What is the recommended approach to assess and treat acute and chronic urticaria?

Approach to Urticaria

Initial Clinical Assessment

The diagnosis of urticaria is primarily clinical, requiring no investigations for most patients with acute urticaria or mild chronic urticaria responding to antihistamines 1.

Key Diagnostic Features to Document

• Wheal characteristics: Confirm presence of itchy wheals with surrounding erythema that resolve within 24 hours (individual wheals lasting >24 hours suggest urticarial vasculitis, not typical urticaria) 1
• Duration of symptoms: Distinguish acute urticaria (<6 weeks) from chronic urticaria (>6 weeks), as this fundamentally changes the diagnostic and treatment approach 1, 2
• Presence or absence of angioedema: Determine if angioedema occurs with wheals (mast cell-mediated) or without wheals (suggests bradykinin-mediated mechanisms requiring different evaluation) 1, 3
• Medication history: Specifically document ACE inhibitors, ARBs, NSAIDs, aspirin, and antibiotics, as these are common culprits 1, 3
• Trigger identification: Ask about physical triggers (pressure, cold, heat, exercise), foods, infections, or temporal patterns to classify as spontaneous versus inducible urticaria 1, 4

Critical Distinction: Angioedema Without Wheals

If angioedema occurs without urticaria, immediately order C4 level, C1 inhibitor antigen, and C1 inhibitor functional activity to screen for hereditary or acquired C1 inhibitor deficiency 3. This presentation will not respond to antihistamines and requires entirely different management 3.

Diagnostic Algorithm by Clinical Presentation

Acute Urticaria (<6 weeks)

No investigations are required except where suggested by the history 1.

• If clear allergic trigger suspected (latex, nuts, fish): Perform skin-prick testing or allergen-specific IgE testing only when results will change management 1
• If drug-related: Discontinue suspected agent and observe for resolution 1
• If infection-associated: Treat underlying infection; routine infectious workup is not indicated 1

Chronic Spontaneous Urticaria (>6 weeks)

Mild Disease Responding to Antihistamines

No investigations required 1.

Moderate-to-Severe or Antihistamine-Refractory Disease

Obtain a focused screening panel 1:

• Complete blood count with differential: Detects eosinophilia (helminth infections) or leukopenia (systemic lupus erythematosus) 1
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP): Usually normal in chronic spontaneous urticaria; elevated levels suggest urticarial vasculitis or autoinflammatory syndromes 1, 3
• Thyroid function tests and thyroid autoantibodies (anti-TPO): Thyroid autoimmunity occurs in 14% of chronic urticaria patients versus 6% of controls, and treatment may improve urticaria 1, 3
• Total IgE level: Elevated levels suggest autoallergic chronic spontaneous urticaria 3

Do not perform extensive allergy testing, infectious disease panels, or malignancy screening routinely, as these have low yield and are not cost-effective unless specifically suggested by clinical features 1, 5.

Special Testing Considerations

• Autologous serum skin test (ASST): Can be performed in specialized centers to screen for histamine-releasing autoantibodies (present in 40-60% of chronic urticaria patients), though this does not change first-line management 1, 2
• Helicobacter pylori testing: Consider in refractory cases, as successful eradication is associated with urticaria resolution in some patients (Quality of evidence I, Strength of recommendation B) 1

Chronic Inducible Urticaria

Perform provocation testing to confirm the diagnosis and identify the specific trigger 4:

• Dermographism: Stroke skin firmly with tongue depressor
• Cold urticaria: Apply ice cube for 5 minutes
• Delayed pressure urticaria: Apply sustained pressure and observe for 2-6 hours 1, 4
• Solar urticaria: Controlled UV exposure testing
• Cholinergic urticaria: Exercise or hot water immersion challenge

Disease Activity and Control Assessment

Assess disease activity, quality of life impairment, and disease control at the first and every follow-up visit using validated patient-reported outcome measures 1:

• 7-Day Urticaria Activity Score (UAS7): Primary tool for determining disease activity and treatment response in patients with wheals 1, 3
• Angioedema Activity Score: For patients with angioedema with or without wheals 3
• Urticaria Control Test (UCT): Assess disease control; score ≥12 indicates well-controlled disease 3, 4

Treatment Algorithm

First-Line Treatment: Second-Generation H1 Antihistamines

Non-sedating second-generation H1 antihistamines are the first-line pharmacotherapy for all forms of urticaria 5, 6, 7:

• Initial dosing: Standard dose for 2-4 weeks 5
• If inadequate response: Increase dose up to 4-fold (up to 4 times daily dosing) before adding other agents 5, 6, 7
• Preferred agents: Cetirizine, loratadine, fexofenadine, desloratadine, levocetirizine 6, 7

First-generation antihistamines (hydroxyzine, diphenhydramine) have not been proven more advantageous than second-generation agents and cause significant sedation, limiting their routine use 5, 6.

Second-Line Treatment: Omalizumab

If high-dose antihistamines fail to achieve at least 50% symptom control, omalizumab 300 mg subcutaneously monthly is the next step 6, 7:

• Efficacy: Effective in approximately 70% of antihistamine-refractory patients 6
• Evidence quality: Strong evidence-based alternative regimen for chronic spontaneous urticaria 5

Third-Line Treatment: Cyclosporine

For patients unresponsive to both antihistamines and omalizumab, cyclosporine (up to 5 mg/kg body weight) is recommended 4, 6:

• Efficacy: Effective in 65-70% of refractory patients 6
• Monitoring required: Blood pressure and renal function must be monitored due to potential side effects 4, 6

Adjunctive Therapies (Limited Evidence)

• Brief corticosteroid courses (3-10 days): Can be used for severe exacerbations but should be infrequent; chronic use is contraindicated due to cumulative toxicity 4, 6, 7
• H2 antihistamines and leukotriene antagonists: No longer recommended as they add little efficacy 6, 7

Fourth-Line Options

For patients unresponsive to antihistamines, omalizumab, and cyclosporine, consider dapsone or sulfasalazine 6.

Treatment Duration and Monitoring

• Continue treatment until complete symptom control is achieved and maintained for at least 3-6 months before considering dose reduction 4
• Reassess disease control at every visit using validated tools (UCT, UAS7) to guide treatment decisions 1, 3
• More than 50% of patients with chronic urticaria will have resolution or improvement within one year 7

Special Populations

Pregnancy

Second-generation antihistamines, particularly loratadine and cetirizine, are preferred due to their established safety profile 4.

Common Pitfalls to Avoid

• Do not perform extensive laboratory workups in acute urticaria or mild chronic urticaria responding to antihistamines 1, 5
• Do not treat bradykinin-mediated angioedema (without wheals) with antihistamines, epinephrine, or corticosteroids—these are ineffective 3
• Do not assume ACE inhibitor-induced angioedema only occurs early in treatment; it can develop after many years of stable therapy 3
• Do not use chronic corticosteroids for urticaria management due to cumulative toxicity 6, 7
• Do not routinely test for occult infections, malignancy, or perform extensive allergy panels without specific clinical indication 1, 5

Non-Pharmacologic Management

Recommend measures to minimize skin hyperresponsiveness 5:

• Prevent skin from drying
• Avoid hot showers and scrubbing
• Limit excessive sun exposure
• Identify and avoid specific triggers when possible