What is the primary diagnosis and differential diagnoses for a patient presenting with erythematous wheals, pruritic rashes, and undocumented fever, who did not respond to hydrocortisone and had spontaneous resolution of symptoms?

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Primary Diagnosis: Erythema Multiforme Minor

The primary diagnosis is Erythema Multiforme (EM) Minor, not acute urticaria, based on the presence of target-like lesions, progression despite antihistamine therapy, and spontaneous resolution over 2 days without response to hydrocortisone. 1

Key Distinguishing Features That Support EM Minor

The clinical evolution reveals critical diagnostic clues:

  • Target-like lesions were documented on the second presentation, which is pathognomonic for EM and not characteristic of urticaria 1
  • Lesions persisted and evolved over days rather than resolving within 24 hours as expected with urticaria 2
  • No response to hydrocortisone, which would typically improve urticaria if mast cell-mediated 3
  • Spontaneous resolution in 2 days is consistent with EM's self-limited course 1
  • Mild leukocytosis (14.39 × 10⁹/L) suggests an inflammatory/reactive process rather than simple urticaria 1

Differential Diagnoses: Comparative Analysis

Diagnosis Diagnostic Criteria/Features Patient Manifestations Why Cannot Be Ruled Out Yet
Acute Urticaria • Pruritic wheals that resolve within 24 hours
• Individual lesions blanch completely
• No target morphology
• Responds to antihistamines [2]
✓ Initial presentation with wheals
✓ Pruritic
✓ Erythematous lesions
✗ Lesions persisted >24 hours
✗ Target-like lesions present
✗ No response to hydrocortisone
Initial presentation mimicked urticaria, but evolution with target lesions and lack of antihistamine response argues against this. The presence of "some target-like lesions" essentially excludes pure urticaria [1]
EM Minor • Target or targetoid lesions (≥3 zones of color)
• Acral distribution (often starts extremities)
• Fixed lesions lasting >7 days
• Often post-infectious trigger
• Self-limited course [1]
✓ Target-like lesions documented
✓ Started extremities, spread centrally
✓ Lesions persisted days
✓ Self-limited (resolved in 2 days)
✓ Recent food exposure (potential trigger)
✓ Undocumented fever
MOST LIKELY DIAGNOSIS. All major criteria met. The "random shape" lesions may represent early/atypical targetoid lesions. Lack of mucosal involvement confirms "minor" classification [1]
Viral Exanthem • Associated with systemic viral symptoms
• Morbilliform or maculopapular rash
• Fever typically documented
• May have respiratory/GI symptoms
• Follows prodrome [1]
✓ Undocumented fever (both visits)
✓ Erythematous macular component
✗ No respiratory symptoms
✗ No clear viral prodrome
✗ Target lesions not typical
Cannot be completely excluded without viral serologies. However, the presence of target-like lesions is atypical for viral exanthems. The "undocumented fever" weakens this diagnosis as viral exanthems typically have documented high fevers [1]
Serum Sickness-Like Reaction (SSLR) • Urticarial lesions with purpuric centers
• Fever, arthralgias, lymphadenopathy
• Follows medication/antigen exposure (7-21 days)
• Facial/acral edema
• Elevated ESR/CRP [1]
✓ Urticarial component initially
✓ Undocumented fever
✗ No documented medication exposure
✗ No arthralgias reported
✗ No lymphadenopathy
✗ No purpuric centers described
✗ Leukocytosis mild, not marked
Less likely given absence of medication history and lack of systemic features (arthralgias, lymphadenopathy). The timing (acute onset within hours of food) is too rapid for SSLR, which typically occurs 7-21 days post-exposure [1]

Critical Diagnostic Features Analysis

Why EM Minor is the Primary Diagnosis:

Morphology is decisive: The documentation of "some target-like lesions" is the single most important diagnostic feature 1. True urticaria does not produce target lesions, which require fixed inflammatory infiltrates rather than transient mast cell degranulation 2.

Temporal evolution:

  • Urticaria wheals resolve within 24 hours by definition 2
  • This patient's lesions persisted and evolved over days before spontaneous resolution 1
  • The 2-day hospital course before resolution matches EM's self-limited nature 1

Treatment response:

  • Hydrocortisone failure argues against mast cell-mediated urticaria 3
  • EM is self-limited and does not require specific treatment beyond supportive care 1

Common Diagnostic Pitfalls:

Urticaria Multiforme vs. EM Minor: These are frequently confused 4, 1. Key differences:

  • Urticaria multiforme: Polycyclic wheals with central clearing that are migratory and resolve within 24 hours, responds dramatically to antihistamines 4, 1
  • EM Minor: Fixed target lesions with three zones of color that persist >24 hours, minimal antihistamine response 1

This patient has EM Minor because:

  • Lesions were fixed and persistent (not migratory)
  • No response to hydrocortisone
  • Target morphology documented
  • Self-limited resolution over days 1

Additional Diagnostic Considerations

Laboratory Findings Interpretation:

The CBC shows mild leukocytosis (14.39 × 10⁹/L) with neutrophil predominance (61%), which is consistent with an inflammatory/reactive process seen in EM 1. This is non-specific but supports an inflammatory dermatosis rather than simple urticaria 3.

The mild microcytosis (MCV 73.8 fL) and hypochromia (MCH 23.9 pg) are incidental findings, possibly representing iron deficiency or thalassemia trait, and are unrelated to the acute presentation 1.

What Additional Testing Would Definitively Distinguish These Diagnoses:

Skin biopsy (if performed during active lesions) would show:

  • EM: Interface dermatitis with keratinocyte necrosis, lymphocytic infiltrate 1
  • Urticaria: Dermal edema, perivascular infiltrate without keratinocyte damage 2
  • Viral exanthem: Variable, often non-specific perivascular lymphocytic infiltrate 1
  • SSLR: Leukocytoclastic vasculitis in some cases 1

However, skin biopsy is rarely necessary when classic target lesions are present, as clinical diagnosis is sufficient for EM Minor 1.


Clinical Management Implications

For EM Minor:

  • Supportive care only (no specific treatment required) 1
  • Identify and avoid potential triggers (recent food exposure: string beans and egg)
  • Reassurance regarding self-limited nature
  • Monitor for mucosal involvement (which would upgrade to EM Major) 1

The initial misdiagnosis as urticaria led to inappropriate treatment with hydrocortisone, which predictably failed 1. Recognition of target lesions should immediately shift diagnosis to EM Minor 1.

References

Research

Urticaria mimickers in children.

Dermatologic therapy, 2013

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acute and Chronic Urticaria: Evaluation and Treatment.

American family physician, 2017

Research

Urticaria multiforme in a 2-year-old girl.

Proceedings (Baylor University. Medical Center), 2019

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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