1) Acute rheumatic fever is an autoimmune disease that can develop as a complication of untreated strep throat. It mainly affects children aged 5-14 and can cause inflammation of the heart, joints, brain, and skin. 2) The presentation and diagnosis is based on revised Jones criteria which looks for evidence of preceding strep infection and manifestations involving two major criteria or one major and two minor criteria. 3) Treatment involves antibiotics to treat the initial strep infection, anti-inflammatory drugs, and long-term antibiotics to prevent recurrent attacks which can further damage the heart valves and lead to rheumatic heart disease.

1. ADAMA HOSPITAL MEDICAL COLLEGE
Department Of Internal Medicine
Seminar on Acute Rheumatic Fever
Presenter: Dr Rebil Heiru (R1)
Moderator: Dr Demu Tesfaye (Assistant professor and Consultant
Internist)
28/6/2011 E.C.

2. Outlines
• Introduction
• Epidemiology
• Pathogenesis
• Clinical manifestation and diagnosis criteria
• Differential diagnosis
• Treatment and Prevention
• Prognosis

4. Introduction
• Acute rheumatic fever (ARF) is a multisystem disease resulting from
an autoimmune reaction to infection with group A streptococcus.
• Although many parts of the body may be affected, almost all of the
manifestations resolve completely.
• The exception is cardiac valvular damage [rheumatic heart disease
(RHD)], which may persist after the other features have disappeared.

5. Introduction…
• ARF and RHD are diseases of poverty.
• It has been estimated that between 15 and 19 million people worldwide
are affected by RHD, with approximately one-quarter of a million
deaths occurring each year.
• Some 95% of ARF cases and RHD deaths now occur in developing
countries.

6. Introduction…
• Although ARF and RHD are
relatively common in all
developing countries, they
occur at particularly elevated
rates in certain regions.
• These "hot spots" are
sub-Saharan Africa,
Pacific nations,
Australasia, and
the Indian
subcontinent

7. Epidemiology
• ARF is mainly a disease of children aged 5–14
years.
• Initial episodes become less common in older
adolescents and young adults and are rare in
persons aged >30 years.
• Recurrent episodes of ARF remain relatively
common in adolescents and young adults.

8. Epidemiology…
• This pattern contrasts with the prevalence of RHD, which peaks
between 25 and 40 years.
• There is no clear gender association for ARF, but RHD more
commonly affects females, sometimes up to twice as frequently as
males.

9. Epidemiology
• The mean incidence of ARF is 19 per 100,000 school-aged
children worldwide.
• Auscultation-based surveys in Ethiopia conducted in the
late 1990's reported a rural prevalence of 4.6/1000 and an
urban prevalence of 6.4/1000 of rheumatic heart disease
(RHD).
• With echo-based screening yielding a prevalence of 19
[13.9-23.4, 95% CI] cases per 1000 school children
between the ages of 6-18years.

10. Pathogenesis
• Based on currently available evidence, ARF is exclusively
caused by infection of the upper respiratory tract with group
A streptococci
• Classically, certain M-serotypes (particularly types 1, 3, 5, 6, 14,
18, 19, 24, 27, and 29) were associated with ARF
(“Rheumatogenic”)
• In high-incidence regions any strain of group A streptococcus has
the potential to cause ARF.

15. Do GAS skin infections (pyoderma/ impetigo)
cause ARF?

16. Pathogenesis
Do GAS skin infections (pyoderma/ impetigo)
cause ARF?

17. Can some GAS strains cause both acute post
streptococcal glomerulonephritis (APSGN) and ARF?

18. Pathogenesis
Genetic Susceptibility
• It is likely that 3–6% of people in any population have an
inherent susceptibility to ARF, although the basis of this
susceptibility is unknown
• And this proportion does not vary dramatically between
populations.
• Findings of familial clustering of cases and concordance in
monozygotic twins—particularly for chorea—confirm that
susceptibility to ARF is an inherited characteristic

19. Pathogenesis
Genetic Susceptibility
• HLA
• Tumor necrosis factor-α (TNF-α)
• mannose-binding lectin (MBL)

20. Pathogenesis
• Historically there have been three major categories of hypotheses
1. Direct infection (for example, by the group A streptococcus);
2. Effects of a streptococcal toxin (streptolysin O has been among the most
commonly discussed); and
3. Most feasibly, the concept of antigenic mimicry in association with an
abnormal immune response.
• During the past half century, it is the concept of antigenic mimicry
and/or an abnormal immune response to group A streptococcal
extracellular or somatic antigens which has been most interesting

21. Pathogenesis
• When a susceptible host encounters a group A streptococcus, an
autoimmune reaction results, which leads to damage to human tissues
as a result of cross-reactivity between epitopes on the organism and the
host
• Cross-reactive epitopes are present in the streptococcal M
protein and the N-acetylglucosamine of group A streptococcal
carbohydrate and are immunologically similar to molecules in
human myosin, tropomyosin, keratin, actin, laminin, vimentin,
and N-acetylglucosamine.

24. Pathogenesis
• It is currently thought that the initial damage is due to cross-reactive
antibodies attaching at the cardiac valve endothelium
• allowing the entry of primed CD4+ T cells, leading to subsequent T
cell-mediated inflammation
• The only recognised natural host (and reservoir) for group A
streptococci is the human, and an appropriate animal model
has not been identified in half a century

25. Pathologic lesions
• Aschoff bodies-fibrinoid degeneration of connective tissue,
inflammatory edema, inflammatory cell infiltration and proliferation of
specific cell results in nodule formation.
• Resulting in:
Pancarditis in the heart
Arthritis in the joints
Ashcoff nodules in the subcutaneous tissue
Basal gangliar lesions resulting in chorea

26. Unanswered questions
1. Why is Mitral valve (and aortic
valve) preferred if it is true
antigen mimicry?
2. Why does one present with
arthritis while another develop
carditis…?
3. Why does one patient with
rheumatic carditis develop RHD
while another do not?

27. Clinical Features
• There is a latent period of ~3 weeks (1–5 weeks) between the
precipitating GAS infection and the appearance of the clinical
features of ARF.
• The exceptions are chorea and indolent carditis, which may
follow prolonged latent periods lasting up to 6 months.

28. Clinical Features
 Carditis and valvulitis (eg, pancarditis) that is clinical or subclinical – 50 to
70 percent
 Arthritis (usually migratory polyarthritis predominantly involving the large
joints) – 35 to 66 percent
 Central nervous system involvement (eg, Sydenham chorea) – 10 to 30 percent
 Subcutaneous nodules – 0 to 10 percent
 Erythema marginatum – <6 percent

29. Clinical Features…Arthritis
• The typical arthritis is migratory, moving from one joint to
another over a period of hours.
• ARF almost always affects the large joints—most commonly
the knees, ankles, hips, and elbows—and is asymmetric.
• The pain is severe and usually disabling until anti-
inflammatory medication is commenced.

30. Clinical Features…Arthritis
Arthralgia without objective joint inflammation usually affects
large joints in the same migratory pattern as polyarthritis.
In some populations, aseptic monoarthritis may be a presenting
feature of ARF.
This may occur because of early commencement of anti-
inflammatory medication before the typical migratory pattern is
established.

31. Clinical Features…Arthritis
• The joint manifestations of ARF are highly responsive to
salicylates and other nonsteroidal anti-inflammatory drugs
(NSAIDs).
• Indeed, joint involvement that persists more than 1 or 2 days
after starting salicylates is unlikely to be due to ARF.
• Synovial fluid analysis shows sterile inflammatory fluid.
• There is absence of long-term joint deformity.

32. Carditis
• The only manifestation which leave sequela and permanent damage to the
organ.
• Presents in 50-70% of cases.
• Valvular damage is the hallmark of rheumatic carditis.
• For asymptomatic patients it can be diagnosed with echocardiography.
• Echocardiography screening of school aged children in population with
high incidence of RHD is becoming more widespread.

33. • Mitral valve is most often affected with RHD(75-80%), followed by
mitral and aortic together, then aortic alone(30%), then mitral, aortic,
and tricuspid together.
• Damage to the pulmonary or tricuspid valves is usually secondary to
increased pulmonary pressures resulting from left-sided valvular
disease (5%).

34. In acute phase
 Valvulitis occur which leads to regurgitation.
 MR : a high-pitched apical holosystolic murmur radiating to
the axilla
 The Carey Coombs murmur, a short mid-diastolic murmur heard
loudest at the apex, is an indicator of moderate-severe MR as a result
of increased blood flow across the mitral valve during left ventricular
filling.
 AR : a high-pitched decrescendo diastolic murmur at the upper
left sternal border

35. • CHF due to severe MR/AR
• ECG-any degree heart block,
• chest xray-cardiomegaly
• Echocardiography-valve lesion
-pericardial effusion
-ventricular/atrial dilation

36. IN Chronic phase
Over several years, usually as a result of recurrent episodes,
leaflet thickening
fibrosis
scarring
calcification, and valvular stenosis develop
Valvular stenosis: appears several years or even decades after the
acute illness
However, in developing countries where ARF often occurs at
earlier age, MS & AS may develop in young children

37. Moderate to severe rheumatic carditis: new heart
murmur, cardiomegaly & CHF with hepatomegaly &
peripheral & pulmonary edema and perciardial friction rub
Myocarditis &/or pericarditis without evidence of
endocarditis: rarely due to RHD

38. Echocardiography diagnosis

39. Echo…

40. Echo…

42. Subclinical carditis
• Refers exclusively to the circumstance in which classic
auscultatory findings of valvulvar dysfunction either
are not present or are not recognized by the diagnosing
clinician but echocardiography/Doppler studies reveal
mitral or aortic valvulitis.

43. Sydenham chorea
• Incidence 10-30%,found mainly in females
• (also known as chorea minor or "St. Vitus dance")
• is a neurologic disorder consisting of purposeless, non rhythmic
involuntary movements, muscular weakness, and emotional
disturbances.
• Antibodies directed to GAS cross react with lysogangloside which
trigger signals.
• The chorieform movement affects mainly the head causing darting
movement of the tongue and upper limbs.

44. Clinical manifestation
• 5-13 yrs, female(2x more common)
• Onset 1-8 month after pharyngitis
• Emotional changes precede(easy crying/in appropriate laughing)
• Usually generalized, unilateral in 20-30%
• Loss of fine motor, muscle weakness,hypotonia
• Psychiatric symptoms-irritability,outburst behavior
(crying,laughing)
• Cease during sleep.

45. Clinical maneuvers to elicit features of chorea include
(1) demonstration of milkmaid's grip (irregular contractions of
the muscles of the hands while squeezing the examiner's fingers)
(2) spooning and pronation of the hands when the patient's arms
are extended
(3) wormian darting movements of the tongue upon protrusion
(4) examination of handwriting to evaluate fine motor movements

46. Diagnosis
• Clinically-with supportive evidence of GAS antibodies
but may not be there.
• Chorea with carditis is confirmatory
• May not have other clinical symptoms but should
undergo echocardiography screening.

48. Subcutaneous Nodules
• Incidence 0-10%
• Firm, painless, symmetric, mobile, small(0.5- 2 cm) lumps at bony prominence
or extensor surface of near tendon.
• There is a correlation between the presence of these nodules and
significant rheumatic heart disease
• Smaller and short lived nodules than rheumatoid arthritis.
• Elbows are mostly involved, in that rheumatic fever on olecranon while in
rheumatoid arthritis 3-4 cm distally.

50. Erythema Marginatum
• Incidence <6%
• begins as pink macules that clear centrally, leaving a serpiginous,
spreading edge.
• Erythema marginatum is an evanescent, pink or faintly red,
non-pruritic rash involving the trunk and sometimes the limbs
but not on the face.
• Heat can induce its appearance, and it blanches with pressure

51. Erythema Marginatum

52. Other features
• Fever >38.50c, but for moderate-high risk areas 380c can be
considered.
• Elevated acute phase reactant(CRP and ESR)
• ECG-prolonged PR interval

53. Late sequelae
• RHD is the most common cause of valvular disease among the
world.
• Occurs 10-20 yrs after original illness
• Mitral valve is commonly involved than aortic valve.
• MS caused by severe mitral calcification, is the classical finding
of rheumatic heart disease.
• Occurs in 50% of carditis at initial presentation.

54. Late sequelae
• Jaccoud arthropathy — Jaccoud arthropathy is a benign,
chronic arthropathy that involves loosening and lengthening of
periarticular structures and tendons in the hands and/or feet
• The deformities are painless, "correctable" with manipulation,
and do not cause functional impairment.
• The arthropathy is not associated with active joint
inflammation.

55. Jaccoud arthropathy

56. Evidence of a preceding Group A
Streptococcal infection
Streptococcal pharyngitis diagnosed by
Positive throat culture for group A beta-hemolytic streptococci
Positive rapid streptococcal antigen test
Elevated or rising antistreptolysin O antibody titer (ASO titer)
or other streptococcal antibody(anti-DNAase)

57. Throat culture
Throat culture remains the
diagnostic gold standard.
Culture of a throat specimen that is
properly collected and properly
processed is the most sensitive and
specific means of definitive
diagnosis.
Sensitivity 90%, specificity 99%

58. Rapid streptococcal antigen test
• A very rapid test, used to early
detection of streptococcal
pharyngitis.
• Usually negative during clinical
appearance of rheumatic fever.

59. Streptococcal Antibody Tests
ASO titer –for children 300todd unit
-for adult-250todd unit
-elevated in 80% of ARF
 Begin to rise 1 wk, peaks 3-6 wks
Single antibody measured: 80-85% of patients
have an elevated titer
If 3 different antibodies (antistreptolysin O, anti-
DNase B, antihyaluronidase) measured: 95-100%
have an elevation

60. Diagnosis

61. Revised Jones criteria 2015

63. “Possible” Rheumatic Fever
1.Where there is genuine uncertainty, it is reasonable to
consider offering 12 months of secondary prophylaxis
• followed by reevaluation to include a careful history and
physical examination in addition to a repeat
echocardiography

64. 2.In a patient with recurrent symptoms (particularly involving the
joints) who has been adherent to prophylaxis recommendations
• but lacks serological evidence of GAS infection and lacks
echocardiographic evidence of valvulitis,
• it is reasonable to conclude that the recurrent symptoms are not
likely related to ARF, and discontinuation of antibiotic
prophylaxis may be appropriate echocardiogram

65. Treatment
• Step I - primary prevention (eradication of streptococci)
• Step II - anti inflammatory treatment (aspirin, steroids)
• Step III- supportive management & management of
complications
• Step IV- secondary prevention(prevention of recurrent
attacks)
• Step V -follow up
65

66. Step I - primary prevention
primary prophylaxis (the timely and complete treatment of
group A streptococcal sore throat with antibiotics)
If commenced with in 9 days of sore throat onset a course of
penicillin will prevent all cases of ARF
Ideally, primary prevention would entail elimination of the
major risk factors for streptococcal infection, particularly
overcrowded housing.

67. Antibiotics used for primary
prevention

68. Step II - anti inflammatory treatment
Bed rest and indoor ambulation
Recommended anti-inflammatory agents
_______________________________________________________________________________________
Arthritis Mild Moderate Severe
alone carditis carditis carditis
__________________________________________________
Prednisone 0 0 0 2-6 wk*
Aspirin 1-2 wk 3-4 wk# 6-8 wk 2-4 mo
___________________________________________________
• Prednisone should be tapered after 2-3 wks and aspirin started during the tapering Aspirin
may be reduced to 60 mg/kg/day
• Aspirin(80 to 100 mg/kg per day in children and 4 to 8 g/day in adults)

69. • Naproxen has a superior side-effect profile to aspirin and can be dosed
twice daily.
• A single, small, open-label, randomized study found that naproxen
had similar efficacy to aspirin with regard to time until resolution of
arthritis but was safer and easier to use.
• Naproxen is dosed at 10 to 20 mg/kg/day in divided doses BID to a
maximum of 1000 mg/day in children aged over two years and 250 to
500 mg BID to a maximum of 1250 mg in adults.

70. Treatment of chorea
• Most patients with SC recover fully without treatment
• mild- keeping patient in a calm environment
• significant impairment of motor function
1. Haloperidol (0.01-0.03 mg/kg/day divided bid PO) 3-4 mo.
2. Corticosteroids ( Prednisolone 1-2 mg/kg daily for 2 wks then
tapered over 2-3 wks)
• Treatment with either valproic acid or carbamazepine is a reasonable
alternative
• chronic treatment with prophylactic antibiotics.

71. Step III- supportive management & management of
complications
• Treatment of congestion
• General measures
• Diuretics
• Surgical management

72. Step IV- secondary prevention
• Patients with ARF should take long term penicillin to
prevent recurrence.
The risk of recurrent rheumatic fever depends
The number of previous attacks
Time since the last attack
Risk of exposure to the streptococcal infections
Patient age
Presence or absence of cardiac involvement

74. Antibiotics used in secondary prophylaxis of RF

75. Prognosis
• Untreated ARF lasts 12 wks
• With treatment patient discharged from hospital after 1-2 wks
• Inflammatory markers should be followed every 1-2 wks
until they normalized(usually with 4-6 wks)
• Echocardiography after 1 month

76. Register form

77. Take home message
• Acute rheumatic fever remains a serious healthcare concern for the
majority of the world’s population, especially for developing countries.
• It causes significant disability, loss of quality of life and length of life
and costs to individuals, their families and to society
• RHD is the only truly preventable chronic heart condition
• Appropriate treatment of group A strep pharyngitis necessary to
prevent disease.
• Preventing recurrences causing chronic heart disease simple,
universally available, and cost-effective.

78. REFERENCES
• Kasper, Hauser, Longo, Jameson, Loscalzo Harrison’s principles of
Internal Medicine 19th Edition Copyright © 2015 by McGraw-Hill
Education
• Newzealand guideline for acute rheumatic fever 2014
• UptoDate version 21.8

79. Reference

80. Thank you!
“He korokoro ora he manawa ora
Mo tatou katoa”
A healthy throat, a healthy heart for us all