What are the possible causes of pleurisy in a patient with uncomplicated pleural inflammation?

Causes of Pleurisy

Pleurisy (pleural inflammation) has multiple etiologies, with the most common serious causes being pulmonary embolism, infection (parapneumonic effusion, tuberculosis), malignancy, and autoimmune diseases, while viral infections represent the most frequent benign cause. 1, 2, 3

Infectious Causes

Bacterial Infections

• Parapneumonic effusions and empyema account for approximately 16% of all pleural effusions and represent a leading infectious cause of pleurisy 1, 2
• Pneumonia-related pleural inflammation can be identified by fever, leukocytosis, and adjacent pulmonary consolidation on imaging 2
• Infectious organisms of all classes—bacteria, viruses, fungi, and protozoa—are capable of causing pleural infection 4

Tuberculosis

• Tuberculosis accounts for approximately 6% of pleural effusions and must always be reconsidered in persistently undiagnosed cases as it is amenable to specific treatment 1, 2
• TB pleuritis typically presents with an exudative lymphocytic effusion and may mimic malignancy with circumferential pleural thickening 5
• Pleural fluid smears for acid-fast bacilli are positive in only 10-20% of tuberculous effusions, with culture positive in 25-50%; adding pleural biopsy improves diagnostic sensitivity to approximately 90% 1

Viral Infections

• Viruses are common causative agents of pleuritic chest pain, including Coxsackieviruses, respiratory syncytial virus, influenza, parainfluenza, mumps, adenovirus, cytomegalovirus, and Epstein-Barr virus 3
• Viral pleuritis typically presents with acute pleuritic chest pain and may be associated with low-grade fever 3, 6

Vascular Causes

Pulmonary Embolism

• Pulmonary embolism is the most common serious cause of pleuritic chest pain, found in 5-21% of patients presenting to emergency departments with this complaint 3
• PE is associated with pleural effusions in up to 40% of cases; approximately 80% are exudates and 80% are bloodstained 5, 1
• Critical pitfall: PE can mimic infectious pleuritis and lead to misdiagnosis or delayed diagnosis, particularly in younger patients 6
• Pleuritic pain occurs in approximately 75% of PE cases, typically with small, unilateral effusions ipsilateral to the embolus 2

Malignant Causes

• Malignancy represents 26% of all pleural effusions and is a leading cause of pleurisy 1, 2
• Lung cancer is the most common malignant cause, followed by breast cancer; lymphoma accounts for approximately 10% of malignant effusions 2
• Many "undiagnosed" effusions ultimately prove to be malignant with continued observation; approximately 15% remain undiagnosed despite repeated cytology and pleural biopsy 1

Autoimmune and Rheumatologic Causes

Rheumatoid Arthritis

• Rheumatoid arthritis affects the pleura in approximately 5% of patients, with pleural effusions more common in men despite the disease generally affecting more women 1, 2, 7
• Rheumatoid pleural effusions can appear serous, turbid, yellow-green, milky, or hemorrhagic 5
• A pleural fluid glucose level above 1.6 mmol/L (29 mg/dL) makes rheumatoid arthritis unlikely as the cause 5

Systemic Lupus Erythematosus

• SLE causes pleural disease in up to 50% of patients during the course of their illness 5, 1, 7
• The presence of LE cells in pleural fluid is diagnostic of SLE 5, 1

Other Autoimmune Conditions

• Scleroderma, polymyositis/dermatomyositis, mixed connective tissue disease, ankylosing spondylitis, Sjögren's syndrome, and Wegener's granulomatosis can all cause pleural involvement 7, 8
• Vasculitis including Churg-Strauss syndrome and adult-onset Still's disease may present with pleural involvement 8

Occupational and Environmental Causes

• Benign asbestos pleural effusion typically occurs within the first two decades after asbestos exposure, with prevalence related to exposure dose 5, 1
• These effusions are usually small and asymptomatic with a propensity to be hemorrhagic 5
• The effusion may resolve within 6 months but often leaves residual diffuse pleural thickening 5, 1

Cardiac Causes

• Heart failure is the dominant cause of transudative pleural effusions, accounting for over 80% of all transudates and representing 29% of all pleural effusions 2, 9
• When unilateral, heart failure effusions characteristically appear on the right side 2, 9
• Pericarditis (including Dressler syndrome) can cause pleuritic chest pain and pleural inflammation 5, 3

Other Important Causes

Trauma

• Traumatic pleurisy may be associated with rib fractures and signs of active bleeding on CT 5
• A pleural fluid red blood cell count exceeding 100,000/mm³ suggests malignancy, pulmonary infarction, or trauma 5

Abdominal Pathology

• Hepatic hydrothorax characteristically appears on the right side due to diaphragmatic defects, accounting for approximately 10% of transudates 2, 9
• Pancreatic disease and other abdominopelvic pathology can cause pleural inflammation 5

Special Populations

• In HIV-infected patients, the differential diagnosis differs significantly, with pleural effusions seen in 7-27% of hospitalized patients 5, 2
• The three leading causes in HIV patients are Kaposi's sarcoma (33%), parapneumonic effusions (28%), and tuberculosis (14%) 5, 2

Critical Diagnostic Approach

In persistently undiagnosed cases of pleurisy, pulmonary embolism and tuberculosis must be reconsidered as they are amenable to specific treatment and can be life-threatening if missed. 5, 1, 2

• A validated clinical decision rule for pulmonary embolism should be employed to guide additional testing such as D-dimer assays, ventilation-perfusion scans, or CT angiography 3
• Myocardial infarction, pericarditis, aortic dissection, pneumonia, and pneumothorax should be ruled out using electrocardiography, troponin assays, and chest radiography 3
• Nonsteroidal anti-inflammatory drugs are appropriate for pain management in those with virally triggered or nonspecific pleuritic chest pain 3