Understanding

Acute Rheumatic
Fever: Diagnosis,
Comparative
Diagnosis,
Treatment, and
Preventiong

DHILNA
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THANATHUPARAMBIL
Introduction:

• Acute Rheumatic Fever (ARF) is a systemic inflammatory condition that can

arise as a complication of untreated or inadequately treated streptococcal
throat infection. It primarily affects children and adolescents, with potentially
severe consequences if left untreated. This presentation aims to elucidate the
diagnosis criteria, comparative diagnosis, treatment, and prevention strategies
associated with ARF.
Pathogenesis of Acute
Rheumatic Fever (ARF)
• The pathogenesis of ARF is multifactorial and involves a complex
interplay between genetic predisposition, immune response, and
environmental factors, particularly group A streptococcal (GAS)
infections. Here's a detailed look at the key aspects of ARF pathogenesis:
1. Streptococcal Infection (Group A Streptococcus):
1. ARF typically develops as a sequel to an untreated or inadequately
treated infection with Group A Streptococcus (GAS), particularly
strains that produce certain antigenic determinants, such as M
protein.
2. The initial infection usually manifests as streptococcal pharyngitis
(strep throat) or less commonly, streptococcal skin infections.
1. Molecular Mimicry:
1. One of the central theories in ARF pathogenesis is molecular mimicry. It
suggests that certain antigenic components of GAS share structural
similarities with human tissues, particularly cardiac and joint proteins.
2. Antibodies generated against GAS antigens may cross-react with host
tissues, leading to tissue damage and inflammation, particularly in the
heart, joints, and other affected organs.
2. Immune Response:
1. The immune response to GAS infection involves both innate and adaptive
immune mechanisms.
2. During the acute phase of infection, innate immune cells like
macrophages and neutrophils are recruited to the site of infection, where
they engulf and destroy bacteria.
3. The adaptive immune response, mediated by T and B lymphocytes, leads
to the production of antibodies against specific GAS antigens.
1. Autoimmune Reaction:
1. In susceptible individuals, the immune response to GAS infection may become
dysregulated, leading to the production of autoantibodies that target self-antigens.
2. Autoantibodies directed against cardiac myosin, tropomyosin, and other cardiac
proteins can induce inflammation and tissue damage in the heart, resulting in
carditis.
3. Similarly, autoantibodies may also target synovial tissues, leading to joint
inflammation and arthritis.
2. Genetic Susceptibility:
1. Genetic factors play a significant role in determining an individual's
susceptibility to ARF.
2. Certain human leukocyte antigen (HLA) alleles, particularly HLA-DR alleles,
have been associated with an increased risk of developing ARF.
3. Additionally, variations in genes involved in immune regulation and host-
pathogen interactions may contribute to the development and severity of ARF.
• Secondary Immune Response:
• Following the initial GAS infection, subsequent
exposures to GAS antigens may trigger recurrent
episodes of ARF, leading to progressive cardiac
damage and the development of chronic rheumatic
heart disease (RHD).
Diagnosis Criteria:
• Jones Criteria:
• The Jones Criteria are widely used for diagnosing ARF. They
encompass major and minor criteria.
• Major criteria include carditis, polyarthritis, chorea, erythema
marginatum, and subcutaneous nodules.
• Minor criteria include fever, arthralgia, elevated acute phase
reactants, prolonged PR interval, and previous rheumatic
fever or rheumatic heart disease.
• Laboratory Tests:
• Blood tests may reveal elevated inflammatory markers like C-
reactive protein (CRP) and erythrocyte sedimentation rate
(ESR).
• Throat swabs can identify streptococcal infection.
Clinical Presentation of Acute Rheumatic
Fever (ARF):
• Acute Rheumatic Fever (ARF) presents with a diverse array of clinical
manifestations, which can vary in severity and may affect multiple
organ systems. The presentation of ARF often follows an initial group
A streptococcal (GAS) infection, typically affecting children and
adolescents. Here's an overview of the clinical features associated with
ARF:
1. Carditis:
1. Carditis, inflammation of the heart, is one of the most serious
manifestations of ARF.
2. Patients may present with symptoms such as chest pain, shortness of
breath, palpitations, and signs of heart failure.
3. Clinical examination may reveal murmurs, suggestive of valvular
involvement, particularly mitral and aortic valves.
2. Polyarthritis:
1. Polyarthritis, characterized by migratory joint pain and swelling, is a
hallmark feature of ARF.
2. Large joints such as the knees, ankles, elbows, and wrists are commonly
affected.
3. Joint symptoms typically resolve spontaneously within weeks, although
residual joint stiffness may persist.
Chorea (Sydenham's Chorea):
• Chorea, a movement disorder characterized by involuntary jerky
movements, is a distinctive feature of ARF.
• Patients may exhibit purposeless, rapid, and irregular movements of the face,
limbs, and trunk.
• Chorea can significantly impair motor coordination and may be associated
with emotional lability and behavioral changes.

Erythema Marginatum:
• Erythema marginatum manifests as transient, non-pruritic, pinkish-red,
serpiginous skin lesions with well-defined borders.
• These lesions typically appear on the trunk and proximal extremities and
may precede or accompany other manifestations of ARF.
Subcutaneous Nodules:
• Subcutaneous nodules are firm, painless, and mobile nodules that
develop beneath the skin, usually over bony prominences.
• These nodules are less common than other manifestations and may
not be present in all cases of ARF.

Fever and Constitutional Symptoms:

• Patients with ARF often present with fever, malaise, fatigue, and
other constitutional symptoms.
• Fever may be low-grade and intermittent, particularly during the
acute phase of the illness.
X-ray findings in rheumatic heart disease
(RHD)
1. Cardiomegaly:
1. Cardiomegaly, or enlargement of the heart, is a common finding in
patients with RHD, especially those with significant valvular
damage.
2. On X-ray, cardiomegaly may be visualized as an enlarged cardiac
silhouette, with an increased cardiothoracic ratio on the frontal
chest radiograph.
2. Pulmonary Congestion:
1. In advanced cases of RHD, especially those involving mitral valve
stenosis or regurgitation, pulmonary congestion may develop.
2. X-ray findings of pulmonary congestion include prominent
vascular markings, perihilar haze, and Kerley B lines (horizontal
lines at the lung bases indicating interstitial edema).
1.Pleural Effusion:
1. Pleural effusion, accumulation of fluid in the pleural space, may occur
secondary to congestive heart failure in patients with RHD.
2. On X-ray, pleural effusion may appear as blunting of the costophrenic angles
or as homogenous opacities along the lung periphery.
2.Calcification of Cardiac Structures:
1. Chronic valvular involvement in RHD can lead to calcification of cardiac
structures, particularly the mitral and aortic valves.
2. On X-ray, calcification may be seen as dense, well-defined opacities within
the cardiac silhouette, especially at the level of the mitral valve annulus.
1.Pulmonary Hypertension:
1. Severe RHD, particularly when it leads to significant mitral valve stenosis,
can result in pulmonary hypertension.
2. X-ray findings suggestive of pulmonary hypertension include enlargement of
the pulmonary arteries, prominence of the main pulmonary artery, and right
ventricular hypertrophy.
2.Atrial Enlargement:
1. Chronic volume overload due to mitral or tricuspid regurgitation in RHD can
lead to atrial enlargement, particularly of the left atrium.
2. X-ray findings suggestive of atrial enlargement include a prominent left atrial
appendage and straightening of the left heart border.
Comparative Diagnosis:

Differential Diagnosis:ARF should be differentiated

from other conditions causing similar symptoms,
such as viral arthritis, systemic lupus erythematosus,
and reactive arthritis.

Clinical history, physical examination, and diagnostic

tests aid in distinguishing ARF from other conditions.
Treatment:

1. Antibiotics:
1. Antibiotics like penicillin or amoxicillin are used to
eradicate streptococcal infection and prevent recurrent
episodes.
2. Patients with ARF may require long-term antibiotic
prophylaxis to prevent further streptococcal infections.
2. Anti-inflammatory Medications:
1. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often
prescribed to alleviate symptoms like joint pain and
inflammation.
2. Corticosteroids may be necessary in severe cases to manage
inflammation, especially in carditis.
DMARD
Methotrexate (MTX):
Methotrexate is often considered the first-line
DMARD for the treatment of rheumatoid
arthritis.
It works by inhibiting the synthesis of DNA,
RNA, and proteins, thereby suppressing the
immune response and reducing inflammation.
Methotrexate is available in oral and injectable
forms and is usually taken once weekly.
Sulfasalazine:
Sulfasalazine is another DMARD commonly
used in the treatment of rheumatoid arthritis, as
well as inflammatory bowel diseases such as
ulcerative colitis and Crohn's disease.
It works by reducing inflammation in the
gastrointestinal tract and joints.
Sulfasalazine is taken orally and may be
combined with other DMARDs or biologic
agents for enhanced efficacy.
Hydroxychloroquine (Plaquenil):

• Hydroxychloroquine is used primarily in the treatment of rheumatoid arthritis and systemic lupus
erythematosus (SLE).
• It exerts its effects by modulating the activity of the immune system and reducing inflammation.
• Hydroxychloroquine is usually taken orally and may take several weeks to months to achieve optimal
therapeutic effects.

Leflunomide (Arava):

• Leflunomide is a DMARD used in the treatment of rheumatoid arthritis.

• It inhibits the proliferation of immune cells and reduces the production of pro-inflammatory cytokines.
• Leflunomide is taken orally and may be used alone or in combination with other DMARDs or biologic
agents.
Tumor Necrosis Factor (TNF) Inhibitors:

TNF inhibitors, such as etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade), certolizumab
(Cimzia), and golimumab (Simponi), are biologic DMARDs used in the treatment of rheumatoid arthritis,
psoriatic arthritis, ankylosing spondylitis, and other inflammatory conditions.

They work by blocking the activity of TNF-alpha, a pro-inflammatory cytokine involved in the pathogenesis of
autoimmune diseases.

TNF inhibitors are administered via subcutaneous injections or intravenous infusions and are often used in
patients who have not responded adequately to traditional DMARDs.
Prevention:
1. Prompt Treatment of Streptococcal Infections:
1. Timely diagnosis and treatment of streptococcal throat
infections with appropriate antibiotics can prevent the
development of ARF.
2. Antibiotic Prophylaxis:
1. Individuals with a history of ARF or rheumatic heart disease
may require long-term antibiotic prophylaxis to prevent
recurrent streptococcal infections.
3. Health Education:
1. Public awareness campaigns and education programs aimed
at recognizing and treating streptococcal infections can help
prevent ARF.
Thanks