Cryptogenic Organizing Pneumonia: Definition, Diagnosis, and Treatment
What is Cryptogenic Organizing Pneumonia?
Cryptogenic organizing pneumonia (COP) is an idiopathic interstitial lung disease characterized by fibroblast proliferation forming polypoid masses (Masson bodies) within small airways and alveolar spaces, presenting as a subacute illness that responds excellently to oral corticosteroids in the majority of patients. 1, 2
COP represents the idiopathic form of organizing pneumonia where no underlying trigger can be identified, distinguishing it from secondary organizing pneumonia associated with infections, drugs, connective tissue diseases, or malignancies. 3, 4
Clinical Presentation
Patients typically present with a subacute illness of less than 3 months duration with the following features: 3, 4, 2
- Respiratory symptoms: Cough (often non-productive), dyspnea, and variable degrees of respiratory distress 3, 4
- Constitutional symptoms: Fever (present in 60% of cases), myalgia, malaise, fatigue, and weight loss 3, 2, 5
- Physical examination: Inspiratory crackles, diminished breath sounds, dull percussion, tachypnea, and tachycardia 3, 2
- Laboratory findings: Elevated inflammatory markers (CRP, ESR) are common but nonspecific 4
A flu-like prodrome heralds the onset in approximately 40% of patients. 3
Diagnostic Approach
High-Resolution CT Imaging
HRCT is the primary imaging modality and demonstrates characteristic patterns that strongly suggest the diagnosis: 4, 2
- Patchy, often migratory consolidation in subpleural, peribronchial, or bandlike distribution 3, 4
- Ground-glass opacities commonly associated with consolidation 3
- Reversed halo (atoll) sign and perilobular opacities are helpful diagnostic features when present 3, 2
- Small pleural effusions occur in 10-30% of patients 3, 4, 6
Pulmonary Function Testing
Lung function tests characteristically show a combined restrictive and obstructive pattern with impaired gas transfer (DLCO). 2, 5
Histopathological Confirmation
Definitive diagnosis requires histopathological confirmation showing three key features: 1, 2
- Cellular interstitial pneumonia
- Cellular bronchiolitis
- Poorly formed nonnecrotizing granulomas
The organizing pneumonia pattern involves a patchy process with granulation tissue in alveolar ducts and alveoli, with or without bronchiolar intraluminal polyps. 3, 1 The presence of Masson bodies confirms the diagnosis and predicts excellent corticosteroid response. 1, 2
Biopsy can be obtained via:
- Transbronchial biopsy (less invasive, adequate in some cases) 5, 7
- Video-assisted thoracoscopic surgery (VATS) or open lung biopsy (gold standard for definitive diagnosis) 5, 7
Exclusion of Secondary Causes
Before diagnosing cryptogenic OP, systematically exclude secondary causes: 1, 4, 2
- Infections (bacterial, viral, fungal, mycobacterial)
- Drug reactions (chemotherapy agents, biologics, PD-1/PD-L1 inhibitors, interferon, monoclonal antibodies) 2, 8
- Connective tissue diseases (rheumatoid arthritis, polymyositis, antisynthetase syndrome) 3, 4, 9
- Malignancies (hematologic malignancies, solid tumors) 4, 5
- Hypersensitivity pneumonitis 4, 2
- Radiation therapy 8
Treatment
Oral corticosteroids are the treatment of choice for non-remitting or progressive cryptogenic organizing pneumonia. 1, 2
Corticosteroid Regimen
- Initial dose: Prednisone approximately 50 mg/day 1, 2, 9
- Duration: Prolonged therapy typically required for several months 5, 9
- Response: The majority of patients recover completely with corticosteroid therapy 3, 4
Alternative Therapies
Macrolide antibiotics have been investigated but lack sufficient evidence for routine recommendation. 4 Steroid-sparing immunosuppressive agents may be considered in specific variants (cicatricial or acute fibrinous types) that require higher immunosuppression doses. 8
Prognosis and Follow-up
Complete recovery occurs in the majority of patients, but relapse is common, occurring in up to two-thirds of cases. 1, 2
Prognostic Factors
- Five-year survival for cryptogenic OP is 73%, significantly better than secondary OP (44%) 1, 2, 9
- Risk factors for relapse include: Fever at presentation, elevated CRP levels, and reduced DLCO % predicted 2
- Poor prognostic variants: Some patients develop residual or progressive interstitial fibrosis despite prolonged treatment, particularly those with fibrosing variants or underlying polymyositis/antisynthetase syndrome 3, 4
Clinical Pitfalls
Maintain high clinical suspicion for COP in patients with non-resolving pneumonia who fail to respond to adequate antibiotic therapy. 6, 5 The clinical presentation often mimics community-acquired pneumonia, leading to diagnostic delays and inappropriate prolonged antibiotic use. 6, 7
Spontaneous recovery is rare; most patients require corticosteroid therapy. 7 One notable exception is focal OP presenting as an asymptomatic solitary pulmonary nodule (14% of cases), which requires no treatment and has excellent prognosis. 9