ALEXANDRIA UNIVERSITY,  FACULTY OF MEDICINE,  DEPARTMENT OF PEDIATRIC MEDICINE.

y Presented by :

Asmaa khairy beltagy

y Supervised by:

194

Prof. Dr. Nadia Hattem

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Rheumatic Fever
Rheumatic fever (RF) is an autoimmune multisystemic inflammatory connective tissue disease . It follows group A streptococcal (GAS) infection of the tonsillopharynx after a latent period of about 3 weeks, during this period the patient may be totally asymptomatic. It involves many organs, primarily the heart, the joints, and the CNS. The major importance of acute RF is its ability to cause fibrosis of heart valves, leading to crippling hemodynamic s of chronic heart disease .RF is the most common cause of acquired heart disease in children and young adults worldwide. Although the incidence of RF declined sharply in many developed countries, the disease remains a major problem in many developing coun tries.

Nomenclature:
rheum : a watery discharge from the eyes or nose

Epidemiology :
y Incidence: The incidence of RF is markedly variable in different countries. in the United States is currently estimated at less than 2 per 100,000. In many developing countries, the incidence of acute RF approaches or exceeds 100 per 100,000.In keeping with the falling incidence of RF in industrialized countries Distribution: Although RF used to be considered a disease of temperate climates, it is now more common in warm tropical climates, particularly in developing countries.

1. 2. 3. 4.
y y y y

The decline in incidence of RF and prevalence of rheumatic heart disease has been attributed to several factors: the use of antimicrobial agents have enhanced the rate of this decline. Improved economic standards, better housing, decreased crowding in homes and schools, and access to medical care. Change in virulence of the organism: periodic shifts in the appearance and disappearance of specific M types in a particular geographical location. Age: Initial attacks of RF occur most commonly between the ages of 6 and 15 years. RF rarely occurs before the age of 5 years. Sex: equal in male and female patients. Season The peak incidence of RF in Europe and the United States is in spring. Race: An association between certain class-II HLA antigens (DR2 in blacks and DR4 in whites) and ARF have been reported.

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Pathogenesis:
Factors that contribute to the pathogenesis of RF are related to the causative agent and the host and the nature of immunological tissue damage.

The Etiological Agent:

ARF is caused by some strains of group A beta hemolytic streptococci, termed rheumatogenic strains. GABS are composed of cytoplasm surrounded by a protoplastic membrane of lipoprotein. Outside the cytoplasmic membrane is the cell wall which consists of three structural components. Some strains are capable of forming a mucoid capsule composed of hyalurinic acid. It can cross react with articular tissue . Protoplast membrane antige n: There is cross reactivity between it and sarcolemmal membrane of the myocardium and neuronal tissu e of the caudate and subthalamic nuclei. cell wall structures. peptidoglycan : This compound with the cell wall polysaccharides produces arthritis and nodular reaction. Polysaccharides : cross-reaction involves the group A carbohydrate moiety N acetylglucosamine and mammalian valvular glycoproteins Mosaic of proteins labeled as M, R, and T proteins. The most important of those is the M protein. M protein is a type specific antigen. There are more than 80 different M proteins. each of which is capable of stimulating specific protective antibodies as well as sharing a common property of being able to avoid phagocytosis by the host's immune system. There is cross reactivity between M protein and myocardial sarcolemma. An untreated GAS tonsillopharyngitis is the recent event that precipitates RF. RF does not follow streptococcal skin infection (impetigo). As many as 3 percent of untreated acute streptococcal sore throats may be followed by RF. About one-third of all cases of acute RF follow mild, almost asymptomatic pharyngitis.

1. 2.

3. a. b. c.

y y y

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Host susceptibility and response to Acute Rheumatic Fever

In populations exposed to rheumatogenic group A streptococci, the incidence of ARF is about 3% the incidence of the disease after streptococcal pharyngitis in patients who have had a previous episode of RF is about 50 percent.
Family History: y Early studies showed a family predilection for ARF. In 1889, it was noted that the chance of an individual with a family history of ARF acquiring the disease is "nearly 5 times as great as that of other individuals. y susceptibility to ARF and RHD is increased concordance in monozygotic twins compared with dizygotic twins . Human Leukocyte Antigens; y In general, HLA class II molecules appear to have a closer association with increased risk of ARF. y A wide variation exists in results of studies in different geographic regions and ethnic populations. y Also, some studies have found HLA associations only with particular clinical features of ARF ; for example, in 1 study, a significant association was found between HLA-A10 and HLA-DR11 in patients with cardiac manifestations compared with ARF without cardia c features, the latter group having a higher frequency of HLA -C2. y The mechanism of HLA association is unknown. One theory is that similarity exists between antigens from rheumatogenic group A streptococcal strains and HLA molecules. y This theory is supported by a study in a population in which HLA -DR4 was associated with ARF. The investigators found that antistreptococcal serum caused significantly increased toxicity to B lymphocytes bearing HLA-DR4 compared with DR4-negative lymphocytes, and they su ggested that a strong antigenic similarity existed between HLA -DR4 and the streptococcal antigen, which led to defective antigen presentation by the HLA molecule (Figure). This in turn could lead to aberrant cytokine production and ultimately antibody formation against proteins on valves, myocardium, brain, and joint tissue. y

Possible mechanisms for HLA association with ARF: The left side of the figure (antibody theory) illustrates how antibodies may be central to the mechanism through which the HLA associa tion is mediated, either through defective presentation by the HLA molecule because of antigenic similarity, or through streptococcal antigens mimicking the HLA molecule. This is proposed to lead to aberrant cytokine production, poor antigenic clearance, p rolonged B cell stimulation and increased production of antibodies against the various tissues affected in ARF The right side of the figure (antigen theory) illustrates how streptococcal antigens may be presented to T cells that have escaped immune tolerance, These T cells recognize and are activated by the peptide, but then they cross react with similar self-antigens that they are unable to identify as self, which initiates the autoimmune process. GpA indicates group A; TCR, T-cell receptor

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B-Cell Alloantigens: y Using alloantisera, they identified a novel B-cell alloantigen, called 883 , which was expressed on the B cells of 71% to 74% of rheumatic fever patients compared with only 17% of control subjects. y A number of studies have investigated the association of antigen D8/17 , and ARF. Most studies have reported D8/17 -positive expression in >85% of individuals with previous ARF, but this is not universal. Immune Gene Polymorphisms: there have been several studies examining the role of polymorphisms in the promoter region of the (TNF- ) gene. Toll-like receptors (TLR) polymorphism showed a strong association with ARF in children. Other Gene Associations: Patients with familial Mediterranean feve r have a higher prevalence of RHD than the general population, due to polymorphisms in the MEFV gene causing impaired control of the type 1 helper T cell (Th1). polymorphisms of the ACE gene have recently been associated with chronic valvular fibrosis and calcification in RHD.

In a disease as complex as ARF, which involves different potential bacterial antigenic triggers, humoral and cellular arms of the immune response, and damage to multiple specific tissues, it is doubtful that a single gene holds the key to understanding the intricacies of its pathogenesis.
Use of dermatoglyphics to determine host susciptibility: In a study concerning observation of dermatoglyphic alterations associated with ARF, 75% of patients had lunar deviation of triradius t. it was associated with distal displacement un about 40% of cases.this alteration resulted in higher mean maximal angle atd. The ulnar deviation was not seen in normal controls. So dermatoglyphics
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may provide an easy, inexpensive non invasive way to determi ne genetic predisposition to ARF. dermatoglyphics have also a diagnostic value especially in patients present with arthritis as the only major manifestation.

Pathology:
The acute phase of RF is characterized by exudative and proliferative inflammatory reactions involving connective tissue. y Although the disease process is diffuse, it affects primarily the heart, joints, brain, and cutaneous and subcutaneous tissues. y A generalized vasculitis affecting small blood vessels is commonly noted, but unlike the vasculitis of some other connective tissue disorders, thrombotic lesions are not seen in RF. y The basic structural change in collagen is fibrinoid degeneration . The interstitial connective tissue becomes edematous and eosinophilic, with fragmentation, and disintegration of collagen fibers. a. Carditis Acute rheumatic fever can involve any of the components of heart tissue. It is most commonly affecting the endocardium and the myocardium . the pericardium may also be involved. The degree of histological changes does not necessarily correlate with the severity of the clinical findings. In the early stage of the disease , whe n cardiac dilatation is present, the histological changes may be minimal , despite the fact that mortality due to acute carditis occur most frequently during this stage. In addition to prolferative and exudative reactions, this stage is characterized by edematous changes followed by a cellular infiltrate of lymphocytes, plasma cells with few granulocytes. This is associated with infiltration of mononuclear cells including large modified fibrohistiocytic cells ( Aschoff's cells ). Some of the histiocytes are multinucleated and form Aschoff's giant cells . Fibrinoid, an eosinophilic granular substance of degenerating collagen in a mixture of fibrin, globulin, and other substances. The Aschoff's nodule in the proliferative stage is considered patho gnomonic of rheumatic carditis. Aschoff's bodies may be seen in any area of the myocardium but not in other affected organs such as joints or brain. they may be angular or spindle shaped.
y

They are most often noted in the interventricular septum , the wall of the left ventricle, or the left atrial appendage. Aschoff's nodules persist for many years after a rheumatic attack, even in patients with no evidence of recent or active inflammation.

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Inflammation of valvular tissue accounts for the most commonly recognized clinical manifestations of rheumatic carditis. Mitral valve is the most common to be involved , aortic valve is the second to be involved .Tricuspid and pulmonary valves are rarely involved. Initial inflammation leads to valvular insufficiency. A lesion characteristic of rheumatic endocarditis is MacCallum patch, a thickened area of tissue seen in the left atrium above the base of the posterior mitral leaflet . Hyaline degeneration of the affected valve leads to the formation of verrucae at its edge, preventing total approximation of the leaflets.

Endocarditis (mitral valve)

Fibrosis and calcification of the valve occur if inflammation persists. This process may eventually lead to valvular stenosis several years after the initial insult to the tissue. y Patients with pancarditis have pericarditis in addition to endocarditis and myocarditis. A fibrinous exudates covers both the visceral and serous surfaces .,and varying amounts of serosanguinous fluid are present in the pericardial space. Arthritis The pathology of arthritis is simila r to that of serositis , cartilage is not involved, but the synovial lining shows fibrinoid degeneration Sydenham`s chorea is thought to be due to vasculitis in the basal ganglia and cerebellum consisting of cellular changes and perivascu lar infiltration of lymphocytes or due to antibodies against neuronal tissues. The pathology of subcutaneous nodule s is also fibrinoid necrosis surrounded by epithelial and mononuclear cells . they are present over bony prominences and on extensor surface of tendons. Vasculitis is the main pathologic process in erythema multiforme .
y

b.

c.

d.

e.

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Manifestations of acute rheumatic fever:

Major Clinical Manifestations: 1. CARDITIS. y It occurs in 50% of patients with ARF y It is t Carditis is often regarded as the most specific manifestation y the most serious cause of morbidity in ARF, and accounts for the most of the mortality during the acute stage of the disease. y The disease is associated with non specific symptoms as easy fatigability, anorexia, shortness of breath, chest pain, and low grade fever. y Carditis may present alone or with other manifestations. Occasionally arthritis precedes the onset of carditis by 1 to 2 weeks. The severity of carditis is quite variable y Evidence of carditis may be very subtle as in patients with Sydenham`s chorea. y Clinically, rheumatic carditis is almost always associated with a murmur of valvulitis..signs of valvular involvement may be mild and transient and may be easily missed on auscultation. Myocarditis is presented with sleeping tachycardia, transient arrhythmias or heart block which is uncommon. Endocarditis is the most characteristic component of rheumatic carditis. Mitral insufficiency is the hallmark of rheumatic carditis. It leads to apical and holosystolic murmur. In the presence of mitral insufficiency, a low frequency mid to late diastolic murmur of relative mitral stenosis may be present. this flow murmur, the carey coombs murmur. Aortic insufficiency occurs in about 20% of patients with ARF. It can be isolated finding, but is usually associated with mitral insufficiency. It is characterized by the presence of early diastolic decrescendo murmur that starts with the aortic component of the second heart sound. It is usually associated with increased pulse pressure (bounding pulse). Severe myocarditis or valvular insufficiency may lead to heart failure. It occurs in about 5% of patients, usually young children. It is manifested by easy fatigability, anorexia, dyspnea, orthopnea, chest pain, tachycardia, cardiomegally, gallop, and enlarged tender liver. Pericarditis Although rare, if present it will manifest by friction rub over the pericardium. 2. polyarthritis y It occurs in about 70% of patients with ARF. y the most common of the major manifestations and the least specific and is often the cause of misdiagnosis of ARF. The arthritis of RF is benign and does not result in joint deformity It is manifested by pain, swelling, redness, and warmth in the joints affected. Pain is accentuated by passive or active movement of the joints. the large joints are mostly affected, particularly the knee, ankles, elbow, and wrist. This arthritis is often migratory. Arthritis resolves within 1 week. It responds quickly to salicylates even in low doses. Indeed, if a patient does not improve substantially after 48 hours of adequate salicylate treatment, the diagnosis of RF should be in doubt 3. Sydenham`s chorea .

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Sydenham's chorea, St. Vitus' dance, or chorea minor occurs in about 20 percent of patients with RF . y more common in females. y Chorea is a delayed manifestation of RF, usually appearing 3 months or longer after the onset of the precipitating streptococcal infection. y The diagnosis of RF can be made in a patient with chorea without strictly adhering to the Jones criteria. y Sydenham's chorea is characterized clinically by purposeless and involuntary movements, muscle incoordination and hypotonia, and emotional lability. The manifestations are more evident when a patient is awake and under stress and may disappear during sleep. All muscles may be involved, but primarily muscles of the face and extremities. Speech may be affected, being explosive and halting. Hand writing deteriorates, and patients become uncoordinated and easily frustrated. y Symptoms usually resolve in 1 to 2 weeks, even without treatment. In severe cases, it may persist for 4 months, and rarely for up to 2 years. Recurrence of symptoms after initial remission may occur occasionally. 4. Erythema marginatm. y This is a rare manifestation of RF, occurring in less than 5 percent of patients. Because of its specificity , it is considered among the major criteria. y It is an erythematous, macular, nonpruritic rash with pale centers and rounded or serpiginous margins. y Lesions vary greatly in size and occur mainly on the trunk and proximal extremities, not on the face. 5. Subcutaneous nodules. y firm, painless, freely movable nodules that measure 0.5 to 2 cm. y They are rarely seen in patients with RF (about 3 percent); when present, they are most often seen in patients with carditis. y They are usually located over extensor surfaces of the joints (particularly elbows, knees, and wrists), in the occipital portion of the scalp, or over spinous processes. The overlying skin is freely movable, shows no discoloration, and is not inflamed.
y MINOR MANIFESTATIONS: 1. Fever; It has no characteristic pattern. it occurs early in the course of the disease. 2. Arthralgia y nonspecific, common findings in patients with acute RF. y Arthralgia is pain in one or more large joints without objective findings on examination and must not be considered a minor manifestation if arthritis is present. 3. Epistaxis and abdominal pain may also occur but are not included as minor diagnostic criteria for RF.

Differential diagnosis of rheumatic fever

y Juvenile rheumatoid arthritis . y Systemic lupus erythematosus . y Infective endocarditis .
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y Reactive arthritis. y Drug reactions. y Other connective tissue diseases . y Leukaemia .

DIAGNOSIS:
y y

No specific clinical, laboratory, or other test establishes the diagnosis of RF. In 1944, T. Duckett Jones formulated criteria for the diagnosis of RF

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LABORATORY FINDINGS:
Elevated acute phase reactants offer objective but nonspecific indications of tissue inflammation. The erythrocyte sedimentation rate ( ESR) and C-reactive protein (CRP) level are almost always elevated during the acute stages of the disease in patients with carditis or polyarthritis but are usually normal in patients with chorea. The ESR is useful in monitoring the course of the disease; it usually returns to normal as the rheumatic activity subsides. Unlike the ESR, the CRP level is unaffected by anemia or cardiac failure. Leukocytosis may be observed in the acute stages of RF. Anemia is usually mild or moderate and normocytic normochromatic. Electrocardiographic findings y normal findings do not exclude the presence of carditis. y A common finding in patients with acute RF is a prolonged PR interval for age and rate on electrocardiography. Other findings on electrocardiography include tachycardia, atrioventricular block, and QRS-T changes suggestive of myocarditis; these changes are not considered minor manifestations. they are almost always benign and self limiting. Chest roentgenograms y normal findings on a chest roentgenogram do not exclude the presence of carditis. y Cardiac enlargement is present. y pulmonary edema, and increased pu lmonary vascularity are also detected by this examination. y Occasionally rheumatic pneumonitis may be seen as diffuse bilateral basal infiltrates.

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Echocardiography may be helpful in detecting endocardial, myocardial, and pericardial involvement: It is also helpful in differentiating mitral insufficiency of acute rheumatic fever from mitral prolapse. Antecedent Group A Streptococcal Infection y A number of illnesses mimic acute RF, and no laboratory test or tests establish a specific diagnosis of RF. It is therefore important to establish an antecedent streptococcal infection by demonstrating GAS in the tonsillopharynx or an elevated or rising streptococcal antibody titer. Evidence of an antecedent streptococcal infection is required for confirmati on of the initial diagnosis of acute RF. y At the time of diagnosis of acute RF, only about 11 percent of patients have throat cultures positive for GAS. The paucity of positive cultures is due, in part, to elimination of the organism by host defense mechan isms during the latent period. y elevated or rising antistreptococcal antibody titers provide more reliable evidence of a recent streptococcal infection than does a positive culture or a positive rapid antigen test result. The most commonly used antibody te sts are the antistreptolysin O (ASO) and antideoxyribonuclease B (anti -DNase B). The ASO test is usually performed first, and if results are not elevated, the anti-DNase B test is done. Elevated titers for both tests may persist for several weeks or months. ASO titers rise and fall more rapidly than anti DNase

TREATMENT
y y y A. GENERAL: Whenever possible, patients should be admitted to a hospital for close observation and appropriate work-up. Bed rest is important as it lessens joint pain. Strenuous physical exercise should be avoided. Although throat cultures are rarely positive for GAS at the time of onset of RF, patients should receive a 10 -day course of penicillin therapy. Patients allergic to penicillin should be treated with erythromycin.

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If heart failure occurs, patients should receive diuretics, oxygen, and digitalis and be on a restricted sodium diet. B. ANTIRHEUMATIC THERAPY. Supportive therapy is aimed at reducing constitutional symptoms, controlling toxic manifestations, and improving cardiac fu nction. a) Salicylates: Patients with mild or no carditis respond well to salicylates. Salicylates are effective in relieving joint pain; such pain usually abates within 24 hours of starting salicylates. For optimal anti-inflammatory effect, serum salicylate levels around 20 mg percent are required. Aspirin, at doses of 100 mg/kg/d, given four to five times daily, usually results in adequate serum levels to achieve a clinical response. b) corticosteroids Patients with significant cardiac involvement respond more to corticosteroids than to salicylates. Indeed, steroids may be life saving in very ill patients. Patients who do not respond to adequate doses of salicylates may occasionally benefit from a trial course of corticosteroids. Prednisone, 1 to 2 mg/kg/d, is the usual dose. There is no evidence that salicylate or corticosteroid therapy diminishes the incidence of residual heart disease. Therefore, the duration of therapy with antiinflammatory agents is based on an estimate of the severity of the episode. y Duration of anti-inflammatory use: Mild attacks with little or no cardiac involvement may be treated with salicylates for about 1 month or until there is sufficient clinical and laboratory evidence of inflammatory inactivity. In severe cases , therapy with corticosteroids may be continued for 2 to 3 months. The medication is then gradually reduced over the next 2 weeks. y Even with prolonged therapy, some patients (approximately 5 percent) continue to demonstrate evidence of rheumatic activity for 6 months or more. y A "rebound," manifested by reappearance of mild symptoms or of acute phase reactants, may occur in some patients after anti-inflammatory medications have been discontinued, usually within 2 weeks. Modest symptoms usually subside without treatment; more severe symptoms may require treatment with salicylates. Some physicians recommend the use of salicylates (aspirin, 75 mg/kg/d) during the period when corticosteroids are being tapered and believe that such an approach may reduce the likelihood of a rebound. C. Treatment of Sydenham`s chorea: patients with mild choreform manifestations require no more than bed rest and avoidance of stress. With more severe symptoms, anti convulsant drug as phenobarbitol , haloperidol or valproate may be of help.

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PREVEN ION
Prim ry Preventi n
. rom t recognition of AS tonsillopharyngitis: by i t t ti f li i l f t , i ti t t Clinical Diagnosis: lt

icrobiological ests

Who should be tested for group A b-hemolytic streptococcal pharyngitis?

y y li i l i i l i l fi i ti bove oul be onsi ered t first. ell documented case of streptococcal A istory of lose ont t it pharyngitis is helpful a. hroat culture. Culture of a throat swab on a sheep-blood agar plate remains the standard f or the presence of AS and for the confirmation of acute streptococcal pharyngitis .culture has a sensitivity of % % . b. RAD . A disadvantage of culturing a throat swab on blood agar plates is the delay overnight or longer) in obtaining the result. A s have been developed for the identification of ABS directly from throat swabs. Although these rapid tests are more expensive than blood agar culture, they provide results faster. apid identification and treatment of patients with streptococcal pharyngitis can reduce the risk of the spread of ABS, allowing the patient to return to school or work sooner, and can reduce the acute morbidity associated with the illness. he great majority of the A s that are currently available have an excellent specificity of %, compared with blood agar plate culture. therapeutic decisions can be made with confidence on the basis of a positive test result. nfortunately, the sensitivity of most of these tests is
P

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80% 0%, or even lower, compared with blood agar plate culture . he first A s used latex agglutination methods, were relatively insensitive, and had unclear end points. ewer tests based on EIA techni ues offer increased sensitivity and a more sharply defined end point . ore recently, A s that use optical immunoassay and chemiluminescent A probes have become available. hese tests may be more sensitive than other A s and perhaps even as sensitive as standard throat culture. c. Antistreptococcal antibody titers reflect past and not present immunologic events and are of no value in the diagnosis of acute pharyngitis. hey are valuable for confirmation of previous streptococcal infections in patients suspected of having A . he diagnosis of acute AS pharyngitis should be suspected on clinical and epidemiological grounds and then supported by laboratory tests. special situations in which asymptomatic persons should have follow-up cultures of throat swabs performed. hey should be performed routinely for patients with a history of rheumatic fever and should also be considered for patients who develop acute pharyngitis during outbreaks of either acute rheumatic fever, as well as during outbreaks of AS pharyngitis in closed or partially closed communities. ollow-up throat cultures may also be indicated when spread of AS has been occurring within a family ith rare exceptions .

Modi i d centor criteri for di nosis of GAS

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2. Eradication of AS from the throat is essential. Although appropriate antimicrobial therapy started up to days after the onset of acute streptococcal pharyngitis is effective in preventing primary attacks of rheumatic fever, early therapy is advisable because it reduces both morbidity and the period of infectivity. In selecting a regimen for the treatment of AS pharyngitis, various Penicillin is the antimicrobial agent of choice for the treatment of AS, except in patients with history of allergy to penicillin. Penicillin has a narrow spectrum of activity, has a longstanding proven efficacy, and is the least expensive regimen. AS resistant to penicillin has not been documented Penicillin may be administered intramuscularly or orally able) , depending on the patient s likely adherence to an oral regimen. Intramuscular benzathine penicillin is preferred, particularly for patients who are unlikely to complete a 0-day course of oral therapy and for patients with a personal or family history of or rheumatic heart disease. he oral antibiotic of choice is penicillin V phenoxymethyl penicillin). Patients should take oral penicillin regularly for an entire 0 -day period, although they are likely to be asymptomatic after the first few days. Although the broader-spectrum amoxicillin is often used for treatment of AS pharyngitis, it offers no microbiological advantage over penicillin. Oral erythromycin is acceptable for patients allergic to penicillin. reatment should also be prescribed for 0 days. Erythromycin estolate 0 to 0 mg/kg/d in two to four divided doses), or erythromycin ethyl succinate 0 mg/kg/d in two to four divided doses) is effective in treating streptococcal pharyngitis. he maximal dose of erythromycin is gm/d. he macrolide azithromycin has similar susceptibility to that of erythromycin against AS but may cause fewer gastrointestinal side effects. Azithromycin can be administered once daily and produces high t onsillar tissue concentrations. he recommended dosage is 00 mg as a single dose on the first day followed by 0 mg once daily for days . A 0-day course of an oral cephalosporin is an acceptable alternative, particularly for penicillin-allergic patients. arrower-spectrum cephalosporins, such as cefadroxil or

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Secondary Prevention
Patients who have suffered a previous attack of and who develop streptococcal . A AS infection need not be pharyngitis are at high risk for a recurrent attack of can recur even when a symptomatic to trigger a recurrence. urthermore, symptomatic infection is optimally treated. or these reasons, prevention of recurrent requires continuous antimicrobial prophylaxis rather than recognition and treatment of acute episodes of streptococcal pharyngitis. Continuous prophylaxis is recommended for patients with a well -documented history of including cases manifested solely by Sydenham's chorea) end those with definite evidence of rheumatic heart disease. Such prophylaxis should be initiat ed as or rheumatic heart disease is diagnosed. A full therapeutic course soon as acute of penicillin as outlined in able -4) should first be given to patients with acute to eradicate residual AS even if a throat culture is negative at that time.

Developmaent of antistreptococcal vaccine:

It was difficult to develop antistreptococcal vaccine due to large serotypes of ABS and the difficulty in isolation of protein. Some studies have isolated an antigen which is pure, immunogenic and safe for human use. Who to give the vaccine? Vaccine should be given to susceptible persons. se of mono clonal antibodies as genetic markers requires expertise and sophisticated technology that may not be available in area of the world whe re A and its sequelae are major health
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problems. So dermatoglyphics may provide an easy, inexpensive, non invasive marker to determine genetic predisposition to ARF.

Long term sequelae of ARF:

y y y y

Among major manifestations of ARF, only carditis can result i n residual disease. RF is the most common cause of acquired heart disease in children and young adults worldwide. The most common cardiac leisions are mitral regurge and aortic regurge. Fibrosis and calcification of the valve occur if inflammation persists. This process may eventually lead to valvular stenosis several years after the initial insult to the tissue.

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Reference:
y Alan L. Bisno,1 Michael A. Gerber,2 Jack M. Gwaltney, Jr.,3 Edward L. Kaplan,5 and Richard H. Schwart , Practice Guidelines for the Diagnosis and Management of Group A Streptococcal Pharyngitis, CID 2002:35 Allan Gibofsky, Elinor L Baron, Daniel J Sexton, John B Zabriskie, Treatment and prevention of acute rheumatic fever, Jan. 2011 Braunwald: Heart Disease: A Textbook of Cardiovascular Medicine 2001 Elia ayoub, Moss and Adam` s Heart Disease in infant, children, and adolescent, 85; 1400 - 1414.

y y y

Dennis L Stevens, Amy Bryant,Daniel J Sexton, Elinor L Baron, Group A streptococcus: Virulence factors and pathogenic mechanisms, January 2011 . Marta Regoli, 1 Elena Chiappini, 1 Francesca Bonsignori, 1 Luisa Galli, 1 and Mauri io de Martino, Update on the management of acute pharyngitis in children, Ital J Pediatr. 2011; 37: 10. Michael A. Gerber, Robert S. Baltimore, Charles B. Eaton, Michael Gewit , Anne H, Rowley, Stanford T. Shulman and Kathryn A. Taubert , Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis Circulation 2009;119;1541-1551. Penelope A. Bryant, Roy Robins -Browne, Jonathan R. Carapetis and Nigel Curtis, Some of the People, Some of the Time: Susceptibil ity to Acute Rheumatic Fever, Circulation 2009;119;742-753 Point of Care Testing for Streptococcal Sore Throat: A Review of Diagnostic Accuracy, Cost-Effectiveness, and Guidelines, 2009

Sanyal SK, Mukerjee DP, Ahmed SH.Dermatoglyphic alterations associated with acute rheumatic fever in children. Am J Dis Child. 1978 Jul;132(7):692-5.

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