What is the treatment for pneumonitis?

Treatment of Pneumonitis

Pneumonitis treatment is severity-based: grade 1 requires monitoring only, grade 2 requires immediate drug discontinuation plus oral prednisone 1 mg/kg daily, and grade 3-4 requires hospitalization with high-dose IV methylprednisolone 2-4 mg/kg/day. 1

Severity Grading and Initial Management

Grade 1 (Asymptomatic or Mild Symptoms)

• Continue the causative therapy with close monitoring without initiating corticosteroids at this stage 1, 2
• Monitor symptoms and oxygen saturation every 2-3 days using pulse oximetry 1, 2
• Obtain CT chest imaging for any new respiratory symptom, as disease progression, infection, and pneumonitis must be formally excluded 3

Grade 2 (Moderate Symptoms)

• Immediately discontinue the suspected causative agent 1, 2
• Initiate oral prednisone 1 mg/kg daily or equivalent 1, 2, 3
• Taper steroids over a minimum of 4-6 weeks after clinical recovery 1, 2
• Perform bronchoscopy with bronchoalveolar lavage to exclude infections 2

Grade 3-4 (Severe or Life-Threatening)

• Hospitalize immediately and permanently discontinue the offending agent 1, 2, 3
• Administer high-dose IV methylprednisolone 2-4 mg/kg/day or equivalent 1, 2, 3
• Taper steroids very slowly over 6+ weeks minimum, as relapses during tapering are well-documented 2, 3
• Consider broad-spectrum antibiotics in parallel if infectious status cannot be reliably assessed 2

Diagnostic Workup

• CT chest imaging is the preferred modality, showing ground-glass opacities, patchy nodular infiltrates, or interstitial patterns 2
• Bronchoscopy with BAL should be performed for grade 2 or higher pneumonitis to exclude infections 2
• Transbronchial or surgical lung biopsy may be considered when etiology is unclear, though not routinely required 2
• Improvement following drug cessation without glucocorticoid therapy strongly supports drug-related pneumonitis 1, 3

Steroid-Refractory Disease Management

If no improvement occurs after 48 hours of corticosteroid therapy, add second-line immunosuppression 2. The evidence regarding specific agents shows important differences:

Preferred Second-Line Agent

• Intravenous immunoglobulin (IVIG) alone demonstrated superior outcomes with 43% mortality compared to 100% mortality with infliximab in steroid-refractory cases 4
• IVIG-treated patients showed improvement in level-of-care and oxygenation requirements 4

Alternative Second-Line Agents

• Mycophenolate mofetil can be considered, with durable improvement achieved in 38% of patients receiving additional immunomodulators 5
• Cyclophosphamide is another option 2
• Avoid infliximab as monotherapy given 100% mortality in steroid-refractory pneumonitis 4

Special Considerations for Immune Checkpoint Inhibitor Pneumonitis

Incidence and Risk Factors

• Anti-PD-1/PD-L1 monotherapy causes pneumonitis in 2-4% of patients, with grade 3-4 events in 1-2% and fatal pneumonitis in 0.2% 1, 3
• Combination immunotherapy increases risk 3-fold, with incidence reaching 10% versus 3% for monotherapy 1, 3
• Median time to onset is 34 weeks but ranges from 1.5 to 127 weeks 6
• Patients with non-small cell lung cancer have more treatment-related deaths from pneumonitis 3

Rechallenge Considerations

• Delay immunotherapy rechallenge until daily steroid dose ≤10 mg prednisone equivalent 2
• Approximately 2% of patients develop chronic pneumonitis persisting despite immune checkpoint inhibitor discontinuation and may not resolve after >3 months of corticosteroids 6, 3

Critical Pitfalls to Avoid

• Do not delay CT imaging for any new respiratory symptom—disease progression, infection, and pneumonitis must be formally excluded 3
• Do not taper steroids too quickly—use minimum 4-6 weeks for grade 2 and 6+ weeks for grade 3-4, as relapses are common 2, 3
• Fatal cases have been reported, making vigilant monitoring of all respiratory symptoms mandatory 3
• Steroid-refractory pneumonitis occurs in 18.5% of cases and is associated with 75% mortality, most commonly exhibiting a diffuse alveolar damage radiographic pattern 4
• Patients requiring additional immunosuppression face 12% mortality from infections possibly associated with immunosuppression 5