Management of Urticaria
Second-generation non-sedating H1 antihistamines are the definitive first-line treatment for urticaria, with dose escalation up to 4 times standard dosing if symptoms persist, followed by omalizumab 300 mg every 4 weeks for refractory cases, and cyclosporine as third-line therapy. 1
First-Line Treatment: Second-Generation Antihistamines
Start with standard-dose second-generation non-sedating H1 antihistamines as the cornerstone of urticaria management. 1, 2 Preferred agents include cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine. 1
Offer patients at least two different non-sedating antihistamines to trial, as individual responses and tolerance vary significantly between agents. 1, 2 This is critical because what fails in one patient may work excellently in another due to pharmacogenetic differences.
Cetirizine reaches maximum concentration fastest, making it the preferred choice when rapid symptom relief is needed. 1 This pharmacokinetic advantage can be clinically meaningful in acute exacerbations.
Dose Escalation Strategy
If symptoms persist after 2-4 weeks on standard dosing, increase the antihistamine dose up to 4 times the standard dose before adding other therapies. 1, 2 This updosing strategy is supported by the most recent international guidelines and represents a streamlined approach compared to older algorithms. 3
The rationale for high-dose antihistamines is based on their pharmacological properties—higher doses achieve greater H1 receptor occupancy without crossing the blood-brain barrier or causing significant sedation. 4 This approach is safer than adding sedating first-generation antihistamines or corticosteroids. 4
Second-Line Treatment: Omalizumab
For chronic spontaneous urticaria unresponsive to high-dose antihistamines, add omalizumab 300 mg subcutaneously every 4 weeks. 1, 2 This recommendation is based on robust double-blind placebo-controlled studies demonstrating efficacy. 3
Allow up to 6 months for patients to respond to omalizumab before declaring treatment failure. 1, 2 This extended trial period is essential because some patients are slow responders.
In patients with insufficient response, updose omalizumab by shortening the interval and/or increasing the dosage, with a maximum recommended dose of 600 mg every 14 days. 3, 1 This is particularly beneficial in patients with high body mass index. 3
Approximately 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria. 1 Patients with low total IgE levels and elevated IgG-anti-thyroid peroxidase antibodies are more likely to have autoimmune chronic spontaneous urticaria and may respond less favorably. 3
Third-Line Treatment: Cyclosporine
For patients who fail to respond to high-dose antihistamines and omalizumab within 6 months, add cyclosporine at 4-5 mg/kg daily. 1, 2 Treatment duration is typically up to 2 months. 1
Cyclosporine is effective in approximately 54-73% of patients, particularly those with autoimmune chronic spontaneous urticaria. 1 However, the risk-benefit profile is inferior to omalizumab due to potential adverse effects. 3
Regular blood pressure and renal function monitoring is mandatory due to risks of hypertension, nephrotoxicity, epilepsy in predisposed individuals, hirsutism, and gum hypertrophy. 3, 1, 2
Role of Corticosteroids: Critical Limitations
Oral corticosteroids should be restricted to short courses for severe acute urticaria or angioedema only—never for chronic management. 1, 2 This is a critical pitfall to avoid.
Corticosteroids have slow onset of action, work by inhibiting gene expression, and are ineffective for acute symptom relief. 1 Chronic use leads to cumulative toxicity that outweighs any benefit. 1 The recent international guidelines have removed corticosteroids from the routine treatment algorithm for chronic urticaria. 3
Trigger Identification and Avoidance
Identify and minimize aggravating factors including overheating, stress, alcohol, aspirin, NSAIDs, and codeine. 1, 2, 5
Avoid NSAIDs in aspirin-sensitive patients with urticaria. 1, 2, 5 This cross-reactivity can significantly worsen symptoms.
Avoid ACE inhibitors in patients with angioedema without wheals, as these medications can precipitate or worsen angioedema. 1, 2, 5
Critical Management Pitfalls
Never use antihistamines or corticosteroids in place of epinephrine for anaphylaxis. 1 Antihistamines take 30-120 minutes to reach peak plasma concentrations and lack the vasoconstrictive, bronchodilatory, and mast cell stabilization properties of epinephrine. 1
Avoid first-generation antihistamines in acute infusion reactions, as they can exacerbate hypotension, tachycardia, and shock through their anticholinergic effects. 1
Special Population Adjustments
In moderate renal impairment: Avoid acrivastine; halve the dose of cetirizine, levocetirizine, and hydroxyzine. 1, 2
In significant hepatic impairment: Avoid mizolastine. 1, 2 Avoid hydroxyzine in severe liver disease. 1, 2
In pregnancy: Avoid antihistamines if possible, especially during the first trimester. 1, 2 If necessary, choose chlorphenamine due to its long safety record. 1, 2
Diagnostic Workup for Chronic Spontaneous Urticaria
Perform basic tests including differential blood count, C-reactive protein or ESR, total IgE, and IgG-anti-thyroid peroxidase levels to identify autoallergic or autoimmune-mediated disease. 3 Patients with autoimmune chronic spontaneous urticaria are more likely to have low total IgE levels and elevated IgG-anti-TPO. 3
A high ratio of IgG-anti-TPO to total IgE is currently the best surrogate marker for autoimmune chronic spontaneous urticaria. 3 This can help predict response to omalizumab versus cyclosporine.
Prognosis and Patient Counseling
Approximately 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months. 1, 2 This provides realistic expectations for patients.
Patients with both wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years. 1, 2 These patients require more aggressive management and longer follow-up.