A 28-year-old woman with SLE presents with a malar rash and arthritis. Her ANA is positive with high-titre anti-dsDNA antibodies. Her complement levels (C3, C4) are low. Which single clinical or serological feature best distinguishes SLE from drug-induced lupus (DIL)?

Explanation

## Distinguishing SLE from Drug-Induced Lupus (DIL) ### Key Serological Differences | Feature | SLE | DIL | |---------|-----|-----| | **Anti-dsDNA** | High-titre, specific | Absent or low-titre | | **Anti-histone** | Present (30–40%) | Present (95%) | | **Complement (C3, C4)** | Low (active disease) | Normal | | **ANA pattern** | Homogeneous, speckled | Homogeneous | **Key Point:** High-titre anti-dsDNA antibodies with depressed complement (C3/C4) are virtually pathognomonic for SLE and virtually never occur in DIL. This combination is the single best discriminator. ### Why Anti-dsDNA + Low Complement? 1. Anti-dsDNA forms immune complexes that deposit in kidneys and activate complement 2. Complement consumption leads to low C3 and C4 levels 3. This triad (anti-dsDNA + low C3 + low C4) indicates active lupus nephritis or systemic disease 4. DIL patients retain normal complement levels because they lack anti-dsDNA-mediated immune complex disease **Clinical Pearl:** A patient with positive ANA but normal complement levels and no anti-dsDNA should raise suspicion for DIL, especially if symptoms began shortly after starting a drug (hydralazine, procainamide, isoniazid, TNF-α inhibitors). **High-Yield:** The 1997 ACR classification criteria for SLE include anti-dsDNA and low complement as separate major criteria; their presence together is highly specific for SLE and excludes DIL. [cite:Harrison 21e Ch 312]