What is the recommended workup for a patient presenting with urticaria (hives)?

Workup for Urticaria (Hives)

Acute Urticaria (< 6 weeks duration)

No routine laboratory testing is recommended for acute urticaria unless the patient's history suggests a specific underlying cause requiring confirmation. 1

• The diagnosis is made clinically based on history and physical examination alone 2
• Testing should only be pursued if the history points to specific triggers such as:
  • Allergic reactions to foods or drugs 3
  • Viral infections 3
  • Contact with chemicals or irritants 3
• Rule out anaphylaxis immediately if present 4

Chronic Spontaneous Urticaria (≥ 6 weeks duration)

For chronic spontaneous urticaria (CSU), perform limited basic laboratory testing along with thorough history and patient-reported outcome measures, avoiding extensive routine workups. 1

Essential Diagnostic Components

History and Clinical Assessment:

• Confirm wheals lasting < 24 hours (if lasting > 24 hours, consider skin biopsy to rule out urticarial vasculitis) 2
• Document presence or absence of angioedema 2
• Review patient photographs of wheals during symptomatic episodes 1, 2
• Obtain medication history, particularly ACE inhibitors, sartans, gliptins, or neprilysin inhibitors 2
• Assess for physical triggers to identify chronic inducible urticaria 1

Basic Laboratory Tests (recommended for CSU): 1

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

The combination of low/very low total IgE and elevated IgG anti-TPO suggests autoimmune CSU, with a high IgG anti-TPO to total IgE ratio being the best surrogate marker for this subtype. 1

Patient-Reported Outcome Measures:

• 7-Day Urticaria Activity Score (UAS7): Have patients score wheal count (0-3 points) and pruritus intensity (0-3 points) daily for 7 consecutive days, then sum all 14 scores (range 0-42) 2, 5
• Urticaria Control Test (UCT): 4-question assessment with scores ≥12 indicating well-controlled disease and <12 requiring treatment escalation 1, 6
• Angioedema Control Test (AECT): Use in patients with angioedema (with or without wheals), with cutoff of 10 points for well-controlled disease 1, 6

Additional Testing (Only If Indicated by History)

Do NOT perform routine extensive testing. 1, 2 Additional workup should be guided by specific clinical clues:

• Autologous serum test: May be considered in antihistamine-refractory patients to identify autoimmune CSU, though omalizumab efficacy is independent of this test result 1
• CU index testing: For patients not responsive to H1 antihistamines, to detect antibodies against IgE, FcεRI, or FcεRII 1
• Skin biopsy: Only if individual wheals persist > 24 hours to exclude urticarial vasculitis 2
• Testing for systemic diseases: Only if history suggests collagenopathies, endocrinopathies, tumors, or other specific conditions 3

Common Pitfalls to Avoid

• Do not order extensive allergy panels routinely - chronic urticaria is idiopathic in 80-90% of cases and rarely allergic 4, 7
• Do not rely on retrospective symptom recall - UAS7 must be completed prospectively for 7 consecutive days to avoid recall bias 5
• Do not assume hereditary angioedema is common - it is exceptionally rare; ACE inhibitor-induced angioedema is far more likely (3-5% of ACE-I users) 7
• Do not perform the same battery of tests for all urticaria presentations - different clinical features should guide targeted diagnostic workup 3