What is the differential diagnosis and management plan for a 39-year-old female, 16 days post-right lung decortication, with a progressive maculopapular rash, eosinophilia, and leukocytosis, despite oral corticosteroid (Prednisolone) treatment, and with a history of exposure to Augmentin (Amoxicillin/Clavulanate) and Voltaren (Diclofenac), and currently on Levofloxacin?

DRESS Syndrome: Immediate Escalation of Immunosuppression Required

This patient has Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome that is progressing despite oral corticosteroids, requiring immediate escalation to high-dose systemic corticosteroids (prednisone 0.5-1 mg/kg/day) and discontinuation of all potential offending agents, particularly Levofloxacin. 1

Differential Diagnosis

The clinical presentation strongly suggests DRESS syndrome as the primary diagnosis based on:

• Progressive maculopapular rash with targetoid lesions and petechial hemorrhage despite corticosteroid treatment 1
• Marked and worsening eosinophilia (1.23 → 3.02, normal <0.5) 1, 2
• Leukocytosis with neutrophilia 1
• Temporal relationship to multiple drug exposures (Augmentin, Voltaren, now Levofloxacin) 2
• Absence of mucosal involvement, fever, and lymphadenopathy makes Stevens-Johnson syndrome/toxic epidermal necrolysis less likely 3

RegiSCAR Score Assessment

Calculate the RegiSCAR score immediately to stratify severity (≥2 indicates possible DRESS, ≥5 indicates definite DRESS): 1

• Fever >38.5°C (0 points currently, but monitor)
• Lymphadenopathy (0 points - absent)
• Eosinophilia: >1.5 × 10⁹/L (2 points - eosinophilia 3.02)
• Atypical lymphocytes (unknown - check peripheral smear)
• Skin involvement >50% body surface area (likely present - 1-2 points)
• Organ involvement (evaluate liver, kidney, lung function)

Other Differential Considerations

• Drug-induced pneumonitis complicating the persistent air leak should be evaluated, as pulmonary involvement occurs in DRESS and can be mistaken for infection 4
• Simple drug hypersensitivity is excluded by progression despite treatment and marked eosinophilia 1
• Eosinophilic granulomatosis with polyangiitis (EGPA) is less likely given acute onset, clear drug exposure, and absence of asthma history 5

Immediate Management Plan

1. Drug Discontinuation (Most Critical Step)

• Immediately discontinue Levofloxacin - fluoroquinolones can cause DRESS syndrome 6, 7
• Review and discontinue all non-essential medications started within the past 2-8 weeks 6, 3
• Augmentin (amoxicillin/clavulanate) and Voltaren (diclofenac) were likely the initial triggers, but cross-reactivity and new sensitization to Levofloxacin must be considered 2

2. Escalate Corticosteroid Therapy

The current dose of Prednisolone 40mg daily is insufficient for progressive DRESS syndrome. 1

• Increase to prednisone 0.5-1 mg/kg/day (approximately 60-80mg daily for a typical adult) 1, 3, 7
• Consider pulse-dose methylprednisolone 500-1000mg IV daily for 3 days if severe organ involvement is present 7
• Do not taper steroids abruptly - DRESS requires prolonged treatment (weeks to months) with slow taper to prevent relapse 1, 8

3. Comprehensive Laboratory Evaluation

Obtain immediately to assess organ involvement: 1, 2, 3

• Complete blood count with differential - look for atypical lymphocytes (supports DRESS diagnosis)
• Comprehensive metabolic panel - assess liver (transaminases, bilirubin) and kidney function (creatinine)
• Troponin and ECG - cardiac involvement occurs in DRESS and carries high mortality
• Chest imaging - evaluate for eosinophilic pneumonitis vs. drug-induced lung injury (may explain persistent air leak) 4
• Repeat eosinophil count in 3-5 days to monitor response 1

4. Skin Biopsy (If Diagnosis Uncertain)

• Perform punch biopsy if clinical diagnosis is unclear, though not required with classic presentation 1
• Histology typically shows interface dermatitis with eosinophils

5. Pulmonary Evaluation

The persistent air leak post-decortication may be complicated by DRESS-related pulmonary involvement: 4

• Obtain chest CT to evaluate for eosinophilic infiltrates, pneumonitis, or pleural involvement 4, 2
• Pulmonary involvement in DRESS is frequently mistaken for bacterial pneumonia - avoid unnecessary antibiotics 4
• Consider pulmonology consultation if infiltrates are present

6. Additional Immunosuppression (If Refractory)

If no improvement after 4 weeks of high-dose corticosteroids: 7

• Intravenous immunoglobulin (IVIG) 2g/kg divided over 3-5 days 7
• Cyclosporine 3-5 mg/kg/day in divided doses 7
• Cyclophosphamide reserved for life-threatening cases 7
• N-acetylcysteine may be beneficial for hepatic involvement 7

Monitoring and Follow-Up

• Reassess within 48-72 hours for progression of rash, organ involvement, or worsening eosinophilia 1
• Monitor for late complications including autoimmune sequelae (thyroiditis, diabetes) that can occur months after resolution 1
• Prolonged steroid taper over 3-6 months is typically required - rapid taper causes relapse 1, 8
• Avoid all implicated drug classes permanently - document allergy in medical record 6, 3

Critical Pitfalls to Avoid

• Do not continue Levofloxacin - ongoing exposure to the offending agent worsens outcomes 6, 7
• Do not use inadequate corticosteroid doses - 40mg prednisolone is insufficient for progressive DRESS 1
• Do not mistake pulmonary DRESS for pneumonia - adding more antibiotics may worsen the reaction 4
• Do not taper steroids too quickly - DRESS requires prolonged treatment with slow taper 1, 8
• Do not overlook cardiac involvement - obtain troponin and ECG as myocarditis carries high mortality 7