What is the recommended management for chronic urticaria persisting longer than six weeks?

Management of Chronic Urticaria

Start with up-dosing second-generation H1-antihistamines to 4 times the standard daily dose for 2-4 weeks, then add omalizumab 300mg subcutaneously every 4 weeks if control remains inadequate, and reserve cyclosporine as third-line therapy. 1, 2

Initial Assessment and Disease Classification

Before initiating treatment, distinguish chronic spontaneous urticaria (CSU) from other urticaria subtypes, as management differs significantly:

• Wheal duration is critical: Individual wheals lasting 2-24 hours indicate ordinary urticaria, while lesions persisting >24 hours suggest urticarial vasculitis requiring skin biopsy and different management 3, 2
• Rule out hereditary angioedema immediately: If angioedema occurs without wheals or accompanies urticaria, order serum C4 level urgently, as a low C4 has high sensitivity for C1 inhibitor deficiency requiring completely different treatment 1
• Identify inducible triggers: Test for physical triggers (dermographism, cold, pressure, heat) through provocation testing, as chronic inducible urticaria requires trigger avoidance as primary management 4

Disease Activity Monitoring

Use validated objective tools rather than subjective assessment:

• Urticaria Control Test (UCT): Assess disease control every 4 weeks using this 4-question validated instrument 3, 1
• 7-Day Urticaria Activity Score (UAS7): Track daily wheal count and pruritus intensity, with scores ranging 0-42 points weekly 3
• Angioedema Control Test (AECT): For patients with angioedema component, use this separate validated tool 3

First-Line Treatment: Second-Generation H1-Antihistamines

Begin with standard dosing of non-sedating antihistamines:

• Initial dose: Cetirizine 10mg, fexofenadine 180mg, loratadine 10mg, desloratadine 5mg, or levocetirizine 5mg once daily 2, 5
• Expected response: Approximately 40% of patients achieve partial or complete response (>50% symptom reduction) at standard doses 6, 7
• Avoid first-generation antihistamines: Do not use diphenhydramine or hydroxyzine for chronic management due to sedation and anticholinergic effects 5

Step-Up Dosing Protocol

If inadequate control after 2-4 weeks at standard dosing:

• Up-dose to 4 times standard daily dose: This achieves sufficient response in an additional 23% of patients who failed standard dosing 2, 7
• Continue for 2-4 weeks: Allow adequate time to assess response before advancing to next step 1, 2
• Examples: Cetirizine 40mg daily, fexofenadine 720mg daily, or loratadine 40mg daily 2

Second-Line Treatment: Omalizumab

Add omalizumab if symptoms remain inadequately controlled despite up-dosed antihistamines:

• Dosing: 300mg subcutaneously every 4 weeks (not dependent on IgE level or body weight for CSU) 1, 8
• Response rate: Approximately 70% of antihistamine-refractory patients respond to omalizumab 6, 7
• Time to response: Allow up to 6 months for patients to demonstrate response before considering it a failure 1, 2
• Administration: First 3 doses must be given under healthcare provider supervision to monitor for anaphylaxis; self-administration may be considered thereafter if no hypersensitivity reactions occur 8

Omalizumab Non-Responders

At least 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria 6:

• Continue antihistamines: Maintain up-dosed second-generation H1-antihistamines throughout omalizumab therapy 2
• Consider adjunctive therapies: H2-antihistamines (cimetidine) or antileukotrienes (montelukast) may provide modest additional benefit in resistant cases 2

Third-Line Treatment: Cyclosporine

If inadequate control persists with omalizumab, add cyclosporine:

• Dosing: Up to 5mg/kg body weight daily, typically starting at 3-4mg/kg 2, 6
• Response rate: 54-73% of patients improve, especially those with autoimmune CSU and omalizumab non-response 6, 7
• Monitoring requirements: Check blood pressure and renal function (BUN, creatinine, urine protein) every 6 weeks 2, 7
• Toxicity concerns: Risk of kidney dysfunction, hypertension, and other immunosuppressive effects limits long-term use 6, 9

Critical Pitfalls to Avoid

Corticosteroid Misuse

Never use prolonged oral corticosteroids as maintenance therapy:

• Restrict to short courses only: 3-10 days maximum for severe acute exacerbations or life-threatening angioedema affecting the mouth 1, 2
• Maximum maintenance dose if unavoidable: No more than 10mg prednisone daily with weekly reduction of 1mg 7
• Cumulative toxicity: Prolonged use causes adrenal suppression, osteoporosis, diabetes, hypertension, and Cushing syndrome without addressing underlying pathophysiology 1, 2

Trigger Avoidance

Counsel patients to avoid known exacerbating factors:

• NSAIDs and aspirin: Can worsen chronic urticaria through non-IgE mechanisms 1, 2
• Codeine and alcohol: Direct mast cell degranulation 1, 2
• ACE inhibitors: Must be avoided in patients with angioedema without wheals and used with extreme caution when angioedema accompanies urticaria 1

Treatment Duration and Step-Down

Once complete symptom control is achieved:

• Maintenance period: Continue effective dose for at least 3 consecutive months before attempting step-down 1, 2
• Step-down protocol: Reduce daily dose by no more than 1 tablet per month 2
• Recurrence management: If symptoms recur during step-down, return immediately to the last effective dose that provided complete control 2
• Long-term prognosis: CSU persists for more than 1 year in most patients, though approximately 50% with wheals alone clear by 6 months 5, 6

Specialist Referral Indications

Consider allergist-immunologist or dermatologist consultation for:

• Diagnostic uncertainty: Lesions lasting >24 hours, ecchymotic/purpuric residua, or pain/burning suggesting urticarial vasculitis 3
• Systemic features: Fever, joint pain, or malaise suggesting autoinflammatory disease or systemic vasculitis 3
• Treatment resistance: Patients requiring regular steroid use or failing third-line therapy 3
• Isolated angioedema: To evaluate for hereditary or acquired angioedema, paraproteinemia, or B-cell malignancies 3