A 42-year-old woman on phenytoin for 6 weeks presents with fever (38.5°C), facial edema, and eosinophilia (2800/μL). Liver function tests show ALT 320 U/L and AST 280 U/L. Skin biopsy reveals perivascular lymphocytic infiltrate with eosinophils. Which of the following is the most appropriate immediate management?

Explanation

## DRESS Syndrome: Clinical Recognition and Management ### Case Analysis This patient presents with the classic triad of **Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)** syndrome: - **Timeline:** 6 weeks after phenytoin initiation (typical latency 2–8 weeks) - **Cutaneous findings:** Facial edema, erythematous rash (implied by biopsy context) - **Systemic involvement:** Fever, hepatomegaly (elevated transaminases), eosinophilia - **Histology:** Perivascular lymphocytic infiltrate with eosinophils (diagnostic hallmark) ### Pathophysiology DRESS is a severe, potentially life-threatening drug hypersensitivity reaction characterized by: 1. Reactivation of latent herpesviruses (HHV-6, HHV-7, EBV) due to drug-induced immune dysregulation 2. Polyclonal T-cell activation and eosinophil recruitment 3. Multi-organ involvement (skin, liver, lymph nodes, lungs, kidneys) ### Management Algorithm ```mermaid flowchart TD A[Suspected DRESS Syndrome]:::outcome --> B{Confirm diagnosis<br/>via clinical + biopsy}:::decision B -->|Confirmed| C[IMMEDIATE: Discontinue<br/>offending drug]:::urgent C --> D[Initiate systemic<br/>corticosteroids]:::action D --> E[Prednisolone 0.5-1 mg/kg/day<br/>or methylprednisolone IV]:::action E --> F[Monitor LFTs, CBC,<br/>viral serology]:::action F --> G[Taper steroids over<br/>8-12 weeks]:::action G --> H[Assess for relapse<br/>or complications]:::outcome ``` ### Why Option 1 (Correct Answer) is Best **Key Point:** The cornerstone of DRESS management is **immediate discontinuation of the culprit drug** followed by systemic corticosteroids. Continuing the drug while adding steroids is ineffective and dangerous. - **Phenytoin must be stopped immediately** — it is the trigger; steroids alone cannot reverse the immune cascade while the antigen persists. - **Systemic corticosteroids are essential:** - Suppress T-cell activation and eosinophil recruitment - Reduce hepatic inflammation and prevent fulminant hepatic failure - Typical dosing: prednisolone 0.5–1 mg/kg/day or methylprednisolone 1–2 g IV daily for severe cases - **Rationale:** Early intervention prevents progression to multi-organ failure, which carries 10–20% mortality if untreated. **High-Yield:** DRESS is a medical emergency requiring dual action: drug withdrawal + corticosteroids. Neither alone is sufficient. ### Supportive Management - Monitor liver function, CBC, and viral serology (HHV-6, EBV) weekly for 4 weeks - Gradual steroid taper over 8–12 weeks (rapid withdrawal risks rebound flare) - Avoid re-challenge with phenytoin or structurally similar anticonvulsants (cross-reactivity risk: carbamazepine, phenobarbital) - Consider alternative anticonvulsants (levetiracetam, lamotrigine, valproate) after recovery **Clinical Pearl:** Hepatic involvement in DRESS can progress to acute liver failure within days if the drug is not stopped. Mortality correlates with delay in diagnosis and treatment initiation. ### DRESS Diagnostic Criteria (RegiSCAR Scoring) Points awarded for: - Fever ≥38.5°C (1 point) - Atypical lymphocytes (1 point) - Eosinophilia ≥1500/μL (2 points) - Lymphadenopathy (1 point) - Hepatomegaly or elevated transaminases (1 point) - Skin involvement (1 point) - **Score ≥4 = definite DRESS** This patient scores ≥4 (fever, eosinophilia, hepatic involvement, skin biopsy findings).