Альбияли Ая рагаб Ахмед

Абделлатиф гр17

Volgograd State Medical University

Faculty of dentistry

My presentation about ( Acute rheumatic fever.

Etiology. Pathogenesis. Classification. Diagnostic
criteria for the disease. Course, complications.
Treatment principles. Primaгу and secondary
prevention. The role of oral cavity sanitation in
preventive measures )

Rheumatic fever (RF) : is an inflammatory

disease that can involve the heart, joints, skin, and
brain.The disease typically develops two to four weeks
after a streptococcal throat infection. Signs and
symptoms include fever, multiple painful joints,
involuntary muscle movements, and occasionally a
characteristic non-itchy rash known as erythema
marginatum.The heart is involved in about half of the
cases. Damage to the heart valves, known as rheumatic
heart disease (RHD), usually occurs after repeated
attacks but can sometimes occur after one. The
damaged valves may result in heart failure, atrial
fibrillation and infection of the valves.
Rheumatic fever may occur following an infection of
the throat by the bacterium Streptococcus pyogenes.If
the infection is left untreated, rheumatic fever occurs
in up to three percent of people.The underlying
mechanism is believed to involve the production of
antibodies against a person's own tissues. Due to their
genetics, some people are more likely to get the
disease when exposed to the bacteria than others.
Other risk factors include malnutrition and poverty.
Diagnosis of RF is often based on the presence of signs
and symptoms in combination with evidence of a
recent streptococcal infection.
Treating people who have strep throat with antibiotics,
such as penicillin, decreases the risk of developing
rheumatic fever. In order to avoid antibiotic misuse this
often involves testing people with sore throats for the
infection; however, testing might not be available in
the developing world. Other preventive measures
include improved sanitation.In those with rheumatic
fever and rheumatic heart disease, prolonged periods
of antibiotics are sometimes recommended. Gradual
return to normal activities may occur following an
attack. Once RHD develops, treatment is more difficult.
Occasionally valve replacement surgery or valve repair
is required. Otherwise complications are treated as
usual.
Rheumatic fever occurs in about 325,000 children each
year and about 33.4 million people currently have
rheumatic heart disease. Those who develop RF are
most often between the ages of 5 and 14, with 20% of
first-time attacks occurring in adults. The disease is
most common in the developing world and among
indigenous peoples in the developed world. In 2015 it
resulted in 319,400 deaths down from 374,000 deaths
in 1990.Most deaths occur in the developing world
where as many as 12.5% of people affected may die
each year. Descriptions of the condition are believed to
date back to at least the 5th century BCE in the
writings of Hippocrates. The disease is so named
because its symptoms are similar to those of some
rheumatic disorders.

Signs and symptoms

The disease typically develops two to four weeks after
a throat infection. Symptoms include: fever, painful
joints with those joints affected changing with time,
involuntary muscle movements, and occasionally a
characteristic non-itchy rash known as erythema
marginatum. The heart is involved in about half of the
cases. Damage to the heart valves usually occurs only
after multiple attacks but may occasionally occur after
a single case of RF. The damaged valves may result in
heart failure and also increase the risk of atrial
fibrillation and infection of the valves.
Pathophysiology
Rheumatic fever is a systemic disease affecting the
connective tissue around arterioles, and can occur
after an untreated strep throat infection, specifically
due to group A streptococcus (GAS), Streptococcus
pyogenes. The similarity between antigens of
Streptococcus pyogenes and multiple cardiac proteins
can cause a life-threatening type II hypersensitivity
reaction. Usually, self reactive B cells remain anergic in
the periphery without T cell co-stimulation. During a
streptococcal infection, mature antigen-presenting
cells such as B cells present the bacterial antigen to
CD4+T cells which differentiate into helper T2 cells.
Helper T2 cells subsequently activate the B cells to
become plasma cells and induce the production of
antibodies against the cell wall of Streptococcus.
However the antibodies may also react against the
myocardium and joints, producing the symptoms of
rheumatic fever. S. pyogenes is a species of aerobic,
cocci, gram-positive bacteria that are non-motile, non-
spore forming, and forms chains and large colonies.
S. pyogenes has a cell wall composed of branched
polymers which sometimes contain M protein, a
virulence factor that is highly antigenic. The antibodies
which the immune system generates against the M
protein may cross-react with heart muscle cell protein
myosin, heart muscle glycogen and smooth muscle
cells of arteries, inducing cytokine release and tissue
destruction. However, the only proven cross-reaction is
with perivascular connective tissue. This inflammation
occurs through direct attachment of complement and
Fc receptor-mediated recruitment of neutrophils and
macrophages. Characteristic Aschoff bodies, composed
of swollen eosinophilic collagen surrounded by
lymphocytes and macrophages can be seen on light
microscopy. The larger macrophages may become
Anitschkow cells or Aschoff giant cells. Rheumatic
valvular lesions may also involve a cell-mediated
immunity reaction as these lesions predominantly
contain T-helper cells and macrophages.
In rheumatic fever, these lesions can be found in any
layer of the heart causing different types of carditis.
The inflammation may cause a serofibrinous pericardial
exudate described as "bread-and-butter" pericarditis,
which usually resolves without sequelae. Involvement
of the endocardium typically results in fibrinoid
necrosis and wart formation along the lines of closure
of the left-sided heart valves. Warty projections arise
from the deposition, while subendocardial lesions may
induce irregular thickenings called MacCallum plaques.

Rheumatic heart disease:

Chronic rheumatic heart disease (RHD) is

characterized by repeated inflammation with
fibrinous repair. The cardinal anatomic changes of
the valve include leaflet thickening, commissural
fusion, and shortening and thickening of the
tendinous cords. It is caused by an autoimmune
reaction to Group A β-hemolytic streptococci (GAS)
that results in valvular damage. Fibrosis and scarring
of valve leaflets, commissures and cusps leads to
abnormalities that can result in valve stenosis or
regurgitation. The inflammation caused by
rheumatic fever, usually during childhood, is
referred to as rheumatic valvulitis. About half of
patients with rheumatic fever develop inflammation
involving valvular endothelium. The majority of
morbidity and mortality associated with rheumatic
fever is caused by its destructive effects on cardiac
valve tissue. The pathogenesis of RHD is complex
and not fully understood, but it is known to involve
molecular mimicry and genetic predisposition that
lead to autoimmune reactions.
Molecular mimicry occurs when epitopes are shared
between host antigens and Streptococcus antigens.
This causes an autoimmune reaction against native
tissues in the heart that are incorrectly recognized
as "foreign" due to the cross-reactivity of antibodies
generated as a result of epitope sharing. The
valvular endothelium is a prominent site of
lymphocyte-induced damage. CD4+ T cells are the
major effectors of heart tissue autoimmune
reactions in RHD. Normally, T cell activation is
triggered by the presentation of bacterial antigens.
In RHD, molecular mimicry results in incorrect T cell
activation, and these T lymphocytes can go on to
activate B cells, which will begin to produce self-
antigen-specific antibodies. This leads to an immune
response attack mounted against tissues in the heart
that have been misidentified as pathogens.
Rheumatic valves display increased expression of
VCAM-1, a protein that mediates the adhesion of
lymphocytes. Self-antigen-specific antibodies
generated via molecular mimicry between human
proteins and streptococcal antigens up-regulate
VCAM-1 after binding to the valvular endothelium.
This leads to the inflammation and valve scarring
observed in rheumatic valvulitis, mainly due to CD4+
T cell infiltration.
While the mechanisms of genetic predisposition
remain unclear, a few genetic factors have been
found to increase susceptibility to autoimmune
reactions in RHD. The dominant contributors are a
component of MHC class II molecules, found on
lymphocytes and antigen-presenting cells,
specifically the DR and DQ alleles on human
chromosome 6. Certain allele combinations appear
to increase RHD autoimmune susceptibility. Human
leukocyte antigen (HLA) class II allele DR7 (HLA-DR7)
is most often associated with RHD, and its
combination with certain DQ alleles is seemingly
associated with the development of valvular lesions.
The mechanism by which MHC class II molecules
increase a host's susceptibility to autoimmune
reactions in RHD is unknown, but it is likely related
to the role HLA molecules play in presenting
antigens to T cell receptors, thus triggering an
immune response. Also found on human
chromosome 6 is the cytokine TNF-α which is also
associated with RHD. High expression levels of TNF-
α may exacerbate valvular tissue inflammation,
contributing to RHD pathogenesis. Mannose-binding
lectin (MBL) is an inflammatory protein involved in
pathogen recognition. Different variants of MBL2
gene regions are associated in RHD. RHD-induced
mitral valve stenosis has been associated with MBL2
alleles encoding for high production of MBL. Aortic
valve regurgitation in RHD patients has been
associated with different MBL2 alleles that encode
for low production of MBL. Other genes are also
being investigated to better understand the
complexity of autoimmune reactions that occur in
RHD.

Diagnosis :
Modified Jones criteria were first published in 1944
by T. Duckett Jones, MD. They have been
periodically revised by the American Heart
Association in collaboration with other groups.
According to revised Jones criteria, the diagnosis of
rheumatic fever can be made when two of the major
criteria, or one major criterion plus two minor
criteria, are present along with evidence of
streptococcal infection: elevated or rising
antistreptolysin O titre or anti-DNase B. A recurrent
episode is also diagnosed when three minor criteria
are present. Exceptions are chorea and indolent
carditis, each of which by itself can indicate
rheumatic fever. An April 2013 review article in the
Indian Journal of Medical Research stated that
echocardiographic and Doppler (E & D) studies,
despite some reservations about their utility, have
identified a massive burden of rheumatic heart
disease, which suggests the inadequacy of the 1992
Jones' criteria. E & D studies have identified
subclinical carditis in patients with rheumatic fever,
as well as in follow-ups of rheumatic heart disease
patients who initially presented as having isolated
cases of Sydenham's chorea. Signs of a preceding
streptococcal infection include: recent scarlet fever,
raised antistreptolysin O or other streptococcal
antibody titre, or positive throat culture. The last
revision of 2015 suggested variable diagnostic
criteria in low-risk and high-risk populations to avoid
overdiagnosis in the first category and
underdiagnosis in the last one. Low-risk populations
were defined as those with acute rheumatic fever
annual incidence ≤2 per 100 000 school-aged
children or all-age rheumatic heart disease
prevalence of ≤1 per 1000. All other populations
were categorised as having a moderate or high risk.
Major criteria
Joint manifestations are the unique clinical signs
that have different implications for different
population-risk categories : Only polyarthritis (a
temporary migrating inflammation of the large
joints, usually starting in the legs and migrating
upwards) is considered as a major criterion in low-
risk populations, whereas monoarthritis,
polyarthritis and polyarthralgia (joint pain without
swelling) are all included as major criteria in high-
risk populations.
Carditis: Carditis can involve the pericardium
(pericarditis which resolves without sequelae), some
regions of the myocardium (which might not
provoke systolic dysfunction), and more consistently
the endocardium in the form of valvulitis. Carditis is
diagnosed clinically (palpitations, shortness of
breath, heart failure, or a new heart murmur) or by
echocardiography/Doppler studies revealing mitral
or aortic valvulitis. Both of clinical and subclinical
carditis are now considered a major criterion.
Subcutaneous nodules: Painless, firm collections of
collagen fibers over bones or tendons. They
commonly appear on the back of the wrist, the
outside elbow, and the front of the knees.
Erythema marginatum: A long-lasting reddish rash
that begins on the trunk or arms as macules, which
spread outward and clear in the middle to form
rings, which continue to spread and coalesce with
other rings, ultimately taking on a snake-like
appearance. This rash typically spares the face and is
made worse with heat.
Sydenham's chorea (St. Vitus' dance): A
characteristic series of involuntary rapid movements
of the face and arms. This can occur very late in the
disease for at least three months from onset of
infection.
Minor criteria
Arthralgia: Polyarthralgia in low-risk populations and
monoarthralgia in others. However, joint
manifestations cannot be considered in both major
and minor categories in the same patient.
Fever: ≥ 38.5 °C (101.3 °F) in low-incidence
populations and ≥ 38 °C (100.4 °F) in high-risk
populations.
Raised erythrocyte sedimentation rate (≥60 mm in
the first hour in lox-risk populations and ≥30 mm/h
in others) or C reactive protein (>3.0 mg/dL).
ECG showing a prolonged PR interval after
accounting for age variability (Cannot be included if
carditis is present as a major symptom).

Prevention:
Rheumatic fever can be prevented by effectively and
promptly treating strep throat with antibiotics.
In those who have previously had rheumatic fever,
antibiotics in a preventative manner are occasionally
recommended. As of 2017 the evidence to support
long term antibiotics in those with underlying
disease is poor.
The American Heart Association suggests that dental
health be maintained, and that people with a history
of bacterial endocarditis, a heart transplant, artificial
heart valves, or "some types of congenital heart
defects" may wish to consider long-term antibiotic
prophylaxis.
Etiology:
Acute rheumatic fever is a nonsuppurative, delayed
sequela of pharyngitis due to S. pyogenes. The exact
disease process is not fully known. However, the
disease is in part due to an autoimmune response to
S. pyogenes infection involving multiple organ
systems. Organ systems involved typically include
the heart, joints, and central nervous system.
Streptococcal pharyngitis typically precedes the
onset of acute rheumatic fever by 1 to 5 weeks.1

S. pyogenes are gram-positive cocci that grow in

chains . They exhibit β-hemolysis (complete
hemolysis) when grown on blood agar plates. They
belong to group A in the Lancefield classification
system for β-hemolytic Streptococcus, and thus are
also called group A streptococci.
Treatment :
The management of rheumatic fever is directed
toward the reduction of inflammation with anti-
inflammatory medications such as aspirin or
corticosteroids. Individuals with positive cultures for
strep throat should also be treated with antibiotics.
Aspirin is the drug of choice and should be given at
high doses.
One should watch for side effects like gastritis and
salicylate poisoning. In children and teenagers, the
use of aspirin and aspirin-containing products can be
associated with Reye's syndrome, a serious and
potentially deadly condition. The risks, benefits, and
alternative treatments must always be considered
when administering aspirin and aspirin-containing
products in children and teenagers. Ibuprofen for
pain and discomfort and corticosteroids for
moderate to severe inflammatory reactions
manifested by rheumatic fever should be considered
in children and teenagers.
Vaccine
No vaccines are currently available to protect
against S. pyogenes infection, although research is
underway to develop one. Difficulties in developing
a vaccine include the wide variety of strains of S.
pyogenes present in the environment and the large
amount of time and people that will be needed for
appropriate trials for safety and efficacy of the
vaccine.
Infection
People with positive cultures for Streptococcus
pyogenes should be treated with penicillin as long as
allergy is not present. The use of antibiotics will not
alter cardiac involvement in the development of
rheumatic fever.Some suggest the use of benzathine
benzylpenicillin.
Monthly injections of long-acting penicillin must be
given for a period of five years in patients having
one attack of rheumatic fever. If there is evidence of
carditis, the length of therapy may be up to 40
years. Another important cornerstone in treating
rheumatic fever includes the continual use of low-
dose antibiotics (such as penicillin, sulfadiazine, or
erythromycin) to prevent recurrence.
Inflammation
While corticosteroids are often used, evidence to
support this is poor. Salicylates are useful for pain.
Steroids are reserved for cases where there is
evidence of an involvement of the heart. The use of
steroids may prevent further scarring of tissue and
may prevent the development of sequelae such as
mitral stenosis.
Heart failure
Some patients develop significant carditis which
manifests as congestive heart failure. This requires
the usual treatment for heart failure: ACE inhibitors,
diuretics, beta blockers, and digoxin. Unlike typical
heart failure, rheumatic heart failure responds well
to corticosteroids.
Thanks a lot.