What is the management of pneumonitis?

Management of Pneumonitis

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

Diagnostic Evaluation

Before initiating treatment, confirm the diagnosis and exclude competing etiologies:

• CT chest is the imaging modality of choice to identify ground-glass opacities, patchy nodular infiltrates, or interstitial patterns characteristic of pneumonitis—chest radiographs are inadequate 3, 1
• Bronchoscopy with bronchoalveolar lavage (BAL) should be performed in all patients with grade 2 or higher pneumonitis to exclude infectious causes 3, 1
• Obtain pulmonology consultation for any patient with suspected pneumonitis, including those with new pulmonary infiltrates, worsening hypoxemia, dyspnea, or cough 3
• Monitor baseline and ongoing oxygen saturation at rest and with ambulation, along with pulmonary function tests and 6-minute walk test 3
• Transbronchial or surgical lung biopsy may be considered when etiology remains unclear, though not routinely required 1

Critical pitfall: Do not delay CT imaging for any new respiratory symptom—disease progression, infection, and pneumonitis must be formally excluded 4

Treatment Algorithm by Grade

Grade 1 Pneumonitis (Asymptomatic with Isolated Radiologic Changes)

• Continue causative therapy with close monitoring—corticosteroids are not required at this stage 1, 4, 2
• Monitor symptoms and oxygen saturation every 2-3 days using pulse oximetry 1, 4
• Repeat chest CT prior to the next scheduled dose of therapy 3
• Re-challenge is reasonable if infiltrates have resolved on repeat imaging, with cautious resumption and close follow-up 3
• Consider bronchoscopy if new or persistent infiltrates develop 3

Grade 2 Pneumonitis (Symptomatic but Not Requiring Oxygen)

• Immediately discontinue the suspected causative agent 1, 4, 2
• Initiate oral corticosteroids: prednisone 1 mg/kg daily or equivalent 3, 1, 4, 2
• Patients may be managed as outpatients if clinically stable 3
• Taper steroids over a minimum of 4-6 weeks after clinical recovery—rapid taper causes recrudescence of symptoms 3, 1, 2
• Perform bronchoscopy with BAL to exclude infections 3, 1
• Consider infectious disease consultation 3

Important nuance: Improvement following drug cessation without glucocorticoid therapy strongly supports drug-related pneumonitis, whereas clinical improvement with glucocorticoid therapy supports but does not definitively confirm the diagnosis 1, 4, 2

Grade 3-4 Pneumonitis (Severe Symptoms, Oxygen Required, or Life-Threatening)

• Hospitalize immediately and permanently discontinue the offending agent 1, 4, 2
• Administer high-dose IV corticosteroids: methylprednisolone 2-4 mg/kg/day or equivalent 3, 1, 4, 2
• Perform bronchoscopy with BAL to exclude infections 3, 1
• Consider broad-spectrum antibiotics in parallel if infectious status cannot be reliably assessed 1
• If no improvement after 48 hours, add additional immunosuppressive agents: infliximab, mycophenolate mofetil, or cyclophosphamide 3, 1, 2
• Taper steroids very slowly over 6+ weeks minimum as relapses during tapering are well-documented 1, 4

Evidence on additional immunomodulators: In steroid-refractory or steroid-resistant immune checkpoint pneumonitis, additional immunomodulators (TNF-alpha inhibitors in 77% and mycophenolate in 23%) achieved durable improvement in 38% of patients, though 90-day all-cause mortality/hospice referral was 50% and pneumonitis-attributable mortality was 23% 5

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% 4, 2
• Combination immunotherapy (anti-PD-1/PD-L1 plus anti-CTLA4) increases pneumonitis risk 3-fold, with incidence reaching 10% versus 3% for monotherapy 4, 2
• Patients with non-small cell lung cancer have more treatment-related deaths from pneumonitis compared to other tumor types 4
• Approximately 2% of non-small cell lung cancer or melanoma patients develop chronic pneumonitis persisting despite ICI discontinuation 4
• Steroid tapering must be very slow (6+ weeks minimum) for ICI-related pneumonitis as relapses during tapering have been reported 1, 4
• Fatal cases have been reported, making vigilant monitoring of all respiratory symptoms mandatory 4

Sarcoidosis-Like Reactions

If sarcoidosis is diagnosed (intrathoracic lymphadenopathy with epithelioid non-caseating granulomas on biopsy):

• Withhold immunotherapy, particularly in patients with extensive disease (stage ≥2), extrapulmonary disease involving critical organs (ocular, myocardial, neurologic, renal), or sarcoid-related hypercalcemia 3
• Treat if there is: (1) progressive radiographic change, (2) persistent/troublesome pulmonary symptoms, (3) lung function deterioration (TLC decline ≥10%, FVC decline ≥15%, DLCO decline ≥20%), (4) critical extrapulmonary organ involvement, or (5) sarcoid-related hypercalcemia 3
• Obtain eye examination and baseline electrocardiogram to investigate other organ system involvement 3

Monitoring and Follow-Up

• Monitor temperature, respiratory rate, pulse, blood pressure, mental status, oxygen saturation, and inspired oxygen concentration at least twice daily, more frequently in severe pneumonitis 3
• Reassess clinical response on Days 2 and 3: check temperature, white blood cell count, chest X-ray, oxygenation, purulent sputum, hemodynamic changes, and organ function 2
• Do not change therapy within the first 72 hours unless marked clinical deterioration occurs 4
• Repeat chest CT if patients are not progressing satisfactorily 3
• Consider further investigations including bronchoscopy in patients with persisting signs, symptoms, and radiological abnormalities about 6 weeks after completing treatment 3

Common Pitfalls

• Never delay CT imaging for any new respiratory symptom in patients on immunotherapy or other pneumonitis-inducing agents 4
• Never taper steroids rapidly—minimum 4-6 weeks is required to prevent recrudescence 3, 1, 4
• Do not assume clinical improvement with steroids confirms drug-related pneumonitis—it supports but does not definitively confirm the diagnosis 1, 4
• Be aware that pneumonitis may develop years after treatment with certain agents like cyclophosphamide 6
• Late-onset pneumonitis (>6 months after starting therapy) appears associated with increased mortality 6