Tuesday, July 6, 2021

methotrexate-induced pulmonary toxicity

 Q: 42 year old female who was started on methotrexate few months ago admitted to ICU with shortness of breath and hypoxemia. She required BiPAP to keep saturation > 90. All of the following are included in criteria to diagnose methotrexate-induced pulmonary toxicity EXCEPT? (select one) 

A) Hypersensitivity pneumonitis 

B) Radiographic evidence 

C) Negative Blood cultures 

D) Productive cough 

E) WBC count ≤15,000 cells/mm3

Answer: D

The diagnosis of methotrexate-induced pulmonary toxicity takes into account various factors including clinical, radiological, and bronchoalveolar lavage (BAL) findings, results of lung biopsy, and response to drug discontinuation. In patients taking methotrexate:

Major criteria are three: 

  1. Hypersensitivity pneumonitis by histopathology without evidence of pathogenic organisms 
  2. Radiographic evidence of patchy or diffuse pulmonary ground glass or consolidative opacities 
  3. Negative blood cultures and initial sputum cultures are negative 

 Minor criteria are five: 

  1. Shortness of breath for less than 2 months 
  2. Nonproductive cough 
  3. Oxygen saturation ≤90 percent on room air at the time of initial evaluation 
  4. DLCO ≤70 percent of predicted for age 
  5. Leukocyte count ≤15,000 cells/mm3 

"Definite" methotrexate pneumonitis is:

major criteria 1 or 2 and 3 with 3/5 minor criteria.

 "Probable" methotrexate pneumonitis is:

major criteria 2 + 3 with 2/5 minor criteria



1. Searles G, McKendry RJ. Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol 1987; 14:1164. 

2. Kremer JM, Alarcón GS, Weinblatt ME, et al. Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum 1997; 40:1829.

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