Rheumatic Fever

Acute rheumatic fever (ARF) is an autoimmune inflammatory process that usually follows Streptococcal pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis. Acute rheumatic fever usually occurs 2–4 weeks after an untreated infection and affects the heart, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, joints, and nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System. This condition commonly presents with fever, arthritis of the large joints, pancarditis and sometimes rash and neurologic manifestations. The diagnosis is made clinically based on the Jones criteria, and confirmed with serologic tests. Prevention of ARF is the key treatment strategy, and is based on timely antibiotic treatment of the primary infection as well as antibiotic prophylaxis of recurrent episodes. Management of acute episodes is largely supportive and includes anti-inflammatory medications. The most serious complication of ARF is development of rheumatic heart disease, which most commonly manifests as mitral valve stenosis.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Acute rheumatic fever (ARF) is an autoimmune condition that develops as a complication of streptococcal infection.

Epidemiology

  • More common in children and adolescents (ages 5–15)
  • Worldwide prevalence: approximately 33.4 million
  • Incidence: 19 cases per 100,000 school-age children worldwide
  • Incidence: < 2 per 100,000 children in developed countries
  • The incidence is higher in socioeconomically deprived areas.

Etiology

  • Recent group A β-hemolytic streptococci (GAS)/ Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pyogenes infection: 
    • Almost exclusively pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis or tonsillitis Tonsillitis Tonsillitis is inflammation of the pharynx or pharyngeal tonsils, and therefore is also called pharyngitis. An infectious etiology in the setting of tonsillitis is referred to as infectious pharyngitis, which is caused by viruses (most common), bacteria, or fungi. Tonsillitis
    • Associated with strains that are heavily encapsulated and rich in M protein
  • Genetic predisposition

Pathophysiology

The pathogenesis is not completely understood.

Genetic predisposition is likely, as rheumatic fever tends to be familial:

  • Associated with the class 2 HLA antigens DR2 and DR4
  • HLA-B5
  • Polymorphisms of transforming growth factor beta (TGF-𝛃) and interleukin-1 (IL-1)

The major implied mechanism is molecular mimicry:

  • Humoral and cellular response to streptococcal antigens as a result of infection
  • Cross-reaction with human proteins that share some structural similarity with bacterial antigens

Acute phase

  • Immune response caused by molecular mimicry between the M protein of GAS and the carbohydrate antigens on human cardiac myosin and laminin
  • Binding of cross-reactive antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins at the valve surface activates CD4 T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells and B lymphocytes B lymphocytes B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. B Cells:
    • T helper and cytokines mediate local tissue damage.
    • Aschoff bodies: rheumatic granulomas
    • Pancarditis and pericardial exudates decrease ventricular filling capacity and can cause congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure.
  • Antibodies against GAS carbohydrate antigen cross-react with neuronal cells in the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia → release excess dopamine → chorea manifestations
  • Joint tissue destruction → arthritis/arthralgia
Aschoff nodules

Aschoff bodies (arrows) in the papillary muscle of the mitral valve

Image: “Histopathological findings” by Valvular Heart Disease Department, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. License: CC BY 4.0

Chronic phase

  • Mostly affects the heart
  • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation leads to neovascularization and healing by fibrosis.
  • Buildup of fibrotic tissue in heart valves
  • Stenosis of heart valves

Clinical Presentation

Signs of rheumatic fever

Typical symptoms of rheumatic fever

Image: “Depiction of a child suffering from Rheumatic Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever” by myupchar.com. License: CC BY 4.0

Clinical diagnostic criteria

  • ARF typically presents 2–4 weeks after streptococcal pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis.
  • Clinical manifestations of ARF are known as Jones criteria.
  • Major manifestations:
    • Arthritis (60%–80%)
    • Carditis/valvulitis (50%–80%)
    • Sydenham chorea (10%–30%)
    • Subcutaneous nodules(< 10%) 
    • Erythema marginatum (< 6%)
  • Minor manifestations:
    • Arthralgia
    • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Elevated acute-phase reactants:
      • ESR
      • CRP
    • Prolonged PR interval on electrocardiography Electrocardiography Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a cathode ray tube display. Normal Electrocardiogram (ECG)

Major symptoms

  • ARF arthritis:
    • Migratory polyarthritis 
    • Affects the larger joints
    • Commonly seen in knees, ankles, elbows, and wrists
  • Rheumatic heart disease:
    • Typically pancarditis: endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis, myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis, and pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis 
    • Endocarditis is usually the most prominent manifestation.
    • Most commonly affects mitral valve (65% of cases):
      • Mitral regurgitation Mitral regurgitation Mitral regurgitation (MR) is the backflow of blood from the left ventricle (LV) to the left atrium (LA) during systole. Mitral regurgitation may be acute (myocardial infarction) or chronic (myxomatous degeneration). Acute and decompensated chronic MR can lead to pulmonary venous congestion, resulting in symptoms of dyspnea, orthopnea, and fatigue. Mitral Regurgitation or prolapse is an early sign.
      • Mitral stenosis Mitral stenosis Mitral stenosis (MS) is the narrowing of the mitral valve (MV) orifice, leading to obstructed blood flow from the left atrium (LA) to the left ventricle (LV). Mitral stenosis is most commonly due to rheumatic heart disease. Mitral stenosis leads to impaired LV diastolic filling, increased LA pressure, and LA dilation. Mitral Stenosis is a late sign (chronic).
    • Patients may have shortness of breath, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea on exertion, chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, or orthopnea, depending on severity.
    • Endocarditis and myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis can lead to dilated cardiomyopathy Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is the most common type of non-ischemic cardiomyopathy and a common cause of heart failure (HF). The cause may be idiopathic, familial, or secondary to a variety of underlying conditions. The disease is characterized by the enlargement of 1 or both ventricles and reduced systolic function. Dilated Cardiomyopathy (10% of cases).
  • Sydenham chorea:
    • Purposeless, involuntary, nonstereotypical movements  
    • Affects the trunk and extremities 
    • Often presents with associated muscle weakness and emotional lability
  • Subcutaneous nodules: 
    • Firm, painless protuberances found on extensor surfaces 
    • Affect the knees, elbows, and wrists
  • Erythema marginatum:
    • Unique, evanescent, pink rash
    • Pale center and rounded or serpiginous margins 
    • Typically on trunk and proximal extremities (spares the face)

Mnemonic

To recall the main clinical manifestations in acute rheumatic fever, remember the Jones criteria (written as J❤NES):

  • Joints (migratory polyarthritis)
  • ❤ (carditis)
  • Nodules (subcutaneous)
  • Erythema marginatum
  • Sydenham chorea

Diagnosis

Diagnostic criteria

  • Evidence of preceding GAS infection
  • Initial episode:
    • 2 major manifestations
    • 1 major + 2 minor manifestations
  • Recurrent episode: 
    • 2 major manifestations
    • 1 major + 2 minor manifestations
    • 3 minor manifestations
  • Exceptions to the above criteria:
    • Chorea as the only manifestation
    • Indolent carditis as the only manifestation becoming evident months after acute infection

Laboratory studies

  • Evidence of streptococcal infection:
    • Throat culture: negative in 75% of cases by the time ARF develops 
    • Streptococcal antigen test: commonly negative by the time of ARF presentation
    • Antibody titers (most helpful for ARF diagnosis):
      • Antistreptolysin O (ASO)
      • Antideoxyribonuclease B (ADB)
      • Antistreptokinase
      • Antihyaluronidase
  • Other findings:
    • Leukocytosis
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview
    • ↑ CRP
    • ↑ ESR
Throat swab

A throat swab sample needs to be obtained for suspected streptococcal pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis.

Image: “10190” by CDC/ Dr. M. Moody. License: Public Domain

Imaging

  • Echocardiography with Doppler: 
    • Required in all cases of confirmed and suspected RF
    • Carditis
    • Valvular vegetations
    • Mitral and/or aortic regurgitation Aortic regurgitation Aortic regurgitation (AR) is a cardiac condition characterized by the backflow of blood from the aorta to the left ventricle during diastole. Aortic regurgitation is associated with an abnormal aortic valve and/or aortic root stemming from multiple causes, commonly rheumatic heart disease as well as congenital and degenerative valvular disorders. Aortic Regurgitation (acute phase)
    • Mitral stenosis Mitral stenosis Mitral stenosis (MS) is the narrowing of the mitral valve (MV) orifice, leading to obstructed blood flow from the left atrium (LA) to the left ventricle (LV). Mitral stenosis is most commonly due to rheumatic heart disease. Mitral stenosis leads to impaired LV diastolic filling, increased LA pressure, and LA dilation. Mitral Stenosis (chronic phase)
  • Chest X-ray:
    • Cardiomegaly
    • Pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema in patients in whom heart failure has developed

Management

Treatment

Goals:

  • Eradication of streptococci and bacterial antigens from the pharyngeal region
  • Supportive/symptomatic treatment for arthritis, carditis, and chorea
  • Prevention of cardiac complications

Eradication of streptococcal infection:

  • Penicillin is the drug of choice.
  • Amoxicillin is used if penicillin is not available.
  • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with "cef-" or "ceph-." Cephalosporins are another option.

Arthritis:

  • Aspirin
  • Nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen, naproxen

Severe carditis:

  • Corticosteroids
  • Bed rest
  • Heart failure medications:
    • Diuretics 
    • Vasodilators such as nitroglycerin can reduce strain on the heart.
    • Digoxin
  • Monitoring and treating for arrhythmias caused by myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
  • Surgery is not performed in the acute phase except for emergent indications:
    • Valve leaflet rupture
    • Chordae tendineae rupture
  • Surgical repair may be required in the chronic phase for mitral stenosis.

Sydenham chorea is usually self-limited and does not require specific treatment.

Prevention

  • Primary: prompt antibiotic treatment of streptococcal pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
  • Secondary:
    • Intramuscular penicillin G benzathine is widely used to prevent recurrence.
    • Administered every 28 days
    • In patients with a penicillin allergy, oral macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides are an alternative.
    • Initiated after treatment for original infection ends
    • Duration of prophylaxis depends on original presentation and severity.
Table: Prophylaxis of recurrent rheumatic fever
Rheumatic fever presentation Duration of prophylaxis
Rheumatic fever with carditis and residual heart disease (persistent valvular disease) 10 years or until age 40 years (whichever is longer); lifetime prophylaxis may be needed
Rheumatic fever with carditis but no residual heart disease (no valvular disease) 10 years or until age 21 years (whichever is longer)
Rheumatic fever without carditis 5 years or until age 21 years (whichever is longer)

Prognosis

  • Carditis will resolve without sequelae in 65%–75% of patients.
  • 90% of acute episodes last < 3 months.
  • Risk of recurrence is greatest within the first year.

Differential Diagnosis

  • Bacterial sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock: a life-threatening syndrome that occurs when a bacterial pathogen and its products move from the infection source into the bloodstream. Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia is the most common known precipitating event. Patients commonly present with fever, tachycardia, tachypnea, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, and/or altered mentation. Management is based on the cause and includes treatment with antibiotics.
  • Kawasaki disease Kawasaki disease Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome or infantile polyarteritis, is a medium-sized necrotizing febrile vasculitis that affects children < 5 years of age. Multiple systems are involved but the most serious is the predilection of the coronary arteries. Kawasaki Disease: a febrile vasculitic syndrome of early childhood characterized by vasculitis of medium-sized arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries. Kawasaki disease Kawasaki disease Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome or infantile polyarteritis, is a medium-sized necrotizing febrile vasculitis that affects children < 5 years of age. Multiple systems are involved but the most serious is the predilection of the coronary arteries. Kawasaki Disease is also known as infantile polyarteritis Infantile polyarteritis Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome or infantile polyarteritis, is a medium-sized necrotizing febrile vasculitis that affects children < 5 years of age. Multiple systems are involved but the most serious is the predilection of the coronary arteries. Kawasaki Disease nodosa and mucocutaneous lymph node syndrome Mucocutaneous lymph node syndrome Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome or infantile polyarteritis, is a medium-sized necrotizing febrile vasculitis that affects children < 5 years of age. Multiple systems are involved but the most serious is the predilection of the coronary arteries. Kawasaki Disease. Multiple systems are involved, but the most serious is involvement of the coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries. Management involves intravenous immunoglobulin and high-dose aspirin. 
  • Septic arthritis Septic arthritis Septic arthritis is an infection of the joint due to direct inoculation, contiguous extension, or hematogenous spread of infectious organisms into the joint space. This process causes an acute, inflammatory, monoarticular arthritis. Septic Arthritis: refers to the invasion of the joint space by microorganisms such as bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, viruses, and fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology: Overview. Septic arthritis Septic arthritis Septic arthritis is an infection of the joint due to direct inoculation, contiguous extension, or hematogenous spread of infectious organisms into the joint space. This process causes an acute, inflammatory, monoarticular arthritis. Septic Arthritis can be caused by a variety of organisms, with the most common being Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus. Orthopedic procedures are a common cause of S. aureus infection. Cultures from joint aspiration are diagnostic, with antibiotic therapy tailored to the specific organism found. Antibiotic treatment is aimed at the causative agent. 
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus): an autoimmune disorder characterized by the production of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins against nuclear and cytoplasmic antigens, multisystem inflammation, and protean clinical manifestations. Symptoms include malar rash, joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, fever, proteinuria, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, anemia, lymphopenia, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, and/or psychosis. Management includes topical steroids, IV steroids, or methotrexate. 
  • Infective endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis: a condition characterized by inflammation of the inner lining of the heart and valves caused by infection. Diagnosis is made with echocardiography, and management is based on treatment of the causative agent. 
  • Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease: a zoonotic infection caused by Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia burgdorferi, which presents initially with a localized rash and ultimately causes systemic infection involving the joints, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, and nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System. Neurologic, cardiac, ocular, and joint manifestations are also common in later stages. Diagnosis relies on clinical findings and a tick exposure and is supported by serologic testing. Antibiotics are used for treatment. 
  • Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis: a chronic inflammatory autoimmune disorder characterized by pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, swelling, and destruction of synovial joints. The main symptoms on presentation are morning stiffness and swelling of small joints of the hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand. Diagnosis is based on a strong clinical suspicion and confirmed by the presence of serologic markers and acute-phase reactants. Treatment involves NSAIDs and immunosuppressive medications.

References

  1. Gewitz MH. (n.d.). Revised Jones Criteria for Acute Rheumatic Fever | Ten Points to Remember—American College of Cardiology. Retrieved January 22, 2020, from: https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2015/05/08/15/22/revision-of-the-jones-criteria-for-the-diagnosis-of-acute-rheumatic-fever
  2. Karthikeyan, G., & Guilherme, L. (2018). Acute rheumatic fever. The Lancet, 392(10142), 161–174.
  3. Meador R. J. 2020. Acute Rheumatic Fever. Retrieved February 8, 2021, from https://emedicine.medscape.com/article/333103-overview
  4. Steer, A. and Gibofsky, A. (2020). Acute rheumatic fever: Clinical manifestations and diagnosis. UpToDate. Retrieved February 7, 2021, from https://www.uptodate.com/contents/acute-rheumatic-fever-clinical-manifestations-and-diagnosis
  5. Steer, A. and Gibofsky, A. (2019). Acute rheumatic fever: Treatment and prevention. Retrieved  February 7, 2021, from https://www.uptodate.com/contents/acute-rheumatic-fever-treatment-and-prevention?search=rheumatic%20fever&source
  6. Wallace, M. (2019). Rheumatic Fever Workup. Emedicine. Retrieved February 8, 2021, from https://emedicine.medscape.com/article/236582-workup#c8

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