Chylopericardium and cholesterol pericarditis

INTRODUCTION — A pericardial effusion is the accumulation of fluid within the pericardial sac surrounding the heart that exceeds the small amount that is normally present (typically less than 50 cc). Pericardial effusion can develop in patients with virtually any condition that affects the pericardium, including acute pericarditis and a variety of systemic disorders. Chylopericardium (pericardial effusion composed of chyle) and cholesterol pericarditis (pericardial inflammation resulting from pericardial effusion with cholesterol crystals and other inflammatory cells) will be reviewed here. Other causes of pericardial effusion and pericarditis are discussed separately. (See "Etiology of pericardial disease" and "Pericardial effusion: Approach to diagnosis", section on 'Identifying the etiology'.)

Chylothorax, with or without chylopericardium, is much more common than isolated chylopericardium. Most cases are nontraumatic, with the major cause being malignancy, although inadvertent surgical trauma is also a common cause. Chylothorax is discussed separately. (See "Etiology, clinical presentation, and diagnosis of chylothorax".)

DEFINITIONS — Chylopericardium is a pericardial effusion comprised of chyle, the normal content of the lacteals (lymphatics of the small intestine) and thoracic duct (figure 1). Chylopericardium may be primary (idiopathic) or, much more often, secondary. The pericardial effusion appears milky white and opaque, with a triglyceride level greater than 500 mg/dL (5.65 mmol/L) and a cholesterol/triglyceride ratio less than 1.

Although the cholesterol content is high, chylopericardium should not be confused with cholesterol pericarditis in which the fluid contains cholesterol crystals, foam cells, macrophages and giant cells. The fluid in cholesterol pericarditis is clear and classically is said to have a glittering "gold paint" appearance, although many other colors have been described [1].

ETIOLOGY — Chylopericardium is a rare disorder that may be primary (ie, idiopathic) or, more often, secondary to injury to the thoracic duct. The thoracic duct carries chyle from the intestinal tract to the blood stream (figure 1). Although wide anatomic variation exists, in most persons the thoracic duct passes in relatively close proximity to the pericardium over its course from the cisterna chyli to the jugular and subclavian veins. (See "Etiology, clinical presentation, and diagnosis of chylothorax".)

Secondary chylopericardium usually results from injury or damage to the thoracic duct. The most common causes of secondary chylopericardium are:

●Trauma (blunt or penetrating)

●Thoracic or cardiac surgery (especially for congenital heart disease) [2-8]

●Congenital lymphangiomatosis

Other documented causes of secondary chylopericardium include radiotherapy, subclavian vein thrombosis, infection (eg, tuberculosis), mediastinal neoplasms (eg, lymphoma, signet ring carcinoma), rheumatologic disease (eg, Behçet syndrome), cystic hygroma, acute pancreatitis, and Gorham disease [9-12]. (See "Treatment for tenosynovial giant cell tumor and other benign neoplasms affecting soft tissue and bone", section on 'Gorham disease'.)

Primary or idiopathic chylopericardium is much less common than secondary chylopericardium and is a diagnosis made by exclusion of other secondary causes [13-18]. In a systematic PubMed and Wangfang database search for English and Chinese studies reporting idiopathic chylopericardium from 1950 to 2015, 104 cases from 92 studies were recovered [19].

CLINICAL MANIFESTATIONS — As with any pericardial effusion, the signs and symptoms related to chylopericardium depend upon the length of time over which pericardial fluid accumulates and the clinical situation. The acute leakage of chyle, as would occur following trauma, can result in rapid pericardial fluid accumulation and increasing intrapericardial pressure resulting in cardiac tamponade, while chronic leakage of chyle is typically associated with significant systemic illness.

The presence of a pericardial effusion may be suspected from the history, physical examination, electrocardiogram (ECG), and chest radiograph, and confirmed from an echocardiogram (see "Pericardial effusion: Approach to diagnosis", section on 'Diagnostic approach'). Clinical features include:

●Most patients without a hemodynamically significant pericardial effusion have no symptoms specific to the effusion, but they may have symptoms related to the underlying cause (eg, chest pain and fever in the setting of pericarditis, etc).

●The most common ECG findings in patients with a hemodynamically significant pericardial effusion are sinus tachycardia, low QRS voltage, and electrical alternans.

●The findings on chest radiograph are variable, depending on the etiology and size of the effusion and underlying comorbidities. Small to moderate effusions may not result in significant findings on the chest radiograph, while larger pericardial effusions typically present with an enlarged cardiac silhouette with clear lung fields.

Significant leakage of chyle causes serious malnutrition, metabolic derangements, and immunologic incompetence. In addition, cardiac complications can occur including cardiac tamponade and, since chyle appears to be a pericardial irritant, acute pericarditis or constrictive pericarditis may also result [1,20]. Rarely, expectoration of chyle (chyloptysis) may accompany chylopericardium [21].

DIAGNOSIS — The diagnosis of chylopericardium, which may be suspected in patients with a pericardial effusion and potential trauma or injury to the thoracic duct (see 'Etiology' above), is confirmed following pericardial fluid analysis. The presence of chylopericardium is suggested by the discovery of a milky, opaque, and opalescent pericardial effusion during pericardial fluid sampling, either with pericardiocentesis or surgical pericardial drainage (picture 1). The pericardial effusion has a high triglyceride level, with analysis of the fluid typically revealing [22]:

●Triglyceride level greater than 500 mg/dL (5.65 mmol/L)

●Cholesterol/triglyceride ratio of less than 1

●Negative cultures and cytology

●Lymphocyte predominance on cytologic examination

●Fat globules seen on Sudan 111 staining

The major cellular component of chyle is the lymphocyte, primarily T lymphocytes. The lymphocyte count ranges between a few hundred to several thousand per milliliter. The electrolyte concentration mirrors that of the plasma, and the protein content exceeds 3 g/dL. The protein content and specific gravity are characteristically high. (See "Pericardial effusion: Approach to diagnosis", section on 'Identifying the etiology'.)

Contrast-enhanced computerized tomography together with lymphangiography/lymphangioscintigraphy can be used to help identify an injury or blockage of the thoracic duct (image 1) [23]. Scintigraphy after the oral administration of I-131 triolein has been used to establish the diagnosis in primary chylopericardium [24].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of a milky white pericardial effusion is limited and generally includes cholesterol pericarditis and purulent pericardial effusions.

●Cholesterol pericarditis is distinguished from chylopericardium by the presence of cholesterol crystals and a lower triglyceride concentration. (See 'Cholesterol pericarditis' below.)

●A purulent pericardial effusion, typically resulting from bacterial or tuberculous infection involving the pericardium, may also appear whitish on fluid sampling. However, a purulent effusion is differentiated from chylopericardium by the cellular content (more neutrophils than lymphocytes), cultures for the causative organism, and significantly lower triglyceride levels than seen with chylopericardium.

TREATMENT — Initial treatment for chylopericardium depends on the presence or absence of symptoms of cardiac tamponade as well as the underlying etiology. Patients with symptoms suggesting cardiac tamponade require urgent fluid removal, while those without symptoms of cardiac tamponade are initially treated with dietary modifications and sometimes with off-label use of somatostatin. A low fat diet supplemented with medium chain triglycerides, which are absorbed by the portal vein rather than the lymphatics, should be initiated [25,26]. Patients with refractory effusions will require surgical therapy to prevent reaccumulation and cardiac tamponade, while those with systemic evidence of malnutrition will frequently require supplemental hyperalimentation. Without treatment, chylopericardium is associated with a high mortality rate.

Cardiac tamponade or large recurrent effusions — Patients with a symptomatic effusion or a large uncontrolled effusion (an average daily loss of chyle of 500 mL/day for five days) usually require more aggressive therapy. Pericardial drainage can initially be accomplished by pericardiocentesis or tube pericardiostomy; additional therapy typically includes fluid and electrolyte replacement and intravenous hyperalimentation (in a malnourished patient who requires supplemental nutrition). This approach is effective in approximately 55 percent of cases [27]. Nonoperative therapy is usually unsuccessful when chylopericardium is secondary to congenital lymphangiomatosis.

Surgical therapy is usually considered if conservative therapy does not reduce pericardial drainage after 7 to 14 days or if the effusion recurs [22,28]. There is no widely accepted daily drainage volume of chyle that indicates the need for surgical treatment, although significant nutritional loss is one criterion. Surgery typically consists of ligation of the thoracic duct and tributary lymphatics, usually via a thoracic approach, along with either pericardiotomy or pericardiectomy [22,28]. A transabdominal surgical approach with successful interruption of the thoracic duct (via ligation or surgical clipping) above the diaphragm has been reported, as has a right-sided thoracoscopic approach to the thoracic duct [18,29].

In patients in whom aggressive therapy is considered inappropriate, a tube can be placed in the pericardium at one end and in the peritoneum at the other to drain the chyle away from the pericardium and into the peritoneal cavity where it can be absorbed [7]. Thoracic duct embolization has been proposed as a simple and effective alternative [30].

Somatostatin for post-operative chylopericardium — Off-label use of the long-acting somatostatin analog, octreotide, has been successful in the treatment of postoperative chylopericardium [31]. The mechanism of action is presumed to be a reduction in chyle production and thoracic duct flow rate.

Mildly symptomatic or asymptomatic patients — Once the diagnosis has been confirmed with pericardial fluid sampling (typically associated with drainage of the effusion concurrent with fluid sampling for laboratory analysis), patients who are otherwise asymptomatic or only mildly symptomatic can have an initial approach of treatment with dietary modifications without surgical therapy. The milky opalescence may disappear or decrease with fasting or dietary modification, but it returns after resuming fat intake. In asymptomatic patients, the effusion may be controlled by adherence to a diet that is low in fat and high in medium chain triglycerides [25,26]. In favorable cases, the chylous effusion does not recur after a few weeks of dietary treatment, presumably because the initiating cause has resolved.

CHOLESTEROL PERICARDITIS — The distinction between chylopericardium and cholesterol pericarditis is analogous to that between chylothorax and chyliform pleural effusion (pseudochylothorax). Cholesterol pericarditis is a complication of chronic pericardial effusion or chronic scarring of the pericardium and is exacerbated by cholesterol crystals [1]. (See "Etiology, clinical presentation, and diagnosis of chylothorax".)

Common underlying causes of cholesterol pericarditis include:

●Tuberculous pericarditis (see "Tuberculous pericarditis")

●Rheumatoid pericarditis (see "Pericardial involvement in systemic autoimmune diseases", section on 'Rheumatoid arthritis')

●Pericardial trauma, a less common cause (see "Post-cardiac injury syndromes")

The clinical manifestations of cholesterol pericarditis are related to the underlying etiology and are similar to other causes of acute pericarditis. Patients may present with systemic symptoms such as fever, flu-like symptoms, and leukocytosis. The major clinical manifestations of pericardial inflammation include pleuritic chest pain, pericardial friction rub, and electrocardiographic changes (eg, widespread ST elevation or PR depression). Pericardial thickening may also be seen on imaging studies (eg, echocardiography, computed tomography, or magnetic resonance imaging), although this is a nonspecific finding. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Clinical features'.)

As with chylopericardium or any other cause of pericardial effusion, pericardial fluid sampling is required to make the diagnosis. Cholesterol crystals are characteristic of this relatively rare disease. When a pericardial effusion is relatively acute, cholesterol remains in solution. However, when the pericardial effusion is chronic, the normal ability to dissolve cholesterol is impaired and cholesterol crystals are deposited in the pericardium and effusion [1]. In contrast to chylopericardium, the fluid is usually clear (although it occasionally may be cloudy or turbid) and classically is said to have a glittering "gold paint" appearance, although many other colors have been described [1]. Blood associated with inflammation is thought to be the source of cholesterol in the pericardial fluid, and evidence of current or previous hemorrhage is usually evident. The pericardium is thicker than normal, and its inner surface is lined with plaques and cholesterol deposits. The histologic findings include fibrosis, inflammatory cells, cholesterol clefts, crystals of variable geometry, and giant cell granulomata.

The effusions in patients with cholesterol pericarditis tend to be large. The concentration of cholesterol equals or exceeds that of the blood, often attaining values above 500 mg/dL (13 mmol/L). The pericardial effusion associated with myxedema also has a high cholesterol concentration, but crystals are usually absent. (See "Clinical manifestations of hypothyroidism".)

Conservative therapy is rarely effective for cholesterol pericarditis. The optimal therapy is radical pericardiectomy plus treatment of the underlying cause of chronic recurrent pericarditis. Pericardiocentesis is seldom effective over the long-term because the cholesterol effusions tend to recur and can cause tamponade at any time. This procedure also fails to address the thick, scarred pericardium and does not prevent the late development of constrictive pericarditis. (See "Cardiac tamponade" and "Constrictive pericarditis: Diagnostic evaluation" and "Recurrent pericarditis", section on 'Treatment'.)

SUMMARY AND RECOMMENDATIONS

●Chylopericardium is a pericardial effusion comprised of chyle, the normal content of the lacteals (lymphatics of the small intestine) and thoracic duct (figure 1). Chylopericardium may be primary (idiopathic) or, much more often, secondary to injury to the thoracic duct (eg, trauma, iatrogenic, malignancy). (See 'Definitions' above.)

●As with any pericardial effusion, the signs and symptoms related to chylopericardium depend upon the length of time over which pericardial fluid accumulates and the clinical situation. The acute leakage of chyle, as would occur following trauma, can result in rapid pericardial fluid accumulation and increasing intrapericardial pressures resulting in cardiac tamponade, while chronic leakage of chyle is typically associated with significant systemic illness. (See 'Clinical manifestations' above.)

●The diagnosis of chylopericardium is confirmed following pericardial fluid analysis. The presence of chylopericardium is suggested by the discovery of a milky opalescent pericardial effusion during pericardial fluid sampling, either with pericardiocentesis or surgical pericardial drainage (picture 1). The pericardial effusion appears milky and opaque, with other findings including a triglyceride level greater than 500 mg/dL, cholesterol/triglyceride ratio of less than 1, negative cultures and cytology, lymphocyte predominance, and fat globules. (See 'Diagnosis' above.)

●Initial treatment for chylopericardium depends on the presence or absence of symptoms of cardiac tamponade as well as the underlying etiology. Patients with symptoms suggesting cardiac tamponade require urgent fluid removal, while those without symptoms of cardiac tamponade are initially treated with dietary modifications and sometimes with off-label use of somatostatin. A low fat diet supplemented with medium chain triglycerides, which are absorbed by the portal vein rather than the lymphatics, should be initiated. Patients with refractory effusions will require surgical therapy to prevent reaccumulation and cardiac tamponade, while those with systemic evidence of malnutrition will frequently require supplemental hyperalimentation. (See 'Treatment' above.)

●Cholesterol pericarditis is a clinical entity distinct from chylopericardium in which the pericardial fluid contains cholesterol crystals, foam cells, macrophages and giant cells. The clinical manifestations of cholesterol pericarditis are related to the underlying etiology and similar to other causes of acute pericarditis. The diagnosis is made following the identification of cholesterol crystals within the pericardial fluid. Conservative therapy is rarely effective for cholesterol pericarditis. The optimal therapy is radical pericardiectomy plus treatment of the underlying cause of chronic recurrent pericarditis. (See 'Cholesterol pericarditis' above.)