US Pharm. 2012;37(7):HS-9-HS-12.
Pleurisy, also referred to as pleuritis, is an inflammation of the parietal pleura in the lungs. Clinically recognized as pain that is sharp, localized, and made worse by deep inspiration or coughing, pleurisy has a diverse array of possible causes.1 This article will review the physiology and generalized symptoms of pleurisy and pleuritic chest pain, as well as discuss causes and treatment options.
Anatomy and Physiology
To comprehend pleurisy and associated pleuritic pain, the anatomy and physiology of the lung and its nerve innervations must be understood. The lungs, chest wall, and rib cage are lined with two continuous layers of epithelium known as the parietal pleura and the visceral pleura (FIGURE 1). The parietal (outer) pleura is the epithelial lining covering the chest wall, rib cage, and mediastinum; the visceral (inner) pleura covers the total surface of the lung.1,2 The parietal pleura is innervated with somatic pain receptors supplied by the phrenic nerve; the pain signals are rapidly transmitted, leading to pain that is sharp and localized. In contrast, the visceral pleura has an autonomic nerve supply that develops from internal organs; pain sensations, if any, are transmitted slowly and are characterized as dull, achy, and slightly localized.2
Between the parietal and visceral pleurae is the pleural space, which contains a serous fluid. Pleural fluid is produced by pleural vessels through negative pressure created upon inspiration. Fluid then exits through the parietal lymphatic system and is absorbed by the visceral pleura in a continuous manner. Pleural fluid provides lubrication between the chest wall and lung, allowing the lungs to slide effortlessly during inspiration and expiration.2 If the smooth surfaces of the pleurae become inflamed or if the pleural space is increased or decreased, a pleural rub—a squeaking or grating sound made when the pleural linings rub together—results. This classic feature of pleurisy, detected by lung auscultation, can help the clinician identify the cause of the chest pain.3
During normal inspiration of the lungs, negative pressure is created in the pleural space as the thoracic cavity expands. When excess fluid accumulates in the pleural space, the negative pressure is diminished, altering the lung’s capacity to expand fully during inspiration. Untreated, this leads to an inadequate exchange of oxygen and carbon dioxide.2,4
Three mechanisms are thought to cause pleural effusion (the accumulation of excess fluid in the pleural space).2,4 In the first mechanism, increased production of fluid by parietal cells in the pleural space surpasses the ability of the lymphatic system to remove the fluid. By another mechanism, pleural fluid accumulates when an increased drainage of fluid into the pleural space occurs due to backflow from the lungs or liver. This can be seen in patients with congestive heart failure, in which the heart is unable to maintain cardiac output, leading to pulmonary congestion. This congestion within the pulmonary circulation can cause fluid to leak from the alveoli into the pleural space. In the third mechanism, a reduction in drainage of fluid from the pleural space secondary to an obstruction may prevent the fluid from being reabsorbed into the bloodstream.2,4 An obstruction of this type could result when a tumor invades the pleura.
Depending upon the underlying cause of pleurisy, patients may present with a wide variety of symptoms. As described above, one common feature in patients with pleurisy is a pleural rub, in which the parietal and visceral pleurae rub together and cause friction. This friction, brought about by pleural inflammation, can be acute or chronic. The pain, which is sharp and localized, tends to be further intensified by coughing, sneezing, deep inspiration, or chest movement.1,2 A physical examination may reveal additional findings, including reduced breath sounds, wheezing, productive cough with sputum production, or rapid, shallow breathing. To accurately diagnose the cause of pleurisy, the clinician should combine a history of the patient’s symptoms with a full physical examination and results of diagnostic tests.1-3
Pleurisy can be indicative of a broad spectrum of disorders, ranging from mild to life-threatening. The clinician must first consider and perform diagnostic tests to exclude critical diagnoses such as pulmonary embolism, myocardial infarction, or pneumothorax. Pneumothorax, pneumonia, and pleural effusions are easily identifiable by chest x-ray or CT scan. Findings and characteristics that can be identified by chest x-ray include infiltrations (i.e., pneumonia), effusions (i.e., pulmonary embolism, malignancy), and/or the lack of identifiable lung markings (i.e., pneumothorax).1
A CT scan can provide many findings similar to those of a chest x-ray, but with a more definitive diagnosis. ECG assessment is suggested if a patient demonstrates signs and symptoms indicative of myocardial infarction, pulmonary embolism, or pericarditis. Laboratory analyses such as CBC, D-dimer, arterial blood gas, and cultures enable the clinician to order further testing for suspected diagnoses. In many cases, the cause of pleurisy can be differentiated by the symptom onset: acute (minutes to hours), subacute (hours to days), chronic (days to weeks), or recurrent. Identifying when symptom onset occurred may aid in differentiating the diagnosis.1
Common causes of pleurisy include trauma, postcardiac injury, infection (i.e., viral, bacterial, or parasitic), respiratory illness, caustic exposure (i.e., drug-induced), autoimmune disease, and malignancy (TABLE 1). While viral infections tend to be one of the more common causes, the cause can also be idiopathic or nonspecific. Nonspecific pleuritis is found in 30% to 40% of patients who undergo pleural biopsy for diagnosis. Idiopathic pleuritis should be utilized as a diagnosis of exclusion after other causes have been ruled out through extensive diagnostic measures.2,5
A retrospective analysis by Branch and McNeil that involved adults aged 40 years or less sought to determine an approach for distinguishing patients with idiopathic or viral pleurisy from those with pulmonary embolism. Idiopathic or viral pleurisy was the most common type, accounting for 53% of cases. The presence of pleural effusion significantly increased the probability that pleurisy was secondary to pulmonary embolism. Of the 97 cases reviewed, 22 had pleural effusions; of these, pulmonary embolism was the primary cause in 12 (55%). Pulmonary embolism is severe, and distinguishing this condition from other causes is imperative, as the clinical features of pulmonary embolism and other causes may be quite similar.6
There are numerous case reports discussing drug-induced lung disorders, but little attention has been paid to drug-induced pleural diseases, including pleural effusion, pleuritis, and/or pleural thickening. As more drugs are introduced, it is imperative to understand the mechanisms by which reported agents have resulted in pleural disease (TABLE 2).7,8 Morelock and Sahn conducted a review of the literature from 1966 to 1998 to identify drugs associated with pleural disease and to examine findings and response to therapy. Drug effect was contributory when exposure to the drug produced pleural disease, when the pleural response remitted upon drug discontinuation, and when drug-induced pleural disease recurred with re-exposure.8 While many mechanisms for most drug-induced pleural diseases remain hypotheses, five mechanisms in which drug-induced pleural disease may occur have been identified: hypersensitivity or allergic reaction; direct toxic effect; increased oxygen free-radical production; suppression of antioxidant defenses; and chemical-induced inflammation.7,9
The management and treatment of pleurisy involve a thorough assessment of the patient, control of pleuritic chest pain, and treatment of the underlying condition (TABLE 3). Treatment is determined after a detailed patient evaluation, which should include inquiries regarding past medical history, social and family history, and current medications, as well as questions specifically addressing the pleuritic pain the patient is experiencing. Factors to discuss include (but are not limited to) pain onset and duration, type of pain, and relieving factors (drugs or positioning).1,2
For pleurisy and associated pleuritic chest pain, nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed as initial therapy to treat inflammation of the pleural space. NSAIDs are ideal because they do not cause a reduction in respiratory drive or affect the cough reflex. If NSAIDs are ineffective, contraindicated, or not tolerated, opioid analgesics may be used with caution.1,2 While it is assumed that a class effect occurs when NSAIDs are used, human studies on the use of NSAIDs to treat pleuritic chest pain have been limited to indomethacin.1 The recommended dosage of indomethacin for pleuritic chest pain is 50 to 100 mg orally up to three times daily with food or milk.1,10
In 1984, Klein evaluated the use of indomethacin in 17 patients with pleurisy. Patients evaluated their pain relief every 24 hours, rating it as excellent, good, fair, or poor. Eleven patients (65%) obtained good-to-excellent pain relief within 24 hours. Although patients had the option of selecting other analgesic treatments, none chose an alternative method; however, five patients (29%) discontinued indomethacin after failure of pain relief after 24 hours of therapy. Pain nonrecurrence following discontinuation of indomethacin after 72 hours of treatment was noted. Indomethacin was concluded to be a viable and recommended option for the treatment of pleuritic pain.10
The use of tricyclic antidepressants or anticonvulsants may have a limited role in the treatment of patients with neuropathic pain and persistent pleuritic pain syndromes.3 Psychological factors may intensify patients’ views and fear of pain. There is a strong relationship between pain intensity and interference with daily activities, thereby reducing overall quality of life.3,11 Measures to minimize these psychological factors can be as important as medications in optimizing pain control. Once the cause of pleurisy has been diagnosed, specific treatment modalities should be initiated.
The remainder of this section will discuss specialized treatment of the more common causes of pleurisy.
Pneumothorax: Pneumothorax, which is the presence of air within the pleural space, may occur spontaneously, after trauma, postsurgery, or iatrogenically.3 While the specific mechanism of pleuritic chest pain secondary to pneumothorax is poorly understood, it is suggested that air in the pleural space may cause eosinophilic pleural inflammation. Although no defined drug treatments exist for pneumothorax, most cases resolve spontaneously or with conventional management. Immediate attention should be given to patients presenting with tension pneumothorax, as this can be a life-threatening cause of pleuritic chest pain. In cases of spontaneous pneumothorax, intrapleural local anesthetic agents (i.e., bupivacaine) have been studied, with limited results.3,12
Pulmonary Embolism: Pleuritic chest pain is caused by irritation of the parietal pleura resulting from inflammation of the underlying visceral pleura affected by the embolus. It may arise following the initial symptoms of pulmonary embolism.3 Prompt identification and management based on current clinical guidelines should be initiated expeditiously.
Malignancy: Pleural malignancies can originate in the pleura and chest wall or may present as metastases from extrapleural cancers (e.g., mesothelioma).3 Pain management in patients with pleural malignancies is aimed at improving pain, alleviating dyspnea, and enhancing the patient’s quality of life. When pharmacologic measures (i.e., NSAIDs, opioid analgesics) cannot control the patient’s pain, radiotherapy may be an alternative for palliative alleviation of chest-wall pain. While not fully maintained, radiotherapy has been demonstrated to relieve chest pain in approximately 60% of patients with mesothelioma.13
Pneumonia or Pleural Infection: Patients who present with pneumonia, either community-acquired or hospital-acquired, often have pleuritic chest pain that is localized to the area of infection. Brandenburg and colleagues conducted a prospective cohort study assessing features of pneumococcal pneumonia and symptoms 30 days after the infection. Thirteen percent of patients had pleuritic chest pain that persisted for 30 days.14 Pain that is associated with these infections is thought to develop from pleural inflammation secondary to involvement of the lung parenchyma with infection.3 Treatment should target the specific causative organism, with appropriate antimicrobial therapy.
Pleurisy is a condition in which pleuritic chest pain may evolve as a symptom secondary to a primary cause. NSAIDs (particularly indomethacin), along with opioid analgesics, remain the mainstay of treatment for pleurisy; identification and treatment of the primary cause are also important. A variety of disorders can cause pleurisy, including pulmonary embolism, pneumonia, and myocardial infarction; the condition may also be drug induced. It is imperative that life-threatening conditions be considered first when a patient presents with pleuritic chest pain.
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