Congenital heart disease

Congenital heart disease refers to a problem with the heart's structure and function due to abnormal heart development before birth. Congenital means present at birth.

Causes
Congenital heart disease (CHD) can describe a number of different problems affecting the heart. It is the most common type of birth defect. Congenital heart disease is responsible for more deaths in the first year of life than any other birth defects. Many of these defects need to be followed carefully. Some heal over time, others will require treatment. Congenital heart disease is often divided into two types: cyanotic (blue discoloration caused by a relative lack of oxygen) and non-cyanotic. The following lists cover the most common of the congenital heart diseases: Cyanotic:

Tetralogy of Fallot Transposition of the great vessels Tricuspid atresia Total anomalous pulmonary venous return Truncus arteriosus Hypoplastic left heart Pulmonary atresia Some forms of total anomalous pulmonary venous return Ebstein's anomaly

Non-cyanotic:

Ventricular septal defect (VSD) Atrial septal defect (ASD) Patent ductus arteriosus (PDA) Aortic stenosis Pulmonic stenosis Coarctation of the aorta Atrioventricular canal (endocardial cushion defect)

These problems may occur alone or together. The majority of congenital heart diseases occurs as an isolated defect and is not associated with other diseases. However, they can also be a part of various genetic and chromosomal syndromes such as Down syndrome, trisomy 13, Turner syndrome, Marfan syndrome, Noonan syndrome, and DiGeorge syndrome.

No known cause can be identified for most congenital heart defects. Congenital heart diseases continue to be investigated and researched. Drugs such as retinoic acid for acne, chemicals, alcohol, and infections (such as rubella) during pregnancy can contribute to some congenital heart problems.

Symptoms
Symptoms depend on the specific condition. While congenital heart disease is present at birth, the symptoms may not be immediately obvious. Defects such as coarctation of the aorta may not cause problems for many years. Other problems, such as a small ventricular septal defect (VSD), may never cause any problems, and some people with a VSD have normal physical activity and a normal life span.

Prevention
Avoid alcohol and other drugs during pregnancy. Doctors should be made aware that a woman is pregnant before prescribing any medications for her. A blood test should be done early in the pregnancy to see if the woman is immune to rubella. If the mother is not immune, she must avoid any possible exposure to rubella and should be immunized immediately following delivery. Poorly controlled blood sugar levels in women who have diabetes during pregnancy are also associated with a high rate of congenital heart defects during pregnancy. Experts believe that some prescription and over-the-counter medications and street drugs used during pregnancy increase the risk of heart defects. There may be some hereditary factors that play a role in congenital heart disease. Genetics does appear to play a role in many diseases, and multiple family members may be affected. Talk to your health care provider about screening. Expectant mothers should receive good prenatal care. Many congenital defects can be discovered on routine ultrasound examinations performed by an obstetrician. The delivery can then be anticipated and the appropriate medical personnel (such as a pediatric cardiologist, a cardiothoracic surgeon, and a neonatologist) can be present, and ready to help as necessary. Such preparation can mean the difference between life and death for some babies.

Rheumatic fever (RF) is a systemic illness that may occur following group A beta hemolytic streptococcal (GABHS) pharyngitis in children. Rheumatic fever and its most serious complication, rheumatic heart disease (RHD), are believed to result from an autoimmune response; however, the exact pathogenesis remains unclear. Studies in the 1950s during an epidemic on a military base demonstrated 3% incidence of rheumatic fever in adults with streptococcal pharyngitis not treated with antibiotics.[1] Studies in children during the same period demonstrated an incidence of only 0.3%. The current incidence of rheumatic fever after GABHS infection is now thought to have decreased to less than 1%. Cardiac involvement is reported to occur in 30-70% of patients with their first attack of rheumatic fever and in 73-90% of patients when all attacks are counted. Clinical manifestations and time course of acute rheumatic fever are shown in the image below.

Pathophysiology
Rheumatic fever develops in children and adolescents following pharyngitis with GABHS (ie, Streptococcus pyogenes). The organisms attach to the epithelial cells of the upper respiratory tract and produce a battery of enzymes, which allows them to damage and invade human tissues. After an incubation period of 2-4 days, the invading organisms elicit an acute inflammatory response, with 3-5 days of sore throat, fever, malaise, headache, and elevated leukocyte count. In a small percent of patients, infection leads to rheumatic fever several weeks after the sore throat has resolved. Only infections of the pharynx initiate or reactivate rheumatic fever. Direct contact with oral (PO) or respiratory secretions transmits the organism, and crowding enhances transmission. Patients remain infected for weeks after symptomatic resolution of pharyngitis and may serve as a reservoir for infecting others. Penicillin treatment shortens the clinical course of streptococcal pharyngitis and more importantly prevents the major sequelae. GABHS organisms are gram-positive cocci, which frequently colonize the skin and oropharynx. These organisms may cause suppurative diseases (eg, pharyngitis, impetigo, cellulitis, myositis, pneumonia, puerperal sepsis). GABHS

organisms also may be associated with nonsuppurative diseases (eg, rheumatic fever, acute poststreptococcal glomerulonephritis). Group A streptococci (GAS) elaborate the cytolytic toxins, streptolysins S and O. Of these 2 toxins, streptolysin O induces persistently high antibody titers that provide a useful marker of GAS infection and its nonsuppurative complications. GAS, as identified using the Lancefield classification, has a group A carbohydrate antigen in the cell wall that is composed of a branched polymer of L-rhamnose and N-acetyl-D-glucosamine in a 2:1 ratio. Surface proteins on the cell wall of the organism may subserotype GAS. The presence of the M protein is the most important virulence factor for GAS infection in humans. More than 120 M protein serotypes or M protein genotypes have been identified,[20] some of which have a long terminal antigenic domain (ie, epitopes) similar to antigens in various components of the human heart. Rheumatogenic strains are often encapsulated mucoid strains, rich in M proteins, and resistant to phagocytosis. These strains are strongly immunogenic, and anti-M antibodies against the streptococcal infection may cross-react with components of heart tissue (ie, sarcolemmal membranes, valve glycoproteins). Currently, emm typing is felt to be more discriminating than M typing.[20] Acute RHD often produces a pancarditis, characterized by endocarditis, myocarditis, and pericarditis. Endocarditis is manifested as mitral and aortic valve insufficiency. Severe scarring of the valves develops during a period of months to years after an episode of acute rheumatic fever, and recurrent episodes may cause progressive damage to the valves. The mitral valve is affected most commonly and severely (65-70% of patients); the aortic valve is affected second most commonly (25%). The tricuspid valve is deformed in only 10% of patients, almost always in association with mitral and aortic lesions, and the pulmonary valve is rarely affected. Severe valve insufficiency during the acute phase may result in congestive heart failure (CHF) and even death (1% of patients). Whether myocardial dysfunction during acute rheumatic fever is primarily related to myocarditis or is secondary to CHF from severe valve insufficiency is not known. When pericarditis is present, it rarely affects cardiac function or results in constrictive pericarditis. Chronic manifestations occur in adults with previous RHD from residual and progressive valve deformity. RHD is responsible for 99% of mitral valve stenosis in adults, and it may be associated with atrial fibrillation from chronic mitral valve disease and atrial enlargement.

Epidemiology

Frequency

United States
Rheumatic fever is now uncommon among children in the United States. Incidence of rheumatic fever and RHD has decreased in the United States and other industrialized countries during the past 80 years. Prevalence of RHD in the United States is now less than 0.05 per 1000 population, with rare regional outbreaks reported in Tennessee in the 1960s and in Utah, Ohio, and Pennsylvania in the 1980s. In the early 1900s, incidence was reportedly 5-10 cases per 1000 population. Decreased incidence of rheumatic fever has been attributed to the introduction of penicillin or a change in the virulence of the streptococci.

International
In contrast to trends in the United States, rheumatic fever and RHD have not decreased in developing countries. Retrospective studies in developing countries demonstrate the highest figures for cardiac involvement and the highest recurrence rates of rheumatic fever. Worldwide, an estimated 5-30 million children and young adults have chronic RHD, and 90,000 patients die from this disease each year. A study using echocardiographic screening in schoolchildren in Cambodia and Mozambique suggests that RHD prevalence may be as much as 10 times that detected using clinical examination with echocardiographic verification.[2]

Mortality/Morbidity
RHD is the major cause of morbidity from rheumatic fever and is the major cause of mitral insufficiency and stenosis in the United States and the world. Variables that correlate with severity of valve disease include the number of previous attacks of rheumatic fever, the length of time between the onset of disease and start of therapy, and sex (the prognosis for females is worse than for males). Insufficiency from acute rheumatic valve disease resolves in 70-80% of patients if they adhere to antibiotic prophylaxis.

Race
Native Hawaiians and Maori (both of Polynesian descent) have a higher incidence of rheumatic fever. Incidence of rheumatic fever in these patients is 13.4 per 100,000 hospitalized children per year, even with antibiotic prophylaxis of streptococcal pharyngitis. Otherwise, race (when controlled for socioeconomic variables) has not been documented to influence the disease incidence.

Sex
Rheumatic fever occurs in equal numbers in males and females. Females with rheumatic fever fare worse than males and have a slightly higher incidence of chorea.

Age
Rheumatic fever is principally a disease of childhood, with a median age of 10 years; However, GABHS pharyngitis is uncommon in children younger than 3 years, and acute rheumatic fever is extremely rare in these younger children in industrialized countries. Although less commonly seen in adults compared with children, rheumatic fever in adults accounts for 20% of cases.

History
Acute rheumatic fever (RF) is a systemic disease. Thus, patients may present with a large variety of symptoms and complaints.

History of an antecedent sore throat 1-5 weeks prior to onset is present in 70% of older children and young adults. Only 20% of younger children can recall an antecedent sore throat. Other symptoms on presentation may include fever, rash, headache, weight loss, epistaxis, fatigue, malaise, diaphoresis, and pallor. Patients also may have chest pain with orthopnea or abdominal pain and vomiting. Finally, history may reveal symptoms more specific to rheumatic fever. o Migratory joint pain o Nodules under the skin o Increased irritability and shortened attention span with personality changes, such as pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) o Motor dysfunction o History of previous rheumatic fever Patients with previous rheumatic fever are at a high risk of recurrence. o Highest risk of recurrence within 5 years of the initial episode o Greater risk of recurrence with younger age at the time of the initial episode o Generally, recurrent attacks similar to the initial attack (however, risk of carditis and severity of valve damage increase with each attack)

Physical
Revised in 1992, the modified Jones criteria provide guidelines for making the diagnosis of rheumatic fever.[3] The Jones criteria require the presence of 2 major or 1 major and 2 minor criteria for the diagnosis of rheumatic fever. Having

evidence of previous group A streptococci (GAS) pharyngitis is also necessary. These criteria are not absolute, and the diagnosis of rheumatic fever can be made in patients with only confirmed streptococcal pharyngitis and chorea.

Major diagnostic criteria o Carditis o Polyarthritis o Chorea o Subcutaneous nodules o Erythema marginatum Minor diagnostic criteria o Fever o Arthralgia o Prolonged PR interval on electrocardiography o Elevated acute-phase reactants (APRs), which are erythrocyte sedimentation rate and C-reactive protein Three notable exceptions to strict adherence to the Jones criteria o Chorea: It may occur late and be the only manifestation of rheumatic fever. o Indolent carditis: Patients presenting late to medical attention months after the onset of rheumatic fever may have insufficient support to fulfill the criteria. o Newly ill patients with a history of rheumatic fever, especially rheumatic heart disease (RHD), who have supporting evidence of a recent GAS infection and who manifest either a single major or several minor criteria: Distinguishing recurrent carditis from preexisting significant RHD may be impossible. Evidence of previous GAS pharyngitis (One of the following must be present): o Positive throat culture or rapid streptococcal antigen test o Elevated or rising streptococcal antibody titer Major clinical manifestations o Arthritis Polyarthritis is the most common symptom and is frequently the earliest manifestation of acute rheumatic fever (70-75%). Characteristically, the arthritis begins in the large joints of the lower extremities (ie, knees, ankles) and migrates to other large joints in the lower or upper extremities (ie, elbows, wrists). Affected joints are painful, swollen, warm, erythematous, and limited in their range of motion. The pain is out of proportion to clinical findings. The arthritis reaches maximum severity in 12-24 hours and persists for 2-6 days (rarely more than 4 wk, but has been reported to persist 44 d) at each site and is migratory but not additive.

The arthritis responds rapidly to aspirin, which decreases symptoms in affected joints and prevents further migration of the arthritis. Polyarthritis is more common and more severe in teenagers and young adults than in younger children. Patients suffering multiple attacks may exhibit destructive arthritis (Jaccoud arthritis). Carditis Pancarditis is the most serious complication and the second most common complication of rheumatic fever (50%). In advanced cases, patients may experience of dyspnea, mild-to-moderate chest discomfort, pleuritic chest pain, edema, cough, or orthopnea. Upon physical examination, carditis is most commonly revealed by a new murmur and tachycardia that is out of proportion to the fever. New or changing murmurs traditionally have been considered necessary for a diagnosis of rheumatic valvulitis. The murmurs of acute rheumatic fever are from valve regurgitation, and the murmurs of chronic rheumatic fever are from valve stenosis. Frequently examine patients in whom the diagnosis of acute rheumatic fever is made due to the progressive nature of the disease. Some cardiologists have proposed that evidence of new mitral regurgitation from Doppler echocardiography, even in the absence of accompanying auscultatory findings, may be sufficient for making the diagnosis of carditis, particularly if the echocardiography findings resolve along with other manifestations of rheumatic fever. This criterion for carditis is not uniformly accepted and remains specifically excluded in the 1992 revised Jones criteria because of insufficient data at the time of publication. Congestive heart failure (CHF) may develop secondary to severe valve insufficiency or myocarditis. Physical findings associated with heart failure include tachypnea, orthopnea, jugular venous distention, rales, hepatomegaly, a gallop rhythm, and peripheral swelling and edema. A pericardial friction rub indicates that pericarditis is present. Increased cardiac dullness to percussion, muffled heart sounds, and a paradoxical pulse are consistent with pericardial effusion and impending pericardial tamponade. Confirm this clinical emergency with ECG, and evacuate the effusion by pericardiocentesis if it is producing hemodynamic compromise. Chorea: In the absence of a family history of Huntington chorea or findings consistent with systemic lupus erythematosus, the diagnosis of acute rheumatic fever is almost certain. A long latency period exists between streptococcal pharyngitis (1-6 mo) and the

onset of chorea, and a history of an antecedent sore throat frequently is not obtained. Patients with chorea often do not demonstrate other Jones criteria. Chorea is slightly more common in females than males. Chorea is also known as rheumatic chorea, Sydenham chorea, chorea minor, and St Vitus dance. Poststreptococcal movement disorders Described poststreptococcal movement disorders have included pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) and Tourette syndrome. Daily handwriting samples can be used as an indicator of progression or resolution of disease. Complete resolution of the symptoms typically occurs, with improvement in 1-2 weeks and full recovery in 2-3 months; however, incidents have been reported in which symptoms wax and wane for several years. The PANDAS disorder appears to have a relapsingremitting symptom complex characterized by obsessivecompulsive personality disorder. Patients with Sydenham chorea and obsessive-compulsive symptoms tend to show aggressive, contamination, and somatic obsessions and checking, cleaning, and repeating compulsions. Neurologic abnormalities include cognitive defects and motoric hyperactivity. The symptoms may also include emotional lability, separation anxiety, and oppositional behaviors, and they are prepubertal in onset. Some have proposed that the streptococcal infection triggers the formation of antibodies that cross-react with the basal ganglia of genetically susceptible hosts in a manner similar to the proposed mechanism for Sydenham chorea and causes the symptom complex. Erythema marginatum: This characteristic rash, also known as erythema annulare, occurs in 5-13% of patients with acute rheumatic fever. Erythema marginatum begins as 1-cm to 3-cm diameter, pink-to-red nonpruritic macules or papules located on the trunk and proximal limbs but never on the face. The lesions spread outward to form a serpiginous ring with erythematous raised margins and central clearing. The rash may fade and reappear within hours and is exacerbated by heat. Thus, if the lesions are not observed easily, they can be accentuated by the application of warm towels, a hot bath, or the use of tangential lighting. The rash occurs early in the course of the disease and remains long past the resolution of other symptoms. Erythema marginatum (shown in the image below) has also been reported in association with sepsis, drug reactions, and glomerulonephritis.

Erythema marginatum, the characteristic rash of acute rheumatic fever. o Subcutaneous nodules: Subcutaneous nodules are now an infrequent manifestation of rheumatic fever. The frequency has declined during the past several years to 0-8% of patients with rheumatic fever. When present, the nodules appear over the extensor surfaces of the elbows, knees, ankles, knuckles, scalp, and spinous processes of the lumbar and thoracic vertebrae (attached to the tendon sheath). The nodules are firm, nontender, and free from attachments to the overlying skin, and they range from a few millimeters to 1-2 cm. The nodules number from 1 to dozens, with a mean of 3-4. Histologically, the nodules contain areas resembling the Aschoff bodies observed in the heart. Subcutaneous nodules generally occur several weeks into the disease and resolve within a month. They are strongly associated with severe rheumatic carditis, and in the absence of carditis, question the diagnosis of subcutaneous nodules. Other clinical manifestations o Abdominal pain: Abdominal pain usually occurs at the onset of acute rheumatic fever, resembles other conditions with acute microvascular mesenteric inflammation, and may mimic acute appendicitis. o Arthralgias: Patients may report arthralgias upon presentation. In the history, determining if the patient has taken aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) is important because these may suppress the full manifestations of the disease. Arthralgia cannot be considered a minor manifestation if arthritis is present. o Epistaxis: Epistaxis may be associated with severe protracted rheumatic carditis. o Fever: Fevers greater than 39C with no characteristic pattern are present initially in almost every patient with acute rheumatic fever. The fever may be low grade (38-38.5C) in children with mild carditis or absent in patients with pure chorea. The fever decreases without antipyretic therapy in approximately 1 week, but lowgrade fevers persist for 2-3 weeks. o Rheumatic pneumonia: Patients present with the same signs as an infectious pneumonia. Differentiate rheumatic pneumonia from respiratory distress related to CHF.

Causes

Rheumatic fever is believed to result from an autoimmune response; however, the exact pathogenesis remains unclear.

Rheumatic fever only develops in children and adolescents following group A beta hemolytic streptococcal (GABHS) pharyngitis, and only infections of the pharynx initiate or reactivate rheumatic fever. At least some rheumatogenic strains of GAS have antigenic domains similar to antigens in components of the human heart, and some authors have proposed that anti-M antibodies against the streptococci may crossreact with heart tissue, causing the pancarditis that is observed in rheumatic fever. So-called molecular mimicry between streptococcal and human proteins is felt to involve both the B and T cells of peripheral blood, with infiltration of the heart by T cells. Some believe that an increased production of inflammatory cytokines is the final mechanism of the autoimmune reaction that causes damage to cardiac tissue in RHD. An insufficiency of interleukin-4 (IL-4)producing cells in the valve tissue may also contribute to the valve lesions. Streptococcal antigens, which are structurally similar to those in the heart, include hyaluronate in the bacterial capsule, cell wall polysaccharides (similar to glycoproteins in heart valves), and membrane antigens that share epitopes with the sarcolemma and smooth muscle.

Medical Care
Prevention of rheumatic fever in patients with group A beta hemolytic streptococci (GABHS) pharyngitis
For patients with GABHS pharyngitis, a meta-analysis supported a protective effect against rheumatic fever (RF) when penicillin is used following the diagnosis.[4]

Oral (PO) penicillin V remains the drug of choice for treatment of GABHS pharyngitis, but ampicillin and amoxicillin are equally effective. When PO penicillin is not feasible or dependable, a single dose of intramuscular benzathine penicillin G, or benzathine/procaine penicillin combination is therapeutic. For patients who are allergic to penicillin, administer erythromycin or a first-generation cephalosporin. Other options include clarithromycin for 10 days, azithromycin for 5 days, or a narrow-spectrum (first-generation) cephalosporin for 10 days. As many as 15% of penicillin-allergic patients are also allergic to cephalosporins. Do not use tetracyclines and sulfonamides to treat GABHS pharyngitis. For recurrent group A streptococci (GAS) pharyngitis, a second 10-day course of the same antibiotic may be repeated. Alternate drugs include narrow-spectrum cephalosporins, amoxicillin-clavulanate, dicloxacillin, erythromycin, or other macrolides. Control measures for patients with GABHS pharyngitis are as follows:

Hospitalized patients: Place hospitalized patients with GABHS pharyngitis of pneumonia on droplet precautions, as well as standard precautions, until 24 hours after initiation of appropriate antibiotics. o Exposed persons: People in contact with patients having documented cases of streptococcal infection first should undergo appropriate laboratory testing if they have clinical evidence of GABHS infection and should undergo antibiotic therapy if infected. o School and childcare centers: Children with GABHS infection should not attend school or childcare centers for the first 24 hours after initiating antimicrobial therapy. GABHS carriage is difficult to eradicate with conventional penicillin therapy. Thus, PO clindamycin (20 mg/kg/d PO in 3 divided doses for 10 d) is recommended. In general, antimicrobial therapy is not indicated for pharyngeal carriers of GABHS. Exceptions include the following: o Outbreaks of rheumatic fever or poststreptococcal glomerulonephritis o Family history of rheumatic fever o During outbreaks of GAS pharyngitis in a closed community o When tonsillectomy is considered for chronic GABHS carriage o When multiple episodes of documented GABHS pharyngitis occur within a family despite appropriate therapy o Following GAS toxic shock syndrome or necrotizing fasciitis in a household contact
o

Treatment for patients with rheumatic fever

Therapy is directed towards eliminating the GABHS pharyngitis (if still present), suppressing inflammation from the autoimmune response, and providing supportive treatment of congestive heart failure (CHF).

Treat residual GABHS pharyngitis as outlined above, if still present. Treatment of the acute inflammatory manifestations of acute rheumatic fever consists of salicylates and steroids. Aspirin in anti-inflammatory doses effectively reduces all manifestations of the disease except chorea, and the response typically is dramatic. o If rapid improvement is not observed after 24-36 hours of therapy, question the diagnosis of rheumatic fever. o Attempt to obtain aspirin blood levels from 20-25 mg/dL, but stable levels may be difficult to achieve during the inflammatory phase because of variable GI absorption of the drug. Maintain aspirin at anti-inflammatory doses until the signs and symptoms of acute rheumatic fever are resolved or residing (6-8 wk) and the acute phase reactants (APRs) have returned to normal.

Anti-inflammatory doses of aspirin may be associated with abnormal liver function tests and GI toxicity, and adjusting the aspirin dosage may be necessary. o When discontinuing therapy, withdraw aspirin gradually over weeks while monitoring the APRs for evidence of rebound. Chorea most frequently is self-limited but may be alleviated or partially controlled with phenobarbital or diazepam. If moderate to severe carditis is present as indicated by cardiomegaly, third-degree heart block, or CHF, add PO prednisone to salicylate therapy. o Continue prednisone for 2-6 weeks depending on the severity of the carditis, and taper prednisone during the last week of therapy. o Discontinuing prednisone therapy after 2-4 weeks, while maintaining salicylates for an additional 2-4 weeks, can minimize adverse effects. Include digoxin and diuretics, afterload reduction, supplemental oxygen, bed rest, and sodium and fluid restriction as additional treatment for patients with acute rheumatic fever and CHF. The diuretics most commonly used in conjunction with digoxin for children with CHF include furosemide and spironolactone. o Initiate digoxin only after checking electrolytes and correcting abnormalities in serum potassium. o The total loading dose is 20-30 mcg/kg PO every day, with 50% of the dose administered initially, followed by 25% of the dose 8 hours and 16 hours after the initial dose. Maintenance doses typically are 8-10 mcg/kg/d PO in 2 divided doses. For older children and adults, the total loading dose is 1.25-1.5 mg PO, and the maintenance dose is 0.25-0.5 mg PO every day. Therapeutic digoxin levels are present at trough levels of 1.5-2 ng/mL. Afterload reduction (ie, using ACE inhibitor captopril) may be effective in improving cardiac output, particularly in the presence of mitral and aortic insufficiency. Start these agents judiciously. Use a small, initial test dose (some patients have an abnormally large response to these agents), and administer only after correcting hypovolemia. When heart failure persists or worsens during the acute phase after aggressive medical therapy, surgery is indicated to decrease valve insufficiency.
o

Treatment for patients following rheumatic heart disease (RHD)

Preventive and prophylactic therapy is indicated after rheumatic fever and RHD to prevent further damage to valves.

Primary prophylaxis (initial course of antibiotics administered to eradicate the streptococcal infection) also serves as the first course of secondary prophylaxis (prevention of recurrent rheumatic fever and RHD). An injection of 0.6-1.2 million units of benzathine penicillin G intramuscularly every 4 weeks is the recommended regimen for secondary prophylaxis for most US patients. Administer the same dosage every 3

weeks in areas where rheumatic fever is endemic, in patients with residual carditis, and in high-risk patients. o Although PO penicillin prophylaxis is also effective, data from the World Health Organization indicate that the recurrence risk of GABHS pharyngitis is lower when penicillin is administered parentally. o The duration of antibiotic prophylaxis is controversial. Continue antibiotic prophylaxis indefinitely for patients at high risk (eg, health care workers, teachers, daycare workers) for recurrent GABHS infection. Ideally, continue prophylaxis indefinitely, because recurrent GABHS infection and rheumatic fever can occur at any age; however, the American Heart Association currently recommends that patients with rheumatic fever without carditis receive prophylactic antibiotics for 5 years or until aged 21 years, whichever is longer.[5] Patients with rheumatic fever with carditis but no valve disease should receive prophylactic antibiotics for 10 years or well into adulthood, whichever is longer. Finally, patients with rheumatic fever with carditis and valve disease should receive antibiotics at least 10 years or until aged 40 years. o Patients with RHD and valve damage require a single dose of antibiotics 1 hour before surgical and dental procedures to help prevent bacterial endocarditis. Patients who had rheumatic fever without valve damage do not need endocarditis prophylaxis. Do not use penicillin, ampicillin, or amoxicillin for endocarditis prophylaxis in patients already receiving penicillin for secondary rheumatic fever prophylaxis (relative resistance of PO streptococci to penicillin and aminopenicillins). Alternate drugs recommended by the American Heart Association for these patients include PO clindamycin (20 mg/kg in children, 600 mg in adults) and PO azithromycin or clarithromycin (15 mg/kg in children, 500 mg in adults). Additional guidelines for endocarditis prophylaxis in patients who are allergic to penicillin or who are unable to receive PO antibiotics are discussed in the Bacterial Endocarditis article. o A recent study investigated the difference in clinical manifestations and outcomes between first episode and recurrent rheumatic fever. [6] The study concluded that subclinical carditis occurred only in patients experiencing the first episode, and that all deaths occurred in patients with recurrent rheumatic fever, emphasizing the need for secondary prophylaxis.

Diet
Advise nutritious diet without restrictions except in patients with CHF, who should follow a fluid-restricted and sodium-restricted diet. Potassium supplementation may be necessary because of the mineralocorticoid effect of corticosteroid and the diuretics, if used.

Medication Summary
Treatment and prevention of group A streptococci (GAS) pharyngitis outlined here are based on the current recommendations of the Committee on Infectious Disease (American Academy of Pediatrics). Medical therapy is directed toward elimination of GAS pharyngitis (if still present), suppression of inflammation from the autoimmune response, and supportive treatment of congestive heart failure (CHF). Attempts are being made to produce vaccines against GAS infection, but the vaccines will not be available for years. Antibiotics for endocarditis prophylaxis are administered to patients with certain cardiac conditions, such as carditis caused by rheumatic fever, before procedures that may cause bacteremia are performed. For more information, see Antibiotic Prophylactic Regimens for Endocarditis.

Antibiotics
Class Summary
The roles for antibiotics are to (1) initially treat GABHS pharyngitis, (2) prevent recurrent streptococcal pharyngitis, rheumatic fever (RF), and rheumatic heart disease (RHD), and (3) provide prophylaxis against bacterial endocarditis. View full drug information

Penicillin VK (Beepen-VK, Pen.Vee K, V-Cillin K, Veetids)

DOC for treatment of GABHS pharyngitis. Although ampicillin or amoxicillin may be used instead, they have no microbiologic advantage. Do not use tetracyclines and sulfonamides to treat GABHS pharyngitis. For recurrent GABHS pharyngitis, a second 10-d course of same antibiotic may be repeated. Alternate drugs include narrow-spectrum cephalosporins, amoxicillin-clavulanate, dicloxacillin, erythromycin, or other macrolides.

Penicillin benzathine (Bicillin L-A) or penicillin procaine (Crysticillin A.S., Wycillin)

Used when PO administration of penicillin is not feasible or dependable. IM therapy with penicillin is painful, but discomfort may be minimized if penicillin G is brought to room temperature before injection or combination of benzathine penicillin G and procaine penicillin G is used. Initial course of antibiotics administered to eradicate streptococcal infection also serves as first course of prophylaxis. An injection of benzathine penicillin G IM q4wk is recommended regimen for secondary prevention for most United States patients. Administer

same dosage q3wk in areas where RF is endemic, in patients with residual carditis, and in high-risk patients. View full drug information

Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)

Used for patients who are allergic to penicillin. Other options include clarithromycin, azithromycin, or a narrow-spectrum cephalosporin (ie, cephalexin). As many as 15% of penicillin-allergic patients are also allergic to cephalosporins. View full drug information

Clarithromycin (Biaxin)
Alternate antibiotic for treating GAS pharyngitis in patients allergic to penicillin. View full drug information

Azithromycin (Zithromax)
Alternate antibiotic for treating GAS pharyngitis in patients allergic to penicillin. View full drug information

Cephalexin (Keflex, Biocef, Keftab)

Alternate antibiotic for treating GAS pharyngitis in patients allergic to penicillin. View full drug information

Amoxicillin (Amoxil, Biomox, Trimox)

DOC used for bacterial endocarditis prophylaxis. Administered as single PO dose 1 h before dental work or surgery.

Anti-inflammatory agents

Class Summary
Manifestations of acute rheumatic fever (including carditis) typically respond rapidly to therapy with anti-inflammatory agents. Aspirin, in anti-inflammatory doses, is DOC. Prednisone is added when evidence of worsening carditis and heart failure is noted. View full drug information

Aspirin (Anacin, Ascriptin, Bayer Aspirin)

Begin administration immediately after diagnosis of RF. Initiation of therapy may mask manifestations of disease. View full drug information

Prednisone (Deltasone, Orasone)

If moderate-to-severe carditis is present as indicated by cardiomegaly, CHF, or third-degree heart block, use 2 mg/kg/d PO prednisone in addition to or in lieu of salicylate therapy. Continue prednisone for 2-4 wk depending on severity of carditis and taper during last week of therapy. Discontinuing prednisone therapy after 2 wk while adding or maintaining salicylates for additional 2-4 wk may minimize adverse effects.

Therapy for congestive heart failure

Class Summary
Heart failure in RHD probably is related in part to severe insufficiency of the mitral and aortic valves and in part to pancarditis. Therapy traditionally has consisted of an inotropic agent (digitalis) in combination with diuretics (furosemide, spironolactone) and afterload reduction (captopril). View full drug information

Digoxin (Lanoxin, Lanoxicaps)

Inotropic agent widely used in past. Its efficacy in CHF is under review. Potential for toxicity is present. Therapeutic levels and clinical effects are observed more quickly if loading doses of digitalis are administered before routine maintenance doses. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and

enhanced sympathetic withdrawal for any given increase in mean arterial pressure. Therapeutic digoxin levels are present at trough levels of 1.5-2 ng/mL. View full drug information

Captopril (Capoten)
Systemic afterload reduction may be helpful in improving cardiac output, particularly in setting of mitral and aortic valve insufficiency. Some patients have unusually large hypotensive response. Use small starting dose, particularly with hypovolemia. View full drug information

Furosemide (Lasix)
Diuretics frequently are used in conjunction with inotropic agents for patients with CHF. When used aggressively, may result in hypokalemia and hypovolemia. Risk of hearing loss in premature infants. Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. View full drug information

Spironolactone (Aldactone)
Used in conjunction with furosemide as potassium-sparing diuretic. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.