What is the appropriate management approach for a patient with pneumonitis?

Management of Pneumonitis

For drug-related pneumonitis, immediately discontinue the offending agent and initiate corticosteroids based on severity grading: grade 1 requires monitoring only, grade 2 requires oral prednisone 1 mg/kg daily, and grade 3-4 requires hospitalization with IV methylprednisolone 2-4 mg/kg/day. 1, 2

Diagnostic Evaluation

Obtain CT chest imaging immediately for any patient with suspected pneumonitis, as chest radiographs are inadequate for identifying the characteristic ground-glass opacities, patchy nodular infiltrates, or interstitial patterns. 1, 2 Never delay CT imaging for any new respiratory symptom in patients on immunotherapy or other pneumonitis-inducing agents. 3

Perform bronchoscopy with bronchoalveolar lavage (BAL) in all patients with grade 2 or higher pneumonitis to exclude infectious causes before escalating immunosuppression. 1, 2 This is critical because infection and pneumonitis can present identically, and treating infection with steroids alone would be catastrophic.

Obtain immediate pulmonology consultation for any patient with new pulmonary infiltrates, worsening hypoxemia, dyspnea, or cough in the setting of potential drug exposure. 1 Monitor baseline and ongoing oxygen saturation at rest and with ambulation. 1

Treatment Algorithm by Severity Grade

Grade 1 Pneumonitis (Asymptomatic with Isolated Radiologic Changes)

• Continue causative therapy with close monitoring every 2-3 days—corticosteroids are not required at this stage. 1, 2, 3
• Monitor symptoms closely as progression can occur rapidly, particularly with immune checkpoint inhibitors. 2

Grade 2 Pneumonitis (Symptomatic but Not Requiring Oxygen)

• Immediately discontinue the suspected causative agent. 1, 2, 3
• Initiate oral prednisone 1 mg/kg daily or equivalent. 1, 2, 3
• Taper steroids over a minimum of 4-6 weeks after recovery—rapid tapering causes recrudescence. 1, 2, 3 This is a critical pitfall: relapses during tapering are well-documented, and the taper must be slow and methodical.

Grade 3-4 Pneumonitis (Severe Symptoms, Hypoxemia, 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
• Consider additional immunosuppression if no improvement after 48 hours: infliximab, mycophenolate mofetil, intravenous immunoglobulin, or cyclophosphamide. 2
• Taper steroids over 6+ weeks minimum after recovery for grade 3-4 pneumonitis. 2
• For grade 3 pneumonitis where infectious status cannot be reliably assessed, administer broad-spectrum antibiotics in parallel to immunosuppressive treatment. 2

Special Considerations for Immune Checkpoint Inhibitor (ICI) Pneumonitis

Anti-PD-1/PD-L1 monoclonal antibodies cause pneumonitis in 2-4% of patients, with grade 3-4 events in 1-2% and fatal pneumonitis in 0.2%. 3 This makes pneumonitis the most common cause of ICI-related mortality, accounting for 35% of all deaths from these agents. 4

Combination immunotherapy (anti-PD-1/PD-L1 plus anti-CTLA4) increases pneumonitis risk 3-fold, with incidence reaching 10% versus 3% for monotherapy. 3 Patients with non-small cell lung cancer have higher treatment-related deaths from pneumonitis compared to other tumor types. 3

Organizing pneumonia (OP) pattern is the most common CT finding (23% of cases), followed by hypersensitivity pneumonitis (HP) pattern (16%). 4 The CT pattern correlates with toxicity grade: diffuse alveolar damage (DAD) pattern has the highest grades, followed by OP pattern, whereas NSIP and HP patterns have lower grades. 4

Monitoring and Clinical Response Assessment

Monitor vital signs and oxygen saturation at least twice daily, more frequently in severe pneumonitis: temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation, and inspired oxygen concentration. 1

Reassess clinical response on Days 2 and 3: check temperature, white blood cell count, chest X-ray, oxygenation, and organ function. 1 Do not change therapy within the first 72 hours unless marked clinical deterioration occurs. 1, 3

Repeat chest CT if patients are not progressing satisfactorily. 1 In patients improving clinically without concerning features, further investigations are not necessary just because radiological improvement lags behind clinical recovery. 4

Critical Pitfalls to Avoid

Never delay CT imaging—disease progression, infection, and pneumonitis must be formally excluded for any new respiratory symptom. 3 Chest radiographs are inadequate for this purpose.

Never taper steroids rapidly—minimum 4-6 weeks is required to prevent recrudescence, and 6+ weeks for severe cases. 1, 2, 3 Relapses during tapering are well-documented and can be severe.

Never assume improvement with steroids confirms the diagnosis—clinical improvement with glucocorticoid therapy supports but does not definitively confirm drug-related pneumonitis. 2 Improvement following drug cessation without glucocorticoid therapy more strongly supports the diagnosis. 2, 3

Fatal cases have been reported—vigilant monitoring of all respiratory symptoms is mandatory. 3 Approximately 2% of non-small cell lung cancer or melanoma patients develop chronic pneumonitis persisting despite immune checkpoint inhibitor discontinuation. 3