Pleurisy

Etiology

Pleurisy has various causes, with 30% to 40% of cases classified as idiopathic.[3] 

Infections

Both viral and bacterial infections are significant contributors to pleuritic pain, with viruses being among the most common causes.[1]

Viral causes of pleurisy: Below is a list of common viral infections that can lead to pleurisy.

• Coxsackieviruses
• Adenovirus
• Epstein-Barr virus
• Influenza virus
• Cytomegalovirus
• Herpes zoster
• Mumps
• Parainfluenza virus
• Respiratory syncytial virus
• Viral pneumonia [1]

Please see StatPearls' companion resource, "Pleural Friction Rub," for more information.

Bacterial causes of pleurisy: Below is a list of common bacterial infections that can lead to pleurisy.

• Empyema
• Tuberculosis
• Legionellae
• Bacterial pneumonia
• Spontaneous bacterial pleuritis
• Mediterranean spotted fever [1][4][5]

Parasitic causes, such as amebiasis and paragonimiasis (caused by consuming undercooked crab or crayfish infected with Paragonimus westermani), are potential contributors to pleurisy.[6]

Trauma

Chest wall trauma and rib fractures are potential sources of pleuritic chest pain.

Inflammatory or Autoimmune Conditions

Inflammatory and autoimmune disorders frequently affecting the pleura include rheumatoid arthritis and SLE.[7][8][9] Additional inflammatory conditions causing pleurisy include:

• Ankylosing spondylitis
• Collagen vascular disease
• Reactive eosinophilic pleuritis
• Familial Mediterranean fever
• Sjögren syndrome [9]

Pulmonary Conditions

• Chronic obstructive pulmonary disease (COPD)
• Hemothorax
• Pneumothorax [10]
• Pulmonary adhesions
• Pulmonary embolism
• Pleural effusion
• Malignancy [11][12]

Renal Conditions

• Chronic renal failure
• Renal capsule hematoma [13]

Gastrointestinal Conditions

• Inflammatory bowel disease [14]
• Pancreatitis

Cardiovascular Conditions

• Myocardial infarction
• Postmyocardial infarction syndrome
• Postpericardiotomy syndrome
• Heart failure
• Cardiothoracic surgery
• Pneumopericardium due to pericardiocentesis, causing a pleural effusion [1]

Hematological Conditions

• Sickle cell crisis

Additional Conditions

• Medications, including isoniazid, hydralazine, nitrofurantoin, and cyclophosphamide
• Asbestosis
• Illicit drugs, including cocaine, heroin, and methadone [15]
• Thoracic endometriosis [10]

Epidemiology

The epidemiology of pleurisy is largely influenced by its underlying cause. Among patients presenting to the emergency department with chest pain, common diagnoses include atypical chest pain, painful respiration, upper respiratory infections, and unspecified lower respiratory diseases, all of which can involve pleuritic chest pain. This variability makes accurately determining the true incidence of pleurisy challenging.[16] Pulmonary embolism is the most common life-threatening cause of pleurisy, occurring in 5% to 20% of patients.[1] Approximately 75% of patients with a pulmonary embolism and pleural effusion report pleuritic chest pain. The implementation of early reperfusion has nearly eliminated pleuritis caused by postmyocardial infarction syndrome, reducing its incidence from 3% to almost nonexistent.[17] Pleuritic pain occurs in nearly 90% of patients with pneumothorax and 50% of those with community-acquired pneumonia.[18] 

A recent study revealed that when surgical pleural biopsy is used to investigate the cause of pleurisy, 56% of cases are attributed to neoplastic diseases, including mesothelioma (23%), lung cancer (16%), and lymphoma (2.5%).[19] Infectious diseases account for 24%, with tuberculosis leading at 16.2%, followed by parapneumonic pleural effusion (3.6%), empyema (3.5%), nontuberculous mycobacteriosis (0.5%), and paragonimiasis (0.1%). Autoimmune diseases account for 2.8% of pleural biopsy findings, with rheumatoid arthritis (1.3%) and SLE (0.3%) being the most common.[19] Pleurisy is the initial symptom in 10% of SLE patients and occurs at some stage in 40% to 60%. Symptomatic pleurisy is also relatively common in rheumatoid arthritis; while 70% of patients show pleural effusion in autopsy studies, only 3% to 5% experience symptoms.[20][21][22] Recent studies indicate that the lymph nodes and pleura are the most commonly involved extrapulmonary sites in tuberculosis.[18][23][24]

Pathophysiology

The parietal and visceral pleurae cover the chest wall, lungs, and rib cage. The parietal pleura, more specifically, lines the chest wall, rib cage, and mediastinum, whereas the visceral pleura covers the lungs. Between these layers lies the pleural space. Pleural vessels continually produce fluid during inspiration, allowing the layers to move freely during respiration. This fluid is drained by the parietal lymphatics and absorbed by the visceral pleura.[25] The normal pleural fluid volume is just a few milliliters.[26] Inflammation of the pleural surfaces or changes in the pleural space can cause the pleural surfaces to rub together, potentially producing an audible pleural friction rub. This sound is often described as resembling "squeaking shoes on a wet surface" or "walking on fresh snow."[27] Please see StatPearls' companion resource, "Pleural Friction Rub," for more information.

While the visceral pleura lacks pain receptors, the parietal pleura is innervated by somatic fibers from the phrenic nerve. Inflammatory mediators released during trauma or inflammation trigger the pain associated with pleurisy. The intercostal nerves innervate the parietal pleura along the rib cage's periphery and lateral hemidiaphragm. Thus, inflammation in these areas can cause pain in the corresponding cutaneous nerve distributions. The phrenic nerve innervates the central diaphragm, and inflammation in this area can cause referred pain to the ipsilateral neck or shoulder. Pleural effusion, an accumulation of excess pleural fluid, arises from increased production by parietal cells, heightened fluid leakage into the pleural space (eg, in congestive heart failure), or impaired drainage due to tumor invasion of the pleura.[28] 

Infectious Causes

Viral and bacterial infections can spread to the pleurae, leading to inflammation. Pleural tuberculosis may present as a primary infection or as a reactivated disease. The pleural effusion seen in tuberculosis results from a delayed hypersensitivity reaction to mycobacteria or their antigens. 

Autoimmune and Inflammatory Conditions

Researchers believe impaired fluid resorption in inflamed pleurae, necrosis of subpleural rheumatoid nodules, and endothelial injury and capillary permeability due to local cytokine and immune complex production contribute to pulmonary effusions and pleural disease in rheumatoid arthritis patients.[21] Long-term pleural inflammation in patients with rheumatoid arthritis can cause the lungs to become "non-expandable" due to restriction of the visceral pleura. If the inflammation results in a "fibrous peel," the lung becomes trapped.[29] 

Inflammation and immune response dysregulation are critical factors in pleural disease associated with SLE. Compliment activation and the recruitment and activation of neutrophils are central to the body's immune response to the initial inflammatory insult, which may involve interferons, autoantibodies, immune complexes, infections, or injury. Epithelial and endothelial cells release inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukins (ILs) 1 and 8, which attract neutrophils, monocytes, macrophages, and T- and B lymphocytes.

Neutrophils further exacerbate the inflammatory response by releasing cytosolic and granule proteins that arrange on decondensed chromatin, forming neutrophil extracellular traps (NETs), which serve as a source of autoantigens during cell death. This process, known as NETosis, is typically part of the host's immune defense, with NETs playing a role in neutralizing and killing bacteria, fungi, viruses, and parasites. However, patients with SLE exhibit aberrant NET production, reduced NET clearance, and alterations in molecules involved in the NETosis pathway exist. NETs can directly damage epithelial and endothelial cells, increase the production of inflammatory cytokines, and promote autoantibody formation due to impaired self-tolerance in SLE patients.[30] 

Pulmonary Conditions

Pneumonia, pneumothorax, pulmonary embolism, hemothorax, and pulmonary adhesions can all cause pleurisy by releasing inflammatory mediators into the pleural space. In pulmonary embolism cases, pleural effusion occurs due to increased interstitial fluid, either from parenchymal ischemia or the release of inflammatory cytokines.[22] Similarly, pneumonia causes increased interstitial edema, leading to pleural effusion. In empyema, the visceral pleura becomes coated with a "collagenous peel," resulting in decreased pleural pressure and fluid accumulation.[31] Additionally, pleural adhesions can cause separation of the parietal pleura from the chest wall, leading to pleuritic pain.

Cardiovascular Conditions

In post-cardiac injury syndromes, such as postpericardiotomy syndrome and Dressler syndrome, initial cardiac injury triggers an immune response. Studies suggest that the NLRP3 inflammasome plays a role in regulating the innate immune system and inflammatory response.[32] Other theories propose that cardiac injury releases antigens that stimulate antibody formation, with antibody-antigen complexes depositing in the lungs, pericardium, and pleurae, triggering inflammation. However, the exact role of anti-cardiac antibodies in this process remains unclear.[33]

Renal Conditions

Pulmonary effusions and pleurisy are common in patients with chronic kidney disease (CKD). Contributing factors include heart failure, fluid overload, tuberculosis, and empyema. Uremia may also directly cause pleurisy, although the exact mechanism remains unclear.[34]

Medication-Induced Injury

Medications can trigger various pulmonary responses, including:

• Drug-induced SLE
• Eosinophilic pleural effusion
• Pleural effusion
• Pleural thickening or fibrosis
• Pneumothorax
• Ovarian hyperstimulation syndrome

Hydralazine, methotrexate, nitrofurantoin, and procainamide are common culprits. PneumoTox, a continually updated website, maintains a comprehensive list of drugs associated with pulmonary toxicity.

Valproic acid and dantrolene are common medications linked to drug-induced eosinophilic pleural effusions. The pleural space typically lacks eosinophils, and researchers suspect that stimulation of pleural cells by factors such as air, malignancy, or medications triggers the release of inflammatory substances, which recruit eosinophils to the pleural space.[35] 

Oxidant-mediated injury: Nitrofurantoin and certain chemotherapy drugs increase the production of free radicals, overwhelming the body's natural antioxidant defenses, such as superoxide dismutase, glutathione peroxidase, and alpha-tocopherol. This accumulation of oxygen-free radicals triggers an inflammatory response.

Immune-mediated injury: Drugs that act as antigens can trigger immune-mediated lung toxicity. The formation of antigen-antibody complexes initiates an inflammatory cascade, leading to pulmonary edema and fibrosis. An example of immune-mediated lung injury is drug-induced SLE, although its exact pathophysiology is not fully understood. Potential genetic factors include specific human leukocyte antigens (HLA) such as HLA-DR4, HLA-DR0*301, and HLA-DR2, as well as the complement C4 null allele. Additionally, individuals who are slow acetylators or have a genetically reduced capacity for hepatic N-acetyltransferase production are at increased risk of developing drug-induced SLE, particularly from medications such as hydralazine or procainamide.[36] 

Deposition of Phospholipids

Amiodarone inhibits phospholipase A, leading to the deposition of phospholipids in liposomes. This results in the formation of drug-phospholipid complexes, which accumulate in lung tissue, disrupt metabolic pathways, and alter the phospholipid bilayer, ultimately leading to cell death. However, the pulmonary toxicity of amiodarone extends beyond phospholipid deposition. This also generates excess toxic oxygen species, forms antigen-antibody complexes, and triggers a hypersensitivity reaction, which can culminate in hypersensitivity pneumonitis.[37]

Central Nervous System Depression

An acute neurological event, followed by a rapid increase in intracranial pressure, can stimulate the hypothalamic and medullary vasomotor centers. The resulting autonomic discharge may lead to neurogenic pulmonary edema. Acute noncardiogenic pulmonary edema can also occur following the administration of various drugs, including:

• Naloxone
• Heroin
• Interleukin-2
• Contrast media
• Intrathecal methotrexate
• Cytarabine
• All-trans retinoic acid

History and Physical

Pleurisy is characterized by sharp, localized pain in the chest, neck, or shoulder exacerbated by respiratory movements, coughing, or sneezing. A hallmark feature is a pleural friction rub caused by the inflamed parietal and visceral pleura rubbing together. The pleural friction rub is typically localized and may be palpable. Please see StatPearls' companion resource, "Pleural Friction Rub," for additional information. Depending on the underlying cause, patients may present with symptoms such as tachypnea, tachycardia, wheezing, decreased breath sounds, fever, chest pain, or a productive cough.

Additional clues from the patient's history and physical examination can help narrow the differential diagnosis and guide diagnostic testing. Dyspnea raises concerns for pulmonary embolism, pneumonia, or pneumothorax. Tachycardia and tachypnea further increase suspicion of pulmonary embolism or pneumothorax. Cough, fever, and sputum production are more indicative of pneumonia. Pain radiating to the arm or neck may suggest a cardiac origin, particularly if accompanied by tachycardia, tachypnea, nausea, diaphoresis, vomiting, or palpitations. Pain that worsens when lying down but improves when leaning forward suggests pericarditis, particularly if accompanied by a pericardial friction rub. Unlike a pleural friction rub, a pericardial friction rub persists even during breath-holding.

Pain radiating to the back, accompanied by hypotension, widened pulse pressure, pulse deficits, neurologic deficits, syncope, or a new diastolic murmur, strongly suggests aortic dissection. Nonspecific symptoms such as weight loss, arthralgias, and night sweats may indicate malignancy, tuberculosis, or inflammatory conditions such as rheumatoid arthritis or SLE. A family history of similar symptoms could point to an underlying inflammatory disorder or familial Mediterranean fever. Additionally, a history of sickle cell disease should raise suspicion of a sickle cell crisis. 

Evaluation

Given the various differential diagnoses, healthcare professionals should adopt a systematic approach when evaluating a patient with pleuritic chest pain. As discussed earlier, clinicians must differentiate between life-threatening causes and less deadly origins. Clinical decision-making rules for diagnosing pulmonary embolism and myocardial infarction assist in guiding diagnostic testing. All patients presenting with pleuritic chest pain should undergo a comprehensive history and physical examination, including a detailed medication history, to rule out medication toxicity as the underlying cause.

Understanding the timing of onset is crucial in differentiating between life-threatening and more indolent causes. Severe conditions such as pulmonary embolism, myocardial infarction, aortic dissection, and pneumothorax typically develop acutely within minutes, whereas inflammatory conditions, viral infections, pneumonia, and malignancy tend to progress over hours, days, or weeks. 

If clinically appropriate, a chest radiograph is often the initial diagnostic test for patients presenting to the emergency department with pleuritic chest pain. Below is a list of chest radiograph findings along with their potential corresponding diagnoses.[25]

• Consolidation: Pneumonia and tuberculosis
• White visceral pleural line: Pneumothorax 
• Pleural effusion: Heart failure, SLE, rheumatoid arthritis, medication toxicity, pulmonary embolism, pneumonia, malignancy, tuberculosis, empyema, pancreatitis, esophageal rupture, post-cardiac injury syndrome, and CKD.
• Widened mediastinum: Aortic dissection
• Cardiomegaly: Pericarditis
• Atelectasis: Pulmonary embolism
• Hilar and mediastinal lymphadenopathy: Tuberculosis

In cases of pleural effusion, thoracentesis may be necessary to analyze pleural fluid and identify the underlying cause. Ultrasound of the chest can guide the procedure by locating the fluid and possibly detecting pleural masses, while computed tomography (CT) may be required for further clarification of the cause. Fluid obtained during thoracentesis is tested for pH, glucose, cell count, lactate dehydrogenase, and bacterial Gram stain and cultures. Clinicians use Light criteria to classify the effusion as either a transudate or exudate. Specific tests, such as an acid-fast bacillus smear, adenosine deaminase level, and tuberculosis culture, are required for patients with suspected tuberculosis.

In cases of suspected malignancy, a pleural biopsy, flow cytometry, and immunohistochemical staining of pleural fluid are necessary for diagnosis. Pleural fluid can also be tested for antinuclear antibodies, anti-histone antibodies, anti–double-stranded DNA antibodies, and rheumatoid factors to assess for autoimmune disorders. The presence of anti-histone antibodies is particularly indicative of drug-induced SLE. Please see StatPearls' companion resource, "Pleural Effusion," for additional information.

Patients with a normal chest radiograph and a history and physical examination suggestive of myocardial infarction, pulmonary embolism, or pericarditis should undergo an ECG, sensitive cardiac troponin test, serum electrolytes, creatinine, and complete blood count within 10 minutes of arrival. For patients without clinical suspicion of these serious causes or other alternative diagnoses, a viral etiology is most likely.

Clinicians should promptly manage acute coronary syndrome when an elevated troponin or evidence of ST-elevation myocardial infarction is detected on ECG during a cardiac evaluation. If the initial troponin is negative, clinicians may observe the patient and calculate the modified HEART Pathway risk score. The HEART score considers the patient's age, history, risk factors, and ECG findings (see Table. 1).[38] 

Table 1. Modified HEART Score Calculation

^a A highly suspicious history is characterized by "typical" chest pain, typically located in the center or left side of the chest, which may (or may not) radiate to the left arm, neck, or jaw. The pain is often described as heavy or squeezing and may be associated with diaphoresis. A moderately suspicious history includes both typical and atypical features. A mildly suspicious history is characterized solely by atypical features. 

^b Clinically significant ST-segment depression is defined as new horizontal or downsloping ST depression of at least 1 mm in 2 contiguous leads or more than 1 mm of T-wave inversion in 2 contiguous leads.

^c Atherosclerotic risk factors include hypertension, a body mass index greater than 30 kg/m², current or prior tobacco use, diabetes, a family history of coronary artery disease in a first-degree relative, and hypercholesterolemia.

High-risk patients, including those with a HEART score of 4 or more, known coronary artery disease, or ischemic changes on their ECG, should be admitted for further monitoring, testing, and evaluation based on their history, ECG, and troponin values. If the HEART score is 0 and an alternative diagnosis better explains the symptoms, no further evaluation for acute coronary syndrome is necessary. However, if the score is 1 or greater, or if the score is 0, and an alternate diagnosis cannot fully explain the patient's symptoms, clinicians should obtain a second troponin 3 hours after the initial measurement.

If the second troponin is elevated, acute coronary syndrome should be managed accordingly. If the second troponin remains normal, clinicians should recalculate the HEART score. A score of 0 to 3 indicates the need to evaluate other potential causes for the patient's symptoms, or if the symptoms have resolved, the patient can be discharged with follow-up and noninvasive cardiac testing, such as a treadmill stress test or pharmacologic stress testing with imaging within 1 week. A score greater than 3 necessitates noninvasive imaging before discharge.

Widespread ST-segment elevation suggests pericarditis. Elevated creatinine levels may indicate uremic pleuritis, while leukocytosis could indicate an infectious origin. Chest radiographs may reveal a widening of the aortic silhouette in 60% to 90% of patients with an aortic dissection.[39] Depending on their hemodynamic stability, patients with suspected aortic dissection may undergo chest magnetic resonance angiography, CT angiography, or multiplane transesophageal echocardiography for further evaluation. Patients with pericarditis may require an echocardiogram to assess for a pericardial effusion. Cardiac MRI or CT can help evaluate the thickness of the pericardium. Serology tests, blood cultures, tuberculosis testing, and a complete blood count may be necessary for those with a suspected infectious etiology. 

Similar to myocardial infarction, clinical decision-making rules are available for patients with suspected pulmonary embolism. Clinicians use a combination of the Wells score, modified Wells score, modified Geneva score, pulmonary embolism rule-out criteria (PERC), and selective D-dimer testing to determine whether additional imaging, such as CT pulmonary angiography (CTPA) of the chest or, in select cases, a ventilation-perfusion (VQ) scan is necessary. Please see StatPearls' companion resource, "Acute Pulmonary Embolism," for additional information on calculating the various risk scores.

Hemodynamically stable patients with a low pretest probability (<15%), corresponding to a Wells score of less than 2, who meet all 8 PERC criteria, require no further testing. A D-dimer test is warranted if any of the 8 PERC criteria are not met. If the D-dimer level is below 500 ng/mL, no further testing is necessary. However, if the D-dimer level exceeds this threshold, imaging is required, ideally with a CTPA.[40] 

The 8 PERC criteria include:

• Individuals aged 50 or younger
• Heart rate below 100 bpm
• Oxygen saturation 95% or higher
• No hemoptysis
• No estrogen use
• No prior deep vein thrombosis (DVT)
• No unilateral leg swelling
• No surgery or trauma requiring hospitalization within the prior 4 weeks [41] 

Patients with intermediate risk, with a Wells score of 2 to 6, should undergo a serum D-dimer evaluation. If the D-dimer is less than 500 ng/mL, pulmonary embolism can be effectively excluded without further testing. However, some experts recommend imaging for patients with a Wells score of 4 to 6 due to their higher risk of pulmonary embolism. Serum D-dimer testing is unnecessary for high-risk patients with a Wells score greater than 6, as the D-dimer result is less reliable for excluding a pulmonary embolism in these cases. These patients should proceed directly to CPTA (see Table 2).

Table 2. Wells Score for Predicting the Pretest Probability of Pulmonary Embolism

The evaluation for autoimmune and inflammatory conditions should be guided by the patient's symptoms. For example, a patient presenting with symmetric swelling in multiple joints—particularly the metacarpophalangeal and proximal interphalangeal joints of the fingers, interphalangeal joints of the thumbs, wrists, and metatarsophalangeal joints of the toes—along with morning stiffness should be tested for rheumatoid arthritis. The evaluation should include testing for anti-citrullinated peptide antibodies and rheumatoid factor, as well as obtaining radiographs, which may reveal joint erosion, periarticular osteopenia, joint space narrowing, or subluxations. Chest CT may be necessary for suspected SLE with pleuritis, and pulmonary function tests can aid in identifying subclinical disease. Potential serious causes of pleurisy and pleuritic chest pain, along with the associated symptoms, physical examination findings, and diagnostic tests, are summarized in Table 3.

Table 3. Severe Causes of Pleurisy and Pleuritic Chest Pain

Treatment / Management

The treatment of pleurisy focuses on 2 primary goals—controlling pain and addressing the underlying cause. NSAIDs, such as indomethacin, are the mainstay of treatment for pain associated with pleurisy. In some cases, opioid medications may be necessary but should be used cautiously due to their potential to depress respiratory drive and cough reflexes. Oral corticosteroids may be considered, particularly for patients with lupus pleuritis or those unable to tolerate NSAIDs. Smoking cessation should be strongly recommended for all patients who smoke.

Treatment modalities should be tailored to the underlying cause. Appropriate antimicrobials should be initiated for conditions such as pneumonia, empyema, or tuberculosis. Patients with empyema should undergo drainage via chest tube or catheter thoracostomy. Surgical management may be necessary for those who do not respond to antibiotics and drainage. However, nonsurgical options, including optimizing antibiotic regimens, performing additional drainage procedures, or administering intrapleural tissue plasminogen activator combined with deoxyribonuclease, can help prevent surgical intervention.[42][43] Patients who smoke, are aged 50 or older, or have persistent symptoms should undergo a follow-up chest radiograph within 6 weeks to confirm resolution and rule out an obstructing lesion, such as malignancy, as the cause of pneumonia.[44][45] (A1)

In addition to NSAIDs, colchicine is effective in treating pericarditis and familial Mediterranean fever. Please see StatPearls' companion resources, "Pericarditis" and "Familial Mediterranean Fever," for a comprehensive discussion. Management of drug-induced pleurisy includes discontinuing the offending medication, providing oxygen therapy, and performing thoracentesis if needed. Treatment for autoimmune conditions such as SLE and rheumatoid arthritis is tailored to the specific disease. Please see StatPearls' companion resources, "Rheumatoid Arthritis," "Systemic Lupus Erythematosus," "Ankylosing Spondylitis," and "Sjögren's Syndrome," for additional information. 

Nitrates, aspirin, antiplatelet medications, anticoagulants, β-blockers, statins, and prompt decisions regarding reperfusion strategies are all essential in managing acute coronary syndrome. Type A aortic dissection involves the ascending aorta and requires immediate consultation with cardiovascular surgery. The tear occurs distal to the subclavian artery in a type B aortic dissection. These cases may be managed conservatively with medications or may require immediate surgical intervention. Pulmonary embolism management involves anticoagulation or reperfusion therapy, including thrombolytics or embolectomy for hemodynamically unstable patients. An inferior vena cava filter may be considered for patients with a high bleeding risk who cannot safely undergo anticoagulation therapy.[46] 

Patients with a pneumothorax may require supportive care, aspiration, or catheter/chest tube insertion. Significant dyspnea or the presence of a tension pneumothorax necessitates immediate catheter or chest tube thoracostomy. If tension pneumothorax is suspected and chest tube insertion is delayed, needle decompression can be performed as a temporary measure. 

Differential Diagnosis

The differential diagnosis for pleurisy or pleuritic chest pain is broad, and clinicians should prioritize evaluating the most critical causes first, including myocardial infarction, pericarditis, aortic dissection, pulmonary embolism, pneumonia, and pneumothorax. Once these have been excluded, other potential diagnoses can be considered, as outlined below.

• Cardiac: Postmyocardial infarction syndrome, congestive heart failure, postpericardiotomy syndrome, and myocarditis.
• Gastrointestinal: Inflammatory bowel disease and pancreatitis.
• Pulmonary: Spontaneous bacterial pleuritis, lupus pleuritis, rheumatoid pleuritis, Sjögren syndrome, COPD, pleural adhesions, and hemothorax.
• Renal: Chronic renal failure.
• Infectious: Empyema, tuberculosis, Legionnaire disease, adenovirus, Epstein-Barr virus, coxsackie viruses, herpes zoster, influenza, mumps, parainfluenza, respiratory syncytial virus, Mediterranean spotted fever, and liver, pulmonary, or splenic abscesses.
• Autoimmune: Familial Mediterranean fever, ankylosing spondylitis, collagen vascular disease, rheumatoid arthritis, SLE, reactive eosinophilic pleuritis, and fibromyalgia.
• Other: Malignancy, trauma, medications, caustic exposures.[1]

Prognosis

The prognosis of pleurisy and pleuritic chest pain largely depends on the underlying etiology and the effectiveness of treatment.

Infectious Causes

Viral pleuritis is generally self-limited, with symptoms typically resolving within a few days or weeks. Patients with bacterial pleural infections usually improve with appropriate treatment. The reported 30-day mortality rate for bacterial infections is 10.5%, with 1-year mortality nearing 19%.[47] Recent studies indicate that affected patients face an increased risk of thromboembolic events due to significant inflammation, prolonged hospitalizations, frequent comorbidities, and the need for operative interventions.[48] 

Autoimmune Conditions

The prognosis of lupus pleuritis is generally favorable. However, the prognosis of pleuritis associated with rheumatoid arthritis varies. While many patients experience spontaneous resolution within 3 months, some may develop persistent effusion and pleural thickening. Anti-inflammatory therapy does not appear to be effective in resolving rheumatoid pleuritis. 

Malignancy

Malignant pleural disease is associated with a poor prognosis. A study reported a median survival of just 13 months following diagnosis.[12]

Pulmonary Conditions

The presence of a pleural effusion is linked to increased mortality, with 15% of patients dying within 30 days and 32% within 1 year of hospital admission.[49] However, with early treatment, the mortality rate for pulmonary embolism decreases from 30% to 8%. Please see StatPearls' companion resource, "Acute Pulmonary Embolism," for more information. 

Cardiovascular Conditions

Acute myocardial infarction has a mortality rate of 30%, with nearly 50% of deaths occurring before patients reach the hospital. Early reperfusion through fibrinolysis or percutaneous coronary intervention within 90 minutes of arrival, along with preserved left ventricular function and short- and long-term treatment with β-blockers, aspirin, and angiotensin-converting enzyme inhibitors, all contribute to improved survival. The strongest predictor of a poor outcome is poorly preserved left ventricular function.[50]

Additional factors that worsen mortality include:

• Older age
• Diabetes
• Delayed reperfusion
• Elevated B-type natriuretic peptide and high-sensitivity C-reactive protein
• Depression
• Involvement of lead aVR on ECG [51]
• Presence of heart failure or pulmonary edema
• History of cerebrovascular disease or peripheral vascular disease
• Elevated thrombolysis in myocardial infarction risk score for unstable angina/non–ST-elevation acute coronary syndrome

The thrombolysis in myocardial infarction risk score includes 7 factors, including age 65 or older, 3 or more risk factors for cardiac disease, previous coronary disease, ST-segment deviation of 0.5 mm or more, 2 or more episodes of angina in the last 24 hours, aspirin use within the prior week, and elevated cardiac enzyme levels.[52] 

The overall prognosis for Dressler syndrome and viral or bacterial pericarditis is generally good, with most patients recovering within a few weeks to 3 months. However, malignant invasion of the pericardium has a poor prognosis, with survival rarely extending beyond 12 to 18 months.

Renal Conditions

Patients with uremic pleuritis generally fare well with more aggressive hemodialysis and, if necessary, thoracentesis. However, approximately 20% may experience persistent effusion and develop fibrinous lung disease.[53]

Drug-Induced Lung Disease

The prognosis of medication-induced pleuritis depends on the medication and the severity of the lung disease. Outcomes for drug-induced lupus pleuritis and pleural effusions are generally favorable, with symptoms resolving within months after discontinuing the offending medication. However, other forms of pulmonary toxicity have variable mortality rates. For example, methotrexate-induced pulmonary toxicity carries a 13% mortality rate.[54] Pulmonary fibrosis due to cyclophosphamide has a 50% mortality rate, while patients with acute respiratory distress syndrome caused by amiodarone have a 10% mortality rate.[55]

Complications

The potential complications of pleurisy vary widely and are closely tied to its underlying cause.

Complications of Cardiovascular Causes

• Papillary muscle rupture
• Left ventricular free wall rupture
• Interventricular septum rupture
• Acute and chronic heart failure
• Death
• Arrhythmias and conduction abnormalities
• Post-cardiac injury syndrome
• Cardiac tamponade

Complications of Respiratory Conditions

• Shock
• Recurrence
• Pneumonia
• Stroke
• Pulmonary hypertension
• Respiratory failure
• Empyema
• Atelectasis
• Tension pneumothorax
• Pneumohemothorax

Complications of Autoimmune Conditions

• Cholesterol effusions
• Lung entrapment

Complications of Infectious Causes

• Sepsis
• Empyema
• Pneumothorax
• Malignancy associated with tuberculosis
• Bronchiectasis
• Broncholithiasis
• Acute respiratory distress syndrome 
• Venous thromboembolism
• Chronic pulmonary aspergillosis [56]
• Pleural lymphoma associated with longstanding chronic pleural infection [57][58]
• Bronchopleural fistula
• Pleural fibrosis

Complications of Renal Causes

• Constrictive pleural thickening
• Pulmonary embolism
• Empyema
• Pulmonary edema

Complications of Drug-Induced Pleural Disease

• Hypoxia
• Pulmonary embolism
• Pleural fibrosis