RHEUMATIC FEVER

By
Dr Bashir Ahmed Dar
Chinkipora Sopore
Kashmir
Associate Professor
Medicine
Email
drbashir123@gmail.com
 RHEUMATIC FEVER
 Is a post streptococcal infection caused by group A
beta hemolytic streptococci.Occurs usually after an
attack of phyrangitis
 Between age group of 5-15years.
 Male and female equally affected
 Can also occur at any age
 What are these Streptococci
A ‘coccus’ is a spherical
bacteria
Staphylococcus tend to
cluster in groups
While Streptococcus
tend to line up in strings
Some are pyogenic while
others are non pyogenic.
 Classification of Streptococci
 Streptococciare classified according to their
hemolytic ability after incubation overnight on
blood agar medium.

 Beta-hemolytic streptococci produce an enzyme

that completely lyses the red blood cells in the
medium, leaving a clear zone of hemolysis around
the colony. This pattern is best characterized by
Streptococcus pyogenes.
 Classification of Streptococci
 Alpha-hemolytic streptococci produce an enzyme
that partially lyses the RBCs and converts red
hemoglobin to green methemoglobin leaving a
greenish discoloration of the culture medium
surrounding the colony. This discolored area
contains unlysed red blood cells and a green-
colored metabolite of hemoglobin. This pattern is
seen with the some Viridans streptococci and
Streptococcus pneumoniae.
 Classification of Streptococci
 Gamma-hemolytic streptococci are unable
to hemolyze the RBCs, and therefore we
should really not use the word "hemolytic"
in this situation. This pattern is seen with
most Lancefield group D streptococci.
 Common streptococci
 The most common Streptococcus species
isolated from humans are as follows
 Streptococcus Pyogenes
 Streptococcus Agalactiae
 Streptococcus bovis
 Streptococcus pneumoniae
 and the Streptococcus Viridans group.
 Common streptococci
 1.Streptococcus Pyogenes is a beta hemolytic
streptococci and cause bacterial phyrangitis
 It also causes Scarlet fever due to the erythrogenic
toxin . They are also known as "flesh eating"
bacteria and can cause life-threatening disease,
necrotising facitis.it also causes Skin infections
and Streptococcal toxic shock syndrome.
Pharyngitis
Scarlet fever
Necrotising fascitis
Skin infections
 Common streptococci
 2.Streptococcus agalacticae is also B beta
streptococci. associated with neonates. They are
normal flora of the GI tract and vaginal secretions.
This bacteria can cause s
 neonatal sepsis during birth, neonatal meningitis,
postpartum fever, and wound infections,
endocarditis, pneumonia, pyelonephritis in the
immunosuppressed individuals.
 Common streptococci
 Post
Streptococcus pyogenes infection also
cause non suppurative infection like
Rheumatic Fever and Post streptococcal
glomerulonephritis
 Common streptococci
 3.Streptococcus bovis is a group D
Streptococcus, non-Enterococcus. It is
usually gamma-hemolytic but may be
alpha-hemolytic. They may cause wound
infection, urinary tract infection, and
abdominal abscesses.
 Common streptococci
 4.Streptococcus pneumoniae are gram-
positive, lancet shaped diplococci. They are
alpha-hemolytic. They are typically normal
respiratory flora but may cause lobar
pneumonia in the elderly and alcoholics,
otitis media in infants and children,
meningitis, and community-acquired
bacterial pneumonia.
 Common streptococci
 5.Streptococcus viridans form large group
of commensal streptococcal bacteria that
are either α-hemolytic, producing a green
coloration on blood agar plates (hence the
name "viridans", from Latin "vĭrĭdis",
green), or non-hemolytic. They possess no
Lancefield antigens.
 Common streptococci
 These organisms are most abundant in the mouth
and one member of the group, S. mutans, is the
etiologic agent of dental caries. Others may be
involved in other mouth or gingival infections.
 Viridans group are difficult to classify due to
changing nomenclature and significant problems
of identification by phenotypic analysis.
 Lancefield classification

Based on antigens on streptococcal cell wall

antigens Ag-17 groups (A, B, C….).those that are
not possessing antigens are non groupable e.g.
Viridans streptococci.
 Common streptococci
 Streptococcal viridans if introduced into
the bloodstream they have the potential of
causing endocarditis, particularly in
individuals with damaged heart valves.
They are the most common causes of
subacute bacterial endocarditis especially
after dental procedures.
 Antigenic Structure
Capsule: . The capsule of group A streptococci is composed of
hyaluronic acid (hyloronidase) that breaks down connective tissue
and is antiphagocytosis

The group B streptococci contain

M protein
binds IgM, IgG and α2-macroglobulin; interfere with phagocytosis.
Lipoteichoic acid: binds to epithelial cells.
F protein: a major adhesin of S. pyogenes, binding with
fibronectin.
 Pathogenesis

So streptococci is able to cause

Adherence to the epithelial cells;
invasion into the epithelial cells;
Which in turn is mediated by M protein and F
protein and is important for persistent infections and
invasion into deep tissues
Enzymes and toxins secreted or produced by S.cocci
Streptokinase (fibrinolysin)
Can lyse blood clots and may be responsible for the rapid spread
of the organism.
Used (IV injection) for treatment of pulmonary emboli, coronary
artery thrombosis and venous thrombosis.
Streptodornase (DNases A to D)
Decreases viscosity of DNA suspension. A mixture of this and
streptokinase is used in enzymatic debridement-liquifies exudates
and facilitates removal of pus and necrotic tissue.
C5a peptidase
Prevents streptococci from C5a-mediated recruitment and
activation of phagocytes, and is important for survival of S.
pyogenes in tissue and blood.
Also produces Hemolysins like

Streptolysin O: O2-labile; causes hemolysis deep in

blood agar plates. ASO (antistreptolysin O) titer >160-200
units suggests recent infection or exaggerated immune
response to an earlier respiratory infection. However, skin
infection does not induce ASO.

Streptolysin S: O2-stable. Causes β-hemolysis on the

surface of blood agar plates. Cell-bound, not antigenic.
Produced in the presence of serum. Kills phagocytes by
releasing the lysosomal contents after engulfment.
pyogenic toxin (erythrogenic) – induces
fever and typical red rash
superantigens – strong monocyte and
lymphocyte stimulants that cause the release of
tissue necrotic factor
 Epidemiology

.
Crowding increases the opportunity for the pathogen to
spread, particularly during the winter months.
the organisms are introduced into the superficial or deep
tissue through a break in the skin.
Low social economic conditions are at risk.
Portal of entry through droplets,contact,food,fomites.
How does streptococci cause
Rheumatic fever
 The streptococci contain antigens as already
said , to these antigens antibodies are
formed in the body.
 But before these antibodies are formed the
streptococcal infection is over
 How does streptococci cause
Rheumatic fever
 So these antibodies are searching streptococci but
find none there
 Instead these antibodies now react to various
tissues in the body.
 Since most cells of body have same constituents as
that of streptococcal cells therefore react with cells
of body causing antigen antibody reaction.thus
rheumatic fever is immune mediated.
How does streptococci cause
Rheumatic fever

 Theseauto immune antibodies produce

inflammatory lesions primarily involving
the heart, joints, and subcutaneous tissue
producing e.g cardiac leisions etc.
 Cardiac Lesions
 Involvement of the interstitial tissue of all
the three layers of the heart, the so-called
pancarditis takes place in RF.
 The characteristic feature of pancarditis in
RF is the presence of Aschoff nodules or
Aschoff bodies.
The Aschoff nodules or bodies
 Are spheroidal or fusiform distinct tiny structures
or granulomas, 1-2 mm in size, occurring in the
interstitium of the heart in RF and may be visible
to naked eye.especially found in the vicinity of
small blood vessels in the myocardium and
endocardium and occasionally in the
pericardium.Lesions similar to the Aschoff
nodules may be found in the extracardiac tissues.
 Vegetation

Stick in Perforation

Mitral Valve
Acute Rheumatic vegetations:
Mitral v.

Va
lve

Vegetations

Papillary muscle
 How are Aschoff bodies
formed
 Formed in 3 stages.
 1. Early (Exudative or degenerative) stage.
 Initially, there is oedema of the connective tissue
and increase in acid mucopolysaccharide in the
ground substance.This results in separation of the
collagen fibres by accumulating ground
substance.Eventually, the collagen fibres are
fragmented and disintegrated,that takes the stain
of a fibrin.hence called fibrinoid degeneration.
 How are Aschoff bodies
formed
 2. 2nd stage (Proliferative or granulomatous)
 This includes infiltration by lymphocytes
(mostly T cells),plasma cells, a few
neutrophils and the characteristic cardiac
 histiocytes (Anitschkow cells) at the margin
of the lesion.
Acute RF: Aschoff body

 Aschoff body:
– Fibrinoid degeneration
– T lymphocytes
– Plasma cells
– Macrophages
 Anitschkow cells
 Aschoff giant cells
– Around blood vessel.
Aschoff body in Acute RF
 Anitschkow cells
 Capillary
 T lymphocyte
 Myocyte
Aschoff body in Acute RF
 Fibrinoid necrosis
 Aschoff giant cells.
 Cardiac Muscle
fibres.
 Cardiac histiocytes or
Anitschkow cells

 Arepresent in small numbers in normal

heart but their number is increased in the
Aschoff bodies; therefore they are not
characteristic of RHD.
 Cardiac histiocytes or
Anitschkow cells
 These are large mononuclear cells having central
round nuclei and contain moderate amount of
amphophilic cytoplasm. The nuclei are vesicular
and contain prominent central chromatin mass
which is longitudinal section appears serrated or
caterpillar-like, while in cross-section the
chromatin mass appears as a small rounded body
in the centre of the vesicular nucleus, just like an
owl's eye.
 Cardiac histiocytes or
Anitschkow cells
 Some of these modified cardiac histiocytes
become multinucleate cells containing 1 to
4 nuclei and are called Aschoff cells and are
characteristic of RHD.
Aschoff Body & Anitskow cell

o d y
o f f B
As c h
Aschoff Giant Cells:
Acute Rheumatic Fever-Rh
nodule
 How are Aschoff bodies
formed

 3. 3rd stage Late (healing or fibrous) stage.

 This stage is healing by fibrosis of the
Aschoff nodule and occurs in about 12 to
16 weeks after the illness resulting in
fibrous scar.
 Rheumatic Valvulitis
 The valves in acute RF show thickening and loss
of translucency of the valve leaflets or cusps. This
is followed by the formation of characteristic,
small (1 to 3 mm in diameter), multiple,warty
vegetations or verrucae, chiefly along the line of
closure of the leaflets and cusps. These tiny
vegetations are almost continuous so that the free
margin of the cusps or leaflets appear as a rough
and irregular ridge.
Acute Rheumatic vegetations:
Mitral v.

Va
lve

Vegetations

Papillary muscle
Fish mouth stenosis:
 Rheumatic Valvulitis
 The vegetations in RF appear grey-brown,
transuuent and are firmly attached so that
they are not likely to get detached to form
emboli, unlike the friable vegetations of
infective endocarditis.
Chronic RHD:
 Valve leaflet
thickening.
 Shortening, thickening
and fusion of chordae
tendineae.
 Acute on Chronic RHD

Note: Thickening of valve, opaque, inflammed, irregular border,

shortening of chordae tendinae also seen.
 Chronic RHD

Note: Thickening of valve, opaque, vascularized irregular border,

shortening of chordae tendinae. (no significant inflammation)
 Rheumatic Valvulitis
 Through all the four heart valves are
affected, their frequency and severity of
involvement varies: mitral valve alone
being most common site, followed in
decreasing order of frequency, by combined
mitral and aortic valve. The tricuspid and
pulmonary valves usually show infrequent
and slight involvement.
 Rheumatic Valvulitis
 The higher incidence of vegetations on
 left side of heart is possibly because of the
greater mechanical stresses on the valves of
the left heart, especially along the line of
closure of the valve cusps.
 Rheumatic Valvulitis
 Due to vegetations and thickening the mitral
valve may look like 'fish mouth' or 'button
hole'. Mitral stenosis and insufficiency are
commonly combined in chronic RHD.
Calcific aortic stenosis may also be found.
Fish mouth Mitral stenosis

Scar nodule

Mitral Valve

Left Atrium
Chronic RHD - Aortic Valve

Sten
otic
, Fu
sed
valv
e

Cor
ona
ry A
rter
y (n
orm
al)
Fish mouth Mitral stenosis:
 Rheumatic Valvulitis

Thickening, shortening and fusion of the

chordae tendineae further contribute to the
chronic valvular lesions.
 Rheumatic Valvulitis
 Vegetations present at the free margins of
cusps appear as tiny structures mainly
consisting of fibrin with superimposed
platelet thrombi and do not contain bacteria.
 Rheumatic Valvulitis
 In the healed (chronic) stage, the
vegetations have undergone organization
and fibrous formation., and often
calcification. Vascularisation of the valve
cusps may still be evident in the form of
thick-walled blood vessels.Aschoff bodies
are rarely seen in the valves at this stage.
 Vegetation

Stick in Perforation

Mitral Valve

Infective endocarditis with perforation of mitral valve leaflet

Rheumatic Mural Endocarditis
 Mural endocardium may also show features
of rheumatic carditis though the changes are
 less conspicuous as compared to valvular
changes.
Rheumatic Mural Endocarditis
 Grossly, the lesions most commonly seen is
MacCallum's patch which is region of endocardial
surface in the posterior wall of the left atrium just
above the posterior leaflet of the mitral valve.
MacCallum's patch appears as a map-like area
 of thickened, roughened and wrinkled part of the
 endocardium.
Rheumatic Mural Endocarditis
 Microscopically, the appearance of
MacCallum's patch is similar to that seen in
rheumatic valvulitis. The affected area
shows oedema, fibrinoid change in the
collagen, and cellular infiltrate of
lymphocytes, plasma cells and macrophages
with many Anitschkow cells.
 Rheumatic Myocarditis
 Grossly in early (acute) stage, the myocardium,
especially of the left ventricle, is soft and flabby.In
the intermediate stage, the interstitial tissue of the
myocardium shows small foci of necrosis. Later,
tiny pale foci of the Aschoff bodies may be visible
throughout the myocardium.
 Microscopically, the most characteristic feature of
rheumatic myocarditis is the presence of
distinctive Aschoff bodies..
 Rheumatic Myocarditis
 These nodules are scattered throughout the
interstitial tissue of the myocardium and are
most frequent in the interventricular
septum, left ventricle and left atrium.
 Rheumatic pericarditis.
 Grossly, the usual findings is fibrinous
pericarditis in which there is loss of normal
shiny pericardial surface due to deposition
of fibrin on its surface and accumulation of
exudate in the pericardial sac. If the parietal
pericardium is pulled off from the visceral
pericardium, the two separated surfaces are
shaggy due to thick fibrin covering them.
 Rheumatic pericarditis
 Thisappearance is often likened to 'bread
and butter appearance' i.e. resembling the
buttered surfaces of two slices in a
sandwich when they are gently pulled
apart.If fibrinous pericarditis fails to resolve
and, instead,undergoes organization, the
two layers of the pericardium form fibrous
adhesions resulting in chronic adhesive
pericarditis.
Granular Visceral Pericardial Surface of Fibrinous Pericarditis
Fibrinous Pericarditis:
 Extracardiac Lesion
 Develop in joint, subcutaneous tissue, arteries,
brain and lungs.
 Polyarthritis acute and painful inflammation of the
 synovial membranes of some of the joints,
especially the larger joints of the limbs, is seen in
about 90% cases of RF in adults and less often in
children. As pain and swelling subside in one
joint, others tend to get involved, producing
 the characteristic 'migratory polyarthritis'
involving two or more joints at a time.
Migratory arthritis
 Subcutaneous nodules
 The subcutaneous nodules of RF occur more often
in children than in adult. These nodules are
 small (0.5 to 2 cm in diameter), spherical or ovoid
and painless. They are attached to deeper
structures like tendons,ligaments, fascia or
periosteum and therefore often remain
 unnoticed by the patient. Characteristic locations
are extensor surface of the wrists, elbows, ankles
and knees.
Subcutaneous nodules
 Subcutaneous nodules
 Subcutaneous nodules of RF are larger,
painful and tender and persist for months to
years than that of rheumatoid arthritis that
are painless and non-tender.
 Erythema marginatum
 This non-pruritic erythematous rash is
characteristic of RF. The lesions occur
mainly on the trunk and proximal parts
 of the extremities. The erythematous area
develops central clearing and has slightly
elevated red margins.The erythema is
transient and migratory.
Acute Rh Fever: Erythema
Marginatum
 Rheumatic Arteritis
 Arteritis in RF involves not only the
coronary arteries and aorta but also occurs
in arteries of various other organs such as
renal,mesenteric and cerebral arteries. The
lesions in the coronaries are seen mainly in
the small intramyocardial branches.
 Chorea Minor
 Chorea minor or Sydenham's chorea or Saint
Vitus' dance is a delayed manifestation of RF as a
result of involvement of the central nervous
system. The condition is characterized by
disordered and involuntary jerky movements of
 the trunk and extremities accompanied by some
degree of emotional instability. The condition
occurs more often in younger age, particularly in
girls.
 Chorea Minor
 Histologically, the lesions are located in the
cerebral hemispheres,brainstem and the
basal ganglia. They consist of small
haemorrhages, oedema and perivascular
infiltration of lymphocytes. There may be
endarteritis obliterans and thrombosis of
cortical and meningeal vessels.
 Rheumatic pneumonitis and
pleuritis
 Involvement of the lungs and pleura occurs
rarely in RF. Pleuritis is often accompanied
 with serofibrinous pleural effusion but
definite Aschoff bodies are not present. In
rheumatic pneumonitis, the lungs are large,
firm and rubbery.
 Diagnosis of RF

 The following set of guidelines called

revised Jones' criteria are followed for
diagnosis of RF.
 Major criteria
 1. Carditis
 2. Polyarthritis.
 3. Chorea (Sydenham's chorea)
 4. Erythema marginatum
 5. Subcutaneous nodules
 Minor criteria
 1. Fever
 2. Arthralgia
 3. Previous history of RF
 4. Laboratory findings of elevated ESR,
raised C reactive protein, and leucocytosis.
 5.ECG finding of prolonged PR interval
 You should have
 Two major or one major and two minor of
the criteria.
 Supportive evidence
 Positive throat culture .
 Raised titers of (antispreptolysin O and S,
antistreptokinase, anti-streptohyaluronidase
and anti DNAase)
 Outcome and complications
 Myocarditis, in particular, is the most life-
threatening due to involvement of the
conduction system of the heart and results
in serious arrhythmias. The long term
sequelae or stigmata are the chronic
valvular deformities,especially the mitral
stenosis, AS, AI,etc as already explained.
 Normal & Rheumatic Mitral
valve:
 Recurrent Inflammation
Scarring 

Normal valve is Transparent,

avascular, thin flexible
membrane.

RHD: Thick, fibrous scarred

stenotic & fixed (MS/MR)
with Blood Vessels.
 Outcome and complications
a stage of compensation occurs, while later
decompensation of the heard leads to full-
blown cardiac failure. Currently, surgical
replacement of the damaged valves can alter
the clinical course of the disease.
 Outcome and complications
 Themajor causes of death in RHD are
cardiac failure, bacterial endocarditis and
embolism:
 Secondary effects
 Marked left atrial dilatation may result
from severe mitral stenosis or insufficiency.
 formation of mural thrombi.
 Cor pulmonale may develop as a
consequence of secondary pulmonary
hypertension induced by severe mitral valve
disease
 Course and diagnosis
 Valvereplacement may become necessary.
those who suffer recurrent attacks and
complications.
Treatment of Rheumatic Fever
 Bed rest
 Patients who have not had carditis should
be advised bed rest until temperature and
ESR become normal.
 Patients who have had carditis should
continue bed rest for 2-6 weeks after ESR
and temperature became normal.
 Anti-streptococcal theraphy
A course of antibiotic should be given to
eradicate the streptococci.
 Even if throat culture is negative.
 One of the following may be used
 1.single injection of benzathine penicillin
1.2 million units intramascularly.
 2.daily injection of procaine penicillin
600000 units I/M x10days.
 Anti-streptococcal theraphy
 Oralerythromycin 250-500mg 6-8 hrly if
patient is sensitive to pencillin.
 Salicylates
 Aspirin is effective in providing symptomatic
relief.
 5-8 grams given daily in divided doses upto six
times a day.until clinical improvement or
systemic toxicity develops like tinnitus
,headache,hyperpnoea.
 Aspirin at this dose continued until ESR is normal
and then gradually tapered over 4-6 weeks.
 Corticosteroids
 Indicationsare
 Severe carditis
 CCF
 Not responding to aspirin
 Prednisolone 60-120 mg/day QID until ESR
normal, then tapered over 2 weeks.
 Monitoring of corticosteroids also based on
ESR, CRP.
 Supportive theraphy
 Includes treatment of CCF, valvular
leisions, heart blocks and chorea.
 Prevention of Rheumatic
Fever
 Primary prevention
 Treat group A streptococcal pharyngitis
when ever it occurs
 Mass pencillin treatment of population if
outbreak of rheumatic fever occurs.
 Treat streptococcal pharyngitis by pencillin
or erythromycin.
 Secondary
prevention(prophylaxis of RF)
 Should be given to all patients who have
experienced attack of rheumatic fever.
 Broad outlines are
 Those under age of 18 should receive
continuous prophylaxis.
 Those who are over 18yrs who develop RF
without carditis should receive prophylaxis
for a minimum period of 5 yrs..
 Secondary
prevention(prophylaxis of RF)
 Decision to continue prophylaxis beyond 5
yrs in second group depend on many factors
like age of patient, relative risks like
acquiring infection, socioecnomic state,
presence of rheumatic heart disease etc.
 Secondary
prevention(prophylaxis of RF)
 One of the following regimens may be used.
 I/M injection of 1.2 million units of
benzathine pencillin G every 3 weeks.
 Oral pencillin V 250 mg twice a day.
 Erythromycin 250 mg BD orally in case
allergic to pencillin.
 Chorea
 Intermittentor continuous fast jerky
involuntary movements of parts of body.
 Movements may be more on one side called
hemichorea.
 Facial chorea results from infrequent
grimacing,blinking and slurring of speech.
 The movements subside in sleep.
 Hypotonia may be present.
 Treatment of Sydenham's
chorea/saint vitus dance
 Padded side boards for bed to prevent
injury.
 Haloperidol/sodium valproate with
diazepam.
 Rheumatic fever prophylaxis.
 Carbamazepine.
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