Pericarditis

Etiology

Infectious pericarditis can be classified as benign, purulent, or granulomatous. Benign pericarditis is caused by viral infection, postinfectious, or postpericardiotomy syndromes; purulent pericarditis is caused by bacterial infection; and granulomatous pericarditis is caused by Mycobacterium tuberculosis and, occasionally, by fungal infection. Although the etiologic distribution varies among studies, in developed countries, upward of 80% of cases are idiopathic. Noninfectious causes include neoplasia, uremia, hypothyroidism, cardiac injury, radiation, drug hypersensitivity, and autoimmune and autoinflammatory diseases.

Viral pericarditis commonly is associated with concurrent myocarditis, and its presentation ranges from subclinical infection to fulminant disease with severe hemodynamic manifestations. A viral etiology is assumed if a pericardial effusion is nonpurulent and if spontaneous resolution occurs. Enteroviruses, especially the coxsackieviruses, are considered the most common causes of viral pericarditis. Other viruses that are implicated commonly include adenovirus, parvovirus B19, human immunodeficiency virus (HIV), Epstein-Barr virus, cytomegalovirus, and other herpesviruses. Less commonly, influenza A and B, hepatitis B and C, mumps, and lymphocytic choriomeningitis viral infections are reported. Cytomegalovirus is an important cause of pericarditis in immunocompromised and HIV-infected people.

Purulent pericarditis occurs when bacteria invade the pericardium as a result of bacteremia, contiguous spread from an intrathoracic infection, or direct inoculation from trauma or surgery. Staphylococcus aureus is the most common cause of purulent pericarditis, accounting for up to 44% of cases in children ( Table 39.1 ). Staphylococcal pericarditis often coincides with infection at other sites, including osteomyelitis, septic arthritis, skin infections, and pneumonia. Historically, Haemophilus influenzae type b, Streptococcus pneumoniae , and Neisseria meningitidis also have been important causes of purulent pericarditis. However, the incidence of invasive disease caused by these pathogens has declined in the postvaccine era. Other bacteria, including group A streptococci, the Streptococcus anginosus group, Salmonella species, Pseudomonas aeruginosa , and other gram-negative bacilli, are implicated less commonly. Rarely, anaerobic bacteria can cause pericarditis, either by hematogenous seeding (especially Bacteroides fragilis ), contiguous spread (especially pulmonary actinomycosis), or as part of a polymicrobial infection. HIV infection is an important predisposing factor worldwide for pericarditis, especially for bacterial and mycobacterial etiologies.

Pericarditis caused by M. tuberculosis occurs in approximately 1% of cases of tuberculosis, either from lymphatic or bacteremic seeding or by direct extension from a pulmonary focus. Although an uncommon cause of pericarditis in developed countries, M. tuberculosis causes up to 70% of cases of pericarditis in Africa and other endemic regions. ^, Tuberculosis also is the most common cause of pericarditis in HIV-infected patients, accounting for 85% of cases.

Pericarditis is occasionally caused by fungal infection, usually in the setting of surgery, instrumentation, neutropenia, or other immunosuppression. Fungi associated with pericarditis include Candida , Aspergillus, Cryptococcus, Coccidioides, Histoplasma, and Blastomyces species. Less common infectious causes of pericarditis include Mycoplasma species , Ureaplasma urealyticum, Rickettsiae , Borrelia burgdorferi , Entamoeba histolytica, Toxoplasma gondii, and Toxocara canis.

Epidemiology

The exact incidence and prevalence of pericarditis are unknown because epidemiologic studies are lacking. However, in a large series of children presenting to an emergency department with chest pain, 0.1%–0.2% had pericarditis. Approximately one-third of pediatric pericarditis cases are classified as idiopathic or viral. Idiopathic pericarditis is more common in adults than in children, and the incidence increases during adolescence. In contrast, purulent pericarditis was once considered a disease of infancy and young childhood. However, with the advent of antibiotics and vaccines, the age distribution has shifted and the incidence has decreased substantially. Bacteria are now rare causes of pericarditis, accounting for 5% or less of all pediatric cases.

Tuberculous pericarditis is the most common cause of pericarditis in regions where M. tuberculosis is endemic. In developed countries, tuberculosis accounts for only 4% of cases of pericarditis and is more common among HIV-infected patients and immigrants from high-risk regions.

Pathogenesis

The pericardium is a fibroserous sac that encompasses the heart and consists of an inner layer, the visceral pericardium, and an outer layer, the parietal pericardium. The visceral pericardium covers the surface of the myocardium with mesothelial cells, which reflect onto the parietal pericardium to form an enclosed sac containing pericardial fluid. The parietal pericardium contains a dense fibrous outer membrane that lines the mediastinal structures and attaches to the sternum, diaphragm, and adventitia of the great vessels. Both layers are 1–2 mm thick, with a space between them that contains 10–15 mL of pericardial fluid in healthy children and 15–35 mL in adults. The pericardium has independent blood supply from the internal mammary arteries and innervation from the vagus nerve. Primary functions of the pericardium are to provide the heart with structural support, lubrication by pericardial fluid, and protection from infection at adjacent sites.

In the setting of infection or acute injury, the pericardial response is nonspecific and limited to exudation of inflammatory cells, fluid, or fibrin. This process may result in a spectrum of disease ranging from dry pericarditis, to pericardial effusion with or without hemodynamic compromise, to fibrosis that may progress to constrictive or effusive-constrictive pericarditis. In effusive pericarditis, the accumulation of fluid within the pericardial sac may be tolerated if the effusion is small or if the rate of fluid accumulation is slow. However, large or rapid increases in fluid secretion can exceed the maximal resorptive capacity of the pericardium. When this occurs, compression of the cardiac chambers can acutely impair diastolic filling, leading to tamponade and death. In contrast, constrictive pericarditis generally is a late complication of chronic pericardial inflammation. Proliferation of fibrous tissue, neovascularization, and scarring result in a loss of pericardial elasticity and impaired cardiac filling. The combination of pericardial effusion under the pressure of a fibrosed pericardium is known as effusive-constrictive pericarditis .

Viral pericarditis typically manifests as dry or effusive pericarditis with a benign, self-limited course. Cardiotropic viruses can spread hematogenously and directly infect the pericardium and myocardium. Pericarditis can be the sole manifestation of viral infection or part of disseminated, multiorgan disease. Although pericarditis typically occurs as a single episode, up to 36% of pediatric patients experience recurrences. The pathogenesis of recurrences is incompletely understood, but immunologic mechanisms are thought to be involved. Patients with recurrent pericarditis have increased rates of circulating antiheart, antiintercalated disk, and antinuclear antibodies, which support the role of autoimmunity in this process. Autoinflammatory diseases, especially familial Mediterranean fever and tumor necrosis factor receptor−associated periodic syndrome, also have known associations with recurrent pericarditis and may underlie the pathogenesis in a minority of patients.

Purulent pericarditis arises from contiguous extension of an adjacent infection, hematogenous seeding, or direct inoculation from trauma or surgery. Contiguous extension of a pulmonary or pleural infection is an important cause of bacterial pericarditis, especially of pneumococcal and staphylococcal etiologies. Less common origins of bacterial pericarditis include suppurative mediastinal, subdiaphragmatic, and intracardiac infections. Bacteria also can be inoculated into the pericardium by hematogenous seeding, which commonly is the pathogenesis of S. aureus pericarditis. In addition, intrathoracic surgical procedures can be complicated by purulent pericarditis, usually in the setting of sternal wound infection with osteomyelitis and mediastinitis. In these cases, S. aureus, S. epidermidis, Candida species , and nosocomial gram-negative bacilli usually are responsible.

Tuberculous pericarditis can result from lymphatic spread, hematogenous (miliary) seeding, or rarely by direct extension of pulmonary disease. Granulomas containing M. tuberculosis initially develop in the pericardium and are followed by serous or serosanguineous effusion containing lymphocytes and monocytes. Healing of tuberculous pericarditis results in deposition of fibrin and collagen, which often leads to constrictive or effusive-constrictive pericarditis.

Clinical Manifestations

Pericarditis causes a variable spectrum of clinical manifestations. The most common presenting symptom is chest pain, which is reported in nearly all pediatric cases. Pericardial chest pain may be felt over the entire precordium, to the left side over the trapezius ridge, and over the scapula. The pain may radiate down the arm and may be aggravated by movement. Chest pain generally is worse when supine and relieved when sitting forward. It is more common in acute infectious pericarditis than in chronic, indolent forms. Pain may be unrecognized in young children, who are more likely to present with irritability and respiratory distress.

Other symptoms of pericarditis in children include fever and respiratory and gastrointestinal complaints. Fever is present in most children with pericarditis, although it is more common in those with purulent etiologies. Respiratory symptoms include coughing, dyspnea, and exercise intolerance. Young children may additionally have tachypnea, use of accessory muscles of respiration, and grunting expiratory sounds as they splint the thoracic cavity. Gastrointestinal symptoms of pericarditis include abdominal pain, vomiting, and poor feeding. Because pericarditis frequently follows an upper respiratory tract infection, a preceding febrile or respiratory tract illness should alert clinicians to consider the diagnosis.

Examination of the heart can reveal tachycardia and muffled heart sounds caused by the surrounding pericardial effusion. A pericardial friction rub can be audible, especially when the effusion is small. Friction rubs are best heard during deep inspiration when a patient is kneeling or in the knee-chest position, leaning forward. Friction rub typically is a to-and-fro, high-pitched, loud, rasping sound heard throughout the cardiac cycle or limited to systole.

Clinical manifestations of tamponade include sinus tachycardia, elevated jugular venous pressure, peripheral vasoconstriction, reduced arterial pulse pressure, and pulsus paradoxus. Pulsus paradoxus represents a drop of more than 10 mm Hg in systolic blood pressure during inspiration due to decreased venous return to the heart. Other findings on examination of patients with pericarditis may include the Kussmaul sign (a rise or failure to fall of jugular venous pressure with inspiration) and the Beck triad (hypotension, muffled heart sounds, and elevated jugular venous pressure).