Rheumatic fever

Rheumatic fever.   Infective endocarditis.

 

 

Rheumatic fever.

 

Rheumatic fever is an inflammatory condition: it involves the connective tissue in the body. The most severe complication is rheumatic heart disease. This condition may permanently damage the heart valves. Symptoms of valve damage often don’t appear for 10-30 years after the initial event. In many developing countries, which account for almost two-thirds of the world’s population, streptococcal infections, rheumatic fever, and rheumatic heart disease remain a very significant public health problem.

Rheumatic fever is common among the children of the poor, where there is overcrowding and delay in the treatment of throat infections. Rheumatic fever is extremely rare under 2 years of age. Most cases of rheumatic fever occur in children aged 5-15 years.

EPIDEMIOLOGY.

Frequency

The incidence of ARF has declined markedly in the past 50 years in both the United States and Western Europe. Most Western physicians see only the late sequelae of rheumatic heart disease; the diagnosis of an acute case is usually reason enough for a ground rounds presentation. This remarkable decline of rheumatic fever likely reflects improved socioeconomic conditions, as well the decline in prevalence of the classically described rheumatogenic strains of group A streptococci.

Following two decades of almost total absence, a resurgence of ARF occurred in the 1980s among middle-class white children in Salt Lake City, Utah.Clusters were also reported in US Army and Navy training camps during the same period.These limited outbreaks were associated with mucoid rheumatogenic strains that were rarely seen in the preceding 20 years. Today, ARF remains a rarity in most of the United States, although Hawaii and American Samoa continue to see a significant number of cases, many of which are caused by streptococcal strains not usually associated with rheumatic fever in persons of Polynesian descent.

In developing countries, the magnitude of ARF is enormous. Recent estimates suggest that 15.6 million people worldwide have rheumatic heart disease and that 470,000 new cases of rheumatic fever (approximately 60% of whom will develop rheumatic heart disease) occur annually, with 230,000 deaths resulting from its complications. Almost all of this toll occurs in the developing world.The incidence rate of rheumatic fever is as high as 50 cases per 100,000 children in many areas. Areas of  hyperendemicity (eg, indigenous populations of Australia and New Zealand) see an incidence of 300-500 cases per 100,000 children, while the rates are approximately 50-fold lower in their nonindigenous compatriots. Rheumatic fever in the 21st century appears to be largely a disease of crowding and poverty.

Mortality/Morbidity

Cardiac involvement is the most serious complication of rheumatic fever and causes significant morbidity and mortality. As stated above, about 60% of the approximately 470,000 patients diagnosed with ARF annually eventually develop carditis, joining the approximately 15 million worldwide with rheumatic heart disease. Those with rheumatic heart disease are at a high risk for additional cardiac damage with subsequent bouts of ARF and require secondary prophylaxis. Morbidity due to congestive heart failure (CHF), strokes, and endocarditis is common among individuals with rheumatic heart disease, and about 1.5% of persons with rheumatic carditis die of the disease annually.

Race

ARF is predominantly a disease of developing countries and is concentrated in areas of deprivation and crowding. It is rampant in the Middle East, in sub-Saharan Africa, in the Indian subcontinent, in certain areas of South America, in Polynesia, and among the indigenous populations of Australia and New Zealand. Although a genetic predisposition to ARF clearly exists, the disease does not seem to have a major racial predisposition, as it was once common in the United States and Europe and seems to decline in any locale where living conditions improve.

Sex

Rheumatic fever does not have a clear-cut sexual predilection, although certain clinical manifestations, such as mitral stenosis and Sydenham chorea, are more common in females who have gone through puberty.

Age

ARF is most common among children aged 5-15 years. It is relatively rare in infants and uncommon in preschool-aged children. ARF occurs in young adults, but the incidence of first episodes of ARF falls steadily after adolescence and is rare after age 35 years. The lower rate of ARF in adults may represent a decreased risk of streptococcal pharyngitis in this cohort. Recurrent episodes, with their predisposition to cause or exacerbate valvular damage, occur until middle age.

Causes

• Group A beta-hemolytic streptococcal infection may lead to rheumatic fever. The overall attack rate after streptococcal pharyngitis 0.3-3%, but certain genetically predisposed individuals, comprising perhaps 3%-6% of the population, account for those who develop rheumatic fever.

 

 

• Studies in developed countries have established that rheumatic fever followed only pharyngeal infections and that not all serotypes of group A streptococci cause rheumatic fever. For example, some strains (eg, M types 4, 2, 12) in a population susceptible to rheumatic disease do not result in recurrences of rheumatic fever. The classic rheumatogenic serotypes are thought to include 3, 5, 6, 14, 18, 19, and 24.More recent data, largely from studies of the indigenous peoples of Australia, suggest that skin infections (pyoderma) can predispose to ARF and that various other serotypes may be involved.

• Two basic theories have been postulated to explain the development of ARF and its sequelae following group A streptococcal infection: (1) a toxic effect produced by an extracellular toxin of group A streptococci on target organs such as the myocardium, valves, synovium, and brain and (2) an abnormal immune response to streptococcal components. Increasing and compelling evidence now strongly favors the autoimmune explanation. It seems clear that an exaggerated immune response in a susceptible individual leads to rheumatic fever. This probably occurs through molecular mimicry, in which the immune response fails to differentiate between epitopes of the streptococcal pathogen and certain host tissues.

 

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PATHOGENESIS More than half a century ago the pioneering studies of Lancefield differentiated beta-hemolytic streptococci into serologic groups. This ultimately led to the association of infection by the group A organism of the pharynx and tonsils (not of the skin) and the subsequent development of acute rheumatic fever. However, the mechanism(s) responsible for the development of rheumatic fever after an infection remains incompletely defined. Historically, approaches to understanding the pathogenesis of rheumatic fever have been grouped into three major categories:

1. direct infection by the group A streptococcus;

2. toxic effect of streptococcal extracellular products on the host tissues;

3. an abnormal or dysfunctional immune response to one or more as yet unidentified somatic or extracellular antigens produced by all (or perhaps only by some) group A streptococci.

There is insufficient evidence to support direct infection of the heart as the inciting event. Additionally, while toxins such as streptolysin O and others have been postulated to have a pathogenetic role, there is relatively little convincing evidence of this at the present time. Major efforts have focused on an abnormal immune response by the human host to one or more group A streptococcal antigens.

The hypothesis of “antigenic mimicry” between human and group A streptococcal antigens has been studied extensively and has concentrated on two interactions. The first is the similarity between the group-specific carbohydrate of the group A streptococcus and the glycoprotein of heart valves; the second involves the molecular similarity among the streptococcal cell membrane, streptococcal M protein sarcolemma, and other moieties of the human myocardial cell.

The possibility of a predisposing genetic influence in some individuals is one of the most tantalizing of the incompletely understood factors that might contribute to susceptibility to rheumatic fever. The precise genetic factors influencing the attack rate have never been adequately defined. Observations have been described that support the concept that this nonsuppurative sequel to a group A streptococcal upper respiratory tract infection results from an abnormal immune response by the human host. Thus, differences in immune responses to streptococcal antigens have been reported. Further, new data suggest that a unique surface marker on non-T lymphocytes in patients with rheumatic fever and rheumatic heart disease may prove helpful in defining which individuals are susceptible to developing rheumatic fever after a streptococcal infection because of abnormal immune responses.

 

Schematic representation of the aetiopathogenic events occurring during the development of carditis

 

Pathophysiology

ARF is characterized by nonsuppurative inflammatory lesions of the joints, heart, subcutaneous tissue, and central nervous system. An extensive literature search has shown that, at least in developed countries, rheumatic fever follows pharyngeal infection with rheumatogenic group A streptococci. The risk of developing rheumatic fever after an episode of streptococcal pharyngitis has been estimated at 0.3-3%. More recent investigations of rheumatic fever occurring in the aboriginal populations of Australia suggest that streptococcal skin infections might also be associated with the development of rheumatic fever. In Oceania and Hawaii, streptococcal strains that are not typically associated with rheumatic fever have been found to cause the disease.

Molecular mimicry accounts for the tissue injury that occurs in rheumatic fever. Both the humoral and cellular host defenses of a genetically vulnerable host are involved. In this process, the patient’s immune responses (both B- and T-cell mediated) are unable to distinguish between the invading microbe and certain host tissues. The resultant inflammation may persist well beyond the acute infection and produces the protean manifestations of rheumatic fever.

 

Classification

 

 

 

Clinical-Anatomical characteristic of involvement of the heart:

1. Acute phase:

a. primary rheumocarditis without valvular involvement.

b. recurrent rheumocarditis with cardiac defect

c. rheumatic fever without obvious cardiac  involvement.

2. nonacute phase:

a. rheumatic myocardiosclerosis

b. cardiac defect

 

Clinical-Anatomical characteristic of involvement of visceral organs and systems:

1. Acute phase: carditis, polyathritis, serositis (pleuritis, peritonitis,abdominal syndrome), chorea, encephalitis, meningoencephalitis, cerebral vasculitis, vasculitis, nephritis, hepatitis, pneumonia, skin alteration, iritis, iridocyclitis, thyroiditis.

2. Nonacute phase: results of the outcardiac involvement.

Course: Acute, subacute, recurrent, latent.

Functional condition of blood circulation:

HF0 – heart failure is absent

HF1 – the first grade of heart failure

HF2 – the second grade of heart failure

HF3 – the third grade of heart failure

3. Structure of clinical diagnosis.

I. Rheumatic fever

II. Phase

a.) acute:

I degree – minimum, II degree – moderate, III degree – maximum

b.) nonacute

 

IV. Cardiac involvement:

1. Acute phase:

a.) primary rheumocarditis without valvular involvement,

b.) recurrent rheumocarditis with cardiac defect,

c). rheumatic fever without obvious cardiac involvement.

2. Nonactive phase:

a.) rheumatic myocardiosclerosis,

b.) cardiac defect

 

V. Involvement of visceral organs and systems:

1.) Acute phase: polyathritis, serositis (pleuritis, peritonitis,abdominal syndrome), chorea, encephalitis, meningoencephalitis, cerebral vasculitis, vasculitis, nephritis, hepatitis, pneumonia, skin alteration, iritis, iridocyclitis, throiditis

2.) Nonacute phase: results of the outcardiac involvement.

VI. Functional condition of blood circulation:

a) HF0 – heart failure is absent

b) HF1 – the first grade of heart failure

c) HF2 – the second grade of heart failure

d) HF3 – the third grade of heart failure

 

Criteria for the grades of activity of rheumatic fever

 

 

 

Clinic

Rheumatic fever manifests as various signs and symptoms that may occur alone or in various combinations.

n       Sore throat: Although estimates vary, only 35%-60% of patients with rheumatic fever recall having any upper respiratory symptoms in the preceding several weeks. Many symptomatic individuals do not seek medical attention, go undiagnosed, or do not take the prescribed antibiotic for acute rheumatic fever (ARF) prevention.

n       Polyarthritis: Overall, arthritis occurs in approximately 75% of first attacks of ARF. The likelihood increases with the age of the patient, and arthritis is a major manifestation of ARF in 92% of adults. A migratory polyarthritis is present in as many as 75% of cases, most often affecting the ankles, wrists, knees, and elbows over a period of days. It usually does not affect the small joints of the hands or feet and seldom involves the hip joints. Since salicylates and other anti-inflammatory drugs usually cause prompt resolution of joint symptoms, it is important that the cliniciaot prescribe these medications until it is determined whether the arthritis is migratory. The arthritis of acute rheumatic fever is extremely painful. Pain can be controlled with codeine or similar analgesics until the diagnosis is established.  The arthritis lasts 1-5 weeks and subsides without residual deformity. The difference between arthralgia (subjective joint pain) and arthritis (joint pain and swelling) must be understood. Too often, arthralgia is used (incorrectly) as a major criterion.

ü       The arthritis of ARF is usually symmetrical and involves large joints, such as the knees, ankles, elbows, and wrists. Tenosynovitis is common in adults and may be severe enough to suggest a diagnosis of disseminated gonococcal disease.

ü       The evolution of arthritis in individual joints tends to overlap; therefore, multiple joints may be inflamed simultaneously, causing more of an additive than a migratory pattern.

ü       In most instances, the entire bout of polyarthritis subsides within 4 weeks without any permanent damage. If not, a different diagnosis should be entertained.

n       Carditis: Of first attacks of ARF, carditis occurs in 30%-60% of cases. It is more common in younger children but does occur in adults.

ü       Severe inflammation can cause congestive heart failure (CHF).

ü       Patients with carditis may present with shortness of breath, dyspnea upon exertion, cough, paroxysmal nocturnal dyspnea, chest pain, and/or orthopnea. Carditis may also be asymptomatic and may be diagnosed solely by auscultation or, perhaps, echocardiography.

 

 

Chest radiograph of an 8 year old patient with acute carditis before treatment

 

Same patient after 4 weeks

 

The clinical picture includes high pulse rate, congestive heart failure, arrhythmias and pericardial friction rubs. On the first attack, valvulitis is suspected in the presence of a new apical systolic murmur of mitral regurgitation (associated or not with an apical mid-diastolic murmur) and/or a basal diastolic murmur of aortic regurgitation. Cardiomegaly is noted on X-Ray and on echocardiogram. Myocarditis and/or pericarditis in the absence of valvular involvement is unlikely due to acute RF. It is contentious if myocardial dysfunction  in acute RF is valvular or myocardial in origin. In fact, in a subset of patients, the initial presentation may be quite severe, with overt heart failure, fever and toxemia, making the differential diagnosis with infective endocarditis very difficult, in particular in patients with recurrent rheumatic heart disease. Carditis is the most serious manifestation of rheumatic fever, involves all the layers of the heart wall simultaneously. It occurs in as many as 40% of patients and may include cardiomegaly, new murmur, congestive heart failure, and pericarditis, with or without a rub and valvular disease. The inflammation of the pericardium (outer coating of the heart) is called pericarditis. The inflammation of the myocardium (heart muscle) is called myocarditis. The inflammation of the endocardium (internal lining of the heart wall) is called endocarditis. The involvement of the heart is revealed by the occurrence of new mitral and aortic murmurs and cardiomegaly. Very severe rheumatic heart disease may lead to heart failure. The heart lesions may remain and worsen with every recurrence of the acute rheumatic fever. However, isolated aortic valve disease as a consequence of acute rheumatic fever is quite rare. In patients with aortic valve disease due to rheumatic fever, the mitral valve is almost always simultaneously affected. Even minor degrees of rheumatic valvular involvement can lead to susceptibilities to infective endocarditis. Although rheumatic pericarditis can cause a serous effusion, fibrin deposits, and even pericardial calcification, it does not lead to constrictive pericarditis. The valvular lesions in RF often result in residual damage. Nevertheless, in milder forms of rheumatic carditis patients may recover from valvulitis without sequel. In the first attack, the lesions are predominantly regurgitant, due to ring dilatation, swollen cusps, chordal rupture or papillary muscle dysfunction. In the chronic phase, obstructive lesions are more frequent.

n       Sydenham chorea: This occurs in up to 25% of ARF cases in children but is very rare in adults. It is more common in girls. Sydenham chorea in ARF is likely due to molecular mimicry, with autoantibodies reacting with brain ganglioside. Sydenham’s chorea occurs in fewer than 10% of patients with rheumatic fever. The latent period between the onset of the initiating streptococcal infection and the onset of Sydenham’s chorea may be as long as several months. While differing from the other manifestations, this central nervous system disorder is a part of the rheumatic fever complex and should be managed as such. Many patients who appear to have only chorea may present several decades later with evidence of typical rheumatic valvular disease. There is no definitive laboratory test for establishing a diagnosis of Sydenham’s chorea, and the diagnosis is one of exclusion. Patients with Sydenham’s chorea should be given secondary prophylaxis for prevention of recurrent attacks, even if they do not appear to have rheumatic heart disease. Sydeman’s chorea – involuntary choreoathetoid movements primarily of the face, tongue, and upper extremities – may be the sole manifestation; only half of cases have other overt signs of rheumatic fever. Girls are more frequently affected, and occurrence in adults is rare.

ü       Sydenham chorea may occur with other symptoms or as an isolated finding. It typically presents 1-6 months after the precipitating streptococcal infection and usually has both neurologic and psychological features.

ü       In the isolated form, laboratory evidence of a preceding streptococcal infection may be lacking.

ü       Like the polyarthritis, Sydenham chorea usually resolves without permanent damage but occasionally lasts 2-3 years and be a major problem for the patient and her family.

n       Erythema marginatum: In first attacks of ARF in children, erythema marginatum occurs in approximately 10%. Like chorea, it is very rare in adults.  Erythema   marginatum  is an uncommon manifestation. It is an evanescent macular eruption with rounded borders-usually concentrated on the trunk and proximal extremities. The former begin as rapidly enlarging macules that assume the shape of rings or crescents with clear centers. They may be confluent, and either transient or persistent.

n       This is an evanescent, erythematous, non-pruritic rash with pale centers and rounded or serpiginous margins. Lesions occur mainly on the trunk and proximal extremities and may be induced by application of heat.

Erythema marginatum on the trunk, showing erythematous lesions with pale centers and rounded or serpiginous margins

Closer view of erythema marginatum in the same patient

n       The minor criteria are nonspecific and may be present in many clinical conditions. These include fever, polyarthralgias, reversible prolongation of the PR interval, rapid erythrocyte sedimentation rate, evidence of an antecedent b-hemolytic streptococcal infection, or a history of rheumatic fever.

ü       Patients or parents may report a nonpruritic, painless, serpiginous, erythematous eruption on the trunk. It is usually noted only in fair–skinned patients.

ü       The lesions may persist intermittently for weeks to months.

n       Subcutaneous nodules are rarely noticed by the patient. Subcutaneous nodules and erythema marginatum are rare major manifestations, usually present in fewer than 10% of cases. Subcutaneous nodules are found over extensor surfaces of joints, are seen most often in patients with long-standing rheumatic heart disease, and are extremely rare in patients experiencing an initial attack. They are small (≤ 2 cm in diameter), firm, and nontender and are attached to fascia or sheaths over bony prominences.  They persist for days or weeks, are recurrent, and are indistinguishable from rheumatoid nodules. Subcutaneous nodule on the extensor surface of elbow of a patient with acute RF Subcutaneous nodules are rarely seen and when present, they are usually associated with severe carditis. They are painless, firm, movable, measuring around 0.5 to 2 cm. They are usually located over extensor surfaces of the joints, particularly knees, wrists and elbows.

 

 

 

n       Other symptoms may include fever, abdominal pain, arthralgia, malaise, and epistaxis.

Diagnostic criteria

Revised Jones Criteria for Acute Rheumatic Fever (ARF)

A firm diagnosis requires that two major or one major and two minor criteria are satisfied, in addition to evidence of recent streptococcal infection.

Major Criteria

1.     Carditis: All layers of cardiac tissue are affected (pericardium, epicardium, myocardium, endocardium) The patient may have a new or changing murmur, with mitral regurgitation being the most common followed by aortic insufficiency.

2.     Polyarthritis: Migrating arthritis that typically affects the knees, ankles, elbows and wrists. The joints are very painful and symptoms are very responsive to anti-inflammatory medicines.

3.     Chorea: Also known as Syndenham´s chorea, or “St. Vitus´ dance”. There are abrupt, purposeless movements. This may be the only manifestation of ARF and is its presence is diagnostic. May also include emotional disturbances and inappropriate behavior.

4.     Erythema marginatum: A non-pruritic rash that commonly affects the trunk and proximal extremities, but spares the face. The rash typically migrates from central areas to periphery, and has well-defined borders.

5.     Subcutaneous nodules: Usually located over bones or tendons, these nodules are painless and firm.

Minor Criteria:

1.     Fever

2.     Arthralgia

3.     Previous rheumatic fever or rheumatic heart disease

4.     Acute phase reactants: Leukocytosis, elevated eritrosedimentation rate (ESR) and C-reactive protein (CRP)

5.     Prolonged P-R interval on electrocardiogram (ECG)

 

Evidence of preceding streptococcal infection: Any one of the following is considered adequate evidence of infection:

• Increased antistreptolysin O or other streptococcal antibodies

• Positive throat culture for Group A beta-hemolytic streptococci

• Positive rapid direct Group A strep carbohydrate antigen test

• Recent scarlet fever.

 

If supported by evidence of preceding group A streptococcal infection, the presence of two major manifestations or one major and two minor manifestations indicates a high probability of ARF. Failure to fulfill the Jones criteria makes the diagnosis unlikely but not impossible. Clinical judgment is required.

The World Health Organization (WHO) follows the Jones criteria for the diagnosis of ARF, but possible recurrences require only two minor criteria plus evidence of recent streptococcal infection.

 

Diagnostics

Laboratory Studies

n       No single specific laboratory test can confirm the diagnosis of acute rheumatic fever (ARF). Evidence of preceding group A streptococcal infection is an integral part of the Jones criteria for ARF diagnosis unless the patient has chorea (which may occur months after the inciting infection) or indolent rheumatic heart disease (see Diagnosis).

n       Throat culture remains the criterion standard for confirmation of group A streptococcal infection. Rapid antigen detection tests are not as sensitive.

ü       If a rapid antigen detection test result is negative, obtain a throat culture in patients with suspected rheumatic fever.

ü       On the other hand, because of the high specificity of these tests, a positive rapid antigen test confirms a streptococcal infection.

n       Antibody titer tests used include ASO test, antistreptococcal DNAse B (ADB) test, and the antistreptococcal hyaluronidase (AH) test.

ü       ASO is a test used to detect streptococcal antibodies directed against streptococcal lysin O. An elevated titer is proof of a previous streptococcal infection. It is usually more elevated after a pharyngeal than skin infection, while the ADB is typically elevated regardless of the site of the infection.

ü       Acute and convalescent sera, if available, are helpful for proving recent streptococcal infection.

ü       The antibody tests must be interpreted with caution in areas with high rates of streptococcal infection and ARF, as relatively high titers are commonly encountered in the population. These tests are of greater utility in areas with lower prevalence (eg, in most Western countries).

n       Acute-phase reactants, the erythrocyte sedimentation rate (ESR), and C-reactive protein levels (CRP) are usually elevated at the onset of ARF and serve as a minor manifestation in the Jones criteria. These tests are nonspecific, but they may be useful in monitoring disease activity.

n       Blood cultures are obtained to help rule out infective endocarditis, bacteremia, and disseminated gonococcal infection.

Imaging Studies

n       Chest radiography can reveal cardiomegaly and CHF in patients with carditis.

n       Echocardiography may demonstrate valvular regurgitant lesions in patients with ARF who do not have clinical manifestations of carditis. This does not qualify as carditis in the most recent Jones diagnostic criteria, as the clinical implications of subclinical carditis remain unclear, but some experts believe the diagnostic criteria for ARF should be modified to allow for specific abnormalities found only on echocardiograms to be included. This is a controversial topic (see Physical).

ü       Valvular stenotic lesions, especially of the mitral valve, can be observed in rheumatic heart disease.

ü       In the absence of mitral valve disease involvement, isolated echocardiographic disease of the aortic valve is uncommon in patients with rheumatic heart disease.

 

The most common finding on electrocardiography is a prolongation of the PR interval, which is a nonspecific finding, but counts as a minor manifestation in the Jones diagnostic criteria. It does not count as proof of carditis.On rare occasions, second- or third-degree heart block is present.In patients with chronic rheumatic heart disease, electrocardiography may show left atrial enlargement secondary to mitral stenosis.Various other studies may be needed to rule out other illnesses in the differential diagnoses. Common tests would include rheumatoid factor, antinuclear antibody (ANA), Lyme serology, blood cultures, and evaluation for gonorrhea.

Histologic Findings

           Rheumatic fever is characterized pathologically by exudative and proliferative inflammatory lesions of the connective tissue in the heart, joints, blood vessels, and subcutaneous tissue.

In the early stage, fragmentation of collagen fibers, cellular infiltration that is predominantly lymphocytic, and fibrinoid deposition followed by the appearance of a myocardial Aschoff nodule (a perivascular focus of inflammation that has an area of central necrosis surrounded by a rosette of large mononuclear and giant multinuclear cells) occur. The nuclei of these cells resemble owl eyes and are called Anichkov cells.

Subcutaneous nodules histologically resemble Aschoff nodules. The brain may show scattered areas of arteritis and petechial hemorrhages, which have an uncertain relationship to Sydenham chorea.

 

 

 

http://commons.wikimedia.org/wiki/File:Rheumatic_heart_disease_-_very_high_mag.jpg

Myocardial Aschoff body – the cells are large, elongated, with large nuclei; some are multinucleate

 

 

 

Microscopic findings include Anitschkow cells (also known as caterpillar cells), and Aschoff bodies. Anitschkow cells are thought to be cardiac histocytes and Aschoff bodies are thought to be granulomas.

TREATMENT OF STREPTOCOCCAL PHARYNGITIS

Treatment of the acute attack:

Benzathine penicillin 1.2 million units i.m. or oral phenoxymethylpenicillin 250 mg 6-hourly for 10 days should be given on diagnosis in order to eliminate any residual streptococcal infection. Treatment of acute rheumatic fever is then directed towards limiting cardiac damage and relieving symptoms. Bed rest and supportive therapy. Bed rest is important as it lessens joint pain and reduces cardiac workload in patients with carditis. The duration of bed rest should be guided by symptoms and markers of inflammation (e.g. temperature, leucocyte count and ESR) and should be continued until these indices of disease activity have settled. In patients who have had carditis, it is conventional to recommend bed rest for 2-6 weeks after the ESR and temperature have returned to normal. Prolonged bed rest, particularly in children or adolescents, produces problems of boredom and depression that need to be anticipated and managed. Cardiac failure should be treated as necessary. Some patients, particularly those in early adolescence, develop a fulminant form of the disease with severe mitral regurgitation and sometimes concomitant aortic regurgitation. If heart failure does not respond to medical treatment in these cases valve replacement may be necessary and is often associated with a dramatic decline in rheumatic activity. Heart block is seldom progressive, and pacemaker therapy is rarely needed.

Aspirin.  Aspirin will usually relieve the symptoms of arthritis rapidly and a prompt response (within 24 hours) helps to confirm the diagnosis. A reasonable starting dose is 60 mg/kg body weight per day, divided into six doses. In adults, 120 mg/kg per day may be needed up to the limits of tolerance or a maximum of 8 g per day. Mild toxic effects include nausea,  tinnitus and deafness; more serious ones are vomiting, tachypnoea and acidosis. Aspirin should be continued until the ESR has fallen, and then gradually tailed off.

Corticosteroids. These produce more rapid symptomatic relief than aspirin, and are indicated in cases with carditis or severe arthritis. There is no evidence that long-term steroids are beneficial. Prednisolone 1.0-2.0 mg/kg per day in divided doses should be continued until the ESR is normal, then gradually tailed off.

 

Primary prevention of rheumatic fever requires adequate therapy for GAS pharyngitis.

Primary Prevention of Rheumatic Fever

                                                                                                                                                                                                                                TABLE 2

Agent	Dosage	Evidence rating*
Penicillins
Amoxicillin	50 mg per kg (maximum, 1 g) orally once daily for 10 days	1B
Penicillin G benzathine	Patients weighing 27 kg (60 lb) or less: 600,000 units IM once	1B
	Patients weighing more than 27 kg: 1,200,000 units IM once
Penicillin V potassium	Patients weighing 27 kg or less: 250 mg orally 2 or 3 times daily for 10 days	1B
	Patients weighing more than 27 kg: 500 mg orally 2 or 3 times daily for 10 days
For patients allergic to penicillin
Narrow–spectrum cephalosporin (cephalexin [Keflex], cefadroxil [formerly Duricef])†	Varies	1B
Azithromycin (Zithromax)	12 mg per kg (maximum, 500 mg) orally once daily for 5 days	2aB
Clarithromycin (Biaxin)‡	15 mg per kg orally per day, divided into 2 doses (maximum, 250 mg twice daily), for 10 days	2aB
Clindamycin (Cleocin)	20 mg per kg orally per day (maximum, 1.8 g per day), divided into 3 doses, for 10 days	2aB

 

 

OTHER RECOMMENDATIONS

Because most patients with GAS pharyngitis respond well to antimicrobial therapy, posttreatment throat cultures are indicated only in those who remain symptomatic, who have recurrent symptoms, or who have had rheumatic fever previously.

With the exception of persons who have had or whose family members have had rheumatic fever, repeated courses of antibiotics are typically not indicated in asymptomatic persons who continue to harbor GAS after appropriate therapy.

Although acute infections with group B and C beta-hemolytic streptococci can appear similar to GAS pharyngitis, rheumatic fever has not been documented as a complication of these infections.

Secondary Prevention of Rheumatic Fever

Continuous prophylaxis is recommended in patients with well-documented histories of rheumatic fever and in those with evidence of rheumatic heart disease (Tables 3 and 4). Prophylaxis should be initiated as soon as acute rheumatic fever or rheumatic heart disease is diagnosed. To eradicate residual GAS, a full course of penicillin should be given to patients with acute rheumatic fever, even if a throat culture is negative.

Duration of Secondary Prophylaxis for Rheumatic Fever

TABLE 3

Type	Duration after last attack	Evidence rating*
Rheumatic fever with carditis and residual heart disease (persistent valvular disease†)	10 years or until age 40 years (whichever is longer); lifetime prophylaxis may be needed	1C
Rheumatic fever with carditis but no residual heart disease (no valvular disease†)	10 years or until age 21 years (whichever is longer)	1C
Rheumatic fever without carditis	5 years or until age 21 years (whichever is longer)	1C

 

Secondary Prevention of Rheumatic Fever

TABLE 4

 

Agent	Dosage	Evidence rating*
Penicillin G benzathine	Patients weighing 27 kg (60 lb) or less: 600,000 units IM every 4 weeks†	1A
	Patients weighing more than 27 kg: 1,200,000 units IM every 4 weeks†
Penicillin V potassium	250 mg orally twice daily	1B
Sulfadiazine	Patients weighing 27 kg or less: 0.5 g orally once daily	1B
	Patients weighing more than 27 kg: 1 g orally once daily
Macrolide or azalide antibiotic (for patients allergic to penicillin and sulfadiazine)‡	Varies	1C

 

IM = intramuscularly.

Patients are susceptible to additional attacks of rheumatic fever if further streptococcal infection occurs, and long-term prophylaxis with penicillin should be given as benzathine penicillin 1.2 million units i.m. monthly (if compliance is in doubt) or oral phenoxymethylpenicillin 250 mg 12-hourly. Erythromycin may be used if the patient is allergic to penicillin. Further attacks of rheumatic fever are unusual after the age of 21, at which age treatment may be stopped. However, treatment should be extended if an attack has occurred in the last 5 years, or the patient lives in an area of high prevalence, or has an occupation (e.g. teaching) with high exposure to streptococcal infection. It is important to appreciate that long-term antibiotic prophylaxis is intended to prevent another attack of acute rheumatic fever and does not protect against infective endocarditis.

 

 

 

Infective endocarditis

 

Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium, or a septal defect. Its intracardiac effects include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial abscesses. IE also produces a wide variety of systemic signs and symptoms through several mechanisms, including both sterile and infected emboli and various immunological phenomena.

Hystory

          The history of IE can be divided into several eras. Lazaire Riviere first described gross autopsy findings of the disease in 1723. In 1885, William Osler presented the first comprehensive description of endocarditis in English. Lerner and Weinstein presented a thorough discussion of this disease in modern times in their landmark series of articles, “Infective Endocarditis in the Antibiotic Era,” published in 1966 in the New England Journal of Medicine.

IE currently can be described as infective endocarditis in the era of intravascular devices, as infection of intravascular lines has been determined to be the primary risk factor for Staphylococcus aureus bloodstream infections (BSIs). S aureus has become the primary pathogen of endocarditis.

IE generally occurs as a consequence of nonbacterial thrombotic endocarditis, which results from turbulence or trauma to the endothelial surface of the heart. A transient bacteremia then seeds the sterile platelet/fibrin thrombus, with IE as the end result. Pathologic effects due to infection can include local tissue destruction and embolic phenomena. In addition, secondary autoimmune effects, such as immune complex glomerulonephritis and vasculitis, can occur.

Epidemiology

            The incidence of IE is approximately 2-4 cases per 100,000 persons per year. This rate has appeared to be unchanged over the past 50 years. However, a recent study indicated that the age-adjusted hospital admission rate increased 2.4 % annually from 1998-2009. This increase may well be driven by the increase in the use of intravascular devices. The incidence of IE in other countries may or may not remain similar to that in the United States.

           Although endocarditis can occur in a person of any age, the mean age of patients has gradually risen over the past 50 years. Currently, more than 50% of patients are older than 50 years.  Mendiratta et al, in their retrospective study of hospital discharges from 1993-2003 of patients aged 65 years and older with a primary or secondary diagnosis of IE, found that hospitalizations for IE increased 26%, from 3.19 per 10,000 elderly patients in 1993 to 3.95 per 10,000 in 2003. This increase in age has continued, with the mean age of patients in 2009 at 60.8 years.

           IE is 3 times as common in males as in females. It has no racial predilection.

 

Etiology

The different types of IE have varying causes and involve different pathogens.

Native valve endocarditis

The following are the main underlying causes of NVE:

• Rheumatic valvular disease (30% of NVE) – Primarily involves the mitral valve followed by the aortic valve

• Congenital heart disease (15% of NVE) – Underlying etiologies include a patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot, or any native or surgical high-flow lesion.

• Mitral valve prolapse with an associated murmur (20% of NVE)

• Degenerative heart disease – Including calcific aortic stenosis due to a bicuspid valve, Marfan syndrome, or syphilitic disease

Approximately 70% of infections in NVE are caused by Streptococcus species, including S viridans, Streptococcus bovis, and enterococci. Staphylococcusspecies cause 25% of cases and generally demonstrate a more aggressive acute course (see the images below).

Prosthetic valve endocarditis

                   Early PVE, which presents shortly after surgery, has a different bacteriology and prognosis than late PVE, which presents in a subacute fashion similar to NVE.

                 Infection associated with aortic valve prostheses is particularly associated with local abscess and fistula formation, and valvular dehiscence. This may lead to shock, heart failure, heart block, shunting of blood to the right atrium, pericardial tamponade, and peripheral emboli to the central nervous system and elsewhere.

                Early PVE may be caused by a variety of pathogens, including S aureus and S epidermidis. These nosocomially acquired organisms are often methicillin-resistant (eg, MRSA). Late disease is most commonly caused by streptococci. Overall, CoNS are the most frequent cause of PVE (30%).

S aureus causes 17% of early PVE and 12% of late PVE. Corynebacterium,nonenterococcal streptococci, fungi (eg, C albicans, Candida stellatoidea, Aspergillus species), Legionella, and the HACEK (ie, Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) organisms cause the remaining cases.

IVDA infective endocarditis

             Diagnosis of endocarditis in IV drug users can be difficult and requires a high index of suspicion. Two thirds of patients have no previous history of heart disease or murmur on admission. A murmur may be absent in those with tricuspid disease, owing to the relatively small pressure gradient across this valve. Pulmonary manifestations may be prominent in patients with tricuspid infection: one third have pleuritic chest pain, and three quarters demonstrate chest radiographic abnormalities.

            S aureus is the most common (< 50% of cases) etiologic organism in patients with IVDA IE. MRSA accounts for an increasing portion of S aureus infections and has been associated with previous hospitalizations, long-term addiction, and nonprescribed antibiotic use. Groups A, C, and G streptococci and enterococci are also recovered from patients with IVDA IE.

Currently, gram-negative organisms are involved infrequently. P aeruginosa  and the HACEK family are the most common examples.

Nosocomial/healthcare-associated infective endocarditis

                Endocarditis may be associated with new therapeutic modalities involving intravascular devices such as central or peripheral intravenous catheters, rhythm control devices such as pacemakers and defibrillators, hemodialysis shunts and catheters, and chemotherapeutic and hyperalimentation lines.  These patients tend to have significant comorbidities, more advanced age, and predominant infection with S aureus. The mortality rate is high in this group.

            The organisms that cause NIE/HCIE obviously are related to the type of underlying bacteremia. The gram-positive cocci (ie, S aureus, CoNS, enterococci, nonenterococcal streptococci) are the most common pathogens.

Fungal endocarditis

             Fungal endocarditis is found in intravenous drug users and intensive care unit patients who receive broad-spectrum antibiotics. Blood cultures are ofteegative, and diagnosis frequently is made after microscopic examination of large emboli.

Risk factors

           The most significant risk factor for IE is residual valvular damage caused by a previous attack of endocarditis.

             Many possible risk factors for the development of pacemaker IE have been described, including diabetes mellitus, age, and use of anticoagulants and corticosteroids. The evidence for these is conflicting. The major risk factor is probably surgical intervention to any part of the pacemaker system, especially elective battery replacements. The rate of infection associated with battery replacements is approximately 5 times that of the initial implantation (6.5% vs 1.4%).

             Other significant risk factors for pacemaker IE include the development of a postoperative hematoma, the inexperience of the surgeon, and a preceding temporary transvenous pacing.

Pathophysiology

             IE develops most commonly on the mitral valve, closely followed in descending order of frequency by the aortic valve, the combined mitral and aortic valve, the tricuspid valve, and, rarely, the pulmonic valve. Mechanical prosthetic and bioprosthetic valves exhibit equal rates of infection.

All cases of IE develop from a commonly shared process, as follows:

1.     Bacteremia (nosocomial or spontaneous) that delivers the organisms to the surface of the valve

2.     Adherence of the organisms

3.     Eventual invasion of the valvular leaflets

 

 

                   The common denominator for adherence and invasion is nonbacterial thrombotic endocarditis, a sterile fibrin-platelet vegetation. The development of subacute IE depends on a bacterial inoculum sufficient to allow invasion of the preexistent thrombus. This critical mass is the result of bacterial clumping produced by agglutinating antibodies.

                 In acute IE, the thrombus may be produced by the invading organism (ie, S aureus) or by valvular trauma from intravenous catheters or pacing wires (ie, NIE/HCIE). S aureus can invade the endothelial cells (endotheliosis) and increase the expression of adhesion molecules and of procoagulant activity on the cellular surface. Nonbacterial thrombotic endocarditis may result from stress, renal failure, malnutrition, systemic lupus erythematosus, or neoplasia.

               The Venturi effect also contributes to the development and location of nonbacterial thrombotic endocarditis. This principle explains why bacteria and the fibrin-platelet thrombus are deposited on the sides of the low-pressure sink that lies just beyond a narrowing or stenosis.

In patients with mitral insufficiency, bacteria and the fibrin-platelet thrombus are located on the atrial surface of the valve. In patients with aortic insufficiency, they are located on the ventricular side. In these examples, the atria and ventricles are the low-pressure sinks. In the case of a ventricular septal defect, the low-pressure sink is the right ventricle and the thrombus is found on the right side of the defect.

                Nonbacterial thrombotic endocarditis may also form on the endocardium of the right ventricle, opposite the orifice that has been damaged by the jet of blood flowing through the defect (ie, the MacCallum patch).

The microorganisms that most commonly produce endocarditis (ie, S aureus; Streptococcus viridans; group A, C, and G streptococci; enterococci) resist the bactericidal action of complement and possess fibronectin receptors for the surface of the fibrin-platelet thrombus. Among the many other characteristics of IE-producing bacteria demonstrated in vitro and in vivo, some features include the following:

• Increased adherence to aortic valve leaflet disks by enterococci, S viridans,and S aureus

• Mucoid-producing strains of S aureus

• Dextran-producing strains of S viridans

• S viridans and enterococci that possess FimA surface adhesin

• Platelet aggregation by S aureus and S viridans and resistance of S aureusto platelet microbicidal proteins

The pathogenesis of pacemaker IE is similar. Shortly after implantation, the development of a fibrin-platelet thrombus (similar to the nonbacterial thrombotic endocarditis described above) involves the generator box and conducting leads. After 1 week, the connective tissue proliferates, partially embedding the leads in the wall of the vein and endocardium. This layer may offer partial protection against infection during a bacteremia.

Bacteremia (either spontaneous or due to an invasive procedure) infects the sterile fibrin-platelet vegetation described above. BSIs develop from various extracardiac types of infection, such as pneumonias or pyelonephritis, but most commonly from gingival disease. Of those with high-grade gingivitis, 10% have recurrent transient bacteremias (usually streptococcal species). Most cases of subacute disease are secondary to the bacteremias that develop from the activities of daily living (eg, brushing teeth, bowel movements).

             The skin is quite resistant to S aureus infection due in great part to its production of antimicrobial peptides. Soong et al discovered that, in vitro, the secretion of alpha toxin by S aureus allows the organism to successfully penetrate the keratinocyte layer. This could explain the presence of staphylococcal bacteremia in the absence of any gross damage to the epithelial layer.

Bacteremia can result from various invasive procedures, ranging from oral surgery to sclerotherapy of esophageal varices to genitourinary surgeries to various abdominal operations. The potential for invasive procedures to produce a bacteremia varies greatly. Procedures, rates, and organisms are as follows:

• Endoscopy – Rate of 0-20%; coagulase-negative staphylococci (CoNS), streptococci, diphtheroids

• Colonoscopy – Rate of 0-20%; Escherichia coli, Bacteroides species

• Barium enema – Rate of 0-20%; enterococci, aerobic and anaerobic gram-negative rods

• Dental extractions – Rate of 40-100%; S viridans

• Transurethral resection of the prostate – Rate of 20-40%; coliforms, enterococci, S aureus

• Transesophageal echocardiography – Rate of 0-20%; S viridans, anaerobic organisms, streptococci

The incidence of nosocomial bacteremias, mostly associated with intravascular lines, has more than doubled in the last few years. Up to 90% of BSIs caused by these devices are secondary to the placement of various types of central venous catheters. Hickman and Broviac catheters are associated with the lowest rates, presumably because of their Dacron cuffs. Peripherally placed central venous catheters are associated with similar rates.

Intravascular catheters are infected from 1 of the following 4 sources:

• Infection of the insertion site

• Infection of the catheter

• Bacteremia arising from another site

• Contamination of the infused solution

Bacterial adherence to intravascular catheters depends on the response of the host to the presence of this foreign body, the properties of the organism itself, and the position of the catheter. Within a few days of insertion, a sleeve of fibrin and fibronectin is deposited on the catheter. S aureus adheres to the fibrin component.

S aureus also produces an infection of the endothelial cells (endotheliosis), which is important in producing the continuous bacteremia of S aureus BSIs. Endotheliosis may explain many cases of persistent methicillin-susceptible S aureus (MSSA) and methicillin-resistant S aureus (MRSA) catheter-related BSIs without an identifiable cause.

S aureus catheter-related BSIs occur even after an infected catheter is removed, apparently attributable to specific virulence factors of certain strains of S aureusthat invade the adjacent endothelial cells. At some point, the staphylococci re-enter the bloodstream, resulting in bacteremia.

Four days after placement, the risk of infection markedly increases. Lines positioned in the internal jugular are more prone to infection than those placed in the subclavian vein. Colonization of the intracutaneous tract is the most likely source of short-term catheter-related BSIs. Among lines in place for more than 2 weeks, infection of the hub is the major source of bacteremia. In some cases, the infusion itself may be a reservoir of infection.

Colonization of heart valves by microorganisms is a complex process. Most transient bacteremias are short-lived, are without consequence, and are ofteot preventable. Bacteria rarely adhere to an endocardial nidus before the microorganisms are removed from the circulation by various host defenses.

Once microorganisms do establish themselves on the surface of the vegetation, the process of platelet aggregation and fibrin deposition accelerate at the site. As the bacteria multiply, they are covered by ever-thickening layers of platelets and thrombin, which protect them from neutrophils and other host defenses. Organisms deep in the vegetation hibernate because of the paucity of available nutrients and are therefore less susceptible to bactericidal antimicrobials that interfere with bacterial cell wall synthesis.

Complications of subacute endocarditis result from embolization, slowly progressive valvular destruction, and various immunological mechanisms. The pathological picture of subacute IE is marked by valvular vegetations in which bacteria colonies are present both on and below the surface.

http://www.sciencedirect.com/science/article/pii/S1054880706000779

 Gross view and drawing of an infective endocarditis of the aortic valve with perforation and tearing of the leaflets in the absence of significant vegetations

 

 

http://www.sciencedirect.com/science/article/pii/S1054880706000779

Infective endocarditis of the aortic valve: (A) vegetations of a bicuspid aortic valve, (B) histology with gram-positive, cocci-like microorganisms

 

 

             The cellular reaction in SBE is primarily that of mononuclear cells and lymphocytes, with few polymorphonuclear cells. The surface of the valve beneath the vegetation shows few organisms. Proliferation of capillaries and fibroblasts is marked. Areas of healing are scattered among areas of destruction. Over time, the healing process falls behind, and valvular insufficiency develops secondary to perforation of the cusps and damage to the chordae tendineae. Compared with acute disease, little extension of the infectious process occurs beyond the valvular leaflets.

levels of agglutinating and complement-fixing bactericidal antibodies and cryoglobulins are markedly increased in patients with subacute endocarditis. Many of the extracardiac manifestations of this form of the disease are due to circulating immune complexes. Among these include glomerulonephritis, peripheral manifestations (eg, Osler nodes, Roth spots, subungual hemorrhages), and, possibly, various musculoskeletal abnormalities. Janeway lesions usually arise from infected microemboli.

            The microscopic appearance of acute bacterial endocarditis differs markedly from that of subacute disease. Vegetations that contaio fibroblasts develop rapidly, with no evidence of repair. Large amounts of both polymorphonuclear leukocytes and organisms are present in an ever-expanding area of necrosis. This process rapidly produces spontaneous rupture of the leaflets, of the papillary muscles, and of the chordae tendineae.

The complications of acute bacterial endocarditis result from intracardiac disease and metastatic infection produced by suppurative emboli. Because of their shortened course, immunological phenomena are not a part of acute IE.

 

Clinic

             In patients with infective endocarditis (IE), the present illness history is highly variable. Symptoms commonly are vague, emphasizing constitutional complaints, or complaints may focus on primary cardiac effects or secondary embolic phenomena. Fever and chills are the most common symptoms; anorexia, weight loss, malaise, headache, myalgias, night sweats, shortness of breath, cough, or joint pains are common complaints as well.

Primary cardiac disease may present with signs of congestive heart failure due to valvular insufficiency. Secondary phenomena could include focal neurologic complaints due to an embolic stroke or back pain associated with vertebral osteomyelitis. As many as 20% of cases present with focal neurologic complaints and stroke syndromes.

                 Dyspnea, cough, and chest pain are common complaints of intravenous drug users. This is likely related to the predominance of tricuspid valve endocarditis in this group and secondary embolic showering of the pulmonary vasculature. A key concern is the distinction between subacute and acute IE. The diagnosis of subacute IE is suggested by a history of an indolent process characterized by fever, fatigue, anorexia, back pain, and weight loss. Less common developments include a cerebrovascular accident or congestive heart failure. The patient should be questioned about invasive procedures and recreational drug use that may be causing the bacteremia. Most subacute disease caused by S viridans infection is related to dental disease. Most cases are not caused by dental procedures but by transient bacteremias secondary to gingivitis. In 85% of patients, symptoms of endocarditis appear within 2 weeks of dental or other procedures.

                The interval between the onset of disease and diagnosis averages approximately 6 weeks. The fact that less than 50% of patients have previously diagnosed underlying valvular disease significantly limits the effectiveness of antibiotic prophylaxis. Acute IE is a much more aggressive disease. The patient notices an acute onset of high-grade fevers and chills and a rapid onset of congestive heart failure. Again, a history of antecedent procedures or illicit drug use must be investigated.

                The distinction between these 2 polar types of IE has become less clear. Intermittent use of antibiotics aimed at treating misdiagnosed endocarditis can suppress bacterial growth within the valvular thrombus, giving rise to the state of muted IE. This is often the case iosocomial infective endocarditis (NIE; also referred to as healthcare-associated IE [HCIE]), which commonly manifests with elements of a sepsis syndrome (ie, hypotension, metabolic acidosis fever, leukocytosis, and multiple organ failure).

The source of the bacteremia may be an infection in another organ (eg, pneumonia, pyelonephritis) or in a central venous catheter. Most often, these patients are in the intensive care unit. Approximately 45% of cases of NIE/HCIE occur in patients with prosthetic valves. Muted IE due to S aureus infection may resemble IE that results from S viridans infection.

 

Subacute native valve endocarditis

             The symptoms of early subacute native valve endocarditis (NVE) are usually subtle and nonspecific. They include low-grade fever (absent in 3-15% of patients), anorexia, weight loss, influenzalike syndromes, polymyalgia-like syndromes, pleuritic pain, syndromes similar to rheumatic fever (eg, fever, dulled sensorium as in typhoid, headaches), and abdominal symptoms (eg, right upper quadrant pain, vomiting, postprandial distress, appendicitis-like symptoms).

            When appropriate therapy is delayed for weeks or months, additional clinical features, embolic or immunological in origin, develop.

Signs and symptoms secondary to emboli include acute meningitis with sterile spinal fluid, hemiplegia in the distribution of the middle cerebral artery, regional infarcts that cause painless hematuria, infarction of the kidney or spleen, unilateral blindness caused by occlusion of a retinal artery, and myocardial infarction arising from embolization of a coronary artery.

              The emboli of right-sided IE commonly produce pulmonary infarcts. The rate of embolization is related to the organism, the size of the vegetation and its rate of growth or resolution, and its location.

             The vegetations of S aureus, Haemophilus influenzae, H parainfluenzae, and the fungi are much more likely to embolize than those of S viridans. Those larger than 10 mm in diameter and mobile or prolapsing have a high rate of embolization. A vegetation that grows during therapy is associated with a significant increase in the risk of embolization but with the persistence of bacteremia.

             Clinically separating the importance of the absolute size and the rate of change in the size of the vegetation from the causative organism is difficult. The vegetations of the mitral valve are much more likely to embolize than those in any other location. The risk of embolization markedly decreases after 1 week of appropriate antibiotic therapy.

The deposition of circulating immune complexes in the kidney may produce interstitial nephritis or proliferative glomerulonephritis, with renal failure progressing to the point of uremia at the time of the patient’s presentation. Similarly, various musculoskeletal symptoms (44% of patients) arise from immunologically mediated synovitis.

                Osler nodes and Roth spots arise from immune-mediated vasculitis. Patients may experience palpitations, ie, the symptoms of an immune-mediated myocarditis.

             The origin of lumbosacral back pain in patients with subacute IE (15%) is unclear but probably results from the deposition of immune complexes in the disk space. However, antibiotic therapy rapidly abolishes these symptoms. In 50% of patients with cerebral emboli, this event is the first manifestation of IE and is associated with a 2- to 4-times higher mortality rate. Stroke in younger people should always raise the possibility of underlying IE.

Bacteria-free infective endocarditis

                   Rarely observed today, the bacteria-free state of IE is one in which patients have multiple negative blood culture results in the presence of severe congestive heart failure, renal failure, multiple sterile emboli, massive splenomegaly, severe anemia, brown facial pigmentation, bilateral thigh pain, and massive leg edema. These patients are usually afebrile. This process appears to indicate prolonged and unchecked stimulation of the immune system.

Acute infective endocarditis

                 The clinical symptoms of acute IE result from either embolic or intracardiac suppurative complications. The onset of illness is abrupt, with rapidly progressive destruction of the infected valve (see the images below). The valvular leaflets are quickly destroyed by bacteria that multiply rapidly within the ever-growing friable vegetations. Complications develop within a week. These include the dyspnea and fatigue of severe congestive heart failure and a wide spectrum of neuropsychiatric complications resulting from CNS involvement.

 

http://emedicine.medscape.com/article/216650-clinical

Acute bacterial endocarditis caused by Staphylococcus aureus with perforation of the aortic valve and aortic valve vegetations

 

 

 

Acute bacterial endocarditis caused by Staphylococcus aureus with aortic valve ring abscess extending into myocardium

 

 

Intravenous-drug-abuse infective endocarditis

                 Patients with right-sided intravenous drug abuse (IVDA) IE (53% of cases) frequently present with pleuropulmonary (pneumonia and/or empyema) manifestations. Symptoms due to metastatic infection develop early in a disease course caused by S aureus. Right-sided disease is associated with a low rate of congestive heart failure and valvular perforation.

Infection with P aeruginosa has a high rate of neurological involvement, with 2 distinctive features:

1.     mycotic aneurysms with a higher-than-average rate of rupture

2.     panophthalmitis (10% of patients).

The course of infection with P aeruginosa is much slower than that of S aureus.

The course of left-sided IVDA IE is similar to that of non-IVDA disease.

Approximately 5-8% of febrile individuals who abuse intravenous drugs have underlying IE. Many users of illicit drugs may lose their fever within a few hours of hospitalization. This phenomenon, termed cotton wool fever, is probably caused by the presence of adulterants contained within the injected drugs.

Prosthetic valve endocarditis

                 Clinical features of prosthetic valve endocarditis (PVE) closely resemble those of NVE. Early PVE is defined as infection occurring within 60 days of valve implantation; late PVE occurs after this period. For valvular infection with coagulase-negative staphylococci (CoNS), this division should be extended to 12 months.

Congestive heart failure occurs earlier and is more severe in persons with PVE. The patient may present with symptoms of myocarditis or pericarditis. The rate of embolic stroke is high in the first 3 days of PVE.

Pacemaker infective endocarditis

                 The clinical presentation in a person with a pacemaker infection and pacemaker IE depends on several factors, including the site of infection (eg, generator pocket vs intravascular leads or epicardial leads), the type of organism, and the origin of the infection (eg, pocket erosion, localized infection of the generator pocket, bacteremia from a remote site).

Early infections, within a few months of implantation, manifest as acute or subacute infections of the pulse-generator pocket. Bacteremia may be present even in the absence of clinical signs and symptoms. Fever is the most common finding and may be the only finding in approximately 33% of patients.

Late infections of the pocket may be due to erosion of the overlying skin without systemic involvement. Such erosions always indicate infection of the underlying device.

The most significant late infections involve the transvenous or epicardial leads. With epicardial infection, signs and symptoms of pericarditis or mediastinitis may be present along with bacteremia. Infection of the transvenous electrode produces signs and symptoms of right-sided endocarditis. Those that occur early after implantation (33% of cases) show prominent systemic signs of infection, often with obvious localization to the pacemaker pocket.

Late infections have much more subtle manifestations. They may occur up to several years after implantation or reimplantation.

Fever is almost universal in persons with pacemaker IE. Signs of right-sided endocarditis (ie, pneumonia, septic emboli) are observed in up to 50% of patients.

 Nosocomial infective endocarditis

NIE commonly manifests with elements of a sepsis syndrome (ie, hypotension, metabolic acidosis fever, leukocytosis, and multiple organ failure). The source of bacteremia may develop from an infection in another organ (eg, pneumonia, pyelonephritis) or from a central venous catheter. Most often, these patients are in the intensive care unit.

Approximately 45% of cases of NIE/HCIE occur in patients with prosthetic valves.

 

Clinical symptoms

               Fever, possibly low-grade and intermittent, is present in 90% of patients.

             Heart murmurs are heard in approximately 85% of patients. Change in the characteristics of a previously noted murmur occurs in 10% of these patients and increases the likelihood of secondary congestive heart failure.

One or more classic signs of IE are found in as many as 50% of patients. They include the following:

• Petechiae – Common but nonspecific finding

• Subungual (splinter) hemorrhages – Dark red linear lesions in the nailbeds.

 

http://www.aafp.org/afp/2010/0601/p1375.html

 

 

• Osler nodes – Tender subcutaneous nodules usually found on the distal pads of the digits.

 

 

http://wacdocs.csp.uwa.edu.au/category/internal–medicine/page/3/

http://handfacts.wordpress.com/tag/osler–nodes/

 

 

 

• Janeway lesions – Nontender maculae on the palms and soles are nontender, erythematous, hemorrhagic, or pustular lesions.

http://www.ijdvl.com/article.asp?issn=0378-6323;year=2013;volume=79;issue=1;spage=136;epage=136;aulast=Reddy

 

• Roth spots – Retinal hemorrhages with small, clear centers; rare and observed in only 5% of patients.A middle-aged man with a history of intravenous drug use who presented with severe myalgias and a petechial rash. He was diagnosed with right-sided staphylococcal endocarditis.

 

http://vps.transpl.ru/inf.html

 

                Signs of neurologic disease occur in as many as 40% of patients. Embolic stroke with focal neurologic deficits is the most common etiology. Other etiologies include intracerebral hemorrhage and multiple microabscesses.

Signs of systemic septic emboli are due to left heart disease and are more commonly associated with mitral valve vegetations. Multiple embolic pulmonary infections or infarctions are due to right heart disease.

                 Signs of congestive heart failure, such as distended neck veins, frequently are due to acute left-sided valvular insufficiency.

Splenomegaly may be present.

Other signs include the following:

• Stiff neck

• Delirium

• Paralysis, hemiparesis, aphasia

• Conjunctival hemorrhage

• Pallor

• Gallops

• Rales

• Cardiac arrhythmia

• Pericardial rub

• Pleural friction rub

Subacute infective endocarditis

               Approximately 3-15% of patients with subacute IE (primarily elderly and chronically ill individuals) have normal or subnormal temperatures. The vast majority of patients have detectable heart murmurs. The presence of a murmur is so common (99% of cases) that its absence should cause clinicians to reconsider the diagnosis of IE. The major exception is right-sided IE, in which only one third of patients have a detectable murmur.

Because many of these murmurs are hemodynamically insignificant and have been present for years, their role in the patient’s illness may be underestimated. The saying “a changing murmur is extremely helpful in diagnosing subacute IE” is a myth. Only 15% do so early in the course of infection.

The peripheral lesions of subacute IE are observed in only approximately 20% of patients, compared with 85% in the preantibiotic era. Currently, the most common of these is petechiae. They may occur on the palpebral conjunctivae, the dorsa of the hands and feet, the anterior chest and abdominal walls, the oral mucosa, and the soft palate.

          Subungual hemorrhages (ie, splinter hemorrhages) are linear and red. They are usually caused by workplace trauma to the hands and feet rather than by valvular infection. Hemorrhages that do not extend for the entire length of the nail are more likely the result of infection rather than trauma.

            Osler nodes are smallish tender nodules that range from red to purple and are located primarily in the pulp spaces of the terminal phalanges of the fingers and toes, soles of the feet, and the thenar and hypothenar eminences of the hands. Their appearance is often preceded by neuropathic pain. They last from hours to several days. They remain tender for a maximum of 2 days. The underlying mechanism is probably the circulating immunocomplexes of subacute IE. They have been described in various noninfectious vasculitides.

               Clubbing of fingers and toes was found almost universally, but it is now observed in less than 10% of patients. It primarily occurs in those patients who have an extended course of untreated IE.

The arthritis associated with subacute IE is asymmetrical and is limited to 1-3 joints. Clinically, it resembles the joint changes found in patients with rheumatoid arthritis, Reiter syndrome, or Lyme disease. The fluid is usually sterile.

              Splenomegaly is observed more commonly in patients with long-standing subacute disease. It may persist long after successful therapy.

Roth spots are retinal hemorrhages with pale centers. The Litten sign represents cotton-wool exudates.

Acute infective endocarditis

             In approximately one third of patients with acute IE, murmurs are absent. The most common type is an aortic regurgitation murmur. Because of the suddenness of onset, the left ventricle does not have a chance to dilate. In this situation, the classic finding of increased pulse pressure in significant valvular insufficiency is absent.

Fever is always present, and it usually is high.

Janeway lesions are irregular erythematosus and painless macules (1-4 mm in diameter). They most often are located on the thenar and hypothenar eminences of the hands and feet. They usually represent an infectious vasculitis of acute IE resulting from S aureus infection.

Acute septic monoarticular arthritis in patients with acute IE most often is caused by S aureus infection.

Purulent meningitis may be observed in patients with acute IE, compared with the aseptic type observed in patients with subacute disease. Other neurological findings are similar to those observed in patients with subacute disease.

Complications

The following are potential complications of IE:

• Myocardial infarction, pericarditis, cardiac arrhythmia

• Cardiac valvular insufficiency

• Congestive heart failure

• Sinus of Valsalva aneurysm

• Aortic root or myocardial abscesses

• Arterial emboli, infarcts, mycotic aneurysms

• Arthritis, myositis

• Glomerulonephritis, acute renal failure

• Stroke syndromes

• Mesenteric or splenic abscess or infarct

Congestive heart failure due to aortic valve insufficiency is the most common intracardiac complication of subacute endocarditis. It develops after months of untreated disease but may occur a full year following microbiological cure.

The complication of arterial embolization is second in frequency to congestive heart failure for both subacute and acute IE. The frequency of this complication has decreased, from 80% in the preantibiotic era to 15-35% today. The emboli are usually sterile because of the minimally invasive nature of the causative organisms (eg, S viridans).

The persons most at risk are younger (20-40 y), have mitral or aortic valve (native or prosthetic) involvement, and are infected with certain organisms such as Candida or Aspergillus species, S aureus, Haemophilus parainfluenzae, group B streptococci, and nutritionally variant streptococci.

The prevalence of embolization appears to be the same for both types of disease. The most common areas of deposition include the coronary arteries, kidneys, brain, and spleen. Infarction at the site of embolization is common; abscess formation is not. Cerebral emboli occur in 33% of patients. The middle cerebral artery is involved most often.

Other neurological embolic damage includes cranial nerve palsies, cerebritis, and mycotic aneurysms caused by weakening of the vessel walls and produced by embolization to the vasa vasorum. Mycotic aneurysms may occur in the abdominal aorta and the splenic, coronary, and pulmonary arteries.

                In acute IE, the frequency of aneurysms and other suppurative intracardiac complications is high. In addition to valvular insufficiency, other intracardiac complications of acute IE include (1) aortocardiac and other fistulas, (2) aneurysms of the sinus of Valsalva, (3) intraventricular abscesses, (4) ring abscesses, (5) myocardial abscesses, (6) mycotic aneurysms, (7) septic coronary arterial emboli, and (8) pericarditis.

             In patients with acute disease, especially disease caused by S aureus infection,emboli almost inevitably lead to abscesses in the areas where they are deposited. Multiple abscesses can occur in almost every organ, including the kidneys, heart, and brain. Mycotic aneurysms may occur in almost any artery. Paradoxically, they are less common in patients with acute IE.

 

Diagnostic criteria

Definitive diagnosis of infective endocarditis (IE) is generally made by using the Duke criteria.

Duke diagnostic criteria

Durack and colleagues developed diagnostic criteria that combine the clinical, microbiological, pathological, and echocardiographic characteristics of a specific case.

Major blood culture criteria include the following:

• Two blood cultures positive for organisms typically found in patients with IE (ie, S viridans, Streptococcus bovis, a HACEK group organism, community-acquired S aureus, or enterococci in the absence of a primary focus)

• Blood cultures persistently positive for one of the above organisms from cultures drawn more than 12 hours apart

• Three or more separate blood cultures drawn at least 1 hour apart

Major echocardiographic criteria include the following:

• Echocardiogram positive for IE, documented by an oscillating intracardiac mass on a valve or on supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomical explanation

• Myocardial abscess

• Development of partial dehiscence of a prosthetic valve

• New-onset valvular regurgitation

Minor criteria include the following:

• Predisposing heart condition or intravenous drug use

• Fever of 38°C (100.4°F) or higher

• Vascular phenomenon, including major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, or Janeway lesions

• Immunological phenomenon such as glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor

• Positive blood culture results not meeting major criteria or serologic evidence of active infection with an organism consistent with IE (eg, Brucella, C burnetii [ie, Q fever], Legionella)

• Echocardiogram results consistent with IE but not meeting major echocardiographic criteria

Definitive pathological diagnosis is established by demonstrating microorganisms, by culture or histology, in vegetations removed by surgery, embolectomy, or drainage of an intracardiac abscess. Alternatively, a definitive clinical diagnosis is made based on the presence of 2 major criteria, 1 major criterion and 3 minor criteria, or by 5 minor criteria.

A diagnosis of possible IE is made when findings consistent with IE fall short of the criteria for definite IE but do not meet the criteria for rejection.

Rejection criteria for the diagnosis of IE are as follows:

• The presence of a firm alternative diagnosis of the manifestations of endocarditis

• Resolution of manifestations of endocarditis after 4 or fewer days of antimicrobial therapy

• No pathologic evidence of IE at surgery or autopsy after 4 or fewer days of antimicrobial therapy

These criteria may, at times, overdiagnose IE and may not be as applicable in patients with subacute disease.

Diagnostic procedures

Blood Culture

            The criterion standard test for diagnosing IE is the documentation of a continuous bacteremia (>30 min in duration) based on blood culture results.

Exceptions are observed in patients with prosthetic valve endocarditis (PVE) and right-sided IE. About 5-10% of patients with IE have false-negative blood culture results. Prior use of antibiotics is the most common cause of false-negative blood culture results. Other causes include fastidious organisms and inadequate blood volume; a blood-to-broth ratio of 1:10 is needed. Currently, with modern automated blood culture systems, fastidious organisms such as nutritionally variant streptococci and members of the HACEK group rarely cause culture-negative IE.

              As many as 50% of positive blood culture results have been estimated to be falsely positive. This rate has probably decreased, but false-positive blood culture results remain a major diagnostic challenge. One such result can lead to 4 days of unnecessary patient hospitalization.

The significance of positive blood culture results correlates with the following:

• The type of organism

• The clinical setting (coagulase-negative staphylococci [CoNS] are significant in patients with prosthetic valves but not in those with native valves)

• Multiple blood cultures positive for the same organism

• Shorter incubation time for recovery

• The degree of severity of clinical illness

Procedure

             Never draw only 1 set of blood cultures; 1 is worse thaone. Two sets of blood cultures have greater than 90% sensitivity when bacteremia is present. Three sets of cultures improve sensitivity and may be useful when antibiotics have been administered previously.

             The AHA (endorsed by IDSA) 2010 guideline update on CIED infections and their management recommends drawing at least 2 sets of blood cultures at evaluation before starting antimicrobial therapy.

For diagnosing subacute IE, draw 3-5 sets of blood cultures over 24 hours. This helps detect 92-98% of cases in patients who have not recently received antibiotics. In the case of acute IE, 3 sets may be drawn over 30 minutes (with separate venipunctures) to help document a continuous bacteremia.

             Using various types of blood culture bottles (with resins added to interfere with antibiotic action) probably has little advantage. Some of these may interfere with bacterial growth.

When blood culture results fail to show an infectious agent after blood is drawn 48 hours after antibiotic therapy has been stopped, the second set of blood for cultures must be drawn approximately 7 days later. If these later culture results remaiegative, the diagnosis of IE must be reconsidered. In general, blood for culture should not be drawn through intravenous (IV) lines unless this is part of an approach for diagnosing line infection.

Catheter infection

           The diagnosis of catheter infection may be made in 1 of 2 ways. Culturing the device via the roll-plate semiquantitative method is the most common approach but requires a catheter removal. In the case of long-term catheters, blood may be drawn simultaneously through the line and the peripheral vein. If it is impossible to draw blood from a peripheral vein in the presence of a multilumen catheter, one sample may be obtained through each of 2 catheter lumens.

            In a catheter infection, the colony count of the sample obtained from the suspected port is 3-fold greater than that drawn from a peripheral vein or from another port of the catheter. Retrieval of organisms from blood drawn from a catheter hub at least 2 hours earlier before their growth is detected in the blood obtained from peripheral vein meets the differential time to positivity criteria of a catheter infection.

A sterile culture of the insertion site has a highly negative predictive value for line infection.

Culture-negative infective endocarditis

             Approximately 5% of cases of possible IE yield negative blood culture results (ie, culture-negative IE). Patients with culture-negative IE occasionally present with signs and symptoms highly suggestive of IE, but the blood cultures remaiegative.

Culture-negative IE may have noninfectious causes (eg, vasculitis) or may be caused by fastidious organisms. Modern blood culture systems recover the vast majority of pathogens within 4-5 days, including members of the HACEK group and Abiotrophia species. Overall, the most common cause of culture-negative IE is prior antimicrobial therapy that can suppress bacterial growth within the vegetation but is insufficient to eliminate the valvular infection.

In certain populations, infections with Coxiella burnetii (in southern France and Israel) and Bartonella species (among homeless persons) have become more frequent causes of culture-negative IE. The blood culture results in fungal valvular infections are often sterile. In S aureus IE, the blood cultures results may be negative when the organism burrows deep within the thrombus, leaving the surface of the valvular thrombus sterile (surface sterilization).

Valvular vegetations may be detected during cardiac ultrasonographic examinations, but the blood culture results are persistently negative. In this situation, 3 separate blood cultures spaced over a 24-hour period are usually sufficient to detect microorganisms in the blood. Additional blood cultures are not usually helpful.

Many pathogens once considered to be fastidious are no longer classified as such (see above). Bartonella, Legionella, and C burnetii remain significant causes of culture-negative IE. These require special culture media or a prolonged incubation period for retrieval.

Serology for Chlamydia, Q fever (C burnetii), and Bartonella may be useful in culture-negative endocarditis. Serologic tests are often the most practical means for diagnosing valvular infection with fastidious organisms (eg, C burnetii andChlamydia, Brucella, and Legionella species). Buffered charcoal and yeast agar are required for the isolation of Legionella. Brucella species require up to 6 weeks. Thuny et al have developed an algorithm for the workup of negative blood cultures. The first stage is to obtain serologies for Q fever and Bartonella. Rheumatoid factor and antinuclear antibody testing is performed to rule out rheumatologic diseases. If testing is negative, then a dedicated PCR for Bartonella species and T whippleishould be performed as well as a broad range PCR for the detection of fungi, especially in the setting of a prosthetic valve. If there is no yield from this second tier, especially with a history of antecedent antibiotic therapy, then a Septifast blood PCR should be performed to detect any staphylococci. In addition, serologic testing for Mycoplasma pneumoniae, Legionella pneumophila and Brucella melitensis should be carried out.

Fungal infective endocarditis

             Most types of fungal IE have a low rate of positive blood culture results. At best, only 50% of Candida species are associated with positive blood culture results.Histoplasma and Aspergillus are almost never retrieved from the bloodstream. Fungal endocarditis must always be considered in the clinical setting of culture-negative IE that fails to respond to appropriate antibiotic therapy.

Pacemaker infective endocarditis

                Establishing the diagnosis of pacemaker IE is difficult because of its subtle presentation, especially late-onset disease. The addition of pocket infection and the presence of pulmonary emboli to the Duke criteria have increased the rate of diagnosis from 16% to 87.5% of cases. Fever and/or a positive blood culture result without evidence of a primary source in patients with a pacemaker or implantable cardioverter-defibrillator should be considered to represent device-associated IE until proven otherwise.

The AHA 2010 guideline update on CIED infections recommends that, when the CIED is explanted, culture of the lead-tip and Gram stain and culture of the generator-pocket tissue be obtained. However, percutaneous aspiration of the generator pocket should not be performed for diagnostic evaluation of CIED infection.

Echocardiography

               Echocardiography has become the indirect diagnostic method of choice, especially in patients who present with a clinical picture of IE but who have nondiagnostic blood culture results (eg, some patients with fungal endocarditis). The diagnosis of IE caever be excluded based oegative echocardiogram findings, either from TTE or from TEE.

              Echocardiography has become the indirect diagnostic method of choice, especially in patients who present with a clinical picture of IE but who have nondiagnostic blood culture results (eg, some patients with fungal endocarditis). The diagnosis of IE caever be excluded based oegative echocardiogram findings, either from TTE or from TEE.

The AHA 2010 guideline update on CIED infections recommends TEE to evaluate the left-sided heart valves for all adults suspected of having CIED-related endocarditis, even if TTE has shown lead-adherent masses. If TTE views are good, TTE may be sufficient for pediatric patients. Patients with positive blood culture results or negative blood culture results taken after recent antimicrobial therapy should undergo TEE for CIED infection or valvular endocarditis.

Visible vegetation suggests a worse prognosis. Both TTE and TEE are highly specific for valvular vegetations; however, sensitivity differs.

            TTE (see the image below) has generally had a sensitivity of approximately 60% for identification of valvular lesions in patients with native valve endocarditis (NVE). However, sensitivity was as high as 82% in a recent series where advanced harmonic imaging and digital processing techniques were used. TTE has a sensitivity of only 20% in patients with PVE.

This is a magnified portion of a parasternal long axis view from a transthoracic echocardiogram. There is a small curvilinear vegetation on the mitral valve as indicated. The patient presented with a headache and fever, and CT scan of the brain revealed an occipital hemorrhage. The patient had a history of intravenous drug use and multiple blood cultures grew Staphylococcus aureus.

 

               TEE was developed to overcome the problems in visualizing prosthetic valve thrombi and right-sided events. TEE eliminates the need for the operator to find a clear field for the beam. The use of higher-frequency waveforms is permitted because of the decreased distance between the heart and the probe. The sensitivity of TEE in detecting the vegetations of NVE is 90-100%. In patients with PVE, the sensitivity of TEE under optimal circumstances is greater than 90%.

             TEE successfully visualizes vegetations of the leads or of the tricuspid valve in more than 90% of cases of pacemaker IE, compared with less than the 50% achieved by TTE.

              Neither TEE nor TTE should be used for screening purposes (ie, patients with fever of unknown origin or those with positive blood culture results and no other signs or symptoms of IE), because nearly 60% of vegetations revealed are sterile. Approximately 15% of positive study results are false-positives because the images are, in reality, not those of vegetations but of thickened valves, nodules, or valvular calcifications.

Echocardiography is useful for predicting the potential complications of IE, especially those that are embolic iature.

Echocardiographic predictors of systemic embolization in patients with IE are the following:

• Large valvular vegetations (>10 mm in diameter)

• Multiple vegetations

• Mobile but pedunculated vegetations

• Noncalcified vegetations

• Vegetations that are increasing in size

• Prolapsing vegetations

Echocardiography is also highly useful for detecting abscesses. As with valvular lesions, the transesophageal technique is generally more sensitive.^[67]

In summary, the indications for performing echocardiography with Doppler in patients with IE are to provide a baseline in proven or highly suggestive cases of IE and to provide a means of documenting complications during therapy.

In most cases, TTE is sufficient. TEE is indicated when mechanical prosthetic valves are present; to detect right-sided lesions; and to visualize myocardial abscesses. Because of the endoscopic portion of the test, TEE carries the risk factor of inducing bacteremias. Approximately 15% of cases of IE do not demonstrate any detectable vegetations at the time of the echocardiographic study.

Ultrasonography

              Two-dimensional cardiac Doppler ultrasound testing has been a significant advance for diagnosing and evaluating IE. It provides information about the presence and size of vegetations, which helps in diagnosis and, to some extent, in predicting embolization.

TTEs are more sensitive for detecting anterior myocardial abscesses and quantitating the degree of valvular dysfunction.

             The Doppler method can detect distorted blood flow and certain types of cardiac pathology not otherwise visualized by standard echocardiography. It is good for visualizing jet lesions and differentiating cusp perforation from valvular insufficiency.The combination of TEE and color Doppler is excellent for detecting intracardiac fistulas. The resolution of either TEE or TTE in real life is approximately 2 mm.

             Conditions that are positively related to the detection of valvular thrombi are the location (ie, right-sided structures are poorly visualized, especially by TTE); disease lasting longer than 2 weeks; abscesses of the valves or myocardium; and aneurysms of the sinus of Valsalva.

Radiography

Pulmonary embolic phenomena on radiographs strongly suggest tricuspid disease .

 

A young adult with a history of intravenous drug use, endocarditis involving the tricuspid valve with Staphylococcus aureus, and multiple septic pulmonary emboli. Pulmonary lesions on chest radiograph are most prominent in the right upper lobe with both solid and cavitary appearance.

 

Multiple embolic pyogenic abscesses may be visualized:

A young adult with a history of intravenous drug use diagnosed with right-sided staphylococcal endocarditis and multiple embolic pyogenic abscesses on chest radiograph.

 

                   Ventilation/perfusion scanning may be useful in right-sided endocarditis.

                 Electrocardiography may help detect the 10% of patients who develop a conduction delay during IE by documenting an increased P-R interval. Nonspecific changes are common. First-degree atrioventricular (AV) block and new interventricular conduction delays may signal septal involvement in aortic valve disease; both are poor prognostic signs.

Catheterization of the heart is rarely required for the diagnosis of IE or any of its complications, though it may be indicated to determine the degree of valvular damage. The findings from echocardiography correlate well with the findings from cardiac catheterization. The characteristic findings of IE are intravascular endocardial vegetations that contain microorganisms surrounded by fibrin and platelets.

                 Various radionuclide scans using, for example, gallium (Ga)-67–tagged white cells and indium (In)-111–tagged white cells, have proven to be of little use in diagnosing IE. Radionuclide scans of the spleen are useful to help rule out a splenic abscess, which is a cause of bacteremia that is refractory to antibiotic therapy.

                    A computed tomography (CT) scan of the head should be obtained in patients who exhibit central nervous system (CNS) symptoms or findings consistent with a mass effect (eg, macroabscess of the brain). This imaging modality has proven most useful for localizing abscesses. With new advanced multislice techniques, CT caow also be used to identify valvular abnormalities and vegetations.

Treatment

The penicillins, often in combination with gentamicin, remain the cornerstones of therapy for endocarditis caused by penicillin-susceptible streptococci. For penicillin-allergic patients, vancomycin is substituted. IV ceftriaxone (Rocephin), given once daily for 4 weeks, is another option, and even a 2-week course in combination with gentamicin has proven successful. However, short-term therapy is not indicated for patients who have PVE, major embolic complications, or symptoms for longer than 2 months. Furthermore, in this study, 24% of patients required urgent valvular heart surgery within 1 to 5 weeks after beginning treatment. Therefore, careful follow-up is essential, especially for patients who leave the hospital to complete antibiotic therapy at home.

 

Treatment of Endocarditis Caused by Penicillin-Sensitive Streptococci