What is pneumonitis?

What is Pneumonitis?

Pneumonitis is focal or diffuse inflammation of the lung parenchyma caused by non-infectious triggers including drugs, environmental exposures, radiation, or immune checkpoint inhibitors—fundamentally distinguishing it from pneumonia, which is infectious. 1

Core Definition and Pathophysiology

Pneumonitis represents a non-infectious inflammatory process of lung tissue triggered by:

• Drug reactions (chemotherapy agents, amiodarone, antibiotics, immunosuppressants) 1
• Immune checkpoint inhibitors (PD-1/PD-L1 inhibitors in cancer therapy) 1
• Inhaled environmental antigens (organic particles causing hypersensitivity reactions) 1, 2
• Radiation exposure 3
• Chemical aspiration 4

The key pathophysiologic mechanism involves an exaggerated immune response rather than microbial invasion, with CD4+ T cell differentiation into Th1 cells promoting granuloma formation in hypersensitivity pneumonitis. 1

Clinical Presentation Spectrum

Pneumonitis severity ranges from asymptomatic to life-threatening, presenting in three temporal patterns: 1

Acute form:

• Flu-like symptoms with dyspnea and dry cough 5
• Fever may be absent or low-grade (unlike pneumonia's high fever) 3
• Symptoms resolve within hours to days after exposure cessation 5

Subacute form:

• Progressive dyspnea and dry cough from recurrent low-level antigen exposure 5
• Fatigue limiting activities of daily living 1
• Constitutional symptoms including anorexia and weight loss 5

Chronic form:

• Insidious progression or evolution from repeated acute episodes 5
• Risk of irreversible pulmonary fibrosis if unchecked 1
• Can mimic other interstitial lung diseases, making diagnosis challenging 6

Diagnostic Features That Distinguish Pneumonitis from Pneumonia

Critical diagnostic clue: Temporal relationship between exposure to a causative agent and symptom onset is essential for diagnosis. 1

Radiologic patterns on chest CT (perform early when suspected): 1

• Bilateral, non-segmental ground-glass opacities (not lobar consolidation) 3
• Small poorly defined nodules with patchy distribution 5
• Mosaic attenuation (characteristic of hypersensitivity pneumonitis) 1
• Cryptogenic organizing pneumonia pattern (most common at 23% of cases) 4
• Diffuse alveolar damage pattern (most severe presentation) 4

Key differences from pneumonia: 3

• Pneumonitis: bilateral, non-segmental, ground-glass predominant
• Pneumonia: lobar/segmental consolidation with air bronchograms

Severity Grading System

The American Thoracic Society classifies pneumonitis into grades 1-5 based on clinical severity: 4

• Grade 1: Asymptomatic with radiographic findings only
• Grade 2: Symptomatic with mild-moderate symptoms limiting daily activities (66% of cases) 4
• Grade 3: Severe symptoms limiting self-care, requiring hospitalization 4
• Grade 4: Life-threatening respiratory compromise requiring mechanical ventilation (9% of cases) 4
• Grade 5: Fatal (approximately 9% of immune checkpoint inhibitor-related cases) 4

Management Algorithm

Primary intervention: Identify and remove the causative agent immediately. 1

For Grade 1 (Asymptomatic):

• Monitor closely with observation 4
• Remove causative agent if identified 1

For Grade 2 (Mild-Moderate):

• Discontinue the offending agent 4
• Initiate oral prednisone 1 mg/kg daily 4
• Taper corticosteroids over 4-6 weeks after recovery 4
• Outpatient management acceptable 4
• Perform bronchoscopy with BAL to exclude infection 4

For Grade 3-4 (Severe-Life-threatening):

• Immediate hospitalization 4
• Permanently discontinue causative agent 4
• High-dose IV methylprednisolone 2-4 mg/kg/day 4
• Add infliximab, mycophenolate, or cyclophosphamide if no improvement after 48 hours 4
• Provide respiratory support (oxygen, mechanical ventilation as needed) 4
• Bronchoscopy with BAL mandatory to exclude infection 4

Common Pitfalls to Avoid

Do not assume all pulmonary infiltrates with fever are infectious—fever, leukocytosis, and infiltrates occur in both pneumonitis and pneumonia. 3 However, never delay antibiotics if pneumonia cannot be excluded, as delayed antimicrobial therapy increases mortality. 3

Delayed diagnosis leads to irreversible fibrosis—early recognition and causative agent removal are essential to prevent progression to chronic, irreversible disease. 1, 4

Patients with pre-existing lung disease face higher risk and worse outcomes. 4

Prognosis

Clinical improvement after cessation of exposure without glucocorticoid therapy strongly supports the diagnosis. 4 Follow-up chest radiograph should be obtained at 6 weeks for patients with persistent symptoms. 4 If untreated, pneumonitis progresses to pulmonary fibrosis with potential respiratory failure. 1