How can I differentiate pneumonitis from pneumonia and what are the appropriate treatments for each condition?

Differentiating Pneumonitis from Pneumonia

Pneumonitis is non-infectious lung inflammation caused by drugs, radiation, or immune reactions, while pneumonia is an infectious process with purulent secretions and fever—the key distinction lies in the temporal relationship to exposure, presence of productive cough with purulent sputum, and bilateral asymmetric infiltrates (pneumonitis) versus lobar consolidation (bacterial pneumonia). 1, 2

Critical Distinguishing Features

Clinical Presentation Differences

Pneumonitis:

• Dry, non-productive cough is the hallmark 1
• Dyspnea as the cardinal symptom, ranging from mild to severe 1
• Fever may be absent or low-grade 1, 3
• Temporal relationship between exposure (drug initiation, radiation) and symptom onset is the single most important diagnostic clue 1, 4
• Insidious onset over days to weeks 3
• Median onset 2.8 months after immune checkpoint inhibitor initiation 1

Pneumonia:

• Productive cough with purulent respiratory secretions 1, 2
• High fever (>38°C) with systemic signs 1
• Leukocytosis or leukopenia 1
• New lung infiltrate with clinical evidence of infection 2
• Acute onset 5

Radiographic Distinctions

Pneumonitis patterns on CT: 6, 1

• Bilateral, typically asymmetric infiltrates 1
• Five common patterns: organizing pneumonia-like, ground-glass opacities, interstitial, hypersensitivity, or not otherwise specified 1
• Radiation pneumonitis: sharp margin conforming to radiation port 3
• Multiple patterns may coexist 6

Pneumonia patterns: 6, 7

• Lobar consolidation (community-acquired) 7
• Bronchopneumonia pattern (hospital-acquired) 7
• Segmental distribution 1
• Purulent secretions visible on imaging 1

Diagnostic Algorithm

Step 1: Establish Exposure History

• Document all medications, especially immune checkpoint inhibitors, targeted agents, amiodarone, antibiotics 4
• Radiation therapy within 3-12 weeks 1, 3
• Environmental exposures for hypersensitivity pneumonitis 4

Step 2: Assess Clinical Features

• If productive cough with purulent sputum + high fever + leukocytosis → strongly suggests pneumonia 1, 2
• If dry cough + dyspnea + temporal relationship to drug/radiation → suggests pneumonitis 1, 4

Step 3: Obtain High-Resolution CT Immediately

• HRCT is the preferred imaging modality and should be obtained promptly 1
• Look for bilateral asymmetric infiltrates (pneumonitis) vs. lobar consolidation (pneumonia) 1, 7

Step 4: Exclude Infection Before Confirming Pneumonitis

• Perform bronchoscopy with bronchoalveolar lavage to exclude infectious etiology before confirming pneumonitis 1
• In cancer patients on immune checkpoint inhibitors, comprehensive work-up must first exclude infectious pneumonia; infectious disease consultation is recommended for grade ≥2 pneumonitis 1
• Negative tracheal aspirate has 94% negative predictive value for ventilator-associated pneumonia 1
• BAL cellular analysis: >15% lymphocytes, >3% neutrophils, >1% eosinophils suggest pneumonitis patterns 4

Treatment Approaches

Management of Pneumonitis

Grade 1 (asymptomatic): 1

• Hold offending immunotherapy agent
• Monitor every 2-3 days
• Consider re-challenge only after complete resolution

Grade 2 or higher: 1

• Permanently discontinue immunotherapy agent
• Initiate systemic corticosteroids (oral or IV) with minimum 4-6 week taper to prevent relapse

Grade 3-4: 1

• Hospital admission required
• IV corticosteroids
• For steroid-refractory cases: add infliximab, mycophenolate mofetil, IVIG, or cyclophosphamide 6

Drug-related pneumonitis (non-ICI): 4, 8

• Immediate discontinuation of causative drug is primary intervention 4, 8
• Corticosteroids for moderate to severe cases 4
• Do not rechallenge with the drug 8

Radiation pneumonitis: 3

• Supportive care
• Corticosteroids for symptomatic cases
• Distinguish from infection using radiographic port conformity 3

Management of Infectious Pneumonia

Empiric therapy: 1

• Initiate prompt empiric antimicrobial therapy; delays are associated with increased mortality 1
• Choose agents based on individual risk factors and local resistance patterns 1
• Re-evaluate at 2-3 days according to clinical response and culture results 1

Pathogen-directed therapy: 6, 5

• Adjust based on culture results and sensitivities 1
• Consider unusual pathogens in non-responders (Legionella, mycobacteria, fungi) 6

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Never assume pneumonitis without excluding infection first—this is the most dangerous pitfall 1
• Absence of fever does not exclude pneumonitis 1
• Asymptomatic pneumonitis is common; many cases identified only on routine imaging 1
• Any new respiratory symptom in patients on molecular-targeted agents or immune checkpoint inhibitors mandates immediate chest CT 1

Differential Diagnosis Beyond Infection

The differential also includes: 6, 1

• Tumor progression 1
• Pulmonary embolism 6, 1
• Cardiac events (heart failure, myocardial infarction) 6, 1
• Diffuse alveolar hemorrhage 4
• Pulmonary edema 4
• ARDS from severe sepsis 6

Special Populations

Combination immunotherapy: 6, 1

• Three-fold increased pneumonitis risk vs. monotherapy 1
• Higher incidence (10% vs. 3%) 6

NSCLC patients: 6, 1

• Higher pneumonitis risk than melanoma patients 6
• Higher mortality from fatal pneumonitis (0.2% overall) 1

Japanese cohorts: 6

• Significantly higher incidence of EGFR-TKI and ALK inhibitor pneumonitis 6

Infection Risk in Immunosuppressed Patients

For patients on TNF inhibitors (e.g., adalimumab): 8

• Significant infection risk including Legionella, Pneumocystis jirovecii, atypical mycobacteria 8
• These infectious complications must be excluded before attributing pneumonitis to drug toxicity 8