ACUTE RHEUMATIC

FEVER
PRESENTER- DR SUBIN JOLLY

MODERATOR- DR REMYA
INTRODUCTION
Acute Rheumatic fever (ARF) is thought to be
• An auto immune consequence.
• Following Streptococcus pyogenes infection
• Age group between 5 to 15 years
• Affects mainly the heart, joints, brain and skin.
• In India, rheumatic fever is endemic
• One of the major causes of cardiovascular disease
• 25-45% of acquired heart disease.
• Incidence varies btw 100-200/100,000 children of school age from
5-17 years of age.
Why Streptococcus?
• Humans are the natural reservoir for GAS.
• Incidence of pharyngeal infections is highest in 5-15
years of age group, esp young school children.
• Group A Streptococcus (GAS) causes serious non
suppurative complications  Rheumatic fever and
Acute Glomerulonephritis.
• 2/3rds of pts with an a/c episode of RF have h/o of GAS
pharyngitis.
• Antibody titres are usually high in these patients.
• Closed communities  boarding schools, military bases.
PATHOPHYSIOLOGY
THEORIES

CYTOTOXIC THEORY

IMMUNOLOGIC
THEORIES
CYTOTOXICITY THEORY

• GAS produces a number of enzymes that are cytotoxic to

mammalian cardiac cells, such as streptolysin O.
• Drawback  inability to explain the substantial latent
period btw GAS pharyngitis and onset of ARF.
IMMUNOLOGIC THEORIES

1. Molecular Mimicry
• Common epitopes are shared btw certain GAS components (eg,
M protein, cell membrane, group A cell wall carbohydrate,
capsular hyaluronate) & specific mammalian tissues as heart
valve, sarcomere, brain, joint.
• A more recently proposed hypothesis  binding of an M
protein N- terminus domain to a region of collagen type 4
 Ab response to the collagen  ground substance
inflammation esp in subendothelial areas like
myocardium and cardiac valves.
CLINICAL MANIFESTATIONS & DIAGNOSIS

• The Jones Criteria revised in 2015 is intended for

diagnosis of initial attack of acute rheumatic fever and
recurrent attacks.
LOW- RISK POPULATION

Those with incidence < 2/100,000 school age children per year or all- age
rheumatic heart disease prevalence of < 1/1000 population.
 MODERATE / HIGH RISK
POPULATION

Those with incidence > 2/100,000 school age children per year or
all- age rheumatic heart disease prevalence of > 1/1000
population
 DIAGNOSIS OF A FIRST/ RECURRENT ATTACK

Evidence of
Pt fulfills 2 1 major & 2 preceding GAS
major minor criteria infection
DIAGNOSIS OF RECURRENT ATTACK
• Only to the moderate / high risk population

Evidence of preceding
Presence of 3 minor
GAS infection
2015 Jones Criteria a major change

Expands the defn of the major criterion – carditis – to include subclinical

evidence ( the absence of a murmur, ECHO evidence of MR meeting specific
criteria to distinguish btw physiologic from pathologic murmur)
Areas in which the Jones criteria differ
in low risk from moderate/ high risk
populations  major criterion of
arthritis and in the minor criteria of
arthralgia, defn of fever, & elevated
inflammatory markers.
• There are 3 circumstances in which diagnosis of acute rheumatic fever
can be made without strict adherence to the Jone’s criteria:
1. When chorea occurs only as the major manifestation of acute rheumatic
fever,
2. When indolent carditis is the only manifestation in patients who first come
to medical attention only months after the apparent onset of ARF, and
3. In a limited number of patients with recurrences of ARF in particularly high
risk population.
MAJOR CRITERIA

Migratory Polyarthritis
• occurs in 75% of patients with acute rheumatic fever
• Arthritis is the earliest manifestation and may correlate with peak
antistreptococcal antibody titres.
• Large joints  knees, ankles, wrists and elbows
• Rheumatic joints  hot, red, swollen, and exquisitively tender
• Migratory in nature.
• Dramatic response to low doses of salicylates is characteristic .
• Rheumatic arthritis is never deforming.
• Synovial fluid  10,000 – 100,000 wbc with predominance of
neutrophils, protein of 4g/dl, normal glucose level, forms a good
mucin clot.
• Inverse relation btw severity of arthritis and severity of cardiac
involvement.
• Moderate/high risk monoarthritis in the absence of prior
inflammatory therapies or even polyarthralgia w/o frank objective
signs of arthritis can fulfill this major criterion.
2. CARDITIS

• Occurs in 50-60% of all cases of a/c rheumatic fever.

• Carditis & chronic rheumatic heart disease  most serious manifestations of acute
rheumatic fever.
• Rheumatic carditis is characterized by pancarditis, with active inflammation of
myocardium, pericardium and endocardium.
• Endocarditis (valvulitis) is a universal finding in rheumatic carditis
• Most rheumatic heart disease is isolated mitral valvular disease or combined aortic
and mitral valvular disease.
VIJAYA’S ECHO CRITERIA
SL NO ECHO FEATURE SCORE
1 Mitral valve and aortic valve thickness > 4mm 2
2 Increased echogenicity of submitral structures 2
3 Rheumatic nodules (beaded appearance) 2
4 MVP/ aortic valve prolapse/tricuspid regurgitation 2
5 MR/ AR/ TR 2
6 Reduced mobility of valves 2
7 Chordal tear 2
8 Pericardial effusion 2
TOTAL SCORE 16
• A/c rheumatic carditis  presents as tachycardia and cardiac
murmurs with/ without evidence of myocardial / pericardial
involvement.
• Moderate to severe rheumatic carditis  cardiomegaly and heart
failure with hepatomegaly and peripheral and pulmonary oedema.
• ECHO  pericardial effusion, decreased ventricular contractility and
aortic and /or mitral regurgitation.
• MR in ARF is usually mild to moderate
• Mechanisms of MR are
• Valvulitis
• Valve prolapse
• Annulitis with annular dilatation
• Ventricular enlargement
• Rarely chordal rupture
• MR is characterized typically by a high pitched apical holo systolic
murmur radiating to axilla.
• Significant MR may be associated with an apical mid- diastolic
murmur of MS.
• Aortic insufficiency  high – pitched decrescendo diastolic murmur at
the left sternal border.
• Major consequence of a/c rheumatic carditis is chronic, progressive
valvular disease, esp valvular stenosis  valve replacement.
3 .CHOREA
• 4-8 weeks after GABHS pharyngitis.
• Presents as an isolated, frequently subtle, movement disorder.
• Emotional lability, incoordination, poor school performance,
uncontrollable movements and facial grimacing exacerbated by stress
and disappearing with sleep are characteristic .
• Occasionally unilateral.
• Cardiac involvement, esp affecting mitral valve occurs in 2/3rds and
arthritis in 1/3rd of SC pts.
• Clinical manoeuvres to elicit features of chorea are
• 1) milmaids grip
• 2) spooning and pronation of the hands when the patients arms
are extended
• 3) wormian darting movements of the tongue upon
protrusion and
• 4) examination of handwriting to evaluate fine motor
movement.
• SC resolves within 1-6 months
• Pathophysiologically  Abs against GABHS that cross react with
molecular mimicry, with either neuronal extracellular surface or
intracellular antigens.
• Alters neuronal cell signal transduction dopamine.
ERYTHEMA MARGINATUM
• Rare (approx. 1% with a/c rheumatic fever)
• Characteristic rash of a/c rheumatic fever.
• Erythematous, serpiginous, macular lesions with pale centres that are not pruritic.
• Seen primarily on the trunk and extremities, but not on face, accentuated by
warming the skin.
5. SUBCUTANEOUS NODULES

• < 1% of patients with a/c rheumatic fever

• Consist of firm nodules approx.1cm in diameter along the extensor surfaces of
tendon near bony prominences.
• Significant correlation between the presence of these nodules and significant
rheumatic heart disease.
MINOR CRITERIA
LOW RISK POPULATION MODERATE/HIGH RISK
POPULATION
Joint manifestation polyarthralgia monoarthralgia

Fever Atleast 38.5 degree C Atleast 38 degree C

Laboratory criteria ESR – 60mmhr ESR– 30mmhr

CRP – 30mg/dl CRP- 30mg/dl
• prolonged PR interval on ECG (unless carditis is a major criterion)

3-12 12-14 >17yrs0.2 sec

yrs0.16sec yrs0.18sec
PITFALLS IN JONES CRITERIA
1. Difficult to diagnose ARF when carditis is the only manifestation of
the disease particularly in recurrence.
2. When pt has subclinical carditis the clinicians fail to detect
clinically.
3. Clinically apparent carditis is present but supportive minor criteria
are not fulfilled.
4. When previous cardiac status is unknown it is not possible to know
in a new case whether the findings are due to a/c carditis or it is
recrudescence or it is established old case of RHD.
5. In cases of polyarthralgia, which is a minor criteria, if the pt is
neglected and not evaluated for ARF, they would go undiagnosed,
could end up with RHD, allegedly w/o any past h/o of ARF, as the pt
and the parents would have long forgotten the joint pains.
Evidence of Antecedent GROUP A Streptococcal Infection
• H/o sore throat or of scarlet fever unsubstantiated by lab data  not
adequate evidence of recent infection.
• Positive throat cultures or rapid streptococcal antigen tests for grp A
 less reliable  do not distinguish btw recent & c/c pharyngeal
carriage.
• Streptococcal ab tests  most reliable of antecedent strep
infection.
1. ASO titre most widely used. ASO titres of atleast 333 Todd units in
children and 250 Todd units in adults are considered elevated. A
single low ASO titre does not exclude ARF.
2. Antideoxyribonuclease B test is favoured over other tests. Titres of
240 Todd units or greater in children and 120 Todd units or greater in
• adults are considered elevated.
• Streptozyme test is a relatively simple agglutination test, but is
less standard and less reproducible than the other antibody
tests. Should not be used as a definitive test of antecedent Grp
A strep infection.
RECURRENCE  New episode following
another GABHS inftn, occurring after 8 weeks
following stopping Rx.
RELAPSE 
Worsening of RF
while under Rx
and often with
carditis.
REBOUND  Occuring within 4-6 weeks of
stopping Rx or while tapering drugs.
 Antibody response of ASO peaks at
approx. 3-5 wks following GAS
pharyngitis, which usually is during 1-
3wks of ARF

ADB titres peak at 6-8 weeks.

INVESTIGATIONS

• CBC – Hb, Plt

• ESR
• CRP
• Throat culture
• ASO, anti DNAse B
• Chest X-ray
• ECG
• ECHO – not mandatory but plays an impt role in Dx of subclinical
carditis.
TREATMENT
GENERAL GUIDELINES FOR BED REST & INDOOR AMBULATION

Arthritis alone Mild carditis Moderate Severe carditis

carditis

Bed rest 1-2 wk 3-4 wk 4-6 wk As long as

congestive heart
failure is prsent
Indoor ambulation 1-2 wk 3-4 wk 4-6 wk 2-3 months
ANTIBIOTIC THERAPY

• Regardless of throat culture results, patients should receive 10 days

of orally administered penicillin or amoxicillin or a single IM injection of
benzathine penicillin to ensure eradication of GAS from upper
respiratory tract.
• If penicillin- allergic, 10 days of erythromycin, azithromycin (5 days) or
clindamycin is indicated.
• After this initial course of Ax therapy, long term Ax prophylaxis should
be initiated.
ANTI-INFLAMMATORY THERAPY

• Salicylates should be with-held if arthralgia or atypical arthritis is the only clinical

manifestation.

• WHY??
• In v/o the rapid response to salicylate treatment thus, obscuring diagnosis of a/c
rheumatic fever.
• Till then  Acetaminophen can be used to control pain and fever.
• Those with migratory polyarthritis and with carditis w/o cardiomegaly/ CHF should
be treated with oral salicylates.
• Aspirin 50-70 mg/kg/day in 4 divided doses PO for 3-5 days, followed by
50mg/kg/day in 4 divided doses PO for 3 wk and half that dose for another 2-4
weeks.
• Pts with carditis /cardiomegaly / congestive heart failure should receive
corticosteroids.
• Prednisolone  2mg/kg/day in 4 divided doses for 2-3 wks followed
• by half the dose for 2-3 weeks and then tapering the dose by 5mg/24 hours every
2-3 days.
• When prednisolone is being tapered , aspirin should be started at 50 mg/kg/day in 4
divided doses for 6 wk to prevent rebound of inflammation.
• Supportive therapy with mod to severe carditis include digoxin, fluid and salt
restriction, diuretics, and oxygen.
RECOMMENDED ANTI-INFLAMMATORY AGENTS
Arthritis alone Mild carditis Moderate Severe carditis
carditis
Prednisolone 0 0 0 2-6wks

Aspirin 1-2wk 3-4wk 4-6wk 2-4mnths

CHF
• Complete bed rest with orthopnoeic position and moist, cool oxygen
• Morphine sulphate, 0.2mg/kg, at 4 hour intervals for severe CHF
with resp distress.
• Restriction of sodium and fluid intake.
• Prednisolone for severe carditis of recent onset.
• Digoxin ( used with caution , because certain patients with
rheumatic carditis are supersensitive to digitalis), beginning with half
the usual recommended dose.
• Fruosemide, 1mg/kg, every 6-12 hours, if needed.
SYDENHAM CHOREA

• Rx includes use of penicillin therapy, symptomatic

medications and immunomodulatory therapy.
• Use of anticonvulsants (valproate, carbamazepine) and
neuroleptics (pimozide, haloperidol, risperidone, olanzapine).
• Phenobarbital every 6-8 hr PO is the drug of choice.
• If phenobarbital is ineffective, then haloperidol divided BD
PO or chlorpromazine every 4-6 hr PO.
• Prednisolone 0.5 mg/kg daily may be commenced , with weaning as
early as possible, preferably after 1 week if symptoms are reduced.
• Ivig may lead to more rapid resolution of chorea but have shown no
benefit on the short or long term outcome of carditis in ARF without
chorea.
 PROGNOSIS

• Prognosis depends on the clinical manifestations present at

the time of the initial episode, the severity of the initial
episode and the presence of recurrence.
• Immunologic determinants
HLA – DR 7
INCREASED
- DR 4 SUSCEPTIBILITY
• Monozygotic twins  44%
• Dizygotic twins  12%
• Protection for ARF

HLA DR 5, DR 6, DR 51, DR 52, DQ

PREVENTION
Primary prevention
• Appropriate Ax therapy instituted before the 9th day of symptoms of a/c GAS
pharyngitis is highly effective in preventing first attacks of a/c rheumatic fever.

Secondary prevention
• Requires continuous Ax prophylaxis which should be begun as soon as the
diagnosis of a/c rheumatic fever has been made and immediately after a full
course of Ax therapy has been completed.
• Ax prophylaxis should continue in these pts until they reach
21 years of age or until 5 years have elapsed since the last
rheumatic fever attack.
CHEMOPROPHYLAXIS FOR RECURRENCE OF ACUTE
RHEUMATIC FEVER (SECONDARY PROPHYLAXIS)
DRUG DOSE ROUTE

Penicillin G benzathine 600,000 IU for children weighing < Intramuscular

60 lb & 1.2 million IU for children
OR >60 lb, every 4 wk
Penicillin V 250 mg, twice daily Oral

OR
Sulfadiazine or sulfisoxazole 0.5 g, once daily for patients Oral
weighing < 60 lb
1.0 g, once daily for patients
weighing > 60 lb
For People who are allergic to Penicillin and Sulfonamide drugs
Macrolide or azalide Variable Oral
DURATION OF PROPHYLAXIS FOR PEOPLE WHO HAVE HAD
ACUTE RHEUMATIC FEVER : AHA RECOMMENDATIONS

CATEGORY DURATION

Rheumatic fever w/o carditis 5yr or until 21yr of age, whichever is longer

Rheumatic fever with carditis but w/o residual 10yr or until 21 yr of age, whichever is longer
heart disease (no valvular disease*)

Rheumatic fever with carditis and residual 10yr or until 40 yr of age, whichever is longer,
heart disease (persistent valvular disease*) sometimes lifelong prophylaxis
REFERENCES
• NELSON
• HARRISON
• ARTICLES
• ACUTE RHEUMATIC FEVER CURRENT SCENARIO IN INDIA..
• TREATMENT OF SYDENHAM’S CHOREA : A REVIEW OF THE
CURRENT EVIDENCE.
• CONSENSUS GUIDELINES ON PAEDIATRIC ACUTE RHEUMATIC
FEVER AND RHEUMATIC HEART DISEASE.