What is the workup and treatment for pneumonitis?

Pneumonitis Workup and Treatment

Initial Diagnostic Workup

When pneumonitis is suspected, immediately obtain high-resolution CT chest with contrast to identify characteristic patterns (ground-glass opacities, patchy nodular infiltrates, or interstitial changes) and exclude alternative diagnoses including pulmonary embolism, tumor progression, cardiac events, and pleural pathology. 1, 2

Essential Baseline Evaluation

• Pulse oximetry to assess oxygenation status 1
• High-resolution CT chest with contrast as the preferred imaging modality—standard chest x-ray has poor sensitivity 1, 2
• Infectious workup for grade 2 or higher severity:
  • Nasal swab for respiratory viruses 1
  • Sputum culture and sensitivity 1
  • Blood cultures 1
  • Urine culture 1
  • COVID-19 testing per institutional protocols 1

Advanced Diagnostic Procedures

• Bronchoscopy with bronchoalveolar lavage (BAL) should be performed for grade 2 or higher pneumonitis to exclude infection and tumor infiltration 1, 2
• Transbronchial biopsy may be considered when etiology remains unclear, though not routinely required 1, 2
• Pulmonary function tests (spirometry, DLCO) if CT is negative but clinical suspicion remains high 1

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Treatment Algorithm by Severity Grade

Grade 1: Asymptomatic (confined to <25% lung parenchyma)

• Hold causative agent or proceed with close monitoring 1, 2
• Monitor weekly with history, physical examination, and pulse oximetry 1
• Repeat chest imaging in 3-4 weeks or sooner if symptoms develop 1
• No corticosteroids required at this stage 3
• May resume causative therapy if radiographic improvement documented; if no improvement, escalate to grade 2 management 1

Grade 2: Symptomatic (25-50% lung involvement, limiting instrumental activities)

Immediately discontinue the causative agent and initiate oral prednisone 1-2 mg/kg/day, tapering over 4-6 weeks after clinical improvement. 1, 2

• Hold causative therapy until clinical improvement to grade 1 1
• Consider bronchoscopy with BAL and transbronchial biopsy 1
• Empiric antibiotics if infection cannot be excluded after workup 1
• Monitor at least weekly with history, physical examination, pulse oximetry, and consider repeat imaging 1
• If no clinical improvement after 48-72 hours of prednisone, escalate to grade 3 management 1
• Pulmonary and infectious disease consultation as needed 1
• Rechallenge with causative therapy may be considered upon complete symptom resolution with close monitoring 1

Grade 3: Severe (>50% lung involvement, limiting self-care, oxygen required)

Hospitalize immediately, permanently discontinue the causative agent, and administer intravenous methylprednisolone 1-2 mg/kg/day. 1, 2, 3

• Empiric broad-spectrum antibiotics should be considered if infectious status cannot be reliably assessed 1, 3
• If no improvement after 48 hours, add second-line immunosuppressive therapy: 1
  • Infliximab 5 mg/kg (repeat every 2 weeks if needed) 1
  • Tocilizumab 8 mg/kg (repeat every 2 weeks if needed) 1
  • Mycophenolate mofetil 1 g twice daily 1
  • IVIG 2 g/kg over 2-5 days 1
  • Cyclophosphamide (alternative option) 1
• Taper corticosteroids over 6-8 weeks after improvement to grade <1 1
• Pulmonary and infectious disease consultation mandatory 1
• Consider bronchoscopy with BAL and transbronchial biopsy if patient can tolerate 1

Grade 4: Life-threatening (urgent intervention/intubation required)

Permanently discontinue causative agent, administer intravenous methylprednisolone 2-4 mg/kg/day, and provide urgent respiratory support including mechanical ventilation as needed. 2, 4, 3

• Same immunosuppressive escalation strategy as grade 3 if no improvement after 48 hours 1, 2
• Immediate pulmonary and infectious disease consultation 1

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Critical Management Considerations

Steroid Tapering

Corticosteroid tapering must be very slow (minimum 6+ weeks) as relapses during tapering are well-documented, particularly in immune checkpoint inhibitor-related pneumonitis. 2, 3

• Grade 2: Taper over 4-6 weeks 1, 2
• Grade 3: Taper over 6-8 weeks 1
• Approximately 2% of patients develop chronic pneumonitis requiring immunosuppression >12 weeks 1, 3

Diagnostic Confirmation

• Improvement following drug cessation without glucocorticoid therapy strongly supports drug-related pneumonitis 2, 3
• Clinical improvement with glucocorticoid therapy supports but does not definitively confirm the diagnosis 2, 3

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Common Pitfalls to Avoid

• Never delay CT imaging for new respiratory symptoms—disease progression, infection, and pneumonitis must be formally excluded 3
• Do not change initial antibiotic therapy within the first 72 hours unless marked clinical deterioration occurs 3
• Do not underestimate severity: fatal cases occur in approximately 9% of immune checkpoint inhibitor-related pneumonitis, with higher mortality in non-small cell lung cancer patients 4, 3
• Patients with pre-existing lung disease (COPD, interstitial lung disease) are at higher risk and require specialist consultation before initiating causative therapy 1
• Previous radiation therapy, smoking history, and squamous histology may increase pneumonitis risk 1