What are the causes of urticaria multiforme?

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Etiology of Urticaria Multiforme

Urticaria multiforme is primarily caused by hypersensitivity reactions, most commonly triggered by infections (particularly upper respiratory infections) and medications (especially antibiotics like amoxicillin). 1, 2

Clinical Characteristics and Differentiation

Urticaria multiforme is a distinct clinical variant of urticaria characterized by:

  • Acute onset of large, annular, polycyclic erythematous wheals
  • Dusky or ecchymotic centers giving a target-like appearance
  • Associated acral and facial angioedema
  • Positive dermatographism
  • Primarily affects infants and young children
  • Self-limiting course with favorable response to antihistamines

Key Etiologic Factors

1. Infectious Triggers

  • Viral infections: Most common infectious cause in children 3
    • Herpesviridae family infections (particularly in children)
    • Upper respiratory tract infections
    • Otitis media

2. Medication-Related Triggers

  • Antibiotics: Particularly amoxicillin 2
  • Other medications: Similar to triggers of ordinary urticaria 4
    • NSAIDs and aspirin
    • Codeine and other opiates
    • Radiocontrast media

3. Non-Immunological Mechanisms

  • Mast cell and basophil degranulation can occur independently of IgE receptor activation 4
  • Medications like codeine and radiocontrast media can directly trigger degranulation
  • NSAIDs and aspirin likely work through leukotriene formation and histamine release 4

Differential Diagnosis Considerations

Urticaria multiforme is frequently misdiagnosed as:

  • Erythema multiforme
  • Serum sickness-like reaction
  • Urticarial vasculitis
  • Acute hemorrhagic edema of infancy (AHOI syndrome) 5

Clinical Course and Management

  • Diagnosis is primarily clinical 5
  • Self-limiting condition typically resolving within two weeks
  • Symptomatic treatment with antihistamines is usually effective 6
  • No need for extensive laboratory evaluations or biopsies when clinical presentation is classic 1

Pitfalls and Caveats

  • The striking appearance of lesions often causes parental anxiety and may lead to unnecessary hospitalizations and testing 2
  • Distinguishing from erythema multiforme is critical as management approaches differ significantly
  • Unlike urticarial vasculitis, individual lesions in urticaria multiforme resolve within 24 hours without residual changes 4
  • The presence of fever does not exclude the diagnosis of urticaria multiforme 2

Diagnostic Approach

  • Thorough history focusing on recent infections and medication use
  • Careful examination of lesion morphology and duration
  • Observation for associated angioedema and dermatographism
  • In typical presentations, avoid unnecessary biopsies or extensive laboratory testing 1

Understanding the benign and self-limiting nature of urticaria multiforme is essential to avoid unnecessary interventions while providing appropriate symptomatic management with antihistamines.

References

Research

Urticaria multiforme.

The Journal of clinical and aesthetic dermatology, 2013

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Urticaria multiforme: difficult to distinguish from other skin conditions].

Nederlands tijdschrift voor geneeskunde, 2018

Research

Urticaria multiforme--a case report.

Pediatric dermatology, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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