A 52-year-old woman develops severe rash, fever, and lymphadenopathy 3 weeks after starting phenytoin for seizure prophylaxis. The reaction is independent of dose and unrelated to the drug's anticonvulsant mechanism. According to Rawlins and Thompson classification, this represents which type of adverse drug reaction?

## Type B (Bizarre) Adverse Drug Reaction — Clinical Recognition ### Clinical Presentation in This Case **Key Point:** The patient's presentation — rash, fever, lymphadenopathy 3 weeks after phenytoin initiation — is classic for **Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome**, a Type B ADR. ### Defining Features of Type B Reactions **High-Yield:** Type B reactions have these hallmarks: - **Dose-independent** — occur at therapeutic doses; not dose-related - **Unpredictable** — cannot be anticipated from the drug's pharmacology - **Unrelated to pharmacological action** — not an exaggeration of intended effect - **Immunological or idiosyncratic basis** — often involve hypersensitivity or genetic factors - **Uncommon** — account for ~20% of ADRs - **Serious** — often require immediate drug discontinuation ### Why Phenytoin DRESS is Type B | Feature | Explanation | |---------|-------------| | **Dose-independent** | Occurs at standard therapeutic doses (300 mg/day); not dose-related | | **Unpredictable** | Cannot be foreseen from phenytoin's anticonvulsant mechanism | | **Immunological** | Involves T-cell activation, eosinophilia, and systemic inflammation | | **Timing** | Typically 2–6 weeks after initiation (not immediate, not dose-dependent) | | **Irreversible** | Requires drug withdrawal; dose reduction does NOT resolve it | ### Common Type B Reactions **Clinical Pearl:** Aromatic antiepileptics (phenytoin, carbamazepine, phenobarbital) carry the highest risk of DRESS and Stevens-Johnson syndrome — both Type B reactions. Genetic polymorphisms in HLA and drug-metabolizing enzymes (CYP2C9, CYP2C19) predispose certain populations. **Mnemonic:** **DRESS** — **D**rug **R**eaction with **E**osinophilia and **S**ystemic **S**ymptoms. Features: Rash (often facial edema), Fever, Lymphadenopathy, Eosinophilia, Atypical lymphocytes, Hepatitis. ### Management 1. **Immediate drug discontinuation** — dose reduction will NOT help 2. Systemic corticosteroids (prednisolone 0.5–1 mg/kg/day) for severe cases 3. Supportive care and monitoring for organ involvement (liver, kidney) 4. Avoid rechallenge with phenytoin or cross-reactive aromatic antiepileptics 5. Switch to non-aromatic alternative (levetiracetam, lamotrigine with slow titration)