Transcript Rheumatic fever

Rheumatic fever
• Rheumatic fever is an inflammatory disease
which may develop after a Group A
Streptococcal infection (such as strep throat or
scarlet fever) and can involve the heart,
joints,skin, and brain.
• It commonly appears in children ages 5
through 15 .
Diagnosis:
• Major criteria
• Joints (Migratory polyarthritis): a temporary migrating
inflammation of the large joints, usually starting in the legs and
migrating upwards.
• Carditis: inflammation of the heart muscle which can manifest
as CHF with shortness of breath, pericarditis with a rub, or a
new heart murmur.
• Nodules (subcutaneous nodules - a form of Aschoff bodies):
painless, firm collections of collagen fibers on the back of the
wrist, the outside elbow, and the front of the knees. These now
occur infrequently.
• Erythema marginatum: a long lasting that begins on the trunk
or arms as macules and spread outward to form a snakelike ring
while clearing in the middle. This rash never starts on the face
and is made worse with heat.
• Sydenham's chorea (St. Vitus' dance): a characteristic series of
rapid movements without purpose, of the face and arms. This
can occur very late in the disease.
•
•
•
•
Minor criteria
Fever: temperature elevation
Arthralgia: Joint pain without swelling
Laboratory abnormalities: increased ESR,
increased C Reactive Protein,leukocytosis.
• ECG abnormalities: a prolonged PR interval
• Evidence of Group A Strep infection: positive
culture for Group A Strep, elevated or rising
Anti-sterptolysin “O” titres.
• Previous rheumatic fever or inactive heart
disease
Other signs & symptoms:
• Abdominal pain.
• Nosebleeds.
Pathophysiology:
• Rheumatic fever is a systemic disease affecting the periarteriolar connective tissue and can occur after an untreated
Group A streptococcal pharyngeal infection.
• It is believed to be caused by antibody cross-reactivity. This
cross-reactivity is a Type II hypersensitivity reaction and is
termed molecular mimicry.
• Usually, self reactive B cells remain anergic in the periphery
without T cell co-stimulation. During a Strep. infection
activated antigen presenting cells such as macrophages
present the bacterial antigen to helper T cells.
• Helper T cells subsequently activate B 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.
• Group A streptococcus pyogenes has a cell wall composed of
branched polymers which sometimes contain "M proteins"
that are highly antigenic.
• The antibodies which the immune system generates against
the "M proteins" may cross react with cardiac myofiber
protein myosin and smooth muscle cells of arteries, inducing
cytokine release and tissue destruction.
• 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 Aschoff giant cells.
• Acute rheumatic valvular lesions may also involve a cellmediated immune reaction as these lesions predominantly
contain T-helper cells andmacrophages.
• In acute RF, these lesions can be found in any layer
of the heart and is hence called pancarditis.
• The inflammation may cause a serofibrinous
pericardial exudates described as “bread-andbutter”pericarditis, which usually resolves without
sequelae.
• Involvement of the endocardium typically results in
fibrinoid necrosis and verrucae formation along the
lines of closure of the left-sided heart valves. Warty
projections arise from the deposition, while
subendothelial lesions may induce irregular
thickenings called MacCallum plaques.
Complications of Acute Rheumatic fever:
• Some patients develop significant carditis
which manifests as congestive heart failure.
• This requires the usual treatment for heart
failure: diuretics and digoxin.
• Unlike normal heart failure, rheumatic heart
failure responds well to corticosteroids.
•
Rheumatic fever
• Annual incidence:
– Western Europe 1/100,000
– Sub-Saharan Africa 5,700/100,000
• Incidence decreases with improving social
circumstances (less crowding).
• Individual (HLA) susceptibility is also
important
Group A b-haemolytic streptococcus
• All cases associated with recent infection (e.g.
pharyngitis, pyoderma).
• Some bacterial serotypes (M antigen) are
more significant in causing rheumatic fever.
• Antibody and cellular immune response
cross-reacts with human connective tissue.
Clinically
•
•
•
•
•
Joints (arthritis)
Heart (arrhythmias etc.)
Skin (erythema marginatum)
Central nervous system (chorea)
Mainly 5-15 years (20% adult)
“Licks the joints but bites the heart”
Pancarditis…
• Pericarditis
• Myocarditis
• Endocarditis – responsible for chronic valvular
damage
Rheumatic vegetations on valve
Fibrinous “Bread & Butter”pericarditis:
Acute, recurring, chronic:
• Symptoms prone to recur with subsequent
Strep. Infections
• Chronic disease leads to fibrosis (chordae of
heart valves + valve cusps)
Histopathology
• Aschoff bodies (small granulomas around
necrotic collagen – T cells, macrophages)
• Anitschkoff cell – an unusual spindly
macrophage
Aschoff nodule and Anitschkow cell
Chronic rheumatic heart disease:
• Chronic rheumatic heart disease is characterized by
repeated inflammation with fibrinous resolution.
• The cardinal anatomic changes of the valve include
leaflet thickening, commissural fusion and shortening
and thickening of the tendinous cords.
• Rheumatic heart disease is the most serious
complication of rheumatic fever.
Rheumatic valve disease
• Most common lesion
is mitral stenosis.
• Aortic valve second
most frequently
involved.
Normal vs. chronic rheumatic valve
Morphology in Chronic rheumatic heart
disease:
• Characterized by organisation of the acute
inflammation & subsequent fibrosis.
• The valvular leaflets become thickened &
retracted,causing permanent deformity.
• MV,TV leaflet thickening,commisural fusion &
shortening,thickening & fusion of tendinous
chords.
• Micro: Diffuse fibrosis, neovascularization of the
originally avascular valve leaflet.