Who guiidelines for rheumatic fever

DR. ANITA LAMICHHANEDEPTT. OF PEDIATRICS

SHAIKH ZAYED HOSPITAL, LAHORE.

WHO guidelines for the treatment of Rheumatic fever

Diseases caused by group A streptococcus

Pharyngitis

Impetigo/pyoderma

Pneumonia, Necrotizing fasciitis

Rheumatic fever

Glomerulonephritis

Osteomyelitis

Scarlet fever & erysipelas

Toxic shock syndrome

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

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

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?

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

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

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

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:

o a primary episode of RF

o recurrent attacks of RF in patients without RHD

o recurrent attacks of RF in patients with RHD

o rheumatic chorea

o insidious onset rheumatic carditis

o chronic RHD.

Clinical features

Major diagnostic criteria

Carditis

Polyarthritis

Chorea

Subcutaneous nodules

Erythema marginatum

Clinical manifestations of rheumatic fever

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

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

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)

Diagnostic categories Criteria

Primary episode of RF Two major or one major and two minormanifestations plus evidence of apreceding group A streptococcalinfection

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 minormanifestations plus evidence of apreceding 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 streptococcalinfection.

Rheumatic choreaInsidious 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

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

New or changing murmur

Tachycardia

Signs of heart failure

Auscultary findings depends upon the valve

involved

Recurrent Rheumatic Carditis

In patients with preexisting RHD, recurrence of

RF is always associated with carditis, manifested

as

o Pericarditis

o New valvular regurgitation and/or aggravation of

the existing valve lesions

o Cardiomegaly

o CCF

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

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

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

Fever-(upto 101 degree F)

Arthralgia

Pallor

Anorexia

Loss of weight

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

• Rapid antigen detection test

specificity >95%

sensitivity 60-90%

Extracellular- ASO

Anti DNAse B

Antihyluronidase

Cellular-Antiteichoic acid

Anti M PROTEIN Ab

Chest x-ray

cardiomegaly

increased cardiothoracic ratio

pulmonary congestion

prominent pulmonary conus

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

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

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)

Drug Dose Mode Duration

Benzathine penicillin G

600 000 U forPatients 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

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

Arthritis only Aspirin 75-100mg/kg/day,give as 4divided doses for 6weeks(Attain a blood level 20-30 mg/dl)

Carditis Prednisolone 2-2.5mg/kg/day, give as twodivided doses for 2weeksTaper over 2 weeks &while tapering addAspirin 75 mg/kg/dayfor 2 weeks.Continue aspirin alone100 mg/kg/day foranother 4 weeks

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

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

Bed rest

Treatment of congestive cardiac failure: Restrict fluids Restrict salt Diuretics therapy Inotropic support After load reduction Digoxin

Treatment of chorea:

- diazepam or haloperidol

Rest to joints & supportive splinting

Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks)

DRUG DOSE ROUTEBenzathine 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

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

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.

Tricuspid regurgitation that complicates mitral

valve disease

Development of atrial fibrillation

Thromboembolism

When endocarditis is suspected to cardiac

decomposition.

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

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 genitourinarytract 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

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

o primordial prevention

o primary prevention

o secondary 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:

o Improvement in socio-economic status

o Prevention of overcrowding

o Prevention of undernutrition and malnutrition

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

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

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

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 .

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