WHO guiidelines for rheumatic fever

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WHO guidelines for the treatment of Rheumatic fever:

Dr. Anita Lamichhane Deptt . Of pediatrics Shaikh zayed hospital, lahore . WHO guidelines for the treatment of Rheumatic fever

Diseases caused by group A streptococcus:

Diseases caused by group A streptococcus Pharyngitis Impetigo/pyoderma Pneumonia, Necrotizing fasciitis Rheumatic fever Glomerulonephritis Osteomyelitis Scarlet fever & erysipelas Toxic shock syndrome

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Rheumatic fever -A new (current) case with acute illness which fulfills the Jones criteria (revised)(with or without cardiac involvement) Rheumatic heart disease -A new or old case without rheumatic activity with a valvular lesion confirmed by reliable auscultation or Echocardiography.

Rheumatic fever:

Rheumatic fever Nonsuppurative complications of Group A streptococcal pharyngitis A latent period of 1-3 weeks A delayed immune response caused by antibody cross-reactivity that can involve the heart, joints , skin, and brain( basal ganglia) Certain serotypes of GAS (M types 1, 3, 5, 6, 18, 24)

Group A Beta Hemolytic Streptococcus:

Group A Beta Hemolytic Streptococcus Gram positive coccus, rich in M protein - the virulence factor Rheumatogenic strains ,Immunogenic Resistant to phagocytosis Pharyngitis - acute rheumatic fever , RHD Skin infection- does not cause Rh.Fever or carditis as skin lipid cholesterol inhibit antigenicity


Epidemiology Age: 5 - 18 years Males & females equally affected Overcrowding, poverty, lack of access to medical care contributes to transmission Virulence of strain important In tropics/subtropics: year-round incidence with peak in colder months

Why rheumatic fever does not occur with every sore throat? :

Why rheumatic fever does not occur with every sore throat ? Streptococcal M-protein multiple streptococcal infections throughout one’s lifetime reinfections with the same serological M type are relatively less common individuals acquire circulating homologous anti-M antibodies following an infection

Pathophysiology :

Pathophysiology The cytotoxicity theory- GAS toxin Produces enzyme- streptolysin O The immune-mediated theory Immunologic cross reactivity between the GAS components and mammalian tissues M proteins (M1, M5, M6, and M19) share epitopes with human tropomyosin and myosin. the involvement of GAS superantigens exotoxins

Pathologic Lesions:

Pathologic Lesions Fibrinoid degeneration of connective tissue,inflammatory edema, inflammatory cell infiltration & proliferation of specific cells resulting in formation of Ashcoff nodules , resulting in- - Pancarditis in the heart Arthritis in the joints Ashcoff nodules in the subcutaneous tissue Basal gangliar lesions resulting in chorea

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2002–2003 WHO criteria for the diagnosis of rheumatic fever and rheumatic heart disease (based on the revised Jones criteria) These revised WHO criteria facilitate the diagnosis of: a primary episode of RF recurrent attacks of RF in patients without RHD recurrent attacks of RF in patients with RHD rheumatic chorea insidious onset rheumatic carditis chronic RHD.

Clinical features:

Clinical features Major diagnostic criteria Carditis Polyarthritis Chorea Subcutaneous nodules Erythema marginatum

Clinical manifestations of rheumatic fever:

Clinical manifestations of rheumatic fever

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

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 :

Closer view of erythema marginatum in the same patient


Minor diagnostic criteria Fever Arthralgia Prolonged PR interval on electrocardiogram Elevated acute-phase reactants (APRs), which are erythrocyte sedimentation rate and C-reactive protein

Supporting Evidence of Antecedent GAS Infection:

Supporting Evidence of Antecedent GAS Infection Elevated or rising antistreptolysin-o or other streptococcal antibody Positive throat culture Rapid antigen test for group A streptococci Recent scarlet fever.

WHO criteria for the diagnosis of RF & RHD (based on the revised Jones criteria):

WHO criteria for the diagnosis of RF & RHD (based on the revised Jones criteria) Diagnostic categories Criteria Primary episode of RF Two major or one major and two minor manifestations plus evidence of a preceding group A streptococcal infection Recurrent attack of RF in a patient without Two major or one major and two minor established rheumatic heart disease Two major or one major and two minor manifestations plus evidence of a preceding group A streptococcal infection. Recurrent attack of RF in a patient with established rheumatic heart disease Two minor manifestations plus evidence of a preceding group A streptococcal infection. Rheumatic chorea Insidious onset rheumatic carditis Other major manifestations or evidence ofgroup A streptococcal infection not required Chronic valve lesions of RHD Do not require any other criteria to be diagnosed as having RHD

Rheumatic Carditis:

Rheumatic Carditis Manifest as pancarditis 40-50% of cases Carditis leaves a sequlae & permanent damage to the organ Valvulitis occur in acute phase Chronic phase- fibrosis, calcification & stenosis of heart valves( fishmouth valve)

Acute rheumatic carditis:

Acute rheumatic carditis New or changing murmur Tachycardia Signs of heart failure Auscultary findings depends upon the valve involved

Recurrent Rheumatic Carditis:

Recurrent Rheumatic Carditis In patients with preexisting RHD, recurrence of RF is always associated with carditis , manifested as Pericarditis New valvular regurgitation and/or aggravation of the existing valve lesions Cardiomegaly CCF

Sydenham Chorea:

Sydenham Chorea 5-10% of cases Mainly in girls of 1-15 yrs age May appear even 6/12 yrs after the attack of rheumatic fever Clinically manifest as-clumsiness, deterioration of handwriting,emotional lability or grimacing of face Clinical signs- pronator sign, jack in the box sign , milking sign of hands

Erythema marginatum:

Erythema marginatum Occur in <5%. Unique,transient,serpiginous-looking lesions of 1-2 inches in size Pale center with red irregular margin More on trunks & limbs & non-itchy Worsens with application of heat Often associated with chronic carditis

Subcutaneous nodules :

Subcutaneous nodules Occur in 10% Painless,pea-sized,palpable nodules Mainly over extensor surfaces of joints,spine,scapulae & scalp Associated with strong seropositivity Always associated with severe carditis

Other minor features:

Other minor features Fever-(upto 101 degree F) Arthralgia Pallor Anorexia Loss of weight

Laboratory Findings:

Laboratory Findings CBC-Anemia, leucocytosis High ESR Elevated CRP ASO titre >200 Todd units.(Peak value attained at 3 weeks, then comes down to normal by 6 weeks) Throat culture-GABH streptococci but negative when RHD appear

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Rapid antigen detection test specificity >95% sensitivity 60-90% Extracellular- ASO Anti DNAse B Antihyluronidase Cellular-Antiteichoic acid Anti M PROTEIN Ab

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Chest x-ray cardiomegaly increased cardiothoracic ratio pulmonary congestion prominent pulmonary conus

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ECG- Prolonged PR interval, 2nd or 3rd degree blocks ST depression T inversion 2D Echo Cardiography- valve edema Mitral regurgitation, LA & LV dilatation, Pericardial effusion Decreased contractility


Diagnosis Rheumatic fever is mainly a clinical diagnosis No single diagnostic sign or specific laboratory test available for diagnosis Diagnosis based on MODIFIED JONES CRITERIA

Exceptions to Jones Criteria:

Exceptions to Jones Criteria Chorea alone, if other causes have been excluded Insidious or late-onset carditis with no other explanation Patients with documented RHD or prior rheumatic fever,one major criterion,or of fever,arthralgia or high CRP suggests recurrence

Valvular invlovement in chronic rheumatic heart disease:

Valvular invlovement in chronic rheumatic heart disease MITRAL VALVE : 65-70% AORTIC VALVE: 25% TRICUSPID : 10% PULMONARY : rarely involved


Treatment Step I - primary prevention (eradication of streptococci) Step II - anti inflammatory treatment (aspirin,steroids) Step III - supportive Tx & management of complications Step IV - secondary prevention (prevention of recurrent attacks)

Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis) :

Drug Dose Mode Duration Benzathine penicillin G 600 000 U for Patients 27 kg ( 60 lb)1 , 200 000 U for>27 kg Intramuscular Once OR Penicillin V 250 mg tds Oral 10 days For individuals allergic to penicillin Erythromycin 20-40 mg/kg/d 2-4 tds Oral 10 days Ethylsuccinate 40 mg/kg/d tds Oral 10 days Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis)

Other alternative drugs used:

Other alternative drugs used Clarithromycin (in patients allergic to penicillin) 7.5 mg/kg PO bid for 10 days Azithromycin (in patients allergic to penicillin) 12 mg/kg (not to exceed 500 mg) PO OD for 5 days

: Anti inflammatory treatment:

: Anti inflammatory treatment

Rheumatic carditis without failure:

Rheumatic carditis without failure Aspirin indicated 100 mg/kg/day q.i.d po x 3-5 days Then, 75 mg/kg/day q.i.d po x for 4 wks

Rheumatic carditis without failure:

Rheumatic carditis without failure Prednisolone 2-3 mg/kg/day x 2-3 weeks Tapered by 5 mg/day every 3-5 days Aspirin Added 75mg/kg Q.I.D for 6 wks

Supportive management & management of complications:

Supportive management & management of complications Bed rest Treatment of congestive cardiac failure: Restrict fluids Restrict salt Diuretics therapy Inotropic support After load reduction Digoxin

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Treatment of chorea: - diazepam or haloperidol Rest to joints & supportive splinting

Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks):

Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks ) DRUG DOSE ROUTE Benzathine penicillin G 1,200,000 U every 4 weeks Intramuscular OR Penicillin V 250 mg, twice a day Oral OR Sulfadiazine or sulfisoxazole 0.5 g OD for patients <=27 kg (<=60 lb) 1 gm OD for patients>=27 kg(>=60lb) Oral FOR PEOPLE WHO ARE ALLERGIC TO PENICILLIN & SULFONAMIDE DRUGS Erythromycin 250 mg twice daily Oral From the American Academy of Pediatrics: Red Book: 2006

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Duration of Secondary Rheumatic Fever Prophylaxis Category Duration Rheumatic fever with carditis and At least 10 y since last residual heart disease episode and at least until (persistent valvar disease*) age 40 y, sometimes lifelong prophylaxis Rheumatic fever with carditis 10 y or well into adulthood, but no residual heart disease whichever is longer (no valvar disease*) Rheumatic fever without carditis 5 y or until age 21 y, whichever is longer *Clinical or echocardiographic evidence.

Indications for surgery:

Indications for surgery Usually performed for chronic rheumatic valve disease asymptomatic., mildly symptomatic ,with progressive left ventricular enlargement on clinical or radiological examination(>0.5 cm/yr) Cardiac failure due to valve lesion Pulmonary hypertension, with physical signs and ECG evidences of changes in Rt. Ventricular hypertrophy, and chest X-ray evidence of pulmonary artery dilatation.

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Tricuspid regurgitation that complicates mitral valve disease Development of atrial fibrillation Thromboembolism When endocarditis is suspected to cardiac decomposition .

Surgical options:

Surgical options Valve palliation commissurotomy cusp thinning cusp excision cusp level chordal shortening post collar annuloplasty Valve replacement

Prophylactic antibiotic regimens for dental, oral, respiratory tract & oesophageal procedures :

Prophylactic antibiotic regimens for dental, oral, respiratory tract & oesophageal procedures Situation Antibiotic Dose Standard oral Amoxicillin One dose Parenteral Ampicillin One dose (IM/IV) Penicillin allergy Clindamycin One dose Oral Cephalexin/Cefadroxil One dose Parenteral Cefazolin One dose

For gastrointestinal and genitourinary tract procedures:

For gastrointestinal and genitourinary tract procedures Situation Antibiotic Dose High risk Ampicillin + gentamicin 2 doses High risk (allergy to penicillin) Vancomycin + gentamicin 1 dose Moderate risk Amoxicillin or ampicillin 1 dose Moderate risk (allergy to penicillin) Vancomycin alone 1 dose

Complications :

Complications Congestive cardiac failure Recurrence of Rheumatic fever Spontaneous Bacterial endocarditis Myocardial dysfunction Severe anaemia Infective endocarditis Arrhythmias


Prevention The three strategies for prevention consist of primordial prevention primary prevention secondary prevention.

Primordial Prevention:

Primordial Prevention Preventing the development of ‘risk factors’ in the community to prevent the disease in the population. Measures for primordial prevention in relation to RF & RHD consist of: Improvement in socio-economic status Prevention of overcrowding Prevention of undernutrition and malnutrition

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Public education regarding the risk of RF from sore throat specially below the age of 15 years. Public education is the most important component for primordial prevention. Availability of prompt medical care

Primary prevention :

Primary prevention Defined as the adequate antibiotic therapy of group A streptococcal upper respiratory tract (URT) infections to prevent an initial attack of acute RF Primary prevention is administered only when there is group A streptococcal URT infection Intermittent therapy ( in contrast to secondary prevention where there is continuous therapy) A cost-effective vaccine for group A streptococci

Secondary prevention:

Secondary prevention Continuous administration of specific antibiotics to patients with a previous attack of RF or a well-documented RHD The purpose is to prevent colonization or infection of the upper respiratory tract (URT) with group A beta-hemolytic streptococci & the development of recurrent attacks of RF Mandatory for all patients who have had an attack of RF, whether or not they have residual rheumatic valvular heart disease.

Prospects For A Vaccine Against Rheumatic Fever :

Prospects For A Vaccine Against Rheumatic Fever Immunity to GAS is type specific & dependent on antibodies to M protein, attempts at vaccine production have focused primarily on M protein purification. Since the extraction of M protein by Rebecca Lancefield , its further purification has led to its molecular definition .

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Bacteriological facilities required to diagnose streptococcal sore throat at the community level for the whole country, at present, do not exist and are not likely in the near future. Hence, each sore throat will need to be treated .


A recombinant, multivalent vaccine containing the type-specific epitopes of some 26 M serotypes associated the great majority of serious GAS infections is currently under field trial . Newly identified M types containing dangerous strains could be added subsequently as necessary.


Prognosis Rheumatic fever can recur whenever the individual experience new GABH streptococcal infection,if not on prophylactic medicines Good prognosis for older age group & if no carditis during the initial attack Bad prognosis for younger children & those with carditis with valvular lesions

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Thank you

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