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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: Brian C Downey, MD, FACC

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2019. | This topic last updated: May 10, 2018.

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

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

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and diagnostic evaluation" and "Diagnosis and treatment of pericardial effusion" and
"Constrictive pericarditis".)

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 HIV
• 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.

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Acute pericarditis — Acute pericarditis can present in a variety of ways, depending on the underlying
etiology (table 2). 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 [2,5,8]:

● 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 diagnostic evaluation", 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 "Diagnosis and treatment of pericardial effusion" and "Cardiac tamponade".)

Several case series have reported estimates of the frequency of specific causes of pericardial
effusion (table 3) [9-13]. 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 malignancy" and "Tuberculous pericarditis".)

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A series from the United States evaluated 96 cases of hemorrhagic pericardial effusion complicated by
tamponade and requiring pericardiocentesis. The following causes were identified [14]:

● 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. In addition, tuberculosis is a frequent cause of
hemorrhagic effusion in areas in which this infection is common. (See "Tuberculous pericarditis".)

Symptomatic pericardial effusion — The distribution of causes of large symptomatic

pericardial effusions was evaluated in a review of 173 consecutive patients undergoing
pericardiocentesis [15]. 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,
patients commonly undergo cardiac catheterization, during which invasive hemodynamic evaluation
is important to confirm the diagnosis. (See "Constrictive pericarditis".)
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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) [16].

ESTABLISHING THE DIAGNOSIS

The yield of a full diagnostic evaluation is much lower in patients presenting primarily with acute
pericarditis than in those whose presentation includes 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 [17,18]. 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, and the time
delay and inaccuracy of viral titers. 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 [2,19].

INFECTION

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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".)

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) [10,20]. 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'.)

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 HIV-infected patients", 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.
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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) [17,18]. In addition,
malignancy accounts for approximately 15 to 20 percent of moderate to large pericardial
effusions (table 3) [9,10]. (See "Pericardial disease associated with malignancy".)

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 malignancy", section on 'Pericardial effusion with or without
cardiac tamponade'.)

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".)

● Postmyocardial 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. [21-24]. 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 "Mechanical complications of acute myocardial infarction", section on 'Rupture
of the left ventricular free wall'.)

● Post-pericardiotomy syndrome – Post-pericardiotomy syndrome occurs in up to 15 percent

of patients following surgery. The presentation and clinical course of the post-pericardiotomy

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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 [25]. 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 [26,27].

● 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", section on 'Pericardial trauma'.)

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 [28]. Late
onset of pericardial disease is common and is not necessarily preceded by acute pericarditis
[29]. The late pericardial disease may consist of effusive constrictive pericarditis or classic
constrictive pericarditis. (See "Constrictive pericarditis".)

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.

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● Doxorubicin and daunorubicin are more often associated with a cardiomyopathy, but may
cause pericardial disease, as may other chemotherapy agents. (See "Cardiotoxicity of non-
anthracycline cancer chemotherapy agents".)

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 [30]. (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 [31,32]. 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 [32]. The presence of ST-T abnormalities suggests some other
cause for the pericarditis. (See "Pericarditis in renal failure".)

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

cause of pericardial effusion but not usually pericarditis [33]. 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".)

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● 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 [34].

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 [17,18]. 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 diagnostic evaluation".)

● 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 [9,10]. (See "Diagnosis and treatment of pericardial effusion".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
th th
The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
th th
detailed. These articles are written at the 10 to 12 grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.

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)")

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SUMMARY

● 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 'Spectrum
of clinical presentation' above.)

● 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 'Acute
pericarditis' above and "Acute pericarditis: Clinical presentation and diagnostic evaluation".)

● 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.)

● In a patient with nontraumatic hemorrhagic pericardial effusion, malignancy and tuberculosis

(particularly in an endemic area) are common. (See 'Hemorrhagic pericardial effusion' above.)

● 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".)

● 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 malignancy".)

● 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'.)

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● 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.)

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cardiac tamponade: is the cause cancerous, tuberculous, or iatrogenic in the 1990s?
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a prospective series of 231 consecutive patients. Am J Cardiol 1985; 56:623.

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for specific etiologic diagnosis of primary acute pericarditis. Am J Cardiol 1995; 75:378.

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23. 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.

24. Shahar A, Hod H, Barabash GM, et al. Disappearance of a syndrome: Dressler's syndrome
in the era of thrombolysis. Cardiology 1994; 85:255.

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26. Hauptman PJ, Couper GS, Aranki SF, et al. Pericardial effusions after cardiac transplantation.
J Am Coll Cardiol 1994; 23:1625.

27. Quin JA, Tauriainen MP, Huber LM, et al. Predictors of pericardial effusion after orthotopic
heart transplantation. J Thorac Cardiovasc Surg 2002; 124:979.

28. Stewart JR, Fajardo LF, Gillette SM, Constine LS. Radiation injury to the heart. Int J
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Arthritis Rheum 1987; 17:126.

31. Rostand SG, Rutsky EA. Pericarditis in end-stage renal disease. Cardiol Clin 1990; 8:701.

32. Gunukula SR, Spodick DH. Pericardial disease in renal patients. Semin Nephrol 2001; 21:52.

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GRAPHICS

Causes of pericardial disease

Idiopathic (presumed to be viral, postviral, 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)

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 Infective endocarditis

with valve ring abscess

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 (Wegener's), polyarteritis nodosa, sarcoidosis, inflammatory bowel disease
(Crohn's, ulcerative colitis), Whipple's, giant cell arteritis, Behçet syndrome, rheumatic fever

Neoplasm

Metastatic - Lung or breast cancer, Hodgkin's disease, leukemia, melanoma

Primary - Rhabdomyosarcoma, teratoma, fibroma, lipoma, leiomyoma, angioma

Paraneoplastic

Cardiac

Early infarction pericarditis

Late postcardiac injury syndrome (Dressler's syndrome), also seen in other settings (eg, post-myocardial infarction
and post-cardiac surgery)

Myocarditis

Dissecting aortic aneurysm

Trauma

Blunt

Penetrating

Iatrogenic - Catheter and pacemaker perforations, cardiopulmonary resuscitation, post-thoracic surgery

Metabolic

Hypothyroidism - Primarily pericardial effusion

Uremia

Ovarian hyperstimulation syndrome

Radiation
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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.

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Acute pericarditis etiologies: Data from published clinical studies with

unselected populations

Permanyer-Miralda Zayas R. Imazio M. Reuter H. Gouriet F.

G. et al. et al. et al. et al. et al.
(n = 231) (n = 100) (n = 453) (n = 233) (n = 933)

Years 1977-1983 1991-1993 1996-2004 1995-2001 2007-2012

Location Spain Spain Italy Africa Western
Europe
Idiopathic 199 (86.0 percent) 78 (78.0 377 (83.2 32 (13.7 516 (55.0
percent) percent) percent) percent)
Specific etiology 32 (14.0 percent) 22 (22.0 76 (16.8 201 (86.3 417 (46.0
percent) percent) percent) percent)
Neoplastic 13 (5.6 percent) 7 (7.0 23 (5.1 22 (9.4 85 (8.9
percent) percent) percent) percent)
Tuberculosis 9 (3.9 percent) 4 (4.0 17 (3.8 161 (69.5 4 (<1.0
percent) percent) percent) percent)
Autoimmune 4 (1.7 percent) 3 (3.0 33 (7.3 12 (5.2 197 (21
etiologies percent) percent) percent) percent)
Purulent 2 (0.9 percent) 1 (1.0 3 (0.7 percent) 5 (2.1 percent) 29 (3.0
percent) percent)

Data from:
1. Permanyer-Miralda G, Sagrista-Sauleda J, Soler-Soler J. Primary acute pericardial disease: A prospective series of 231
consecutive patients. Am J Cardiol 1985; 56:623.
2. Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific etiologic diagnosis of
primary acute pericarditis. Am J Cardiol 1995; 75:378.
3. Imazio M, Cecchi E, Demichelis B, et al. Indicators of poor prognosis of acute pericarditis. Circulation 2007; 115:2739.
4. 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.
5. Gouriet F, Levy PY, Casalta JP, et al. Etiology of pericarditis in a prospective cohort of 1162 cases. Am J Med 2015;
128:784.

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Case series of moderate-large pericardial effusions

Corey, Strobbe,
Sagrista-Sauleda, Levy, 2003 Ma, 2012
1993 (N = 2017 (N =
2000 (N = 322) (N = 204) (N = 140)
57) 269)

Size of effusion, >10 >10 NR >10 >10 (98 percent)

mm
Tamponade, 37 NR NR 100 88
percent

Etiologies, percent

Idiopathic* 29 (9 percent chronic) 7 48 0 26

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.

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Drugs and toxins associated with pericardial disease

Drug-induced lupus erythematosus Idiosyncratic reaction or hypersensitivity

(con't)
Procainamide

Tocainide Cyclophosphamide

Hydralazine Cyclosporine

Methyldopa Mesalazine

Mesalazine 5-Fluorouracil

Reserpine Vaccines (Smallpox, Yellow fever)

Isoniazid GM-CSF
Hydantoins Anthracycline derivatives

Hypersensitivity reaction Doxorubicin

Penicillins Daunorubicin

Tryptophan Serum sickness

Cromolyn sodium Foreign antisera (eg, antitetanus)

Idiosyncratic reaction or hypersensitivity Blood products

Methysergide Venom
Minoxidil Scorpion fish sting

Practolol Foreign-substance reactions (direct

Bromocriptine pericardial application)

Psicofuranine Talc (Mg silicate)

Phenylbutazone Silicones

Cytarabine Tetracycline/other sclerosants

Amiodarone Iron in β-thalassemia

Streptokinase Asbestos
p-Aminosalicylic acid Secondary pericardial
Thiazides bleeding/hemopericardium

Streptomycin Anticoagulants

Sulfa drugs Thrombolytic agents

Thiouracils Polymer fume fever

Inhalation of the burning fumes of

polytetrafluoroethylene (Teflon)

Reproduced 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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Contributor Disclosures
Brian D Hoit, MD Speaker's Bureau: Philips Medical [Heart valve disease (3D Transesophageal echo)].
Martin M LeWinter, MD Nothing to disclose Jae K Oh, MD Nothing to disclose Brian C Downey, MD, FACC
Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.

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