A 32-year-old man on carbamazepine for temporal lobe epilepsy presents with a 3-week history of fever, pruritic rash, and cervical lymphadenopathy. Laboratory investigations show WBC 12,000/μL with 18% eosinophils, and liver function tests reveal AST 180 U/L and ALT 210 U/L. A skin biopsy shows perivascular lymphocytic infiltrate with eosinophils. Which of the following is the most appropriate immediate management?

Explanation

## DRESS Syndrome: Recognition and Management ### Clinical Presentation **Key Point:** DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe, delayed drug hypersensitivity reaction typically occurring 2–8 weeks after drug initiation. This patient demonstrates the classic tetrad: - **Fever** (>38.5°C in most cases) - **Rash** (pruritic, maculopapular, often facial edema) - **Lymphadenopathy** (cervical, axillary, inguinal) - **Systemic involvement** (hepatomegaly, elevated transaminases, eosinophilia) ### Diagnostic Criteria (RegiSCAR Scoring) The patient meets multiple major criteria: - Atypical lymphocytes on blood smear or lymphocytosis - Eosinophilia (≥1500/μL or atypical lymphocytes ≥5%) - Skin involvement (pruritic rash) - Lymphadenopathy - Hepatic involvement (AST/ALT elevation) - Temporal relationship to carbamazepine (aromatic antiepileptic) ### Causative Agents **High-Yield:** Aromatic antiepileptics are the most common culprits: - Carbamazepine (highest risk) - Phenytoin - Phenobarbital Other drugs: allopurinol, sulfonamides, NSAIDs, minocycline. ### Management Algorithm ```mermaid flowchart TD A["Suspected DRESS Syndrome<br/>(fever + rash + lymphadenopathy<br/>+ eosinophilia + organ involvement)"]:::outcome A --> B{"Causative drug<br/>identified?"}:::decision B -->|Yes| C["DISCONTINUE drug<br/>immediately"]:::urgent B -->|No| D["Investigate for<br/>other causes"]:::action C --> E["Initiate systemic<br/>corticosteroids<br/>(0.5-1 mg/kg/day<br/>prednisolone)"]:::action E --> F["Supportive care<br/>+ monitor LFTs"]:::action F --> G{"Clinical improvement<br/>in 1-2 weeks?"}:::decision G -->|Yes| H["Taper steroids<br/>over 6-12 weeks"]:::action G -->|No| I["Consider second-line:<br/>IVIG, cyclosporine,<br/>or mycophenolate"]:::action ``` ### Why Immediate Discontinuation is Critical **Clinical Pearl:** Continuing the offending drug while on steroids does NOT improve outcomes and delays resolution. The drug must be removed first. **Key Point:** Systemic corticosteroids are the cornerstone of treatment: - Dosing: 0.5–1 mg/kg/day prednisolone (or equivalent) - Taper gradually over 6–12 weeks to prevent rebound - Response typically seen within 1–2 weeks ### Prognosis and Complications - Mortality: 5–10% if untreated (organ failure, secondary infection) - With prompt treatment: >90% recovery - Reactivation syndrome: Rare flare on corticosteroid withdrawal (managed with re-escalation) **Warning:** Do NOT re-challenge with the same drug or structurally similar agents (e.g., switching carbamazepine to phenytoin carries 25–30% cross-reactivity risk). ### Why Biopsy Confirmation is NOT Needed First The clinical and laboratory picture is sufficiently diagnostic (RegiSCAR score likely ≥4, indicating "probable" DRESS). Delaying drug discontinuation while awaiting biopsy results increases morbidity and mortality risk.