4/19/2021

Update:
Rheumatic Fever &
Rheumatic Heart Disease
Shirley F. Delair, M.D., M.P.H.
Associate Professor of Pediatrics
Chief, Division of Pediatric Infectious Diseases

Objectives
 Review epidemiology of Acute Rheumatic Fever (ARF) &
Rheumatic Heart Disease (RDH) in low- and middle-income
countries
 Describe clinical/laboratory criteria to diagnose ARF & RHD
 Discuss the management ARF and RHD

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Acute Rheumatic Fever (ARF)

 Leading cause of acquired heart disease in children & young adults
worldwide
 Occurs most commonly in children 5 to 15 years of age
 300,000-500,000 new cases of rheumatic fever occur annually
 ~ 60% of rheumatic fever develop rheumatic heart disease
 Almost all of this toll occurs in the developing world

Watkins, N Engl J Med 2017; 377:713-722

Rheumatic Heart Disease (RHD)

 33.4 million people worldwide with rheumatic heart disease
 10.5 million disability-adjusted life-years due to rheumatic heart disease
 230,000 deaths from rheumatic heart disease complications
 In Africa, rheumatic heart disease remains the highest globally (15-20 per
1,000 pop)
 In 2018, rheumatic heart disease deaths in Ghana
 489 or 0.24% of total deaths
 Adjusted death rate about 3.79 per 100,000

Watkins, N Engl J Med 2017; 377:713-722 https://www.worldlifeexpectancy.com/

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Global Burden of Rheumatic Heart Disease

https://www.scielo.br/scielo.php?pid=S0102-76382020000600958&script=sci_arttext&tlng=en

Global Burden of ARF and RDH

Incidence of ARF and Incidence of ARF and
prevalence of RHD in high prevalence of RHD in low-
income countries middle income countries
- Decline attributed to reduce - Most burden of disease due to
household crowding, hygiene, ongoing social and economic
access to antibiotics and disadvantages
medical care - ARF is more endemic
- Incidence of ARF follows an
outbreak pattern

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A previously healthy 8 yo male was brought to you for 2 weeks of easy fatigue.
Parents report that 2 months prior he had complained about throat pain. He
received over the counter amoxicillin for about 24 hours at the time and since he
felt better the antibiotic was not continued.

 On physical examination you note a sweaty child but afebrile. Other vitals:
HR=120bpm, RR=42cpm
 Heart: Tachycardic with a 3/6 holosystolic murmur at apex radiating to the
axillae. No diastolic murmur appreciated.
 Lungs: Bilateral basal crackles otherwise good air entry.
 Abdomen: palpable liver that is 3cm below the costal margin.

What is your thought on what is going on and how do you manage this patient?

Acute Rheumatic Fever (ARF)

 Occurs 2-4 weeks following an episode of untreated/inadequately treated
group A Streptococcus (GAS) pharyngitis
 Caused by immunological reaction to GAS pharyngitis
 May consist of arthritis, carditis, chorea, erythema marginatum, and
subcutaneous nodules
 Damage to cardiac valves may be chronic and progressive, resulting in
cardiac decompensation

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https://gafacom.website/acute-rheumatic-fever-arf-causes

https://www.cfp.ca/content/61/10/881

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Dooley, Autoimmunity Reviews,Volume 20, Issue 2, 2021

GAS Pharyngitis

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Erythema marginatum
 Rarest of the major signs in ARF.
 Usually present over trunk not seen
over face
 Evanescent pink eruption last for hours
w/ irregular but well-demarcated
borders
 If seen careful cardiac exams as greater
risk to develop carditis

Subcutaneous Nodules
 Usually small and non frequent finding
 Located over prominent areas leading to
rubbing and microtrauma
 Presence heralds severe carditis

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Migrating polyarthritis
 Usually one joint involved initially then
resolves, then another joint…
 Two or more joints are considered polyarthritis
 Most common joints large weightbearing joints
 Joint pain typically very severe though visual
findings not impressive Okello, J Am Heart Assoc. 2020 Aug 4; 9(15)

A 13 yo female is brought to you for “abnormal behavior” for

the past several months. She is talking to herself and
wringing her hands. Family is worried about “spiritual intent”
and had spent some time at a church house. On your
examination she looks well but does not answer your
questions, you realized she has facial grimacing and
constant hand movement. Family does not recall a history of
sore throat.

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Sydenham Chorea
 Also known as St. Vitus dance
 Causes purposeless and involuntary movements
 Hands and tongue often involved
 Mood swings or "not acting right”  emotional lability
 Occasionally occurs so late in illness that labs are normal
 Patients can develop cardiac disease
 Not present while sleeping
 Usually resolves with time

Sydenham Chorea

https://www.youtube.com/watch?v=GolFWx4RYH4

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Sydenham Chorea

https://www.youtube.com/watch?v=GolFWx4RYH4

Sydenham Chorea

https://www.youtube.com/watch?v=GolFWx4RYH4

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Sydenham Chorea

https://www.youtube.com/watch?v=GolFWx4RYH4

The following are included in the revised Jones criteria EXCEPT:

A. Migrating polyarthritis
B. Chorea
C. Subcutaneous Nodules
D. New murmur (carditis)
E. Maculopapular rash

Poll 1

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The following are included in the revised Jones criteria EXCEPT:

A. Migrating polyarthritis
B. Chorea
C. Subcutaneous Nodules
D. New murmur (carditis)
E. Maculopapular rash

Poll 1

Acute Rheumatic Fever (ARF)

 Mnemonic JONES
 J = Joints!  Migratory polyarthritis
 O = “O” ~ Shaped like a heart  Carditis
 N = Nodules!  Subcutaneous nodules
 E = Erythema!  Erythema marginatum
 S = Sydenham!  Sydenham chorea

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Acute Rheumatic Fever (ARF)

Revised Jones Criteria
Dx of ARF is now based on
 Population risk with variability in clinical presentation
 One of most important causes of cardiovascular morbidity and
mortality among socially and economically disadvantaged
 Doppler echocardiography as tool to dx cardiac involvement
 Cornerstone for screening to evaluate prevalence of
rheumatic heart disease

You see a febrile 7 yo male in your clinic who also has a tender and
swollen right knee. Parents report that he also had more recently a
swollen left wrist that improved and that 2 months prior he had a sore
throat.
A. 2 Majors
B. 1 Minor
C. 1 Major 1 minor
D. 1 Major
E. 2 Minors
Poll 2

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You see a febrile 7 yo male in your clinic who also has a tender and
swollen right knee. Parents report that he also had more recently a
swollen left wrist that improved and that 2 months prior he had a sore
throat.
A. 2 Majors
B. 1 Minor
C. 1 Major 1 minor
D. 1 Major
E. 2 Minors
Poll 2

Acute Rheumatic Fever (ARF)

Revised Jones Criteria
Low risk
 ARF incidence <2 per 100 000 school-aged children per year
 RHD prevalence ≤1 per 1000 of an all-age population per year
For all patient populations with evidence of preceding GAS infection
2 Major manifestations or 1 major plus
Diagnosis: initial ARF
2 minor manifestations
2 Major or 1 major and 2 minor or 3
Diagnosis: recurrent ARF
minor

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Acute Rheumatic Fever (ARF)

Evidence of preceding GAS infection:

 Evidence of bacteria
o Positive throat culture for GAS
o Positive rapid throat test for GAS

 Elevated or rising anti-streptococcal antibodies

o Anti-streptolysin O titers
o Anti-DNase B

Acute Rheumatic Fever (ARF)

Revised Jones Criteria
Major criteria
Low-risk populations
Carditis
•Clinical and/or subclinical
Arthritis
•Polyarthritis only
Chorea
Erythema marginatum
Subcutaneous nodules
Moderate- and high-risk populations
Carditis
•Clinical and/or subclinical
Arthritis
•Monoarthritis or polyarthritis
•Polyarthralgia
Chorea
Erythema marginatum
Subcutaneous nodules

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Acute Rheumatic Fever (ARF)

Revised Jones Criteria
Minor criteria
Low-risk populations Moderate- and high-risk populations
Polyarthralgia Monoarthralgia
Fever (≥38.5°C) Fever (≥38°C)
ESR ≥60 mm in the first hour and/or
ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL
CRP ≥3.0 mg/dL
Prolonged PR interval, after accounting Prolonged PR interval, after accounting
for age variability (unless carditis is a for age variability (unless carditis is a
major criterion) major criterion)

Acute Rheumatic Fever (ARF)

Echocardiographic criteria developed by AHA in 2012
Echocardiographic (Doppler) criteria:
 Pathological mitral regurgitation – 4 criteria (all must be met)
 Pathological aortic regurgitation – 4 criteria (all must be met)

Echocardiographic (morphological) criteria:

 In acute mitral valve involvement
 In chronic mitral valve involvement
 Lesions in acute and chronic aortic valve involvement

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Acute Rheumatic Fever (ARF)

Diagnostic work up
 Full blood count (FBC)
 Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)
 Throat swab for culture
 Anti-streptolysin O titer
 Sickling status
 Chest X-ray
 12-lead ECG
 Echocardiogram

GHANA-STG-2017

Challenges of diagnosis of ARF

ARF largely a disease of exclusion
Malaria is endemic and incidental malaria parasitemia is common
Overlap between malaria and ARF

Sickle cell disease (SCD) can mimic ARF symptoms

SCD can have mitral regurgitation and pulmonary hypertension.
SCD should be ruled out in all children presenting with fever and joint pain

Diagnosis of ARF in settings with high rates of premedication wi/ NSAIDs.

NSAIDs rapidly reduce joint symptoms
Self‐prescription can mask severity of both joint manifestations and fever

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ARF vs RHD symptoms

Symptoms ARF: Symptoms RHD:
 Sore throat  Shortness of breath
 Joint pain  Chest pain
 Fever  Edema
 Feeling sick  Heart palpitation
 Skin rash  Breathlessness on exertion
 Uncontrollable movement  Fainting syncope
 Changes in mood  Stroke
 Nodules lump under the skin  Fever due to infection or damaged
 Shortness of breath heart valves
 Chest discomfort
 Weakness

A 10 yo male is brought to your clinic after parents noticed small

painless bumps/swellings over his elbows and knuckles. They
have there for about 2 months and were not going away. Parents
also report that he had complained of some pain in some of his
joints, the pain did not last long and resolved spontaneously.

On examination, he is afebrile, and you note the painless nodules on

his extensor surfaces. You also appreciate a 3/6 systolic murmur at
the apex that radiates to the left axilla.

Poll 3 & 4

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The most common valvular lesion in RHD is on the:

A. Pulmonary valve stenosis

B. Tricuspid valve regurgitation

C. Mitral valve regurgitation

D. Aortic valve stenosis

Poll 3

The most common valvular lesion in RHD is on the:

A. Pulmonary valve stenosis

B. Tricuspid valve regurgitation

C. Mitral valve regurgitation

D. Aortic valve stenosis

Poll 3

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What is the main difference between Acute Rheumatic Fever (ARF)

and Rheumatic Heart Disease (RHD)?

A. In ARF there is evidence of subcutaneous nodules

B. In RHD there is a prolonged P-R interval
C. In ARF there is an elevated ESR
D. In ARF there is a history of arthralgias
E. In RHD there is evidence of chronic heart disease

Poll 4

What is the main difference between Acute Rheumatic Fever (ARF)

and Rheumatic Heart Disease (RHD)?

A. In ARF there is evidence of subcutaneous nodules

B. In RHD there is a prolonged P-R interval
C. In ARF there is an elevated ESR
D. In ARF there is a history of arthralgias
E. In RHD there is evidence of chronic heart disease

Poll 4

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Rheumatic Heart Disease (RHD)

 Most common form of affects heart valves &
almost always w/ valvulitis murmur (hallmark)
 Most common valvular lesion:
o Mitral valve incompetence in early stages
o Mitral stenosis from persistent/recurrent
valvulitis
o Aortic regurgitation often w/ mitral
regurgitation
o Tricuspid regurgitation often functional
• Caused by mitral stenosis w/ high
pulmonary pressures & consequent
right ventricular dilatation

17 yo male comes to your clinic with easy fatigue and

difficulty with swallowing for the past several months. He
denies any in his throat and mom recall several years ago
he was treated for a sore throat. He report occasional
intermittent fast heart beat.

On examination he has a 2/4 diastolic murmur at the apex.

CXR showed a steep left side heart border.

Poll 5

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The most likely findings of this patient’s RHD is:

A. Tricuspid valve regurgitation

B. Pulmonary valve stenosis

C. Mitral valve stenosis with left atrial dilation

D. Aortic valve stenosis

Poll 5

The most likely findings of this patient’s RHD is:

A. Tricuspid valve regurgitation

B. Pulmonary valve stenosis

C. Mitral valve stenosis with left atrial dilation

D. Aortic valve stenosis

Poll 5

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Rheumatic Heart Disease (RHD)

 RHD might also present after complications:
o Atrial arrhythmia
o Embolic event
o Acute heart failure
o Infective endocarditis
 First episode of rheumatic carditis:
 No history of prior ARF or RHD w/
 New apical systolic murmur of mitral
regurgitation (w/w out apical mid-
diastolic murmur)
 And/or basal early diastolic murmur of
aortic regurgitation
 W/ previous RHD
 Change murmur character

Diagnostic criteria for rheumatic heart

disease based on history, cardiac
auscultation, and echocardiographic
findings

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ARF and RHD Treatment Goals

 Eradicate streptococcal throat infection
 Suppress inflammatory response
 Prevent recurrent episodes of rheumatic fever and further
heart valve damage
 Treat heart failure if co-existent

GHANA-STG-2017

A 9 yo female is brought to your clinic because parents were concerned about her
right knee which has been swollen for the past 6 days and she feels warm. A week
prior, she complained of right ankle pain, her mother thought she might have
twisted her ankle and gave her some ibuprofen and the pain resolved.

On exam, she is febrile and has a slightly inflamed right knee on examination, but
which is very tender even to light palpation.

What is your differential diagnosis, how do you manage her going forward, what long
term sequel should you be concerned about and how do you prevent that?

Poll 6

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What primary symptom of ARF are you using salicylates for?

A. Fever
B. Chorea
C. Rash
D. Arthritis
E. Carditis

Poll 6

What primary symptom of ARF are you using salicylates for?

A. Fever
B. Chorea
C. Rash
D. Arthritis
E. Carditis

Poll 6

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ARF Treatment
 Benzathine benzylpenicillin, IM,
o ≥ 30 kg body weight; 1,200,000 U as a
single dose
o < 30 kg body weight; 600,000 U as a single
dose
OR
 Phenoxymethyl penicillin (Penicillin V), oral,
o Adults 500 mg 12 hourly for 10 days
o Children
 6-12years; 250 mg 12 hourly for 10 days
 1-5 years; 125 mg 12 hourly for 10 days
OR
 Erythromycin, oral, (for patients allergic to
penicillin)
o Adults 500 mg 12 hourly for 10 days
o Children
 8-12 years; 500 mg 12 hourly for 10 days
 3-8 years; 250 mg 12 hourly for 10 days
 1-2 years; 125 mg 12 hourly for 10 days
GHANA-STG-2017
AND
 Aspirin, oral,
o Adults: 300-900 mg 4-6 hourly until
joint symptoms relieved, and
gradually withdraw over 1-2 weeks.
o Children: 1 month-18 years; 25
mg/kg 6 hourly until joint symptoms
relieved, and gradually withdraw
over 1-2 weeks.
OR
 Ibuprofen, oral,
o Adults: 200-800 mg 6-8 hourly (max.
2400 mg daily)
o Children: 10-15 mg/kg 6-8 hourly
(max. 40 mg per kg daily)

A previously healthy 8 yo male was brought to you for 2 weeks of easy fatigue.
Parents report that 2 months prior he had complained about throat pain. He
received over the counter amoxicillin for about 24 hours at the time and since he
felt better the antibiotic was not continued.

 On physical examination you note a sweaty child but afebrile. Other vitals:
HR=120bpm, RR=42cpm
 Heart: Tachycardic with a 3/6 holosystolic murmur at apex radiating to the
axillae. No diastolic murmur appreciated.
 Lungs: Bilateral basal crackles otherwise good air entry.
 Abdomen: palpable liver that is 3cm below the costal margin.

What is your thought on what is going on and how do you manage this patient?

Poll 7

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What primary symptom of ARF are you using corticosteroids for?

A. Fever
B. Chorea
C. Severe Carditis
D. Erythema marginatum
E. Arthritis

Poll 7

What primary symptom of ARF are you using corticosteroids for?

A. Fever
B. Chorea
C. Severe Carditis
D. Erythema marginatum
E. Arthritis

Poll 7

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ARF Treatment with carditis

 Benzathine benzylpenicillin, IM
OR
 Phenoxymethyl penicillin
(Penicillin V), oral
OR
 Erythromycin, oral, (for patients
allergic to penicillin)
AND
 Prednisolone, oral
Adults and Children:
2 mg/kg daily for 2 weeks and then
gradually taper off by 20-25% per
week for 1-3 weeks

AND
 Aspirin, oral
OR
 Ibuprofen, oral
GHANA-STG-2017

ARF Treatment with heart failure

 Benzathine benzylpenicillin, IM
OR
 Phenoxymethyl penicillin
(Penicillin V), oral AND
OR  Treatment for heart failure
 Erythromycin, oral, (for patients
allergic to penicillin)

AND
 Aspirin, oral
OR
 Ibuprofen, oral
GHANA-STG-2017

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Secondary prophylaxis for ARF & RHD

 Benzathine benzylpenicillin, IM,
o ≥ 30 kg body weight; 1,200,000 U as a single dose every 4 weeks
o < 30 kg body weight; 600,000 U as a single dose every 4 weeks
OR
 Phenoxymethyl penicillin (Penicillin V), oral,
o Adults 500 mg 12 hourly  Following Rx if ARF of an acute
o Children
 6-12years; 250 mg 12 hourly episode, secondary ppx for
 1-5 years; 125 mg 12 hourly minimum 10 y or until age 21 y
OR (whichever is longer)
 Erythromycin, oral, (for patients allergic to penicillin)
o Adults 500 mg 12 hourly for 10 days  With severe RHD secondary
o Children ppx indefinitely
 8-12 years; 500 mg 12 hourly
 3-8 years; 250 mg 12 hourly
 1-2 years; 125 mg 12 hourly

GHANA-STG-2017

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Primary Prevention of ARF and RHD  Vaccine

Challenges
 Serotypical and epidemiological diversity of the organism
 Paucity of animal models that reliably mimic Strep A
infections & immune sequelae Nitsche-Schmitz, Development and Therapy. 2014;4:39-54

 Concerns over the safety of the vaccine

Vaccine candidates
30-valent M protein Jim Dale, Phase 1 complete
vaccine (HVR region) PREVENT, USA (awaiting results)
(StreptAnova)
www.who.int/immunization/research/meetings_workshops/21_Steer_Kim_GroupA_strep.pdf?ua=1

Secondary Prevention of ARF and RHD

Screening for Rheumatic Heart Disease

Evaluation of a Focused Cardiac Ultrasound
Approach

Mariana Mirabel. Circulation: Cardiovascular Imaging. Screening for

Rheumatic Heart Disease, Volume: 8, Issue: 1, DOI:
(10.1161/CIRCIMAGING.114.002324) © 2015 American Heart Association, Inc.

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