What is the differential diagnosis for a patient with targetoid lesions and dusky red patches, neutropenia, elevated liver enzymes, and lactate dehydrogenase, who was recently diagnosed with chicken pox and treated with valacyclovir (Valacyclovir), ibuprofen (Ibuprofen), and Augmentin (Amoxicillin/Clavulanate)?

Differential Diagnosis: Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

This patient most likely has drug-induced Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN), with the primary culprits being valacyclovir, ibuprofen, or Augmentin, rather than a complication of varicella infection itself. The combination of targetoid lesions, dusky red patches, neutropenia, and elevated liver enzymes/LDH occurring 5 days into treatment strongly suggests a severe cutaneous adverse drug reaction rather than varicella progression 1.

Primary Differential Diagnoses

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (Most Likely)

• SJS/TEN presents with flat atypical targets or purpuric macules with epidermal detachment, systemic symptoms, and involvement of multiple mucosal surfaces 2, 1
• The timing (5 days post-drug initiation) aligns with typical SJS/TEN onset, which usually occurs 1-3 weeks after drug exposure but can occur earlier 1
• Augmentin (amoxicillin/clavulanate) is a high-risk drug for SJS/TEN, as aminopenicillins and cephalosporins are well-documented triggers 1
• NSAIDs (ibuprofen) of various types are also recognized SJS/TEN triggers 1
• The neutropenia, elevated liver enzymes, and elevated LDH are consistent with the systemic involvement seen in SJS/TEN 1
• Mortality risk is 1-5% for SJS and 25-35% for TEN, requiring immediate SCORTEN assessment and specialized intensive care 1

Erythema Multiforme (Less Likely but Consider)

• EM typically presents with typical target lesions (dark red center, pink ring, well-defined circular appearance) predominantly on limbs and extremities 2, 3
• EM is mostly related to HSV infection or Mycoplasma pneumoniae, not typically drug-induced, and has better prognosis than SJS/TEN 2
• The presence of neutropenia and significantly elevated liver enzymes makes EM less likely, as EM is usually a more benign hypersensitivity reaction without severe systemic involvement 3, 2
• EM lesions remain fixed for minimum 7 days and are usually self-limited 2

Drug Hypersensitivity Reaction/Drug Eruption

• Nonspecific drug eruptions can present as maculopapular rashes, urticaria, or erythematous macules 4, 5
• However, the presence of targetoid lesions with systemic involvement (neutropenia, elevated LDH) suggests a more severe reaction than simple drug eruption 3

Disseminated Varicella with Secondary Bacterial Infection (Less Likely)

• While varicella can cause disseminated lesions, targetoid morphology is not typical of varicella progression 6, 7
• The patient was already on appropriate antiviral therapy (valacyclovir) which should control varicella progression 6
• Secondary bacterial infection would more likely present with purulence and localized inflammation rather than targetoid lesions 3

Critical Differentiating Features to Assess Immediately

Skin Examination Details

• Determine if lesions show epidermal detachment or positive Nikolsky sign (pathognomonic for SJS/TEN) 1, 2
• Assess percentage of body surface area involved: <10% suggests SJS, 10-30% is SJS-TEN overlap, >30% is TEN 1
• Examine for mucosal involvement (oral, ocular, genital) which is characteristic of SJS/TEN 1, 3
• Document if lesions are raised (more consistent with EM) versus flat atypical targets (more consistent with SJS/TEN) 2, 8

Laboratory Confirmation Needed

• Immediate skin biopsy showing full-thickness epidermal necrolysis with extensive keratinocyte apoptosis confirms SJS/TEN 1, 3
• The neutropenia and elevated liver enzymes/LDH support systemic involvement consistent with SJS/TEN 1
• Blood cultures to exclude sepsis, as immunocompromised patients with skin breakdown are at high risk for secondary bacterial/fungal infections 3

Additional Differential Considerations (Lower Priority)

Vasculitis

• Leukocytoclastic vasculitis can present with targetoid-appearing lesions but typically shows palpable purpura 3, 9
• Biopsy would show leukocytoclastic changes rather than full-thickness epidermal necrosis 3

Fixed Drug Eruption

• Presents with well-demarcated round plaques that recur in same location with drug re-exposure 9
• Less likely given the disseminated nature and systemic involvement 9

Ecthyma Gangrenosum

• Presents in neutropenic patients with necrotic ulcers, typically from Pseudomonas infection 9
• Would show bacterial organisms on culture and different histopathology 9

Immediate Management Priorities

Stop all potentially causative medications immediately (valacyclovir, ibuprofen, Augmentin) - this is the single most important intervention 1.

Calculate SCORTEN to assess mortality risk and determine need for ICU transfer 1:

• Age >40 years
• Heart rate >120
• Cancer/malignancy
• Body surface area involved >10%
• Serum urea >10 mmol/L
• Serum glucose >14 mmol/L
• Serum bicarbonate <20 mmol/L

Obtain urgent dermatology consultation and consider transfer to burn unit or intensive care setting 1.

Perform skin biopsy immediately to confirm diagnosis and exclude other blistering diseases 3, 1.

Consider high-dose intravenous immunoglobulin (IVIG) therapy if SJS/TEN confirmed, though evidence is mixed 1.

Common Pitfalls to Avoid

• Do not attribute targetoid lesions to varicella progression without considering drug reaction - the timing and morphology strongly suggest drug-induced pathology 1, 8
• Do not delay stopping suspected causative drugs while awaiting biopsy results - mortality increases with continued drug exposure 1
• Do not use systemic corticosteroids without specialist consultation - their role in SJS/TEN is controversial and may increase infection risk 3, 1
• Do not overlook the need for meticulous supportive care including fluid/electrolyte management, wound care, and infection prevention - these patients require burn unit-level care 1, 3