What is the recommended management for recurrent urticaria?

Management of Recurrent Urticaria

Start immediately with a second-generation non-sedating H1-antihistamine at standard dose, and if symptoms persist after 2–4 weeks, increase the dose up to four-fold before adding any other therapy. 1, 2

First-Line Treatment: Second-Generation H1-Antihistamines

• Offer at least two different second-generation antihistamines to each patient because individual response and tolerance vary markedly between agents. 1, 2

• Preferred agents include cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine. 1

• Cetirizine reaches peak plasma concentration fastest and should be selected when rapid symptom control is required. 1, 2

• Schedule dosing so peak drug levels coincide with anticipated urticaria flares to optimize symptom control. 1, 2

• Desloratadine has the longest elimination half-life (~27 hours) and must be stopped at least 6 days before skin-prick testing to avoid false-negative results. 1, 2

Dose Escalation Strategy

• If symptoms remain inadequately controlled after 2–4 weeks of standard dosing, increase the antihistamine dose up to four-fold the standard dose before adding second-line agents. 1, 2, 3

• This up-dosing strategy achieves adequate control in approximately 23% of patients who failed standard dosing. 1, 2

• Up-dosing to four times the standard dose is an accepted off-label practice when anticipated therapeutic benefit outweighs potential risks. 1

Second-Line Treatment: Omalizumab

• Add omalizumab 300 mg subcutaneously every 4 weeks for patients still symptomatic after four-fold antihistamine dosing. 1, 2, 4

• Allow up to 6 months of omalizumab treatment before declaring treatment failure. 1, 2

• If the 300 mg dose is insufficient, increase to a maximum of 600 mg every 2 weeks. 2

• Omalizumab is effective in approximately 70% of antihistamine-refractory patients. 5, 3

• Dosing of omalizumab in chronic spontaneous urticaria is not dependent on serum IgE level or body weight, unlike its use in asthma. 4

Third-Line Treatment: Cyclosporine

• Introduce cyclosporine (up to 5 mg/kg body weight) after 6 months of omalizumab if disease remains uncontrolled. 1, 2, 5

• Cyclosporine produces clinical improvement in approximately 65–70% of patients with severe urticaria, particularly those with IgG-mediated autoimmune urticaria who fail omalizumab. 2, 5, 3

• Monitor blood pressure and renal function every 6 weeks because of nephrotoxicity and hypertension risk. 1, 2, 5

• A treatment course of 16 weeks is more effective than 8 weeks in reducing therapeutic failures. 2, 6

Role of Corticosteroids: Critical Pitfall to Avoid

• Restrict oral corticosteroids to short courses of 3–10 days for severe acute exacerbations only—they should never be used as maintenance therapy. 1, 2, 5, 3

• Long-term corticosteroid use leads to cumulative toxicity including adrenal suppression, osteoporosis, diabetes, hypertension, and Cushing-type features. 1, 2

• Corticosteroids should not be employed chronically except in very selected cases under regular specialist supervision. 6, 5

Adjunctive Therapies for Resistant Cases

• H2-antihistamines (cimetidine) may be added to H1-antihistamine therapy, though evidence is limited and benefits are unclear. 7, 1, 2

• Leukotriene receptor antagonists (montelukast) can be used as add-on therapy, but efficacy data are sparse. 7, 1, 2

• Sedating antihistamines taken 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

Trigger Identification and Avoidance

• Advise patients to avoid known aggravating factors including overheating, emotional stress, and alcohol. 2, 6

• Discontinue aspirin, NSAIDs, and codeine, which can exacerbate urticaria. 1, 2

• Avoid ACE-inhibitors in individuals with angioedema without wheals. 2

• Recommend cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief. 2, 6

Disease Monitoring

• 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

• 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 dose that provided adequate control. 1, 2

Critical Diagnostic Distinctions

• Individual wheals in chronic spontaneous urticaria typically last 2–24 hours. 1, 2

• Urticarial vasculitis is characterized by lesions persisting >24 hours with ecchymotic or purpuric residues or pain/burning sensations and requires skin biopsy for confirmation. 7, 1, 2

• For isolated angioedema without wheals, screen for C1-inhibitor deficiency using serum C4 as the initial test; confirm abnormal results with quantitative and functional C1-inhibitor assays. 2

Special Population Considerations

Renal Impairment

• Avoid acrivastine in moderate renal impairment (creatinine clearance 10–20 mL/min). 1, 2

• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate impairment; avoid cetirizine and levocetirizine in severe impairment (creatinine clearance <10 mL/min). 1, 2

Hepatic Impairment

• Mizolastine is contraindicated in significant hepatic impairment. 1, 2

• Avoid chlorphenamine and hydroxyzine in severe liver disease. 1, 2

Pregnancy

• Antihistamines should be avoided during pregnancy, especially in the first trimester, unless absolutely necessary. 1, 2

• When antihistamine therapy is required, chlorphenamine has the longest safety record. 1, 2

• Loratadine and cetirizine are classified as FDA Pregnancy Category B. 1, 2

Referral Criteria

• Refer urgently for lesions persisting >24 hours with ecchymotic or purpuric residues or pain/burning (possible urticarial vasculitis). 1, 2

• Refer when fever, arthralgia, or malaise accompany urticaria (suggesting systemic vasculitis or autoinflammatory disease). 1, 2

• Refer patients with isolated or recurrent angioedema without wheals for evaluation of hereditary or acquired angioedema. 1, 2

• Refer any patient requiring regular oral corticosteroids or who has failed third-line therapies. 1, 2