This document discusses acute rheumatic fever and rheumatic heart disease, which are nonsuppurative sequelae of group A streptococcal (GAS) infection. Acute rheumatic fever develops in 0.3% of individuals after GAS pharyngitis and can lead to cardiac involvement in 39% of cases. Chronic rheumatic heart disease is the leading cause of mitral valve stenosis requiring valve replacement and has mortality rates of 1-10%. Prevention involves adequate antibiotic treatment of initial GAS infections and long-term antibiotic prophylaxis for those with a history of rheumatic fever to prevent recurrence.

1. Acute Rheumatic fever leading to Rheumatic heart
disease – major health problem worldwide –
most prevalent heart disease in children
RF and RHD are nonsuppurative sequel of GAS
infection due to delayed immune response
Exact pathogenesis unclear, possible autoimmune
response
0.3% of group A β-hemolytic strep. pharyngitis
develop Acute Rheumatic fever
@ 39% of Acute Rheumatic fever develop varying
degree of cardiac involvement
Chronic Rheumatic heart disease – leading cause of
mitral valve stenosis needing valve replacement
Mortality rates 1-10%

2. Rheumatic fever caused by Group A β hemolytic strep.
(Strep. Pyogenes) pharyngitis
Group A β hemolytic strep. Gram positive coccoid shaped
bacteria
GAS – Lancefield carbohydrate A ( A-V)
Subdivision by M protein - >90 serotypes
most common strains causing pharyngitis –
1,12,28,3,4,2,&6 rarely causes skin infections
49,55,57,60 & few of 12 associated with AGN
Rheumatogenic strains - encapsulated mucoid strains rich in
M protein & resistant to phagocytosis
Hemolysis patterns -
β – complete hemolysis
α – partial hemolysis – green
γ – no hemolysis

3. ARF typically follows GAS pharyngitis, Strep cellulitis never
implicated
GAS produces cytolytic toxins S and O
O antibodies persists for long periods
GAS causes – suppurative disease – pharyngitis, impetigo,
cellulitis, myositis, pneumonia, puerperial
sepsis
- nonsuppurative - ARF, Post streptococcal
glomerulonephritis
Host susceptibility factors unclear,
- possible genetic predisposition - ↑ family cluster
- no associations with class I HLAs
- ↑ in class II HLA DR2 in blacks & DR4 in whites
HLA B5 have ↑immune-complex

4. Streptococcal antigens – epitopes cross reacting with myocardium, synovia and brain -
- hyaluronate in bacterial capsule
- cell wall polysaccharides – glycoproteins/laminin of valves
- membrane antigens – sarcolemma and smooth muscles
- other similar M protein structures - tropomyosin, keratin
Streptococcal superantigens – group of antigens synthesized by bacteria (and viruses)
able to bridge ClassII major histocompatibility antigens to non-polymorphic V β-
chains of T cell receptor  stimulation & release of cytokines or become cytotoxic, B
cell stimulation  autoreactive antigens
Acute rheumatic heart disease  pancarditis
Endocarditis  valvular disease
-mitral – 65- 70%
- aortic – 25%
- tricuspid – 10%
- pulmonary valve – rare
Myocarditis  dysfunction ? Myocarditis ? Congestive failure
Pericarditis  rare to affect cardiac function or cause constrictive pericarditis
Residual and progressive deformity of valves – fusion of valve apparatus at commisures,
cusps, chordae attachments or combination  stenosis and insufficiency in 9-39%
cases of ARF

5. Incidence – GAS most common bacterial cause of
pharyngitis in developed/developing country
Most common in 5-15 yrs age group less frequent
in <3 yrs and adults
Most develop at least 1 episode of pharyngitis/yr -
@ 80% viral – 15-20% GAS
Incidence varies & influenced by season, age
group, socioeconomic conditions, environmental
factors, quality of health care
Presence of GAS  true infection or carrier state,
carrier state does not produce rising ASOT

6. Healthy school children 6-10yrs
ASOT >200 in 15 – 70% (Upper limit of normal = no
more than 20% of general population)
Carrier rates for β hemolytic strep. - 10 – 50%
of asymptomatic school children, 50-60%
Group A
Patients with true infection only at risk of RF
and spreading GAS to contacts
Prevalence of rheumatic heart disease in school
children Kathmandu 1997reported incidence
1.2/000

7. Diagnosis of RF
Duckett Jones 1944 criteria –
Major criteria –
Carditis, Polyarthritis, Chorea, Erythema Marginatum, Subcutaneous
nodules
Minor criteria –
Arthralgia, Fever, Elevated ESR or CRP, Prolonged PR interval,
Evidence of preceding GAS infection – +ve throat culture or
rapid antigen test, Elevated or rising antibody titre
Role of echocardiography is considered supportive
Carditis is the single most important prognostic factor in RF suggested by
significant murmurs indicating mitral or aortic regurgitation, pericardial
rub, unexplained cardiomegaly with CHF.
Only valvulitis leads to permanent damage
RF tend to recur & cardiac involvement invariably occurs if initial episode
involved the heart
Jones criteria not absolute eg Chorea with h/o documented GAS
Carditis diagnosed as symptoms consistent with heart failure, dyspnoea, exercise
intolerance, tachycardia out of proportion to fever

10. Physical findings –
Cardiac manifestation - acute
Pancarditis most common – dyspnea/orthopnea,
chest discomfort, pleuritc chest pain, cough, edema
Carditis – new murmur or changing murmur&
tachycardia, findings of echo-Doppler only is
controversial
Congestive heart failure due to valve insufficiency or myocarditis–
tachypnea, orthopnea, ↑JVP, rales, hepatomegaly, gallop rhythm,
oedema
Pericarditis – friction rub, increased cardiac dullness with muffled heart
sounds, paradoxical pulse (dropin systolic BP in inspiration),
diastolic indentation of RV in echo = cardiac tamponade
Murmurs typically of valve insufficiency
Apical high pitched, blowing, radiating to axilla,
unaffected by respiration/position, grade 2or>/6
Apical diastolic murmur (Carey-Coombs) low
pitched, rumbling, best heard with bell in left
lateral position
Basal diastolic murmur of aortic regurgitation – high pitched,
blowing, decrescendo, best heard upper right sternal
border after deep expiration and leaning forward

11. Non cardiac –
Polyarthritis – 70 - 75% - common in teens and
young adults typically starts with larger joints
of lower extremeties (knees & ankles) migrates to
other joints elbows, wrists, pain severe than
clinical, swelling, hot & erythematous, limitation
of movements max. severity in 12 -24 hrs lasting
2-6 days rarely >3wks.
Chorea (Sydenham, St. Vitus dance, chorea minor) –
10 – 30% common in females, latency after
pharyngitis 1-6mos, improvement in 1-2wks
full recovery in 2-3 mos. Slow onset
presenting as writing difficulty ∴daily
handwritibng samples for progress, involuntary
movements, hypotonia, emotional labilty, speech
impairment, hyperextended joints ↓ tendon
reflexes, tongue fasciculations, relapsing grip
(milking sign)

12. Paediatric autoimmune neuropsychiatric disorders
associated with strep. infection (PANDAS) –
proposed involvement of Basal Ganglia -
prepubertal (3yrs to puberty) and dramatic
“overnight” in onset, may be associated with
chorea – OCD (somatic obsession),
cognitivedefects, motor hyperactivity, may have
emotional lability, separation anxiety,
oppositional behaviour. Or OCD and/or tic
disorder like Tourette Syndrome worsening
after strep. Infection
Other associated symptoms – ADHD, sleep
disturbances, nocturnal enuresis, urinary
frequency, fine/gross motor changes e.g.
handwriting changes, joint pains

13. Erythema marginatum (erythema annulare) –
5- 13 %, appears early in the course as 1-3
cm macule or papule over trunk or proximal
limbs – never on face, spread outwards
forming serpiginous ring with erythematous
margins and central clearing, fade and
reappear in hours, nonpruritic, exacerbated
by heat, may remain after resolution of other
symptoms.
Not specific to RF – seen in sepsis, drug
reactions, glomerulonephritis

14. Subcutaneous nodules – frequency diminishing 0-8%
appearing several weeks of disease, strongly associated with
carditis, firm, nontender, free from skin, upto 1-2cms,
usually 3-4 in nos., appearing over extensor surfaces of
elbows, knees, ankles, and knuckles , scalp & lumbar and
thoracic spinous processes attached to tendon sheaths.
Histologically similar with Aschoff bodies of heart
Fever – no characteristic pattern, usually 39°c, may be low
grade in carditis, absent in chorea, resolves usually in 1wk.
Epistaxis may be related to cardiac problems
Arthralgia - reactive
Abdominal pain – usually during onset of RF
Rheumatic pneumonia – similar presentation to infectious type
with consolidation and presence of nodules in fibrous septa
of lungs, frequently fatal, cf. respiratory distress due to
congestive failure
Use of NSAIDs suppresses full manifestation of RF

15. Cardiac manifestation of chronic RF
Valve deformity –
Mitral valve – stenosis in 25%, associated insufficiency in another
40%. Progressive fibrosis thickening, calcification  stenosis  valve
funnel shaped + fish mouth appearance  enlargement of LA +
formation of mural thrombi. S1 initially accentuated – reduced after
thickening of leaflets. P2 accentuated, ↓ splitting as pulm. hypertension
sets. Mitral opening snap, diastolic murmur at apex
Aortic valve – stenosis frequently associated with incompetence.
Diminished valve orifice due to adherence and fusion of cusps. S2
becomes single due to immobile cusps. Systolic and diastolic murmur at
base
Thromboembolism complicates mitral stenosis  dilatation, atrial
fibrillation.
Atrial arrhythmia – chronic enlargement of atrium – anti coagulation
before cardioversion
Cardiac hemolytic anemia – due to disruption of RBC by deformed valve
leaflets + increased turnover of platelets

16. D/D
Aortic valvular diseases
Mitral valve diseases
Myocarditis
Pericarditis
CCF
Kawasaki disease
Cardiomyopathy – dilated
Carnitine deficiency
Bacterial endocarditis
HIV infection
SLE

17. Investigations
Throat culture – usually negative
Rapid antigen detection test
Antistreptococcal antibodies – check at 2wks. Interval for rising titer ASOT, anti
DNAse B, antihyaluronidase, antistreptokinase, antistreptococcal esterase,
anti-DNA
Antibodies to cellular components – antistreptococcal polysaccharide,
antiteichoic acid antibody, anti-M protein antiobody
Antibodies to extracellular component rises in 3-6wks after infection, plateaus for 3-
6mos falls to normal after 6-12mos. antiDNAse B rises in 6-8 weeks.
Antihyaluronidase persists longer than ASO
Acute phase reactants – CRP, ESR, useful for progress monitoring, detect relapse
during aspirin treatment, identify recurrence of disease
Heart reactive antibodies – tropomysin
Rapid detection test for D8/17 to detect at risk individuals

18. Imaging studies –
CXr – cardiomegaly, pulmonary congestion,
rheumatic pneumonia
Echocardiography – Doppler
Cardiac catheterization – not indicated in acute
stage. Evaluation of valvular involvement in chronic
disease, balloon dilatation of stenotic valves
ECG – sinus tachycardia, A-V blocks,
elevated ST in acute phase, atrial
flutter, fibrillation, tachycardia

19. Management - Medical –
Admission –
Investigations – throat swab, rapid
strep.antigen test, ASO and/or DNaseB, ESR, CRP,
CXray, ECG, Echo if available, blood c/s to r/o
endocarditis
Monitor for onset of carditis – if present
bed rest for four weeks
Protective environment for cases of Chorea
Eradication of Strep. infection by antibiotics
followed by secondary prophylaxis.
Antibiotic treatment does not alter
the course of ARF.

20. Suppression of inflammatory process –
Only after confirmed diagnosis –
Salicylates – Aspirin 100mg/kg -125mg/kg in children (÷4-
5doses). Optimal dose = adequate response without side effects.
Symptoms of toxicity if present usually subside in few days
despite continuation. Reduce to 60-70mg/kg after desired
steady state blood level maintained for 2 weeks continue for 3-
6wks.
Naproxen 10-20mg/kg if salicylates not tolerated
Prednisone 1-2mg/kg/d in patients not responding
favourably to salicylates, pericarditis, heart failure
I/V Methylprednisolone in life threatening
situation
Aspirin / steroids ? Does not reduce
subsequent heart disease
Duration depends on clinical response and normalization
of acute phase reactants
@ 5% cases continue to demonstrate rheumatic activity
for longer periods & may need longer treatment with drugs

21. Rebound of lab. & clinical features may be noticed 2-3wks
after stopping treatment, severe symptoms only needs
retreatment
Management of heart failure –
Bed rest
Steroids
In symptomatic patients –
diuretics
ACE inhibitors
Digoxin
Management of Chorea – usually self limiting
Neuroleptics
Benzodiazepines
AED
Steroid role questioned

22. Surgical management – Indications
Symptoms progressing beyond NYHA class II
Patients mild or asymptomatic with progressive LV enlargement of
clinical or radiological examination - >0.5 cm/yr
Cardiac failure due to valve lesions
Pulmonary hypertension – ECG – RVH, Pulmonary artery dilatation
in CXR
Tricuspid regurgitation complicating mitral valve disease
Development of AF
Thromboembolism
Endocarditis leading to cardiac decompensation
Echo findings –
MS – valve area <1.5cm², pulmonary hypertension, presence of
thrombus
MR – LV EF <50%, LV end systolic dimension>55mm, pulmonary
hypertension
AS – valve area <0.8cm², jet velocity >4.0m/sec, LVEF <50%
AR – LVEF <50%, LV endsystolic dimension >55mm
Balloon valvotomy/ commissurotomy
Surgical valve repair/replacement

23. Post-op complications –
structural valve deterioration – time dependent for biological and
bioprosthetic valves
valve thrombosis
thromboembolism
prosthetic endocarditis
major bleeding 2° to anticoagulant
paravalvular leak
Referral if –
recurrent symptoms
evidence of cardiac failure
muffled prosthetic heart sounds
a new regurgitant murmur
any thromboembolic episode
s/s suggestive of endocarditis
Anticoagulation – INR of 2·5 – 3, higher if LV function
impaired, thrombogenic prosthesis

24. Prevention of RF –
Primary – Adequate antibiotic therapy of URTI (pharyngitis)
with GAS to prevent an initial attack of ARF.
Benzathene Penicillin - single IM
Phenoxymethyl Pen. - oral x 10 days
Amoxicillin - oral x 10 days
1st. Gen. Cephalosporins - oral x 10 days
Erythromycin ethylsuccinate - oral x 10 days
Recurrence of pharyngitis – confirm GAS by throat culture,
M typing of strains for treatment failure or new
infection.
New infection – same antibiotic used, if penicillinase
producers – amoxycillin/clavulanate
GAS carriers – no antibiotics necessary ∵ spread unlikely +
low risk of ARF
? Vaccines

25. Secondary prevention of RF
continuous administration of specific antibiotics to patients
with h/o previous attack of RF to prevent colonization or
infection of URT with GAβHS and development of recurrent
attacks of RF. Secondary prophylaxis mandatory for
ducumented RF irrespective of residual heart disease.
Penicillin is d.o.c.
Benzathene Penicillin - Every 3wks. in high risk areas &
4wks. in low risk areas.
Oral penicillin – serum levels less predictable, problem with
compliance, recurrence of RF more frequent
used only in low risk group & IM not accepted Penicillin
V 250 mg x 2/d
Oral Sulphonamide – Sulphadiazine or sulfasoxazole –
effective in preventing colonization not eradicate
500mg/d in <30kg wt
1Gm/d in >30 kg wt
Erythromycin – 250mg x2/d

26. Duration of 2° prophylaxis
In absence of proven carditis – 5 years after last
attack or till 18yrs of age whichever is longer
With carditis ( milld mitral regurgitation or healed carditis)
– 10years after last attack or at least 25 years
of age whichever is longer
Severe valvular heart disease & after valve
surgery – lifelong
Cautions – sulpha in pregnancy
presence of endocarditis
IM in patients in anticoagulants
Penicillin allergy less in <12 yrs group