What is the best treatment approach for a patient with new onset urticaria?

Treatment of New Onset Urticaria

Start immediately with second-generation non-sedating H1 antihistamines at standard doses as first-line therapy for new onset urticaria. 1, 2

Initial Management Approach

Begin with a second-generation antihistamine such as cetirizine 10mg, fexofenadine 180mg, desloratadine 5mg, or levocetirizine 5mg once daily. 1 Cetirizine has the shortest time to maximum concentration, making it advantageous when rapid relief is needed. 1

Key Clinical Distinctions

Before initiating treatment, distinguish between different presentations:

• Acute urticaria (most common in new onset): Individual wheals last less than 24 hours and resolve completely, typically caused by post-viral illness or idiopathic triggers. 3
• Urticarial vasculitis: Lesions persist beyond 24 hours—if this occurs, obtain a lesional skin biopsy to confirm small-vessel vasculitis. 4, 1
• Angioedema without wheals: Check serum C4 as initial screening for hereditary/acquired C1 inhibitor deficiency. 5, 1

Treatment Escalation Algorithm

Step 1: Standard Dose Antihistamines (First 2-4 weeks)

• Prescribe one second-generation H1 antihistamine at manufacturer's recommended dose. 1
• Instruct patients to avoid aggravating factors: overheating, stress, alcohol, aspirin, NSAIDs, and codeine. 4, 1
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can provide symptomatic relief. 4, 1

Step 2: High-Dose Antihistamines (If inadequate control after 2-4 weeks)

• Increase the antihistamine dose up to 4 times the standard dose. 4, 1 This is safe and guideline-recommended. 1
• Consider switching between at least two different non-sedating antihistamines, as individual responses vary. 1
• You may add H2-antihistamines (cimetidine) or antileukotrienes for resistant cases, though evidence is limited. 1, 6

Step 3: Short-Course Corticosteroids (For severe flares only)

• Use prednisolone 0.5-1mg/kg/day for 3-4 weeks maximum as a short tapering course. 4, 2
• Never use systemic corticosteroids as maintenance therapy—they cause significant morbidity including adrenal suppression, osteoporosis, hypertension, and diabetes with prolonged use. 1
• Monitor blood glucose in diabetics and blood pressure in hypertensives during corticosteroid treatment. 1

Step 4: Omalizumab (If inadequate response to high-dose antihistamines)

• Add omalizumab 300mg subcutaneously every 4 weeks. 4, 1
• Allow up to 6 months for patients to respond before considering alternatives. 4, 1
• For insufficient response, consider updosing to 600mg every 14 days. 4

Step 5: Cyclosporine (For refractory cases)

• Use cyclosporine up to 5mg/kg body weight for patients failing high-dose antihistamines and omalizumab. 4, 1
• Monitor blood pressure and renal function every 6 weeks due to nephrotoxicity and hypertension risks. 4, 1

Critical Pitfalls to Avoid

Do not prescribe epinephrine auto-injectors for isolated new onset urticaria or angioedema unless there is documented hypotension, hypoxia, or respiratory compromise suggesting anaphylaxis. 3 Most new onset urticaria is post-infectious or idiopathic, not IgE-mediated allergy. 3

Avoid first-generation sedating antihistamines (diphenhydramine, hydroxyzine) as first-line therapy—they cause significant sedation and cognitive impairment without superior efficacy. 1

Do not order extensive laboratory workups for new onset urticaria unless the history suggests specific triggers or systemic disease. 5, 3 The diagnosis is clinical. 5

Systemic corticosteroids do not help acute idiopathic urticaria and may cause unnecessary morbidity. 3 Reserve them only for severe flares unresponsive to antihistamines. 4

Special Considerations

• If lesions last >24 hours: Obtain skin biopsy and full vasculitis screen including complement levels (C3, C4) to rule out urticarial vasculitis. 4, 1
• If angioedema without wheals: Check C4 level; if low, confirm with quantitative and functional C1 inhibitor assays. 5, 1 Avoid ACE inhibitors in these patients. 1
• If anaphylaxis suspected (hypotension, hypoxia): Give intramuscular epinephrine immediately and obtain acute tryptase within 1-3 hours before referring to Allergy. 3

Monitoring and Duration

Continue treatment until complete symptom control is achieved and maintained for at least 3-6 months before considering dose reduction. 2 More than half of patients with chronic urticaria will have resolution or improvement within one year. 7