RHEUMATIC FEVER

As. Univ. Dr. Claudiu Stoicescu

SPITALUL UNIVERSITAR DE URGENTA BUCURESTI, ROMANIA

UMF CAROL DAVILA BUCURESTI, ROMANIA
 Objectives

• Etiology
• Epidemiology
• Pathogenesis
• Pathologic lesions
• Clinical manifestations & Laboratory findings
• Diagnosis & Differential diagnosis
• Treatment & Prevention
• Prognosis
• References
 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
 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.
 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 glomerulonephritis only. It will
not result in Rh. Fever or carditis as skin lipid
cholesterol inhibit antigenicity
Diagrammatic structure of the group A
beta hemolytic streptococcus
Capsule Antigen of outer
protein cell wall
Cell wall of GABHS
Protein antigens
induces antibody
response which
Group carbohydrate
result in AI
damage to
Peptidoglycan valves, sub-
cutaneous
Cyto.membrane tissue, tendons,
joints & basal
Cytoplasm ganglia of brain

……………………………………………
……...
 Pathologic Lesions

• Fibrinoid degeneration of connective tissue,

inflammatory edema, inflammatory cell infiltration
& proliferation of specific cells resulting in
formation of Aschoff nodules, resulting in-
-Pancarditis in the heart
-Arthritis in the joints
-Ashcoff nodules in the subcutaneous
tissue
-Basal gangliar lesions resulting in
chorea
Rheumatic Carditis Histology (40X)
Rheumatic Carditis Histology (200X)
 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
 Clinical Features

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)
 Rheumatic
heart
disease.
Abnormal
mitral valve.
Thick, fused
chordae
Another view
of thick and
fused mitral
valves in
Rheumatic
heart disease
 Clinical Features

3.Sydenham Chorea
• Occur in 5-10% of cases
• Mainly in girls of 1-15 yrs. age
• May appear even 6/12 mth. after the attack of R.F.
• 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
 Clinical Features

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
Erythema Marginatum
 Clinical Features

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
Subcutaneous nodule
 Clinical Features

Other features (Minor features)

• Fever-(up to 40 degree )
• Arthralgia
• Pallor
• Anorexia
• Loss of weight
 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
 Paraclinic Findings

• 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
 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

Exceptions to Jones Criteria

 Choreaalone, 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
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)
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

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
 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
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

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
 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
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.
World Health Organization Study Group: Rheumatic Fever &
Rheumatic Heart Disease,technical Report Series No.
764.Geneva,world Health Organization, 1988
 “Vara este in capul meu,
dar eterna primavara este in inima mea”