Acute Rheumatic Fever

Maj Gen Devendra B. Khatri (Retd)

Prof. of Medicine and
Senior consultant Cardiologist,
NAIHS
Why should we know?

Not uncommon
Long term implication
Economic burden on country
Preventable
 Introduction
Acute Rheumatic fever (ARF) – a multisystem
autoimmune disease resulting from
autoimmune reaction to infection with group
A streptococcus.
Non-infectious delayed complication of
streptococcal sore throat due to group A
beta hemolytic streptococcus (GABHS).
Affects Heart, Joints, CNS & Skin.
Occurs usually 2-3 weeks (1-5 weeks) after
streptococcal infection, mainly pharyngitis.
But may occur with skin infections (impetigo)
Most common cause of acquired heart
disease in children and adolescence.
Disease of the poverty
Overcrowding and low socio-economy,
under nutrition and less access to
medicine as risk factor
 Epidemiology
Major public health problem in developing countries.
Indigenous population in wealthy countries
Over 15 million people have evidence for rheumatic
heart disease. responsible for >300,000 deaths in
young people worldwide each year.
Greatest burden - 97 % in developing world
Peak incidence: 5 – 15 yrs. Incidence declines and
rare after the age 30; < 5% under 5 years; Unheard
< 2 yrs of age.
Recurrent episodes of ARF remain common in
adolescents and young adults- thus RHD peaks
between 20 and 40 years.
No ethnic preponderance, no clear gender
association
 Pathogenesis
ARF is exclusively caused by infection of upper
respiratory tract with Group A, B-haemolytic
streptococcus – in susceptible host.
Any strain of group A streptococcus has the
potential to cause disease.
Certain M serotypes – 1,3,5,6,14,18,19,24,27
and 29 - thought to be associated in high
incidence regions.
3-6% of any population susceptible.
Susceptibility is inherited characteristics.
Immunogenic determinants- Association
between disease and HLA class II alleles HLA-
DR7 &HLADR4 have been identified.

Exact mechanism of initial insult is still unclear.
Molecular mimicry theory:
-Antibodies or cellular immune response directed
against streptococcal antigens (mainly thought to
be on M protein and N-acetylglucosamine of group
A streptococcal carbohydrate) also recognizes and
cross react with epitope on host tissues.
-Cross reacting antibodies bind to endothelial
cells on heart valves – lead to activation of
adhesion molecules - recruitment of activated
lymphocytes and lysis of endothelial cells in
presence of complement.
-later leads to release of peptides (laminin,
keratin, tropomycin) – in turn activates cross
reactive T cells that invade the heart, amplifying
the damage and epitope spreading.
 Cardiac myosin
Antibody (Ab)
against β- Laminin in valvular
haemolytic Cross
reaction basement
streptococci
(M protein & Sarcolemmal
carbohydrate membrane protein
antigen)
lysogangloside
T- cells,
Macrophage Heart

The above is present Joints

in Caudate nucleus in
brain
Pathologic lesion:
Aschoff’s body
- a granulomatous
lesion containing T & B
cells, large mononuclear
cells, multi-nucleated
(Aschoff’s) giant cells and
polymorphonuclear
leucocytes in the
myocardium.
 Clinical Presentation
With h/o sore throat - 2-5 wks prior (exceptions
are chorea and indolent carditis)
Acute febrile illness – high grade 39 C.
Undue tachycardia
Most attacks begin with migratory polyarthritis
of large joints occasionally with abdominal pain
and fleeting signs of peritoneal inflammation.
Variable combination of arthritis & arthralgia,
carditis (pancarditis), chorea and skin
manifestation (erythema marginatum and skin
infection)
 Diagnosis
Jones criteria: - Duckett Jones established these
criteria in 1944. Revised over the years.
Either two major criteria or one major and two
minor criteria with evidence of antecedent
group A streptococcal infection.
Diagnosis of recurrent ARF : either 2 major
criteria or 1 major plus 2 minor criteria or 3
minor criteria
Rheumatic chorea (Sydenham’s chorea): no
other major manifestation or evidence of
streptococcal infection required for the diagnosis
of rheumatic fever.
 The 2015 Revised Jones
Criteria

Previous rheumatic fever

leukocytosis

Previous rheumatic fever

leukocytosis
Plus supporting evidence of preceding streptococcal
Evidence of streptococcal infection
(within last 45 days)
-Elevated or rising streptococcal antibody (anti
strptolysin O) titer.
-Streptococcal antibodies (anti-DNAse B)
-Positive throat swab cultural for GABHS or
-Rapid antigen test for group A streptococci
(streptococcal carbohydrate antigen).
-Recent scarlet fever.
 Arthritis
Most common major manifestation but least
specific
2/3 of patients
Migratory polyarthritis of large joints with lower
limb joint involved first. Large joints particularly
knees, ankles, elbows and wrist are mostly
involved.
Always asymmetrical
Characteristically there is swelling, heat, redness,
severe pain (usually disabling), tenderness to
touch and limitation of movement.
Hips and spine or axial joint are rarely affected.
 May be sole manifestation in older
patients with ARF
Striking feature is dramatic response to
saliycylates, NSAIDs
If untreated last only for 2-3 weeks.
Does not result in permanent joint
deformity
Carditis
Considered most specific manifestation
Noted in at least 50 % cases of acute RF.
Single most important component of the
disease in determining the prognosis
Pancarditis involving pericardium,
myocardium and endocardium
Involves mitral and aortic valve. chordae of
mitral valve is considered most characteristics
of rheumatic carditis.
Early valvular damage leads to regurgitations
(MR,AR)
Presentations:
- Subclinical cardiac involvement with 1st
degree AV block.
- pericardial pain and pericardial rub,
pericardial effusion
- unexplained tachycardia, gallop rhythm
- new murmur or changing murmur
- apical pansystolic murmur - MR
- transient apical mid diastolic murmur
(carey-coombs murmur)
- early diastolic murmur - AR
- acute fulminant congestive heart failure
Mitral valve most often involved followed
by aortic valve.
Pericarditis along with valvular involvement
Cardiac tamponade and constrictive
pericarditis do not occur.
Healing of Rheumatic valvulitis leads to the
most serious complications of RF, valvular
stenosis and / or regurgitation.
 Sydenhams chorea
(St. Vitus Dance)
Neurological disorder characterized by rapid,
involuntary, purposeless and abrupt movements.
Associated with muscular weakness and emotional
lability (personality changes with inappropriate
behavior, restlessness and outbursts of anger or
crying)
Occurs in 20% of patients due to rheumatic
inflammatory involvement of basal ganglia and
caudate nuclei.
Involves all muscles but primarily muscles of face
and extremities are involved.
Severe cases – individuals are unable to perform
activities of daily living.
May be the sole expression or
associated with carditis.
Late presentation – after a prolonged
latent period
Females- Girls of 7-14 yrs of age
Self limiting with complete recovery
within 6 weeks.
Erythema marginatum
Non itchy, evanescent pink rash over
the trunk and flexor aspect of limbs.
Begins as pink macules- skin in center
of lesion returns towards normal leaving
a serpinginous, spreading edge.
Fleeting and disappears within hours.
Indicative of underlying carditis.
In 5% cases.
Subcutaneous nodules
Firm, painless nodules about 0.5 to 2.0
cm in size
present over the extensor surface of
certain joints particularly elbow, knee,
wrist, in occipital region or spinous
process of thoracolumbar vertebrae.
Rare and seen most commonly in
patients with carditis.
Appears after 2-3 wks
Last for just a few days to 3 wks.
 Laboratory investigations
No definite Laboratory test for ARF.
TLC, DLC, Hb, ESR , peripheral blood film.
C-Reactive protein
ASO titer - >240 Todd’s unit(adult)> 330
Todd’s unit in children
Throat swab culture
Streptococcal antigen test; streptococcal
antibody (anti-DNAseB)
ECG: first and rarely second-degree
atrioventricular block; features of pericarditis;
T-wave inversion; reduction in QRS voltages
Chest radiography: : cardiomegaly; pulmonary
To exclude other disease –
- repeated blood cultures for IE,
- copper, ceruloplasmin
- ANA, drug screen for choreiform movements
- serology or other autoimmune markers for
reactive arthritis, joint aspirate for septic
arthritis.
 Management
[Link] management
 Hospitalization when ever possible
 Bed rest to reduce joint pain. Usually 6
weeks.
 Ambulation started when fever has
subsided and joint pain and heart failure
controlled and markers of acute
inflammation ( total count, ESR, C -RP)
normalizes.
2. Anti – inflammatory agents
Salicylates (Aspirin)
- for milder attacks
- relieve joint pain within 24 hours of starting
treatment.
-Aspirin at dose of 80-120 mg/kg/day - four
divided doses results in adequate serum level
to achieve clinical response (max 8gm/day).
Children are treated with lower doses
Usually used in high dose for 2 weeks &
tapered by 20% each week depending upon
clinical response and laboratory measurement
of inflammatory markers.
Other NSAID can also be used
Antibiotic:
Penicillin is antimicrobial agent of choice for
eradication of GABHS from throat
Benzathine penicillin G: 600 000 U for patients < 27
kg IM Once 1200,000 U (1.2 million unit) for patients
> 27kg
Penicillin V: Children: 250 mg 2-3 times daily, PO,10
days
Adults: 500 mg 2-3 times daily, PO, 10 days
For individuals allergic to penicillin
Erythromycin : 20-40 mg/kg/d 2-4 times daily PO,10
days
(maximum 1 g/d)
Steroids
-Produce more rapid symptomatic relief than aspirin
-Indicated in cases with carditis or severe arthritis.
-Prednisone 1 to 2mg/kg/day is the usual dose; one
week (till ESR comes down to normal) and tapered
over 2 weeks
-while tapering steroids – overlap with aspirin to
prevent rebound of disease.
If Heart failure intervenes, patient should receive
diuretics, oxygen and digitalis and have a restricted
sodium diet. Sometimes surgical intervention.
Milder cases of chorea can usually be managed by
providing a calm environment. In patients with
severe chorea, carbamazepine or sodium valproate
is used. Prednisolone may be added for early
recovery
Inflammatory markers should be monitored
every 1–2 weeks until they have normalized
(usually within 4–6 weeks), and an
echocardiogram should be performed after 1
month to determine if there has been
progression of carditis.
Administration of secondary prophylaxis
before the patient is discharged.
Education of Patients and their families about
their disease, emphasizing the importance of
adherence to secondary prophylaxis.
 Prevention
Primary prevention
Early detection and treatment of streptococcal sore
throat
Clinical, Throat swab culture, Antigen detection test,
Streptococcal antibody test
Appropriate anti microbial therapy for 10 days
Early therapy-reduces both morbidity & period of
infectivity
Secondary prevention
Long term administration of antibiotics to prevent
recurrences
Started as soon as RF or RHD is diagnosed
Duration of therapy depends upon clinical
manifestation.
Antibiotic for secondary prophylaxis:
 Benzathine Penicillin G
- 1200,000 U deep i/m
- 600,000 U for children weight less than 27 kg.)
- every 4 weeks is the recommended regimen
but dosages at interval of 3 weeks is prescribed
in most developing countries
Oral Penicillin V 250 mg twice a day
For those allergic to Penicillin
Erythromycin 250 mg twice a day. ( both for
children/adult)
 Duration of Penicillin Prophylaxis

Category Duration

Rheumatic fever without 5 years or until age

carditis 21, which ever is
longer
ARF with carditis but no
residual valvular disease
10 yrs. from last
ARF recurrence or 21
with carditis and
residual valvular disease years of age, which
ever is longer
At least 10 yrs. after
last episode and at
least until age 40
 Prognosis
Untreated, ARF lasts on average 12 weeks.
With treatment, patients are usually
discharged from hospital within 1–2 weeks.
Immediate mortality is 1-2%. Persistent
rheumatic carditis with cardiomegaly, heart
failure and pericarditis implies poor prognosis
After 10 years atleast half to 2/3 patients of
ARF with carditis will have detectable valvular
abnormality.
In developing countries evolution of chronic
valvular disease is more rapid and severe.
 Conclusion

Cardiac involvement - most serious manifestation –

leads to chronic valvular heart disease in 60%
cases.
ARF – licks the joint and bites the heart.
Episodes of ARF tend to recur in the same
individual unless preventive measures are
instituted.
Life long morbidity
Long term even life time antibiotic prophylaxis is
needed. Economic burden for developing countries.
It is preventable. Early detection and treatment of
streptococcal sore throat can prevent ARF.