ACUTE RHEUMATIC FEVER

INTRODUCTION
Acute rheumatic fever (ARF) is a delayed, nonsuppurative
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. The
exception is cardiac valvular damage [rheumatic heart disease
(RHD)], which may persist after the other features have
disappeared
 EPIDEMIOLOGY
World wide there are 470,000 new cases of rheumatic
fever (95% of this cases occur in developing countries)
It is a disease of poverty
The incidence of RF declined in industrialized nations after early
twentieth century
 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
rates ranging from 1.0 per 100 000 school-age children in Costa
Rica ,72.2 per 100 000 in French Polynesia, 100 per 100 000 in Sudan,
to 150 per 100 000 in China
ARF is mainly a disease of children aged 5–14 years
Initial episodes become less common in older adolescents and young
adults and are rare in persons aged >30 years
By contrast, recurrent episodes of ARF remain relatively common in
adolescents and young adults
There is no clear gender association for ARF
 ROLE OF STREPTOCOCCUS
Epidemiologic and immunologic evidence indirectly implicates GAS
in the initiation 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 (if not all) three antistreptococcal antibodies (streptolysin "O",
hyaluronidase, and streptokinase), whether or not they recall an
antecedent sore throat
 IMPORTANCE OF PHARYNGITIS
Streptococcal pharyngitis is less frequent among children in the
first three years of life and among adults.
It has been estimated that most children develop at least one
episode of pharyngitis per year, 15–20% of which are caused by
group A streptococci and nearly 80% by viral pathogens
Why is ARF only associated with streptococcal pharyngitis?
1. Genetic makeup of the organism

2. The large repository of lymphoid tissue in the pharynx

 RHEUMATOGENIC STRAINS
The observation in some studies that only a few M serotypes
(types 3, 5, 6, 14, 18, 19, 24, and 29) were implicated in
outbreaks of rheumatic fever in the United States suggested a
particular "rheumatogenic" potential of certain strains of GAS

It is now thought that any strain of group A streptococcus has

the potential to cause ARF
 PATHOGENESIS
The pathogenic mechanisms that lead to the development of
acute rheumatic fever remain incompletely understood

1. Streptococcal pharyngeal infection

2. Host genetic susceptibility

 Concordance rate in identical twins is approximately 20%
 Only 0.3–3% of individuals with acute streptococcal
pharyngitis go on to develop RF
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.
 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. By contrast, isolated aortic
regurgitation and hemodynamically significant stenotic lesions of the aortic or mitral
valves are unusual at presentation. In particular, mitral stenosis is a manifestation of
late scarring and calcification of damaged valves rather than acute injury
Myocardial involvement is almost never responsible in itself for cardiac failure
Myocardial inflammation may affect electrical conduction pathways, leading to P-R
interval prolongation (first-degree AV block or rarely higher-level block) and 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
 ARTHRITIS
Arthritis usually is the earliest symptomatic manifestation of ARF, although
asymptomatic carditis may come first
Joint involvement is more common and more severe in teenagers and young adults
than in children
In the classic, untreated case, the arthritis of rheumatic fever affects several joints
in quick succession, each for a short time (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 (migratory polyarthritis)
ARF almost always affects the large joints—most commonly the knees, ankles,
hips, and elbows—and is asymmetric
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
 ARTHRITIS
The joint manifestations of ARF are highly responsive to salicylates and
other nonsteroidal anti-inflammatory drugs (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
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
Analysis of the synovial fluid in well-documented cases of rheumatic fever
with arthritis generally reveals a sterile inflammatory fluid
 CHOREA
Sydenham chorea, chorea minor, or "St. Vitus dance" is a neurologic
disorder consisting of abrupt, purposeless, nonrhythmic involuntary
movements, muscular weakness, and emotional disturbances
It is found mainly in females
o The movements commonly are more marked on one side, are
occasionally unilateral (hemichorea), and cease during sleep.The
choreiform movements affect particularly the head (causing
characteristic darting movements of the tongue) and the upper
limbs
o Muscle weakness is best revealed by asking the patient to squeeze
the examiner's hands; the pressure of the patient's grip increases
and decreases continuously and capriciously, a phenomenon known
as relapsing grip or "milking sign’’
 CHOREA
o Emotional changes manifest themselves in outbursts of
inappropriate behavior, including crying and restlessness. In rare
cases, the psychologic manifestations may be severe and may
result in transient psychosis
o Neurologic examination fails to reveal sensory losses or
involvement of the pyramidal tract. Diffuse hypotonia may be
present
 Chorea may have a longer latent period after streptococcal
infections than do other rheumatic manifestations, up to eight
months in one retrospective review. Some patients with chorea
have no other symptoms, although careful examination of the
heart may reveal murmurs
 SUBCUTANEOUS NODULES
The nodules are firm and painless
The overlying skin is not inflamed and usually can be moved over the nodules
The diameter varies from a few millimeters to one or two centimeters
The nodules most commonly are located 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; when numerous, the nodules usually are symmetric
Nodules are present for one or more weeks, rarely for more than a month.
They are smaller and more short-lived than the nodules of rheumatoid
arthritis. Furthermore, although the elbows are involved most frequently in
both diseases, rheumatic fever nodules are more common on the olecranon,
whereas rheumatoid nodules usually are found 3 to 4 cm distally
Rheumatic subcutaneous nodules generally appear only after the first weeks
of illness and usually only in patients with carditis
SUBCUTANEOUS NODULES
 ERYTHEMA MARGINATUM
Erythema marginatum is an evanescent, non-pruritic rash, pink or faintly red, usually
affecting the trunk and sometimes the proximal parts or the limbs, but not the face
The name derives from the observation that the lesion 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
A hot bath or shower may make them more evident or may even reveal them for the
first time
Erythema marginatum usually occurs early in the disease. It often persists or recurs
when all other manifestations of disease have disappeared
In some cases, the lesions appear for the first time (or more likely are first noticed) late
in the course of the illness or even during convalescence.
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
Elevated acute-phase reactants are also present in most cases
C-reactive protein (CRP) and erythrocyte sedimentation rate
(ESR) are often dramatically elevated
Occasionally the peripheral leukocyte count is mildly elevated
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
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)
Summary of 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, which may be life-saving
in cases of severe carditis, 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 with penicillin 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) may be used 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 80–100 mg/kg per day in children (4–8 g/d in
adults) 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
Such patients should be treated with conventional therapy for heart failure
Patients with severe carditis are often treated with corticosteroids, but studies of the effects
of corticosteroids in the treatment of rheumatic carditis have shown conflicting results
 A 2003 meta-analysis from the Cochrane database concluded that there was no significant
difference in outcome when corticosteroids and aspirin treatment were compared
When corticosteroids are used, the usual dose is 1 to 2 mg/kg (maximum 80mg) per day of
oral prednisone for the first one to two weeks. Depending upon the clinical and laboratory
response, the dose is then tapered over the next two weeks. During this time, aspirin may be
added in the dose recommended for arthritis to achieve a serum concentration of 20 to 30
mg/dL
Valve surgery may be necessary when heart failure is due to regurgitant lesions that cannot
be adequately managed with medical therapy
 TREATMENT OF ARF (CHOREA)
Sydenham chorea typically improves gradually, with a mean duration of 12 to 15 weeks
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 valproic acid , phenobarbital, haloperidol , pimozide ,
diazepam, chlorpromazine, and carbamazepine , corticosteroids, plasma exchange, and intravenous
immune globulin
Haloperidol, a centrally acting drug, is effective in controlling chorea but may be associated with adverse
extrapyramidal reactions
Authors of UpToDate recommend that corticosteroids as the initial treatment: 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.
They also mentioned that treatment with either valproic acid or carbamazepine is a reasonable
alternative, with fewer side effects.The use of neuroleptics, haloperidol, or pemozide should be reserved
for resistant or chronic patients
 PRIMARY PREVENTION
Ideally, primary prevention would entail elimination of the major
risk factors for streptococcal infection, particularly overcrowded
housing and inadequate hygiene infrastructure. This is difficult to
achieve in most places where ARF is common
Therefore, the mainstay of primary prevention for ARF remains
primary prophylaxis, i.e., the timely and complete treatment of
group A streptococcal sore throat with antibiotics
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 episode 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 potassium 400,000 units (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
 RHEUMATIC HEART DISEASE: LATE SEQUELA OF ARF

Although the incidence of rheumatic heart disease is variable

after an episode of acute rheumatic fever, approximately 50
percent of those with evidence of carditis develop organic
valvular damage

Up to 75 percent of patients with documented recurrences of

rheumatic fever have some form of valvular disease after 45
years of follow-up
 CARDIOVASCULAR DISEASES
RHEUMATIC HEART DISEASE
 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
In a retrospective study of deaths between 1995 and 2001 at the Tikur
Anbassa Teaching Hospital, Addis Ababa, Ethiopia, Oli and Asmera
reported that 26.5% of the cardiovascular deaths were due to RHD and
70% of patients with RHD died from congestive heart failure at a mean age
of 25 years (11% died from systemic embolisation and comorbid conditions)
1. Frequent recurrence
2. ? Strain difference
TYPES OF VALVULAR LESIONS
 RHD IN ETHIOPIA
Prevalence: 19 per 1000 population
Accounts for 50 % of all cardiovascular disease
admisions to hospital
26.5% of the cardiovascular deaths are due to RHD
The mean and median age of patients with RHD is 23+/- 8 years
and 22 years respectively
F:M ratio is 1.9
Frequently encountered valve lesions were combined MR and
MS (25.4%),pure MS (21.9%) and pure MR (18.4%)
Cardiovascular disease Epidemiology in Ethiopia
Distribution of the different cardiovascular diagnosis in patients
seen at six referral hospitals
Rheumatic Heart Disease
Rheumatic Heart Disease Registry
National initiative
Major hospitals in Ethiopia
Started September 2017
On good progress
 10,260 people aged 15-69 years participated
The prevalence of raised blood pressure (SBP≥ 140 and/ or
DBP ≥ 90 mmHg) was 15.8% (16.3% in females and 15.5% in
males).
The prevalence of diabetes mellitus (FBS ≥ 126 mg /dl)
including those on medication was 3.2% (3.5% males and
3.0% females).
The prevalence of impaired fasting glucose was 9.1%
with ADA criteria and 3.8% with WHO criteria.
Hypercholesterolemia was found in 5.2%,
hypertriglyceridemia in 21.0%, high LDL cholesterol
occurred in 14.1% and low HDL cholesterol occurred in
68.7%.

The prevalence of metabolic syndrome using IDF

definition was 4.8% (8.6% in females and vs. 1.8% in
males).
Adult Cardiac Surgery at Black Lion Hospital, Ethiopia
Adult Cardiac Surgery at Black Lion Hospital, Ethiopia