What are the possible differential diagnoses for a patient presenting with acute urticaria and pruritic rashes, and why can't they be ruled out yet?

Differential Diagnoses for Acute Urticaria with Target-Like Lesions in a Toddler

The presence of target-like lesions, non-raised macular components, and persistence beyond 24 hours in this child requires urgent consideration of erythema multiforme, urticarial vasculitis, and urticaria multiforme before accepting a diagnosis of simple acute urticaria. 1

Primary Differential Diagnoses That Cannot Be Ruled Out

1. Erythema Multiforme (EM)

Cannot be ruled out because:

• Target-like lesions are pathognomonic for EM, consisting of three concentric zones with a dusky center, intermediate pale zone, and erythematous outer ring 1
• The patient exhibits non-raised, macular components which are characteristic of EM rather than typical urticarial wheals 1
• Fever is present (38°C), which commonly accompanies EM, particularly when triggered by infections 2
• The rash involves face, scalp, trunk, and extremities in a distribution consistent with EM 2

Distinguishing features to assess:

• Individual lesion duration >24 hours strongly suggests EM over urticaria, as urticarial wheals typically resolve within 24 hours 3, 1
• Fixed lesions (non-migratory) favor EM, whereas the history states "migratory" which is more consistent with urticaria 3
• Mucosal involvement (oral, conjunctival, genital) would strongly support EM but is not documented in this case 2
• Residual hyperpigmentation or purpura after lesion resolution indicates EM or vasculitis rather than simple urticaria 1

Why definitive exclusion requires:

• Lesional skin biopsy is mandatory when target-like lesions are present to differentiate urticaria from EM histologically 1
• Documentation of whether individual lesions persist beyond 24 hours in the same location 3, 1

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2. Urticarial Vasculitis

Cannot be ruled out because:

• Target-like lesions can occur in urticarial vasculitis, mimicking both urticaria and EM 1
• The patient has mild leukocytosis (14.39 × 10⁹/L) which may indicate underlying inflammatory or vasculitic process 3
• Fever is present, which can accompany urticarial vasculitis as a systemic manifestation 3

Distinguishing features to assess:

• Lesion duration >24 hours is characteristic of urticarial vasculitis, with lesions potentially lasting up to 3 days 3
• Pain or burning sensation rather than pure pruritus suggests vasculitis over simple urticaria 3
• Residual purpura, ecchymosis, or hyperpigmentation after lesion resolution is pathognomonic for urticarial vasculitis 3, 1
• Systemic symptoms including arthralgias, abdominal pain, or renal involvement would support vasculitis 3

Why definitive exclusion requires:

• ESR and CRP measurement to evaluate for vasculitis or autoinflammatory disease 1
• Complement levels (C3, C4) should be checked if urticarial vasculitis is suspected 1
• Skin biopsy showing leukocytoclastic vasculitis is the gold standard for diagnosis 3, 1

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3. Urticaria Multiforme

Cannot be ruled out because:

• Target-like or polycyclic annular wheals are the hallmark of urticaria multiforme, exactly matching this patient's presentation 4, 2
• Rapid spread over 24 hours involving face, trunk, and extremities is characteristic 4
• Age 1 year 11 months falls within the typical pediatric age range for urticaria multiforme 4, 2
• Pruritic nature is consistent with urticaria multiforme 4

Distinguishing features to assess:

• Individual wheals are transient (<24 hours) and migratory, which the history suggests ("migratory rashes") 4, 2
• Acral edema (hands, feet, face) is commonly present in urticaria multiforme but not specifically documented here 2
• Blanching with pressure indicates urticaria multiforme rather than fixed erythema of EM 4, 2
• Benign clinical course with rapid response to antihistamines within 24 hours supports urticaria multiforme 4

Why definitive exclusion requires:

• Careful documentation of lesion behavior over the next 24-48 hours to confirm transience and migration 4, 2
• Response to antihistamine therapy - dramatic improvement within 24 hours strongly supports urticaria multiforme over EM 4
• Recognition that urticaria multiforme is commonly misdiagnosed as EM, leading to unnecessary testing 4, 2

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4. Acute Hemorrhagic Edema of Infancy (AHEI)

Cannot be ruled out because:

• Age 1 year 11 months falls within the typical range (4-24 months) for AHEI 2
• Fever is present, which commonly precedes or accompanies AHEI 2
• Facial involvement is characteristic of AHEI, which typically affects face and extremities 2
• Target-like or cockade lesions can occur in AHEI, mimicking other conditions 2

Distinguishing features to assess:

• Palpable purpura rather than blanching wheals is the hallmark of AHEI, not clearly documented here 2
• Non-pitting edema of face, ears, and extremities is characteristic but not specifically noted 2
• Distribution favoring face and acral sites (hands, feet) with relative sparing of trunk would support AHEI 2
• Benign self-limited course despite dramatic appearance is typical of AHEI 2

Why definitive exclusion requires:

• Careful assessment for purpura versus blanching wheals - the description states "blanchable" which argues against AHEI 2
• Platelet count is normal (275 × 10⁹/L), which is consistent with AHEI but doesn't exclude it 2
• Skin biopsy showing leukocytoclastic vasculitis would confirm AHEI if clinical suspicion is high 2

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5. Serum Sickness-Like Reaction (SSLR)

Cannot be ruled out because:

• Recent medication exposure (paracetamol, cetirizine) could trigger SSLR, though these are less common culprits 2
• Fever is present, which is a cardinal feature of SSLR 2
• Urticarial or target-like rashes are characteristic cutaneous manifestations of SSLR 2
• Age and acute onset are consistent with SSLR in pediatric patients 2

Distinguishing features to assess:

• Timing of medication exposure - SSLR typically occurs 7-21 days after initial drug exposure or 1-3 days after re-exposure 2
• Arthralgias or arthritis are present in most SSLR cases but not documented here 2
• Lymphadenopathy is common in SSLR but not noted on examination 2
• Facial and acral edema with periarticular distribution would support SSLR 2

Why definitive exclusion requires:

• Detailed medication timeline to establish temporal relationship between drug exposure and symptom onset 2
• ESR elevation is typical in SSLR but not yet measured 2
• Complement levels (C3, C4) are typically normal in SSLR, distinguishing it from true serum sickness 2

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Critical Diagnostic Steps Required

Immediate actions needed:

• Photograph and document lesion characteristics including size, shape, color zones, and distribution 1
• Mark individual lesions to assess whether they persist >24 hours in the same location 3, 1
• Obtain ESR and CRP to evaluate for vasculitis or systemic inflammation 1
• Consider skin biopsy if lesions persist >24 hours, show purpura, or fail to respond to antihistamines within 24-48 hours 1

Common pitfall: The British Journal of Dermatology emphasizes that no routine investigations are required for acute urticaria unless the history suggests specific triggers 3. However, the presence of target-like lesions changes this recommendation entirely and mandates further evaluation 1.

Key decision point: If lesions demonstrate complete resolution within 24 hours and dramatic response to antihistamines, urticaria multiforme is most likely and no further workup is needed 4. If lesions persist beyond 24 hours or leave residual changes, biopsy is mandatory to differentiate EM, urticarial vasculitis, or other mimickers 1.