ACUTE RHEUMATIC FEVER

Stephanie Grace C. Lucero

Clinical Clerk
 Introduction
RF and RHD remain significant
causes of cardiovascular
diseases in the world
RHD - most common acquired
heart disease in children,
especially in developing
countries
RF global burden of disease
falls especially where poverty is
widespread

- World Heart Federation

 epidemiology
2011: ~15.6 million people are estimated to be
currently affected by RHD
usually children and adolescents (5-14years old) living in
developing countries
233,000 deaths annually
More commonly in women (M:F1:2)

Clin Epidemiol. 2011; 3: 6784.

Published online 2011 Feb 22. doi: 10.2147/CLEP.S12977
The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease
 Acute rheumatic fever
diffuse inflammation of
connective tissues
Autoimmune reaction
Group A beta-hemolytic
streptococcal infection
Almost all manifestations will
resolve completely
Can cause persisting heart
damage, termed Rheumatic
Heart Disease (RHD)
 Factors
Host
Organism
Environment
 Host factors
Susceptibility to ARF is an inherited characteristic
HLA-DR5, HLA-DR6, HLA-DR52, and HLA-DQ-
associated with protection
HLA-DR7 and HLA-DR4- associated with susceptibility
Associations with polymorphisms at the tumor
necrosis factor locus (TNF--308 and TNF--238)
high levels of circulating mannose-binding lectin &
Toll-like receptors
 Organism
(Group A B-Hemolytic Streptococcus GABHS)

Cell wall group A carbohydrate

Mucoid strains (rheumatogenicity)
Cell wall M-proteins (virulence)
Serotypes 1,3,5,6,14,18,19, 24, and 29
Superantigens: pyrogenic exotoxins
Enzymes: streptolysin, fibrinolysin, deoxyribonuclease
 VIRULENCE DESCRIPTION
FACTOR
Streptokinase Enzymatically activates
plasminogen, a proteolytic
enzyme, into plasmin, which
in turn digests fibrin and
other proteins
Hyaluronidase facilitate the spread of the
bacteria through tissues by
breaking down hyaluronic
acid, an important
component of connective
tissue.
 VIRULENCE DESCRIPTION
FACTOR
Streptolysin O An exotoxin
Streptolysin S A cardiotoxic exotoxin,
another beta-hemolytic
component, not immunogenic
and O2 stable
VIRULENCE FACTOR DESCRIPTION
Streptodornase AKA DNases, which protect the
bacteria from being trapped in
neutrophil extracellular traps
(NETs) by digesting the NETs' web
of DNA
C5a Peptidase cleaves a potent neutrophil
chemotaxin called C5a, which is
produced by the complement
system which minimizes the influx
of neutrophils early in infection as
the bacteria are attempting to
colonize the host's tissue.
 VIRULENCE DESCRIPTION
FACTOR
Streptococcal Prevents the migration of
chemokine neutrophils to the spreading
protease infection. ScpC degrades the
chemokine IL-8, which would
otherwise attract neutrophils
to the site of infection.
 M Protein (Virulence)

M-protein - best-defined
determinants of bacterial
virulence
streptococcal M-protein extends
from the surface of the
streptococcal cell as an alpha
helical coiled coil dimer, and
shares structural homology with
cardiac myosin
this homology is responsible for
the pathological findings in
acute rheumatic carditis.
 Environmental factors

Poor living conditions

Overcrowding
Poor access to health care
Seasonal variations
 Pathophysiology
develops following pharyngitis with group A beta-
hemolytic Streptococcus (ie, Streptococcus
pyogenes)
incubation period of 2-4 days
acute inflammatory response with 3-5 days (sore
throat, fever, malaise, headache, and an elevated
leukocyte count)
 Pathophysiology
0.3-3% of cases, leads to rheumatic fever several
weeks after the sore throat has resolved.
latent period of 2-4 weeks
chorea and indolent carditis- lasting up to 6 months
 pathophysiology
Precise mechanism is unknown
Two theories suggested
 Pathophysiology
THEORIES
1. Cytotoxicity theory - GABHS produces several
enzymes streptolysin S & O*, that are directly cytotoxic
for mammalian cardiac cell

2. Immunologic theory - Autoimmune reaction to GABHS

produces pathogenic autoantibodies to cardiac tissues
 Diagnosis
No clinical or laboratory finding pathognomonic of
RF
No definitive test
Relies on the presence of a combination of typical
clinical features together with evidence of the
precipitating group A streptococcal infection, and
the exclusion of other diagnoses
 Evidence of preceding GABHS
absolute requirement : supporting evidence of
recent Group A strep infection
Positive Throat culture
Elevated ASO titers is the basis in determining a previous group A
strep infection
Positive rapid group A streptococcal carbohydrate antigen test
Diagnosis
 JOINT INVOLVEMENT
Arthritis (75%)
Affects the large jointsknees, ankles, wrists,
elbows
asymmetric.
hot, swollen, red, tender
polyarthritis, migratory
pain is severe, disabling
nondeforming
Relieved by anti-inflammatory medication (NSAIDs,
salicylates)
most frequent major manifestation of RF
aspirated sample of synovial fluid may reveal a high
average leukocyte count (29000mm-3 , range 2000
96 000mm-3 ), normal glucose and a good mucin
clot
 involvement
Up to 60% RHD
Most serious manifestations
Pancarditis
RHD and carditis account for all of the associated M&M
Endocarditis universal finding in rheumatic carditis
Mitral valve is almost always affected
Damage to the pulmonary or tricuspid valves
(secondary)
Early valvular damage leads to regurgitation
 Morphology

focal inflammatory lesions are found in various

tissues
Aschoff bodies - consisting of foci of T
lymphocytes, occasional plasma cells, and
plump activated macrophages called
Anitschkow cells (pathognomonic for RF)
 verrucae

along the lines of closure are

small (1 to 2 mm)
vegetations, called
verrucae.
Mitral Stenosis Aortic regurgitation Softening of S1
Mitral regurgitation Prolonged P-R interval
Diagnosis of rheumatic carditis
 2015 revision in the Jones Criteria:
clinical carditis with a valvulitis murmur
subclinical carditis without a murmur of valvulitis but with
echocardiographic evidence of valvulitis
 Murmur
Mitral regurgitation: apical holosystolic murmur
radiating to the axilla
Significant MR - apical mid-diastolic murmur of
relative mitral stenosis
Aortic insufficiency - high-pitched decrescendo
diastolic murmur at the left sternal border
 Remember:
Carditis - single most important prognostic factor
only valvulitis - permanent damage and its
presence determines the prophylactic strategy
Dx of Carditis: significant murmurs, pericardial rub, or
an unexplained cardiomegaly with CHF
SUBCUTANEOUS NODULES
<1% (rare)
painless, small (~1 cm), mobile lumps
beneath the skin overlying extensor
surfaces of tendons near bony
prominences
delayed manifestation, appearing 23
weeks after the onset
last for just a few days up to 3 weeks
commonly associated with significant
carditis
 ERYTHEMA MARGINATUM
(<1%) -rare
erythematous, nonpruritic,
serpiginous, macular lesions with
pale centers
evanescent, appearing and
disappearing before the
examiners eyes.
trunk, limbs, but almost never on
the face
 SYDENHAM CHOREA
10-15% of px with ARF
prolonged latent period
muscular weakness
Present as: emotional lability, incoordination, poor
school performance, uncontrollable movements,
and facial grimacing, all exacerbated by stress and
disappearing with sleep
 May be insidious
Occasionally unilateral, most bilateral
Females more affected; rare after age 20 years old
 Rarely leads to permanent sequelae
Longer latency: 1-7 months (2-4 months)
Duration: 1wk to >2 yrs (median 15 wks; within 6
months)
May wax and wane
(+) strep. Infection in only 2/3 of cases
One criterion that can stand alone
 Clinical maneuvers: Chorea
milkmaids grip
involuntary repetitive squeezing motion
pronation or spooning of hands on arm extension
darting tongue upon protrusion
changes in handwriting
 MINOR CRITERIA
Clinical
a. joint manifestations
Low risk: polyarthralgia
Moderate/High-Risk: monoarthralgia
b. fever
Low risk: 38.5C
Moderate/High-Risk: 38.0C
 MINOR CRITERIA
Laboratory
a.elevated acute phase reactants
ESR CRP
LOW RISK >= 60 mm/hr >= 3.0 mg/dl [30 mg/L]
HIGH RISK >= 30 mm/hr >= 3.0 mg/dl [30 mg/L]

a.prolonged P-R interval on ECG (unless carditis is a major

criterion)
 Exceptions to Jones Criteria
1. Chorea occurs as the only major manifestation of acute
rheumatic fever
2. Indolent carditis is the only manifestation in patients
who first come to medical attention only months after the
apparent onset of acute rheumatic fever
3. In a limited number of patients with recurrences of
acute rheumatic fever in particularly high-risk
populations
Differentials
MANAGEMENT
 Primary prevention
defined as the adequate antibiotic therapy of group
A streptococcal upper respiratorytract (URT)
infections to prevent an initial attack of acute RF
administered only when there is group A
streptococcal URT infection
therapy is intermittent
ideally before 9th day of symptoms of acute GAS
pharyngitis
 Antibiotic therapy
10 days of orally administered penicillin or amoxicillin
Benzathine penicillin IM to ensure eradication of GAS
from the upper respiratory tract
Penicillin-allergic: 10 days of erythromycin, azithromycin
(5 days) or clindamycin is indicated.
After this initial course of antibiotic therapy, long-term
antibiotic prophylaxis should be instituted
Antibiotic therapy
 Anti-inflammatory therapy
Typical migratory polyarthritis
Carditis with NO cardiomegaly or congestive heart failure
Treatment:
Oral salicylates: Aspirin
50-70 mg/kg/day in 4 divided doses PO for 3-5 days,
Then 50 mg/kg/day in 4 divided doses PO for 3 wk
Then half that dose for another 2-4 wk
 Anti-inflammatory therapy
Carditis + more than minimal cardiomegaly and/or
congestive heart failure
Treatment:
Corticosteroids: Prednisone
2 mg/kg/day in 4 divided doses for 2-3 wk
Then half the dose for 2-3 wk
Then tapering the dose by 5 mg/24 hr every 2-3 days
When tapering, Aspirin should be started at 50 mg/kg/day in 4
divided doses for 6 wk
 Supportive therapy:
Moderate to severe carditis
Digoxin
Fluid and salt restriction
Diuretics
Oxygen
 Chorea
Sedatives:
Phenobarbital: 16-32 mg every 6-8 hr PO
If nonresponsive:
Haloperidol 0.01-0.03 mg/kg/24 hr divided bid PO
Chlorpromazine 0.5 mg/kg every 4-6 hr PO
 Secondary prevention
continuous administration of specific antibiotics
patients with a previous attack of RF, or a well-
documented rheumatic heart disease (RHD)
prevent colonization or infection of the upper respiratory
tract (URT) with group A beta-hemolytic streptococci and
development of recurrent attacks of RF
Secondary prophylaxis is mandatory for all patients who
have had an attack of RF, whether or not they have
residual rheumatic valvular heart disease
Secondary Prophylaxis
 duration of secondary prophylaxis

factors influencing the risk of RF recurrence:

the age of the patient the risk of streptococcal infection

the presence of RHD in the area
the time elapsed from the last whether a patient is willing to
attack receive injections
the number of previous attacks the occupation and place of
the degree of crowding in the employment of the patient (school
family teachers, physicians, employees in
a family history of RF/RHD crowded areas).
the socioeconomic and
educational status of the individual
 Prognosis
50-70% of patients with carditis during the initial episode
of acute rheumatic fever recover with no residual heart
disease
the more severe the initial cardiac involvement, the
greater the risk is for residual heart disease
50% risk of reinfection of the upper respiratory tract with
GAS once patients have had ARF
THANK YOU!