What drugs can cause urticaria and how is it managed?

Drugs Causing Urticaria and Their Management

Multiple drugs can cause urticaria, including aspirin, NSAIDs, codeine, ACE inhibitors, and opioids, and management primarily involves drug avoidance and treatment with second-generation non-sedating H1 antihistamines. 1

Common Drugs That Cause Urticaria

• NSAIDs (including aspirin): One of the most common medication triggers for urticaria, likely involving leukotriene formation and histamine release 1
• Codeine and opioids: Can cause non-immunological urticaria through direct mast cell degranulation 1
• ACE inhibitors: Particularly associated with angioedema without wheals, believed to result from inhibition of kinin breakdown 1
• Radiocontrast media: Can trigger mast cell degranulation independent of IgE receptor activation 1
• Antibiotics: Particularly penicillins and sulfonamides, which are common causes of drug-induced urticaria 2

Clinical Presentation and Diagnosis

• Drug-induced urticaria typically occurs within 24 hours of drug ingestion 2
• May present with:
  • Isolated urticaria (wheals/hives)
  • Angioedema (deeper swelling of dermis and subcutaneous tissue)
  • Combination of both 3
• Diagnosis requires a detailed medication history and knowledge of common causative agents 2
• Cross-reactions between aspirin and other NSAIDs are common, related to potency of cyclooxygenase inhibition 1

Management Approach

1. Immediate Measures

• Identify and discontinue the causative drug 1, 4
• Avoid cross-reacting medications (e.g., avoid all NSAIDs in aspirin-sensitive patients) 1
• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 1

2. Pharmacological Management

First-Line Treatment:

• Second-generation non-sedating H1 antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, mizolastine) 4, 5
• Offer at least two different non-sedating antihistamines as responses vary between individuals 4
• For inadequate symptom control, increase dose up to 4 times the standard dose 4, 5

For Severe or Refractory Cases:

• Add a sedating antihistamine at night (e.g., chlorphenamine 4-12 mg, hydroxyzine 10-50 mg) to help with sleep 1
• Consider adding an H2 antihistamine which may provide better control than H1 antihistamine alone 1, 6
• Short course of oral corticosteroids for severe acute urticaria or angioedema affecting the mouth 4, 7

For Chronic Urticaria Unresponsive to Antihistamines:

• Omalizumab (anti-IgE monoclonal antibody) at 300 mg every 4 weeks 4, 8
• Cyclosporine for patients who don't respond to high-dose antihistamines and omalizumab 4, 8

3. Special Considerations

• Renal impairment: Avoid acrivastine in moderate renal impairment; halve the dose of cetirizine, levocetirizine, and hydroxyzine 1
• Hereditary angioedema: Requires specialized management with C1 inhibitor concentrate 4
• Urticarial vasculitis: Requires skin biopsy for diagnosis and may need different treatment approach 1

Prognosis

• Acute urticaria typically resolves within 3 weeks 6
• For chronic urticaria, about 50% of patients with wheals alone will be clear by 6 months 4
• Patients with both wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 4

Common Pitfalls to Avoid

• Failure to identify the causative drug: Always take a thorough medication history 2
• Continuing NSAIDs in aspirin-sensitive patients: This can worsen urticaria; all NSAIDs should be avoided in these patients 1
• Using ACE inhibitors in patients with angioedema: These should be avoided in patients with angioedema without wheals 1
• Inadequate antihistamine dosing: Many patients require higher than standard doses for symptom control 4, 5
• Prolonged corticosteroid use: Should be restricted to short courses for severe acute episodes to avoid cumulative toxicity 9