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

Critical Clinical Assessment

The presence of target-like lesions with persistent, non-raised, blanchable macular components lasting >24 hours mandates immediate consideration of erythema multiforme (EM) rather than simple acute urticaria, and requires urgent skin biopsy to exclude urticarial vasculitis. 1, 2

Table: Differential Diagnoses That Cannot Be Ruled Out

Differential Diagnosis	Key Diagnostic Features	Patient's Manifestations	Why Cannot Be Ruled Out Yet	What's Missing/Needed
Erythema Multiforme Minor	• Target-like lesions (pathognomonic) • Fixed lesions persisting >24 hours • Symmetrical distribution on extremities, face • May have central vesiculation • Preceded by HSV or Mycoplasma infection [2]	• (+) Target-like lesions on scalp, face, back, abdomen, groin, arms, legs • (+) Persistent rashes for >24 hours • (+) Fever • (+) Symmetrical distribution	• Target morphology is pathognomonic for EM, not urticaria [2] • Lesions persisting >24 hours favor EM over urticaria (which resolves within 24 hours) [1,2] • Previous episode suggests recurrent EM pattern	• Skin biopsy showing interface dermatitis with keratinocyte necrosis and lymphocytic infiltrate [2] • HSV serology or PCR • Mycoplasma serology • Document if individual lesions are truly fixed vs. migratory
Urticarial Vasculitis	• Individual lesions lasting >24 hours • Burning/pain rather than pure pruritus • Residual purpura, ecchymosis, or hyperpigmentation after resolution • Elevated ESR/CRP • Low complement (C3, C4) [1]	• (+) Lesions present for >24 hours • (+) Pruritic (but need to assess for burning/pain) • (+) Mild leukocytosis (14.39 × 10⁹/L) • (+) Some lesions have random shapes	• Lesion duration >24 hours strongly suggests vasculitis [1] • Mild leukocytosis may indicate inflammatory/vasculitic process [1] • Target-like appearance can occur in vasculitis	• Lesional skin biopsy showing leukocytoclastic vasculitis with fibrinoid necrosis [1] • ESR and CRP levels [1] • Complement levels (C3, C4) [1] • Document if lesions leave purpura or hyperpigmentation [1]
Urticaria Multiforme	• Annular, polycyclic urticarial plaques with dusky, ecchymotic centers • Acral edema (hands, feet, face) • Pruritic • Individual lesions resolve within 24 hours • Benign, self-limited (typically viral trigger) [3,4]	• (+) Target-like lesions (could be polycyclic plaques) • (+) Pruritic • (+) Face and scalp involvement • (+) Fever • (+) Recent urticaria episode	• Polycyclic urticarial plaques can mimic target lesions [3,4] • Fever and viral prodrome common [3] • Age-appropriate (common in toddlers) [3]	• Document lesion duration (should resolve within 24 hours) [3] • Assess for acral edema [3] • Skin biopsy shows dermal edema and perivascular infiltrate WITHOUT keratinocyte damage [2,3]
Acute Hemorrhagic Edema of Infancy (AHEI)	• Age 4-24 months (peak incidence) • Large targetoid purpuric plaques on face and extremities • Marked acral edema • Fever • Benign, self-limited • Normal platelet count [3]	• (+) Age 23 months (within range) • (+) Face and extremity involvement • (+) Fever • (+) Normal platelet count (275 × 10⁹/L) • (?) Need to assess for purpura vs. blanching	• Age-appropriate for AHEI [3] • Distribution matches (face, extremities) [3] • Fever present [3] • Need to clarify if lesions are truly purpuric or blanchable	• Clarify if lesions are purpuric (non-blanching) or erythematous (blanching) [3] • Assess for marked acral edema [3] • Skin biopsy shows leukocytoclastic vasculitis in small vessels [3]
Viral Exanthem with Urticarial Features	• Acute onset with fever • Maculopapular or urticarial rash • Systemic symptoms (malaise, fever) • Self-limited • May have atypical morphology [2,3]	• (+) Fever • (+) Acute onset • (+) Erythematous macular rash • (+) Pruritic • (+) Mild leukocytosis	• Viral infections commonly cause urticarial or maculopapular rashes in toddlers [3] • Fever and leukocytosis support viral etiology • Target-like appearance can occur in viral exanthems [2]	• Viral serologies (EBV, CMV, enterovirus, adenovirus) • Skin biopsy shows variable non-specific perivascular lymphocytic infiltrate [2] • Clinical observation for evolution and resolution pattern
Serum Sickness-Like Reaction (SSLR)	• Urticarial rash with purpuric or targetoid features • Fever, arthralgia, lymphadenopathy • Occurs 7-14 days after medication/infection exposure • Elevated ESR [3]	• (+) Urticarial rash with target-like features • (+) Fever • (+) Recent medication exposure (cetirizine, paracetamol) • (?) Need to assess for arthralgia, lymphadenopathy	• Target-like lesions can occur in SSLR [3] • Fever present [3] • Recent medication exposure (though timing unclear) [3]	• Detailed medication timeline (7-14 days before onset) [3] • Assess for arthralgia and lymphadenopathy [3] • ESR level [3] • Skin biopsy shows perivascular lymphocytic infiltrate [3]

Algorithmic Approach to Differentiation

Step 1: Document Individual Lesion Duration

If lesions resolve within 24 hours: Favors acute urticaria or urticaria multiforme 1, 2, 3
If lesions persist >24 hours: Strongly suggests erythema multiforme or urticarial vasculitis 1, 2

Step 2: Assess Lesion Characteristics After Resolution

No residual marks: Favors urticaria or urticaria multiforme 1, 2
Purpura, ecchymosis, or hyperpigmentation: Pathognomonic for urticarial vasculitis 1

Step 3: Evaluate Symptom Quality

Pure pruritus: Favors urticaria, urticaria multiforme, or viral exanthem 1, 3
Burning or pain: Suggests urticarial vasculitis 1

Step 4: Assess for Acral Edema

Marked acral edema (hands, feet, face): Suggests urticaria multiforme or AHEI 3
No significant edema: Favors EM, viral exanthem, or SSLR 2, 3

Step 5: Determine if Lesions Are Blanching

Completely blanching: Favors urticaria, urticaria multiforme, EM, or viral exanthem 2, 3
Non-blanching (purpuric): Suggests AHEI or urticarial vasculitis 1, 3

Mandatory Investigations

Immediate (Within 24-48 Hours)

Lesional skin biopsy (mandatory given target-like lesions and persistence >24 hours) 1, 2
- Interface dermatitis with keratinocyte necrosis → EM 2
- Leukocytoclastic vasculitis → Urticarial vasculitis or AHEI 1, 3
- Dermal edema without keratinocyte damage → Urticaria or urticaria multiforme 2, 3

Laboratory Workup

ESR and CRP (to evaluate for vasculitis or autoinflammatory disease) 1, 3
Complement levels (C3, C4) (if urticarial vasculitis suspected) 1
Viral serologies (EBV, CMV, enterovirus, adenovirus) 2, 3
HSV serology or PCR (EM commonly triggered by HSV) 2
Mycoplasma serology (EM trigger in children) 2

Clinical Documentation

Mark lesion borders with ink and photograph to assess migration vs. fixed nature 5
Document exact duration of individual lesions (set timer for 24 hours) 1, 2
Assess for acral edema (hands, feet, face) 3
Detailed medication timeline (7-14 days before onset for SSLR) 3

Critical Pitfalls to Avoid

Pitfall 1: Assuming All Pruritic Rashes Are Urticaria

Target-like lesions are NOT characteristic of ordinary urticaria and mandate consideration of EM or vasculitis 1, 2
Do not dismiss target morphology as "atypical urticaria" without biopsy 1, 2

Pitfall 2: Delaying Skin Biopsy

Lesions persisting >24 hours with target morphology require immediate biopsy to differentiate EM from urticarial vasculitis 1, 2
Biopsy is the only definitive way to distinguish these entities 1, 2

Pitfall 3: Over-Relying on Antihistamine Response

Lack of response to cetirizine does NOT rule out urticaria but increases suspicion for EM or vasculitis 1, 2
EM and vasculitis do not respond to antihistamines 2, 3

Pitfall 4: Missing AHEI in This Age Group

AHEI is age-appropriate (4-24 months) and presents with targetoid purpuric plaques that can mimic EM 3
Key differentiator is purpura (non-blanching) vs. erythema (blanching) 3

Pitfall 5: Ignoring Recurrence Pattern

Previous episode of "acute urticaria" may have been misdiagnosed EM 2
Recurrent EM is common and often HSV-triggered 2

Management Pending Definitive Diagnosis

Supportive Care

Continue antihistamines (cetirizine) for symptomatic relief, though response is limited in EM or vasculitis 2, 3
Topical corticosteroids for pruritus 5
Avoid NSAIDs until urticarial vasculitis is excluded (may worsen vasculitis) 1

Monitoring

Daily assessment for development of mucosal involvement (would upgrade to EM major) 2
Monitor for systemic symptoms (arthralgia, abdominal pain, renal involvement) suggesting vasculitis or systemic disease 1, 3
Photograph lesions daily to document evolution 5, 2

When to Escalate

Mucosal involvement (oral, ocular, genital) → EM major or Stevens-Johnson syndrome 2
Respiratory distress or angioedema → Anaphylaxis (though unlikely given presentation) 5, 6
Systemic symptoms (arthralgia, abdominal pain, hematuria) → Urticarial vasculitis or systemic disease 1, 3

What are the possible differential diagnoses for a patient presenting with sudden onset of pruritic, erythematous, migratory rashes, and what are their diagnostic criteria?

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