Pleurisy is a symptom characterized by localized chest pain caused by a disease-causing inflammation of the pleura. Pleurisy can be caused by a primary pleural disease or secondary to a systemic illness. Hippocrates first described "pleuritis" in the 5 century B.C. as "pain in his side, fever and shivering" accompanied by "orthopnea" and tachypnea." Different types of pleuritis were described, including "bilious," "sanguineous," and "dry." Location of the pain was also used to describe pleuritis in these early texts, e.g., "pleuritis in the back," "extending along the spine and to the chest and groin," etc. The definition was then expanded by Galen, who tied Hippocrates' ideas on pleuritis to inflammation of the lining of the lungs. The lining of the lungs was referred to in these texts as the "hypezokos membrane." Galen also noted tachycardia in pleurisy and described it as a "hard pulse" that was noted to be "fast and frequent." In 1723, the term "pleurisy" came from an English translation of a text by Giorgio Baglivi in 1699. Baglivi also describes a "hardness of the pulse" as "an infallible sign of all pleurisies" and additionally mentions. "fever, spitting, and pain-in-the-side." The more recent definition of pleurisy was by Giambattista Morgagni in 1961, who performed post-mortem examinations on patients suffering from pleurisy. He defined "pleurisy" as disease-related primarily to the pleura and "peripneumony" as disease relating to the lung tissue. Through his work, he discovered that these were not distinct entities and re-termed this "pleuripneumony." Laennec, who invented the stethoscope, added egophony to the definition of pleurisy. Laennec also reclassified the terminology and referred to "pleuritic" to denote inflammation of the pleura and "pleurisy" to refer to the disease that caused the inflammation.
Two layers of pleura separate the lung and inner chest wall. Visceral pleura surrounding the lung tissue and is composed of a single mesothelial cell layer. They receive blood supply from the bronchial arteries supplying lung. The parietal pleura lines the inner chest wall, and in contrast to the visceral pleura, it contains stomata that drain pleural fluid to lymphatic capillaries in the loose connective tissue, which also contains systemic blood vessels and nerves. The lymphatics drain into their regional lymph nodes along the sternum or vertebra, and eventually into the thoracic and right lymphatic ducts. The lymphatics are 10um-12um in diameter, large enough to accommodate intact erythrocytes.
The normal volume of pleural fluid is 0.1 to 0.2 mL/kg, with an influx of 0.5 mL/hr in adults. The maximal removal rate, calculated from instilling artificial pleural effusion into a bovine model, is 0.28 mL/kg/hr. Pleural fluid accumulates when the inflow exceeds removal (increased capillary plasma filtration) or if the rate of removal is impaired (blockage of lymphatic drainage). The normal amount of pleural fluid separates the two pleura by 10 to 20 micrometers, except at the hilum of the lung where they are contiguous. The parietal pleura has connective tissue and is innervated by sensory nerve fibers, while the visceral pleura lacks connective tissue and is innervated by the vagus nerve, hence insensitive to pain. The parietal pleura in the central diaphragmatic region is supplied predominantly by the phrenic nerve, the involvement of which may cause referred pain to the ipsilateral shoulder. The other areas of the parietal pleura are supplied by the intercostal nerves of the corresponding intercostal spaces.
The primary function of the pleural membranes and pleural fluid is to allow for frictionless movement/sliding of the lung relative to the chest wall. On inspiration, a negative pressure caused by the outward movement of the chest cavity and the downward excursion of the diaphragm is transmitted to the pleural space leading to lung expansion. It generates a negative pressure relative to atmospheric pressure. This gradient allows atmospheric air to enter into the lungs.
Pleural inflammation can occur in a variety of conditions. The hyperacute onset of pleurisy (minutes to hours) occurs in emergencies such as pneumothorax, acute coronary syndromes, pulmonary emboli, acute pericarditis, and chest wall trauma. Acute and hyperacute causes generally present with tachypnea and dyspnea. Viral and bacterial pneumonia-causing synpneumonic pleurisy can also develop over hours to days. Parapneumonic effusions occur in 20 to 40% of hospitalized patients with pneumonia. Thoracentesis is recommended for any new onset effusion, especially those associated with suspected pneumonia. Recurrent pleuritis can occur in Familial Mediterranean fever, thoracic endometriosis, and recurrent spontaneous pneumothoraces.
Rheumatoid arthritis, malignancy, or tuberculosis are typical examples of subacute or chronic pleurisy (days to weeks).  Metastases to the pleura is more common than primary pleural tumors such as pleural lymphomas, a solitary fibrous tumor of the pleura, angiosarcoma of the pleura, pleuropulmonary blastoma and synovial sarcoma, all of which may also present with pleuritic pain. Mesothelioma is a rare cause of pleurisy, occurs in men over the age of 60 years who have a history of occupational asbestos-exposure and causes chronic, severe, and refractory pleural pain.
The epidemiology depends on the cause of pleuritis or pleurisy. The causes of pleurisy vary depending on geographic, demographic, occupational, comorbid, and other host factors.
Pleuritis is characterized by sharp and localized thoracic or shoulder pain. It is exacerbated by respiratory movements, coughing, sneezing, or chest wall/trunk movement. Pain characteristics can be dull aching, burning, or simply as a “catch.” Duration and recurrence of symptoms may be helpful in determining the cause. As in the other causes of chest pain, diagnosis of the cause of pleurisy relies heavily on the history and physical exam.
The acuity of the onset (e.g., hyperacute - pulmonary embolism, primary spontaneous pneumothorax, and traumatic pleural inflammation/traumatic pneumothorax), duration, and progression of symptoms are useful in establishing a differential diagnosis. A comprehensive medical history may help to uncover underlying systemic illness such as systemic lupus erythematosus, human immunodeficiency virus infection, tuberculosis infection.
Social history, including travel history, tobacco/electronic cigarette use, alcohol use history, illicit (specifically intravenous) drug use history may provide clues to the underlying cause of pleurisy. Dullness to percussion and diminished breath sounds and vocal/tactile resonance in the affected hemithorax differentiates effusion from a pneumothorax (resonant to percussion). A pleural rub can be heard in auscultation during inspiration and may also be palpable, and is differentiated from a pericardial friction rub that is audible in both inspiration and expiration and can still be heard with the cessation of respiratory movements.
Because chest pain is the most common symptom at presentation, it is left-sided, then evaluation for an acute coronary syndrome is important. A careful history, electrocardiogram, and serum troponin should be considered if clinical suspicion prevailed. Though pleuritic chest pain is not the typical presentation of ischemic heart disease, it can occur in acute pericarditis and aortic dissection, both of which can cause localized substernal pain or referred pain to the shoulder.
A chest radiograph may help to identify lung consolidation, pleural effusion, or pneumothorax. Laboratory testing should include complete blood counts, a metabolic panel including serum protein, albumin, and lactate dehydrogenase. If acute pancreatitis related pancreatic pleurisy and effusion are suspected then, serum lipase may be considered. If a pleural or pericardial effusion is present, a sample of the fluid should be obtained and sent for pH, glucose, cell count, lactate dehydrogenase, and bacterial Gram stain and cultures.
A chest X-ray can be helpful, but smaller nodules and loculated or minimal pleural effusions may be missed. A computed tomography(CT) of the chest may be necessary for better assessment for pneumothorax, acute pulmonary embolism (with intravenous contrast), and pulmonary nodules/masses. The apparent involvement of the pleura should prompt pleural fluid cytological evaluation for malignant cells.
Treatment depends on the cause. Acute coronary syndromes should be managed per local expert cardiologist's guidance. Aortic dissections, especially type A (ascending aorta), should prompt emergent cardiovascular surgery consultation. If a pneumothorax is present, immediate evacuation of the air should be undertaken in patients with large pneumothorax (>2 cm from the chest wall at the level of the hilum), hemodynamic instability, new oxygen requirement, significant dyspnea or in those without a known underlying lung disease (secondary spontaneous pneumothorax) or trauma (traumatic pneumothorax). Options include a needle aspiration (non-inferior to tube thoracostomy) for hemodynamically stable primary spontaneous pneumothorax)and tube thoracostomy for hemodynamic unstable, secondary spontaneous pneumothoraces, traumatic pneumothoraces or hemopneumothoraces.
Pulmonary embolism can be treated through multiple modalities, including home treatment with anticoagulants, inpatient initiation of anticoagulants, systemic fibrinolytic medications, catheter-directed fibrinolytic medications. The main determinants of in-hospital versus out-of-hospital management include oxygen requirement, the severity of pain, signs of right heart strain CT pulmonary angiography or echocardiogram, impending or apparent hemodynamic compromise despite volume resuscitation, social conditions which may impede immediate follow-up or comorbid acute or chronic conditions which may warrant hospitalization.
The treatment and analysis of pleural fluid in the case of pleural effusion depends on the size and imaging characteristics of the effusion. Categories of pleural effusion have been proposed based on the radiographic characteristics, culture, and chemistry values from the pleural fluid.
Category 1 pleural effusions are less than 10 mm on lateral decubitus film. Category 1 pleural effusions are very low risk for poor outcomes and are generally not recommended to be sampled.
Category 2 pleural effusions are >10 mm but less than half of the hemithorax. Category 2 to 4 pleural effusions are recommended to have diagnostic thoracentesis performed, and empyema ruled out (must have negative culture, gram stain, and a pH>7.20). A category 3 effusion involves more than half of the hemithorax, loculations noted within the pleural space, or thickening of the parietal pleura.
A category 3 effusion may also be defined as a pH of <7.20 or a positive gram stain/culture (empyema). Category 4 effusions are defined by purulent material on thoracentesis. Category 3 and 4 effusions are recommended to have thoracostomy drainage. Empyema, or category 4 effusions, may require surgical evacuation and decortication. Due to the high mortality of the categories 3 and 4 pleural effusions (30%), additional methods for the complete drainage of the infected pleural fluid include intrapleural fibrinolytic followed by drainage and/or surgical decortication. The MIST 2 trial compared intrapleural placebo, intrapleural DNase, intrapleural tPA, and combination tPA/DNAse in patients with category 3 or 4 effusions.
The combination of tPA/DNase showed significant improvements in hospital length of stay, effusion size on x-ray, and referral for surgery within 3 months compared to placebo. The tPA alone and DNase alone groups did not show significant changes in hospital length of stay or effusion size on X-ray compared to placebo. The DNase alone group showed an increase in surgical referral within 3 months compared to placebo.
The most important disease states to evaluate in the setting of pleuritic pain are acute coronary syndromes, aortic dissection, pneumothorax, pericardial effusion/tamponade, and pulmonary embolism. Once these have been evaluated with imaging and serum chemistry, other considerations would be pleural effusions, pericarditis, pulmonary infectious processes, or intrathoracic malignancies.
The prognosis of pleurisy and pleuritic chest pain depends on the etiology and effectiveness of treatment. Acute coronary syndromes, aortic dissection, pneumothorax, pulmonary embolism carry high morbidity and mortality if left untreated. Category 3 and 4 pleural effusion (alternatively known as complicated parapneumonic effusion or empyema) have a high mortality rate (30%) and high morbidity if left untreated or are treated suboptimally. Lupus pleuritis does not have high mortality but has significant morbidity. Lupus pleuritis occurs in 43% of patients with systemic lupus erythematosus at some point in the course of their disease. Malignant pleural disease has a very poor prognosis with one series reporting a median survival of 13 months after the time of diagnosis.
Parapnuemonic effusions and empyemas may result in pleural thickening leading to trapped lung, recurrent pneumonia, bloodstream infections if not adequately evacuated. Malignant effusions may also lead to pleural thickening and fibrosis which may result in restrictive lung disease. Pulmonary emboli may lead to pulmonary hypertension, which can lead to chronic dyspnea, exertional intolerance, or hypoxemia. Pulmonary emboli may also lead to death or prolonged hospitalization if not treated in a timely manner.
Acute coronary syndromes, pericarditis, and pericardial effusions may warrant cardiology consultation. Pneumothorax, pleural effusion (especially complicated pleural effusion and empyema), lung masses, pulmonary embolism may warrant pulmonary or thoracic surgery consultation.
Pleuritis and pleurisy require an interprofessional approach. The treatment requires a broad differential diagnosis and exclusion of the emergent causes of pleurisy. History, physical examination, laboratory, and radiological evaluation provide useful diagnostic information. Validated risk scores for coronary disease and pulmonary emboli are available and should be used to refine the list of differential diagnoses. The treatment and prognosis of pleurisy depend on the etiology. Pain control should be generally be attempted with non-steroidal anti-inflammatory drugs until the cause can be determined.
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