## Phenytoin and Cosmetic Adverse Effects **Key Point:** Phenytoin is notorious for causing a triad of cosmetic side effects: gingival hyperplasia, hirsutism, and coarsening of facial features — collectively termed the **phenytoin syndrome**. ### Mechanism of Gingival Hyperplasia 1. Phenytoin stimulates fibroblast proliferation in gingival tissue 2. Increases collagen synthesis and deposition 3. Impaired folate metabolism may contribute 4. Effect is dose-dependent and partially reversible with good oral hygiene ### Clinical Features of Phenytoin Syndrome | Feature | Mechanism | Reversibility | |---------|-----------|----------------| | Gingival hyperplasia | Fibroblast proliferation, collagen ↑ | Partial (with oral hygiene) | | Hirsutism | Androgen-like effects, increased vellus hair | Reversible on withdrawal | | Facial coarsening | Subcutaneous tissue thickening | Partially reversible | | Acne | Sebaceous gland stimulation | Reversible | **High-Yield:** Gingival hyperplasia occurs in 10–50% of phenytoin-treated patients and is the most common cosmetic complaint leading to drug discontinuation in young patients. **Clinical Pearl:** Good oral hygiene, regular dental care, and plaque control can reduce the severity of gingival hyperplasia by 30–50%, even while continuing phenytoin. ### Why Phenytoin Over Other Anticonvulsants - **Valproic acid:** Causes weight gain and alopecia (hair loss), NOT hirsutism or gingival hyperplasia - **Lamotrigine:** Causes rash (Stevens-Johnson syndrome risk) and photosensitivity, not cosmetic changes - **Levetiracetam:** Minimal cosmetic side effects; behavioral changes and dizziness are more common **Mnemonic:** **PHENYTOIN = Gingival Hyperplasia, Hirsutism, Facial Coarsening** — the "ugly drug" of anticonvulsants.
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