1. Dr.Said Alavi
MD,DCH,DNB,FCPS
Dept. of Pediatrics and Neonatology
Saqr Hospital,Ras Al Khaimah
UNITED ARAB EMIRATES
E-mail: drsaid@emirates.net.ae

2. Objectives
Etiology
Epidemiology
Pathogenesis
Pathologic lesions
Clinical manifestations & Laboratory
findings
Diagnosis & Differential diagnosis
Treatment & Prevention
Prognosis
References
05/05/1999 2 Dr.Said Alavi

3. Etiology
Acute rheumatic fever is a systemic
disease of childhood,often recurrent that
follows group A beta hemolytic
streptococcal infection
It is a delayed non-suppurative sequelae
to URTI with GABH streptococci.
It is a diffuse inflammatory disease of
connective tissue,primarily involving
heart,blood vessels,joints, subcut.tissue
and CNS
05/05/1999 3 Dr.Said Alavi

4. Epidemiology
Ages 5-15 yrs are most susceptible
Rare <3 yrs
Girls>boys
Common in 3rd world countries
Environmental factors-- over crowding,
poor sanitation, poverty,
Incidence more during fall ,winter &
early spring
05/05/1999 4 Dr.Said Alavi

5. Pathogenesis
Delayed immune response to infection
with group.A beta hemolytic
streptococci.
After a latent period of 1-3 weeks,
antibody induced immunological
damage occur to heart valves,joints,
subcutaneous tissue & basal
ganglia of brain
05/05/1999 5 Dr.Said Alavi

6. Group A Beta Hemolytic Streptococcus
Strains that produces rheumatic fever -
M types l, 3, 5, 6,18 & 24
Pharyngitis- produced by GABHS can
lead to- acute rheumatic fever ,
rheumatic heart disease &
post strept. Glomerulonepritis
Skin infection- produced by GABHS leads
to post streptococcal glomerulo nephritis
only. It will not result in Rh.Fever or
carditis as skin lipid cholesterol inhibit
antigenicity
05/05/1999 6 Dr.Said Alavi

7. Diagrammatic structure of the group A
beta hemolytic streptococcus
Capsule Antigen of outer
protein cell wall
Cell wall of GABHS
induces antibody
Protein antigens response in
victim which
Group carbohydrate result in
autoimmune
Peptidoglycan damage to heart
valves,
Cyto.membrane
sub cutaneous
tissue,tendons,
Cytoplasm joints & basal
ganglia of brain
……………………………………………
……...
05/05/1999 7 Dr.Said Alavi

8. 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
05/05/1999 8 Dr.Said Alavi

9. Rheumatic Carditis Histology (40X)
05/05/1999 9 Dr.Said Alavi

10. Histology of Myocardium in Rheumatic Carditis
(200X)
05/05/1999 10 Dr.Said Alavi

11. Clinical Features
1.Arthritis
Flitting & fleeting migratory polyarthritis,
involving major joints
Commonly involved joints-
knee,ankle,elbow & wrist
Occur in 80%,involved joints are
exquisitely tender
In children below 5 yrs arthritis usually
mild but carditis more prominent
Arthritis do not progress to chronic
disease
05/05/1999 11 Dr.Said Alavi

12. Clinical Features (Contd)
2.Carditis
Manifest as pancarditis(endocarditis,
myocarditis and pericarditis),occur in 40-
50% of cases
Carditis is the only manifestation of
rheumatic fever that leaves a sequelae &
permanent damage to the organ
Valvulitis occur in acute phase
Chronic phase- fibrosis,calcification &
stenosis of heart valves(fishmouth
valves)
05/05/1999 12 Dr.Said Alavi

13. Rheumatic
heart
disease.
Abnormal
mitral
valve.
Thick,
fused
chordae
05/05/1999 13 Dr.Said Alavi

14. Another view of
thick and fused
mitral valves in
Rheumatic
heart disease
05/05/1999 14 Dr.Said Alavi

15. Clinical Features (Contd)
3.Sydenham Chorea
Occur in 5-10% of cases
Mainly in girls of 1-15 yrs age
May appear even 6/12 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
05/05/1999 15 Dr.Said Alavi

16. Clinical Features (Contd)
4.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
05/05/1999 16 Dr.Said Alavi

17. Clinical Features (Contd)
5.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
05/05/1999 17 Dr.Said Alavi

18. Clinical Features (Contd)
Other features (Minor features)
Fever-(upto 101 degree F)
Arthralgia
Pallor
Anorexia
Loss of weight
05/05/1999 18 Dr.Said Alavi

19. Laboratory Findings
High ESR
Anemia, leucocytosis
Elevated C-reactive protien
ASO titre >200 Todd units.
(Peak value attained at 3 weeks,then
comes down to normal by 6 weeks)
Anti-DNAse B test
Throat culture-GABHstreptococci
05/05/1999 19 Dr.Said Alavi

20. Laboratory Findings (Contd)
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
05/05/1999 20 Dr.Said Alavi

21. 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
05/05/1999 21 Dr.Said Alavi

22. Jones Criteria (Revised) for Guidance in the
Diagnosis of Rheumatic Fever*
Major Manifestation Minor Supporting Evidence
Manifestations of Streptococal Infection
Carditis Clinical Laboratory
Polyarthritis Previous Acute phase
Chorea rheumatic reactants: Increased Titer of Anti-
Erythema Marginatum fever or Erythrocyte Streptococcal Antibodies ASO
Subcutaneous Nodules rheumatic sedimentation (anti-streptolysin O),
heart disease rate, others
Arthralgia C-reactive Positive Throat Culture
Fever protein, for Group A Streptococcus
leukocytosis Recent Scarlet Fever
Prolonged P-
R interval
*The presence of two major criteria, or of one major and two minor criteria,
indicates a high probability of acute rheumatic fever, if supported by evidence of
Group A streptococcal nfection.
Recommendations of the American Heart Association
05/05/1999 22 Dr.Said Alavi

23. 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
05/05/1999 23 Dr.Said Alavi

24. Differential Diagnosis
Juvenile rheumatiod arthritis
Septic arthritis
Sickle-cell arthropathy
Kawasaki disease
Myocarditis
Scarlet fever
Leukemia
05/05/1999 24 Dr.Said Alavi

25. Treatment
Step I - primary prevention
(eradication of streptococci)
Step II - anti inflammatory treatment
(aspirin,steroids)
Step III- supportive management &
management of complications
Step IV- secondary prevention
(prevention of recurrent attacks)
05/05/1999 25 Dr.Said Alavi

26. STEP I: Primary Prevention of Rheumatic Fever
(Treatment of Streptococcal Tonsillopharyngitis)
Agent Dose Mode Duration
Benzathine penicillin G 600 000 U for patients Intramuscular Once
27 kg (60 lb)
1 200 000 U for patients >27 kg
or
Penicillin V Children: 250 mg 2-3 times daily Oral 10 d
(phenoxymethyl penicillin) Adolescents and adults:
500 mg 2-3 times daily
For individuals allergic to penicillin
Erythromycin: 20-40 mg/kg/d 2-4 times daily Oral 10 d
Estolate (maximum 1 g/d)
or
Ethylsuccinate 40 mg/kg/d 2-4 times daily Oral 10 d
(maximum 1 g/d)
Recommendations of American Heart Association
05/05/1999 26 Dr.Said Alavi

27. Step II: Anti inflammatory treatment
Clinical condition Drugs
Arthritis only Aspirin 75-100
mg/kg/day,give as 4
divided doses for 6
weeks
(Attain a blood level 20-
30 mg/dl)
Carditis Prednisolone 2-2.5
mg/kg/day, give as two
divided doses for 2
weeks
Taper over 2 weeks &
while tapering add
Aspirin 75 mg/kg/day
for 2 weeks.
Continue aspirin alone
100 mg/kg/day for
another 4 weeks
05/05/1999 27 Dr.Said Alavi

28. 3.Step III: Supportive management &
management of complications
Bed rest
Treatment of congestive cardiac failure:
-digitalis,diuretics
Treatment of chorea:
-diazepam or haloperidol
Rest to joints & supportive splinting
05/05/1999 28 Dr.Said Alavi

29. STEP IV : Secondary Prevention of Rheumatic Fever
(Prevention of Recurrent Attacks)
Agent Dose Mode
Benzathine penicillin G 1 200 000 U every 4 weeks* Intramuscular
or
Penicillin V 250 mg twice daily Oral
or
Sulfadiazine 0.5 g once daily for patients 27 kg (60 lb Oral
1.0 g once daily for patients >27 kg (60 lb)
For individuals allergic to penicillin and sulfadiazine
Erythromycin 250 mg twice daily Oral
*In high-risk situations, administration every 3 weeks is justified and
recommended
Recommendations of American Heart Association
05/05/1999 29 Dr.Said Alavi

30. 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.
Recommendations of American Heart Association
05/05/1999 30 Dr.Said Alavi

31. 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 valvar lesions
05/05/1999 31 Dr.Said Alavi

32. References
Hoffman JIE: Rheumatic Fever . Rudolph's Pediatrics; 20th Ed:
1518 - 1521,1996.
Stollerman GH: Rheumatic Fever . Harrison's Principles Of Internal
Medicine; 13th Ed: 1046 - 1052,1995.
Special Writing Group of the Committee on Rheumatic
Fever,endocarditis & Kawasaki Disease of the Council on
Cardiovascular Disease in the Young of the American Heart
Association: Guidelines for the Diagnosis of Rheumatic Fever. In
Jones Criteria, 1992 Update JAMA 268:2029,1992
Todd J: Rheumatic Fever . Nelson's Textbook Of Pediatrics; 15th
Ed: 754 - 760, 1996.
Warren R, Perez M, Wilking A: Pediatric Rheumatic Diseases .
Pediatric Clinics of North America; 41: 783 - 818,1994.
WorldHealth Organization Study Group: Rheumatic Fever &
Rheumatic Heart Disease,technical Report Series No.
764.Geneva,world Health Organization, 1988
05/05/1999 32 Dr.Said Alavi

33. 05/05/1999 33 Dr.Said Alavi