How do pneumonitis and pneumonia differ in etiology, clinical presentation, imaging findings, and management?

Pneumonitis vs. Pneumonia: Key Distinctions

Pneumonitis is a non-infectious inflammatory process of the lung parenchyma caused by drugs, radiation, or immune-mediated mechanisms, while pneumonia is an acute infectious inflammation of the alveoli and distal airways caused by bacteria, viruses, or fungi. 1, 2

Etiology

Pneumonitis

• Caused by non-infectious triggers including immune checkpoint inhibitors, chemotherapy agents, radiation therapy, environmental antigens (hypersensitivity pneumonitis), and other drugs like amiodarone and antibiotics 1
• Drug-related pneumonitis occurs in approximately 4% of patients on anti-PD-1 therapy, 2% on anti-PD-L1 therapy, and <1% on anti-CTLA-4 monotherapy 3
• Combination immunotherapy increases risk three-fold compared to monotherapy 4

Pneumonia

• Infectious etiology from bacteria (most commonly Streptococcus pneumoniae), respiratory viruses, or fungi 2
• Community-acquired pneumonia typically presents as lobar consolidation, while hospital-acquired pneumonia often manifests as bronchopneumonia 5
• Atypical organisms like Mycoplasma pneumoniae produce interstitial patterns 5

Clinical Presentation

Pneumonitis

• Dyspnea is the cardinal symptom, with typically dry, non-productive cough 4
• Fever may be absent, particularly in subacute or chronic forms 4
• Many cases are asymptomatic and detected only on routine imaging 4
• The temporal relationship between exposure to the causative agent and symptom onset is the single most important diagnostic clue 1, 4
• For immune checkpoint inhibitors, median onset is 2.8 months after drug initiation 4
• Radiation pneumonitis typically emerges 3-12 weeks post-exposure with a characteristic triad of dyspnea, dry cough, and chest pain 4

Pneumonia

• Presents with productive cough, fever, and purulent secretions 3
• Systemic symptoms are prominent including high fever (>38°C), leukocytosis or leukopenia 3
• Acute onset over hours to days rather than the subacute presentation of pneumonitis 2

Imaging Findings

Pneumonitis

• High-resolution CT is the imaging modality of choice and should be performed early when pneumonitis is suspected 3, 1
• Five radiological patterns: cryptogenic organizing pneumonia-like, ground-glass opacities, interstitial, hypersensitivity, and pneumonitis not otherwise specified 3
• Mosaic attenuation is characteristic of hypersensitivity pneumonitis 1
• Bilateral infiltrates that are typically asymmetric 3
• Two distinct patterns with prognostic significance: (1) diffuse ground-glass opacities correlating with acute lung injury and poor prognosis, and (2) consolidations or patchy subsolid opacities correlating with organizing pneumonia and favorable outcomes 6

Pneumonia

• Lobar consolidation is typical of community-acquired bacterial pneumonia 5
• New or progressive infiltrate plus purulent secretions on chest radiograph 3
• Bronchopneumonia shows patchy, multifocal consolidations 5

Management

Pneumonitis

• Immediate identification and removal of the causative agent is the primary intervention 1, 7
• For grade 1 (asymptomatic), withhold the offending drug and monitor closely every 2-3 days; re-challenge may be considered after resolution 3
• For grade 2 or higher, discontinue the drug permanently and initiate corticosteroids (oral or intravenous depending on severity) with a minimum 4-6 week taper to prevent recrudescence 3, 1
• For grade 3-4 pneumonitis, hospitalization is required with intravenous corticosteroids 3
• Additional immunosuppression with infliximab and/or cyclophosphamide is warranted for recalcitrant disease 3, 1
• Do not rechallenge with anti-TNF agents, as these require permanent discontinuation 7
• Bronchoscopy with bronchoalveolar lavage should be performed to exclude infectious causes 3, 7

Pneumonia

• Prompt empiric antimicrobial therapy is essential, as delayed appropriate antibiotic therapy increases mortality 3
• Selection based on risk factors for specific pathogens and local resistance patterns 3
• Therapy modified based on clinical response at days 2-3 and culture results 3
• A negative tracheal aspirate in patients without recent antibiotic changes has 94% negative predictive value for ventilator-associated pneumonia 3

Critical Diagnostic Pitfalls

When evaluating new pulmonary infiltrates in patients on immune checkpoint inhibitors or molecular-targeted agents, any new respiratory symptom mandates immediate chest CT to exclude pneumonitis—do not wait for fever, as it is frequently absent 4

The diagnosis of pneumonitis in cancer patients is challenging due to competing diagnoses including infectious pneumonia, tumor progression, pulmonary embolism, cardiac events, and radiation effects 3

A full clinical work-up must exclude infectious pneumonia before attributing symptoms to pneumonitis, particularly in patients with grade ≥2 severity where infectious disease consultation is warranted 3

Fatal pneumonitis occurs in approximately 0.2% of immune checkpoint inhibitor-treated patients, with higher mortality in non-small cell lung cancer patients 4