Etiology of Pericardial Disease

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Etiology of pericardial disease

AUTHOR: Brian D Hoit, MD
SECTION EDITORS: Martin M LeWinter, MD, Jae K Oh, MD
DEPUTY EDITOR: Susan B Yeon, MD, JD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024.

This topic last updated: Nov 30, 2022.
INTRODUCTION
The pericardium is a fibroelastic sac made up of visceral and parietal layers separated by a
(potential) space, the pericardial cavity. In healthy individuals, the pericardial cavity contains
15 to 50 mL of an ultrafiltrate of plasma. Pericardial diseases are relatively common in clinical
practice and may have different presentations either as isolated disease or as a
manifestation of a systemic disorder.
Although the etiology is varied and complex, the pericardium has a relatively non-specific
response to these different causes with inflammation of the pericardial layers and possible
increased production of pericardial fluid. Chronic inflammation with fibrosis and calcification
can lead to a rigid, usually thickened and calcified pericardium, with possible progression to
pericardial constriction. In some cases, the clinical presentation of acute pericardial
inflammation predominates, and the presence of excess pericardial fluid is clinically
unimportant. In other cases, the effusion and its clinical consequences (ie, cardiac
tamponade and constrictive pericarditis) are of primary importance.
Diseases of the pericardium present clinically in one of several ways [1,2]:
● Acute and recurrent pericarditis

● Pericardial effusion without major hemodynamic compromise
● Cardiac tamponade
● Constrictive pericarditis
● Effusive-constrictive pericarditis
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This topic will provide a brief overview of the major causes of pericardial disease. Details of
the specific pericardial disorders are discussed separately. (See "Acute pericarditis: Clinical
presentation and diagnosis" and "Pericardial effusion: Approach to diagnosis" and
"Constrictive pericarditis: Diagnostic evaluation".)
CLASSIFICATION
The etiology of pericardial diseases is best considered by using a modification of the time-
honored pathologic classification of disease into inflammatory, neoplastic, vascular,
congenital, and idiopathic causes ( table 1) [3-5]. The major causes include:
● Infectious
• Viral, including human immunodeficiency virus (HIV) and coronavirus disease 2019
(COVID-19)
• Bacterial, fungal (purulent)
• Others (Rickettsia, Chlamydia, Borrelia, Mycoplasma, Treponema, Ureaplasma,
Nocardia, Tropheryma)
● Radiation
● Post cardiac injury syndrome
• Post-myocardial infarction
• Post-pericardiotomy
• Post-traumatic (including iatrogenic)
● Drugs and toxins
● Metabolic (uremia, dialysis-associated, myxedema, ovarian hyperstimulation syndrome)
● Malignancy (especially lung and breast cancer, Hodgkin lymphoma, and mesothelioma)
● Collagen vascular disease
● Idiopathic or immune-mediated [6,7]
Pericardial disease may also be a component of other, systemic disorders, including

inflammatory bowel disease and familial Mediterranean fever. Aortic dissection or left
ventricular free wall rupture should also be considered in patients with unstable
hemodynamics and pericardial effusion.
Most of the etiologies of pericardial disease listed above can cause both "dry" pericarditis
(that is, pericardial inflammation with minimal or no effusion) and pericardial effusive
disease with or without inflammation.
SPECTRUM OF CLINICAL PRESENTATION
The frequency of the specific causes of pericardial disease varies in published reports,
depending in part upon geography, the patient population, and how the diagnosis was
established.
Acute pericarditis — Acute pericarditis can present in a variety of ways, depending on the
underlying etiology ( table 2) [8-12]. Patients with an infectious etiology may present with
signs and symptoms of systemic infection such as fever and leukocytosis. Viral etiologies in
particular may be preceded by "flu-like" respiratory or gastrointestinal symptoms. Patients
with a known autoimmune disorder or malignancy may present with signs or symptoms
specific to their underlying disorder.
The major clinical manifestations of acute pericarditis include [2,5,13]:
● Chest pain – Typically sharp and pleuritic, improved by sitting up and leaning forward.
● Pericardial friction rub – A superficial scratchy or squeaking sound best heard with the
diaphragm of the stethoscope over the left sternal border.
● Electrocardiogram (ECG) changes – New widespread ST elevation or PR depression.
● Pericardial effusion.
At least two of these features should be present to make the diagnosis. (See "Acute
pericarditis: Clinical presentation and diagnosis", section on 'Clinical features'.)
Pericardial effusion — Patients with a hemodynamically significant pericardial effusion

leading to cardiac tamponade usually present with signs and symptoms related to impaired
cardiac function (ie, dyspnea, elevated jugular venous pressure, hypotension and impaired
perfusion). However, in the absence of cardiac tamponade, most patients with a pericardial
effusion have no symptoms specific to the effusion, but may have symptoms related to the
underlying cause (eg, fever in the setting of pericarditis, etc). Thus, pericardial effusions are
often discovered incidentally during evaluation of other cardiopulmonary diseases, and are
typically diagnosed by echocardiography. (See "Pericardial effusion: Approach to diagnosis"
and "Cardiac tamponade".)
Several case series have reported estimates of the frequency of specific causes of pericardial
effusion ( table 3) [14-18]. Not surprisingly, the distribution of causes varies with
demographics and diagnostic strategies. For example, polymerase chain reaction (PCR) is
more sensitive for the detection of infection than cultures; therefore, a study employing PCR
will likely have an increased incidence of infectious etiologies. The increased incidence of
iatrogenic effusions in the more contemporary series ( table 3) reflects the growing
number of invasive cardiovascular procedures being performed.
Hemorrhagic pericardial effusion — Patients with hemorrhagic pericardial effusions have

a different distribution of causes than those with serous effusions, although there is
considerable overlap. Malignancy should always be considered, and tuberculosis is a
frequent cause of hemorrhagic effusion in areas in which this infection is common. (See
"Pericardial disease associated with cancer: Clinical presentation and diagnosis" and
"Tuberculous pericarditis".)
A series from the United States evaluated 96 cases of hemorrhagic pericardial effusion
complicated by tamponade and requiring pericardiocentesis. The following causes were
identified [19]:
● Malignancy – 26 percent
● Percutaneous interventional procedures – 18 percent
● Post-pericardiotomy syndrome – 13 percent
● Complications of myocardial infarction (free wall rupture, thrombolysis) – 11 percent
● Idiopathic – 10 percent
● Other causes (including uremia, aortic dissection, trauma, etc) – 22 percent
Because efforts to diagnose viral infections were not undertaken, the frequency of
hemorrhagic effusions in viral pericarditis was not addressed.
Symptomatic pericardial effusion — The distribution of causes of large symptomatic

pericardial effusions was evaluated in a review of 173 consecutive patients undergoing
pericardiocentesis [20]. Symptomatic was defined as cardiorespiratory symptoms (eg,
dyspnea), signs (eg, tachycardia), echocardiographic features of right heart compromise, or if
pericardiocentesis was deemed therapeutically indicated by the clinician.
The following distribution of causes was noted:
● Malignancy – 33 percent (45 of the 58 patients previously known to have a malignancy)

● Chronic-idiopathic – 14 percent
● Acute pericarditis – 12 percent
● Trauma – 12 percent
● Uremia – 6 percent
● Post-pericardiotomy – 5 percent
● Indeterminate – 8 percent
● Other causes (including infection, collagen vascular disease, radiation, heart failure, etc)
– 10 percent
Constrictive pericarditis — Patients with constrictive pericarditis typically present with

symptoms related to fluid overload (ranging from peripheral edema to anasarca), symptoms
related to diminished cardiac output in response to exertion (eg, fatigability and dyspnea on
exertion) or at rest, or both. Patients typically present months to years after an initial insult
involving the pericardium, although the majority of patients with prior involvement of the
pericardium do not develop constrictive pericarditis. While the diagnosis of constrictive
pericarditis is often made by echocardiography and cardiac magnetic resonance, patients
commonly undergo cardiac catheterization to confirm the diagnosis. (See "Constrictive
pericarditis: Diagnostic evaluation".)
Effusive constrictive pericarditis — Pericardial pathology consistent with constrictive

pericarditis with a concomitant effusion is called effusive constrictive pericarditis. Most cases
of effusive constrictive pericarditis are idiopathic, reflecting the frequency of idiopathic
pericardial disease in general. Effusive constrictive pericarditis is relatively uncommon
(similar to constrictive pericarditis). The diagnosis of effusive constrictive pericarditis often
becomes apparent following pericardiocentesis in patients initially considered to have
uncomplicated cardiac tamponade. In such cases, the right atrial pressure remains elevated
after removal of the pericardial effusion due to underlying constriction. In a study of 205
patients undergoing pericardiocentesis at Mayo Clinic, effusive constrictive pericarditis was
diagnosed in 33 (16 percent); the etiology was procedure-related hemopericardium in 11 (33
percent), idiopathic in 9 (27 percent), post-cardiac surgery in 6 (18 percent), post-viral
pericarditis in 3 (9 percent), malignancy in 2 (6 percent), and other in 2 (6 percent) [21]. (See
"Constrictive pericarditis: Diagnostic evaluation".)
ESTABLISHING THE DIAGNOSIS
The yield of a full diagnostic evaluation is much lower in patients presenting primarily with
acute pericarditis without a significant pericardial effusion than in those who present with a
significant pericardial effusion. In two series with a total of 331 patients with acute
pericarditis, a specific diagnosis was established in only 16 percent [8,9]. The most common
were neoplasia (6 percent), tuberculosis (4 percent), nontuberculous infection (2 percent),
and collagen vascular disease (2 percent).
In patients with acute pericarditis in whom no cause is identified (idiopathic pericarditis), the
etiology is frequently presumed to be viral or immune-mediated [6,7], but evidence for this is
usually not sought because of the expense involved, the inaccessibility of pericardial
tissue/fluid, the time delay and inaccuracy of viral titers, and the general lack of impact of
this information on management. It is possible that many cases in which an identifiable
cause exists are labeled "idiopathic pericarditis" as a result of an insufficiently rigorous
diagnostic evaluation. However, a complex and exhaustive testing strategy is typically not
justified in such patients given the limited implications for clinical management. One
clinically important exception to this approach is the absence of a prompt and adequate
response to standard treatment, in which case more aggressive efforts at establishing a
diagnosis are warranted.
Epicardial/pericardial biopsy using pericardioscopy has improved the diagnostic yield, but it
is not widely available. It may be useful for relapsing cardiac tamponade, suspected bacterial
or neoplastic pericarditis, worsening pericarditis without a definitive diagnosis despite
medical treatment, and symptomatic moderate to large pericardial effusions [2,22].
INFECTION
Virtually any infectious organism can infect the pericardium ( table 1). While most
infectious causes of pericardial disease result in a typical acute presentation (ie, acute
pericarditis or pericardial effusion), some organisms, especially bacteria and fungi, can cause
a purulent inflammatory exudate. (See "Purulent pericarditis".)
The frequency of specific pathogens in infectious pericardial disease has been changing in
recent decades and continues to vary with geography. Tuberculous pericarditis has become
much less common in developed countries, while HIV infection remains an important cause
of pericardial disease in the developing world.
The clinical manifestations are often confined to the pericardium, as in viral pericarditis, but
extrapericardial infection may be a prominent component of the clinical picture, as in
pneumonia or empyema with associated pericardial involvement. In some cases, particularly
with tuberculous or fungal infection, an infectious pericarditis can result in chronic
constrictive pericarditis. (See "Tuberculous pericarditis" and "Constrictive pericarditis:
Diagnostic evaluation".)
Viral — Though the most common viral infections causing pericarditis are reported to be
coxsackievirus (types A and B) and echovirus, most of these data come from children
diagnosed by serologic testing in the 1960s. More recent data suggest that adult patients are
more commonly infected with cytomegalovirus and herpes viruses as well as HIV ( table 1)
[15,23]. There are many viruses that have been associated with transient pericardial
inflammation, which resolves without sequelae. Pericarditis, usually with myocarditis, has
also been described as an infrequent complication of smallpox vaccination. (See
"Myopericarditis", section on 'Vaccinia-associated myopericarditis'.)
Pericardial effusion is prevalent in patients hospitalized with COVID-19, but is infrequently

attributable to pericarditis [24]; it has been associated with myocardial dysfunction and all-
cause mortality. (See "COVID-19: Cardiac manifestations in adults".)
Viral infection is less common among patients who present with pericardial effusion without
pericarditis, especially if the effusion is large ( table 3). An exception to this may be
patients with HIV, in whom pericardial effusion seems more prevalent. However, this high
frequency may well be decreasing as more and more patients infected with HIV are receiving
aggressive therapy. (See "Cardiac and vascular disease in patients with HIV", section on
'Pericardial disease'.)
Bacterial — While any bacterial infection may involve the pericardium ( table 1), the most
notable organisms include Staphylococcus, Pneumococcus, Streptococcus (rheumatic
pancarditis), Haemophilus, and M. tuberculosis. Less common bacteria have the potential to
invade the pericardium when the bacterial flora have been altered by prolonged antibiotic
use and when the immune system is seriously compromised. (See "Purulent pericarditis" and
"Tuberculous pericarditis".)
Other infectious causes — A variety of fungi and parasites are also known to cause
pericardial disease ( table 1), particularly in endemic areas or in immunocompromised
patients.
MALIGNANCY
In two large series, malignancy was responsible for approximately 6 percent of cases of
acute pericardial disease (acute pericarditis or tamponade without apparent cause) [8,9]. In
addition, malignancy accounts for approximately 15 to 20 percent of moderate to large
pericardial effusions ( table 3) [14,15]. (See "Pericardial disease associated with cancer:
Clinical presentation and diagnosis".)
Virtually any malignant tumor can metastasize to the pericardium, with the most common
being lung and breast cancer and Hodgkin lymphoma. Primary tumors of the pericardium
are rare and include several different types. In many cases, it is not easy to decide whether
pericardial disease is a manifestation of the malignancy itself or of treatment with radiation
or chemotherapy. (See "Pericardial disease associated with cancer: Clinical presentation and
diagnosis", section on 'Pericardial effusion'.)
POST-CARDIAC INJURY SYNDROMES
Pericarditis with or without a pericardial effusion resulting from injury of the pericardium
constitutes the post-cardiac injury syndrome. The principal conditions considered under this
rubric are postmyocardial infarction syndrome, post-pericardiotomy syndrome, and
posttraumatic pericarditis. (See "Post-cardiac injury syndromes".)
● Post-myocardial infarction syndrome – Pericardial disease, manifested as pericarditis

and/or effusion, is a common event following acute myocardial infarction (MI), but has
become fairly rare in the era of primary reperfusion therapy. [25-28]. An effusion that
occurs early after infarction is related to the acute inflammation associated with the
infarct, while immunologic mechanisms are responsible for effusions that occur several
weeks to months after the infarct. The acute effusions are usually silent. (See
"Pericardial complications of myocardial infarction", section on 'Post-MI pericardial
effusion'.)
Left ventricular free wall rupture can also occur after a myocardial infarction. Affected
patients have a large hemorrhagic pericardial effusion and tamponade, and the
diagnosis is suggested by the development of sudden, profound heart failure and
shock. This syndrome is discussed separately. (See "Acute myocardial infarction:
Mechanical complications", section on 'Rupture of the left ventricular free wall'.)
● Postpericardiotomy syndrome – Postpericardiotomy syndrome occurs in up to 15

percent of patients following surgery. The presentation and clinical course of the post-
pericardiotomy syndrome is comparable to that of acute pericarditis. (See "Post-cardiac
injury syndromes", section on 'Clinical features'.)
Pericardial effusion occurring within hours after cardiac surgery is more often
associated with pericardial bleeding, is presumably not due to the post-cardiac injury
syndrome, and is frequently associated with cardiac tamponade [29]. Post-cardiac
surgery tamponade is often atypical and may be associated with left rather than right
ventricular compression on echocardiography.
Pericardial effusion also occurs in 9 to 21 percent of patients after cardiac

transplantation [30,31].
● Posttraumatic pericarditis – Trauma causing pericarditis may be blunt, as with a

steering wheel injury, or sharp, as with bullet or knife wounds. Iatrogenic causes
include virtually all cardiac invasive diagnostic and therapeutic procedures, and rarely
cardiopulmonary resuscitation. (See "Post-cardiac injury syndromes".)
RADIATION
Prior mediastinal radiation is an important cause of pericardial disease. Most cases are
secondary to radiation therapy for Hodgkin lymphoma or breast or lung cancer. Less
commonly, radiation exposure occurs with thoracic radiation for other conditions (eg,
esophageal cancer). However, improved shielding and dose calculation have reduced the
incidence of this complication. (See "Cardiotoxicity of radiation therapy for breast cancer and
other malignancies".)
Soon after radiation, the patient may develop acute pericarditis with or without effusion [32].
Late onset of pericardial disease is common and is not necessarily preceded by acute
pericarditis [33]. The late pericardial disease may consist of effusive constrictive pericarditis
or classic constrictive pericarditis. (See "Constrictive pericarditis: Diagnostic evaluation".)
DRUGS AND TOXINS
The list of drugs and toxins that can cause pericardial disease is long ( table 4).
● Procainamide, tocainide, hydralazine, isoniazid, methyldopa, and phenytoin, can induce

a lupus-like syndrome. (See "Drug-induced lupus".)
● The penicillins may cause a hypersensitivity pericarditis with eosinophilia.
● Minoxidil (among other drugs) may produce an idiosyncratic reaction with pericardial
effusion.
● Doxorubicin and daunorubicin are more often associated with a cardiomyopathy, but
may cause pericardial disease, as may other chemotherapy agents. Immune mediated
and non-immune mediated cytotoxicity with tyrosine kinase inhibitors and immune
checkpoint inhibitors have been reported to cause pericardial syndromes [34]. (See
"Cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-
targeted agents, and fluoropyrimidines".)
Asbestos exposure, resulting in asbestosis, can also induce pericardial lesions, commonly in
conjunction with pleural and parenchymal lung disease. (See "Asbestos-related
pleuropulmonary disease".)
SYSTEMIC DISORDERS
A variety of systemic disorders have pericardial involvement:
● Collagen vascular disease – A number of rheumatic diseases can involve the

pericardium. Symptomatic pericarditis can occur with all of these disorders, while
pericardial effusion, when present, is usually clinically silent. This is most likely to occur
in systemic lupus erythematosus (SLE) and rheumatoid arthritis. In SLE, for example,
the pericardium is involved in almost one-half of patients [35]. (See "Non-coronary
cardiac manifestations of systemic lupus erythematosus in adults".)
● Uremia and dialysis – Important causes of metabolic pericardial disease are uremia
(which causes pericarditis in 6 to 10 percent of patients with advanced renal failure who
are not being dialyzed) and dialysis-related pericardial effusion (occurring in
approximately 13 percent of patients). Both inadequate dialysis (ie, uremic pericarditis)
and fluid overload may contribute to the latter disorder [36,37]. An important clinical
feature of uremic pericarditis is that the electrocardiogram does not usually show
typical diffuse ST elevation, presumably because epicardial injury is uncommon [37].
The presence of ST-T abnormalities suggests some other cause for the pericarditis.
● Hypothyroidism – Severe hypothyroidism, especially with classic myxedema, may be a

cause of pericardial effusion but not usually pericarditis [38]. The effusion is typically
slow to accumulate, which frequently results in a large (hundreds of milliliters) effusion,
which is rarely hemodynamically significant. (See "Cardiovascular effects of
hypothyroidism".)
● Ovarian hyperstimulation syndrome – Severe ovarian hyperstimulation syndrome is

a potential complication of gonadotropin therapy for the induction of ovulation. The
syndrome includes the combination of underlying ovarian enlargement due to multiple
ovarian cysts and an acute fluid shift out of the intravascular space that can lead to
ascites and pericardial and pleural effusions. (See "Pathogenesis, clinical
manifestations, and diagnosis of ovarian hyperstimulation syndrome".)
● GI disease – The pericardium can also be involved in gastrointestinal diseases. These

include inflammatory bowel disease (ulcerative colitis and Crohn's disease) and
Whipple's disease. (See "Whipple's disease".)
● Immunoglobulin G4-related disease – This fibroinflammatory disease characterized

by elevated serum levels of IgG4 and multiorgan involvement was reported as a cause
of constrictive pericarditis [39].
IDIOPATHIC
In many cases, the etiology of pericardial disease cannot be determined.
● In patients with acute pericarditis, a cause is identified in only about 16 percent, based
on two large series [8,9]. The etiology in the remaining patients is frequently presumed
to be viral, but evidence for this is often not sought because of the expense involved,
the inaccessibility of pericardial tissue/fluid, and the time delay and inaccuracy of viral
titers. (See "Acute pericarditis: Clinical presentation and diagnosis".)
● By comparison, a specific etiology can be established in many patients with moderate

to large pericardial effusions ( table 3). In two series, a diagnosis of idiopathic disease
was made in only 7 to 29 percent of patients [14,15]. (See "Pericardial effusion:
Approach to diagnosis".)
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Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Pericarditis in adults (The Basics)")
● Beyond the Basics topic (see "Patient education: Pericarditis (Beyond the Basics)")
SUMMARY
● Causes of pericardial disease – Pericardial disease can be a result of inflammatory,

neoplastic, vascular, iatrogenic, and idiopathic causes ( table 1). The specific causes of
pericardial disease vary depending in part upon geography, the patient population, and
how the diagnosis is established. (See 'Classification' above and 'Spectrum of clinical
presentation' above.)
• Infection, most commonly viral – Though the most common viral infections
causing pericarditis are reported to be coxsackievirus (types A and B) and echovirus,
most of these data come from children diagnosed by serologic testing in the 1960s.
More recent data suggest that adult patients are more commonly infected with
cytomegalovirus and herpes viruses as well as HIV ( table 1). (See 'Viral' above.)
• Malignancy – Malignancy (usually due to metastatic spread) is responsible for

approximately 6 percent of cases of acute pericardial disease (acute pericarditis or
tamponade without apparent cause) as well as 15 to 20 percent of moderate to large
pericardial effusions. (See 'Malignancy' above and "Pericardial disease associated
with cancer: Clinical presentation and diagnosis".)
• Radiation – Prior mediastinal radiation is an important cause of pericardial disease,

with most cases following radiation therapy for Hodgkin lymphoma, breast cancer,
or lung cancer. Soon after radiation, the patient may develop acute pericarditis with
or without effusion. Late onset of pericardial disease is common and may consist of
effusive constrictive pericarditis, classic constrictive pericarditis, or pericardial
effusion with or without tamponade. (See 'Radiation' above and "Cardiotoxicity of
radiation therapy for breast cancer and other malignancies".)
• Post-cardiac injury syndromes – Both pericarditis and pericardial effusion can

occur following an acute myocardial infarction (MI). An effusion that occurs early
after MI is related to the acute inflammation associated with the infarct, while
immunologic mechanisms are responsible for effusions that occur several weeks to
months after the infarct. (See 'Post-cardiac injury syndromes' above and "Pericardial
complications of myocardial infarction", section on 'Post-MI pericardial effusion'.)
• Systemic disorders – A number of rheumatic diseases, most commonly systemic

lupus erythematosus and rheumatoid arthritis, can involve the pericardium, leading
to either pericardial inflammation with pleuritic pain, pericardial effusion with or
without cardiac tamponade, and occasionally constrictive pericarditis. (See 'Systemic
disorders' above.)
● Evaluating the cause of acute pericarditis – In patients with acute pericarditis in

whom no cause is identified (idiopathic pericarditis), the etiology is frequently
presumed to be viral, and extensive evaluation for a specific diagnosis is usually not
necessary. However, if a prompt and adequate response to standard treatment is not
seen, more aggressive efforts at establishing a specific etiology are warranted. (See
'Establishing the diagnosis' above and "Acute pericarditis: Clinical presentation and
diagnosis".)
● Causes of pericardial effusion – The distribution of causes of pericardial effusion

varies with demographics and diagnostic strategies ( table 3). In a patient with
nontraumatic hemorrhagic pericardial effusion, malignancy and tuberculosis
(particularly in an endemic area) are common. (See 'Pericardial effusion' above and
'Hemorrhagic pericardial effusion' above.)
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22. Imazio M, Spodick DH, Brucato A, et al. Controversial issues in the management of
pericardial diseases. Circulation 2010; 121:916.
23. Campbell PT, Li JS, Wall TC, et al. Cytomegalovirus pericarditis: a case series and review
of the literature. Am J Med Sci 1995; 309:229.
24. Ghantous E, Szekely Y, Lichter Y, et al. Pericardial Involvement in Patients Hospitalized

With COVID-19: Prevalence, Associates, and Clinical Implications. J Am Heart Assoc 2022;
11:e024363.
25. Galve E, Garcia-Del-Castillo H, Evangelista A, et al. Pericardial effusion in the course of
myocardial infarction: incidence, natural history, and clinical relevance. Circulation 1986;
73:294.
26. Correale E, Maggioni AP, Romano S, et al. Comparison of frequency, diagnostic and
prognostic significance of pericardial involvement in acute myocardial infarction treated
with and without thrombolytics. Gruppo Italiano per lo Studio della Sopravvivenza
nell'Infarto Miocardico (GISSI). Am J Cardiol 1993; 71:1377.
27. Belkin RN, Mark DB, Aronson L, et al. Pericardial effusion after intravenous recombinant
tissue-type plasminogen activator for acute myocardial infarction. Am J Cardiol 1991;
67:496.
28. Shahar A, Hod H, Barabash GM, et al. Disappearance of a syndrome: Dressler's

syndrome in the era of thrombolysis. Cardiology 1994; 85:255.
29. Stevenson LW, Child JS, Laks H, Kern L. Incidence and significance of early pericardial
effusions after cardiac surgery. Am J Cardiol 1984; 54:848.
30. Hauptman PJ, Couper GS, Aranki SF, et al. Pericardial effusions after cardiac
transplantation. J Am Coll Cardiol 1994; 23:1625.
31. Quin JA, Tauriainen MP, Huber LM, et al. Predictors of pericardial effusion after
orthotopic heart transplantation. J Thorac Cardiovasc Surg 2002; 124:979.
32. Stewart JR, Fajardo LF, Gillette SM, Constine LS. Radiation injury to the heart. Int J Radiat
Oncol Biol Phys 1995; 31:1205.
33. Applefeld MM, Wiernik PH. Cardiac disease after radiation therapy for Hodgkin's disease:
analysis of 48 patients. Am J Cardiol 1983; 51:1679.
34. Ala CK, Klein AL, Moslehi JJ. Cancer Treatment-Associated Pericardial Disease:
Epidemiology, Clinical Presentation, Diagnosis, and Management. Curr Cardiol Rep
2019; 21:156.
35. Mandell BF. Cardiovascular involvement in systemic lupus erythematosus. Semin

Arthritis Rheum 1987; 17:126.
36. Rostand SG, Rutsky EA. Pericarditis in end-stage renal disease. Cardiol Clin 1990; 8:701.
37. Gunukula SR, Spodick DH. Pericardial disease in renal patients. Semin Nephrol 2001;
21:52.
38. Kabadi UM, Kumar SP. Pericardial effusion in primary hypothyroidism. Am Heart J 1990;
120:1393.
39. Sekiguchi H, Horie R, Suri RM, et al. Constrictive pericarditis caused by immunoglobulin
G4-related disease. Circ Heart Fail 2012; 5:e30.
Topic 4957 Version 28.0
GRAPHICS
Causes of pericardial disease
Idiopathic (presumed to be viral or immune-mediated)

In most case series, the majority of patients are not found to have an identifiable cause of
pericardial disease. Frequently such cases are presumed to have a viral or autoimmune etiology.
Infectious
Viral – Coxsackievirus, echovirus, adenovirus, Epstein-Barr virus, cytomegalovirus, influenza,

varicella, rubella, HIV, hepatitis B, mumps, parvovirus B19, vaccina (smallpox vaccine), severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2)
Bacterial – Mycobacterium tuberculosis (most common cause in countries where tuberculosis is

endemic), Staphylococcus, Streptococcus, Haemophilus, Neisseria (N. gonorrhoeae or N. meningitidis),
Chlamydia (C. psittaci or C. trachomatis), Legionella, Salmonella, Borrelia burgdorferi (the cause of Lyme
disease), Mycoplasma, Actinomyces, Nocardia, Tropheryma whippelii, Treponema, Rickettsia
Fungal – Histoplasma, Aspergillus, Blastomyces, Coccidioides, Candida
Parasitic – Echinococcus, amebic, Toxoplasma
Noninfectious
Autoimmune and autoinflammatory
Systemic inflammatory diseases, especially lupus, rheumatoid arthritis, scleroderma, Sjögren

syndrome, vasculitis, mixed connective disease
Autoinflammatory diseases (especially familial Mediterranean fever and tumor necrosis factor
associated periodic syndrome [TRAPS], IgG4-related disease)
Postcardiac injury syndromes (immune-mediated after cardiac trauma in predisposed individuals
Other – Granulomatosis with polyangiitis, polyarteritis nodosa, sarcoidosis, inflammatory bowel

disease (Crohn, ulcerative colitis), Whipple, giant cell arteritis, Behçet syndrome, rheumatic fever
Neoplasm
Metastatic – Lung or breast cancer, Hodgkin disease, leukemia, melanoma
Primary – Rhabdomyosarcoma, teratoma, fibroma, lipoma, leiomyoma, angioma
Paraneoplastic
Cardiac
Early infarction pericarditis
Myocarditis
Dissecting aortic aneurysm
Trauma
Blunt
Penetrating
Iatrogenic – Catheter and pacemaker perforations, cardiopulmonary resuscitation, complication

of thoracic surgery
Metabolic
Hypothyroidism (primarily pericardial effusion)
Uremia
Ovarian hyperstimulation syndrome
Radiation
Drugs (rare)
Procainamide, isoniazid, or hydralazine as part of drug-induced lupus
Other – Cromolyn sodium, dantrolene, methysergide, anticoagulants, thrombolytics, phenytoin,

penicillin, phenylbutazone, doxorubicin
References:
1. LeWinter M. Clinical practice. Acute pericarditis. N Engl J Med 2014; 371:2410.
2. Imazio M, Gaita F. Diagnosis and treatment of pericarditis. Heart 2015; 101:1159.
3. Imazio M. Contemporary management of pericardial diseases. Curr Opin Cardiol 2012; 27:308.
Graphic 67851 Version 11.0
Acute pericarditis etiologies: Data from published clinical studies with

unselected populations
Western Europe Africa

[1]
(2007-2012) (1995-2001) [2]
Idiopathic * 516 (55.3%) 32 (13.7%)
Specific etiology 417 (44.7%) 201 (86.3%)
Neoplastic ¶ 85 (8.9%) 22 (9.4%)
Tuberculosis ¶ 4 (<1.0%) 161 (69.5%)
Autoimmune etiologies ¶ 25 (2.6%) Δ 12 (5.2%)
Purulent ¶ 29 (3.0%) 5 (2.1%)
* Most idiopathic cases are likely viral.
¶ As a fraction of the entire sample.
Δ Autoimmune pericarditis can be caused by autoimmune disease or as a complication of myocardial

infarction (MI) or cardiac surgery. In this table, we only report pericarditis caused by autoimmune
disease, while the original paper (Gouriet et al) reports an additional 188 cases related to MI or
cardiac surgery.
Data from:
1. Gouriet F, Levy PY, Casalta JP, et al. Etiology of pericarditis in a prospective cohort of 1162 cases. Am J Med 2015;
128:784.
2. Reuter H, Burgess LJ, Louw VJ, et al. The management of tuberculous pericardial effusion: experience in 233 consecutive
patients. Cardiovasc J S Afr 2007; 18:20.
Case series of moderate-large pericardial effusions
Sagrista- Corey, 1993 Levy, 2003 Ma, 2012 Strobbe,

Sauleda, (n = 57) (n = 204) (n = 140) 2017
2000 (n = 269)
(n = 322)
Size of effusion, >10 >10 NR >10 >10 (98%)
mm
Tamponade, 37 NR NR 100 88
percent
Etiologies, percent
Idiopathic* 29 (9% 7 48 0 26
chronic)
Malignancy 13 23 15 38 25
Uremia 6 12 2 6 3
Iatrogenic 16 0 0 9 21
Post-acute 8 0 0 5 1
myocardial
infarction
Infection 6 27 16 28 7
Collagen 5 12 10 6 3
vascular
disease
Hypothyroidism 2 0 10 5 0
Other 15 23 0 3 14
NR: not reported.
* Includes both acute and chronic pericardial effusions.
Adapted from:
1. Sagrista-Sauleda J, Merce J, Permanyer-Maralda G, et al. Clinical clues to the causes of large pericardial effusions. Am J
Med 2000; 109:95.
2. Corey GR, Campbell PT, VanTrigt P, et al. Etiology of large pericardial effusion. Am J Med 1993; 95:209.
3. Levy PY, Corey R, Berger P, et al. Etiologic diagnosis of 204 pericardial effusion. Medicine (Baltimore) 2003; 82:385.
4. Ma W, Liu J, Zeng Y, et al. Causes of moderate to large pericardial effusion requiring pericardiocentesis in 140 Han
Chinese patients. Herz 2012; 37: 183.
5. Strobbe A, Adriaenssens T, Bennett J, et al. Etiology and long-term outcome of patients undergoing pericardiocentesis. J
Am Heart Assoc 2017; 6: e007598.
Drugs and toxins associated with pericardial disease
Drug-induced lupus erythematosus Idiosyncratic reaction or
Procainamide
hypersensitivity (con't)
Tocainide Cyclophosphamide
Hydralazine Cyclosporine
Mesalazine
Methyldopa
Mesalazine 5-Fluorouracil
Reserpine Vaccines (Smallpox, Yellow fever)
Isoniazid GM-CSF
Hydantoins Anthracycline derivatives
Hypersensitivity reaction Doxorubicin
Penicillins Daunorubicin
Tryptophan Targeted chemotherapy cytotoxicity
Cromolyn sodium Tyrosine kinase inhibitors
Idiosyncratic reaction or Immune checkpoint inhibitors

hypersensitivity Serum sickness
Methysergide Foreign antisera (eg, antitetanus)
Minoxidil Blood products
Practolol
Venom
Bromocriptine
Scorpion fish sting
Psicofuranine
Foreign-substance reactions (direct
Phenylbutazone pericardial application)
Cytarabine Talc (Mg silicate)
Amiodarone
Silicones
Streptokinase
Tetracycline/other sclerosants
p-Aminosalicylic acid
Iron in β-thalassemia
Thiazides
Asbestos
Streptomycin
Secondary pericardial
Sulfa drugs bleeding/hemopericardium
Thiouracils Anticoagulants
Thrombolytic agents
Polymer fume fever
Inhalation of the burning fumes of

polytetrafluoroethylene (Teflon)
Adapted with permission from: Maisch B, Seferovic PM, Ristic AD, et al. Guidelines on the diagnosis and management of
pericardial diseases executive summary; The Task force on the diagnosis and management of pericaridal diseases of the
European society of cardiology. Eur Heart J 2004; 25:587. Copyright © 2004 European Society of Cardiology.

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23/2/24, 14:11 Etiology of pericardial disease - UpToDate

Official reprint from UpToDate®

Literature review current through: Jan 2024.

Diseases of the pericardium present clinically in one of several ways [1,2]:

● Acute and recurrent pericarditis

Pericardial disease may also be a component of other, systemic disorders, including

SPECTRUM OF CLINICAL PRESENTATION

The major clinical manifestations of acute pericarditis include [2,5,13]:

● Electrocardiogram (ECG) changes – New widespread ST elevation or PR depression.

Pericardial effusion — Patients with a hemodynamically significant pericardial effusion

Hemorrhagic pericardial effusion — Patients with hemorrhagic pericardial effusions have

Symptomatic pericardial effusion — The distribution of causes of large symptomatic

The following distribution of causes was noted:

● Malignancy – 33 percent (45 of the 58 patients previously known to have a malignancy)

Constrictive pericarditis — Patients with constrictive pericarditis typically present with

Effusive constrictive pericarditis — Pericardial pathology consistent with constrictive

ESTABLISHING THE DIAGNOSIS

Pericardial effusion is prevalent in patients hospitalized with COVID-19, but is infrequently

POST-CARDIAC INJURY SYNDROMES

● Post-myocardial infarction syndrome – Pericardial disease, manifested as pericarditis

● Postpericardiotomy syndrome – Postpericardiotomy syndrome occurs in up to 15

Pericardial effusion also occurs in 9 to 21 percent of patients after cardiac

● Posttraumatic pericarditis – Trauma causing pericarditis may be blunt, as with a

DRUGS AND TOXINS

● Procainamide, tocainide, hydralazine, isoniazid, methyldopa, and phenytoin, can induce

● The penicillins may cause a hypersensitivity pericarditis with eosinophilia.

A variety of systemic disorders have pericardial involvement:

● Collagen vascular disease – A number of rheumatic diseases can involve the

● Hypothyroidism – Severe hypothyroidism, especially with classic myxedema, may be a

● Ovarian hyperstimulation syndrome – Severe ovarian hyperstimulation syndrome is

● GI disease – The pericardium can also be involved in gastrointestinal diseases. These

● Immunoglobulin G4-related disease – This fibroinflammatory disease characterized

In many cases, the etiology of pericardial disease cannot be determined.

● By comparison, a specific etiology can be established in many patients with moderate

INFORMATION FOR PATIENTS

● Basics topics (see "Patient education: Pericarditis in adults (The Basics)")

● Causes of pericardial disease – Pericardial disease can be a result of inflammatory,

• Malignancy – Malignancy (usually due to metastatic spread) is responsible for

• Radiation – Prior mediastinal radiation is an important cause of pericardial disease,

• Post-cardiac injury syndromes – Both pericarditis and pericardial effusion can

• Systemic disorders – A number of rheumatic diseases, most commonly systemic

● Evaluating the cause of acute pericarditis – In patients with acute pericarditis in

● Causes of pericardial effusion – The distribution of causes of pericardial effusion

Use of UpToDate is subject to the Terms of Use.

1. Imazio M. Contemporary management of pericardial diseases. Curr Opin Cardiol 2012;

e, Braunwald E, Zipes D, Libby P (Eds), Saunders, New York 2001. p.183.

8. Permanyer-Miralda G, Sagristá-Sauleda J, Soler-Soler J. Primary acute pericardial disease:

14. Sagristà-Sauleda J, Mercé J, Permanyer-Miralda G, Soler-Soler J. Clinical clues to the

24. Ghantous E, Szekely Y, Lichter Y, et al. Pericardial Involvement in Patients Hospitalized

28. Shahar A, Hod H, Barabash GM, et al. Disappearance of a syndrome: Dressler's

35. Mandell BF. Cardiovascular involvement in systemic lupus erythematosus. Semin

Causes of pericardial disease

Idiopathic (presumed to be viral or immune-mediated)

Viral – Coxsackievirus, echovirus, adenovirus, Epstein-Barr virus, cytomegalovirus, influenza,

Bacterial – Mycobacterium tuberculosis (most common cause in countries where tuberculosis is

Fungal – Histoplasma, Aspergillus, Blastomyces, Coccidioides, Candida

Parasitic – Echinococcus, amebic, Toxoplasma

Autoimmune and autoinflammatory

Systemic inflammatory diseases, especially lupus, rheumatoid arthritis, scleroderma, Sjögren

Postcardiac injury syndromes (immune-mediated after cardiac trauma in predisposed individuals

Other – Granulomatosis with polyangiitis, polyarteritis nodosa, sarcoidosis, inflammatory bowel