Rheumatic fever is an autoimmune disease that can develop after a streptococcal throat infection. It causes inflammation in various body systems like the heart, joints, brain and skin. The pathogenesis involves antibodies produced against streptococci that cross-react with human tissues due to molecular mimicry. Rheumatic fever is diagnosed using the modified Jones criteria and treated with antibiotics to eliminate the streptococcal infection as well as anti-inflammatory drugs. Long-term prevention involves continued antibiotic prophylaxis to prevent recurrent attacks that can lead to chronic rheumatic heart disease.

1. Update of Rheumatic Fever :
Prevention and Treatment
Teddy Ontoseno
Cardiology Division
Department of Child Health Dr Sutomo Hospital
Airlangga University

2. Rheumatic Fever:
Definition:
• Autoimmune
• Multisystem
• Inflammatory disorder
• Following group A, (ß-hemolytic)
streptococcal pharyngitis.

3. Rheumatic fever-pathogenesis
•Group A streptococcal(GAS) pharyngeal infection
•Body produce antibodies against streptococci ->
•These antibodies cross react with human tissues
because of the antigenic similarity between
streptococcal components and human connective tissues
(molecular mimicry)[there is certain amino acid sequence that
is similar btw GAS and human tissue]->
•Immunologically mediated inflamation & damage
(autoimmune) to human tissues which have antigenic
similarity with streptococcal components- like heart,
joint, brain connective tissues

4. Rheumatic fever-pathogenesis

5. Rheumatic fever-pathogenesis

6. Philosophical - Practical considerations
“Rheumatic fever”
• Immunologically mediated inflammatory
• Major public health problem
• Preventable and easily treatable
• Causing severe cardiac dysfuction
decades later

7. Background

8. Scope of the Problem

9. History

10. Rheumatic fever-epidemiology
• Parallels with epidemiology of streptococcal
pharyngitis(only when there is GAS throat infection,
there R.F.)
• Incidence –
• 3% in epidemics of exudative streptococcal
pharyngitis in closed community(school,army)
• 0.3% in civilian population with sporadic
streptococcal throat infection
• 50% if there is a past history of rheumatic
fever(thus secondary prophylaxis is important)
• first attack between 5-15 years(a childhood disease)
• poor socioeconomic conditions and overcrowding

11. 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

12. EPIDEMIOLOGY
• Infection of the skin - younger than 6 yr
• Streptococcal pharyngitis - between 5
and 15 yr of age
• Scarlet fever - common in children > 3 yr
of age

13. EPIDEMIOLOGY in INDONESIA
Today
?
Tomorrow
?
?
Yesterday

14. ETIOLOGY
• Streptococci - gram-positive cocci
• classified : ability to hemolyze red
blood cells
1. complete hemolysis (β-hemolytic)
2. partial hemolysis (α-hemolytic)
3. no hemolysis (γ-hemolytic)

15. ETIOLOGY

16. Structure of Group A cell wall

17. Capsule
Cell wall
Protein antigens
Group carbohydrate
Peptidoglycan
Cyto.membrane
Cytoplasm
Antigen of outer
protein cell wall of
GABHS induces
antibody response in
victim which result
in autoimmune
damage to heart
valves, sub
cutaneous tissue,
tendons, joints &
basal ganglia of
brain
ETIOLOGY

18. AETHIOPATHOGENESIS
Immune Disorders:
• Immunodeficiency disorders
• AIDS, antibody deficiency
• Hypersensitivity Disorders (allergy)
–Type-I (IgE), II-IgG, III-Immunecomplex, IV-
Cell mediated.
• Autoimmune disorders
–SLE, Rhematoid, Rheumatic fever.

19. AETHIOPATHOGENESIS
C. Anti-M antibodies against the streptococci
may cross-react with heart tissue, causing the
pancarditis that is observed in RF.
B. Rheumatogenic strains of
GABHS M types l, 3, 5, 6,18
& 24 have antigenic domains
similar to antigens in
components of the human heart
A. Only infections
GABHS of the pharynx
initiate or reactivate
RF.

20. Rheumatic Fever: Cross Reactive Epitopes

21. Rheumatic Fever: Cross Reactive Epitopes

22. Molecular mimicry is one way in which infectious agents can break self-
tolerance. An immune response to bacterial antigens with similarities to
self tissue antigens can lead to an autoimmune reaction against the self
tissue

23. Throat
Heart
Rheumatic Fever: TissueDamage
The Recent Concept :
HUMORAL and
CELLULAR

24. Clinical Features:
• R.F. can be presented in many ways:
a. arthritis without cardiac involvement
b. rheumatic chorea without arthritis nor carditis
c. carditis with or without arthritis

25. Clinical Features:
•Acute Rheumatic Fever
– Acute Inflammatory Phase
– Heart – Pancarditis (40-50%)
– Skin – Erythema Marginatum/ S.nodule (10%)
– CNS – Sydenham Chorea (15%)
– Migratory polyarthritis (75%)
•Chronic Rheumatic Fever
–Deforming fibrotic valvular disease.

27. Electrocardiogram
• Persistent sinus tachycardia
• Sinus bradycardia
• Prolonged PR interval
• Transient complete heart block
• Atrial fibrillation or flutter
• Bundle branch block
• Low QRS voltage

29. The Jones Criteria for Rheumatic
Fever, Updated 1992
• Major Criteria
– Carditis
– Migratory polyarthritis
– Sydenham's chore
– Subcutaneous nodules
– Erythema marginatum
•Minor Criteria
– Clinical
• fever
• Arthralgia
– Laboratory
• Elevated acute phase
reactants
• Prolonged PR interval
plus
 Supporting evidence of a recent group A streptococcal infection
• positive throat culture or
• rapid antigen detection test; and/ or elevated or
• increasing streptococcal antibody test
(e.g., anti-streptolysin O, anti-deoxyribonuclease B, anti-hyaluronidase).

31. Major criteria of Jones
Help to remember :
CAPOCHES
Carditis
Polyarthritis
Chorea
Erythema Marginatum
Subcutan nodule

32. Carditis of ARF
• Pancarditis
• 40 and 60% of patients with ARF
• Characterised by
– sinus tachycardia,
–Organic cardiac murmurs not previously
present (mitral regurgitation)
– pericardial friction rub
– cardiomegaly
– prolonged PR interval and evidence of heart failure
may be present – nonspecific

33. Carditis
• Course : mild – fulminant
• Onset : first 3 weeks of illness
• Cardiac enzymes: normal or
minimally elevated

34. Subcutaneous nodules
• Rarely seen and when
present
• Usually associated with
severe carditis.
• Painless, firm, movable,
measuring around 0.5 to
2 cm.
• Located over extensor
surfaces of the joints,
particularly knees, wrists
and elbows

35. Subcutaneous nodules

36. Erythema Marginatum
erythematous lesions with
pale centers and rounded
or serpiginous margins

37. Rheumatic Valve Disease:
• Gross:
– Leaflet thickening
– Commissural fusion
– Shortening, Thickening & fusion of chordae
tendinae.
• Microscopic:
– Fibrosis
– Neovascularisation
– Calcification
• Mitral 68%, Mitral+Aortic 25%,
• 99% of Mitral stenosis is due to RHD.

38. Acute Rheumatic vegetations:

39. Aortic valve showing active valvulitis. The valve is slightly
thickened and displays small vegetations – "verrucae"
Valvulitis

40. Valve Pathology:
Rheumatic SLE Thrombotic Infective

41. Fibrinous Pericarditis:

42. Mitral regurgitation
• Apical blowing holosystolic murmur
Pure rheumatic MR
due to shortening of
valve cusps and of
papillary muscles
chordae tendineae
that become matted
and adherent to the
valve.

43. Chronic RHD:
• Valve leaflet
thickening.
• Shortening,
thickening and
fusion of
tendinous cords.

44. Mitral Stenosis
• Apical diastolic rumbling murmur
• Almost always caused by previous
rheumatic fever
• Rheumatic fever cause
– *a chronic process of valvular
fibrosis
– *commissures are fused
– * the cusps are severely thickened
– *calcification with shortened,
thickened chordae tendineae

46. Laboratory Investigations:
No specific laboratory investigations
I. Acute phase reactant
(CRP, SAA, SAP, Complements, Coagulation
Proteins)
2. Serologis and bacteriologis (ASO, Anti-
DNAse B titres, Culture)
3. Electrocardiography, radiology,
echocardiograpphy

47. RADIOLOGIS

48. RADIOLOGIS
Same patient after 4 weeks

49. Echocardiogram
• Valvular nodules or thickening
on body or tip of leaflets
• Annular dilatation
• Elongated chordae to the
anterior leaflet with
posterolateral jet
• Low cardiac output
• Pericardial effusion

50. Clinical Judgement

51. Differential diagnosis of
rheumatic fever

52. Differential diagnosis of
rheumatic fever
• Rheumatic fever and rheumatoid arthritis are completely
different diseases although both are immmunologically
mediated diseases.
• But remmember R.F. is more serious and more important as it
can be prevented.

53. Treatment
The reduction of inflammation
with anti-inflammatory medications such
as aspirin or corticosteroids.
Individuals with positive cultures (?) for
strep throat should also be treated with
antibiotics.

54. Treatment
• Another important cornerstone in treating
rheumatic fever includes the continuous
use of low dose antibiotics (such as
penicillin, sulfadiazine, or erythromycin)
to prevent recurrence.

55. Plan Of Action
• Step 0 : Primordial prevention
• 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)

56. Plan of Action
Step o : Primordial prevention
Pharyngitis GABHS strain 1,3,5,6,18,24
Step I : Primary prevention
Latent periode
Rheumatic Fever (by Jones criteria)
Step II : Anti inflammation
Step III : supportive and complications management
Step IV : Secondary prevention
Carditis + Carditis –
(Mur-mur,Pericarditis,Tacycardia)
Mild Mod Severe
Cardiomegali - + +
MR gr 2 >2 >2
CHF - - -

57. Step 0: Primordial Prevention
• Primordial prevention of the disease
– Immunization (?)
– Socio economic
– Nutrition
– Public education (school going age, parents,
teachers, all personil involve with children, etc)
• Control spread of disease to others
– Reduce risk of cross-transmission of organisms
– Infection control policies
– Handwashing
– Overcrowding
– Availability to prompt medical care

58. STEP I: Primary Prevention of
Rheumatic Fever
• The most important way to prevent
rheumatic fever is by proper and
prompt treatment of strep throat and
scarlet fever (eradication of GABHS)

59. Treatment of Streptococcal
Pharyngitis
• Objective of therapy
–Eliminate streptococci from the
pharynx
–Prevent rheumatic fever
–Prevent suppurative
complications
–Hasten clinical recovery

60. Treatment of Streptococcal
Pharyngitis
• Penicillin - drug of choice
–One intramuscular injection of
long acting penicillin
(benzathine) or oral therapy for
10 days
–No significant penicillin
resistance
• Erythromycin - if penicillin allergic

61. STEP I: Primary Prevention of Rheumatic Fever
(Treatment of GABHS 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

67. 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
Step II: Anti inflammatory treatment
Clinical condition Drugs

68. • Bed rest
• Treatment of congestive cardiac failure:
-digitalis,diuretics
• Treatment of chorea:
-diazepam or haloperidol
• Rest to joints & supportive splinting
Supportive & management of
complications
Step III

69. 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

70. 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

71. The roles for antibiotics in Rheumatic
Fever
• (1) initially treat GABHS pharyngitis
• (2) prevent recurrent streptococcal
pharyngitis, RF, and RHD
• (3) provide prophylaxis against bacterial
endocarditis.

72. Prevent bacterial endocarditis
• Patients who had RF without valve damage do
not need endocarditis prophylaxis.
• Do not use penicillin, ampicillin, or amoxicillin
for endocarditis prophylaxis in patients already
receiving penicillin for secondary RF
prophylaxis (relative resistance of oral
streptococci to penicillin and aminopenicillins).

73. Prevent bacterial endocarditis
• Alternate drugs recommended by the
American Heart Association for these
patients include oral clindamycin
(children: 20 mg/kg; adults: 600 mg) and
oral azithromycin or clarithromycin
(children: 15 mg/kg; adults: 500 mg)

74. Antibiotic prophylaxis
o Finally, patients with RF with
carditis and valve disease should
receive antibiotics at least 10
years or until aged 40 years.

75. Therapy for congestive heart failure
• Heart failure in RHD probably is related in
part to severe insufficiency of the mitral and
aortic valves and in part to pancarditis.
• Traditionally : inotropic agent (digitalis) in
combination with diuretics (furosemide,
spironolactone) and afterload reduction
(vasodilating Ca blockers, hydralazine, ACE inhibitors, or
nitrates).

76. Surgical vs Non Surgical Care:
• Surgery for patients who remain symptomatic
despite medical management.
• Critical MS requiring valvotomy or valve
replacement is associated with an oval orifice
<= 1.75 × 0.85 cm.
–balloon valvuloplasty
–open valvotomy and valvuloplasty can be
done.
–valve replacement is necessary

77. Diet:
• Without restrictions except in patients
with CHF, who should follow a fluid-
restricted and sodium-restricted diet.
• Potassium supplementation may be
necessary because of the
mineralocorticoid effect of corticosteroid
and the diuretics, if used.

78. Activity:
Initially, on bed rest, followed by a period of
indoor activity before they are permitted to
return to school.
Do not allow full activity until the APRs have
returned to normal.
Patients with chorea may require a
wheelchair and should be on homebound
instruction until the abnormal movements
resolve.

79. Complications:
 * CHF from valve insufficiency (acute RF) or
 stenosis (chronic RF).
 * Atrial arrhythmias
 * Pulmonary edema
 * Recurrent pulmonary emboli
 * Infective endocarditis
 * Thrombus formation
 * Systemic emboli.

80. Patient Education:
–Timely evaluation and treatment of
pharyngitis in children.
–Secondary prophylaxis of patients with
previous RF and valve involvement with
penicillin injections every 3-4 weeks
decrease the recurrence of RHD.
–Additional prophylactic antibiotics prior to
dental and surgical procedures.

81. Rheumatic Fever - Prognosis
• Is good if recurrence is prevented by
continuous antibiotic prophylaxis- particularly if
no carditis in the initial attack
• 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

85. In the future………

86. In the future………