IE and ARF (UTD)

Question 1

Define infective endocarditis

Answer 1

infection of the endocardium and/or heart valves that involves thrombus formation (vegetation), which may damage the endocardial tissue and/or valves

Question 2

Estimated annual incidence of IE in USA among infants?

Answer 2

3.3 per 100,000 per year among infants <1 year old

Question 3

Estimated annual incidence of IE in USA among older children/adolescents?

Answer 3

0.3 to 0.8 per 100,000 per year in older children and adolescents

Question 4

Risk factors for developing IE?

Answer 4

CHD (especially cyanotic HD), central venous catheters, RHD

Question 5

Rate of underlying CHD in children with IE?

Answer 5

35-60%

Question 6

Risk of IE is highest in patients with?

Answer 6

complex cyanotic heart disease, especially in those who have had surgical intervention

Question 7

Reported incidence rates of IE in children with CHD range from…

Answer 7

40 to 60 per 100,000 person-years, which is several orders of magnitude higher than in the general pediatric population

Question 8

CHD lesions at highest risk for IE include…

Answer 8

cyanotic lesions, endocardial cushion defect, left-sided lesions, and ventricular septal defects (VSD). Other risk factors include cardiac surgery within six months and age <3 years.

Question 9

What devices may be a factor in IE development in kids?

Answer 9

Indwelling CVCs, intracardiac devices (ventriculoatrial shunts, pacemakers, implantable cardioverter-defibrillators, and prosthetic and bioprosthetic valves). As use of these devices becomes more common, the relative proportion of device-related IE increases

Question 10

In developed countries, the incidence of rheumatic heart disease has […] dramatically since the 1960s

Answer 10

declined

Question 11

in the modern era, rheumatic heart disease is an […] predisposing condition for IE in children

Answer 11

uncommon

Question 12

In resource-limited settings, rheumatic heart disease remains […] IE

Answer 12

an important risk factor for developing

Question 13

Other risk factors for IE (other than CHD/RHD/central access devices)?

Answer 13

IVDU, degenerative heart disease –> not commonly seen in children

Question 14

Overall pathogenesis of IE?

Answer 14

interactions among blood-borne pathogens, damaged endothelium, fibrin, and platelets

Question 15

3 steps in pathogenesis of IE?

Answer 15

1. Endocardial surface is injured by shear forces associated with turbulent blood flow 2. fibrin, platelets and sometimes RBCs deposit and form a non-infected thrombus 3. bacteraemia or fungaemia –> adherence of pathogens to injured endothelium and thrombus. Subsequent fibrin and platelet deposition –> protective sheath isolating from host defences and allows rapid proliferation of infection

Question 16

1st step in pathogenesis of IE?

Answer 16

The endocardial surface is initially injured by shear forces associated with turbulent blood flow in children with congenital heart disease (CHD), or indwelling central venous catheters in children without CHD.

Question 17

2nd step in pathogenesis of IE?

Answer 17

At the site of endothelial damage, fibrin, platelets, and occasionally red blood cells are deposited and initially form a noninfected thrombus.

Question 18

3rd step in pathogenesis of IE?

Answer 18

Transient bacteremia (which occurs in normal children) or fungemia results in adherence of microbial pathogens to the injured endocardium and thrombus. Subsequent fibrin and platelet deposition over the infected vegetation result in a protective sheath that isolates the organisms from host defenses and permits rapid proliferation of the infectious agent.

Question 19

Most common microorganisms causing IE?

Answer 19

Staphlococci and Streptococci species

Question 20

Among children with underlying heart disease, what are the most common causes of IE?

Answer 20

• Viridans streptococci – 33 percent
• Staphylococcus aureus – 28 percent
• Other streptococci – 17 percent
• Other Staphylococcus species – 7 percent
• Polymicrobial – 11 percent
• Gram-negative bacilli – 5 percent

Question 21

Among children without underlying heart disease, what are the most common causes of IE?

Answer 21

• S. aureus – 47 percent
• Viridans streptococci – 18 percent
• Polymicrobial – 12 percent
• Other streptococci – 10 percent
• Gram-negative bacilli – 8 percent
• Other Staphylococcus species – 6 percent

Question 22

Overall presentation of S.aureus IE?

Answer 22

acute fulminant process with a high mortality rate, as compared with IE due to most other pathogens

Question 23

Patient with in-dwelling catheters are at risk for bacteremia with […] in infective endocarditis?

Answer 23

Gram-negative organisms

Question 24

Gram-negative bacterial endocarditis is rare or common?

Answer 24

rare

Question 25

Why is gram-negative endocarditis rare?

Answer 25

probably due to the poor ability of gram-negative bacteria to adhere to the endocardium

Question 26

Most likely microbial cause of IE in neonates?

Answer 26

S. aureus, coagulase-negative staphylococci, Klebsiella pneumonia, and Enterobacter species, among others

Question 27

Blood cultures remain negative in what percentage of kids with IE?

Answer 27

5 to 7 percent

Question 28

Mechanisms for blood cultures to remain negative in IE?

Answer 28

previous administration of antimicrobial agents, inadequate microbiologic techniques, or infection with highly fastidious bacteria or nonbacterial pathogen

Question 29

Fungal endocarditis is rare and is typically caused by…

Answer 29

Candida species

Question 30

factors predisposing to fungal endocarditis especially in premature neonates?

Answer 30

Indwelling catheters and high glucose concentrations in parenteral nutrition

Question 31

Fungal endocarditis is frequently associated with…

Answer 31

large, friable vegetations that can embolize, producing important complications

Question 32

Subacute IE presents as?

Answer 32

prolonged course of low-grade fever and nonspecific complaints including fatigue, arthralgias, myalgias, weight loss, exercise intolerance, and diaphoresis. The presence of a cluster of these symptoms in a patient at risk for IE (ie, those with preexisting heart disease or indwelling central venous catheter) should raise the possibility of IE as a potential diagnosis. immune-mediated glomerulonephritis.

Question 33

Usual causes of subactue IE?

Answer 33

The less virulent pathogens, such as viridans group streptococci and coagulase-negative staphylococci, are usually the causative agents for subacute IE.

Question 34

Acute IE presents as?

Answer 34

Acute IE is a rapidly progressive and fulminant disease. These patients typically have high spiking fevers, and appear severely ill.

Question 35

Classic pathogen associated with acute IE? what can it cause?

Answer 35

An acute presentation is commonly seen in patients with IE due to S. aureus, which can cause rapid destruction of heart valve tissue, abscess formation, embolic phenomena, and a rapidly progressive deterioration in hemodynamic status.

Question 36

clinical findings of IE correspond to the underlying pathologic phenomena of ?

Answer 36

bacteremia/fungemia, valvulitis, immunologic response, and embolization

Question 37

Symptoms associated with bacteraemia or fungaemia include?

Answer 37

fever, and vasodilation and tachycardia due to decreased systemic vascular resistance

Question 38

Valvulitis may result in a?

Answer 38

new or changing murmur. In some patients, tachypnea and hypotension are signs of heart failure, which occurs because of perforation of a valve, chordal rupture, or poor ventricular function.

Question 39

In kids with cyanotic CHD with either a systemic-pulmonary shunt or conduit procedure, IE may present as?

Answer 39

the murmur may not change, but a decline in systemic oxygen saturation may occur due to obstruction of blood flow

Question 40

immune-mediated disease may result in […] in children who present with subacute IE

Answer 40

Glomerulonephritis

Question 41

Other immunologic phenomenon such as […] are less common in children than they are in adults with IE

Answer 41

Roth’s spots, Janeway lesions, and Osler nodes

Question 42

In children with IE, septic emboli are common, resulting in…

Answer 42

extracardiac infection (eg, osteomyelitis or pneumonia) or infarction to major vessels and organs

Question 43

Emboli to the brain may result in…

Answer 43

neurologic symptoms (eg, seizures, headache, strokes, or altered mental status)

Question 44

Other major organs that may be at risk for embolic episodes include the

Answer 44

kidney, gastrointestinal tract, limbs, and lungs

Question 45

Neonatal signs and symptoms of IE?

Answer 45

Variable and non-specific. feeding intolerance, tachycardia, respiratory distress, hypotension, and a new or changing murmur. Fever may not be present with either subacute or acute IE

Question 46

Neonates with right-sided IE in association with central venous catheters characteristically have little clinical evidence of disease other than…

Answer 46

persistently positive blood cultures in the setting of appropriate antibiotic treatment

Question 47

Fungal IE is […] in the newborn infant and may present as an acute fulminant disease

Answer 47

more common

Question 48

Neonatal IE presentation may be indistinguishable from …

Answer 48

septicemia or heart failure

Question 49

Diagnostic criteria for IE?

Answer 49

modified Duke criteria, which categorize patients as “definite IE,” “possible IE,” and “rejected IE” based on pathologic and clinical criteria

Question 50

What are the modified Duke criteria for IE?

Answer 50

Definite IE is established in the presence of any of the following:

Pathologic criteria

• Pathologic lesions – Vegetation or intracardiac abscess demonstrating active endocarditis on histology, OR
• Microorganism – Demonstrated by culture or histology of a vegetation or intracardiac abscess

Clinical criteria

Using specific definitions listed in Table B:

2 major clinical criteria, OR

1 major and 3 minor clinical criteria, OR

5 minor clinical criteria

Possible IE*

Presence of 1 major and 1 minor clinical criteria OR presence of 3 minor clinical criteria

Rejected IE

A firm alternate diagnosis is made, OR

Resolution of clinical manifestations occurs after ≤4 days of antibiotic therapy, OR

No pathologic evidence of infective endocarditis is found at surgery or autopsy after antibiotic therapy for 4 days or less

Clinical criteria for possible or definite IE not met

Major criteria

Positive blood cultures for IE (1 of the following):

Typical microorganisms consistent with IE from 2 separate blood cultures:

• Staphylococcus aureus
• Viridans streptococci
• Streptococcus gallolyticus (formerly S. bovis), including nutritional variant strains (Granulicatella spp and Abiotrophia defectiva)
• HACEK group – Haemophilus aphrophilus (subsequently called Aggregatibacter aphrophilus and Aggregatibacter paraphrophilus), Actinobacillus actinomycetemcomitans (subsequently called Aggregatibacter actinomycetemcomitans), Cardiobacterium hominis, Eikenella corrodens, Kingella kingae
• Community-acquired enterococci in the absence of a primary focus, OR

Persistently positive blood culture:

• For organisms that are typical causes of IE – At least 2 positive blood cultures from blood samples drawn >12 hours apart
• For organisms that are more commonly skin contaminants – 3 or a majority of ≥4 separate blood cultures (with first and last drawn at least 1 hour apart)

Single positive blood culture for Coxiella burnetii or phase I IgG antibody titer >1:800*

Evidence of endocardial involvement (1 of the following):

Echocardiogram positive for IE:

• Vegetation (oscillating intracardiac mass on a valve or on supporting structures, in the path of regurgitant jets, or on implanted material, in the absence of an alternative anatomic explanation), OR
• Abscess, OR
• New partial dehiscence of prosthetic valve

New valvular regurgitation

• Increase in or change in preexisting murmur not sufficient

Minor criteria

• Predisposition – Intravenous drug use or presence of a predisposing heart condition (prosthetic heart valve or a valve lesion associated with significant regurgitation or turbulence of blood flow)
• Fever – Temperature ≥38.0°C (100.4°F)
• Vascular phenomena – Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, or Janeway lesions
• Immunologic phenomena – Glomerulonephritis, Osler nodes, Roth spots, or rheumatoid factor
• Microbiologic evidence – Positive blood cultures that do not meet major criteria, OR serologic evidence of active infection with organism consistent with IE

Question 51

Pathologic criteria for IE?

Answer 51

One of the following two pathologic criteria are required for the diagnosis of IE:

• Direct evidence of endocarditis based upon histologic findings
• Positive Gram stain results or cultures of specimens obtained from surgery or autopsy

Question 52

Clinical criteria for IE?

Answer 52

The clinical criteria are divided into major and minor findings. The clinical diagnosis of definitive IE requires the presence of either two major criteria, one major and three minor criteria, or five minor criteria

Question 53

Discuss the utility of Blood cultures in IE

Answer 53

performed in all patients since one of the two major diagnostic criteria is positive blood cultures for typical organisms associated with IE from at least two separate specimens

Question 54

How often should blood cultures be collected in suspected IE?

Answer 54

A minimum of three blood cultures should be obtained over a time period of a few hours to two days depending upon the severity of the illness. In most patients, three blood cultures are obtained from separate venipunctures in the first 24 hours and an additional two blood cultures in the next 24 hours if there is no growth

Question 55

How often should blood cultures be taken in children with suspected IE who are critically unwell?

Answer 55

In critically ill children, three separate venipunctures for blood cultures should be performed as quickly as possible (with <1 hour) and empiric antibiotic therapy started promptly. In children who are not acutely ill, antibiotic therapy can be withheld for at least 48 hours while the blood cultures are collected

Question 56

Do blood cultures need to be taken at a particular time during the fever cycle in IE?

Answer 56

Since bacteremia is generally continuous, the blood cultures do not have to be obtained at any particular time in the fever cycle

Question 57

Are more than 5 blood cultures needed in suspected IE?

Answer 57

Unless there has been prior antibiotic therapy, more than five blood cultures over two days is generally not warranted

Question 58

If limited blood is available in suspected IE, which culture bottles should be used?

Answer 58

If there is a limited volume of blood, preferential culturing of the aerobic culture bottle is suggested because almost all cases of bacterial IE are due to aerobic organisms, and culturing for anaerobes is rarely useful

Question 59

What risk factors should prompt early evaluation for IE?

Answer 59

preexisting heart disease, indwelling central lines, presence of prosthetic material, persistent bacteremia, or infection with organisms most associated with IE

Question 60

Echo findings of IE?

Answer 60

presence of a vegetation, intracardiac abscess, new or progressive valvular regurgitation, and, in patients with a prosthetic valve, evidence of partial dehiscence

Question 61

What is the utility of Echo in IE?

Answer 61

can identify the size and location of a vegetation, extent of valve damage and the degree of valvar stenosis or regurgitation, perivalvar extension of infection, conduit or shunt obstruction, ventricular function, and the presence of a pericardial effusion. It can be used to serially monitor hemodynamic and valvular function, and the resolution of vegetations in response to medical treatment

Question 62

Is TTE or TOE better for IE evaluation?

Answer 62

In most pediatric cases of suspected IE, transthoracic echocardiography (TTE) is adequate to detect the presence of a vegetation, especially in infants and younger children (<10 years and <60 kg), and to monitor hemodynamic and valvular function. TTE is a much more sensitive diagnostic tool in children compared with adults

Question 63

When can TTE be inadequate in evaluating IE in kids? (And thus TOE be warranted?)

Answer 63

Inadequate TTE imaging is most likely to occur in the following patients:

●Overweight children.

●Muscular children.

●Children with significant respiratory disease.

●Children with surgically repaired complex congenital heart disease (CHD), as artifacts from prosthetic material (grafts and conduits) and valves may interfere with TTE imaging. Suboptimal echocardiographic windows are frequently present in the postoperative patient.

●Children with chest wall disruption from prior surgery or trauma.

●Children with congenital anomalies involving the thoracic cage (eg, severe pectus excavatum).

Question 64

In children with aortic valve IE, is TOE advised? Why?

Answer 64

In children with aortic valve IE, TEE is superior to TTE for the detection of aortic root abscess and therefore may be warranted if there are findings on TTE consistent with periannular extension (eg, changing aortic root dimensions)

Question 65

When might TTE or TOE not be useful?

Answer 65

Both TTE and TEE may give false-negative results if the vegetations are small or if embolization of the vegetation has occurred

Question 66

What other tests may support diagnosis of IE?

Answer 66

●Low hemoglobin/hematocrit demonstrating anemia (either hemolytic or anemia of chronic disease), which is a common feature of IE

●Elevated erythrocyte sedimentation rate and C-reactive protein indicative of inflammation

●Urinalysis showing hematuria, proteinuria, and red cell casts is suggestive of glomerulonephritis, a minor diagnostic criterion

Question 67

How may IE show on an ECG?

Answer 67

Electrocardiography is generally not helpful in the diagnosis of IE with the exception of IE with periannular extension, in which prolongation of the PR interval or frank heart block can occur

Question 68

How may IE show on a CXR?

Answer 68

Chest radiography is also not useful in the diagnosis of IE. Findings that may be seen include cardiomegaly, heart failure, and focal pulmonary infiltrates in patients with pulmonary septic emboli

Question 69

Viridans group streptococci and Streptococcus bovis treatment options in IE?

Answer 69

Question 70

IE Enterococci treatment options?

Answer 70

Question 71

IE Staphlococcus treatment options?

Answer 71

Question 72

HACEK IE treatment options?

Answer 72

Question 73

Describe culture negative endocarditis (CNE) and what consideration need to be made in management?

Answer 73

Culture-negative endocarditis (CNE) occurs rarely in children and may be diagnosed when a patient has clinical or echocardiographic evidence of IE but persistently negative blood cultures. Important considerations in determining the treatment regimen include prior antibiotic exposure, route of acquisition of the infection, whether the infection is community acquired or nosocomial, whether the valve infected is native or prosthetic, and whether the infection is acute or subacute

Question 74

Indications for surgical intervention in IE?

Answer 74

congestive heart failure, progressive valve dysfunction, and embolic phenomena

Question 75

What ongoing monitoring tests may be useful in monitoring IE patients?

Answer 75

Antimicrobial levels (e.g. gentamicin or vancomicin levels)

TTE: repeat testing needing to assess changes in vegetations and evaluate valve and myocardiacl function. Once Tx completed, repeat TTE may allow establishment of new baseline in valvular and myocardiac function

Repeat BC: recurrant sfymptoms, can help determine adequacy of Tx

Question 76

Indications for prophylactic Abx in patients at highest risk for IE? (7)

Answer 76

●Prosthetic heart valves, including mechanical, bioprosthetic, and homograft valves (transcatheter-implanted as well as surgically implanted valves are included)

●Prosthetic material used for cardiac valve repair, such as annuloplasty rings and chords

●A prior history of IE

●Unrepaired cyanotic congenital heart disease

●Repaired congenital heart disease with residual shunts or valvular regurgitation at the site or adjacent to the site of the prosthetic patch or prosthetic device

●Repaired congenital heart defects with catheter-based intervention involving an occlusion device or stent during the first six months after the procedure

●Valve regurgitation due to a structurally abnormal valve in a transplanted heart

Question 77

What antibiotics can be used for prophylaxis in IE?

Answer 77

Question 78

What is the mortality rates in children with IE?

Answer 78

1 to 5 percent

Question 79

Mortality is highest in which group of patients with IE?

Answer 79

underlying cyanotic congenital heart disease (CHD) and with infection caused by S. aureus

Question 80

Factors associated with higher risk of mortality in IE?

Answer 80

heart failure, perivalvular abscess, stroke, or septic emboli with distant abscesses

Question 81

Factors that predispose to the development of complications in children with IE include?

Answer 81

●Prosthetic cardiac valves

●Left-sided involvement

●S. aureus or fungal IE

●Previous IE

●Prolonged symptoms (≥3 months)

●Cyanotic congenital heart disease

●Systemic-to-pulmonary shunts

●Poor clinical response to antimicrobial therapy

Question 82

What are the cardiac complications of IE?

Answer 82

• Heart failure – Heart failure can be caused by perforation of the valve, rupture of an infected chordae, or perivalvar leaks or dehiscence in patients with prosthetic valve. Poor ventricular function often accompanies worsening valvar regurgitation. Heart failure is the most common reason for cardiac surgery in patients with IE.
• Perivalvular abscess – Extension of infection beyond the endothelium may result in a fistula tract or perivalvular infection (eg, abscess), which may cause an arrhythmia or atrioventricular heart block. Transesophageal echocardiography (TEE) is more sensitive for detection of myocardial abscess than transthoracic echocardiography (TTE).
• Extension of infection into a prosthetic shunt or conduits may occlude the graft. These infections require surgical intervention because they rarely respond to medical management.

Question 83

Can metastatic infection occur in IE? Where?

Answer 83

Yes. Infection at other sites can occur from septic emboli resulting in osteomyelitis, pneumonia, or distal abscesses in the kidneys, spleen, brain, or soft tissues.

Question 84

In what percentage of patients does stroke occur in IE?

Answer 84

Stoke occurs in 5 to 15 percent of pediatric IE cases, chiefly in the setting of left-sided IE

Question 85

How does AKI occur as a complication of IE? What percentage of patients does it occur in?

Answer 85

AKI can be caused by renal infarction, glomerulonephritis (as a result of an immune-mediated secondary process), and drug-induced acute interstitial nephritis. AKI occurs in approximately 10 percent of pediatric patients with IE

Question 86

What other embolic events may complicate IE?

Answer 86

• Pulmonary embolism (typically occurs in the setting of right-sided IE)
• Ischemia of the extremities
• Splenic infarction
• Visual impairment (due to embolism or due to endophthalmitis as a result of bacteremic seeding)
• Acute myocardial infarction

Question 87

What are the potential complications of Group A Strep (GAS) pharyngeal infection?

Answer 87

suppurative (eg, peritonsillar abscess, otitis media, sinusitis) and inflammatory, nonsuppurative conditions. Acute rheumatic fever (ARF) is one of the nonsuppurative complications (others include scarlet fever and acute glomerulonephritis [AGN])

Question 88

What time difference is there between initial pharyngitis and the subsequent development of signs of ARF?

Answer 88

2-3 weeks

Question 89

What signs/symptoms may ARF present with?

Answer 89

arthritis or arthralgia, carditis, chorea, subcutaneous nodules, and erythema marginatum

Question 90

What is the burden of acute rheumatic rever in the developing world?

Answer 90

In developing areas of the world, severe disease caused by group A Streptococcus (GAS; eg, ARF, rheumatic heart disease, glomerulonephritis, and invasive infections) is estimated to affect over 33 million people and is the leading cause of cardiovascular death during the first five decades of life

Question 91

What age group does ARF most commonly affect?

Answer 91

5-15 years of age

Question 92

What is the overall global burden for ARF?

Answer 92

470,000 new cases of ARF and 275,000 deaths attributable to rheumatic heart disease each year

Question 93

Most cases of ARF occur in […] and among […]

Answer 93

low- and middle-income countries….Indigenous groups

Regions with the highest rates are likely to have the least accurate data with substantial underreporting

Question 94

The mean incidence of ARF is […] per 100,000 school-aged children worldwide

Answer 94

19

Question 95

The rate of ARF among indigenous australians is […] to […] cases per 100, 000 children aged […] to […] years

Answer 95

153 to 380, 5 to 14

Question 96

The higher incidence in developing countries is primarily explained by …

Answer 96

environmental factors, especially household overcrowding, which favors increased transmission of GAS, and in smaller part by routine use of antibiotics for acute pharyngitis

Question 97

What is the overall pathogenic mechanism in ARF infection?

Answer 97

Streptococcal pharyngeal infection, genetic susceptibility may be present, molecular mimicry may play a role in initiation of tissue injury

Question 98

Describe the immune-mediated pathogenesis of ARF?

How does this lead to symptoms?

Answer 98

GAS pharyngeal infection –> activation of innate immune system leads to GAS Ag presentation to T cells –> B and T cells produce IgG and IgM Ab and activation of CD4+ T cells –> cross-reactive immune response via molecular mimicry involving humoral and cellular components of adaptive immune system

This cross-reactive response results in the clinical features of rheumatic fever including transient arthritis due to the formation of immune complexes, chorea due to binding of antibody to basal ganglia, and carditis due to antibody binding and infiltration of T cells

Question 99

What is the role of Strep Pyogenes (GAS) in ARF pathogenesis?

Answer 99

Epidemiologic evidence indirectly implicates GAS in the initiation of disease, although evidence for direct involvement of GAS in the affected tissues of patients with ARF is lacking:

●Outbreaks of ARF closely follow epidemics of streptococcal pharyngitis or scarlet fever with associated pharyngitis.

●Adequate treatment of a documented streptococcal pharyngitis reduces the incidence of subsequent ARF by nearly 70 percent.

●Appropriate antimicrobial prophylaxis prevents the recurrence of disease in patients who have had ARF.

●Most patients with ARF have elevated antibody titers to at least one of three antistreptococcal antigens (streptolysin “O,” hyaluronidase, and streptokinase), whether or not they recall an antecedent sore throat

Question 100

How does GAS bacteral strain specificity affect site of infection?

Answer 100

There are five chromosome patterns of emm genes, labeled A to E, that code for M and M-like cell surface virulence proteins. GAS fall into two main classes based upon differences in the C repeat regions of the M protein. Pharyngeal strains typically have patterns A to C, whereas almost all impetigo strains show D and E patterns

Question 101

Why is pharyngitis important in the diagnosis of ARF?

Answer 101

Streptococcal pharyngitis is the only streptococcal infection that is clearly associated with ARF, although streptococcal pyoderma appears capable of triggering the condition in tropical areas. Streptococcal skin infections (such as impetigo or pyoderma) have not been proven to lead to ARF. In addition, viral pharyngitis and pharyngitis caused by other bacteria do not result in ARF.

The pharyngeal site of infection, with its large repository of lymphoid tissue, may be important in the initiation of the abnormal host response to those antigens cross-reactive with target organs.

Impetigo strains do colonize the pharynx. However, they do not appear to elicit as strong an immunologic response to the M protein moiety as the pharyngeal strains

Question 102

What is the role of molecular mimicry in ARF pathogenesis?

Answer 102

Molecular mimicry implies structural similarity between some infectious or other exogenous agent and human proteins, such that antibodies and T cells activated in response to the exogenous agent react with the human protein. In ARF, antibodies directed against GAS antigens crossreact with host antigens . In addition, human heart-intralesional T cell clones react with meromyosin, myosin, and valve-derived proteins, leading to an immunologic response to cardiac tissue and production of inflammatory cytokines

The alpha-helical protein structures found in M protein and N-acetyl-beta-D-glucosamine (NABG, the immunodominant carbohydrate antigen of GAS) share epitopes with myosin, and antibody crossreactivity has been demonstrated in humans

Autoreactive T cells appear to play an important role in the formation of Aschoff nodules in cardiac valves. Vascular cell adhesion molecule 1 (VACM1) appears to be the link between humoral and cellular immunity at the valve surface [63]. VCAM1 is upregulated on the surface of the valve endothelium following binding of cross-reactive antibodies. This leads to adherence of T cells (predominantly CD4+) to the endothelium, with subsequent infiltration of these cells into the valve resulting in the formation of granulomatous lesions (Aschoff bodies) underneath the endocardium

Molecular mimicry may also be involved in the development of Sydenham chorea in patients with ARF. In an animal model, monoclonal antibodies that caused chorea bound to both NABG and mammalian lysoganglioside [60]. Exposure of cultured human neuronal cells to either monoclonal antibodies or serum from patients with chorea led to induction of calcium/calmodulin protein kinase. Exposure to serum from patients following streptococcal infection that was not complicated by chorea did not have this effect on neuronal cells

Question 103

Is genetic susceptibility involed in ARF pathogenesis? How?

Answer 103

risk was 44 percent in monozygotic twins and 12 percent in dizygotic twins

susceptibility signal in the immunoglobulin heavy chain locus suggesting a central role of humoral immunity in the pathogenesis of rheumatic fever

variation at the class II region of the human leukocyte antigen

Question 104

What are the five major manifestations (and percent of patients with each) in ARF?

Answer 104

●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

Question 105

What are the four minor manifestations in ARF?

Answer 105

●Arthralgia

●Fever

●Elevated acute phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP])

●Prolonged PR interval on electrocardiogram

Question 106

What are the two primary forms of presentation of ARF?

Answer 106

Question 107

Describe the arthritis typically associated with ARF. Early or late symptoms? when does it present? what age group?

Answer 107

usually earliest symptomatic manifestation of ARF

generally presenting within 21 days of GAS infection, although asymptomatic carditis may develop first.

more common and more severe in teenagers and young adults than in children

Joint pain typically is more prominent than objective signs of inflammation and is almost always transient. However, the arthritis may be severe enough to severely limit movement.

Question 108

Describe the clinical presenatation and progression of arthritis associated with ARF?

Answer 108

• affects several joints in quick succession, and each joint is inflamed for a day or two to a week.
• The knees, ankles, elbows, and wrists are most commonly affected, with the leg joints typically involved first.
• onset of arthritis in different joints usually overlaps, giving the appearance that the disease “migrates” from joint to joint. Thus, the terms “migrating” or “migratory” are used to describe the polyarthritis of ARF, and it is also regarded as an additive polyarthritis.
• The arthritis resolves without treatment in approximately four weeks, and there is no long-term joint deformity

Question 109

How does arthritis in ARF respond to treatment with NSAIDs

Answer 109

The natural history of arthritis in ARF is altered by empiric treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids. In such cases, arthritis subsides quickly in the joint(s) affected and does not “migrate” to new joints. The diagnosis of ARF should be reconsidered if joint symptoms do not respond to NSAID treatment within 48 hours

Patients treated with NSAIDs early in the course of ARF, particularly before the other signs and symptoms of ARF become distinct, may appear to have monoarthritis rather than polyarthritis.

The presence of monoarthritis rather than polyarthritis can make it difficult to establish the diagnosis of ARF and determine the need for secondary ARF prophylaxis. Commencement of NSAID therapy can be delayed if the diagnosis of ARF is suspected but only a single joint is involved, with acetaminophen used for analgesia in the meantime, since there is no evidence that temporarily withholding such therapy has any adverse effects. NSAIDs may be commenced once a second joint is involved and the diagnosis is clear.

Question 110

Does radiology play a role for evaluation of arthritis in ARF?

Answer 110

Radiography of an affected joint may demonstrate a slight effusion but is usually unremarkable. Thus, radiographic evaluation of affected joints is not routinely performed. Joint aspiration and synovial fluid evaluation, including culture, is indicated if there is significant effusion of one joint or septic arthritis is suspected. Analysis of the synovial fluid generally demonstrates sterile inflammatory fluid in patients with ARF

Question 111

Describe the overall presentation of carditis in ARF

Answer 111

The carditis associated with ARF is classically considered to be a pancarditis that can involve the pericardium, epicardium, myocardium, and endocardium. While myocarditis and pericarditis may occur in ARF, the predominant manifestation of carditis is involvement of the endocardium presenting as a valvulitis, especially of the mitral and aortic valves

The presence of valvulitis is established by auscultatory findings together with echocardiographic evidence of mitral or aortic regurgitation

Question 112

When does Carditis classicaly present in ARF?

Answer 112

within three weeks of GAS infection

Question 113

What is the Carey Coombs murmur? When is it heard?

Answer 113

Heard in ARF

a short mid-diastolic murmur heard loudest at the apex, is an indicator of moderate-severe mitral regurgitation as a result of increased blood flow across the mitral valve during left ventricular filling

Question 114

How can subclinical carditis be diagnosed in rheumatic fever?

Answer 114

Subclinical carditis can be diagnosed by echocardiography/Doppler studies that reveal mitral or aortic regurgitation in the absence of ausculatory findings (either because the clinical exam findings are absent or are not recognized). Damage to cardiac valves may be progressive and chronic, resulting in cardiac decompensation

Question 115

What is syndenham chorea?

Answer 115

Sydenham chorea (also known as chorea minor or “St. Vitus dance”) is a neurologic disorder consisting of abrupt, nonrhythmic, involuntary movements, muscular weakness, and emotional disturbances

Question 116

When does syndenham chorea present in rheumatic fever?

Answer 116

Chorea has a longer latent period than other rheumatic manifestations, typically presenting one to eight months after a GAS infection, and may occur as an isolated finding

Question 117

Does chorea have a sex predisposition?

Answer 117

Yes.

It is more common in girls and may present as refusal to go to school and self-isolation due to shame and embarrassment

Question 118

Can there be recurrance of syndenham chorea? How long does it last?

Answer 118

Recurrence of rheumatic chorea is not uncommon, sometimes associated with pregnancy or the oral contraceptive pill. Most patients with Sydenham chorea recover fully within six weeks and nearly all within six months, with only rare cases described lasting longer than that.

Question 119

Describe the findings of syndenham chorea on physical exam

Answer 119

• choreiform movements frequently are more marked on one side, are occasionally unilateral (hemichorea), and cease during sleep.
• Movements may be subtle and intermittent, sometimes only seen after a 10- to 15-minute period of quiet observation.
• Muscle weakness is best demonstrated by asking the patient to squeeze the examiner’s hands. The pressure of the patient’s grip increases and decreases capriciously, a phenomenon known as relapsing grip or “milk maid’s sign.”
• Head is often involved, with erratic movements of the face that resemble grimaces, grins, and frowns. The tongue, if affected, can resemble a “bag of worms” when protruded, and protrusion cannot be maintained.
• Chorea disappears with sleep and is made more pronounced by purposeful movements.
• Diffuse hypotonia may be present.
• Neurologic examination fails to reveal sensory losses or involvement of the pyramidal tract.

Question 120

What are the emotional/psychiatric manifestations of syndenham chorea?

Answer 120

• Emotional changes manifest with outbursts of inappropriate behavior including crying and restlessness.
• obsessive-compulsive disorder (OCD).
• Halting and jerky speech patterns
• transient psychosis.

Question 121

What is erythema marginatum?

Answer 121

evanescent, pink or faintly red, nonpruritic rash involving the trunk and sometimes the limbs but not the face

Question 122

When does erythema marginatum occur in ARF?

Answer 122

• early in the course of ARF, but, in some cases, the lesions are first noticed late in the illness or even during convalescence.
• can persists or recur after all other manifestations have resolved.
• Erythema marginatum most commonly occurs in patients with acute carditis but has been reported in patients with chronic carditis
• rarely occurs as the sole manifestation of ARF.

Question 123

Describe how erythema marginatum looks

Answer 123

The lesion extends centrifugally, with return of the skin in the center to a normal appearance. The outer edge of the lesion is sharp; the inner edge is diffuse. The lesion is also known as “erythema annulare” since the margin of the lesion is usually continuous, making a ring. Individual lesions may appear, disappear, and reappear in a matter of hours. A hot bath or shower may make them more evident.

Question 124

Describe the subcutaneous nodules in ARF

Answer 124

firm, painless lesions ranging from a few millimeters to 2 cm in size. They are smaller and shorter lived than the nodules of rheumatoid arthritis

The nodules are usually located over a bony surface or prominence or near tendons (usually extensor surfaces) and are usually symmetric. The elbows are involved most frequently in both ARF and rheumatoid arthritis. However, ARF nodules occur most commonly on the olecranon, whereas rheumatoid nodules are usually found 3 to 4 cm distally. The overlying skin is not inflamed and usually can be moved over the nodules. The number of nodules varies from a single lesion to a few dozen; the average number is three to four.

Question 125

Describe when and for how long subcutaneous nodules can present in ARF

Answer 125

Subcutaneous nodules associated with ARF generally appear after the first weeks of illness, usually in patients with relatively severe carditis. They rarely appear as the only manifestation of ARF. Typically, nodules are present for one or more weeks, but they rarely persist for more than a month.

Question 126

What are the minor manifestations of ARF?

Answer 126

fever, arthralgia, elevated ESR and CRP, and prolonged PR interval on electrocardiogram

Question 127

Describe fever as a minor criteria in ARF

Answer 127

Fever associated with ARF is usually ≥38.5°C orally (101.3°F). However, low-grade fever (≥38°C [100.4°F]) is more common in high-risk groups, such as the Indigenous Australian population.

Question 128

Describe arthralgia as a minor criteria in ARF

Answer 128

Arthralgia usually involves several joints (polyarthralgia) when it occurs in patients with ARF. However, it is a common manifestation in many other rheumatologic disorders and therefore is highly nonspecific.

Question 129

Describe elevated acute phase reactants as a minor criteria in ARF

Answer 129

Acute phase reactants are almost always elevated in patients with ARF, except in some patients with isolated chorea or in those treated with antirheumatic drugs [14]. Typical elevations of acute phase reactants seen in ARF include an ESR ≥60 mm/hour and CRP ≥3 mg/dL (≥30 mg/L). As with fever, lower levels (ie, ESR ≥30 mm/hour) can be seen in high-risk groups.

Question 130

Describe prolonged PR interval as a minor criteria in ARF

Answer 130

Interpretation of PR prolongation depends upon age and heart rate and is >0.2 seconds in adults. It is important to note that up to one-third of children with uncomplicated streptococcal infections have a prolonged PR interval. Abnormal atrioventricular conduction is common in ARF, with first degree block the most common abnormality observed. Severe first-degree block can occasionally lead to a junctional rhythm, and second-degree and complete heart block can occur

Question 131

What are some of the “other findings” which may support a diagnosis of ARF?

Answer 131

abdominal pain, precordial pain, malaise, epistaxis, rapid sleeping pulse rate, and tachycardia out of proportion to fever. Laboratory findings include leukocytosis and mild normochromic, normocytic anemia of chronic inflammation. Complement levels are usually normal in ARF. In contrast, hypocomplementemia is typically observed in the setting of poststreptococcal glomerulonephritis.

Question 132

What is the late sequelae of ARF?

Answer 132

Rheumatic heart disease (RHD) is the most common and severe sequela of ARF. Jaccoud arthropathy is a rare complication associated with recurrent episodes of ARF with polyarthritis

Question 133

What is rheumatic heart disease?

Answer 133

• occurs 10 to 20 years after the original illness, although it may present earlier after a severe or recurrent episode of ARF.
• most common cause of acquired valvular disease in the world
• mitral valve is more commonly involved than the aortic valve, and mitral regurgitation is the most common finding of RHD. This may progress to mitral stenosis in severe cases due to fibrosis and calcification of the mitral valve.
• valvular damage manifesting as a murmur later in life occurs in approximately 50 percent of patients who had carditis during the initial episode of ARF

Question 134

What is Jaccoud Arthropathy?

Answer 134

Jaccoud arthropathy is a benign, chronic arthropathy that involves loosening and lengthening of periarticular structures and tendons in the hands and/or feet (picture 4). The deformities are painless, “correctable” with manipulation, and do not cause functional impairment. The arthropathy is not associated with active joint inflammation.

Question 135

What are the two sets of criteria in the 2015 modified Jones criteria?

Answer 135

one for low-risk populations (ie, those with a rheumatic fever incidence <2 per 100,000 school-aged children per year or all-age rheumatic heart disease [RHD] prevalence ≤1 per 1000 population) and one for moderate- to high-risk populations

Question 136

How many major and minor criteria are needed to diagnose ARF?

Answer 136

Joint (arthritis or arthralgia) and cardiac (carditis or prolonged PR interval) manifestations can only be counted once, not twice, as either a major or a minor criterion.

●Two major manifestations or one major plus two minor are sufficient for diagnosis of an initial episode of ARF in a patient with evidence of a preceding GAS infection.

●Patients with a history of ARF are at risk of subsequent episodes of ARF with GAS reinfection, and repeat episodes are associated with a greater likelihood of severe cardiac involvement. In these patients, two major, one major plus two minor, or three minor manifestations are sufficient for diagnosis of recurrent ARF.

All patients undergo cardiac evaluation, even if they do not present with clinical evidence of carditis

Question 137

What are the 3 exceptions to the Jones criteria rules in making a diagnosis of ARF?

Answer 137

●Chorea as the only manifestation. These patients should undergo evaluation for carditis with echocardiogram.

●Indolent carditis as the only manifestation in patients who come to medical attention months after acute GAS infection. An echocardiogram should be performed in these patients to look for evidence of carditis.

●Recurrent ARF in patients with a history of ARF-associated carditis or RHD. It may be difficult to establish a diagnosis of acute carditis during an acute attack in the absence of pericarditis or involvement of a new valve. Thus, a presumptive diagnosis of recurrent ARF may be made with one major or two minor criteria if there is evidence of a recent GAS infection. Caution against using a single clinical finding (eg, monoarthritis, fever, arthralgia) as a criterion for the diagnosis of recurrent disease is suggested

Question 138

What is the problem with strict adherence to the Jones Criteria in areas of higher prevalence? What defines an area of higher prevalance?

Answer 138

Strict adherence to the Jones Criteria in areas of higher prevalence (defined as ARF incidence >2 per 100,000 school-aged children per year or all-age RHD prevalence of >1 per 1000 population) may result in under-diagnosis

Question 139

How are the Jones criteria different/modified in moderate-high risk populations?

Answer 139

●The major criterion of arthritis includes monoarthritis or polyarthralgia in addition to polyarthritis. Polyarthralgia should only be considered as a major manifestation after exclusion of other causes.

●The minor criterion for joint involvement is monoarthralgia rather than polyarthralgia.

●A lower cutoff for fever is used (≥38°C [100.4°F] rather than ≥38.5°C [101.3°F]).

●A lower cutoff for erythrocyte sedimentation rate (ESR) is used (≥30 mm/hour rather than ≥60 mm/hour), although the C-reactive protein (CRP) cutoff is unchanged (≥3 mg/dL [≥30 mg/L]).

Question 140

Is a confirmed/documented GAS infection required to diagnose ARF?

Answer 140

Confirmation of group A streptococcal (GAS) infection is helpful but not necessary to make the diagnosis of ARF. A high index of suspicion of ARF is important, particularly in children or young adults presenting with signs of arthritis and/or carditis, even in the absence of a documented episode of pharyngitis. Laboratory confirmation is required because the clinical documentation of an antecedent pharyngitis is unreliable and has an age-related variability

Question 141

How might evidence of prior GAS infection be sought?

Answer 141

●Positive throat culture for group A beta-hemolytic streptococci

●Positive rapid streptococcal antigen test

●Elevated or rising antistreptococcal antibody titer – Either antistreptolysin O (ASO) or antideoxyribonuclease B (ADB)

Question 142

How are ASO and ADB titres evaluated in ARF?

Answer 142

• ASO and ADB titers may be interpreted either by comparison of acute with convalescent titers or against a reference upper limit of normal (ULN).
• increase in titer from acute to convalescent (at least two weeks apart) is considered the best evidence of antecedent GAS infection.
• The antibody response of ASO peaks at approximately three to five weeks following GAS pharyngitis, which usually is during the first to third week of ARF, while ADB titers peak at six to eight weeks .Antibody titers fall off rapidly in the next several months and, after six months, have a slower decline. For these reasons, it may be useful to collect one specimen when the diagnosis of ARF is first suspected and another two weeks later.
• Approximately 80 percent of patients with documented ARF demonstrate a rise in ASO titer above the ULN value for age, defined by the 80th centile, although this cannot be used as a measure of rheumatic activity.

Question 143

Describe post-streptococcal reactive arthritis

Answer 143

Several investigators have speculated that some cases of arthritis occurring after a streptococcal infection may not be caused by ARF. This disorder has been called poststreptococcal reactive arthritis (PSRA). However, an unusual clinical course should not be sufficient to exclude the diagnosis of ARF. Migratory arthritis without evidence of other major Jones Criteria, if supported by two minor manifestations, must still be considered ARF, especially in children. Defining this reactive arthritis as an ARF variant has important implications for secondary prophylactic treatment.

Question 144

What observations support post-strep reactive arthritis as a separate disorder from ARF?

Answer 144

●The latent period between the antecedent streptococcal infection and the onset of migratory arthritis is shorter (one to two weeks) than the two to three weeks usually seen in classic ARF.

●The response of the arthritis to aspirin and other nonsteroidal medications is poor in comparison to the dramatic response seen in classic ARF.

●Evidence of carditis is not seen in these patients, and the severity of the arthritis is quite marked.

●Extra-articular manifestations, such as tenosynovitis and renal abnormalities, often are seen in these patients.

●Acute phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) tend to be lower than in the setting of ARF.

Question 145

What are the treatment goals of ARF?

Answer 145

Treatment of ARF consists of anti-inflammatory therapy, antibiotic therapy, and heart failure management.

Goals of treatment — The four major goals of treatment are:

●Symptomatic relief of acute disease manifestations (eg, arthritis)

●Eradication of group A beta-hemolytic Streptococcus (GAS)

●Prophylaxis against future GAS infection to prevent progression of cardiac disease

●Provision of education for the patient and patient’s caregivers

There is no therapy that slows progression of valvular damage in the setting of ARF.

Question 146

How do you treat GAS pharyngitis in ARF?

Answer 146

• Treatment should proceed as delineated for management of GAS pharyngitis, whether or not pharyngitis is present at the time of diagnosis (table 1).
• Treatment is given even if throat cultures are negative to ensure eradication of streptococci that may persist in the upper respiratory tract.
• In practice, the most convenient and sensible approach is to administer long-acting intramuscular penicillin G benzathine, which serves two purposes: to eradicate GAS carriage and also as the first dose of secondary prophylaxis that is given every 21 to 28 days.
• Oral alternatives, which should be used in the case of shortages of penicillin G benzathine or in the case of penicillin allergy, are listed in the table
• Penicillin allergy should be verified by history and confirmed with testing by an allergy specialist if necessary before choosing an alternative to penicillin G benzathine.

Question 147

How do you treat GAS pyoderma in ARF?

Answer 147

Patients from tropical regions such as Northern Australia, in whom ARF may be triggered by group A Streptococcus (GAS) pyoderma, require appropriate therapy for any skin infections present (e.g. Bactrim)

Question 148

Describe treatment of household contacts in ARF

Answer 148

Throat cultures (or evaluation for pyoderma if that was the GAS infection that identified the patient) should be performed on household contacts. Those with positive results should also receive a full course of antibiotic therapy, even if asymptomatic.

Question 149

How do you manage arthritis in ARF?

Answer 149

• Anti-inflammatory agents are the mainstay of symptomatic management of ARF-associated arthritis. Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) may also prevent involvement of new joints.
• Aspirin (up to 80 to 100 mg/kg per day in children and 4 to 8 g/day in adults, given in four to five divided doses) traditionally has been the first-line therapy
• Newer NSAIDs, particularly naproxen, have supplanted aspirin in the anti-inflammatory management of ARF.
• NSAIDs are given as a standing dose until symptoms resolve, typically in one to two weeks, although longer courses (6 to 12 weeks) are needed for persistent or rebound symptoms and elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
• glucocorticoids are reserved for patients who do not tolerate or are allergic to aspirin and/or naproxen.

Can add a PPI if the patient develops GI upset on an NSAID or is being treated with an oral glucocorticoid.

Anti-inflammatory therapy should be continued until all joint symptoms have resolved, as long as the medication is well tolerated. Most patients require treatment for one to two weeks, although some patients require a longer course of treatment up to eight weeks. Recurrence of arthritis with reduction in the dose of anti-inflammatory treatment most likely reflects the “rebound phenomenon” of ARF; this does not represent a recurrent episode of ARF, but rather that a longer course of treatment is required

Question 150

Naproxen vs. Aspirin in Tx of arthritis in ARF?

Answer 150

Naproxen has a superior side-effect profile to aspirin and can be dosed twice daily. Naproxen is dosed at 10 to 20 mg/kg/day in divided doses every 12 hours to a maximum of 1000 mg per day in children aged over two years and 250 to 500 mg twice daily to a maximum of 1250 mg in adults. Ibuprofen has been used successfully in younger children with rheumatic fever, but there are no specific published data to support its use.

Question 151

How do you manage carditis in ARF?

Answer 151

• early diagnosis and assessment of severity using echocardiography, management of heart failure and other complications when present, and commencement of secondary prophylaxis.
• no evidence that anti-inflammatory treatment improves cardiac outcomes.
• NSAIDs, glucocorticoids, and intravenous immune globulin (IVIG) are not routinely recommended for the treatment of carditis without joint symptoms.
• Patients with severe carditis (significant cardiomegaly, congestive heart failure, and/or third-degree heart block) should be treated with conventional therapy for heart failure. There may be a role for glucocorticoids in patients with severe carditis with acute cardiac failure.
• Valve surgery is rarely necessary in patients with acute rheumatic carditis, usually only in patients with valve leaflet or chordae tendineae rupture where surgery can be lifesaving. It may be necessary in patients with severe lesions that are identified later in life and in whom heart failure due to regurgitant mitral or aortic valve lesions cannot be managed with medical therapy alone.

Question 152

How do you manage syndenham chorea in ARF?

Answer 152

• Sydenham chorea is generally self-limited, and most cases do not require treatment beyond the usual chronic antibiotic therapy to prevent recurrence of ARF and minimize the risk of RHD.
• Psychologic and social support, including support for the educational needs of the child, are important elements of management
• Rest in a quiet setting can help minimize stressful factors that may worsen symptoms.
• Symptomatic treatment (eg, a dopamine 2 receptor blocking agent, carbamazepine, or valproic acid) is reserved for patients with symptoms that are distressing for the patient and their family or that interfere with activities of daily living or that place the patient at risk of injury.
• Anti-inflammatory/immunomodulatory therapies (eg, glucocorticoids, IVIG) are restricted to patients with severe chorea who have failed other therapy.
• In patients with moderate to severe chorea, referral to a pediatric neurologist or movement disorder specialist can help guide management.

Question 153

How do you treat erythema marginatum in ARF?

Answer 153

The rash associated with ARF is temporary and does not require specific treatment, although antihistamines may help to alleviate pruritus.

Question 154

How do you monitor patients that have had/are having ARF?

Answer 154

• Measurement of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) may be useful for monitoring the acute disease process.
• CRP is probably more useful since it typically normalizes over a matter of days once an episode of acute inflammation has resolved, while the ESR may stay elevated for up to two months after a transient inflammatory stimulus.
• However, the susceptibility of this measurement to artefact and other causes of inflammation may limit its use for this purpose. This monitoring can be performed by an experienced primary care clinician or ARF specialist.

Normalization of inflammatory markers is an indication of resolution, whereas an increase as treatment is tapered suggests a rebound of inflammation. A normal result obtained a few weeks after discontinuing anti-inflammatory therapy suggests that the course of the illness is complete (unless chorea appears)

Question 155

What are the risk factors associated with recurrent ARF?

Answer 155

●Poor adherence to secondary prophylaxis.

●A greater number of previous attacks.

●A shorter time interval since the last attack.

●A higher likelihood of ongoing exposure to streptococcal infections, which includes children, those in close contact with children (parents, health care workers), and those living in crowded situations (college students, military personnel)

●Younger age.

●Presence of cardiac involvement. Patients who have had rheumatic carditis (with or without valvular disease) are at relatively high risk for recurrent carditis and are likely to sustain increasingly severe cardiac involvement with each recurrence

Question 156

What is primary prevention of ARF?

Answer 156

Prevention of initial development of rheumatic fever (primary prevention) is accomplished by prompt diagnosis and antibiotic treatment of GAS tonsillopharyngitis.

Appropriate antibiotic treatment of streptococcal pharyngitis prevents ARF in most cases. However, at least one-third of ARF episodes occur in the setting of subclinical streptococcal infection. In addition, ARF is not preventable in symptomatic patients who do not seek medical care.

Question 157

What is secondary prevention (antibiotic prophylaxis) in ARF?

Answer 157

• Patients who have had an attack of ARF and develop subsequent GAS pharyngitis are at high risk for a recurrent attack of ARF.
• Rheumatic heart disease (RHD) becomes more severe with each recurrent episode.
• the most effective method to limit progression of RHD severity is prevention of recurrent GAS pharyngitis.
• recommend continuous antimicrobial prophylaxis, rather than recognition and treatment of acute GAS pharyngitis episodes, because GAS infection does not need to be symptomatic to trigger a recurrent attack of ARF.
• Continuous prophylaxis is warranted for patients with a well-documented history of ARF (including cases with Sydenham chorea as the sole manifestation), as well as those with definite evidence of RHD.
• Antibiotic prophylaxis is usually provided in the primary care setting rather than by tertiary care organizations and consulting cardiologists.

During the course of prophylaxis, patients and their household contacts who develop acute episodes of GAS pharyngitis should be evaluated and treated promptly. Patients with breakthrough GAS pharyngitis on penicillin should be treated with an alternative agent such as clindamycin.

Question 158

How long should secondary prevention of ARF last?

Answer 158

• years of prophylactic antibiotic administration.
• The total duration depends upon risk of recurrent ARF and severity of disease.
• In the setting of carditis, prophylaxis should continue until the patient is a young adult (21 years of age), which is usually approximately 10 years from the initial acute attack with no recurrence.
• Antibiotic prophylaxis should continue even after valve surgery, including prosthetic valve replacement.

ARF prophylaxis can be discontinued safely in young adults judged to be at low risk for recurrence who are maintained under careful prospective surveillance.

The risk for GAS exposure and severity of valvular disease should be reviewed upon reaching the end of a planned course for secondary prophylaxis. A decision regarding cessation or continuation of antibiotic prophylaxis should be made based upon individual clinical risks and benefits.

Question 159

What antibiotic should be used in secondary prophylaxis in ARF? how after are they treated? IM vs. oral?

Answer 159

• Parenteral prophylaxis with penicillin G benzathine is preferred for all patients.
• Oral agents are used in the case of shortages of penicillin G benzathine and are also appropriate for patients who are allergic to penicillin.
• Switching from intramuscular to oral prophylaxis once patients have reached young adulthood and have remained free of rheumatic attacks is appropriate if antibiotic prophylaxis is continued.
• preferred parenteral antibiotic for prophylaxis is long-acting penicillin G benzathine administered intramuscularly every 21 to 28 days. Most patients are started on a 28-day regimen. Patients that develop a breakthrough episode of ARF despite good adherence to a 28-day regimen can be switched to a 21-day regimen .
• A shorter dosing interval (eg, administration every two to three weeks) is appropriate for populations in which the incidence of ARF is particularly high. also warranted for individuals in low-incidence regions who have had recurrent ARF despite adherence to a regimen administered every four weeks.
• Options for oral prophylaxis include penicillin V, macrolides, and sulfadiazine. The preferred oral agent is penicillin V. A macrolide (eg, azithromycin) is usually the most appropriate agent for patients allergic to penicillin. Sulfadiazine and sulfisoxazole are less frequently used.
• Success with oral prophylaxis depends on patient adherence, so clear communication regarding the importance of prophylaxis and how antibiotics should be taken is critical. Even with optimal adherence, the risk of recurrence is higher in individuals receiving oral prophylaxis than those receiving intramuscular penicillin G benzathine.

Patients and their household contacts who develop symptoms suggestive of GAS pharyngitis during the course of prophylaxis should be evaluated and treated promptly

Question 160

What is post-strep reactive arthritis?

Answer 160

Poststreptococcal reactive arthritis (PSRA) is a reactive arthritis that occurs after a symptom-free interval following group A Streptococcus (GAS) pharyngitis. Whether it is a separate entity from arthritis associated with ARF is somewhat controversial since PSRA can be difficult to distinguish from arthritis associated with ARF on clinical grounds. In addition, a small proportion of patients with PSRA have been observed to develop valvular heart disease

Question 161

How to you manage PSRA if it is difficult to distinguish from ARF?

Answer 161

• some favor administering secondary prophylaxis to children from a low-risk group with suspected PSRA for one to two years after the onset of symptoms
• The echocardiogram is repeated at 12 to 24 months. Evidence of valvular disease after one year should prompt continued prophylaxis, and it may be presumed that the presenting symptoms were manifestations of ARF.
• Antibiotic prophylaxis is discontinued if the echocardiogram is normal, and the patient is re-evaluated annually over a period of a few years. However, children from high-risk groups (eg, an Aboriginal patient or Pacific Islander) are treated as having ARF.