What are the diagnosis and treatment options for urticaria?

Urticaria Diagnosis and Treatment

Diagnosis

Urticaria diagnosis is primarily clinical, based on the characteristic presentation of intensely pruritic wheals (hives) lasting 2-24 hours, with or without angioedema, and extensive laboratory testing should be avoided unless specific clinical features suggest underlying systemic disease. 1, 2

Clinical Classification

The duration of individual wheals is the most critical diagnostic feature:

• Acute urticaria: Continuous activity up to 6 weeks, most common in children, often triggered by viral infections, food/drug allergies, or physical stimuli 1, 2
• Chronic spontaneous urticaria (CSU): Daily or near-daily wheals for ≥6 weeks without identifiable physical triggers 1
• Physical urticarias: Reproducibly induced by specific stimuli (pressure, cold, heat, vibration, water contact), with wheals typically resolving within 1 hour except delayed pressure urticaria (2-48 hours) 1
• Urticarial vasculitis: Wheals persisting >24 hours, often leaving bruising or hyperpigmentation—requires skin biopsy for diagnosis 1, 2

Diagnostic Workup

For acute urticaria: No routine testing is needed unless history suggests specific allergic triggers requiring confirmation 1

For chronic spontaneous urticaria, the "7 Cs" approach includes 1:

• Basic laboratory tests only: Complete blood count, C-reactive protein or ESR, total IgE, and IgG anti-thyroid peroxidase (anti-TPO) 1
• Rationale: Low total IgE with elevated anti-TPO suggests autoimmune CSU (better predictor of omalizumab response); high anti-TPO/total IgE ratio is the best surrogate marker 1
• Avoid extensive testing: Most chronic urticaria (80-90%) is idiopathic, and routine allergy panels, complement studies, or autoimmune workups are not warranted unless specific clinical features suggest systemic disease 1, 3, 4

For angioedema without wheals: Screen with serum C4 level (high sensitivity for C1 esterase inhibitor deficiency); if low, proceed with C1 inhibitor quantitative and functional assays 1, 2

For suspected urticarial vasculitis: Lesional skin biopsy is mandatory, plus vasculitis workup including complement levels 1, 2

Disease Monitoring Tools

• Urticaria Control Test (UCT): For patients with wheals ± angioedema; score <12 indicates poor control requiring treatment escalation 1
• Angioedema Control Test (AECT): For patients with angioedema ± wheals; score <10 indicates poor control 1
• Quality of life: Use CU-Q2oL questionnaire for wheals, Angioedema QoL questionnaire for angioedema 1

Treatment

The treatment goal is complete disease control, achieved through a streamlined 3-step algorithm: (1) second-generation H1-antihistamines at standard or updosed levels, (2) omalizumab 300 mg every 4 weeks with updosing if needed, and (3) cyclosporine for refractory cases. 1

Step 1: Antihistamine Therapy (First-Line)

• Start with second-generation, non-sedating H1-antihistamines at standard doses (e.g., cetirizine 10 mg, loratadine 10 mg, fexofenadine 180 mg daily) 1, 3, 4, 5
• Updose up to 4 times the standard dose if inadequate response after 2-4 weeks—this is now common practice despite exceeding manufacturer's licensed recommendations, as benefits outweigh risks 1, 6
• Adjunctive options if monotherapy insufficient 1, 3, 4:
  • Add H2-antihistamines (e.g., ranitidine, famotidine)
  • Add first-generation sedating antihistamine at bedtime for nocturnal symptoms
  • Add leukotriene receptor antagonist (montelukast 10 mg daily)—benefits a small subset of patients

Avoid first-generation antihistamines as monotherapy due to sedation and anticholinergic effects, though they may be used adjunctively at night 1, 3

Step 2: Omalizumab (Second-Line)

For patients with CSU who remain symptomatic (UCT <12) despite updosed antihistamines, omalizumab is the second-line treatment. 1, 7

• Starting dose: 300 mg subcutaneously every 4 weeks 1, 7
• Updosing protocol if insufficient response after 3 months 1:
  • Shorten interval to every 2-3 weeks, OR
  • Increase dose to 450-600 mg every 4 weeks
  • Maximum: 600 mg every 2 weeks
• Duration: Allow up to 6 months for full response; particularly effective in patients with high body mass index 1
• Monitoring: Works independently of autoimmune markers (autologous serum test not predictive of response) 1
• FDA indication: Approved for CSU in patients ≥12 years who remain symptomatic despite H1-antihistamine treatment 7

Critical safety consideration: Omalizumab carries a black box warning for anaphylaxis, which can occur after any dose including the first; must be administered in a healthcare setting with observation and emergency equipment available 7

Step 3: Cyclosporine (Third-Line)

For patients unresponsive to high-dose omalizumab after 6 months, cyclosporine is the third-line option. 1

• Dosing: Low-dose cyclosporine (2.5-5 mg/kg/day divided twice daily) 1
• Monitoring requirements 1:
  • Blood pressure and renal function (BUN, creatinine) every 6 weeks
  • Watch for hypertension, renal dysfunction, hirsutism, gingival hyperplasia
• Duration: Can be used long-term in refractory cases, but risk-benefit profile is less favorable than omalizumab 1

Corticosteroids: Limited Role

• Short courses only (3-7 days) for severe acute urticaria or acute exacerbations of chronic urticaria 1, 3, 4
• Avoid long-term use due to adverse effects; exception is delayed pressure urticaria or urticarial vasculitis where longer courses may be necessary 1
• Not part of routine chronic urticaria management 1

Step-Up/Step-Down Approach

Use an "as much as needed, as little as possible" strategy: Escalate treatment based on UCT/AECT scores, then de-escalate once control is achieved (UCT ≥12, AECT ≥10) 1

Trigger Avoidance and General Measures

• Identify and avoid triggers when possible (though identified in only 10-20% of chronic cases) 3, 4
• Avoid nonspecific aggravators: NSAIDs, aspirin, ACE inhibitors, overheating, tight clothing, stress, alcohol 1, 6, 3
• Physical urticarias: Specific avoidance strategies based on trigger (e.g., barrier creams before water exposure for aquagenic urticaria, cold avoidance for cold urticaria) 6

Special Populations

Pediatric patients (6-11 years): Follow same treatment algorithm but with age-appropriate antihistamine dosing; omalizumab approved for ages ≥12 years for CSU 1, 7

Angioedema without wheals: Different management—if C1 inhibitor deficiency confirmed, requires C1 inhibitor replacement therapy, not antihistamines 1

Prognosis

More than 50% of patients with chronic urticaria will have resolution or significant improvement within 1 year, though some cases persist longer 1, 3, 4

Referral Indications

Refer to allergist-immunologist for 1:

• Chronic urticaria unresponsive to standard antihistamine therapy
• Suspected autoimmune urticaria requiring advanced testing
• Need for omalizumab or cyclosporine initiation
• Angioedema without wheals requiring C1 inhibitor evaluation
• Urticarial vasculitis or systemic disease suspected