How should urticaria be managed, including acute and chronic treatment strategies?

Management of Urticaria

Begin with a standard dose of second-generation H1-antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine) as first-line treatment for all forms of urticaria, and if symptoms persist after 2-4 weeks, increase the dose up to four-fold before considering any other therapy. 1, 2, 3

Initial Classification and Assessment

Distinguish between acute urticaria (≤6 weeks) and chronic urticaria (>6 weeks), as management strategies differ. 3

Key diagnostic features to identify:

• Wheal duration: Individual wheals lasting 2-24 hours indicate chronic spontaneous urticaria, whereas lesions persisting >24 hours suggest urticarial vasculitis and require skin biopsy for confirmation. 1, 2
• Angioedema pattern: Isolated or recurrent angioedema without wheals warrants evaluation for hereditary or acquired angioedema, ACE-inhibitor-induced angioedema, or C1-inhibitor deficiency. 2, 3
• Physical triggers: Physical urticaria typically produces wheals lasting <1 hour (except delayed pressure urticaria). 4

Stepwise Treatment Algorithm

Step 1: First-Line Antihistamine Therapy

• Start with a standard dose of a second-generation H1-antihistamine. 1, 2
• Offer at least two different second-generation antihistamines because individual response and tolerance vary markedly. 2
• Pharmacokinetic considerations for selection:
  • Cetirizine reaches peak plasma concentration fastest—preferred when rapid symptom control is required. 2
  • Desloratadine has the longest half-life (~27 hours) and must be stopped at least 6 days before skin-prick testing. 2
  • Schedule dosing so peak drug levels coincide with anticipated urticaria flares. 2

Step 2: Dose Escalation (If Inadequate Response After 2-4 Weeks)

• Increase the antihistamine dose up to four times the standard dose. 1, 2, 3
• Approximately 23% of patients who fail standard dosing achieve adequate control after up-dosing. 1, 2
• This off-label practice is accepted when anticipated therapeutic benefit outweighs potential risks. 1

Step 3: Add Omalizumab (If Up-Dosing Fails)

• Add omalizumab 300 mg subcutaneously every 4 weeks. 1, 2, 3
• Allow up to 6 months for patients to demonstrate a response before declaring treatment failure. 1, 2
• If the 300 mg dose is insufficient, increase to a maximum of 600 mg every 2 weeks. 2

Step 4: Add Cyclosporine (If Omalizumab Inadequate After 6 Months)

• Introduce cyclosporine up to 5 mg/kg body weight per day. 1, 2, 3
• Produces clinical improvement in approximately 65-70% of patients with severe urticaria. 2
• Monitor blood pressure and renal function every 6 weeks due to nephrotoxicity and hypertension risk. 1, 2
• A 16-week treatment course is more effective than 8 weeks. 2

Adjunctive Therapies for Resistant Cases

• H2-antihistamines (cimetidine): May be added to H1-antihistamine therapy, particularly when dyspeptic symptoms coexist, though evidence is limited. 1, 2, 3
• Leukotriene receptor antagonists (montelukast): Can be considered as add-on therapy; efficacy data are sparse. 1, 2, 3
• Sedating antihistamines at night (chlorphenamine 4-12 mg or hydroxyzine 10-50 mg): May improve sleep quality but provide minimal additional urticaria control when H1 receptors are already saturated. 1, 2

Role of Corticosteroids: Critical Limitations

Restrict oral corticosteroids to short courses of 3-10 days for severe acute exacerbations only. 1, 2, 3

• Long-term corticosteroid use causes cumulative toxicity including adrenal suppression, osteoporosis, diabetes, hypertension, and Cushing syndrome. 1
• Corticosteroids should never be used as maintenance therapy for chronic urticaria. 2
• A 2020 meta-analysis shows corticosteroids likely improve urticaria activity by only 14-15% but increase adverse events in approximately 15% more patients (OR 2.76; 95% CI 1.00-7.62). 1
• Short courses may serve as bridge therapy to other systemic treatments in acute severe exacerbations, but only after antihistamines have been optimized. 1

Trigger Avoidance and General Measures

• Advise patients to avoid NSAIDs, aspirin, codeine, alcohol, and stress. 1, 2, 3
• Discontinue ACE-inhibitors in individuals with angioedema without wheals. 2
• Recommend cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief. 2, 3
• Prevent skin from drying, avoid hot showers, scrubbing, and excessive sun exposure. 5

Disease Monitoring and Treatment Tapering

• Use the Urticaria Control Test (UCT) every 4 weeks to assess disease control. 1, 2
• Record the 7-Day Urticaria Activity Score (UAS7) for objective measurement of disease activity. 1, 2
• Apply the Angioedema Control Test (AECT) when angioedema is present. 1, 2

Treatment tapering protocol:

• After achieving complete symptom control, maintain the effective dose for at least 3 consecutive months before initiating dose reduction. 1, 2
• Reduce the dose by no more than one tablet per month. 1, 2
• If symptoms recur during step-down, return to the last effective dose that provided complete control. 1, 2

Special Population Considerations

Renal Impairment

• Avoid acrivastine in moderate renal impairment (creatinine clearance 10-20 mL/min). 1, 2, 3
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate impairment. 1, 2
• Avoid cetirizine and levocetirizine in severe renal impairment (creatinine clearance <10 mL/min). 1, 2

Hepatic Impairment

• Mizolastine is contraindicated in significant hepatic impairment. 1, 2, 3
• Avoid chlorphenamine and hydroxyzine in severe liver disease. 1, 2, 3

Pregnancy

• Avoid all antihistamines during pregnancy, especially in the first trimester, unless absolutely necessary. 1, 2, 3
• When antihistamine therapy is required, chlorphenamine has the longest safety record. 1, 2, 3
• Loratadine and cetirizine are FDA Pregnancy Category B drugs. 1, 2, 3

Specialist Referral Indications

Refer urgently when:

• Lesions persist >24 hours with ecchymotic or purpuric residues or pain/burning sensations (possible urticarial vasculitis). 1, 2
• Fever, arthralgia, or malaise accompany urticaria (suggesting systemic vasculitis or autoinflammatory disease). 1, 2
• Isolated or recurrent angioedema without wheals occurs (evaluation for hereditary or acquired angioedema required). 1, 2
• Patient requires regular oral corticosteroids or has failed third-line therapies. 1, 2

Common Pitfalls to Avoid

• Do not use first-generation sedating antihistamines as first-line therapy: They change REM-sleeping patterns and learning curves and have not been shown superior to non-sedating antihistamines in head-to-head trials. 6
• Do not perform extensive laboratory investigation routinely: Routine laboratory testing is not cost-effective in chronic spontaneous urticaria unless clinical features suggest autoimmune diseases. 5
• Do not delay epinephrine in anaphylaxis: Administer epinephrine before any antihistamine or corticosteroid; epinephrine remains the sole first-line medication for anaphylaxis. 1