What is the recommended workup and treatment for chronic urticaria (hives)?

Workup for Chronic Urticaria (Hives)

Start with a thorough history, physical examination including review of patient photos, and use the Urticaria Control Test (UCT) to assess disease control—then perform limited basic laboratory testing including differential blood count, C-reactive protein or ESR, total IgE, and IgG-anti-thyroid peroxidase levels. 1

Initial Diagnostic Approach: The 7 Cs Framework

The workup should systematically address seven key objectives 1:

• Confirm the diagnosis by verifying that individual wheals resolve within 24 hours (if lasting >24 hours, consider urticarial vasculitis and obtain skin biopsy) 1
• Look for underlying causes including autoimmune and autoallergic mechanisms 1
• Identify cofactors that modify disease activity (stress, NSAIDs, alcohol, overheating) 1
• Check for comorbidities including autoimmune thyroid disease and chronic inducible urticaria 1
• Assess consequences on sleep, mental health, and quality of life 1
• Evaluate predictors of disease course and treatment response 1
• Monitor disease activity using validated patient-reported outcome measures 1

Essential History Elements

Ask specifically about:

• Duration of individual wheals: Each wheal should last <24 hours; if >24 hours, suspect urticarial vasculitis 1
• Presence of angioedema: Occurs in deeper tissues, can last up to 72 hours 1
• Triggers and timing: Physical stimuli (pressure, cold, heat, vibration), foods, medications (especially ACE inhibitors, NSAIDs), infections 1, 2
• Family history: Hereditary conditions like hereditary angioedema or autoinflammatory syndromes 1
• Associated symptoms: Fever, joint pain, malaise suggesting systemic disease 1

Required Laboratory Testing

Basic Tests for All Patients with Chronic Spontaneous Urticaria

• Differential blood count 1
• C-reactive protein level or erythrocyte sedimentation rate 1
• Total IgE level: Low or very low levels suggest autoimmune CSU 1
• IgG-anti-thyroid peroxidase (anti-TPO): Elevated levels suggest autoimmune CSU 1
• Calculate the ratio of IgG-anti-TPO to total IgE: High ratio is the best surrogate marker for autoimmune CSU 1

Additional Testing for Specific Scenarios

• Skin biopsy: Mandatory if individual wheals last >24 hours to rule out urticarial vasculitis 1, 3
• Complement levels (C4, C1-INH): If angioedema without wheals to exclude hereditary or acquired angioedema 1
• Provocation testing: For suspected chronic inducible urticaria to confirm specific triggers 1, 2
• Autologous serum test: May be considered in antihistamine-refractory patients, though clinical relevance is limited 1

What NOT to Do

Avoid routine extensive testing in the absence of specific clinical indicators 1:

• No routine allergy testing unless history strongly suggests specific allergen 1
• No routine autoimmune panels unless systemic symptoms present 1
• No testing for acute urticaria unless history suggests specific underlying cause 1

Assessment Tools to Use at Every Visit

• Urticaria Control Test (UCT): Score ≥12 indicates well-controlled disease; score <12 requires treatment escalation 1, 2
• 7-Day Urticaria Activity Score: Tracks disease activity and treatment response 1
• Quality of life assessments: Document impact on daily functioning 1

Treatment Algorithm Based on Workup

First-Line Treatment

• Start with standard-dose second-generation H1-antihistamines (cetirizine, loratadine, fexofenadine) 1
• Avoid first-generation sedating antihistamines 1

Second-Line: If Inadequate Control After 2-4 Weeks

• Increase antihistamine dose up to 4-fold the standard dose 1
• Continue for at least 3 consecutive months once complete control achieved before considering step-down 1

Third-Line: If Still Inadequate Control

• Add omalizumab 150-300mg subcutaneously every 4 weeks 1, 4
• Dosing for chronic spontaneous urticaria is NOT dependent on IgE level or body weight 4
• Allow up to 6 months for response 1

Fourth-Line: Refractory Cases

• Add cyclosporine up to 5mg/kg body weight 1
• Monitor blood pressure and renal function (BUN, creatinine) every 6 weeks 1
• Low-dose long-term therapy can be safe and effective for severe cases 5

Critical Pitfalls to Avoid

• Do not use long-term systemic corticosteroids except in very selected cases under specialist supervision 3
• Do not re-test IgE levels during omalizumab treatment as they remain elevated up to one year after discontinuation 4
• Do not step down antihistamines too quickly: Reduce by only 1 tablet per month after 3 months of complete control 1
• Do not miss urticarial vasculitis: Always ask about individual wheal duration 1, 3