A 38-year-old woman undergoes renal transplantation for end-stage renal disease. She is started on a triple immunosuppressive regimen: prednisolone, azathioprine, and cyclosporine. At 6 weeks post-transplant, she develops severe gingival hyperplasia, hirsutism, and tremor. Her serum creatinine remains stable at 1.2 mg/dL. Which drug is most likely responsible for these adverse effects, and what is the mechanism by which it causes gingival hyperplasia?

Explanation

## Cyclosporine and Gingival Hyperplasia **Key Point:** Cyclosporine is the immunosuppressant most commonly associated with gingival hyperplasia (20–30% of transplant patients), along with hirsutism and tremor. ### Mechanism of Gingival Hyperplasia 1. **Calcineurin inhibition** → reduced IL-2 production and T-cell suppression 2. **Increased TGF-β signalling** in gingival fibroblasts 3. **Fibroblast proliferation and collagen deposition** → gingival overgrowth 4. **Enhanced by poor oral hygiene** — preventable with meticulous plaque control ### Clinical Features of Cyclosporine Toxicity | Feature | Mechanism | Reversibility | |---------|-----------|----------------| | Gingival hyperplasia | TGF-β-mediated fibroblast proliferation | Partial (may persist after drug withdrawal) | | Hirsutism | Androgen-like effect on hair follicles | Reversible | | Tremor | CNS penetration; unclear mechanism | Reversible | | Nephrotoxicity | Afferent arteriole vasoconstriction | Dose-dependent | | Hypertension | Renal vasoconstriction + sodium retention | Reversible | **High-Yield:** The triad of **gingival hyperplasia + hirsutism + tremor** is pathognomonic for cyclosporine toxicity in transplant patients. **Clinical Pearl:** Gingival hyperplasia is **NOT** seen with tacrolimus (another calcineurin inhibitor), making it a key distinguishing feature. Tacrolimus has a better side-effect profile for gingival health. ### Management - Excellent oral hygiene and regular dental review - Gingivectomy if severe and functionally impairing - Switch to tacrolimus or mTOR inhibitor if hyperplasia is intolerable - Graft function remains stable in this case (Cr 1.2), so drug continuation is justified [cite:KD Tripathi 8e Ch 72]