A 38-year-old woman on allopurinol for gout presents with a 2-week history of fever (39°C), a widespread pruritic rash involving the face, trunk, and flexural areas, and cervical lymphadenopathy. Laboratory investigations show WBC 12,000/μL with 18% eosinophils, elevated transaminases (AST 120 U/L, ALT 140 U/L), and atypical lymphocytes on blood smear. Skin biopsy shows perivascular lymphocytic infiltration with eosinophils. Which of the following is the most appropriate immediate management?

Explanation

## DRESS Syndrome: Clinical Recognition and Management ### Clinical Presentation and Diagnosis **Key Point:** DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe, potentially life-threatening drug reaction characterized by the classic triad of fever, rash, and systemic involvement (lymphadenopathy, hepatosplenomegaly, and/or hematologic abnormalities). This patient meets the diagnostic criteria for DRESS syndrome: - **Temporal relationship:** Symptom onset 2 weeks after allopurinol initiation (typical latency 2–8 weeks) - **Fever:** 39°C - **Rash:** Widespread pruritic maculopapular eruption with facial and flexural involvement - **Lymphadenopathy:** Cervical nodes palpable - **Eosinophilia:** 18% (>1.5 × 10^9^/L is diagnostic) - **Atypical lymphocytes:** Suggests viral reactivation (HHV-6, EBV, CMV) - **Hepatic involvement:** Elevated transaminases (AST 120, ALT 140) - **Histology:** Perivascular lymphocytic infiltrate with eosinophils (consistent with DRESS) ### Management Algorithm ```mermaid flowchart TD A[Suspected DRESS Syndrome]:::outcome --> B[Identify Culprit Drug]:::decision B --> C[Discontinue Offending Agent]:::action C --> D{Severity Assessment}:::decision D -->|Mild-Moderate| E[Systemic Corticosteroids<br/>0.5-1 mg/kg/day Prednisolone]:::action D -->|Severe/Hepatic Dysfunction| F[High-Dose Corticosteroids<br/>1-2 mg/kg/day + ICU Monitoring]:::action E --> G[Taper over 6-12 weeks]:::action F --> G G --> H[Monitor LFTs, CBC, Rash]:::action H --> I[Reactivation of HHV-6/EBV<br/>may occur during taper]:::outcome ``` ### Rationale for Correct Answer (Option 1: Discontinue + Systemic Corticosteroids) **High-Yield:** The two pillars of DRESS management are: 1. **Immediate withdrawal of the culprit drug** (allopurinol in this case) 2. **Systemic corticosteroids** (first-line immunosuppression) **Clinical Pearl:** Allopurinol is one of the most common causes of DRESS in India and worldwide. Discontinuation alone is insufficient in moderate-to-severe cases; systemic corticosteroids are mandatory to prevent progression to multi-organ failure. **Dosing:** Prednisolone 0.5–1 mg/kg/day (typically 30–40 mg/day) for 4–6 weeks, then gradual taper over 6–12 weeks. Rapid taper risks rebound flare or viral reactivation. ### Why Each Distractor Is Wrong | Option | Reasoning | |--------|----------| | **Option 0: Continue allopurinol + corticosteroids** | Continuing the offending drug while treating with steroids is contraindicated. The drug must be withdrawn immediately to prevent ongoing sensitization and systemic inflammation. Masking the reaction with steroids while the trigger remains is dangerous and delays resolution. | | **Option 2: Discontinue + topical steroids + antihistamines** | Topical corticosteroids and antihistamines are inadequate for DRESS syndrome. This is a systemic, multi-organ disease with hepatic involvement and eosinophilia. Topical therapy addresses only the cutaneous manifestation and fails to suppress the underlying immune dysregulation. Risk of progression to hepatic failure, disseminated intravascular coagulation (DIC), or death. | | **Option 3: Continue allopurinol + topical steroids + antibiotics** | This combines two errors: (1) continuing the culprit drug, and (2) using only topical therapy. Antibiotics are not indicated unless secondary bacterial infection is present; DRESS is an immune-mediated reaction, not an infection. | ### Key Discriminators for Exam **Mnemonic: DRESS** - **D**rug reaction - **R**ash (maculopapular, often with facial edema) - **E**osinophilia (>1.5 × 10^9^/L) or atypical lymphocytes - **S**ystemic symptoms (fever, lymphadenopathy, hepatosplenomegaly) - **S**evere (can progress to multi-organ failure if untreated) **Warning:** Do not confuse DRESS with simple drug allergy or urticaria. The presence of eosinophilia, atypical lymphocytes, and hepatic involvement is the red flag that systemic corticosteroids are needed. **Tip:** In NEET PG exams, if you see a drug reaction with fever + rash + eosinophilia + lymphadenopathy + liver involvement, always think DRESS and choose systemic corticosteroids + drug withdrawal. Topical therapy alone is a trap answer. ### Monitoring During Treatment 1. **Baseline and weekly:** CBC, LFTs, renal function 2. **Watch for reactivation:** HHV-6, EBV, or CMV reactivation may occur during taper (managed with antivirals if symptomatic) 3. **Taper schedule:** Reduce by 5–10 mg/week after 4–6 weeks of full dose 4. **Duration:** Total treatment typically 6–12 weeks [cite:Robbins 10e Ch 25; Harrison 21e Ch 356]