To help rule out drug-induced lupus, which antibody is most appropriate to test for?

• A. ANA
• B. Anti-dsDNA
• C. Anti-histone Ab
• D. Anti-Smith Ab

Answer: (C)

Drug-induced lupus is most likely when there are antihistone antibodies. This antibody is the strongest association with drug-induced lupus, helping distinguish it from idiopathic SLE. While ANA can be positive in many autoimmune conditions and isn't specific, and anti-dsDNA and anti-Smith antibodies are more characteristic of idiopathic SLE (often with kidney involvement), antihistone antibodies point toward a drug-related etiology. In practice, if a patient on a known offending drug develops lupus-like symptoms and tests positive for antihistone antibodies, stopping the drug often leads to symptom resolution. Remember, this marker isn’t perfect—some cases of drug-induced lupus may be antihistone-negative, and a minority of idiopathic SLE patients can have antihistone antibodies—but overall it’s the best test to help rule out drug-induced lupus in the appropriate clinical context.