2854 Fraenkel L et al: 2021 American College of Rheumatology guide- register-based RHD control programs, which have been

register-based RHD control programs, which have been proven to be

line for the treatment of rheumatoid arthritis. Arthritis Rheumatol cost-effective in reducing the burden of RHD. Enhancing awareness
73:1108, 2021. of RHD and mobilizing resources for its control in LMICs are issues
Gravallese EM, Firestein GS: Rheumatoid arthritis: Common ori- requiring international attention. In 2018, member states of the World
gins, divergent mechanisms. N Engl J Med 388:529, 2023. Health Organization (WHO) unanimously adopted a Global Resolu-
Karimi J et al: Genetic implications in the pathogenesis of rheumatoid tion on Rheumatic Fever and Rheumatic Heart Disease, calling on all
PART 11

arthritis; an updated review. Gene 702:8, 2019. states as well as international stakeholders and the WHO itself to take
Moreland LW et al: A randomized comparative effectiveness study practical actions to control these diseases.
of oral triple therapy versus methotrexate plus etanercept in early
aggressive rheumatoid arthritis: The Treatment of Early Aggressive EPIDEMIOLOGY
ARF is mainly a disease of children aged 5–14 years. Initial episodes
Immune-Mediated, Inflammatory, and Rheumatologic Disorders

Rheumatoid Arthritis Trial. Arthritis Rheum 64:2824, 2012.

become less common in older adolescents and young adults and are rare
VIDEO 370-1 Transverse view of 2nd MCP demonstrating synovial hypertrophy in persons aged >30 years. By contrast, recurrent episodes of ARF remain
with abnormal power doppler signal (yellow) consistent with synovitis. Synovial relatively common in adolescents and young adults. This pattern con-
proliferation is displacing the overlying extensor tendon of the digit above the trasts with the prevalence of RHD, which peaks between 25 and 40 years.
joint space. This view demonstrates small erosions of the dorsal metacarpal head. There is no clear gender association for ARF, but RHD more commonly
(Courtesy of Dr. Philip Chu.) affects females, sometimes up to twice as frequently as males.
VIDEO 370-2 Longitudinal dorsal view of the 2nd MCP demonstrating synovial
hypertrophy with abnormal power doppler signal (yellow) consistent with synovitis. PATHOGENESIS
(Courtesy of Dr. Philip Chu)
■■ORGANISM FACTORS
VIDEO 370-3 Transverse view of 2nd MCP demonstrating synovial hypertrophy and
intrasynovial effusion with abnormal power doppler signal (yellow) consistent with
Conventional teaching has it that ARF is exclusively caused by infection
synovitis. Fluid and synovial proliferation is displacing the overlying extensor tendon of the upper respiratory tract with group A streptococci (Chap. 153).
of the digit above the joint space. (Courtesy of Dr. Philip Chu.) Although classically, certain M-serotypes (particularly types 1, 3, 5, 6,
14, 18, 19, 24, 27, and 29) were associated with ARF, recent evidence
demonstrates that many more M-serotypes are rheumatogenic and
that so-called “rheumatogenic motifs” are found in only a minority of
serotypes associated with rheumatic fever. This epidemiologic evidence
also points to a clear role of skin infection in the pathogenesis of ARF.

371 Acute Rheumatic Fever

Joseph Kado, Jonathan Carapetis
The potential role of groups C and G streptococci is unclear at this time.
■■HOST FACTORS
Based on epidemiologic evidence, ~3–6% of any population may be sus-
ceptible to ARF, and this proportion does not vary dramatically between
Acute rheumatic fever (ARF) is a multisystem disease resulting from populations. Findings of familial clustering of cases and concordance
an autoimmune reaction to infection with group A Streptococcus. in monozygotic twins—particularly for chorea—confirm that suscep-
Although many parts of the body may be affected, almost all of the tibility to ARF is an inherited characteristic, with 44% concordance in
manifestations resolve completely. The major exception is cardiac monozygotic twins compared to 12% in dizygotic twins and heritability
valvular damage (rheumatic heart disease [RHD]), which may persist more recently estimated at 60%. Most evidence for host factors focuses
after the other features have disappeared. on immunologic determinants. Initial studies found associations with
human leukocyte antigen (HLA) class II alleles, some protective and
some associated with increased susceptibility, as well as polymorphisms
GLOBAL CONSIDERATIONS in tumor necrosis factor and mannose binding lectin. Recent genome-
ARF and RHD are diseases of poverty. They were common in all coun- wide association studies and genomic sequencing analyses have identi-
tries until the early twentieth century, when their incidence began to fied associations with a range of genes including the immunoglobulin
decline in industrialized nations. This decline was largely attributable heavy chain (IGH) locus (specifically the IGHV4-61*02 allele), comple-
to improved living conditions—particularly less crowded housing and ment factor H, and some HLA class II (a range of HLA-DQ A and B
better hygiene—which resulted in reduced transmission of group A alleles) and III loci. The associations are often population dependent,
streptococci. The introduction of antibiotics and improved systems of although increasing consistency is being found across populations in
medical care had a supplemental effect. meta-analyses of genomic studies. Over coming years, further genomic
The virtual disappearance of ARF and reduction in the incidence of analyses are expected to provide additional insights into ARF and RHD
RHD in high-income countries during the first half of the twentieth pathogenesis, as well as host protective and susceptibility factors.
century unfortunately was not replicated in low- and middle-income
countries (LMICs), where these diseases continue unabated. RHD is ■■THE IMMUNE RESPONSE
the most common cause of acquired heart disease in children in LMICs The most widely accepted theory of rheumatic fever pathogenesis
and is a major cause of mortality and morbidity in adults as well. It is based on the concept of molecular mimicry, whereby an immune
is estimated that >40 million people worldwide are affected by RHD, response targeted at streptococcal antigens (mainly thought to be on
with >300,000 deaths occurring each year. Some 95% of ARF cases and the M protein) also recognizes human tissues. In this model, antigen
RHD deaths now occur in developing countries, with particularly high processing cells of the innate immune system present streptococcal
burdens in sub-Saharan Africa, Pacific nations, Australasia, China, antigens after throat (and possibly skin) group A streptococcal infec-
and South and Central Asia. The pathogenetic pathway from exposure tion to T cells, which then lead to activation of both humoral and cellu-
to group A Streptococcus followed by pharyngeal or superficial skin lar immunity. Cross-reactive antibodies bind to endothelial cells on the
infection and subsequent development of ARF, ARF recurrences, and heart valve, leading to activation of the adhesion molecule VCAM-1,
development of RHD and its complications is associated with a range with resulting recruitment of activated lymphocytes and lysis of endo-
of risk factors and, therefore, potential interventions at each point thelial cells in the presence of complement. The latter leads to release
(Fig. 371-1). In affluent countries, many of these risk factors are well of peptides including laminin, keratin, and tropomyosin, which, in
controlled, and where needed, interventions are in place. Unfortu- turn, activates cross-reactive T cells that invade the heart, amplifying
nately, the greatest burden of disease is found in LMICs, most of which the damage and causing epitope spreading. An alternative hypothesis
do not have the resources, capacity, and/or interest to tackle this multi- proposes that the initial damage is due to streptococcal invasion of
faceted disease. In particular, few of these countries have coordinated, epithelial surfaces, with binding of M protein to type IV collagen
 2855
Asymptomatic infection Inherited susceptibility Poor access to health care Poor access to health care
Overcrowded living
conditions
Failure to seek health care Female gender (chorea) Poor delivery of secondary Lack of medication
Risk for sore throat prophylaxis

CHAPTER 371 Acute Rheumatic Fever

Poverty
factors Poor access to health care Lack of cardiac surgical
Asymptomatic or facilities
Rural residence Inadequate diagnosis and
treatment of streptococcal undiagnosed acute
pharyngitis rheumatic fever
Urban slum residence

Treatment failure

Recurrent Heart
acute rheumatic failure
fever
Exposure to Group A streptococcal Rheumatic Surgery
Acute rheumatic
group A upper respiratory tract heart Disability
fever
streptococcus infection* disease (RHD) Death

Stroke
Endocarditis

Economic Better diagnosis and Improved access Secondary prophylaxis

Good treatment of sore throat in to health care Better primary care
development
evidence primary care Register-based programs
base Register-based control programs
Better living
conditions Integration of RHD control
into primary care, childhealth, Specialist services
and noncommunicable • Cardiology
Opportunities disease programs • Cardiac surgery
for
Intervention

Systematic sore throat Echocardiographic screening

Unproven/ screening and treatment
Hypothesized/ programs
Future (Immunotherapies)
(Vaccine)

(Skin infection
control programs)
*Increasing evidence of the role of streptococcal skin infection
FIGURE 371-1 Pathogenetic pathway for acute rheumatic fever and rheumatic heart disease (RHD), with associated risk factors and opportunities for intervention at each
step. Interventions in parentheses are either unproven or currently unavailable.

allowing it to become immunogenic, but not through the mechanism regurgitation, sometimes accompanied by aortic regurgitation. Myo-
of molecular mimicry. cardial inflammation may affect electrical conduction pathways, lead-
ing to P-R interval prolongation (first-degree atrioventricular block or
CLINICAL FEATURES rarely higher-level block) and softening of the first heart sound.
There is a latent period of ~3 weeks (1–5 weeks) between the precipitat- People with RHD are often asymptomatic for many years before their
ing group A streptococcal infection and the appearance of the clinical valvular disease progresses to cause cardiac failure. Moreover, particularly
features of ARF. The exceptions are chorea and indolent carditis, which in resource-poor settings, the diagnosis of ARF is often not made, so
may follow prolonged latent periods lasting up to 6 months. Although children, adolescents, and young adults may have RHD but not know it.
many patients report a prior sore throat, the preceding group A strep- These cases can be diagnosed using echocardiography; auscultation is
tococcal infection is commonly subclinical; in these cases, it can only poorly sensitive and specific for RHD diagnosis in asymptomatic patients.
be confirmed using streptococcal antibody testing. The most common Echocardiographic screening of school-aged children in populations with
clinical features are polyarthritis (present in 60–75% of cases) and car- high rates of RHD is becoming more widespread and has been facilitated
ditis (50–75%). The prevalence of chorea in ARF varies substantially by improving technologies in portable echocardiography and the avail-
between populations, ranging from <2 to 30%. Erythema marginatum ability of consensus guidelines for the diagnosis of RHD on echocardiog-
and subcutaneous nodules are now rare, being found in <5% of cases. raphy (Table 371-1). These guidelines replace the previous “definite,”
“borderline,” and “latent” diagnostic category terms with a classification
■■HEART INVOLVEMENT based on the risk of progression to more advanced valvular heart disease
Up to 75% of patients with ARF progress to RHD. The endocardium, and provide recommendations on secondary prophylaxis for each group.
pericardium, or myocardium may be affected. Valvular damage is
the hallmark of rheumatic carditis. The mitral valve is almost always ■■JOINT INVOLVEMENT
affected, sometimes together with the aortic valve; isolated aortic valve The most common form of joint involvement in ARF is arthritis, i.e.,
involvement is rare. Damage to the pulmonary or tricuspid valves is objective evidence of inflammation, with hot, swollen, red, and/or ten-
usually secondary to increased pulmonary pressures resulting from der joints, and involvement of more than one joint (i.e., polyarthritis).
left-sided valvular disease. Early valvular damage leads to regurgita- Polyarthritis is typically migratory, moving from one joint to another
tion. Over ensuing years, usually as a result of recurrent episodes, leaf- over a period of hours. ARF almost always affects the large joints—
let thickening, scarring, calcification, and valvular stenosis may develop most commonly the knees, ankles, hips, and elbows—and is asymmet-
(Fig. 371-2). See Videos 371-1 and 371-2. Therefore, the characteristic ric. The pain is severe and usually disabling until anti-inflammatory
manifestation of carditis in previously unaffected individuals is mitral medication is commenced.
 2856
TABLE 371-1 Staging of Rheumatic Heart Disease Detected by
Echocardiographya,b
Stage A: Minimal Echocardiographic Criteria for RHD
RV
Applies only to individuals aged ≤20 years old
• Clinical risk: might be at risk of valvular heart disease progression
PART 11

• Echocardiographic features: the presence of mildc MR or AR without

morphologic features
AV
LV Stage B: Mild RHD
Can apply to any age
Immune-Mediated, Inflammatory, and Rheumatologic Disorders

• Clinical risk: at moderate or high risk of progression and at risk of developing

MV
symptoms of valvular heart disease
• Echocardiographic features: evidence of mildc valvular regurgitation plus at
LA least one morphologic feature in individuals aged ≤20 years and at least two
morphologic features in individuals aged >20 yearsd; or mild regurgitation in
both mitral and aortic valves
Stage C: Advanced RHD at Risk of Clinical Complications
Can apply to any age
• Clinical risk: at high risk of developing clinical complications that require
medical or surgical intervention
• Echocardiographic features: moderate or severe MR, moderate or severe AR,
FIGURE 371-2 Transthoracic echocardiographic image from a 5-year-old boy any MS or ASe, pulmonary hypertension, and decreased LV systolic function
with chronic rheumatic heart disease. This diastolic image demonstrates leaflet
thickening, restriction of the anterior mitral valve leaflet tip, and doming of the body Stage D: Advanced RHD with Clinical Complications
of the leaflet toward the interventricular septum. This appearance (marked by the Can apply to any age
arrowhead) is commonly described as a “hockey stick” or an “elbow” deformity.
• Clinical risk: established clinical complications include cardiac surgery, heart
AV, aortic valve; LA, left atrium; LV, left ventricle; MV, mitral valve; RV, right ventricle.
failure, arrhythmia, stroke, and infective endocarditis
(Courtesy of Dr. Bo Remenyi, Department of Paediatric and Congenital Cardiac
Services, Starship Children’s Hospital, Auckland, New Zealand.) • Echocardiographic features: moderate or severe MR, moderate or severe AR,
any MS or ASe, pulmonary hypertension, and decreased LV systolic function
a
To be applied in high-risk settings and requires other causes of valvular heart
Less severe joint involvement is also relatively common and has disease to have been excluded. bAfter the application of the confirmatory
been recognized as a potential major manifestation in high-risk echocardiographic criteria, diagnostic categories might include “normal” and
“other,” which encompasses other diseases such as congenital heart disease,
populations in the most recent revision of the Jones criteria. Arthralgia cardiomyopathies, and pericardial effusion. cFulfilling the confirmatory criteria for
without objective joint inflammation usually affects large joints in the pathologic regurgitation (see Source). dThis cutoff value is derived from expert
same migratory pattern as polyarthritis. In some populations, aseptic consensus. eAortic stenosis is defined in accordance with international guidelines on
valvular heart disease. A diagnosis of rheumatic aortic stenosis requires the exclusion
monoarthritis may be a presenting feature of ARF, which may, in turn, of other causes, including bicuspid aortic valve and degenerative calcific AS.
result from early commencement of anti-inflammatory medication Abbreviations: AR, aortic regurgitation; AS, aortic stenosis; LV, left ventricular; MR,
before the typical migratory pattern is established. mitral regurgitation; MS, mitral stenosis, RHD, rheumatic heart disease.
The joint manifestations of ARF are highly responsive to salicylates Source: Reproduced with permission from J Rwebembera et al: 2023 World Heart
and other nonsteroidal anti-inflammatory drugs (NSAIDs). Federation guidelines for the echocardiographic diagnosis of rheumatic heart
disease. Nat Rev Cardiol 21:250; 2023.
■■CHOREA
Sydenham’s chorea commonly occurs in the absence of other manifes- ■■OTHER FEATURES
tations, follows a prolonged latent period after group A streptococcal Fever occurs in most cases of ARF, although rarely in cases of pure
infection, and is found mainly in females. The choreiform movements chorea. Although high-grade fever (≥39°C) is the rule, lower grade
affect particularly the head (causing characteristic darting movements temperature elevations are not uncommon. Elevated acute-phase reac-
of the tongue) and the upper limbs (Chap. 447). They may be gen- tants are also present in most cases.
eralized or restricted to one side of the body (hemi-chorea). In mild
cases, chorea may be evident only on careful examination, whereas in ■■EVIDENCE OF A PRECEDING GROUP A
the most severe cases, the affected individuals are unable to perform STREPTOCOCCAL INFECTION
activities of daily living. There is often associated emotional lability With the exception of chorea and low-grade carditis, both of which
or obsessive-compulsive traits, which may last longer than the chorei- may become manifest many months later, evidence of a preceding
form movements (which usually resolve within 6 weeks but sometimes group A streptococcal infection is essential in making the diagnosis of
may take up to 6 months). More than 50% of patients presenting with ARF. Because most cases do not have a positive throat swab culture or
chorea will have carditis, for which reason echocardiography should be rapid antigen test, serologic evidence is usually needed. The most com-
part of the workup. mon serologic tests are the anti-streptolysin O (ASO) and anti-DNase
B (ADB) titers. Where possible, age-specific reference ranges should
■■SKIN MANIFESTATIONS be determined in a local population of healthy people without a recent
The classic rash of ARF is erythema marginatum (Chap. 21), which group A streptococcal infection.
begins as pink macules that clear centrally, leaving a serpiginous,
spreading edge. The rash is evanescent, appearing and disappearing ■■CONFIRMING THE DIAGNOSIS
before the examiner’s eyes. It occurs usually on the trunk, sometimes Because there is no definitive test, the diagnosis of ARF relies on the
on the limbs, but almost never on the face. presence of a combination of typical clinical features together with
Subcutaneous nodules occur as painless, small (0.5–2 cm), mobile evidence of the precipitating group A streptococcal infection, and the
lumps beneath the skin overlying bony prominences, particularly of the exclusion of other diagnoses. This uncertainty led Dr. T. Duckett Jones
hands, feet, elbows, occiput, and occasionally the vertebrae. They are a in 1944 to develop a set of criteria (subsequently known as the Jones
delayed manifestation, appearing 2–3 weeks after the onset of disease, criteria) to aid in the diagnosis. The most recent revision of the Jones
last for just a few days up to 3 weeks, and are commonly associated criteria (Table 371-2) requires the clinician to determine if the patient
with carditis. is from a setting or population known to experience low rates of ARF.
 2857
TABLE 371-2 Jones Criteria TABLE 371-3 Testing and Monitoring of ARF in the Acute Setting
A. For All Patient Populations with Evidence of Preceding Group A Investigations
Streptococcal Infection Always request:
Diagnosis: initial ARF 2 major manifestations or 1 major plus • Electrocardiogram (ECG)

CHAPTER 371 Acute Rheumatic Fever

2 minor manifestations
• Echocardiogram
Diagnosis: recurrent ARF 2 major or 1 major and 2 minor or • Complete blood count (CBC)
3 minor
• C-reactive protein (CRP)
B. Major Criteria
• Streptococcal serology (antistreptolysin and anti-DNase B)
Low-risk populationsa Moderate- and high-risk populations In relevant situations:
Carditisb Carditis • Throat swab
• Clinical and/or subclinical • Clinical and/or subclinical • Skin sore swab
Arthritis Arthritis • Blood cultures
• Polyarthritis only • Monoarthritis or polyarthritis • Synovial fluid aspirate
• Polyarthralgiac • Ensure sample does not clot by using correct tubes that have been well
Chorea Chorea mixed and transported promptly to the laboratory
• Include request for cell count, microscopy, culture, and gonococcal
Erythema marginatum Erythema marginatum
polymerase chain reaction (PCR)
SC nodules SC nodules • Pregnancy test
C. Minor Criteria • Creatinine test (UEC [urea, electrolytes, creatinine]) since nonsteroidal
Low-risk populationsa Moderate- and high-risk populations anti-inflammatory drugs can affect renal function
Polyarthralgia Monoarthralgia Tests to exclude alternative diagnoses, depending on clinical presentation
and locally endemic infections:
Fever (≥38.5°C) Fever (≥38°C)
• Autoantibodies, double-stranded DNA, anti–cyclic citrullinated peptide
 ESR ≥60 mm in the first hour and/or  ESR ≥30 mm/h and/or CRP ≥3.0 mg/dLd (anti-CCP) antibodies
CRP ≥3.0 mg/dLd
• Urine for Neisseria gonorrhoeae molecular test
 Prolonged PR intervale, after  Prolonged PR intervale, after • Urine for Chlamydia trachomatis molecular test
accounting for age variability (unless accounting for age variability (unless
carditis is a major criterion) carditis is a major criterion) • Serologic or other testing for viral hepatitis, Yersinia spp., cytomegalovirus
(CMV), parvovirus B19, respiratory viruses, Ross River virus, Barmah Forest
a
Low-risk populations are those with ARF incidence ≤2 per 100,000 school-age virus
children or all-age rheumatic heart disease prevalence of ≤1 per 1000 population
per year. bSubclinical carditis indicates echocardiographic valvulitis. (See source Source: Reproduced with permission from RDHAustralia, Menzies School of Health
document.) cPolyarthralgia should only be considered as a major manifestation Research. RHDAustralia (ARF/RHD writing group). The 2020 Australian guideline
in moderate- to high-risk populations after exclusion of other causes. As in past for prevention, diagnosis and management of acute rheumatic fever and rheumatic
versions of the criteria, erythema marginatum and SC nodules are rarely “stand- heart disease (3rd edition); 2020. Available at [Link]
alone” major criteria. Additionally, joint manifestations can only be considered in arf-rhd-guideline.
either the major or minor categories but not both in the same patient. (See source
document for more information.) dCRP value must be greater than upper limit of penicillin, 500 mg [250 mg for children ≤27 kg] PO twice daily, or
normal for laboratory. Also, because ESR may evolve during the course of ARF, peak amoxicillin, 50 mg/kg [maximum, 1 g] daily, for 10 days) or as a
ESR values should be used. eProlonged PR interval can only be considered in the
absence of carditis as a major criterion. single dose of 1.2 million units (600,000 units for children ≤27 kg)
Abbreviations: ARF, acute rheumatic fever; CRP, C-reactive protein; ESR, erythrocyte IM benzathine penicillin G.
sedimentation rate; SC, subcutaneous.
SALICYLATES AND NSAIDS
Source: Reproduced with permission from MH Gewitz et al: Revision of the
Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler These may be used for the treatment of arthritis, arthralgia, and
echocardiography: A scientific statement from the American Heart Association. fever once the diagnosis is confirmed. They are of no proven value
Circulation 131(20):1806, 2015. [Link] in the treatment of carditis or chorea. Aspirin has traditionally
CIR.0000000000000205.
been the first-line choice, delivered at a dose of 50–60 mg/kg per
day, up to a maximum of 80–100 mg/kg per day (4–8 g/d in
For this group, there is a set of “low-risk” criteria; for all others, there is adults) in 4–5 divided doses. At higher doses, the patient should
a set of more sensitive criteria. be monitored for symptoms of salicylate toxicity such as nausea,
vomiting, or tinnitus; if symptoms appear, lower doses should be
TREATMENT used. Owing to the frequency of gastrointestinal side effects and
the potential of more severe adverse effects of aspirin, many clini-
Acute Rheumatic Fever cians now prefer to use naproxen at a dose of 10–20 mg/kg per day
Patients with possible ARF should be followed closely to ensure because it may be safer than aspirin and has the advantage of twice-
that the diagnosis is confirmed, treatment of heart failure and other daily dosing. When the acute symptoms are substantially resolved,
symptoms is undertaken, and preventive measures including com- usually within the first 2 weeks, patients on higher doses of anti-
mencement of secondary prophylaxis, inclusion on an ARF registry, inflammatory medications can have the dose reduced for a further
and health education are commenced. Echocardiography should be 2–4 weeks. Fever, joint manifestations, and elevated acute-phase
performed on all possible cases to aid in making the diagnosis and reactants sometimes recur up to 3 weeks after the medication is
to determine the severity at baseline of any carditis. Other tests that discontinued. This does not indicate a recurrence and can be man-
should be performed are listed in Table 371-3. aged by recommencing anti-inflammatory agents for a brief period.
There is no treatment for ARF that has been proven to alter the CONGESTIVE HEART FAILURE
likelihood of developing, or the severity of, RHD. With the excep-
tion of treatment of heart failure, which may be lifesaving in cases Glucocorticoids The use of glucocorticoids in ARF remains con-
of severe carditis, the treatment of ARF is symptomatic. troversial. Two meta-analyses have failed to demonstrate a benefit
of glucocorticoids compared to placebo or salicylates in improving
ANTIBIOTICS the short- or longer-term outcome of carditis. However, the studies
All patients with ARF should receive antibiotics sufficient to treat the included in these meta-analyses all took place >40 years ago and did
precipitating group A streptococcal infection (Chap. 153). Penicil- not use medications in common usage today. There are some recent
lin is the drug of choice and can be given orally (as phenoxymethyl data that suggest corticosteroids improve laboratory, radiologic,
 2858 and echocardiographic parameters in carditis. Many clinicians treat A streptococcal sore throat with antibiotics). If commenced within 9
cases of severe carditis (causing heart failure) with glucocorticoids days of sore throat onset, a course of penicillin (as outlined above for
in the belief that they may reduce the acute inflammation and result treatment of ARF) will prevent almost all cases of ARF that would oth-
in more rapid resolution of failure. However, the potential benefits erwise have developed. In settings where ARF and RHD are common
of this treatment should be balanced against the possible adverse but microbiologic diagnosis of group A streptococcal pharyngitis is not
effects. If used, prednisone or prednisolone is recommended at a available, such as in resource-poor countries, primary care guidelines
PART 11

dose of 1–2 mg/kg per day (maximum, 80 mg), usually for a few sometimes recommend that all patients with sore throat be treated with
days or up to a maximum of 3 weeks. penicillin (an approach that has the potential drawbacks that come
MANAGEMENT OF HEART FAILURE from antibiotic overuse, including side effects and increasing pres-
sure on antimicrobial resistance in group A Streptococcus or bystander
See Chap. 265.
Immune-Mediated, Inflammatory, and Rheumatologic Disorders

pathogens) or, alternatively, that a clinical algorithm be used to identify

BED REST patients with a higher likelihood of group A streptococcal pharyngitis.
Traditional recommendations for long-term bed rest, once the cor- Although imperfect, such approaches recognize the importance of ARF
nerstone of management, are no longer widely practiced. Instead, prevention at the expense of overtreating many cases of sore throat that
bed rest should be prescribed as needed while arthritis and arthral- are not caused by group A Streptococcus. Although there is no proof
gia are present and for patients with heart failure. Once symptoms that antibiotic treatment of group A streptococcal skin infections can
are well controlled, gradual mobilization can commence as tolerated. prevent ARF, the increasing evidence that impetigo is strongly associ-
ated with ARF in some populations argues for a focus on treatment
CHOREA and prevention of group A streptococcal skin infections as part of a
Medications to control the abnormal movements do not alter the comprehensive ARF control strategy in regions with endemic impetigo.
duration or outcome of chorea. Milder cases can usually be man-
aged by providing a calm environment. In patients with severe cho- ■■SECONDARY PREVENTION
rea, carbamazepine or sodium valproate is preferred to haloperidol. The mainstay of controlling ARF and RHD is secondary prevention.
A response may not be seen for 1–2 weeks, and medication should Because patients with ARF are at dramatically higher risk than the gen-
be continued for 1–2 weeks after symptoms subside. There is recent eral population of developing a further episode of ARF after a group
evidence that corticosteroids are effective and lead to more rapid A streptococcal infection, they should receive long-term penicillin
symptom reduction in chorea. They should be considered in severe prophylaxis to prevent recurrences. The best antibiotic for secondary
or refractory cases. Prednisone or prednisolone may be commenced prophylaxis is benzathine penicillin G (1.2 million units, or 600,000
at 0.5 mg/kg daily, with weaning as early as possible, preferably units if ≤27 kg) delivered intramuscularly every 4 weeks. It can be given
after 1 week if symptoms are reduced, although slower weaning or every 3 weeks, or even every 2 weeks, to persons considered to be at
temporary dose escalation may be required if symptoms worsen. particularly high risk, although in settings where good compliance
with an every-4-week dosing schedule can be achieved, more frequent
INTRAVENOUS IMMUNOGLOBULIN (IVIG) dosing is rarely needed. Evidence has emerged recently that subcutane-
Small studies have suggested that IVIg may lead to more rapid reso- ous delivery of benzathine penicillin G provides more optimal pharma-
lution of chorea but have shown no benefit on the short- or long- cokinetics than intramuscular delivery and may have added advantages
term outcome of carditis in ARF without chorea. In the absence of reducing pain and allowing for larger doses to be delivered less
of better data, IVIg is not recommended except in cases of severe frequently, although this approach is yet to be recommended in clinical
chorea refractory to other treatments. guidelines. Oral penicillin V (250 mg) can be given twice daily instead
but is less effective than benzathine penicillin G. Penicillin-allergic
patients can receive erythromycin (250 mg) twice daily.
PROGNOSIS The duration of secondary prophylaxis is determined by many fac-
Untreated, ARF lasts on average 12 weeks. With treatment, patients tors, in particular the duration since the last episode of ARF (recur-
are usually discharged from hospital within 1–2 weeks. Inflammatory rences become less likely with increasing time), age (recurrences are
markers should be monitored every 1–2 weeks until they have normal- less likely with increasing age), and the severity of RHD (if severe, it
ized (usually within 4–6 weeks), and an echocardiogram should be may be prudent to avoid even a very small risk of recurrence because
performed after 1 month to determine if there has been progression of of the potentially serious consequences) (Table 371-4). Secondary
carditis. Cases with more severe carditis need close clinical and echo- prophylaxis is best delivered as part of a coordinated RHD control pro-
cardiographic monitoring in the longer term. gram, based around a registry of patients. Registries improve the ability
Once the acute episode has resolved, the priority in management is to follow patients and identify those who default from prophylaxis and
to ensure long-term clinical follow-up and adherence to a regimen of to institute strategies to improve adherence.
secondary prophylaxis. Patients should be entered onto the local ARF
registry (if present) and contact made with primary care practitioners
to ensure a plan for follow-up and administration of secondary prophy- TABLE 371-4 American Heart Association Recommendations for
laxis before the patient is discharged. Patients and their families should Duration of Secondary Prophylaxisa
also be educated about their disease, emphasizing the importance of CATEGORY OF PATIENT DURATION OF PROPHYLAXIS
adherence to secondary prophylaxis. Rheumatic fever without carditis For 5 years after the last attack or 21
years of age (whichever is longer)
PREVENTION Rheumatic fever with carditis but no For 10 years after the last attack, or 21
residual valvular disease years of age (whichever is longer)
■■PRIMARY PREVENTION
Rheumatic fever with persistent For 10 years after the last attack, or
Ideally, primary prevention would entail elimination of the major risk valvular disease, evident clinically or 40 years of age (whichever is longer);
factors for streptococcal infection, particularly overcrowded housing. on echocardiography sometimes lifelong prophylaxis
This is difficult to achieve in most places where ARF is common but
must remain a priority in ongoing efforts to achieve global control of
a
These are only recommendations and must be modified by individual
circumstances as warranted. Note that some organizations recommend a minimum
ARF and RHD. of 10 years of prophylaxis after the most recent episode, or until 21 years of age
Concerted international efforts are underway to develop a vaccine (whichever is longer), regardless of the presence of carditis with the initial episode.
against group A Streptococcus that would prevent infection of the throat Source: Reproduced with permission from MA Gerber et al: Prevention
or skin and consequently prevent ARF in the absence of a suitable vac- of rheumatic fever and diagnosis and treatment of acute streptococcal
pharyngitis. Circulation 119:1541, 2009. [Link]
cine; however, the mainstay of primary prevention for ARF remains CIRCULATIONAHA.109.191959?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.
primary prophylaxis (i.e., the timely and complete treatment of group org&rfr_dat=cr_pub%20%200pubmed.