Pneumonitis: Definition and Clinical Understanding
Pneumonitis is defined as focal or diffuse inflammation of the lung parenchyma that can be caused by various agents including drugs, environmental exposures, and immune checkpoint inhibitors. 1
Types and Causes of Pneumonitis
- Drug-related pneumonitis (DRP) is one of the most common forms, with cancer drugs (e.g., bleomycin), drugs for autoimmune diseases (e.g., methotrexate), amiodarone, and antibiotics (e.g., nitrofurantoin) being frequent causes 1
- Hypersensitivity pneumonitis (HP) results from an exaggerated immune response to inhaled antigens from environmental sources, occupational exposures, or medications 1, 2
- Immune-related interstitial lung disease (IR-ILD) or immune-related pneumonitis can occur with immune checkpoint inhibitor therapy 1
Clinical Presentation
Pneumonitis can present with varying severity, from asymptomatic to life-threatening 1
Common symptoms include:
- Dyspnea (shortness of breath)
- Dry cough
- Chest pain
- Fever
- Reduced exercise tolerance
- Fatigue with activities of daily living 1
The onset may be:
Diagnostic Features
Clinical Assessment
- Temporal relationship between exposure to potential causative agent and symptom onset is crucial for diagnosis 1
- Exclusion of other causes such as infection, pulmonary edema, and malignancy 1
Imaging
- Chest CT is essential and should be performed as early as possible when pneumonitis is suspected 1
- Common radiologic patterns include:
- Ground-glass opacities
- Consolidation
- Reticular opacities
- Nodular patterns
- Mosaic attenuation (in hypersensitivity pneumonitis) 1
Laboratory Testing
- Laboratory tests are not specific for pneumonitis but help exclude other causes 1
- Pulmonary function tests typically show:
- Restrictive ventilatory defect (reduced FVC and/or total lung capacity)
- Reduced diffusion capacity 1
Bronchoalveolar Lavage (BAL)
- In hypersensitivity pneumonitis, BAL typically shows increased lymphocytes (>40%) 3
- In acute forms, neutrophils may also be increased 3
Lung Biopsy
- May be necessary in subacute or chronic cases when diagnosis remains unclear 1, 3
- Typical findings include:
- Bronchiolitis
- Lymphocytic alveolitis
- Loosely formed granulomas
- Various interstitial pneumonia patterns (organizing pneumonia, diffuse alveolar damage, nonspecific interstitial pneumonia) 1
Differential Diagnosis
Pneumonitis must be distinguished from:
- Pneumonia (infectious): characterized by fever, productive cough, positive microbiology culture 1, 4
- Diffuse alveolar hemorrhage: often presents with hemoptysis and anemia 1
- Pulmonary edema: associated with cardiac or renal failure 1
- Radiation pneumonitis: occurs 3-12 weeks after radiation exposure 1
- Pulmonary metastases: progressive dyspnea related to malignancy 1
Management
- The primary approach is to identify and remove the causative agent 1, 3
- For drug-related pneumonitis:
- For hypersensitivity pneumonitis:
- Avoidance of the causative antigen
- Corticosteroids for subacute and chronic forms 3
- For immune checkpoint inhibitor-related pneumonitis:
- Grading of severity guides management
- Discontinuation of immunotherapy and corticosteroids for grade ≥2 1
Prognosis
If unchecked, pneumonitis can lead to:
Early recognition and treatment are essential to prevent progression to chronic, irreversible disease 1, 3
Common Pitfalls in Diagnosis
- Misdiagnosis as infectious pneumonia, especially in immunocompromised patients 1, 4
- Failure to identify the causative agent, particularly in hypersensitivity pneumonitis 5, 6
- Delayed diagnosis in cases with insidious onset 1, 3
- Overlooking pneumonitis in patients with pre-existing lung diseases such as COPD or pulmonary fibrosis 1