Janet A. Stockheim and Stanford T. Shulman
ENDOCARDITIS
PATHOGENESIS
Infective endocarditis (IE) in pediatric patients is often associated with an underlying congenital heart defect. However, structurally normal hearts may also be infected.
Establishment of infective endocarditis results from the interaction of several host and microbial factors. Endocardial surfaces damaged by turbulent blood flow attract platelets and fibrin, leading to the formation of a non-bacterial thrombotic lesion. The endocardium, especially when damaged, appears to be a preferential site of microbial adherence and may have some specificity for binding with certain bacteria.1-3
Following endocardial damage, bacterial access to the bloodstream and adherence to endocardial surfaces are required for the establishment of infective endocarditis. It is now thought that the great majority of infective endocarditis develops as the result of transient bacteremia related to activities of daily life,2 but not all bacteria are capable of initiating this process. The presence of several factors, including bacterial surface polysaccharides, endothelial binding proteins, and agglutinating antibodies that clump bacteria, promote adherence of organisms to damaged endocardial surfaces.
Many of the classic manifestations of infective endocarditis (IE) are immunologically mediated. In IE patients with arthralgias and arthritis, splenomegaly, Roth spots, glomerulonephritis, and thrombocytopenia, circulating immune complex levels are significantly higher than in IE patients without these manifestations.
Bacteremia in patients with infective endocarditis is generally low grade and continuous. As much as 10% of cases of infective endocarditis yield consistently negative blood cultures, most often as a result of prior antibiotic therapy. Fastidious organisms with special growth requirements may be difficult to culture. Bacteria infecting right-sided heart lesions may be filtered by pulmonary phagocytes, significantly reducing the number of bacteria in a peripheral blood sample. In evaluating patients for infective endocarditis, it is preferable to obtain at least three separate blood cultures over a 24- to 48-hour period if the patient is stable. Blood should not be drawn through indwelling vascular catheters because contamination may be misleading. If only one of several blood cultures is positive, infective endocarditis is less likely.
Etiologic Agents
Classically, viridans streptococci have been the most common cause of infective endocarditis, progressing along a subacute course in patients with preexisting cardiac lesions in which fever, fatigue, and immune-complex-mediated clinical manifestations develop slowly over weeks or months. Infective endocarditis caused by Staphylococcus aureus has historically followed an acute course with rapid progression and poor outcome, including death, often in patients with normal hearts. Coagulase-negative staphylococci and S aureus tend to infect prosthetic heart valves within 2 months after implantation and are significant pathogens in neonates who require intensive care and intracardiac central lines. Enterococci (especially E faecalis) are well known and important infective endocarditis pathogens. Gram-negative infections of the heart, although infrequent, are increasing in frequency and are most often associated with intravenous drug use, prosthetic or otherwise abnormal valves, invasive procedures, or nosocomial acquisition.
HACEK is an acronym for a group of small, fastidious Gram-negative coccobacilli—Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. These organisms that normally inhabit the upper respiratory tract are often associated with infective endocarditis when recovered from the bloodstream. Candidal infective endocarditis occurs occasionally, often associated with indwelling catheters. Aspergillus infective endocarditis has been reported in children following open heart surgery. Streptococcus pneumoniae accounts for a small minority of cases of childhood infective endocarditis in both structurally normal and abnormal hearts. Infections at additional sites (eg, meningitis and pneumonia) often accompany S pneumoniae infective endocarditis and, despite antibiotic therapy, intracardiac complications are frequent.6 Widespread use of the conjugate pneumococcal vaccine has reduced the incidence of invasive infection due to S pneumoniae, including infective endocarditis.
CLINICAL MANIFESTATIONS
Fever and fatigue are common manifestations of infective endocarditis (IE) in children, whereas other symptoms and physical signs occur with lower frequency (Table 235-1). In a child with underlying congenital heart disease and fever, fatigue, or worsening cardiac function, the diagnosis of IE requires a high index of suspicion. Among all pediatric series, most of the classic peripheral manifestations of IE are infrequent, including Roth spots (small hemorrhagic retinal lesions with pale centers), Osler nodes (small, tender, reddish-purple nodules typically found on the digital pads), Janeway lesions (painless hemorrhagic macules on palms or soles), and splinter hemorrhages (linear streaks in nail beds). Hematuria and associated hypocomplementemia reflecting immune-complex-mediated nephritis occur in less than half of patients, and aseptic meningitis has been reported in a minority of children with infective endocarditis.
Table 235–1. Presenting Features in Children with Infective Endocarditis
DIAGNOSIS
Several laboratory tests offer supportive evidence for the diagnosis of infective endocarditis. Continuous bacteremia is typical; multiple blood cultures should be obtained over a 24-to 48-hour period before antibiotic therapy is instituted, if the patient is not highly toxic or septic in appearance. Other common laboratory findings include anemia and elevated erythrocyte sedimentation rate. The presence of rheumatoid factor is dependent on the duration of infection. When present, it offers supportive evidence for the diagnosis of infective endocarditis and is useful for following the patient’s response to therapy.
In 1994, the Duke University Endocarditis Service developed new diagnostic criteria for infective endocarditis based on pathologic evidence or on a combination of clinical findings, and these were modified somewhat in 2000.7According to the Duke criteria, clinically diagnosed definite infective endocarditis must meet two major criteria, or one major and three minor criteria, or five minor criteria. Major criteria are (1) multiple positive blood cultures for typical infective endocarditis organisms and (2) evidence of endocardial involvement, either echocardiographically or by the development of a new valvular regurgitant murmur. Minor criteria are a predisposition to infective endocarditis (eg, congenital heart defect), fever, vascular phenomena, immuno-logic phenomena, minor echocardiographic findings, and microbiological or serologic evidence that does not meet major criteria. (See also Chapter 490.)
Echocardiography aids in the diagnosis of infective endocarditis. Transesophageal echo-cardiography may improve the sensitivity of detection of vegetations and is especially useful for visualizing prosthetic valves and the aortic outflow tract. Transthoracic 2D echocardiography has resolution of approximately 2 mm, with sensitivities for diagnosis of infective endocarditis from 59% to 82% in children. Use of transesophageal echocardiography should be considered, when transthoracic views are inadequate, when aortic lesions are suspected, or for optimal evaluation of prosthetic valves.8
TREATMENT
Prior to the availability of antibiotics, infective endocarditis (IE) was uniformly fatal. When patients are clinically stable, at least three blood cultures should be collected over a period of 24 to 48 hours before empiric antibiotic therapy is initiated. In patients with cardiac compromise related to valvular or other cardiac dysfunction or with clinical features highly suggestive of acute IE, collection of multiple blood cultures over a much shorter time period is appropriate, followed by initiation of empiric antibiotic therapy. Following identification of an infecting organism, selection of antibiotics should be based on results of susceptibility testing, eg, penicillin minimal inhibitory concentration for streptococcal isolates.
Some basic considerations apply in determining therapy for infective endocarditis. A prolonged course of therapy with high-dose parenteral bactericidal antibiotics is required. Therapy should be bactericidal rather than bacteriostatic, because the relatively avascular vegetations of infective endocarditis offer little access to host defenses. Guidelines for therapy of specific pathogens, based on susceptibility testing and the presence or absence of prosthetic material, were published by the American Heart Association in 2005.8 Beta-lactams (including penicillins and cephalosporins) and vancomycin are used most frequently. Gentamicin is commonly added for a period of time to achieve synergy with a beta-lactam or vancomycin, especially when S aureus, viridans streptococci, or enterococci are the causative organisms. Rifampin is useful as an adjunct when S aureus infects prosthetic valves. High doses of antibiotics are required to exceed the minimum bactericidal concentration for the infecting organism, and synergistic combinations are recommended in some situations (classically, enterococci) to improve therapy or to shorten its duration. All antibiotic regimens are administered over several weeks, with exact durations dependent on identification and antibiotic susceptibility of the organism, choice of antibiotic or synergistic combination, and the presence or absence of prosthetic material. Generally, regimens are extended approximately 2 weeks in the presence of prosthetic material.
Surgical intervention, in addition to medical therapy, is generally indicated in fungal infective endocarditis or when bacteremia persists despite appropriate antibiotic therapy, when congestive heart failure is uncontrolled by medical therapy, or when abscess of the valve annulus or the myocardium, systemic embolic events, rupture of a valve leaflet or chordae, or acute valvular insufficiency with cardiac failure supervenes. Prosthetic valve endocarditis per se is not an indication for surgery, but early surgical intervention may improve the outcome, especially with staphylococcal infections. Among pediatric infective endocarditis patients, the most frequent indications for surgical intervention are persistent infection despite appropriate medical therapy, embolic events, and worsening congestive heart failure. The aortic valve is most often involved in infective endocarditis that requires surgery, followed by the mitral valve.
COMPLICATIONS AND OUTCOMES
The most frequent complications of infective endocarditis are congestive heart failure and arterial embolization. Intracardiac lesions that may lead to congestive heart failure include leaflet dysfunction and valvular insufficiency caused directly by vegetations or by chordal rupture, abscesses of the myocardium or valvular annulus, and myocardial infarction or conduction defects. Pericarditis may result from bacteremic spread of infection or direct extension and usually is associated with S aureus infective endocarditis. Arterial emboli occur most frequently when large mobile vegetations develop on valves, particularly the aortic valve. Although vegetations slowly regress with effective therapy, sudden disappearance of a vegetation should raise the possibility of embolization.
Emboli originating from left-sided vegetations can affect vascular beds in the systemic or cerebral circulation, whereas right-sided lesions produce pulmonary emboli. Mycotic aneurysms most commonly occur at vessel bifurcations and can involve any artery.
PREVENTION
The American Heart Association’s most recent recommendations for prevention of bacterial endocarditis were published in 20072 and are substantially different from previous recommendations. These revisions recognize the lack of evidence to support widespread use of antibiotic prophylaxis and consider its cost effectiveness. Only patients with cardiac conditions with the very highest risk of adverse outcome from infective endocarditis are now recommended to receive prophylaxis for dental procedures (Table 235-2). The mouth appears to be the most common source for organisms responsible for infective endocarditis, and the updated guidelines acknowledge that the risk of transient bacteremia during routine daily activities of oral hygiene greatly outweigh the risk associated with bacteremia related to the occasional dental visit. The importance of good oral hygiene and routine dental care (personal and professional) should be emphasized to all cardiac patients. Table 235-3 provides the AHA’s definition of dental procedures for which prophylactic antibiotics are indicated and their antibiotic recommendations for the limited group of qualified patients. Because normal oral flora may be altered in patients already taking antibiotic prophylaxis (eg, penicillin for rheumatic fever prophylaxis), a different class of drugs (clindamycin, azithromycin, or clarithromycin) may provide more protection against the patient’s own oral microbes in that circumstance.
The genitourinary and gastrointestinal tracts are additional sources of infective endocarditis–causing bacteria, especially enterococci. Prophylactic antibiotic regimens for high-risk genitourinary and gastrointestinal procedures are no longer recommended. However, when patients with cardiac lesions at highest risk of an adverse outcome listed in Table 235-2 have established gastrointestinal or genitourinary infections or receive antibiotics for wound or sepsis prophylaxis during a gastrointestinal or genitourinary procedure, their antibiotic regimen should include enterococcal coverage.
ACUTE RHEUMATIC FEVER
Acute rheumatic fever is a nonsuppurative sequela of pharyngeal infection with group A streptococcus. Target organs of the inflammatory process include the heart, joints, central nervous system, and subcutaneous tissues. Cardiac involvement may be lifelong and is the most important consequence of this disease.
EPIDEMIOLOGY
Acute rheumatic fever (ARF) occurs most often in the winter and spring seasons, and most commonly in children ages 5 to 15. Familial susceptibility to ARF may be related to the presence of specific human leukocyte antigens or other genetic markers.9-11 Asian/Pacific Islander children have recently been identified as a group with a possibly increased genetic susceptibility.12 Patients with ARF have a high likelihood of developing it again when rein-fected with group A streptococcus; this tendency declines with age and with increased time since the last episode.
Antigenic differences among group A streptococcus serotypes are related to the bacteria’s M protein, found within its cell wall. Recent data demonstrated a shift in prevalence of many of the “rheumatogenic” M types13-15 to “nonrheumatogenic” M types causing streptococcal pharyngitis in the United States over the past 40 years that parallels the decrease in the incidence of acute rheumatic fever over this period.13
Table 235–2. Cardiac Conditions with the Highest Risk of Adverse Endocarditis for Which Prophylaxis with Dental Procedures Is Recommended
|
Prosthetic cardiac valves |
|
Previous infective endocarditis |
|
Congenital heart diseasea |
|
Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits |
|
Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedureb |
|
Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) |
|
Cardiac transplantation recipients who develop cardiac valvulopathy |
aExcept for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of congenital heart disease.
bProphylaxis is recommended because endothelialization of prosthetic material occurs within 6 months after the procedure.
(From Wilson W, Taubert KA, Gewitz M, et al, for the American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease. Prevention of infective endocarditis—guidelines from the American Heart Association. Circ J Am Heart Assoc. 2007;116:1736-1754.)
PATHOPHYSIOLOGY
Organ damage that occurs during acute rheumatic fever (ARF) is immune-mediated. The time interval of 10 days to 3 weeks between streptococcal pharyngitis and ARF is consistent with a cellular and humoral immune response. Cross-reactivity of streptococcal antigens and human cardiac, synovial, and brain antigens also supports an immune mechanism of ARF.
Pathologic changes are found throughout the body in connective tissue and around small blood vessels. The pathognomonic lesion of rheumatic fever is the Aschoff body, a painless nodular lesion consisting of fibrinoid changes in connective tissue and a collection of lymphocytes, plasma cells, and histiocytes. Within the heart, the endocardium and myocardium are most often affected. The pericardium may also be involved as a result of the inflammatory process within the myocardium or a manifestation of serositis. Active valvulitis results in variable degrees of valve insufficiency, with chronic changes possibly leading to valvular stenosis. The mitral and aortic valves are affected most commonly, the tricuspid less frequently, and the pulmonary valve rarely.
Table 235–3. Regimens for All Dental Procedures That Involve Manipulation of Gingival Tissue or the Periapical Region of Teeth or Perforation of the Oral Mucosaa
Pathologic changes in the joints consist of exudation with edema of synovial membranes, focal necrosis in the joint capsule, edema and inflammation in periarticular tissue, and joint effusion. These changes are completely reversible. Subcutaneous nodules seen during the acute phase of the disease histologically resemble Aschoff bodies. “Rheumatic pneumonia” consists of exudative and inflammatory changes without Aschoff bodies. Pathologic changes in patients with chorea are not consistent, and little postmortem information is available because patients with active chorea rarely die.
CLINICAL FEATURES AND DIAGNOSIS
Many of the clinical manifestations of acute rheumatic fever occur in infectious, inflammatory, and other collagen vascular disorders. Diagnostic consideration of a patient presenting with a combination of cardiac, joint, and dermatologic abnormalities may include rheumatoid arthritis, systemic lupus erythematosus, Kawasaki disease, rubella, parvovirus, infective endocarditis, or inflammatory bowel disease.
Diagnosis criteria of rheumatic fever, known as the “Jones criteria”, require that an individual have either two major criteria, or on major criterion plus two minor criteria along with evidence of streptococcal infection. Exceptions are chorea or indolent carditis, which each may by themselves indicate rheumatic fever. The five major criteria include:
1. Migratory polyarthritis
2. Carditis
3. Subcutaneous nodules
4. Erythema marginatum
5. Syndenham’s chorea
Minor criteria include:
1. Fever
2. Arthralgia
3. Increased erythrocyte sedimentation rate or C-reactive protein
4. Leukocytosis
5. Electrocardiogram changes showing features of heart block
6. Evidence of Streptococcal infection such as elevated Antistreptolysin O or DNAase
7. Previous episode of rheumatic fever
Classic acute rheumatic fever presents with acute migratory polyarthritis associated with fever. The joints are red, hot, swollen, exquisitely tender, and painful if moved. In general the larger joints of the extremities are affected, but arthritis rarely may occur in the spine and other joints such as the temporomandibular and sternoclavicular joints; arthritis of fingers and toes is more common in older than younger patients. Polyarthritis is the most common of the major criteria and lasts less than 4 to 6 weeks, even if untreated. Characteristic is a dramatic response to salicylates.
Rheumatic carditis may be asymptomatic. Carditis may affect the endocardium (valves), myocardium, or pericardium. Endocarditis manifested by pathologic murmurs is the hallmark of carditis of acute rheumatic fever. The most frequent murmur is an apical systolic murmur of mitral regurgitation.
Myocarditis may be manifested by tachycardia disproportionate to the fever, a gallop rhythm, or arrhythmias. Cardiomegaly may be evident on x-ray. Severe myocarditis may result in congestive heart failure with signs including jugulo-venous distention, hepatomegaly, and pulmonary edema with rales. Prolongation of the P-R interval is common but does not indicate carditis.
Pericarditis in acute rheumatic fever may appear suddenly and may be associated with precordial pain and a friction rub. More often, however, patients with pericarditis are asymptomatic. Pericarditis seldom appears without endocarditis and myocarditis, the combination being termed pancarditis. Death may occur during the acute phase of carditis or after clinical recovery; permanent cardiac damage may result in long-term disability, usually because of mitral or aortic valvular insufficiency and/or stenosis.
Sydenham chorea is characterized by sudden, aimless, irregular movements of the extremities frequently associated with emotional instability and muscle weakness. Whereas carditis and arthritis develop within 3 to 4 weeks after an inciting streptococcal infection, chorea presents after several months and is not often associated with other features of acute rheumatic fever except perhaps mild carditis. The onset may be gradual, with complaints that the child is nervous. The patient may become clumsy and stumble, fall, or drop objects. Often there are complaints of poor attention and deteriorating handwriting and school performance. Facial grimacing and various speech disorders occur. The choreiform movements subside during sleep and are exaggerated by emotion. Characteristically, when the patient is asked to extend the arms, hands, and fingers, flexion of the wrists and hyperextension of the metacarpophalangeal joints (“silver forking”) are observed. Chorea can also be caused by diseases other than acute rheumatic fever, such as lupus or Wilson’s disease, and patients who present with chorea as the only manifestation of acute rheumatic fever should undergo a full evaluation.
Subcutaneous nodules are rare and manifest as painless small (0.5 to 1 cm) swellings over bony prominences, primarily over the extensor tendons of the hands, feet, elbows, scalp, scapulae, and vertebrae. Nodules tend to occur in crops and may persist for days to months after the onset of acute rheumatic fever, generally with severe carditis. Subcutaneous nodules are not specific for acute rheumatic fever and may occur in rheumatoid arthritis as well as systemic lupus erythematosus.
Erythema marginatum occurs in less than 10% of acute rheumatic fever patients; it may be seen more frequently in children less than 5 years old.19 The characteristic rash consists of an evanescent, pink, erythematous macule, with a clear center and serpiginous outline (Fig. 235-1). The rash is transient, migratory, and nonpruritic; it blanches with pressure, is exacerbated by warmth, and is found primarily on the trunk and proximal extremities, sparing the face.
LABORATORY EVALUATION
The erythrocyte sedimentation rate and C-reactive protein are virtually always elevated in acute rheumatic fever (ARF), the degree of elevation being influenced by previous salicylate or steroid therapy, anemia, and congestive heart failure. Because these studies may be abnormal in virtually any other inflammatory state, they are of little value for the specific diagnosis of ARF. Leukopenia or urinalysis abnormalities probably do not occur in rheumatic fever, and if found in a patient with joint and cardiac abnormalities, they are more suggestive of systemic lupus erythematosus.
Isolation of group A streptococci from the throat of a patient suspected of having ARF provides strong evidence for the diagnosis. Caution is needed, however, as most ARF patients clear their streptococcal pharyngitis without antibiotic therapy, and many children may be chronic pharyngeal carriers of streptococci unrelated to ARF without consequence.
FIGURE 235-1. Erythema marginatum of rheumatic fever. Enlarging and shifting transient annular and polyclic lesions. (From: Wolff K, et al. Fitzpatrick’s Dermatology in General Medicine. 7th Edition.)
Elevated serum antistreptococcal antibody titers are probably the most specific and reliable proof of previous streptococcal infection. A rising antibody titer to specific streptococcal antigens is more specific than a single elevated value. However, if the patient presents more than 3 months after acute streptococcal infection, antibody titers may be declining or low. The most widely used serologic test is antibody formation against streptolysin O. Titers of at least 333 U in children and 250 U in adults are usually considered elevated. Other available antibody tests are antideoxyribonuclease B, antihyaluronidase, antistreptokinase, and antinicotinamide-adenine-dineucleotidase. A fourfold rise in titer to one or more of the above antigens can be demonstrated in virtually all cases of acute or recurrent rheumatic fever if serum samples are obtained within 2 to 3 months of the streptococcal infection. Patients who present with fever, rash, arthritis, or carditis should also have studies to exclude systemic lupus erythematosus and rheumatoid arthritis. These include antinuclear antibodies, anti-DNA titers, and rheumatoid factor.
TREATMENT
A full course of oral or intramuscular penicillin should be given to all patients with acute rheumatic fever even if cultures for group A streptococci are negative. An oral cephalosporin is an acceptable alternative; macrolide antibiotics, such as erythromycin, clarithromycin, or azithromycin should be limited to penicillin-allergic patients. Tetracyclines and sulfonamide drugs are not appropriate for treatment of the streptococcal infection.
If a child with acute rheumatic fever is free of clinical carditis, normal activity can be resumed once the pain and fever. If there is mild carditis, 1 to 2 weeks at home is reasonable. Patients with severe carditis, as evidenced by marked cardiomegaly or congestive heart failure, should remain at bed rest for several weeks, until the heart size returns to normal or is at least stable.
Salicylates, nonsteroidal anti-inflammatory drugs, and steroids are beneficial in controlling the acute clinical manifestations of acute rheumatic fever. Arthritis and fever respond dramatically to salicylate therapy, often within hours of initiation. Acetylsalicylic acid is usually used in relatively high doses (50–70 mg/kg/d) for a duration related to the course and severity of the disease; the minimum period is usually 6 weeks. Prior to discontinuation, the dose should be reduced gradually over 2 to 4 weeks. If rebound of rheumatic activity occurs, full therapy may have to be reinstituted for an additional 4 to 6 weeks.
In patients with moderate to severe carditis, neither salicylates nor steroids demonstrate superiority over the other drug in modifying the duration of acute disease or lessening the residual heart damage. However, steroids are indicated in patients who develop congestive heart failure. Digoxin may not benefit the patient with severe myocarditis, but it is often successful in controlling congestive heart failure in patients with valvular insufficiency. Digoxin should be used cautiously, because toxicity may occur with relatively small doses when acute myocarditis is present. Occasionally, severe incompetence of aortic or/and mitral valves leads to refractory heart failure, which requires surgical implantation of a prosthetic valve.
Specific treatment for chorea is not available. Physical and mental stress should be minimized, and protective measures to prevent injury during severe episodes should be instituted. In very severe cases, steroids, phenobarbital, and valproic acid have been helpful.
Prophylaxis against recurrent acute rheumatic fever (ARF) should be instituted immediately following acute therapy. The most effective prophylaxis consists of benzathine penicillin G intramuscular injections every four weeks. Alternative therapy consists of either oral penicillin V twice daily or oral sulfisoxazole once daily. In pediatric ARF patients without carditis, prophylaxis should continue for at least 5 years or until age 21, whichever is longer. When ARF includes carditis but no clinical or echocardiographic evidence of residual valvular disease, the duration of prophylaxis should be extended to at least 10 years, or well into adulthood, whichever is longer. Patients with persistent valvular disease following ARF with carditis should continue prophylaxis for at least 10 years since the last episode of ARF and until at least age 40. Lifelong prophylaxis should be considered in this group.20
PROGNOSIS
Approximately 75% of patients with acute rheumatic fever are well after 6 weeks. By 6 months, fewer than 5% remain symptomatic with chorea or intractable carditis. Up to 70% of patients who develop carditis during the initial episode of acute rheumatic fever recover without any residual heart disease. Whereas 70% of acute rheumatic fever patients with congestive heart failure and pericarditis develop permanent heart disease, only 20% of patients with mild carditis are permanently affected. When more than 8 weeks have elapsed after stopping treatment, acute rheumatic fever does not recur in the absence of recurrent streptococcal infection. In individual patients, the clinical features of recurrent episodes of acute rheumatic fever tend to be similar to that of the initial episode. Compared to a single episode, however, the likelihood of permanent residual heart damage following carditis increases with each recurrence. Patients who have had chorea without apparent carditis may present years later with mitral stenosis.
PERICARDITIS
The pericardium is made up of two layers, which form a sac around the heart, anchored at the origins of the great vessels. The visceral layer is a single layer of mesothelial cells adherent to the myocardium. The parietal layer lies against the mediastinal and pleural spaces and is made up of collagen and elastin fibers. Serous fluid fills the potential space, lubricating the two layers. Pathologic conditions of the pericardium include acute pericarditis, pericardial effusion, tamponade, constrictive pericarditis, and congenital defects of the pericardium.
ACUTE PERICARDITIS
Acute pericarditis is an acute inflammation of the pericardial layers. It is most often manifested by pain, irritability, and sometimes fever. The pain is precordial or referred to the epigastrium, neck, shoulder, or left arm; it may be relieved by leaning forward and made worse by deep inspiration or coughing. A friction rub may be heard along the left sternal border as a high-pitched grating sound, similar to the sound of sandpaper rubbing on wood. The electrocardiogram initially shows elevation of the ST segments in most leads; after about 1 week the S-T segments return to normal and are associated with T-wave flattening and then inversion in the same leads. These changes may persist for months after the acute lesion resolves.
PURULENT PERICARDITIS
Purulent pericarditis occurs either by hematogenous spread or extension from a septic focus in the lung (pneumonia or empyema) or, rarely, after cardiac surgery. The most common organisms are staphylococci, pneumococci, streptococci, Haemophilus influenzae type b, and meningococci21; these organisms can usually be isolated from blood and pericardial fluid. S aureus may also be found in other distant sites such as bone, lung, joint, or skin. H influenzae infection has declined sharply with immunization. The illness has an acute onset, with a high spiking fever, marked polymorphonuclear leukocytosis, and severe toxicity. Specific antibiotic treatment depends on the pathogen identified, but initial empiric antibiotic therapy should include coverage of all the usual organisms. Antibiotic therapy should be continued for 3 to 4 weeks. Close observation for tamponade is essential. Surgical drainage of the pericardial cavity reduces mortality and the risk of constrictive pericarditis, which may follow cure; extended follow-up is necessary. Fungal pericarditis generally occurs in immunocompromised hosts.
ACUTE NONSPECIFIC PERICARDITIS
Pericarditis that is usually suspected to be viral often follows a respiratory infection. Enteroviruses, especially the coxsackie B viruses, are well known to affect the pericardium, with or without associated myocarditis. Sometimes the causative agent can be identified in pericardial fluid by antigen detection tests, viral culture, or polymerase chain reaction (PCR), or may be isolated from blood, nasopharyngeal, or rectal cultures. The pericar-dial phase is manifested by fever, malaise, anorexia, and pericardial pain; infants may have tachycardia, poor feeding, and tachypnea, especially if the myocardium is also affected. There is usually a polymorphonuclear leukocytosis, a pericardial friction rub and transudative effusions are common, and typical electrocardiographic changes are seen. Patients outside the neonatal period are not usually very ill, and tamponade and constrictive pericarditis are rare. Recovery occurs spontaneously in 2 to 4 weeks. Treatment is usually symptomatic with or without nonsteroidal anti-inflammatory agents, but steroids may be needed occasionally for recurrent or unusually severe or long-lasting disease.
POSTPERICARDIOTOMY SYNDROME
Pericarditis may follow any operation in which the pericardium is opened. The syndrome is not common in infants. Up to 30% of patients have attacks of acute pericarditis and fever beginning about 1 to 4 weeks (range 3 days to 6 months) after surgery. There is often a pericar-dial effusion and sometimes a pleural effusion that need not be on the side of the thoracotomy. Because 50% of children who have had a pericardiotomy have a small effusion at the time of discharge, visualization of an effusion per se on echocardiography does not make the diagnosis. A mild polymorphonuclear leukocytosis and an increased sedimentation rate are typical findings, and patients with the syndrome have high titers of heart-reactive antibodies. Seventy percent show an acute rise of antibodies to adenoviruses, coxsackie B, or cytomegalovirus. The current theory is that an immune response is triggered by viral invasion of traumatized myocardial tissue.22 A similar syndrome can occur after pulmonary infarction. Treatment by bed rest and acetylsalicylic acid (120 mg/kg/d) or NSAIDs is usually effective. Once the acute attack is under control, acetylsalicylic acid can be slowly withdrawn over 6 weeks; more rapid withdrawal may lead to recurrences, which may occur in 10% to 15% of patients in any event. Occasionally steroids may be needed if there is no response to this treatment.
OTHER CAUSES OF PERICARDITIS
Tuberculous pericarditis is now rare and when present usually complicates tuberculosis elsewhere. It starts insidiously with malaise, anorexia, low-grade fever, and night sweats, and then the typical features of pericarditis develop; there may be an effusion. Diagnosis is by a positive tuberculin test; isolation of tubercle bacilli from pericardial fluid, sputum, or gastric washings; and histologic examination of the pericardium. Antituberculous therapy along with a long, tapering course of steroids is effective, but because constrictive pericarditis is a common sequela, some experts advocate early pericardiectomy to avoid having to remove dense fibrous tissue later.
Acute rheumatic fever with extensive pancarditis is now uncommon in the United States. Acute rheumatic fever rarely if ever causes pericarditis without valvulitis.
Collagen vascular diseases may involve the pericardium. In juvenile rheumatoid arthritis, pericarditis and high fevers may precede joint involvement. Salicylates are first-line treatment, with steroids reserved for refractory lesions. Systemic lupus erythematosis may have associated pericarditis with effusion and occasionally cardiac tamponade. Other collagen vascular diseases may also cause pericarditis.
Pericarditis and effusion, even tamponade, may occur with chronic uremia. The disorder may be difficult to diagnose because of cardiomegaly and heart failure in some patients. Pericarditis and effusions may occur after radiation of the chest, with foreign bodies in or near the pericardium, and rarely with tumors. Effusions following radiation that persist beyond 2 to 3 months may require a pericardial window (created surgically) to permit drainage. Kawasaki disease, dissecting aneurysm, hypothyroidism, neoplasms, sarcoidosis, acute myocardial infarction, and acute pancreatitis are rare causes of pericardial disease. Pericardial effusions are also seen with fetal hydrops.