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
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
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
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
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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