What lab tests are recommended for chronic hives (urticaria)?

Laboratory Tests for Chronic Urticaria

For most patients with chronic urticaria, no laboratory tests are required, especially for those with mild disease responding to H1 antihistamines. 1

Basic Approach to Laboratory Testing

Laboratory investigations for chronic urticaria should be guided by the clinical history and not performed routinely in all patients. The diagnostic approach should be tailored based on the presentation and severity of symptoms.

Initial Screening for Moderate to Severe Cases

For patients with more severe disease not responding to antihistamines, a basic screening profile should include:

• Complete blood count with white cell differential
  • Helps detect eosinophilia (suggesting helminth infections)
  • Can identify leucopenia (suggesting systemic lupus erythematosus)
• Erythrocyte sedimentation rate (ESR)
  • Usually normal in chronic ordinary urticaria
  • Elevated in urticarial vasculitis and autoinflammatory syndromes
• Thyroid autoantibodies and thyroid function tests
  • Particularly important when autoimmune etiology is suspected
  • Thyroid autoimmunity is more prevalent in chronic urticaria (14%) than in general population (6%) 1

Special Considerations Based on Clinical Presentation

For Suspected Urticarial Vasculitis

If urticarial lesions persist for more than 24 hours, resolve with bruising/purpura, or are painful rather than pruritic, consider:

• Skin biopsy (essential for confirmation)
  • Look for leucocytoclasia, endothelial damage, and perivascular fibrin deposition 1, 2
• Complete vasculitis screen
  • Serum complement assays (C3, C4)
  • Antinuclear antibody titer
  • ESR/CRP 2

For Angioedema Without Wheals

• Serum C4 as initial screening test for hereditary and acquired C1 inhibitor deficiency
  • If C4 is low, confirm with quantitative and functional C1 inhibitor assays
  • C1q levels (reduced in acquired C1 inhibitor deficiency) 1

For Suspected Autoimmune Urticaria

• Autologous serum skin test (ASST)
  • Reasonably sensitive and specific screening test for histamine-releasing autoantibodies
  • Should be performed in centers with experience 1
• Basophil histamine release assay (gold standard where available) 1

Additional Tests Based on Clinical Suspicion

• For suspected food or environmental allergies:

  • Skin-prick testing and/or CAP fluoroimmunoassay (formerly RAST) 1

• For suspected infection-related urticaria:

  • H. pylori testing (evidence suggests resolution of urticaria is more likely when H. pylori treatment is successful) 1
  • Consider testing for other infections based on clinical presentation

• For suspected physical urticarias:

  • Challenge testing according to international standards 1

Common Pitfalls and Caveats

1. Avoid unnecessary testing: Most cases of chronic urticaria are idiopathic and do not require extensive laboratory evaluation.

2. Interpret test results in clinical context: Positive allergy tests should be correlated with clinical symptoms.

3. Don't miss urticarial vasculitis: This requires different management than ordinary urticaria and can be associated with systemic involvement.

4. Consider rare associations: While uncommon, chronic urticaria can occasionally be associated with underlying malignancy, though there is no statistical association requiring routine screening 1.

5. Recognize limitations: There is currently no routine laboratory test for histamine-releasing autoantibodies outside of specialized centers.

By following this structured approach to laboratory testing in chronic urticaria, clinicians can avoid unnecessary tests while ensuring appropriate evaluation of patients with more severe or treatment-resistant disease.