What is the recommended approach to managing pneumonitis?

Management of Pneumonitis

Immediately discontinue the suspected causative agent and initiate corticosteroids based on severity grading: prednisone 1 mg/kg/day for grade 2, or IV methylprednisolone 2-4 mg/kg/day for grade 3-4 pneumonitis. 1, 2

Initial Diagnostic Evaluation

Obtain CT chest imaging immediately for any patient with new respiratory symptoms, as chest radiographs are inadequate for identifying the ground-glass opacities, patchy nodular infiltrates, or interstitial patterns characteristic of pneumonitis. 1, 2 High-resolution CT distinguishes patterns: lobar consolidation suggests bacterial pneumonia, while ground-glass opacities with centrilobular nodules suggest hypersensitivity pneumonitis. 3

Perform bronchoscopy with bronchoalveolar lavage (BAL) in all patients with grade 2 or higher pneumonitis to exclude infectious causes before initiating immunosuppression. 1, 2 This is critical because starting corticosteroids empirically without ruling out infection can worsen bacterial or fungal pneumonia. 3

Obtain targeted exposure history including:

• Occupational and home environmental exposures to organic antigens (birds, mold, hay, chemicals) 3
• Complete medication review: recent chemotherapy, immunotherapy (checkpoint inhibitors), amiodarone, or biologics 3
• Timing of symptom onset relative to drug initiation 4

Obtain pulmonology consultation for any patient with suspected pneumonitis, including those with new pulmonary infiltrates, worsening hypoxemia, dyspnea, or cough. 1

Treatment Algorithm by Severity Grade

Grade 1 Pneumonitis (Asymptomatic, Radiologic Changes Only)

• Continue causative therapy with close monitoring every 2-3 days, as corticosteroids are not required at this stage. 1, 2
• Repeat chest CT prior to next scheduled dose of the causative agent. 4
• Monitor oxygen saturation at rest and with ambulation. 1

Grade 2 Pneumonitis (Symptomatic, Not Interfering with ADLs)

• Immediately discontinue the suspected causative agent. 1, 2
• Initiate oral prednisone 1 mg/kg daily (or equivalent). 4, 3, 1, 2
• Consider gastroprotection with proton pump inhibitors. 5
• Taper steroids over minimum 4-6 weeks after recovery—rapid tapering causes recrudescence. 1, 2 The taper should be gradual, with approximately 10 mg prednisone decrease per week. 5
• Monitor symptoms every 2-3 days. 2
• Patients may be managed as outpatients. 4

Grade 3-4 Pneumonitis (Severe, Limiting Self-Care ADLs or Life-Threatening)

• Hospitalize immediately and permanently discontinue the offending agent. 1, 2
• Administer high-dose IV methylprednisolone 2-4 mg/kg/day (or equivalent) for 3 days prior to transitioning to oral corticosteroids. 1, 2, 5
• Add second-line immunosuppression (infliximab, mycophenolate mofetil, intravenous immunoglobulin, or cyclophosphamide) if no improvement after 48 hours of corticosteroid therapy. 2
• Administer broad-spectrum antibiotics in parallel if infectious status cannot be reliably assessed. 2
• Monitor temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation, and inspired oxygen concentration at least twice daily. 1
• Taper steroids over 6+ weeks minimum after recovery. 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%. 1 Combination immunotherapy (anti-PD-1/PD-L1 plus anti-CTLA-4) increases pneumonitis risk 3-fold, with incidence reaching 10% versus 3% for monotherapy. 4, 1

ICI-related pneumonitis is one of the most common causes of ICI-related death. 4 Pneumonitis onset appears earlier in non-small cell lung cancer (median 2.1 months) versus melanoma (median 5.2 months). 4

For ICI pneumonitis specifically:

• Re-challenge following resolution is reasonable for grade 1 pneumonitis only. 4
• Do not rechallenge for grade 3-4 pneumonitis—permanent discontinuation is required. 1, 2
• Delay immunotherapy rechallenge until daily steroid dose ≤10 mg prednisone equivalent. 2

Monitoring and Reassessment

Reassess clinical response on Days 2 and 3: check temperature, white blood cell count, chest X-ray, oxygenation, hemodynamic changes, and organ function. 1

Do not change therapy within the first 72 hours unless marked clinical deterioration occurs. 1 However, failure to improve mandates diagnostic bronchoscopy and consideration of non-infectious causes. 3

Repeat chest CT if patients are not progressing satisfactorily or to assess for progression, parapneumonic effusion, or abscess. 3, 1

Critical Pitfalls to Avoid

• Never delay CT imaging for any new respiratory symptom in patients on immunotherapy or other pneumonitis-inducing agents. 1
• Never assume all infiltrates are infectious—hypersensitivity pneumonitis and drug reactions are common mimics, and the lingula is a frequent site for both aspiration and hypersensitivity pneumonitis. 3
• Never start corticosteroids empirically without ruling out infection, as this can worsen bacterial or fungal pneumonia. 3
• Never taper steroids rapidly—minimum 4-6 weeks is required to prevent recrudescence, and 6+ weeks for severe cases. 1, 2
• Never rely on clinical improvement with antibiotics alone to confirm bacterial etiology—hypersensitivity pneumonitis and drug-induced pneumonitis may improve spontaneously or with supportive care. 3
• Never overlook dual pathology—immunosuppressed patients can have both infection and drug-induced pneumonitis simultaneously. 3
• Never continue ineffective antibiotics beyond 72 hours without bronchoscopy and consideration of non-infectious causes. 3

Distinguishing Infectious from Non-Infectious Pneumonitis

Improvement following cessation of drug administration without glucocorticoid therapy strongly supports drug-related pneumonitis. 2 However, clinical improvement with glucocorticoid therapy supports but does not definitively confirm the diagnosis. 2

For patients requiring mechanical ventilation with acute interstitial pneumonitis, use low-tidal-volume ventilation (approximately 6 mL per kilogram of ideal body weight) when diffuse bilateral infiltrates are present. 2