Cryptogenic Organizing Pneumonia

• Daniel Katzman, M.D.
• Bishoy Zakhary, M.D.

 Basic Information

Definition

Cryptogenic organizing pneumonia is a type of idiopathic interstitial pneumonia, which has a histologic pattern of organizing pneumonia combined with characteristic clinical and radiographic features. The histologic pattern of organizing pneumonia consists of intraluminal organizing fibrosis in distal airways with intraalveolar buds of granulation tissue composed of connective tissue, fibroblasts, and myofibroblasts. Foci of organizing pneumonia tend to have a patchy distribution and uniform appearance with relative preservation of underlying lung architecture. Cryptogenic organizing pneumonia has no known underlying cause. Secondary causes associated with a histologic pattern of organizing pneumonia must be clinically excluded.

Synonyms

Bronchiolitis obliterans organizing pneumonia (BOOP)

ICD10-CM CODES
J84.116	Cryptogenic organizing pneumonia

Epidemiology & Demographics

Incidence

Estimated incidence is 6 to 7 cases per 100,000 per year

Peak Incidence

Typically, age of onset is 50 to 60 years old

Prevalence

Unknown

Predominant Sex and Age

No sex predominance

Genetics

Unknown

Risk Factors

Unknown

Physical Findings & Clinical Presentation

The clinical presentation ranges from an acute onset of flulike symptoms to a subacute illness with cough and dyspnea. Common presenting symptoms are fevers, dyspnea, nonproductive cough, malaise, and weight loss. Symptoms are typically present for less than 3 months in the majority of cases. A lack of response to antibiotics for the treatment of community-acquired pneumonia may raise suspicion for cryptogenic organizing pneumonia. Lung examination may be remarkable for inspiratory crackles or may be normal.

Etiology

The etiology of cryptogenic organizing pneumonia is unknown. The pathogenesis may begin with alveolar epithelial injury of an unknown cause.

Diagnosis

Differential Diagnosis

Community-acquired pneumonia, chronic eosinophilic pneumonia, and hypersensitivity pneumonitis can have similar clinical presentations and radiographic features. The differential diagnosis also includes other types of idiopathic interstitial pneumonias and secondary causes of organizing pneumonia, which need to be excluded (Table 1).

Workup

Chest imaging is commonly performed (see “Imaging Studies”). Pulmonary function testing may show a mild to moderate restrictive pattern with a reduced diffusion capacity. Bronchoscopy with bronchoalveolar lavage (BAL) is performed to evaluate for other disease processes, such as active infection, eosinophilic pneumonia, hypersensitivity pneumonitis, and malignancy. Transbronchial biopsies may be unreliable for detecting organizing pneumonia due to the patchy distribution of the disease. Additionally, when foci of organizing pneumonia are detected (Fig. 1), the relatively small tissue specimens may not be sufficient to exclude other coexisting histopathologic processes. A surgical lung biopsy may be needed to make a definitive diagnosis, especially if clinical and radiographic features are not typical. After a histologic diagnosis of organizing pneumonia is made, additional evaluation for secondary causes is necessary. This may include serologic testing for connective tissue diseases and human immunodeficiency virus, in addition to infectious and hematologic evaluation (Table 1).

Laboratory Tests

Leukocytosis without peripheral eosinophilia and elevated inflammatory markers, including elevated erythrocyte sedimentation rate and C-reactive protein, are frequently present. BAL cell counts are remarkable for a mixed pattern, typically with increased lymphocytes (20%-40%), neutrophils (approximately 10%), and eosinophils (approximately 5%). CD4/CD8 ratio is also decreased in the majority of cases. However, these laboratory tests are all nonspecific.

Imaging Studies

Chest radiograph and chest computed tomography (CT) scan will typically show unilateral or bilateral peripheral airspace consolidations that may be migratory. On chest CT scan, consolidations are often subpleural or peribronchial in location. Additionally, a perilobular pattern (airspace consolidation at the periphery of a secondary pulmonary lobule) can be present in over half of cases. Ground-glass opacities, nodular or mass-like opacities, and small ill-defined nodules are common (Fig. 2). The reverse halo sign (central ground-glass opacity surrounded by airspace consolidation) is infrequently seen.

Treatment

Acute General Rx

For patients with persistent or progressive symptoms, prednisone is initiated at a dose of 0.75 to 1 mg/kg PO daily. Most cases have a rapid improvement with initiation of prednisone.

Chronic Rx

Prednisone is weaned over months. Relapse is common but rarely associated with poor outcomes. Prolonged prednisone therapy can be considered for relapsing cases after weighing risks and benefits. Other immunosuppresses, such as cyclophosphamide or azathioprine, can be considered as adjunctive or steroid-sparing therapies.

Pearls & Considerations

1. •

   Chest imaging with peripheral airspace consolidations combined with a clinical presentation of an acute, flulike illness or subacute dyspnea and cough that does not respond to antibiotics should raise suspicion for cryptogenic organizing pneumonia.

2. •

   Cryptogenic organizing pneumonia has no known underlying cause. Secondary causes associated with a histologic pattern of organizing pneumonia must be clinically excluded.

3. •

   When cryptogenic organizing pneumonia is suspected, bronchoscopy with bronchoalveolar lavage can evaluate for disease mimics, including infection, eosinophilic pneumonia, hypersensitivity pneumonitis, and malignancy. However, tissue biopsies are needed to make a definitive diagnosis, which may require a surgical lung biopsy.

Suggested Readings

• F. Drakopanagiotakis, et al.: Cryptogenic and secondary organizing pneumonia: clinical presentation, radiographic findings, treatment response, and prognosis. Chest. 139 (4):893–900 2011 20724743

• T.E. King: Cryptogenic organizing pneumonia. UpToDate. 2017

• D. Travis, et al.: An Official American Thoracic Society/European Respiratory Society statement: update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med. 188:733–748 2013 24032382

Related Content

1. Interstitial Lung Disease (Related Key Topic)