Introduction to

Acute Rheumatic Fever (ARF)

It is critical not to miss cases of Acute Rheumatic Fever (ARF) in

children. If missed, this condition can be life-threatening, potentially
damaging a child's entire youth and old age.
Often, we get caught up in differential diagnoses such as septic
arthritis, strep arthritis, or Kawasaki's disease, and we fail to arrive
at the correct diagnosis of ARF.

Pathophysiology of Acute Rheumatic Fever

ARF begins with a simple infection: Group A Streptococcal
pharyngitis. This initial infection triggers a complex antigen-
antibody [Link] core mechanism is antigenic mimicry. The
antigens of the streptococcus bacteria are very similar to, or
"mimic," the antigens found in our own body tissues.
• The antibodies produced by our immune system to fight the
streptococcal pharyngitis cross-react with our own cells.
• These antibodies mistakenly attack:
o Heart tissue
o Brain (specifically, the nerves)
o Joints
o Skin
This autoimmune attack, triggered by the body's response
to the streptococcus bacteria, is what causes the
symptoms of ARF.
There is a characteristic time lag. The manifestations of ARF, such
as joint pain or heart problems, typically appear at least 2 to 3
weeks after the initial throat infection, which is the time it takes for
the antibody response to build up and cause damage.
Clinical Manifestations of ARF
ARF is a multi-system disorder. The infection that started in the
throat leads to manifestations in several parts of the body:
• Cardiac System: Carditis (inflammation of the heart)
• Musculoskeletal System: Arthritis (inflammation of the joints)
• Neurological System: Neurological symptoms
• Dermatological System: Skin manifestations

1. Cardiac Involvement (Carditis)

When ARF involves the heart, it often causes Pancarditis, meaning
all three layers of the heart become inflamed.
• Pericarditis: Inflammation of the pericardium (the outer
layer).
• Myocarditis: Inflammation of the myocardium (the middle,
muscular layer).
• Endocarditis: Inflammation of the endocardium (the inner
lining, which also covers the heart valves).
A. Endocarditis
• This primarily affects the heart valves.
• The Mitral Valve is the most affected valve (in 65-70% of
cases).
• In the acute phase, the key finding is Mitral Regurgitation
(MR), where the valve becomes leaky. The backflow of blood is
visible as a thick regurgitant jet on a 2D Echocardiogram.
• Important Distinction:
o Acute Rheumatic Fever causes regurgitant lesions
(leaky valves).
o Rheumatic Heart Disease (the chronic condition that
develops over years) causes stenotic lesions (e.g., Mitral
Stenosis, where the valve narrows).
• Patients often present with symptoms of congestive cardiac
failure (CCF), such as shortness of breath, pulmonary edema,
orthopnea, PND, and pedal edema.

B. Myocarditis
• Inflammation of the heart muscle impairs its ability to pump.
• This leads to poor contractility, LV dysfunction, and heart
failure.
• The Ejection Fraction (EF) can drop dramatically to 15-20%.
• Patients can present in CCF or even cardiogenic shock. Over
time, this can lead to Dilated Cardiomyopathy (DCMP), where
the heart becomes enlarged and weak.
C. Pericarditis
• Inflammation of the outer sac of the heart.
• In the long term, this can lead to Constrictive Pericarditis and
heart failure.

2. Musculoskeletal Involvement (Arthritis)

• This is often the earliest manifestation of ARF, appearing even
before carditis.
• Children will present with joint pain and swelling a few weeks
after having a fever and sore throat. It's often mistaken for
Juvenile Idiopathic Arthritis (JIA).
• It typically affects the large joints: ankles, knees, elbows, and
shoulders.
• A key feature is that it is a migratory arthritis. The pain and
swelling move from one joint to another. A child might
complain about their ankle one day, and their knee the next.
This can be confusing, and sometimes parents or doctors may
think the child is making it up.
• This is the most common feature, occurring in 60-80% of
patients.
• Clinical Picture: The child may refuse to play, have difficulty
climbing stairs, or hesitate to get on the school bus because of
the joint pain and stiffness.
• Signs to Look For: Redness, swelling, and morning stiffness in
the affected joints.
3. Dermatological (Skin) Manifestations
These are less common but are important diagnostic clues.

• Subcutaneous Nodules:
o These are firm, painless,
small lumps ("guthli")
found under the skin.
o They typically appear
over bony prominences
(like the spine or elbow)
or on the extensor
surfaces of the hands.

• Erythema Marginatum:
o A characteristic rash that is seen in only about 5-6% of
cases.
o It appears as red, ring-shaped (annular) lesions with pale
centers (central clearing).
o The rash is non-pruritic (not itchy).
4. Neurological Manifestations (Sydenham's Chorea)
• This is a late manifestation,
appearing up to 7-8 months
after the initial infection.
• It is caused by the antibody-
mediated damage to the brain.
• Chorea refers to involuntary,
jerky, "dancing-like" or
"writhing" movements.
o The child cannot control these movements of their head,
hands, or feet.

• Milkmaid's Sign: This is an almost diagnostic clinical sign for

Sydenham's Chorea.
o When you ask the patient to squeeze your fingers, they
cannot maintain a steady grip. Instead, they will
repeatedly squeeze and release, mimicking the motion of
milking a cow.
• Sydenham's Chorea is usually self-resolving and does not last
a lifetime, typically clearing up in a few weeks to months.
Revised Jones Criteria for Diagnosis
The Jones Criteria are used to formally diagnose ARF. The diagnosis
requires evidence of a preceding Group A Strep infection PLUS a
combination of Major and Minor criteria.
The criteria vary for low-risk vs. high-risk populations. The following
are for high-risk populations (like India).
Diagnostic Rule for a First Episode:
• 2 Major Criteria OR
• 1 Major Criterion + 2 Minor Criteria
Diagnostic Rule for a Recurrent Episode:
• 2 Major Criteria OR
• 1 Major Criterion + 2 Minor Criteria OR
• 3 Minor Criteria
Major Criteria:
1. Carditis (clinical or subclinical evidence on echo).
2. Arthritis (can be monoarthritis, polyarthritis, or even
polyarthralgia).
3. Chorea (Sydenham's Chorea).
4. Erythema Marginatum.
5. Subcutaneous Nodules.
Minor Criteria:
1. Fever (≥ 38°C / 100.4°F).
2. Elevated Inflammatory Markers: ESR ≥ 30 mm/hr OR CRP ≥ 3
mg/dL.
3. Prolonged PR Interval on ECG.
Diagnostic Workup
To establish a diagnosis of ARF, a systematic approach is needed.
1. History & Physical Examination: Take a thorough history,
looking for a preceding sore throat. Perform a detailed cardiac,
neurological, and skin examination.
2. Evidence of Preceding Strep Infection:
o Throat Culture for Group A Strep.
o Antibody Titers: These confirm a recent strep infection.
▪ ASO (Anti-Streptolysin O) Titer
▪ Anti-DNase B (ADB) Titer
o Note: Normal values for these titers are age-dependent. A
rising trend or a doubled titer is highly significant.

3. Investigations based on Jones Criteria:

o Inflammatory Markers: ESR and CRP.
o ECG: To check for a prolonged PR interval.
o 2D Echocardiogram: Crucial for detecting carditis, such
as new-onset MR or AR, heart failure, or reduced ejection
fraction.
Making an accurate and timely diagnosis is vital. It dictates
whether treatment is needed for a few weeks or for many
years (prophylaxis) and can prevent the devastating long-term
complications of Rheumatic Heart Disease.

Management of
Acute Rheumatic Fever (ARF)

The management of acute rheumatic fever is a three-pronged attack

on the disease:
1. Eradication Therapy: To eliminate the root cause, the Group A
Streptococcus bacteria, using antibiotics.
2. Symptomatic Treatment: To manage the specific symptoms
the patient is experiencing, such as arthritis, carditis, etc.
3. Prevention of Recurrence: To provide long-term prophylaxis
to prevent the disease from coming back, as recurrences are
very common.
1. Eradication Therapy: Eliminating Group A Streptococcus
The primary goal is to kill the bacteria responsible for the illness.
Primary Drug of Choice: Penicillin
The main treatment is Penicillin, Penicillin, Penicillin. It is available
in both oral and intramuscular forms.
 • For patients weighing less than 27 kg:
o Oral: Penicillin V, 250 mg given 2-3 times a day (BD or
TDS) for 10 days.
o Intramuscular (IM): A single dose of Benzathine
Penicillin, 6 lakh International Units (IU). A sensitivity test
should be performed before administration. This is a good
option if compliance with a 10-day oral course is a
concern.

• For patients weighing more than 27 kg:

o Oral: Penicillin V, 500 mg given 2-3 times a day (BD or
TDS) for 10 days.
o Intramuscular (IM): A single dose of Benzathine
Penicillin, 1.2 million IU (double the dose for smaller
patients).

Alternative Drugs (for Penicillin Allergy)

• Amoxicillin: Can be used at a dose of 50 mg/kg per day for 10
days. It can be given as a single daily dose or divided into two
doses (BD). This is often more readily available than Penicillin
V, especially in smaller towns.
• Cephalosporins: 1st, 2nd, and 3rd generation cephalosporins
(e.g., Cefalexin, Cefuroxime, Cefpodoxime) are effective
against Streptococcus and can be given for 10 days.
• Macrolides (for patients allergic to all penicillin-class
drugs):
 o Azithromycin: The most common choice.
▪ Dose: 12 mg/kg per day (maximum of 500 mg/day).
▪ Duration: Only 5 days.
▪ Azithromycin is a long-acting drug that accumulates
and is stored in the body's white blood cells,
meaning a 5-day course provides therapeutic
effects for 10-12 days.

2. Symptomatic Treatment
This involves treating the specific manifestations of rheumatic fever.
A. Arthritis
• Aspirin: This is the most effective drug for the arthritis of ARF.
The effect is so dramatic that a patient's family might think you
are a magician.
o Dose: 60-100 mg/kg per day, given in divided doses until
symptoms resolve.

• Naproxen: A less commonly known but highly effective

alternative for rheumatic arthritis.
o Dose: 5-10 mg/kg, given twice a day (BD), up to a
maximum of 500 mg BD. Continue until symptoms have
completely resolved.

• Ibuprofen: Can be used in weight-based doses ranging from

200 mg TDS to 800 mg TDS.
B. Carditis
Carditis involves inflammation of the heart's layers:
• Pericarditis: Inflammation of the outer sac.
• Myocarditis: Inflammation of the heart muscle, which can
lead to heart failure.
• Endocarditis: Inflammation of the inner lining, often affecting
the valves and causing regurgitation (e.g., Mitral, Aortic, or
Tricuspid regurgitation), which can also lead to heart failure.
• Management:
o Aspirin: It is the primary treatment for the inflammation
of carditis, used at the same dose as for arthritis (60-100
mg/kg/day).
o Steroids & IVIG: The role of these is questionable and not
standard.
o Heart Failure Management: If the patient develops heart
failure:
▪ Restrict salt (less than 2g/day) and water (less than
1L/day).
▪ Standard heart failure therapy with ACE inhibitors,
ARBs, and diuretics can be started.

C. Dermatological Symptoms (Subcutaneous Nodules &

Erythema Marginatum)
• These symptoms are helpful for diagnosis but require no
specific treatment.
 • They are self-resolving and will disappear on their
own within a few weeks to a couple of months. No
special intervention is needed.
D. Sydenham's Chorea
This involves involuntary, dancing-like movements. The underlying
cause is an antigen-antibody reaction affecting the brain, so
treatment focuses on suppressing the immune system.
• Counseling: It is important to explain that this condition is
often self-limited and will resolve on its own over time.
• Steroids:
o Start with IV Methylprednisolone pulse therapy (e.g., 500
mg daily for 3 days).
o Follow with oral Prednisolone (1 mg/kg) which is then
slowly tapered over subsequent weeks.

• IVIG (Intravenous Immunoglobulin): Also has a good

therapeutic role in suppressing the autoimmune reaction.
• Symptomatic Control of Movements: Drugs like
Carbamazepine, Valproate, Haloperidol, and Pimozide can be
used to control the involuntary movements. Haloperidol and
Pimozide are more commonly used in clinical practice for this
purpose.
• Plasmapheresis: May be used in refractory cases that do not
respond to other treatments.
3. Secondary Prophylaxis: Preventing Recurrence
This is crucial because each subsequent streptococcal infection
can trigger another episode of ARF, leading to worsening heart
damage. The duration of this preventive antibiotic therapy depends
on the severity of the initial episode.
Prophylaxis Regimen:
• Drug: Intramuscular (IM) Benzathine Penicillin
• Dose: 1.2 million units
• Frequency: Every 21 to 28 days. In high-risk countries like
India, it is given every 21 days.
Duration of Prophylaxis:
Clinical Scenario Duration of Example
Prophylaxis
ARF with Carditis 10 years from the A 28-year-old patient
and (Chronic last episode OR will need prophylaxis
Rheumatic Heart until age 40, until age 40 (i.e., for 12
Disease is present) whichever is years), as this is longer
LONGER. than 10 years.
ARF with Carditis 10 years from the A 17-year-old patient
but NO Residual last episode OR will need prophylaxis
Heart Disease until age 21, for 10 years (until age
(Heart has fully whichever is 27), as this is longer
recovered) LONGER. than continuing only
until age 21 (4 years).
ARF without 5 years from the A 13-year-old patient
Carditis (e.g., only last episode OR will need prophylaxis
Arthritis or Chorea) until age 21, until age 21 (i.e., for 8
whichever is years), as this is longer
LONGER. than 5 years.