Do Acute Urticaria and Erythema Multiforme Have the Same Therapeutics?
No, acute urticaria and erythema multiforme require fundamentally different therapeutic approaches because they are distinct pathophysiologic entities with different underlying mechanisms, clinical courses, and treatment targets.
Key Clinical Distinctions That Drive Different Management
The most critical distinguishing feature is lesion duration: acute urticaria wheals last 2-24 hours and resolve completely, while erythema multiforme lesions are fixed for a minimum of 7 days 1, 2. This fundamental difference reflects distinct disease mechanisms—urticaria is a mast cell-mediated immediate hypersensitivity reaction, whereas erythema multiforme is a cell-mediated immune reaction (most commonly triggered by HSV-DNA) 2, 3.
Treatment of Acute Urticaria
First-Line Therapy
- Second-generation H1-antihistamines are the cornerstone of treatment: cetirizine, desloratadine, fexofenadine, levocetirizine, or loratadine at standard doses initially for 2-4 weeks 4, 5
- If inadequate response after 2-4 weeks, increase antihistamine dose up to four times the standard dose 4
Second-Line Options
- Add H2-antihistamines (ranitidine or famotidine) for resistant cases 4
- Consider adding leukotriene receptor antagonists (montelukast) as adjunctive therapy 4, 5
- Short courses of oral corticosteroids may be used (e.g., prednisolone 50 mg daily for 3 days in adults), but avoid long-term use 4
Symptomatic Measures
- Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) 4, 5
- Minimize aggravating factors: overheating, stress, alcohol 4
- Avoid NSAIDs in aspirin-sensitive patients 5
Treatment of Erythema Multiforme
Acute Erythema Multiforme
- Symptomatic treatment with topical corticosteroids or antihistamines (note: antihistamines here are for itch relief, not disease modification) 2, 6
- Identify and treat the underlying etiology if known (stop causative medication, treat infection) 2, 6
- Severe mucosal involvement requires hospitalization for intravenous fluids and electrolyte repletion 2
Recurrent Herpes Simplex Virus-Associated Erythema Multiforme
- First-line: Prophylactic antiviral therapy (acyclovir, valacyclovir, or famciclovir) 2, 6, 7
- If resistant to one antiviral agent, switch to an alternative antiviral drug 7
- For patients non-responsive to antivirals, consider dapsone, JAK-inhibitors, or apremilast 7
Mucosal Involvement
- High-potency topical corticosteroids 6
- Antiseptic or anesthetic solutions for mucosal sites 6
- Systemic corticosteroid therapy may be used for severe cases 6
Why the Treatments Differ
Urticaria responds to antihistamines because it is driven by mast cell degranulation and histamine release 4, 5. The therapeutic goal is to block histamine receptors and prevent wheal formation. Antihistamines are disease-modifying in urticaria.
Erythema multiforme does not respond to antihistamines as disease-modifying therapy because it is a T cell-mediated immune reaction 3. When antihistamines are used in erythema multiforme, they provide only symptomatic itch relief, not disease control 2, 6. The therapeutic focus is on treating the trigger (especially HSV with antivirals) and providing supportive care 2, 6, 7.
Common Pitfall to Avoid
Do not confuse urticaria multiforme (a pediatric variant of urticaria with annular polycyclic wheals) with erythema multiforme 8. Despite the similar name, urticaria multiforme is treated identically to standard urticaria with antihistamines and resolves within two weeks 8. The key distinguishing feature remains lesion duration: urticaria multiforme wheals still resolve within 24 hours, while erythema multiforme lesions persist for at least 7 days 1, 2, 8.
Special Consideration: Azithromycin
While azithromycin is mentioned in acne guidelines, it is notable that azithromycin can cause erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis as adverse effects 9. This underscores that these are distinct entities from urticaria, with different risk profiles and management needs.