A 28-year-old woman from Delhi presents with a 3-month history of polyarthritis affecting the hands, wrists, and knees, along with a malar rash that worsens in sunlight. She reports fatigue, low-grade fever, and recent hair loss. Laboratory investigations show: ANA positive (1:320, homogeneous), anti-dsDNA antibodies positive, anti-Smith antibodies positive, complement C3 and C4 levels low, and urinalysis shows 2+ proteinuria with RBC casts. What is the most likely diagnosis?

Explanation

## Diagnosis: Systemic Lupus Erythematosus (SLE) with Lupus Nephritis ### Clinical Presentation This patient meets **≥4 ACR/EULAR 2019 classification criteria** for SLE: 1. **Malar rash** (photosensitive) — constitutional manifestation 2. **Polyarthritis** (hands, wrists, knees) — non-erosive arthritis 3. **Hematologic involvement** — RBC casts in urinalysis 4. **Immunologic findings** — ANA+, anti-dsDNA+, anti-Smith+, low complement 5. **Renal involvement** — proteinuria + RBC casts = lupus nephritis ### Serologic Hallmarks | Antibody | Specificity | Significance | |----------|-------------|---------------| | **Anti-dsDNA** | 70% SLE | High specificity; correlates with lupus nephritis | | **Anti-Smith (Sm)** | 30% SLE | Pathognomonic for SLE; never in other diseases | | **ANA (homogeneous)** | 95% SLE | Sensitive but not specific; high titer supports SLE | | **Low C3/C4** | Active disease | Indicates immune complex deposition | **Key Point:** Anti-Smith antibodies are **100% specific** for SLE — if positive, SLE is virtually certain. ### Lupus Nephritis Classification The presence of **RBC casts + proteinuria + low complement** indicates **active proliferative lupus nephritis** (Class III or IV), requiring urgent immunosuppressive therapy. **Clinical Pearl:** Lupus nephritis occurs in ~40% of SLE patients and is a major cause of morbidity and mortality; early recognition and treatment prevent end-stage renal disease. **High-Yield:** The combination of **anti-dsDNA positivity + low complement + active urinary sediment** is the classic triad for lupus nephritis diagnosis. ### Management Implications - Induction therapy: corticosteroids + cyclophosphamide or mycophenolate mofetil - Maintenance: azathioprine or mycophenolate - Monitoring: serum creatinine, urinalysis, complement levels every 3 months