A 58-year-old woman with seropositive rheumatoid arthritis on weekly methotrexate 17.5 mg for 6 months presents with subacute non-productive cough, fever, and progressive dyspnea on exertion over 3 weeks. SpO₂ is 90% on room air. HRCT shows bilateral ground-glass opacities and patchy consolidation. Spirometry reveals the pattern marked **A** in the diagram. Which of the following is the most appropriate IMMEDIATE management step?

Question

Accepted Answer

A. Immediately discontinue methotrexate and exclude infection with bronchoalveolar lavage; initiate supplemental oxygen and consider high-dose corticosteroids for moderate-to-severe disease. ## Why option 1 is right

The spirometry pattern marked **A** — restrictive with reduced DLCO (FVC 62% predicted, FEV₁/FVC 86%, TLC 65%, DLCO 48% predicted) — is pathognomonic for methotrexate-induced pneumonitis (MTX-P), a non-dose-related idiosyncratic hypersensitivity reaction. The Searles & McKendry criteria require new dyspnea, radiographic infiltrates, and restrictive physiology with reduced DLCO. Critical management is: (1) IMMEDIATELY HOLD methotrexate (do not rechallenge); (2) aggressively exclude infection (PCP, viral, atypical bacteria mimic MTX-P) with bronchoalveolar lavage and PCR/cultures; (3) initiate supplemental oxygen; (4) start high-dose corticosteroids (prednisolone 0.5–1 mg/kg/day) for moderate-to-severe disease with slow taper. Mortality is 13–17%, and recovery may take months (Searles & McKendry, J Rheumatol 1987; Conway et al., Arthritis Rheumatol 2014).

## Why each distractor is wrong

- **Option 2**: Continuing methotrexate is contraindicated — MTX-P is an idiosyncratic reaction, not dose-dependent, and rechallenge risks fatal progression. Folinic acid (leucovorin) is used for acute MTX toxicity (e.g., mucositis, myelosuppression), not for established pneumonitis.
- **Option 3**: The pattern **A** is restrictive, not obstructive; asthma presents with obstructive physiology (pattern **B** — reversible airflow obstruction). Bronchodilators are ineffective and delay diagnosis.
- **Option 4**: Switching to a biologic without stopping MTX and without corticosteroids ignores the acute, life-threatening nature of MTX-P. Observation alone without steroids risks rapid deterioration and death.

**High-Yield:** MTX-induced pneumonitis = restrictive + low DLCO + bilateral infiltrates → STOP MTX immediately, exclude infection, give high-dose steroids. Do NOT rechallenge.

[cite: Searles & McKendry, J Rheumatol 1987; Conway et al., Arthritis Rheumatol 2014; Harrison 21e Ch. on Drug-Induced Lung Disease]

Answer

B. Switch methotrexate to a biologic DMARD and monitor with serial chest X-rays without corticosteroids

Answer

C. Perform pulmonary function testing to assess for asthma and initiate inhaled bronchodilators

Answer

D. Continue methotrexate at the same dose and start folinic acid (leucovorin) rescue to reverse the pneumonitis

Explanation

Why option 1 is right

Why each distractor is wrong

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