What treatment should be given to a patient with an urticarial rash?

Treatment of Urticarial Rash

Start with a second-generation non-sedating H1 antihistamine at standard dosing (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine) as first-line treatment. 1, 2, 3

First-Line Treatment: Second-Generation Antihistamines

• Begin with standard-dose second-generation H1 antihistamines immediately—these are the definitive first-line treatment for all forms of urticaria. 1, 2, 3

• Offer the patient at least two different non-sedating antihistamines to trial, as individual responses and tolerance vary significantly between agents. 2, 3

• If rapid symptom relief is critical, choose cetirizine, as it reaches maximum concentration fastest among available options. 2, 4

• Preferred agents include: cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine. 2, 3

Dose Escalation Strategy

• If symptoms persist after 2-4 weeks on standard dosing, increase the dose up to 4 times the standard dose before adding other therapies. 1, 2, 3, 4

• This updosing approach is now standard practice when potential benefits outweigh risks, and has become common in clinical practice. 1

• Do not add second-line agents until you have maximized antihistamine dosing to 4x standard dose. 1, 2

Role of Corticosteroids in Acute Urticaria

• Restrict oral corticosteroids to short courses (3-10 days maximum) for severe acute urticaria or angioedema affecting the mouth only—never use for chronic management. 1, 2, 3

• One older study from 1995 showed prednisone 20 mg every 12 hours for 4 days added to antihistamines improved symptoms faster in acute urticaria 5, but a more recent 2024 systematic review found that adding corticosteroids to antihistamines did not improve symptoms in 2 out of 3 randomized controlled trials. 6

• Corticosteroids have slow onset of action, work by inhibiting gene expression, and are ineffective for acute symptom relief. 2

• Chronic corticosteroid use leads to cumulative toxicity that outweighs any benefit. 2, 4

Second-Line Treatment: Omalizumab

• For chronic spontaneous urticaria unresponsive to high-dose antihistamines (up to 4x standard dose), add omalizumab 300 mg subcutaneously every 4 weeks. 1, 2, 3, 4

• The dose can be increased to 600 mg every 2 weeks in patients with insufficient response, particularly those with high body mass index. 1, 2, 4

• Allow up to 6 months for patients to respond to omalizumab before declaring treatment failure. 1, 2, 3, 4

• Omalizumab has a response rate close to 75% and the best efficacy-to-toxicity profile among second-line agents. 7

• Approximately 30% of patients have insufficient response to omalizumab, particularly those with IgG-mediated autoimmune urticaria. 2

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 for up to 2 months. 1, 2, 3, 4

• Cyclosporine is effective in approximately 54-73% of patients, particularly those with autoimmune chronic spontaneous urticaria. 2, 7

• Monitor blood pressure and renal function (blood urea nitrogen and creatinine) every 6 weeks while on cyclosporine due to risks of hypertension and nephrotoxicity. 1, 2, 3, 4, 7

• Refractoriness to both omalizumab and cyclosporine is expected in less than 5% of patients. 7

Adjunctive Therapies for Resistant Cases

• First-generation sedating antihistamines (hydroxyzine, diphenhydramine) can be added at night for additional symptom control in patients with sleep disruption from pruritus. 1, 3

• Combinations with H2 antihistamines or antileukotrienes can be useful for resistant cases, though evidence is limited. 1

Critical Management Pitfalls

• Never use antihistamines or corticosteroids in place of epinephrine for anaphylaxis—antihistamines take 30-120 minutes to reach peak plasma concentrations and lack the vasoconstrictive, bronchodilatory, and mast cell stabilization properties of epinephrine. 2

• Avoid first-generation antihistamines in acute infusion reactions, as they can exacerbate hypotension, tachycardia, and shock. 2

Trigger Identification and Avoidance

• Identify and minimize aggravating factors: overheating, stress, alcohol, aspirin, NSAIDs, and codeine. 2, 3, 4

• Avoid NSAIDs in aspirin-sensitive patients with urticaria. 2, 3, 4

• Avoid ACE inhibitors in patients with angioedema without wheals. 2, 3

Special Population Adjustments

• In moderate renal impairment: Avoid acrivastine; halve the dose of cetirizine, levocetirizine, and hydroxyzine. 2, 3

• In significant hepatic impairment: Avoid mizolastine and hydroxyzine in severe liver disease. 2, 3

• In pregnancy: Avoid antihistamines if possible, especially during the first trimester; if necessary, choose chlorphenamine due to its long safety record. 2, 3

Prognosis and Patient Counseling

• Approximately 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months. 1, 2, 3

• Patients with both wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years. 1, 2, 3