A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 57-year-old man comes to the physician because of sudden-onset fever, malaise, and pain and swelling of his wrists and ankles that began a week ago. One month ago, he was started on hydralazine for adjunctive treatment of hypertension. His temperature is 37.8°C (100°F). Examination shows swelling, tenderness, warmth, and erythema of both wrists and ankles; range of motion is limited. Further evaluation is most likely to show an increased level of which of the following autoantibodies?
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A
Anti-dsDNAIncorrect. Anti-dsDNA is highly specific for idiopathic SLE (correlates with lupus nephritis) and is typically NEGATIVE in drug-induced lupus.
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B
Anti-SmithIncorrect. Anti-Smith is very specific for idiopathic SLE but not seen in drug-induced lupus.
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C
Anti-β2-glycoproteinIncorrect. Anti-β2-glycoprotein I is part of the antiphospholipid antibody panel, associated with thromboses and pregnancy loss — not drug-induced lupus.
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D
Anti-histoneCorrect. Hydralazine-induced lupus is characterized by anti-histone antibodies (>95% sensitivity); anti-dsDNA and anti-Smith are typically negative, distinguishing DILE from idiopathic SLE.
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E
Anti-Jo-1Incorrect. Anti-Jo-1 (anti-tRNA synthetase) is associated with antisynthetase syndrome and polymyositis with interstitial lung disease, not hydralazine-induced lupus.
↑ Tap an answer to reveal the reasoning
Answer: D. This patient developed acute joint swelling, fever, and malaise one month after starting hydralazine — classic for drug-induced lupus erythematosus (DILE). Hydralazine is one of the most well-known causes (along with procainamide, isoniazid, minocycline, methyldopa, quinidine, etanercept). DILE typically presents with arthralgia/arthritis, myalgia, fever, and serositis (pleuritis, pericarditis); CNS and renal involvement (common in SLE) are rare.
The characteristic serology of DILE is positive anti-histone antibodies, present in >95% of cases. Anti-dsDNA and anti-Smith antibodies (specific for idiopathic SLE) are typically NEGATIVE in drug-induced lupus, which is a key distinguishing feature on tests. ANA is positive in both. Resolution of symptoms after discontinuing the offending drug is also diagnostic — symptoms usually resolve within weeks-months.
The distractors:
- Anti-dsDNA: specific for idiopathic SLE, correlates with nephritis and disease activity; typically NEGATIVE in DILE.
- Anti-Smith: very specific for SLE (but not sensitive), not seen in DILE.
- Anti-β2-glycoprotein: antiphospholipid syndrome — venous/arterial thromboses, recurrent miscarriages.
Mnemonic: "HIP" drugs cause drug-induced lupus (Hydralazine, Isoniazid, Procainamide) — and the antibody is anti-Histone (also starts with H).
Management: stop the offending drug; symptoms resolve. NSAIDs and short-course steroids for severe symptoms.
**Why each option:**
**A.** Anti-dsDNA is highly specific for idiopathic SLE (correlates with lupus nephritis) and is typically NEGATIVE in drug-induced lupus.
**B.** Anti-Smith is very specific for idiopathic SLE but not seen in drug-induced lupus.
**C.** Anti-β2-glycoprotein I is part of the antiphospholipid antibody panel, associated with thromboses and pregnancy loss — not drug-induced lupus.
**D.** Correct. Hydralazine-induced lupus is characterized by anti-histone antibodies (>95% sensitivity); anti-dsDNA and anti-Smith are typically negative, distinguishing DILE from idiopathic SLE.