A 28-year-old woman with newly diagnosed generalized tonic-clonic seizures is started on phenytoin. After 3 weeks of therapy, she develops a maculopapular rash with fever and lymphadenopathy. Which investigation is most appropriate to confirm the diagnosis of phenytoin-induced hypersensitivity syndrome?

Explanation

## Phenytoin Hypersensitivity Syndrome: Diagnostic Approach ### Clinical Presentation Phenytoin hypersensitivity syndrome (also called anticonvulsant hypersensitivity syndrome or DRESS syndrome when associated with phenytoin) presents with: - Fever, rash (maculopapular), and lymphadenopathy (classic triad) - Onset typically 2–6 weeks after drug initiation - Systemic involvement: hepatitis, hematologic abnormalities, atypical lymphocytosis ### Investigation of Choice **Key Point:** Complete blood count with differential and liver function tests is the most appropriate initial confirmatory investigation because: 1. **Detects hematologic abnormalities:** - Atypical lymphocytosis (activated T cells) - Eosinophilia - Thrombocytopenia or leukopenia 2. **Identifies hepatic involvement:** - Elevated transaminases (ALT, AST) - Elevated bilirubin - These are hallmark features of DRESS syndrome 3. **Supports diagnosis:** The combination of systemic findings (fever, rash, lymphadenopathy) + hematologic abnormalities + hepatic dysfunction = diagnostic criteria for phenytoin hypersensitivity syndrome ### Why This Investigation Matters **High-Yield:** Phenytoin hypersensitivity is a severe, potentially life-threatening reaction. Early recognition via CBC + LFTs allows: - Immediate drug discontinuation - Prevention of progression to multi-organ failure - Initiation of corticosteroids if severe ### Differential Approach to Other Investigations | Investigation | Role | Why Not First-Line | |---|---|---| | **Skin biopsy** | Confirms dermatologic pattern (interface dermatitis, lymphocytic infiltrate) | Histology is supportive but not diagnostic; clinical + lab findings are sufficient | | **Serum phenytoin level** | Assesses drug accumulation or toxicity | Does not confirm hypersensitivity; hypersensitivity is immune-mediated, not dose-dependent | | **Patch testing** | Identifies delayed-type hypersensitivity to phenytoin | Performed after acute phase resolves; not useful for acute diagnosis | **Clinical Pearl:** Phenytoin hypersensitivity is cross-reactive with other aromatic antiepileptics (carbamazepine, phenobarbital). Always check CBC + LFTs when these drugs are initiated, especially in the first 6 weeks. **Warning:** Do NOT rely on serum drug levels alone — hypersensitivity is an immune reaction, not a pharmacokinetic problem. A "therapeutic" phenytoin level does not rule out hypersensitivity.