Differential Diagnoses for Acute Urticaria with Target-Like Lesions
This child most likely has acute ordinary urticaria, but the presence of target-like lesions, fever, and non-raised blanchable macular rash raises critical concerns for urticarial vasculitis, viral exanthem (particularly erythema multiforme), or an autoinflammatory syndrome that cannot be ruled out without further evaluation. 1
Key Clinical Features Guiding Differential Diagnosis
The following features are atypical for simple acute urticaria and warrant expanded differential consideration:
- Target-like lesions (not typical of ordinary urticaria) 1
- Non-raised, blanchable macular component (suggests possible vasculitic or viral etiology) 1
- Fever (uncommon in uncomplicated acute urticaria) 1
- Persistence despite antihistamine therapy (suggests alternative diagnosis) 1
- Mild leukocytosis with neutrophilia (consistent with inflammatory or infectious process) 1
Five Differential Diagnoses That Cannot Be Ruled Out Yet
1. Urticarial Vasculitis
Why ruled IN:
- Target-like lesions and macular component suggest possible vasculitic changes 1
- Persistence of lesions (patient has had symptoms for >24 hours with recurrence) 1
- Burning quality can occur with vasculitis rather than pure pruritus 2, 3
- Fever and elevated WBC are consistent with systemic inflammation 3, 4
Why CANNOT be ruled out yet:
- Lesion duration unclear: Urticarial vasculitis lesions typically persist >24 hours in the same location and resolve with hyperpigmentation or bruising 1, 2. The case describes "migratory" rashes, but individual lesion duration is not specified 1
- No skin biopsy performed: Diagnosis requires histologic confirmation showing leukocytoclastic vasculitis with endothelial damage, perivascular fibrin deposition, and red cell extravasation 1, 3
- No residual skin changes documented: Vasculitic lesions leave hyperpigmentation or purpura, which has not been assessed 1, 2
- ESR/CRP not checked: Usually elevated in urticarial vasculitis 1
Critical next steps: Observe if individual lesions persist >24 hours in same location, check for residual hyperpigmentation/bruising, obtain lesional skin biopsy if lesions persist, measure ESR/CRP 1, 3
2. Erythema Multiforme (Viral Exanthem)
Why ruled IN:
- Target-like lesions are the hallmark of erythema multiforme 5
- Acute onset with fever suggests viral trigger (common in this age group) 5
- Distribution on face, scalp, trunk, and extremities is typical 5
- Mild leukocytosis consistent with viral infection 1
- Age-appropriate presentation (common in children) 5
Why CANNOT be ruled out yet:
- True target lesions not confirmed: Classic erythema multiforme has three-zone targets (central dusky area, pale edematous ring, erythematous outer ring) with fixed location 5. Case describes "some target-like lesions" without detailed morphology 5
- Mucosal involvement not assessed: Erythema multiforme often involves oral, ocular, or genital mucosa 5
- Lesion evolution not documented: EM lesions are fixed (not migratory) and evolve over days 5
- No viral serologies or PCR performed: Common triggers include HSV, mycoplasma, other viral infections 5
Critical next steps: Examine mucous membranes carefully, document if lesions are truly fixed or migratory, consider HSV/mycoplasma testing if mucosal involvement present 5
3. Autoinflammatory Syndrome (Cryopyrin-Associated Periodic Syndrome or Schnitzler Syndrome)
Why ruled IN:
- Urticarial rash with fever is characteristic of autoinflammatory syndromes 1
- Persistent/recurrent symptoms (previous ER visit 10/18/2025, now recurring) 1, 2
- Leukocytosis suggests systemic inflammation 3, 4
- Poor response to antihistamines (symptoms persisted despite cetirizine) 2, 3
- Systemic symptoms (fever, malaise implied by presentation) 1, 2
Why CANNOT be ruled out yet:
- Age consideration: CAPS typically present in early childhood (patient is 1 year 11 months, within range), but Schnitzler syndrome is extremely rare in children 1, 3
- Inflammatory markers not checked: ESR, CRP, and serum amyloid A are characteristically elevated in autoinflammatory syndromes 1, 3
- No assessment for systemic features: Joint pain, hearing loss, neurologic symptoms, or other organ involvement not evaluated 1, 2
- Serum protein electrophoresis not performed: Required to rule out monoclonal gammopathy in Schnitzler syndrome 3
- Genetic testing not done: NLRP3 mutations confirm CAPS 2, 3
Critical next steps: Check ESR, CRP, serum amyloid A; assess for arthralgia, hearing changes, neurologic symptoms; consider serum protein electrophoresis; refer to immunology if inflammatory markers elevated 1, 3
4. Drug-Induced Urticaria/Hypersensitivity Reaction
Why ruled IN:
- Recent medication exposure: Patient received paracetamol and cetirizine 1
- Acute onset temporally related to medication administration 1
- Fever can occur with drug hypersensitivity reactions 1
- Maculopapular component suggests possible drug reaction rather than pure urticaria 5
Why CANNOT be ruled out yet:
- Temporal relationship unclear: Rash onset was 1 day prior to receiving medications, but previous ER visit medications not documented 1
- No drug challenge or rechallenge performed: Definitive diagnosis requires correlation with drug exposure 1
- Eosinophilia absent: Drug reactions often show eosinophilia, but this patient has 0% eosinophils (though this may be acute phase) 1
- No assessment for DRESS or other severe reactions: Systemic symptoms warrant evaluation for drug reaction with eosinophilia and systemic symptoms (DRESS), though timing may be too acute 5
Critical next steps: Obtain detailed medication history including over-the-counter medications, supplements, and medications from previous ER visit; monitor for eosinophilia on repeat CBC; assess liver and renal function if drug reaction suspected 1, 5
5. Acute Infectious Urticaria with Viral Exanthem
Why ruled IN:
- Fever strongly suggests infectious etiology 1
- Acute onset in previously healthy child 1
- Leukocytosis with neutrophilia (WBC 14.39 × 10⁹/L with 61% neutrophils) suggests bacterial or viral infection 1
- Age-appropriate presentation: Viral exanthems with urticarial features common in toddlers 5
- Mild microcytosis and hypochromia may suggest chronic low-grade infection or nutritional deficiency 1
Why CANNOT be ruled out yet:
- No specific infectious workup performed: No viral PCR, bacterial cultures, or specific serologies 1
- Respiratory and gastrointestinal symptoms not fully assessed: Many viral infections causing urticaria have associated systemic symptoms 5
- No assessment for streptococcal infection: Post-streptococcal urticaria can occur 1
- Hepatitis serologies not checked: Hepatitis B can present with urticaria and fever 1
- EBV/CMV not excluded: These can cause urticarial eruptions with fever 5
Critical next steps: Obtain throat culture or rapid strep test, consider viral PCR panel if systemically ill, check hepatitis serologies if risk factors present, monitor clinical course for evolution of specific viral exanthem pattern 1, 5
Critical Diagnostic Pitfalls to Avoid
Do NOT assume this is simple acute urticaria because:
- Target-like lesions are NOT typical of ordinary urticaria 1
- Fever is uncommon in uncomplicated urticaria 1
- Non-raised macular component suggests alternative diagnosis 1, 5
- Persistence despite antihistamines warrants investigation 1
Essential immediate actions:
- Document individual lesion duration precisely: Set timer and photograph specific lesions to determine if they persist >24 hours in same location 1
- Examine for residual changes: Check if lesions leave hyperpigmentation, purpura, or bruising when they fade 1, 2
- Assess mucous membranes: Look for oral, conjunctival, or genital involvement 5
- Obtain inflammatory markers: ESR, CRP before dismissing as simple urticaria 1, 3
When to obtain skin biopsy:
- If individual lesions persist >24 hours in same location 1
- If lesions resolve with hyperpigmentation or purpura 1, 2
- If patient has burning rather than itching 2, 3
- If systemic symptoms (fever, arthralgia) persist 3, 4
- If no response to appropriate-dose antihistamines after 48-72 hours 1