What are the possible differential diagnoses for a patient presenting with acute urticaria, characterized by erythematous wheals, pruritic rashes, and undocumented fever, with a complete blood count (CBC) showing mild leukocytosis and normal red and platelet parameters?

Differential Diagnoses for Acute Urticaria with Target-Like Lesions

Primary Working Diagnosis

This patient most likely has acute urticaria secondary to food allergen exposure (egg or string beans), but the presence of target-like lesions and persistent, non-raised macular components raises significant concern for erythema multiforme or urticarial vasculitis that cannot be ruled out without further evaluation. 1

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Five Differential Diagnoses That Cannot Be Ruled Out Yet

1. Acute Ordinary Urticaria (Food-Induced)

Rule IN:

• Classic presentation with erythematous wheals appearing within 2 hours of food exposure (string beans and egg) 1
• Pruritic, migratory rashes affecting face, scalp, trunk, and extremities 1
• Age-appropriate presentation (acute urticaria common in pediatric population) 1
• Initial episode resolved but recurred, consistent with re-exposure pattern 1
• No respiratory distress or systemic involvement suggesting uncomplicated urticaria 1

Cannot Rule OUT Yet:

• Target-like lesions are NOT typical of ordinary urticaria, which presents with transient wheals lasting <24 hours 1
• Description includes "non-raised, blanchable macular rash" which contradicts classic urticarial wheals that should be raised 1
• Persistence beyond typical urticarial timeframe (individual wheals should resolve within 24 hours) 1
• Need skin-prick testing or CAP fluoroimmunoassay to confirm IgE-mediated food allergy 1

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2. Erythema Multiforme (EM)

Rule IN:

• CRITICAL FINDING: Presence of target-like lesions is pathognomonic for EM, not urticaria 2
• Distribution pattern (face, scalp, trunk, extremities) consistent with EM 2
• Associated fever documented on both presentations 2
• Non-raised macular component described, which fits EM better than urticaria 2
• Recent viral prodrome possible (fever suggests infectious trigger) 2

Cannot Rule OUT Yet:

• No documentation of mucosal involvement (oral, conjunctival, genital), which would confirm EM major 2
• No clear history of HSV infection or medication exposure (common EM triggers) 2
• Pruritus is prominent here, whereas EM is typically more painful or burning 2
• Requires clinical correlation and possibly skin biopsy to differentiate from urticaria 1
• Target lesions in EM should have three distinct zones (central dusky area, pale edematous ring, erythematous outer ring) - documentation unclear 2

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3. Urticarial Vasculitis

Rule IN:

• Lesions described as persistent (lasting >24 hours based on timeline from first to second visit) 1
• Some lesions have "random shape" which could represent palpable purpura 1, 2
• Fever present on both occasions, suggesting systemic inflammation 1, 2
• Mild leukocytosis (14.39 × 10⁹/L) consistent with inflammatory process 1, 2
• Target-like appearance could represent early vasculitic changes 2

Cannot Rule OUT Yet:

• No documentation of post-inflammatory hyperpigmentation or bruising after lesion resolution (hallmark of urticarial vasculitis) 1, 2
• ESR/CRP not checked - should be elevated in urticarial vasculitis 1, 2
• Lesional skin biopsy not performed - ESSENTIAL to confirm vasculitis (leucocytoclasia, endothelial damage, fibrin deposition, RBC extravasation) 1
• No complement levels (C3, C4) checked - low levels suggest hypocomplementemic urticarial vasculitis with worse prognosis 1
• Individual wheals in urticarial vasculitis are typically painful rather than pruritic 2

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4. Autoinflammatory Syndrome (Cryopyrin-Associated Periodic Syndrome or Early Schnitzler Syndrome)

Rule IN:

• Recurrent urticarial plaques with systemic inflammation (fever, elevated WBC) 1, 2
• Persistent/recurrent nature despite antihistamine therapy 2
• Fever accompanying each urticarial episode suggests systemic autoinflammatory process 1, 2
• Young age appropriate for hereditary cryopyrin-associated periodic syndromes (CAPS) 1
• Mild leukocytosis supporting inflammatory process 2

Cannot Rule OUT Yet:

• No documentation of other systemic features (arthralgia, conjunctivitis, hearing loss, CNS involvement) typical of CAPS 1, 2
• CRP/serum amyloid A not measured - should be markedly elevated in autoinflammatory syndromes 2
• Serum protein electrophoresis not performed - essential to rule out monoclonal gammopathy in Schnitzler syndrome 2
• No family history documented for hereditary periodic fever syndromes 1
• Lesions in autoinflammatory syndromes typically last >24 hours and are less responsive to antihistamines 2
• Schnitzler syndrome extremely rare in pediatric population 2

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5. Viral Exanthem with Urticarial Features

Rule IN:

• Fever documented on both presentations suggests viral infection 1
• Acute onset in previously healthy child 3, 4
• Mild leukocytosis (14.39 × 10⁹/L) with neutrophil predominance (61%) consistent with viral or early bacterial infection 1
• Migratory, polymorphous rash pattern can occur with viral infections 3
• Age-appropriate (viral exanthems common in toddlers) 3

Cannot Rule OUT Yet:

• No specific viral prodrome documented (cough, coryza, diarrhea) 3
• Viral exanthems typically have more morbilliform or maculopapular pattern rather than true wheals 3
• No exposure history to sick contacts documented 3
• Pruritus is prominent, which is less typical for viral exanthems 3
• Viral serologies or PCR not performed to identify specific pathogen 1

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Critical Next Steps for Definitive Diagnosis

Immediate Actions Required:

1. Lesional skin biopsy - MANDATORY if lesions persist >24 hours or have target-like appearance to differentiate urticaria from urticarial vasculitis or EM 1, 2

2. Laboratory workup:

   • ESR and CRP to assess for vasculitis or autoinflammatory disease 1, 2
   • Complement levels (C3, C4) if urticarial vasculitis suspected 1
   • Serum protein electrophoresis if autoinflammatory syndrome considered 2

3. Document lesion characteristics precisely:

   • Duration of individual wheals (should be <24 hours in urticaria) 1
   • Presence of bruising or hyperpigmentation after resolution 1, 2
   • Pain vs. pruritus predominance 2

4. Allergy evaluation if acute urticaria confirmed:

   • Skin-prick testing or CAP fluoroimmunoassay for egg and legume allergens 1
   • Consider oral food challenge in controlled setting 1

Common Pitfalls to Avoid:

• Do NOT assume all urticarial-appearing rashes are benign urticaria - target lesions demand investigation for EM or vasculitis 2
• Do NOT delay skin biopsy if lesions persist >24 hours or have atypical features 1
• Do NOT perform extensive laboratory workup for typical acute urticaria responding to antihistamines 1
• Do NOT miss anaphylaxis - always assess for respiratory compromise, hypotension, or GI symptoms 1, 5