ACUTE RHEUMATIC FEVER

Ermias Argaw(MD, Internist)

 INTRODUCTION
 Acute rheumatic fever (ARF) is a multisystem disease
resulting from an autoimmune reaction delayed, non-
suppurative sequela of a pharyngeal infection with the group
A streptococcus (GAS)
 The disease presents with various manifestations that may

include arthritis, carditis, chorea, subcutaneous nodules, and

erythema marginatum
 Almost all of the manifestations resolve completely with the

exception is cardiac valvular damage, which may persist after

the other features have disappeared.
 EPIDEMIOLOGY
 World wide there are 470,000 new cases of rheumatic fever
(95% in developing countries)
 B/n 15 and 19 million people worldwide are affected by

RHD
 It is a disease of poverty

 The incidence of RF declined in industrialized nations after

early 20thcentury largely attributable to
 improved living conditions

 the introduction of antibiotics

 change of streptococcal strain

 improved systems of medical care

EPIDEMIOLOGY
 EPIDEMIOLOGY
 In developed nations the incidence of RF is below 1.0 per
100 000
 A few studies conducted in developing countries report

incidence rate of
 Sudan :100 per 100 000

 China :150 per 100 000

 no clear gender association

 mainly affects children aged 5–15 years
 Initial episodes are less common in older adolescents and young adults
in contrast to recurrent episodes.
 rare in persons aged < 3years and >30 years
 ARF is exclusively caused by infection of the upper respiratory
tract with group A streptococci.
 Classically, certain M-serotypes (types 1, 3, 5, 6, 14, 18, 19,
24, 27, and 29) were associated with ARF
 Any strain has the potential to cause ARF

ETIOLOGIES OF PHARYNGITIS
 15–20%: group A streptococci

 80%: viral pathogens

 Redness & swelling
of throat & tonsils;

Beefy, swollen, red

uvula; Soft palate
petechiae
(“doughnut
lesions”)

Tonsillopharyngeal
erythema &
Sore throat: fever, exudates
white draining
patches on the
throat & swollen or
tender lymph glands
in the neck
 EVIDENCES FOR THE ROLE OF GAS IN THE
INTIATION OF ARF
o Outbreaks of rheumatic fever closely follow epidemics of
streptococcal pharyngitis or scarlet fever with associated
pharyngitis
o Adequate treatment of a documented streptococcal
pharyngitis markedly reduces the incidence of subsequent
rheumatic fever
o Appropriate antimicrobial prophylaxis prevents the
recurrence of disease in patients who have had ARF
o Most patients with ARF have elevated antibody titers to at
least one of three antistreptococcal antibodies
 WHY IS ARF ASSOCIATED WITH
STREPTOCOCCAL PHARYNGITIS ALONE?

1. Genetic makeup of the organism

2. The large repository of lymphoid
tissue in the pharynx
 PATHOGENESIS
 The pathogenic mechanisms that lead to the
development of acute rheumatic fever remain
incompletely understood
1. Streptococcal pharyngeal infection
2. Host genetic susceptibility
 Only 0.3–3% of individuals with acute
streptococcal pharyngitis go on to develop RF
 Concordance rate in identical twins is
approximately ~44%
3. Environmental factors
 THE IMMUNE RESPONSE

 Molecular mimicry
 most widely accepted theory
 an immune response targeted at streptococcal antigens (mainly the
M protein and the N-acetylglucosamine) also recognizes human
tissues.
 Cross-reactive antibodies bind to endothelial cells on the heart valve,
leading to recruitment of activated lymphocytes and lysis of
endothelial cells in the presence of complement.
 Complement also activates cross-reactive T cells that invade the
heart, amplifying the damage
 Alternative hypothesis
initial damage is due to streptococcal invasion of epithelial surfaces,
with binding of M protein to type IV collagen allows it to
become immunogenic
PATHOGENESIS
 CLINICAL FEATURES
 Latent period: ~3 weeks (1–5 weeks)
 But chorea and indolent carditis may follow prolonged latent periods
lasting up to 6 months
 The onset of the disease usually is characterized by an acute febrile
illness that may manifest itself in one of several ways:
 Polyarthritis: 60–75%
 Carditis: 50–60% (almost always occurs in recurrent episoids)
 Chorea: <2% to 30%
 Erythema marginatum and subcutaneous nodules are now rare, being found
in <5% of cases.
 POLYARTHRITIS
 It usually is the earliest manifestation of ARF
 Joint involvement is more common and more severe in

teenagers and young adults than in children

 Each joint is inflamed for no more than one week

 The onset of arthritis in different joints usually overlaps,

giving the appearance that the disease "migrates" from joint

to joint
 ARF almost always affects the large joints—most

commonly the knees, ankles, hips, and elbows—and is

asymmetric
 POLYARTHRITIS
 The leg joints are typically involved first
 Joint pain usually is more prominent than are objective
signs of inflammation and almost always is transient
 The pain is severe and usually disabling

 The joint manifestations of ARF have a dramatic response

to salicylates and other NSAIDs
 Joint involvement that persists more than 1 or 2 days after
starting salicylates is unlikely to be due to ARF
 Conversely, if salicylates are commenced early in the illness,
before fever and migratory polyarthritis have become
manifest, it may be difficult to make a diagnosis of ARF
 POLYARTHRITIS
 For this reason, salicylates and other NSAIDs should be
withheld—and pain managed with acetaminophen or
codeine—until the diagnosis is confirmed
 Radiographs of an affected joint may show a slight effusion,
but most likely will be unremarkable
 Synovial fluid analysis generally reveals a sterile
inflammatory fluid
 Migratory polyarthralgia and monoarhritis are considered
minor manifestaions
 CARDITIS
 Rheumatic fever produces a pancarditis affecting the pericardium,
epicardium, myocardium, and endocardium
 Valvular damage is the hallmark of rheumatic carditis
 The mitral valve is almost always affected, sometimes together
with the aortic valve; isolated aortic valve involvement is rare
 Mitral regurgitation is the most common finding and often

occurs with aortic regurgitation.

 By contrast, isolated aortic regurgitation and hemodynamically

significant stenotic lesions of the aortic or mitral valves are

unusual at presentation
 Stenosis lesions are the manifestations of late scarring and

calcification of damaged valves rather than acute injury

 CARDITIS
 Myocardial involvement is almost never responsible
in itself for cardiac failure
 Myocardial inflammation leads to

 Prolonged PR-interval
 Softening of the first heart sound

 Pericarditis most commonly causes a friction rub or

a small effusion on echocardiography and may
occasionally cause pleuritic central chest pain
 CHOREA
 Sydenham chorea, chorea minor, or "St. Vitus dance" is a
neurologic disorder consisting of
 Abrupt, purposeless, nonrhythmic involuntary movements-

choreioathetotic movements and hypotonia

 Muscular weakness

 Emotional disturbances- emotional lability, hyperactivity,

separation anxiety, obsessions & compulsions

 It is found mainly in females

• The movements commonly are more marked on one side, are

occasionally unilateral(Hemichorea) and cease during sleep.
• The choreiform movements affect particularly the head ( darting
movements of the tongue) and the upper limbs
 CHOREA
o Muscle weakness is best revealed by asking the patient to
squeeze the examiner's hands ("milk maids sign." )
o Spooning, pronation of hands when arms are extended.
o Chorea may have a longer latent period after streptococcal
infections than do other rheumatic manifestations
o Doesn’t lead to permanent neurologic injury.
 SUBCUTANEOUS NODULES
 The nodules are firm and painless
 Size varies from a few millimeters to one or two centimeters
 The nodules most commonly are located on the extensor surface over
a bony surface or prominence or near tendons
 The number of nodules varies from a single lesion to a few dozen and
averages three or four
 Nodules are present for one or more weeks, rarely for more than a
month.
 Rheumatic subcutaneous nodules generally appear only after the first
weeks of illness and usually only in patients with carditis
SUBCUTANEOUS NODULES
 ERYTHEMA MARGINATUM
 It is an evanescent, non-pruritic rash, pink or faintly red,

usually affecting the trunk and sometimes the proximal

parts of the limbs, but not the face
 extends centrifugally while the skin in the center returns to

normal
 The outer edge of the lesion is sharp, whereas the inner edge

is diffuse
 Because the margin of the lesion usually is continuous,

making a ring, it also is known as "erythema annulare”

 Individual lesions may appear, disappear, and even reappear

in a matter of hours
 ERYTHEMA MARGINATUM
 A hot bath or shower may make them more evident or may
even reveal them for the first time
 It usually occurs early in the disease

 It often persists or recurs when all other manifestations of

disease have disappeared

 This skin disorder, like the subcutaneous nodule, usually

occurs only in patients with carditis

ERYTHEMA MARGINATUM
 OTHER FEATURES
 Fever occurs in most cases of ARF, although rarely
in cases of pure chorea
 Although high-grade fever (39°C) is the rule, lower

grade temperature elevations are not uncommon

 Arthralgia without objective joint inflammation

usually affects large joints in the same migratory

pattern as polyarthritis
DDx FOR POLYARTHRITIS
DDx FOR CARDITIS AND CHOREA
Recommended Tests in Cases of Possible Acute Rheumatic Fever
 EVIDENCE OF RECENT STREPTOCOCAL
INFECTION

 Only 30 to 50 % of individual will remember history of preceeding

streptococal pharyngitis
 Only 10-20% of the throat culture or rapid streptococcal antigen
test results are positive
 Therefore, evidence of an antecedent GABHS infection is usually
based on elevated or increasing serum antistreptococcal antibody
titers
 Anti-streptolysin O (ASO) and
 anti-DNase B
(ADB) titers
2002–2003 WHO criteria for the diagnosis of rheumatic fever and
rheumatic heart disease (based on the revised Jones criteria)
2002–2003 WHO criteria for the diagnosis of rheumatic fever and
rheumatic heart disease (based on the revised Jones criteria)
 TREATMENT OF ARF
 There is no treatment for ARF that has been proven to alter
the likelihood of developing, or the severity of RHD
 With the exception of treatment of heart failure the

treatment of ARF is symptomatic

 Three major goals in the treatment of acute rheumatic fever

are:
o Symptomatic relief of acute disease manifestations

o Eradication of the group A beta-hemolytic streptococcus

o Prophylaxis against future infection to prevent recurrent

cardiac disease
 TREATMENT OF ARF (ANTIBIOTIC THERAPY)
 Antibiotic therapy should be started and maintained for at
least 10 days, regardless of the presence or absence of
pharyngitis at the time of diagnosis
o Penicillin V (500 mg po two to three times daily)

o Erythromycin(250 mg po bid) for patients with penicillin

allergy
o A depot penicillin, such as benzathine penicillin G, in one

single intramuscular dose should be given if compliance is

an issue:
 600,000 units for children who weigh <=27 kg

 1.2 million units for children who weigh >27 kg and

adults
TREATMENT OF ARF (ARTHRITIS, ARTHRALGIA AND FEVER)

 Aspirin is the drug of choice

 An initial dose of 4–8 g/d in adults (80–100 mg/kg per day in
children) in 4–5 divided doses is often needed for the first few days
up to 2 weeks
 A lower dose should be used if symptoms of salicylate toxicity emerge,
such as nausea, vomiting, or tinnitus
 When the acute symptoms are substantially resolved, the dose can be
reduced to 60–70 mg/kg per day for a further 2–4 weeks
 Although less well studied, naproxen at a dose of 10–20 mg/kg per
day has been reported to lead to good symptomatic response
 TREATMENT OF ARF (CARDITIS)
 Severe carditis is marked by the presence of significant cardiomegaly,
congestive heart failure, or third-degree heart block
 Patients with severe carditis are often treated with corticosteroids, but
their use in the treatment of rheumatic carditis have shown conflicting
results
 Usual dose is 1 to 2 mg/kg (maximum 80mg) per day of oral
prednisone for the first one to two weeks then tapered over the next
two weeks based on response.
 During this time, aspirin may be added in the dose recommended for
arthritis
 Conventional therapy for heart failure should be provided as well
 Valve surgery may be necessary when heart failure is due to
regurgitant lesions that are refractory to medical therapy
 TREATMENT OF ARF (CHOREA)
 Full recovery occurs in almost all patients, but symptoms of SC
occasionally persist for two years or more
 The patient with chorea should be treated when significant
impairment of motor function and the possibility of self injury are
present
 Treatments reported to be effective include carbamazepine, valproic
acid , phenobarbital, haloperidol .
 In severe and refractory cases
 Corticosteroids : prednisone 1 mg/kg per day as a single dose for

two weeks and then tapered over two to three weeks. A repeat
course may be required if an exacerbation occurs.
 Intravenous immune globulin
 PRIMARY PREVENTION
 Elimination of the major risk factors for streptococcal
infection
 Overcrowded housing

 Inadequate hygiene infrastructure

 Early treatment

 If commenced within 9 days of sore throat onset, a course

of 10 days of penicillin V (500 mg bid PO in adults) or

a single IM injection of 1.2 million units of benzathine
penicillin G will prevent almost all cases of ARF that
would otherwise have developed
 SECONDARY PROPHYLAXIS
 The mainstay of controlling ARF and RHD is secondary prevention
 Because patients with ARF are at dramatically higher risk than the general
population of developing a further episodes of ARF after a group A
streptococcal infection (75%), they should receive long-term penicillin
prophylaxis to prevent recurrences
 The classic parenteral regimen is benzathine penicillin G 1.2 million units
(600,000 units for individuals who weigh<=27 kg) intramuscularly every
four weeks .
 However, injections every three weeks may be more effective in preventing
recurrences of acute rheumatic fever
 Acceptable oral regimens include:
 Penicillin V 250 mg twice per day and
 Sulfadiazine 500 mg per day for individuals who weigh <=27 kg and 1000 mg per
day for children >27 kg and adults
 Penicillin allergic patients can receive erythromycin (250 mg) twice daily
Suggested Duration of Secondary Prophylaxis
 Course of ARF

 ARF follows 0.3-3% of GAS pharyngitis.

 50-60% of ARF develop carditis.
 Severe CHF & death 1%
 Recovery
. Without carditis- 95% on regular prophylaxis
. With carditis- 70% with regular prophylaxis
 Insufficiency from ARF carditis resolves in 60-80%
of patients who adhere to antibiotic prophylaxis.
 Residual disease( chronic RHD) develops in about 20-40%
RHEUMATIC HEART DISEASE
CARDIOVASCULAR DISEASES
 EPIDEMIOLOGY
 World wide 15.6–19.6 million people have RHD (2.4 million
children aged 5–14 years) causing 233 364–294 398 deaths from
RHD each year (based on annual mortality of 1.5% per year)
 The highest prevalence of RHD is in sub-Saharan Africa with a
prevalence of 5.7 per 1000, compared with 1.8 per 1000 in North
Africa, and 0.3 per 1000 in economically developed countries with
established market economies
 RHD is the most common cause of heart disease in children in
developing countries and is a major cause of mortality and morbidity
in adults as well
Prevalence of rheumatic heart disease in children aged 5–14 years
STUDIES OF PREVALENCE OF RHD IN AFRICA
 MALIGNANT COURSE OF RHD
 Valvular disease in developed nations afflicts the elderly, is insidious
in onset, and is frequently associated with other comorbidities
 In Africa valvular disease is encountered in the young, not
infrequently in children of school-going age or young females of
child-bearing potential, and with a course that is much more rapid

 WHY RHD IS HAVING A MALIGNANT COURSE IN

DEVELOPING COUNTRIES?
1. Frequent recurrence
2. ? Strain difference
 In rheumatic heart disease,
 the mitral valve is involved in nearly all cases
 the aortic valve is involved in about 20 to 30 percent
 the tricuspid valve is commonly affected but is frequently subclinical
 Younger patients under the age of 30 years present predominantly
with pure mitral regurgitation
 Middle aged adult patients develop mitral stenosis from the third
decade and
 Mixed mitral valve disease is more dominant in older patients.
TYPES OF VALVULAR LESIONS
Thank you