Prof. Pavlyshyn H.A.

ACUTE RHEUMATIC FEVER

DEFINITION
Rheumatic fever is an inflammatory process which
can involve the joints, heart, skin and brain
It is caused by antibody cross reactivity and occurs 2-
3 weeks after a Group A Streptococcal infection.
EPIDEMIOLOGY
470,000 new cases of Acute Rheumatic Fever/year
233,000 deaths due to Rheumatic Fever/year
Majority of deaths occur in developing countries
Incidence in the US: 2-14 cases/100,000
Historically, there is a temporal relationship between
epidemics of streptococcal pharyngitis and scarlet
fever with the epidemics of acute rheumatic fever
No clear gender predilection overall, but mitral
stenosis and syndenhams chorea occur more in
females than males.
BACKGROUND
Primarily affects children between ages 5-12
Generally occurs 2-3 weeks after Group A
Streptococcal infection (strep throat or scarlet fever)
In the US, Rheumatic fever has become fairly rare
due to use of antibiotics to treat streptococcal
infections
Globally, 3% of those with an untreated streptococcal
infection develop rheumatic fever
40% of those with Acute Rheumatic Fever develop
mitral stenosis as adults
BACKGROUND
Cutaneous streptococcal infections have not been
shown to initiate Acute Rheumatic Fever.
Strains of certain M serotypes/genotypes of
streptococci have higher associations than other
genotypes
Epidemics of Acute Rheumatic Fever in Trinidad and
Chile showed that streptococci causing Acute
Rheumatic Fever belonged to different serotypes
than those that cause Acute Glomerulonephritis.
PATHOPHYSIOLOGY
Exact mechanism of how Group A streptococcal
infection causes Acute Rheumatic Fever is unknown
however it is believed to be caused by a cross
reactivity of antibodies
Suggested Theories
Toxic effects of streptococcal products (streptolysin S or O)
which then cause direct tissue injury
Serum Sickness-like reaction mediated by antigen-antibody
complexes
Autoimmune phenomenon
PATHOPHYSIOLOGY
More support for an autoimmune phenomenon
(Type II hypersensitivity reaction)
During strep infection, antigen presenting cells
present bacterial antigen to helper T cells. These
helper T cells then activate B cells to induce
production of antibodies against the Streptococcal
cell wall. These antibodies can also interact with
other cells in the body (for example, myocardium or
joints, etc) producing the symptoms responsible with
acute rheumatic fever
PATHOGENESIS
Most patient have elevated antibody titers to at least
one streptococcal antibody
Streptolysin O
Hyaluronidase
Streptokinase

PATHOPHYSIOLOGY (CARDIAC)
Aschoff nodule with owl-eyed shape in the cross section and catapillar-shaped
in the longitudinal section
PATHOPHYSIOLOGY (CARDIAC)
Thickened fused chordae of the mitral valve
CLINICAL MANIFESTATIONS
Latent period: time between preceding streptococcal
pharyngitis and Acute Rheumatic fever is about 19
days (range 1-5 weeks)
If initial complaint is polyarthritis, disease generally
has more abrupt onset compared to if initial
presentation is with myocarditis.
Arthritis occurs in 75% of initial attacks, carditis in
40-50% and chorea in 15% with subcutaneous
nodules and erythema marginatum in <10%
CLINICAL MANIFESTATIONS (CARDITIS)
Usually manifests within the first 3 weeks of Acute
Rheumatic Fever
Signs: new heart murmur, cardiomegaly, CHF,
perciardial friction rub, effusions
Chronic inflammatory changes may lead to development
of rheumatic heart disease.
Characteristic murmur or Rheumatic heart disease:
mitral regurgitation
Low-pitched mid diastolic flow murmur at the apex (Carey Coombs
murmur
Aortic regurgitation
Can also get AV conduction delays
CARDITIS
Cardiomegaly
Cardiomegaly
primarily prolonged PR interval
AV conduction delays
CLINICAL MANIFESTATIONS (JOINTS)
Arthralgias and arthritis (may be migratory)
Warm, swollen, tender joints
Usually involves the knees, ankles, elbows
and wrists
Lasts 2-3 weeks
Arthralgias and arthritis
CLINICAL MANIFESTATIONS
Subcutaneous Nodules: usually associated with
severe carditis and occur several weeks after onset.
Firm, painless nodules (up to 2cm) found over bony surfaces
and tendons
Occur near elbows, knees, wrists, achilles tendon, vertebral
joints
Usually persist for 1-2 weeks

SUBCUTANEOUS NODULES
SUBCUTANEOUS NODULES
CLINICAL MANIFESTATIONS
Erythema Marginatum: nonpruritic,
painless erythematous rash on trunk
and/or proximal extremities
Macular lesions with raised margins and
central clearing
May last from weeks to months
ERYTHEMA MARGINATUM
CLINICAL MANIFESTATIONS
Sydenhams Chorea: neurologic disorder
with muscular weakness, emotional lability
and involuntary, uncoordinated,
purposeless movements
Disappear during sleep
Mainly occur in hands, feet and face
Sensation intact
Lasts 2-4 months

Sydenhams Chorea
DIFFERENTIAL DIAGNOSIS
Poststreptococcal reactive arthritis: is non-migratory
Rheumatoid Arthritis
SLE
Infective endocarditis
Sickle Cell disease
Drug reactions
TB
Lyme Disease
Serum Sickness
DIAGNOSIS
JONES CRITERIA
Developed by Dr. T Duckett Jones in 1944
Need 2 major criteria or 1 major and 2 minor criteria in the
presence of a prior strep infection to make the diagnosis
Evidence of prior strep infection with positive throat culture or
antigen test, elevated streptococcal antibody titer, or history of
rheumatic fever/heart disease
MAJOR CRITERIA
Migratory Polyarthritis: migrating arthritis with
inflammation involving the large joints (knees, ankles,
elbows, wrists) and typically affects the leg joints first
Carditis: can manifest with new murmur, pericarditis,
congestive heart failure
Subcutaneous Nodules: a form of aschoff bodies. Are
painless nodules on the back of the wrists, elbows, knees
Erythema Marginatum: rash beginning on the arms or
trunk and spreads outward. Lesion with ring with central
clearing. Worsens with heat. Does not involve the face
Sydenhams Chorea (St. Vitus Dance): purposeless
movements of the face and arms. Late finding
MINOR CRITERIA
Fever
Arthralgia: joint pain without inflammation
Elevated CRP, ESR or leukocytosis
EKG changes: primarily prolonged PR interval
Evidence of Group A Streptococcal infection via
elevated antistreptolysin O titer or DNAase
Prior history of rheumatic fever or heart disease
TREATMENT
Anti-inflammatory Agents
Antibiotics
Prophylaxis
ANTI-INFLAMMATORY AGENTS
Aspirin 4-8grams/day for adults
Continue anti-inflammatory therapy until ESR or
CRP are normal
May need steroids if there is cardiac involvement to
help prevent sequelae such as mitral stenosis
Corticosteroids, if indicated, are given at prednisone
2mg/kg/day for 2 weeks and then tapered
ANTIBIOTICS
Penicillin for at least 10 days
Penicillin 500mg BID-TID
Can use erythromycin for PCN allergic patients
(given at 40mg/kg/day given in 2-4 doses/day)
PROPHYLAXIS
Prophylaxis needed to prevent recurrence of Acute
Rheumatic Fever
Start prophylaxis after acute episode resolves
Can use:
Penicillin V 250mg BID or,
Sulfadiazine 1000mg daily, or
Penicillin G 1.2 million units IM q4weeks
For PCN allergic patients: erythromycin 250mg PO BID
Recurrence of disease generally occurs in the first
couple years

PROPHYLAXIS
WHO GUIDELINES
At least 5 years of prophylaxis or if child until age 18 if not
cardiac involvement
10 years prophylaxis or if child until age 25 if has mild mitral
regurgitation
Lifelong prophylaxis if has severe valve disease
Complications
Complications
Complications