chronic Urticaria with Angioedema
- Serum C4 as initial screening test for hereditary/acquired C1 inhibitor deficiency
- If C4 is low, proceed with quantitative and functional C1 inhibitor assays
- C1q levels (reduced in acquired C1 inhibitor deficiency)
Physical Urticarias
- Provocation testing to confirm diagnosis and assess trigger thresholds
- Examples: ice cube test for cold urticaria, pressure testing for delayed pressure urticaria
Urticarial Vasculitis
- Skin biopsy is essential for diagnosis
- Full vasculitis screen including complement levels (C3, C4)
- Autoimmune panel if systemic involvement suspected
Common Pitfalls to Avoid
Overinvestigation: Extensive laboratory testing is rarely helpful and not cost-effective for most patients with urticaria
Underinvestigation: Missing potential systemic causes in patients with chronic, treatment-resistant urticaria
Misinterpretation: Positive autoantibody tests without clinical correlation may lead to unnecessary treatments
Delayed diagnosis: Failing to recognize urticarial vasculitis or hereditary angioedema which require specific management
Clinical Pearls
- The diagnostic algorithm should be guided by clinical presentation and response to initial therapy
- Consider thyroid autoimmunity testing as it's present in 14% of chronic urticaria patients versus 6% in the general population 1
- Chronic urticaria may have an autoimmune basis in approximately 40-45% of cases 2, 3
- For patients with chronic urticaria, consider testing for Helicobacter pylori if other causes are not identified 1
- Recognize that in most cases of chronic urticaria (up to 80%), a specific cause will not be identified despite testing 4
Remember that urticaria diagnosis is primarily clinical, and laboratory investigations should be tailored to the individual presentation rather than ordered as a standard panel for all patients.