A 28-year-old woman presents with a 6-month history of polyarthritis, photosensitive malar rash, and oral ulcers. ANA is positive at 1:640 with anti-dsDNA and anti-Smith antibodies. Urinalysis shows 2+ proteinuria. What is the drug of choice for initial management of her lupus nephritis?

Explanation

## First-Line Immunosuppression in Lupus Nephritis **Key Point:** Intravenous cyclophosphamide (IV CYC) remains the gold standard for induction therapy in proliferative lupus nephritis (Class III and IV), particularly in patients with active renal disease and proteinuria. ### Rationale for IV Cyclophosphamide 1. **Efficacy**: Induces complete or partial remission in 60–80% of patients with proliferative nephritis 2. **Mechanism**: Potent alkylating agent causing cross-linking of DNA; suppresses both T and B cell proliferation 3. **Evidence Base**: NIH protocol and EURO-Lupus trials established IV CYC + corticosteroids as standard induction therapy 4. **Dosing**: 0.5–1 g/m² IV monthly for 6 months (NIH protocol) or fixed-dose regimen ### Treatment Algorithm for Lupus Nephritis ```mermaid flowchart TD A[Lupus Nephritis Diagnosed]:::outcome --> B{Histological Class?}:::decision B -->|Class I-II| C[Corticosteroids + Hydroxychloroquine]:::action B -->|Class III-IV| D[IV Cyclophosphamide + High-dose Corticosteroids]:::action B -->|Class V| E[Corticosteroids + Mycophenolate/Azathioprine]:::action D --> F[Maintenance: Azathioprine or Mycophenolate]:::action C --> G[Monitor: Proteinuria, Creatinine, ANA]:::outcome F --> G ``` **High-Yield:** The patient has Class III–IV nephritis (evidenced by proteinuria and active serology). IV CYC is the induction agent of choice; mycophenolate or azathioprine follows for maintenance. ### Comparison: Induction Agents in Proliferative Lupus Nephritis | Agent | Role | Timing | Key Advantage | Key Drawback | |-------|------|--------|---------------|---------------| | **IV Cyclophosphamide** | Induction | First-line | Highest remission rate (60–80%) | Infertility, hemorrhagic cystitis, infection | | **Mycophenolate Mofetil** | Induction/Maintenance | Alternative induction | Safer, oral, fewer infections | Slightly lower remission rate (~50%) | | **Azathioprine** | Maintenance | Post-induction | Well-tolerated, long-term use | Not first-line induction | | **Rituximab** | Salvage | Refractory disease | B-cell targeted, steroid-sparing | Expensive, reserved for resistant cases | **Clinical Pearl:** Although mycophenolate mofetil (MMF) has emerged as an alternative induction agent with a more favorable safety profile, IV cyclophosphamide remains superior for severe proliferative disease with high activity indices and is preferred when rapid remission is critical. **Warning:** Do not confuse maintenance therapy (azathioprine, mycophenolate) with induction therapy (cyclophosphamide). This patient requires induction.