What is the recommended approach to managing pneumonitis, including identification and removal of the trigger, supportive oxygen therapy, corticosteroid treatment, empirical antibiotics if infection cannot be excluded, and appropriate follow‑up?

Management of Pneumonitis

For drug-induced pneumonitis, implement a severity-based treatment algorithm: 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, 2

Initial Assessment and Trigger Identification

Identify and permanently discontinue the causative agent immediately for grade 2 or higher pneumonitis. 1, 2

• Obtain high-resolution CT chest imaging to characterize patterns: ground-glass opacities suggest acute processes, patchy nodular infiltrates suggest hypersensitivity pneumonitis, and diffuse alveolar damage (DAD) pattern indicates severe disease with highest toxicity grades 3, 1
• Perform bronchoscopy with bronchoalveolar lavage (BAL) for grade 2 or higher pneumonitis to exclude infectious etiologies, particularly in immunosuppressed patients 1
• Document detailed exposure history including all medications (especially immune checkpoint inhibitors, chemotherapy, amiodarone), occupational exposures, and environmental antigens 1, 4
• Consider transbronchial or surgical lung biopsy only when etiology remains unclear after initial workup, though not routinely required 3, 1

Severity-Based Treatment Protocol

Grade 1 Pneumonitis (Asymptomatic with Isolated Radiologic Changes)

• Continue causative therapy with close monitoring every 2-3 days using pulse oximetry to assess symptoms and oxygen saturation 1, 2
• Corticosteroids are not required at this stage 1, 2
• Improvement following drug cessation without glucocorticoid therapy strongly supports drug-related pneumonitis diagnosis 1, 2

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 corticosteroid) 1, 2, 5
• Taper steroids over minimum 4-6 weeks after clinical recovery to prevent relapse 1, 2
• Monitor clinical response on days 2 and 3 by checking temperature, white blood cell count, chest X-ray, oxygenation, and organ function 2

Grade 3-4 Pneumonitis (Severe Symptoms, Limiting Self-Care 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) 1, 2, 5
• For severe radiation pneumonitis specifically, expert consensus supports IV methylprednisolone for 3 days prior to transitioning to oral corticosteroids 5
• Initiate broad-spectrum empirical antibiotics in parallel if infectious status cannot be reliably assessed, particularly in immunosuppressed patients 1
• Taper steroids over minimum 6+ weeks after recovery, as relapses during tapering are common in immune checkpoint inhibitor-related pneumonitis 1

Supportive Care Measures

• Provide supplemental oxygen therapy with monitoring to maintain PaO2 >8 kPa and SaO2 >92% 3
• Administer high-concentration oxygen safely in uncomplicated pneumonitis; guide therapy with repeated arterial blood gases in patients with pre-existing COPD 3
• Assess for volume depletion and provide intravenous fluids as needed 3
• Consider gastroprotection when initiating corticosteroid therapy 5
• Monitor temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation, and inspired oxygen concentration at least twice daily 3

Management of Steroid-Refractory Disease

If no clinical improvement occurs after 48 hours of high-dose corticosteroid therapy, add second-line immunosuppression. 1, 6

• Intravenous immunoglobulin (IVIG) alone demonstrates superior outcomes compared to infliximab, with 43% mortality versus 100% mortality with infliximab in steroid-refractory cases 6
• Alternative second-line agents include mycophenolate mofetil, cyclophosphamide, or IVIG, though evidence remains limited 1, 7
• Cyclophosphamide may be considered as steroid-refractory pneumonitis has shown some response in small case series 7
• Steroid-refractory pneumonitis occurs in approximately 10-18.5% of ICI-pneumonitis cases and carries high mortality (67-75%) 6, 7
• Diffuse alveolar damage (DAD) pattern on imaging is most commonly associated with steroid-refractory disease 6

Follow-Up and Monitoring

• Repeat chest radiograph at 6 weeks for patients with persistent signs, symptoms, or radiological abnormalities 3
• Clinical review is not necessary prior to hospital discharge in patients with satisfactory clinical recovery 3
• Consider bronchoscopy for patients with persisting abnormalities to remove retained secretions, obtain cultures, and exclude endobronchial abnormality 3
• Delay immunotherapy rechallenge until daily steroid dose is ≤10 mg prednisone equivalent 1

Critical Pitfalls to Avoid

• Do not rely solely on clinical improvement with corticosteroid therapy to confirm diagnosis, as other interstitial lung diseases may also respond to steroids 4
• Recognize that combination immunotherapy increases pneumonitis risk 3-fold (10% versus 3% for monotherapy) 2
• Be aware that immune checkpoint inhibitor pneumonitis is fatal in 0.2% of cases and accounts for 35% of all PD-1/PD-L1-related deaths 3, 2
• Consider dual pathology, particularly coexisting infection and drug-induced pneumonitis in immunosuppressed patients 4
• Avoid rapid steroid tapering, as pneumonitis flare-ups can occur even without ICI re-treatment 3