A 42-year-old woman with established seronegative (RF-negative) rheumatoid arthritis on methotrexate presents with progressive dyspnea and nonproductive cough over 2 months. High-resolution CT chest shows bilateral ground-glass opacities, interlobular septal thickening, and traction bronchiectasis predominantly in the lower lobes. Pulmonary function tests show a restrictive pattern with reduced DLCO. Which medication is the most likely cause of this pulmonary toxicity?
- A Hydroxychloroquine
- B Methotrexate ✓
- C Etanercept
- D Sulfasalazine
Correct answer: B. Methotrexate
Explanation
Methotrexate can cause hypersensitivity pneumonitis and pulmonary fibrosis independent of RA-associated ILD. The lower-lobe-predominant pattern with ground-glass and fibrosis is characteristic of methotrexate pneumonitis. RA-ILD typically shows a usual interstitial pneumonia pattern but drug-induced toxicity must be excluded first. Hydroxychloroquine rarely causes pulmonary toxicity; etanercept and sulfasalazine are not typical causes of this pattern.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.