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1. Unit 2:
Acute Rheumatic Fever

2. • To know about the epidemiology of ARF
• To understand the pathogenesis of ARF
• To know about the clinical features of ARF
• To learn about the diagnosis of ARF
• To understand management of ARF
• To know about the prevention of ARF
• To discuss the principles of management of
ARF
LEARNING OBJECTIVES

3. • ARF is a post infectious, non-suppurative sequel of
pharyngeal infection with Streptococcus pyogenes
• RHD is the only long-term sequel of ARF
• RHD manifests after several years of ARF with
heart failure or complications like stroke or infective
endcocarditis.
• ARF and RHD can easily be prevented by early
identification and treatment of streptococcal
pharyngeal infection.
• Currently, the 2015 AHA/ACC criteria are used to
diagnose ARF
Introduction

4. • Rheumatic heart disease currently affects over 33 million
people worldwide.
• RHD is found all over the world, but most commonly
affects women, adolescents and children living in
conditions of poverty and overcrowding.
• RHD kills 275,000 people every year, even though it is
a preventable disease.
• A few rich countries (including the USA and UK) and
some LMIC Countries like Cuba have managed to
reduce their burden of RHD, but other countries
continue to struggle with the disease.
• RHD is a lifelong condition, which is often fatal if not
treated properly.
EPIDEMIOLOGY

5. RHD in Ethiopia
• Recent school and community based studies in
Ethiopia have shown the prevalence of RHD in 4-
24 years age groups to be from 14-38/1000,which
is one highest in the world.
• Approximately 250, 000 people in the age group 5-
15 suffer from RHD in Ethiopia.
• More than 500,000 people of all age groups live
with RHD.
• Only few give history of Acute Rheumatic Fever

6. • RHD is the main cardiovascular diagnosis
accounting for 30-60% of all cardiac patients in
main hospitals of Ethiopia
• Patients usually come late with heart failure , stroke
or during pregnancy with severe valvular disease
• Mortality from RHD may reach 12.5% every year in
rural Ethiopia.
• It is also reported that 70% of RHD patients die before
the age of 26 years.
RHD in Ethiopia…

7. Risk Factors for Rheumatic Fever
• Socioeconomic status:
– Poverty
– Poorly made and overcrowded housing
– Lack of adequate health care
– Untreated GAS infections
• Sex
• Rheumatic fever occurs in equal numbers in males and females,
but the prognosis is worse for females than for males.
• Age
– Rheumatic fever principally affects children between 5-15
years of age with a median age of 10 years, although it also
occurs in adults (20% of cases).
• Risk factor for RHD
– Recurrent ARF

8. Risk factors for Rheumatic Fever
Determinants Effects Impact on ARF and RHD
burden
Socioeconomic &
environmental factors
1. Poverty
2. Poor nutrition
3. Overcrowding
4. Poor standard of living
1. Rapid spread of
GABHS
2. Difficulties accessing
health care
1. Higher incidence of acute strep
pharyngitis and complications
2. Higher incidence of ARF and
recurrent ARF
Health System Related Factors
1. Shortage of resources for
health care
2. Low level of knowledge of
disease among health care
providers
3. Low level of awareness of
disease in the community
1. Inadequate diagnosis
and treatment of strep
pharyngitis
2. Misdiagnosis or late
diagnosis of ARF
3. Inadequate secondary
prophylaxis delivery
1. Higher incidence of ARF and
recurrent ARF
2. Missed first ARF episode
3. Inadequate secondary prophylaxis
delivery
4. Higher rates of recurrent ARF with
more frequent and severe heart valve
involvement
5. Higher rates of repeated hospital
admissions and expensive heart
valve surgery

9. • Rheumatic fever is thought to result from an
inflammatory autoimmune response with antibodies
produced against streptococcal antigen induces
inflammation in host tissue having similar molecules
(ANTIGEN MIMICKERY THEORY)
• Only group A beta-hemolytic streptococcal infections
of the pharynx initiate or reactivate rheumatic fever.
• In 0.3-3% of streptococcal pharyngeal infection,
rheumatic fever develops several weeks after the sore
throat has resolved.
• Studies show the existence of genetic predisposition in
addition to bacterial factors.
Etiology and Pathogenesis

10. Etiology and Pathogenesis…
• After recovery from the initial episode of RF, up
to 60% to 65% of patients develop valvular heart
disease and the risk of RF recurrence following
GAS infection rises to 50%.
• Repeated GAS infections without appropriate
treatment (with benzathine penicillin G) leads to
RF recurrences and progressive valve damage-the
defining characteristic of RHD which can, in turn,
cause atrial fibrillation, heart failure, stroke and
endocarditis.

11. Pathogenesis of Acute Rheumatic Fever

12. Cascade of RF and RHD

13. Pathogenesis of Acute Rheumatic Fever …

14. Clinical Features
• Following sore throat with GABHS:
– Silent period of 2 - 6 weeks
– Sudden onset of fever, pallor, malaise, fatigue
• After which characteristic manifestations rheumatic fever
start to appear:
– Arthritis
– Carditis
– Erythema marginatum
– Subcutaneous nodules
– Sydenham’s chorea
• In one third of patients the streptococcal infection passes
unnoticed and 54 to 70% of recurrences of ARF were
caused by asymptomatic streptococcal infection.

15. Clinical Manifestations

16. 1. Arthritis
• It occurs in about 75% of cases.
• Usually a polyarthritis involving big joints: knees,
ankles, elbows, wrists
• Asymmetrical
• Migratory (fleeting)
• Joints are hot, red, tender, swollen with limited
mobility
• It is unusual to involve the central joints as spines,
hips and the peripheral ones as the fingers and toes.
Infrequently it involves the tempromandibular
joint.

17. Arthritis…
• No residual deformity (licks)
• It is more common and more severe in
teenagers and young adults than in children
• Lasts 2-6 weeks
• Dramatic response to salicylates

18. 2. Carditis
• Occurs in 40% of patients during the first attack
and almost 100% if ARF recurs.
• It may be the only major manifestations and
usually appears in the first week of the illness.
• Most serious manifestation
• May lead to death in acute phase or at later stage
• Any cardiac tissue may be affected
• Valvular lesion most common: mitral and aortic
• Seldom see isolated pericarditis or myocarditis

19. Pancarditis is the most serious and second most
common complication of rheumatic fever (50%).
In advanced cases, patients may complain of
dyspnea, mild-to-moderate chest discomfort,
pleuritic chest pain, edema, cough, or orthopnea if
they develop congestive heart failure and
pericarditis.
Upon physical examination, carditis is most
commonly detected by a new murmur and
tachycardia out of proportion to fever.
The murmurs of acute rheumatic fever are
typically due to valve insufficiency.
Carditis….

20. Carditis..
• Clinical signs:
High pulse rate
Murmurs : Mitral and aortic regurgitation most
common
 Pericarditis usually asymptomatic
 Occasionally causes chest pain, friction rubs or distant
heart sounds
 Cardiomegaly
 Rhythm disturbances (prolonged PR interval)
 Heart failure

21. Clinical Features of Carditis

22. 3. Sydenham’s Chorea(10-20%)
• Due to basal ganglia involvement.
• May be associated with normal laboratory findings.
• Involuntary, sudden, semi-purposeful movements of
limbs face and tongue. Disappear during sleep.
• Hypotonia and hyporeflexia.
• Emotional labiality and instability.
• More in females.
• Latent period (2-6 months). No arthritis and ESR is
usually normal.
• Self-limiting.

23. Chorea..

24. 4. Subcutaneous Nodule
– Small, painless, firm, free.
– Accumulated Aschoff nodules.
– Over bony prominences,
tendons .
– Often associated with severe
carditis.
– Can occur with other diseases
like rheumatoid arthritis
– They last for a week or two and
rarely more than a month, and
sometimes disappear within
several days.

25. 5. Erythemia Marginatum (10%)
– Erythema with central pallor.
– More on trunk and proximal
limbs.
– It usually occurs in the covered
parts and may be manifested by
local application of heat.
– Nonpruritic, nonpainful.
– Often associated with acute
carditis.
– They disappear within hours and
may appear intermittently within
weeks to months

26. Clinical manifestations of ARF

27. Laboratory findings in ARF
1. Elevated acute phase reactants
1. Erythrocyte sedimentation rate(>30mm/hr)
2. Leukocytosis
3. C-reactive protein
2. Recent Evidence of Group A Streptococcal infection :
– Raised ASO titer (80% of cases)
– Anti DNAase B
– Antihyaluronidase
– Rapid Stretococcal antigen test.
– Positive throat culture for (GAS),
– Recent scarlet fever
3. Increased PR interval on EKG (first degree heart block )

28. Imaging
• Cardiomegaly and signs of Heart failure on
Chest x-ray
• 2D and Doppler Echocardiography
– To identify and assess severity of carditis

29. Diagnosis of ARF
• No specific diagnostic test for ARF
• Diagnosis is based on 2015 AHA/ACC with
constellation of major and minor
manifestations used as diagnostic criteria
• For diagnosis of ARF the evidence of recent
streptoccal infection should be demonstrated in
addition to the criteria.

30. Revised Jone’s Criteria for Diagnosis of ARF
(2015 ACC/AHA )
Evidence of preceding group A streptococcal infection (other than chorea):
 Raised ASO titer ,OR
 Positive throat culture for GABH,OR
 Positive Rapid antigen test, OR
 Clinical evidence of bacterial Tonsilo-pharyngitis
Diagnosis : Initial ARF 2 major or 1 major plus 2 minor manifestations PLUS evidence of
recent strep infection (other than chorea)
Recurrent ARF
2 major or 1 major and 2 minor or 3 minor PLUS evidence of
recent strep infection(other than chorea)
Criteria
A. Major B. Minor
 Arthritis (Monoarthritis or
polyarthritis or polyarthralgia)a
 Monoarthralgia
 Carditisb (Clinical and/or subclinical)  Fever (≥38°C)
 Chorea  ESR ≥30 mm/h and/or CRP ≥3 mg/dLc
 Erythema marginatum  Prolonged PR on ECG (for age) (unless carditis is a
major criterion
 Subcutaneous nodules

31. Diagnostic Classes of New ARF
Definite ARF: 2 major, or 1 major plus 2 minor
manifestations PLUS evidence of recent strep
infection (other than chorea)
Highly Probable ARF: If an ARF diagnosis is
considered highly probable (but not confirmed due to
lack of evidence for recent streptococcal infection)
Uncertain ARF: in patients from high-risk groups
with only one major manifestation of acute Rheumatic
fever or borderline echocardiographic findings .

32. Treatment for ARF
• Admission to hospital
–Admit all patients suspected to have ARF
• Confirmation of the diagnosis:
–Observation prior to anti-inflammatory
treatment: paracetamol may be given for
fever or joint pain
–Investigations: CBC,ESR,CXR,ECG,
Echocardiography

33. Treatment for ARF…
1. Treat Infection: Antibiotics: :
o A single intramuscular injection of benzathine
penicillin G (BPG) to eradicate GAS from upper
respiratory tract.
600 000 IU for those less than 7 years and
1.2 million IU for those who are 7 years of age or more.
o After this initial course of antibiotic therapy the
patient should be started on long term monthly BPG
secondary prophylaxis.
o Oral erythromycin if allergic to penicillin

34. Treatment for ARF…
2. Arthritis and fever
o Paracetamol until diagnosis is confirmed
o Mild arthralgia and fever may respond to paracetamol alone.
o Arthritis or Severe arthralgia :Aspirin, naproxen or ibuprofen once diagnosis is
confirmed, if present
 Start Aspirin 75 mg per kilogram per day divided 6 hourly after meals for 4
weeks , OR
 Ibuprofen 30mg/kg per day 8 hourly.
 Do ESR 2 weekly, taper aspirin by decreasing the dose by 2 tablets every week
o Patients not responding or not tolerating aspirin:
 start Prednisolone 2mg per kilogram per day for 2 weeks; then aspirin is added
at dose 60 mg per kilogram per day divided into 4 doses for another 2 weeks;
then Prednisolone is tapered & discontinued.
 Do ESR 2 weekly, taper aspirin by decreasing the dose by 2 tablets every
week.

35. Treatment for ARF…
3. Carditis/heart failure
• Bed rest, with mobilization as symptoms permit
• Urgent echocardiography
• Management of Heart Failure:
– fluid restriction for mild or moderate failure
– Furosemide 1-2mg/kg PO per day
– ACE inhibitors for more severe failure, particularly if
AR present
– Digoxin and anticoagulants, if AF present
– Prednisolone can be given for severe carditis
– Valve surgery for life-threatening acute carditis(rare)

36. Treatment for ARF…
4. Chorea
– No treatment for most cases.
– Carbamazepine or valproic acid if treatment necessary
(for severe cases)
5. Other management considerations
– Register patient in a RHD Register
– Ask about family members: those with sore throat are
given one injection of benzathine penicillin or oral
antibiotics for 10 days.
– Educate client and family on dental care and
importance of secondary prophylaxis

37. Management of Probable ARF
A. Highly-Probable ARF: manage as for definite ARF
B. Uncertain ARF:
• Administer 12 months of secondary prophylaxis initially,
and reassess (including echocardiography) at 1 year.
• If there is no evidence of recurrent ARF, and no evidence of
cardiac valvular damage on echocardiography at 12 months,
consider ceasing secondary prophylaxis.

38. Prevention of ARF:
Depends on eradication of group A streptococci from upper respiratory tract. It is
divided into:
1. Primordial Prevention:
• Improving socioeconomic conditions, nutrition, housing conditions (decreasing
crowding) and improving access to health care can all decrease the incidence of
ARF.
2. Primary prevention:
• Prompt treatment of GAS pharyngitis with one injection of IM BPG is highly
effective in preventing first attacks of ARF.
• However, about 1/3 of patients with ARF do not recall preceding episode of
pharyngitis
• A vaccine for GAS is being developed but has not yet been used in clinical
practice
3. Secondary Prophylaxis
• Monthly injection of BPG IM to prevent recurrences of rheumatic fever

39. Forest plots of studies preventing rheumatic fever
through school and/or community projects
Source: Robertson KA et al. Antibiotics for the primary prevention of acute rheumatic fever: a
meta-analysis. BMC Cardiovasc Disord. 2005 5: 1-9

40. • Community and combined school and
community sore throat treatment interventions
could be expected to reduce the incidence of
ARF by up to 60%.
• GAS pharyngitis is droplet-spread and the rate
of GAS pharyngitis cross-infection within a
household is between 19-50%.So household
contact tracing to interrupt the spread of GAS
following a case of rheumatic fever

41. Case Study (2)
Sara is 15 year old girl who has been diagnosed as RHD 2
years ago, she presented with ankle pain for 2 days, which of
the following is true:
a. If there is leucocytosisand high ASO, she should receive
aspirin in a high dose
b. Recurrence of ARF needs to be considered only if she has
fever.
c. We need 2 major criteria to diagnose recurrence of ARF
d. If she is compliant with BPG , no need to request further
investigations
e. Ankle pain is considered a minor Jones criteria

42. Summary
• A long-term Management Plan should be established to
prevent recurrence of ARF and development or worsening of
RHD
• Probable ARF cases should also be monitored.