What is the management of methotrexate (MTX) induced lung toxicity?

Management of Methotrexate-Induced Lung Toxicity

The management of methotrexate (MTX) induced lung toxicity requires immediate discontinuation of the medication, supportive care, and corticosteroid therapy in severe cases, with careful monitoring for clinical improvement.

Clinical Presentation and Diagnosis

Methotrexate-induced pneumonitis presents with:

• Progressive shortness of breath and dry, nonproductive cough
• Fever
• Hypoxemia and tachypnea
• Crackles on auscultation
• Diffuse interstitial or mixed interstitial and alveolar infiltrates on chest radiography, with predilection for lower lung fields 1
• Restrictive pattern with decreased diffusion capacity on pulmonary function tests

Diagnostic approach:

• High-resolution CT scan showing ground-glass opacities, interstitial infiltrates, septal lines, or widespread consolidation 2
• Bronchoalveolar lavage to rule out infectious etiologies
• Lung biopsy (when necessary) may show cellular interstitial infiltrates, granulomas, or diffuse alveolar damage pattern 1

Immediate Management

1. Discontinue methotrexate immediately upon suspicion of pulmonary toxicity 3, 1
2. Implement supportive measures:
   • Supplemental oxygen
   • Aggressive hydration
   • Respiratory support as needed

Pharmacological Management

1. Corticosteroid therapy:

   • Indicated for severe or fulminant cases 2
   • Starting dose: 0.5-1 mg/kg/day of prednisone 4
   • Taper by 10 mg every 2 weeks until reaching 30 mg/day, then slow the taper 4

2. Leucovorin (folinic acid) rescue:

   • Should be initiated as soon as possible (within 24 hours) 4
   • Dosing based on methotrexate levels
   • Continue until methotrexate levels are <0.05 μmol/L 4

Monitoring and Follow-up

1. Daily monitoring during acute phase:

   • Complete blood count
   • Renal function
   • Serum methotrexate levels (if available) 4
   • Oxygen saturation
   • Respiratory status

2. Follow-up imaging:

   • Repeat chest imaging after 4 weeks to assess resolution 5
   • Pulmonary function tests to document improvement

Risk Factors and Prevention

Risk factors for MTX-induced pneumonitis include:

• Pre-existing lung disease
• Cigarette smoking
• Advanced age
• Rheumatoid arthritis (more common than in psoriasis) 6

Preventive measures:

• Screen patients for pulmonary disease before initiating MTX 6
• Perform chest X-ray and respiratory assessment in high-risk patients (>40 years, smokers, pre-existing lung disease) 6
• Educate patients about early symptoms and importance of prompt reporting 1
• Consider folic acid supplementation (1-5 mg daily except on day of MTX) 6

Prognosis

• Most cases resolve with prompt discontinuation of MTX and appropriate treatment
• Complete resolution typically occurs within 4-8 weeks
• Fatalities have been reported, emphasizing the importance of early recognition and treatment 3, 1

Special Considerations

• MTX-induced pneumonitis is more common in rheumatoid arthritis than in psoriasis 6
• Incidence ranges from 0.5% to 14% of patients receiving low-dose MTX 2
• The reaction is not dose-dependent and can occur at any time during therapy 3
• Rechallenge with MTX after pneumonitis is generally not recommended due to risk of recurrence with potentially more severe manifestations

Remember that MTX-induced pneumonitis is a diagnosis of exclusion, and infectious causes must be ruled out before attributing pulmonary symptoms to MTX toxicity.