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, significant eosinophilia, and a history of recent antibiotic use, including Augmentin (amoxicillin/clavulanate) and Levofloxacin, despite treatment with oral corticosteroids (Prednisolone)?

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome

This patient has DRESS syndrome induced by Augmentin (amoxicillin-clavulanate), and requires immediate escalation to high-dose intravenous corticosteroids given the progressive rash with targetoid lesions and rising eosinophilia despite oral prednisolone. 1, 2

Differential Diagnosis

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

• Progressive maculopapular rash with targetoid lesions developing 2-3 weeks after Augmentin exposure 1, 3, 4
• Marked eosinophilia (initially 1.23, now 3.02 × 10⁹/L) with leukocytosis and neutrophilia 1, 2, 3
• Progression despite oral corticosteroids (prednisolone 40mg daily), indicating severe disease 1, 2
• Timing: Symptoms began within the typical 2-6 week window after drug exposure 5, 3

Calculate the RegiSCAR score immediately to stratify severity, assessing: fever (absent in this case), lymphadenopathy (absent), eosinophilia (present, >1.5 × 10⁹/L = 2 points), atypical lymphocytes, skin involvement (>50% body surface area with targetoid lesions), and organ involvement. A score ≥2 indicates possible DRESS, ≥4-5 indicates probable/definite DRESS. 1, 6

Other Considerations to Rule Out:

• Simple drug hypersensitivity reaction: Excluded by progressive course, rising eosinophilia, and failure to resolve after drug discontinuation 1
• Viral exanthem mimicking DRESS: Less likely given the marked eosinophilia (viral rashes typically lack eosinophilia), absence of fever, and timing 7
• Occupational eosinophilic bronchitis: Not relevant given no occupational exposures and systemic features 8
• Drug-induced pneumonitis: Must be considered given persistent air leak post-decortication, though the cutaneous findings dominate 1

Augmentin is the most likely culprit given the temporal relationship (rash onset shortly after exposure) and well-documented association with DRESS syndrome. 5, 3, 4 Levofloxacin is less commonly implicated but should also be discontinued. 2

Immediate Management

1. Drug Discontinuation

• Stop all potential culprit medications immediately: Discontinue Levofloxacin (current antibiotic) 1, 2, 6
• Flag Augmentin and all beta-lactams as severe allergies in the medical record 4
• Consider alternative antibiotic coverage if needed: Aztreonam or linezolid are safer alternatives if ongoing infection requires treatment 2

2. Escalate Corticosteroid Therapy

The progression of rash with targetoid lesions and rising eosinophilia despite oral prednisolone 40mg daily indicates severe DRESS requiring IV corticosteroids. 1, 2

• Initiate high-dose IV methylprednisolone 1 mg/kg/day (or prednisone equivalent 0.5-1 mg/kg/day IV) 1, 2
• Oral prednisolone 40mg daily is insufficient for this degree of severity 1
• Duration: Expect 3-6 months of treatment with very slow taper to prevent flares 2, 6
• Monitor closely for steroid-related complications during prolonged therapy 2

3. Monitoring Protocol

• Daily clinical assessment for progression of rash, new organ involvement, or systemic deterioration 2
• Eosinophil count every 2-3 days to track response 2
• Liver function tests (AST, ALT, bilirubin) twice weekly to detect hepatic involvement 2, 6
• Renal function (creatinine, BUN) twice weekly 2
• Complete blood count with differential to monitor leukocytosis and atypical lymphocytes 2
• Reassess within 48-72 hours after treatment initiation to evaluate response 1

4. Specialist Consultation

• Dermatology consultation for skin biopsy if diagnosis unclear (though clinical picture is highly suggestive) 1, 2
• Allergy/Immunology consultation for refractory cases and long-term management 2
• Skin biopsy would show interface dermatitis with eosinophilic infiltrates if performed 4

Addressing the Persistent Air Leak

Evaluate for drug-induced pneumonitis as a complicating factor, which can worsen respiratory status and delay healing. 1 The persistent air leak 16 days post-decortication may be:

• Related to underlying surgical complications (primary consideration)
• Potentially exacerbated by drug-induced pulmonary involvement from DRESS 1

Coordinate with Cardiothoracic Surgery regarding the air leak management, as DRESS-related pulmonary involvement could impair healing. 1

Critical Pitfalls to Avoid

1. Do not taper steroids too quickly: DRESS has a prolonged course with high risk of flares during taper, requiring 3-6 months of treatment 2, 6
2. Do not dismiss rising eosinophilia: This indicates disease progression and inadequate treatment 1, 2
3. Do not continue oral steroids at current dose: The progression despite prednisolone 40mg daily mandates escalation to IV therapy 1, 2
4. Do not overlook late complications: Monitor for autoimmune sequelae (thyroiditis, diabetes) that can develop months after resolution 1
5. Do not rechallenge with beta-lactams: This is a life-long contraindication 4

Expected Course

• Clinical improvement should begin within 48-72 hours of IV corticosteroids 1
• Eosinophil count normalization typically lags behind clinical improvement 2, 3
• Complete resolution may take weeks to months 2, 6
• Relapse risk is high if steroids tapered prematurely 2, 6