Tikrit university collage of medicine pediatric lecture dr.Emad Alsadoon

1. Rheumatic fever
• 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
•Gram stain of Streptococcus species

2. • 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
• 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
• evidence for Strep pyogenes as a cause of
ARF:
– close temporal relationship between
epidemics of streptococcal pharyngitis /
scarlet fever & epidemics of ARF

3. – most patients with ARF give a history of
pharyngitis, & if absent serology supports
this
– continuous antibiotic prophylaxis that
prevents Strep pyogenes pharyngitis also
prevents ARF
– M protein share epitiopes which ARF
patients mount IgG response
– serotypes vary in their ability cause ARF,
certain M types are strongly associated
with ARF while others are not
• Exact mechanism that lead to the
development of ARF not completely
understood
• Requirements
– Strep pharyngitis
– Host susceptibility
– NO evidence that streptococcal toxins are
important

4. • 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

5. • M proteins
• consist of two chains with a-helical structure, very rare in
bacteria, but a common in mammalian proteins
• > 80 distinct M proteins
• Antigenic variation is due primarily to single amino acid
substitutions
• the M protein types of GAS associated with impetigo and
other skin infections are different from those associated
with clinical pharyngitis
• Rheumatic fever always follows pharyngitis and is more
commonly associated with certain M types (1,3,5,16,18)
• Glomerulonephritis can follow pharyngitis (commonly M-
types 1,4,12,15) or impetigo (M-types 49,52,55,59-61)
and appears to be restricted to a smaller list of
"nephritogenic" strains
• 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

6. • Rheumatic Carditis Histology (40X)
• 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

7. • 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(fishmouthvalves)
• Rheumatic heart disease. Abnormal
mitral valve. Thick, fused chordate
• Another view of thick and fused
mitral valves in Rheumatic heart
disease

8. • 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
• 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

9. 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 associatedwith severe carditis
Other features (Minor features)
• Fever-(upto 101 degree F)
• Arthralgia
• Pallor
• Anorexia
• Loss of weight

10. • 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
• 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,decreasedcontractility
• 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

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

12. • Differential Diagnosis
• Juvenile rheumatiod arthritis
• Septic arthritis
• Sickle-cell arthropathy
• Kawasaki disease
• Myocarditis
• Scarlet fever
• Leukemia
• 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)

13. • STEP I: Primary Prevention of Rheumatic
Fever (Treatmentof 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)

14. • Step II: Anti inflammatory
treatment
Clinical condition Drugs
• 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
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

15. • 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

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