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Chapter 371 | Acute Rheumatic Fever

Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders · Part 11 – Rheumatology & Immunology

Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition

🔑 Key Clinical Points

  1. Acute rheumatic fever (ARF) is a multisystem autoimmune disease resulting from infection with group A Streptococcus (GAS).
  2. Valvular damage is the hallmark of rheumatic carditis; the mitral valve is almost always affected.
  3. Diagnosis requires evidence of preceding GAS infection plus 2 major or 1 major + 2 minor Jones criteria manifestations.
  4. Secondary prophylaxis with benzathine penicillin G (1.2 million units IM every 4 weeks) is the mainstay of preventing recurrence.
  5. Rheumatic heart disease (RHD) is the most common cause of acquired heart disease in children in low- and middle-income countries (LMICs).
  6. Molecular mimicry is the accepted pathogenesis theory: immune response to streptococcal antigens (M protein) cross-reacts with human tissues.
  7. Chorea (Sydenham's) may occur in the absence of other manifestations and follows a prolonged latent period (up to 6 months).
  8. Echocardiography is essential for diagnosing subclinical carditis and staging RHD (Stages A-D).
  9. Low-risk populations (ARF incidence ≤ 2 per 100,000) have different Jones criteria thresholds compared to moderate/high-risk populations.
  10. Primary prevention focuses on timely treatment of GAS pharyngitis; secondary prevention focuses on long-term antibiotic prophylaxis.

📑 Table of Contents

📋 Figures in This Chapter

# Type Description
1 🔀 Flowchart Pathogenetic pathway for acute rheumatic fever and rheumatic heart step
1 🖼 Figure Transthoracic echocardiographic image from a 5-year-old boy with chronic rheumatic heart disease
2 🖼 Figure Figure / Illustration

1. DEFINITION & OVERVIEW

📖 Harrison's defines this as:

Acute rheumatic fever (ARF) is a multisystem disease resulting from an autoimmune reaction to infection with group A Streptococcus.

  • Acute rheumatic fever (ARF) is a multisystem disease resulting from an autoimmune reaction to infection with group A Streptococcus.
  • Although many parts of the body may be affected, almost all of the manifestations resolve completely.
  • The major exception is cardiac valvular damage (rheumatic heart disease [RHD]), which may persist after the other features have disappeared.
  • RHD is the most common cause of acquired heart disease in children in low- and middle-income countries (LMICs).
  • It is estimated that >40 million people worldwide are affected by RHD, with >300,000 deaths occurring each year.
  • Some 95% of ARF cases and RHD deaths now occur in developing countries, with particularly high burdens in sub-Saharan Africa, Pacific nations, Australasia, China, and South and Central Asia.

1.1 Historical Context

  • ARF and RHD were common in all countries until the early twentieth century, when their incidence began to decline in industrialized nations.
  • This decline was largely attributable to improved living conditions—particularly less crowded housing and better hygiene—which resulted in reduced transmission of group A streptococci.
  • The introduction of antibiotics and improved systems of medical care had a supplemental effect.
  • The virtual disappearance of ARF and reduction in the incidence of RHD in high-income countries during the first half of the twentieth century unfortunately was not replicated in low- and middle-income countries (LMICs), where these diseases continue unabated.

1.2 Global Considerations

  • ARF and RHD are diseases of poverty.
  • In affluent countries, many of these risk factors are well controlled, and where needed, interventions are in place.
  • Unfortunately, the greatest burden of disease is found in LMICs, most of which do not have the resources, capacity, and/or interest to tackle this multifaceted disease.
  • In 2018, member states of the World Health Organization (WHO) unanimously adopted a Global Resolution on Rheumatic Fever and Rheumatic Heart Disease, calling on all states as well as international stakeholders and the WHO itself to take practical actions to control these diseases.

2. EPIDEMIOLOGY

  • ARF is mainly a disease of children aged 5–14 years.
  • Initial episodes become less common in older adolescents and young adults and are rare in persons aged >30 years.
  • Recurrent episodes of ARF remain relatively common in adolescents and young adults.
  • This pattern contrasts with the prevalence of RHD, which peaks between 25 and 40 years.
  • There is no clear gender association for ARF.
  • RHD more commonly affects females, sometimes up to twice as frequently as males.
  • Based on epidemiologic evidence, ~3–6% of any population may be susceptible to ARF, and this proportion does not vary dramatically between populations.

2.1 Risk Factors

  • Exposure to Group A streptococcal upper respiratory tract infection.
  • Overcrowded living conditions.
  • Rural residence.
  • Urban slum residence.
  • Poverty.
  • Poor access to health care.
  • Failure to seek health care.
  • Female gender (chorea).
  • Inadequate diagnosis and treatment of streptococcal pharyngitis.
  • Treatment failure.
  • Recurrent acute rheumatic fever.

3. ETIOLOGY & PATHOPHYSIOLOGY

  • Conventional teaching has it that ARF is exclusively caused by infection of the upper respiratory tract with group A streptococci (Chap. 153).
  • 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.
  • 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.
  • The potential role of groups C and G streptococci is unclear at this time.
  • An alternative hypothesis proposes that the initial damage is due to streptococcal invasion of epithelial surfaces, with binding of M protein to type IV collagen allowing it to become immunogenic, but not through the mechanism of molecular mimicry.

3.1 Host Factors

  • Findings of familial clustering of cases and concordance in monozygotic twins—particularly for chorea—confirm that susceptibility to ARF is an inherited characteristic.
  • Concordance is 44% in monozygotic twins compared to 12% in dizygotic twins.
  • Heritability more recently estimated at 60%.
  • Most evidence for host factors focuses on immunologic determinants.
  • Initial studies found associations with human leukocyte antigen (HLA) class II alleles, some protective and some associated with increased susceptibility.
  • Polymorphisms in tumor necrosis factor and mannose binding lectin.
  • Recent genome-wide association studies and genomic sequencing analyses have identified associations with a range of genes including the immunoglobulin heavy chain (IGH) locus (specifically the IGHV4-61*02 allele), complement factor H, and some HLA class II (a range of HLA-DQ A and B alleles) and III loci.
  • The associations are often population dependent, although increasing consistency is being found across populations in meta-analyses of genomic studies.

3.2 The Immune Response

  • The most widely accepted theory of rheumatic fever pathogenesis is based on the concept of molecular mimicry.
  • An immune response targeted at streptococcal antigens (mainly thought to be on the M protein) also recognizes human tissues.
  • In this model, antigen processing cells of the innate immune system present streptococcal antigens after throat (and possibly skin) group A streptococcal infection to T cells.
  • This leads to activation of both humoral and cellular immunity.
  • Cross-reactive antibodies bind to endothelial cells on the heart valve, leading to activation of the adhesion molecule VCAM-1.
  • This results in recruitment of activated lymphocytes and lysis of endothelial cells in the presence of complement.
  • The latter leads to release of peptides including laminin, keratin, and tropomyosin, which, in turn, activates cross-reactive T cells that invade the heart, amplifying the damage and causing epitope spreading.

4. CLINICAL FEATURES

  • There is a latent period of ~3 weeks (1–5 weeks) between the precipitating group A streptococcal infection and the appearance of the clinical features of ARF.
  • The exceptions are chorea and indolent carditis, which may follow prolonged latent periods lasting up to 6 months.
  • Although children, adolescents, and young adults may have RHD but not know it, these cases can be diagnosed using echocardiography.
  • The most common clinical features are polyarthritis (present in 60–75% of cases) and carditis (50–75%).
  • The prevalence of chorea in ARF varies substantially by between populations, ranging from <2 to 30%.
  • Erythema marginatum and subcutaneous nodules are now rare, being found in <5% of cases.
  • Fever occurs in most cases of ARF, although rarely in cases of pure chorea.
  • Although high-grade fever (≥39°C) is the rule, lower grade temperature elevations are not uncommon.
  • Elevated acute-phase reactants are also present in most cases.

4.1 Heart Involvement

  • Up to 75% of patients with ARF progress to RHD.
  • The endocardium, pericardium, or myocardium may be affected.
  • Valvular damage is the hallmark of rheumatic carditis.
  • The mitral valve is almost always affected, sometimes together with the aortic valve; isolated aortic valve involvement is rare.
  • Damage to the pulmonary or tricuspid valves is usually secondary to increased pulmonary pressures resulting from left-sided valvular disease.
  • Early valvular damage leads to regurgitation.
  • Over ensuing years, usually as a result of recurrent episodes, leaflet thickening, scarring, calcification, and valvular stenosis may develop.
  • Therefore, the characteristic manifestation of carditis in previously unaffected individuals is mitral regurgitation, sometimes accompanied by aortic regurgitation.
  • Myocardial inflammation may affect electrical conduction pathways, leading to P-R interval prolongation (first-degree atrioventricular block or rarely higher-level block) and softening of the first heart sound.
  • People with RHD are often asymptomatic for many years before their valvular disease progresses to cause cardiac failure.

4.2 Joint Involvement

  • The most common form of joint involvement in ARF is arthritis, i.e., objective evidence of inflammation, with hot, swollen, red, and/or tender joints.
  • Involvement of more than one joint (i.e., polyarthritis).
  • Polyarthritis is typically migratory, moving from one joint to another over a period of hours.
  • ARF almost always affects the large joints—most commonly the knees, ankles, hips, and elbows—and is asymmetric.
  • The pain is severe and usually disabling until anti-inflammatory medication is commenced.
  • Less severe joint involvement is also relatively common and has been recognized as a potential major manifestation in high-risk populations in the most recent revision of the Jones criteria.
  • Arthralgia without objective joint inflammation usually affects large joints in the same migratory pattern as polyarthritis.
  • In some populations, aseptic monoarthritis may be a presenting feature of ARF, which may, in turn, result from early commencement of anti-inflammatory medication before the typical migratory pattern is established.
  • The joint manifestations of ARF are highly responsive to salicylates and other nonsteroidal anti-inflammatory drugs (NSAIDs).

4.3 Chorea

  • Sydenham's chorea commonly occurs in the absence of other manifestations.
  • It follows a prolonged latent period after group A streptococcal infection.
  • It is found mainly in females.
  • The choreiform movements affect particularly the head (causing characteristic darting movements of the tongue) and the upper limbs.
  • They may be generalized or restricted to one side of the body (hemi-chorea).
  • In mild cases, chorea may be evident only on careful examination.
  • In the most severe cases, the affected individuals are unable to perform activities of daily living.
  • There is often associated emotional lability or obsessive-compulsive traits, which may last longer than the choreiform movements (which usually resolve within 6 weeks but sometimes may take up to 6 months).
  • More than 50% of patients presenting with chorea will have carditis, for which reason echocardiography should be part of the workup.

4.4 Skin Manifestations

  • The classic rash of ARF is erythema marginatum, which begins as pink macules that clear centrally, leaving a serpiginous, spreading edge.
  • The rash is evanescent, appearing and disappearing before the examiner's eyes.
  • It occurs usually on the trunk, sometimes on the limbs, but almost never on the face.
  • Subcutaneous nodules occur as painless, small (0.5–2 cm), mobile lumps beneath the skin overlying bony prominences, particularly of the hands, feet, elbows, occiput, and occasionally the vertebrae.
  • They are a delayed manifestation, appearing 2–3 weeks after the onset of disease.
  • They last for just a few days up to 3 weeks.
  • They are commonly associated with carditis.

5. DIFFERENTIAL DIAGNOSIS

  • Because there is no definitive test, the diagnosis of ARF relies on the presence of a combination of typical clinical features together with evidence of the precipitating group A streptococcal infection, and the exclusion of other diagnoses.
  • Tests to exclude alternative diagnoses, depending on clinical presentation and locally endemic infections include:
  • Autoantibodies, double-stranded DNA, anti–cyclic citrullinated peptide (anti-CCP) antibodies.
  • Urine for Neisseria gonorrhoeae molecular test.
  • Urine for Chlamydia trachomatis molecular test.
  • Serologic or other testing for viral hepatitis, Yersinia spp., cytomegalovirus (CMV), parvovirus B19, respiratory viruses, Ross River virus, Barmah Forest virus.

5.1 Carditis Mimics

  • Congenital heart disease.
  • Cardiomyopathies.
  • Pericardial effusion.
  • Infective endocarditis.
  • Mitral valve prolapse.

5.2 Arthritis Mimics

  • Juvenile idiopathic arthritis.
  • Systemic lupus erythematosus.
  • Reactive arthritis.
  • Septic arthritis.

5.3 Chorea Mimics

  • Tourette syndrome.
  • Drug-induced movement disorders.
  • Wilson disease.
  • Huntington disease.

6. INVESTIGATIONS & DIAGNOSIS

  • With the exception of chorea and low-grade carditis, both of which may become manifest many months later, evidence of a preceding group A streptococcal infection is essential in making the diagnosis of ARF.
  • Because most cases do not have a positive throat swab culture or rapid antigen test, serologic evidence is usually needed.
  • The most common serologic tests are the anti-streptolysin O (ASO) and anti-DNase B (ADB) titers.
  • Where possible, age-specific reference ranges should be determined in a local population of healthy people without a recent group A streptococcal infection.
  • The diagnosis of ARF relies on the presence of a combination of typical clinical features together with evidence of the precipitating group A streptococcal infection, and the exclusion of other diagnoses.
  • This uncertainty led Dr. T. Duckett Jones in 1944 to develop a set of criteria (subsequently known as the Jones criteria) to aid in the diagnosis.
  • The most recent revision of the Jones criteria requires the clinician to determine if the patient is from a setting or population known to experience low rates of ARF.

Table 1 — Table 371-1 Staging of Rheumatic Heart Disease Detected by Echocardiography

Stage Clinical Risk Echocardiographic Features Age Applicability
Stage A: Minimal Echocardiographic Criteria for RHD Might be at risk of valvular heart disease progression Presence of mild MR or AR without morphologic features Applies only to individuals aged ≤20 years old
Stage B: Mild RHD At moderate or high risk of progression and at risk of developing symptoms of valvular heart disease Evidence of mild valvular regurgitation plus at least one morphologic feature in individuals aged ≤20 years and at least two morphologic features in individuals aged >20 years; or mild regurgitation in both mitral and aortic valves Can apply to any age
Stage C: Advanced RHD at Risk of Clinical Complications At high risk of developing clinical complications that require medical or surgical intervention Moderate or severe MR, moderate or severe AR, any MS or AS, pulmonary hypertension, and decreased LV systolic function Can apply to any age
Stage D: Advanced RHD with Clinical Complications Established clinical complications include cardiac surgery, heart failure, arrhythmia, stroke, and infective endocarditis Moderate or severe MR, moderate or severe AR, any MS or AS, pulmonary hypertension, and decreased LV systolic function Can apply to any age

Table 2 — Table 371-2 Jones Criteria

Category Low-risk populations Moderate- and high-risk populations
Diagnosis: initial ARF 2 major manifestations or 1 major plus 2 minor manifestations 2 major manifestations or 1 major plus 2 minor manifestations
Diagnosis: recurrent ARF 2 major or 1 major and 2 minor or 3 minor 2 major or 1 major and 2 minor or 3 minor
Major Criteria Carditis, Arthritis, Chorea, Erythema marginatum, SC nodules Carditis, Arthritis, Chorea, Erythema marginatum, SC nodules
Minor Criteria Polyarthralgia, Fever (≥38.5°C), ESR ≥60 mm in the first hour and/or CRP ≥3.0 mg/dL, Prolonged PR interval Monoarthralgia, Fever (≥38°C), ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL, Prolonged PR interval

Table 3 — Table 371-3 Testing and Monitoring of ARF in the Acute Setting

Investigations Always request In relevant situations Tests to exclude alternative diagnoses
Electrocardiogram (ECG) • Electrocardiogram (ECG) • Throat swab • Autoantibodies, double-stranded DNA, anti–cyclic citrullinated peptide (anti-CCP) antibodies
Echocardiogram • Echocardiogram • Skin sore swab • Urine for Neisseria gonorrhoeae molecular test
Complete blood count (CBC) • Complete blood count (CBC) • Blood cultures • Urine for Chlamydia trachomatis molecular test
C-reactive protein (CRP) • C-reactive protein (CRP) • Synovial fluid aspirate • Serologic or other testing for viral hepatitis, Yersinia spp., cytomegalovirus (CMV), parvovirus B19, respiratory viruses, Ross River virus, Barmah Forest virus
Streptococcal serology (antistreptolysin and anti-DNase B) • Streptococcal serology (antistreptolysin and anti-DNase B) • Ensure sample does not clot by using correct tubes that have been well mixed and transported promptly to the laboratory • Include request for cell count, microscopy, culture, and gonococcal polymerase chain reaction (PCR)
Creatinine test (UEC) • Creatinine test (UEC [urea, electrolytes, creatinine]) since nonsteroidal anti-inflammatory drugs can affect renal function • Pregnancy test

Table 4 — Table 371-4 American Heart Association Recommendations for Duration of Secondary Prophylaxis

Category of Patient Duration of Prophylaxis
Rheumatic fever without carditis For 5 years after the last attack or 21 years of age (whichever is longer)
Rheumatic fever with carditis but no residual valvular disease For 10 years after the last attack, or 21 years of age (whichever is longer)
Rheumatic fever with persistent valvular disease, evident clinically or on echocardiography For 10 years after the last attack, or 40 years of age (whichever is longer); sometimes lifelong prophylaxis

6.1 Jones Criteria

  • Diagnosis: initial ARF requires 2 major manifestations or 1 major plus 2 minor manifestations.
  • Diagnosis: recurrent ARF requires 2 major or 1 major and 2 minor or 3 minor.
  • Major Criteria: Carditis, Arthritis, Chorea, Erythema marginatum, Subcutaneous nodules.
  • Minor Criteria: Fever, Prolonged PR interval, Elevated ESR/CRP, Polyarthralgia (Low-risk) / Monoarthralgia (Moderate/high-risk).
  • Low-risk populations are those with ARF incidence ≤ 2 per 100,000 school-age children or all-age rheumatic heart disease prevalence of ≤ 1 per 1000 population per year.
  • As in past versions of the criteria, erythema marginatum and SC nodules are rarely 'stand-alone' major criteria.
  • Additionally, joint manifestations can only be considered in either the major or minor categories but not both in the same patient.

6.2 RHD Staging

  • These guidelines replace the previous 'definite,' 'borderline,' and 'latent' diagnostic category terms with a classification based on the risk of progression to more advanced valvular heart disease.
  • These guidelines provide recommendations on secondary prophylaxis for each group.
  • Staging applies to high-risk settings and requires other causes of valvular heart disease to have been excluded.
  • After the application of the confirmatory echocardiographic criteria, diagnostic categories might include 'normal' and 'other,' which encompasses other diseases such as congenital heart disease, cardiomyopathies, and pericardial effusion.

6.3 Diagnostic Algorithm

  • Step 1: Assess clinical features (Carditis, Arthritis, Chorea, Erythema, Nodules, Fever, PR interval, ESR/CRP).
  • Step 2: Confirm evidence of preceding Group A Streptococcal infection (Throat swab, Skin swab, Serology ASO/Anti-DNase B).
  • Step 3: Exclude other diagnoses (Autoantibodies, Gonorrhea, Chlamydia, Viral hepatitis, etc.).
  • Step 4: Apply Jones Criteria (2 Major OR 1 Major + 2 Minor for initial; 2 Major OR 1 Major + 2 Minor OR 3 Minor for recurrent).
  • Step 5: Perform Echocardiogram on all possible cases to aid in making the diagnosis and to determine the severity at baseline of any carditis.
  • Step 6: Determine RHD Stage (A, B, C, D) based on Echo findings.

7. MANAGEMENT & TREATMENT

  • Patients with possible ARF should be followed closely to ensure that the diagnosis is confirmed, treatment of heart failure and other symptoms is undertaken, and preventive measures including commencement of secondary prophylaxis, inclusion on an ARF registry, and health education are commenced.
  • Echocardiography should be performed on all possible cases to aid in making the diagnosis and to determine the severity at baseline of any carditis.
  • There is no treatment for ARF that has been proven to alter the likelihood of developing, or the severity of, RHD.
  • With the exception of treatment of heart failure, which may be lifesaving in cases of severe carditis, the treatment of ARF is symptomatic.
  • Once the acute episode has resolved, the priority in management is to ensure long-term clinical follow-up and adherence to a regimen of 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 prophylaxis before the patient is discharged.
  • Patients and their families should also be educated about their disease, emphasizing the importance of adherence to secondary prophylaxis.

Table 5 — Drug Therapy for ARF

Drug Dose Frequency Monitoring Key Side Effects Contraindications
Penicillin (Oral) 500 mg (250 mg for children ≤27 kg) PO twice daily None specific GI upset Penicillin allergy
Penicillin (IM) 1.2 million units (600,000 units for children ≤27 kg) Every 4 weeks None specific Pain at injection site Penicillin allergy
Erythromycin 250 mg Twice daily None specific GI upset Penicillin allergy
Aspirin 50–60 mg/kg/day (max 80–100 mg/kg/day) 4–5 divided doses Salicylate toxicity (nausea, vomiting, tinnitus) GI bleeding, Reye syndrome Renal impairment, Peptic ulcer
Naproxen 10–20 mg/kg/day Twice daily None specific GI upset Renal impairment
Prednisone 1–2 mg/kg/day (max 80 mg) Daily (taper over 3 weeks) Monitor for infection, hyperglycemia Hyperglycemia, Osteoporosis Active infection
Carbamazepine/Valproate Standard dosing Daily Monitor drug levels Drowsiness, Dizziness Pregnancy (Valproate)

7.1 Antibiotics

  • All patients with ARF should receive antibiotics sufficient to treat the precipitating group A streptococcal infection.
  • Penicillin is the drug of choice and can be given orally (as phenoxymethyl penicillin, 500 mg [250 mg for children ≤27 kg] PO twice daily, or amoxicillin, 50 mg/kg [maximum, 1 g] daily, for 10 days).
  • Alternatively, a single dose of 1.2 million units (600,000 units for children ≤27 kg) IM benzathine penicillin G.
  • If commenced within 9 days of sore throat onset, a course of penicillin (as outlined above for treatment of ARF) will prevent almost all cases of ARF that would otherwise have developed.
  • In settings where ARF and RHD are common but microbiologic diagnosis of group A streptococcal pharyngitis is not available, such as in resource-poor countries, primary care guidelines sometimes recommend that all patients with sore throat be treated with penicillin.
  • Although there is no proof that antibiotic treatment of group A streptococcal skin infections can prevent ARF, the increasing evidence that impetigo is strongly associated with ARF in some populations argues for a focus on treatment and prevention of group A streptococcal skin infections as part of a comprehensive ARF control strategy in regions with endemic impetigo.
  • Penicillin-allergic patients can receive erythromycin (250 mg) twice daily.

7.2 Salicylates and NSAIDs

  • These may be used for the treatment of arthritis, arthralgia, and fever once the diagnosis is confirmed.
  • They are of no proven value in the treatment of carditis or chorea.
  • Aspirin has traditionally 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 adults) in 4–5 divided doses.
  • At higher doses, the patient should be monitored for symptoms of salicylate toxicity such as nausea, vomiting, or tinnitus; if symptoms appear, lower doses should be used.
  • Owing to the frequency of gastrointestinal side effects and the potential of more severe adverse effects of aspirin, many clinicians now prefer to use naproxen at a dose of 10–20 mg/kg per day because it may be safer than aspirin and has the advantage of twice-daily dosing.
  • When the acute symptoms are substantially resolved, usually within the first 2 weeks, patients on higher doses of anti-inflammatory medications can have the dose reduced for a further 2–4 weeks.
  • Fever, joint manifestations, and elevated acute-phase reactants sometimes recur up to 3 weeks after the medication is discontinued. This does not indicate a recurrence and can be managed by recommencing anti-inflammatory agents for a brief period.

7.3 Glucocorticoids

  • The use of glucocorticoids in ARF remains controversial.
  • Two meta-analyses have failed to demonstrate a benefit of glucocorticoids compared to placebo or salicylates in improving the short- or longer-term outcome of carditis.
  • However, the studies included in these meta-analyses all took place >40 years ago and did not use medications in common usage today.
  • There are some recent data that suggest corticosteroids improve laboratory, radiologic, and echocardiographic parameters in carditis.
  • Many clinicians treat cases of severe carditis (causing heart failure) with glucocorticoids in the belief that they may reduce the acute inflammation and result in more rapid resolution of failure.
  • However, the potential benefits of this treatment should be balanced against the possible adverse effects.
  • If used, prednisone or prednisolone is recommended at a dose of 1–2 mg/kg per day (maximum, 80 mg), usually for a few days or up to a maximum of 3 weeks.
  • There is recent evidence that corticosteroids are effective and lead to more rapid symptom reduction in chorea. They should be considered in severe or refractory cases.
  • Prednisone or prednisolone may be commenced at 0.5 mg/kg daily, with weaning as early as possible, preferably after 1 week if symptoms are reduced, although slower weaning or temporary dose escalation may be required if symptoms worsen.

7.4 Intravenous Immunoglobulin (IVIG)

  • Small studies have suggested that IVIg may lead to more rapid resolution of chorea but have shown no benefit on the short- or long-term outcome of carditis in ARF without chorea.
  • In the absence of better data, IVIg is not recommended except in cases of severe chorea refractory to other treatments.

7.5 Management of Heart Failure

  • See Chap. 265.
  • Traditional recommendations for long-term bed rest, once the cornerstone of management, are no longer widely practiced.
  • Instead, bed rest should be prescribed as needed while arthritis and arthralgia are present and for patients with heart failure.
  • Once symptoms are well controlled, gradual mobilization can commence as tolerated.

7.6 Chorea Management

  • Medications to control the abnormal movements do not alter the duration or outcome of chorea.
  • Milder cases can usually be managed by providing a calm environment.
  • In patients with severe chorea, carbamazepine or sodium valproate is preferred to haloperidol.
  • A response may not be seen for 1–2 weeks, and medication should be continued for 1–2 weeks after symptoms subside.
  • There is recent evidence that corticosteroids are effective and lead to more rapid symptom reduction in chorea.
  • They should be considered in severe or refractory cases.

8. PROGNOSIS & COMPLICATIONS

  • Untreated, ARF lasts on average 12 weeks.
  • With treatment, patients are usually discharged from hospital within 1–2 weeks.
  • Inflammatory markers should be monitored every 1–2 weeks until they have normalized (usually within 4–6 weeks).
  • An echocardiogram should be performed after 1 month to determine if there has been progression of carditis.
  • Cases with more severe carditis need close clinical and echocardiographic monitoring in the longer term.
  • RHD is the most common cause of acquired heart disease in children in LMICs.
  • It is a major cause of mortality and morbidity in adults as well.
  • People with RHD are often asymptomatic for many years before their valvular disease progresses to cause cardiac failure.
  • In resource-poor settings, the diagnosis of ARF is often not made, so these cases can be diagnosed using echocardiography.

8.1 Long-term Follow-up

  • Once the acute episode has resolved, the priority in management is to ensure long-term clinical follow-up and adherence to a regimen of secondary prophylaxis.
  • Patients should be entered onto the local ARF registry (if present).
  • Contact should be made with primary care practitioners to ensure a plan for follow-up and administration of secondary prophylaxis before the patient is discharged.
  • Patients and their families should also be educated about their disease, emphasizing the importance of adherence to secondary prophylaxis.

9. SPECIAL CONSIDERATIONS

  • Low-risk populations are those with ARF incidence ≤ 2 per 100,000 school-age children or all-age rheumatic heart disease prevalence of ≤ 1 per 1000 population per year.
  • In settings where ARF and RHD are common but microbiologic diagnosis of group A streptococcal pharyngitis is not available, such as in resource-poor countries, primary care guidelines sometimes recommend that all patients with sore throat be treated with penicillin.
  • Although imperfect, such approaches recognize the importance of ARF prevention at the expense of overtreating many cases of sore throat that are not caused by group A Streptococcus.
  • Although there is no proof that antibiotic treatment of group A streptococcal skin infections can prevent ARF, the increasing evidence that impetigo is strongly associated with ARF in some populations argues for a focus on treatment and prevention of group A streptococcal skin infections as part of a comprehensive ARF control strategy in regions with endemic impetigo.
  • Pregnancy test should be included in investigations for relevant situations.

9.1 Pregnancy

  • Pregnancy test should be included in investigations for relevant situations.
  • Valproate is generally avoided in pregnancy.

9.2 Resource-Poor Settings

  • In resource-poor settings, the diagnosis of ARF is often not made.
  • These cases can be diagnosed using echocardiography.
  • Primary care guidelines sometimes recommend that all patients with sore throat be treated with penicillin.
  • Although imperfect, such approaches recognize the importance of ARF prevention at the expense of overtreating many cases of sore throat that are not caused by group A Streptococcus.

10. KEY PEARLS & CLINICAL TRAPS

  • Valvular damage is the hallmark of rheumatic carditis.
  • Polyarthritis is typically migratory, moving from one joint to another over a period of hours.
  • ARF almost always affects the large joints—most commonly the knees, ankles, hips, and elbows—and is asymmetric.
  • The pain is severe and usually disabling until anti-inflammatory medication is commenced.
  • Erythema marginatum is evanescent, appearing and disappearing before the examiner's eyes.
  • Subcutaneous nodules are a delayed manifestation, appearing 2–3 weeks after the onset of disease.
  • Chorea may occur in the absence of other manifestations and follows a prolonged latent period after group A streptococcal infection.
  • Diagnosis of rheumatic aortic stenosis requires the exclusion of other causes, including bicuspid aortic valve and degenerative calcific AS.
  • Low-risk populations have different Jones criteria thresholds compared to moderate/high-risk populations.
  • Joint manifestations can only be considered in either the major or minor categories but not both in the same patient.

10.1 Diagnostic Clues

  • Look for: Valvular damage (hallmark of rheumatic carditis).
  • Look for: Migratory polyarthritis affecting large joints.
  • Look for: Evanescent erythema marginatum on trunk/limbs (not face).
  • Look for: Subcutaneous nodules over bony prominences.
  • Look for: Chorea with emotional lability.
  • Look for: Prolonged PR interval (unless carditis is a major criterion).
  • Look for: Elevated acute-phase reactants.

10.2 Exclusion Criteria

  • Exclusion of other diagnoses is essential in making the diagnosis of ARF.
  • Low-risk populations are those with ARF incidence ≤ 2 per 100,000 school-age children or all-age rheumatic heart disease prevalence of ≤ 1 per 1000 population per year.
  • A diagnosis of rheumatic aortic stenosis requires the exclusion of other causes, including bicuspid aortic valve and degenerative calcific AS.
  • Tests to exclude alternative diagnoses include autoantibodies, gonorrhea, chlamydia, viral hepatitis, etc.

Flowcharts & Algorithms

Reproduced from Harrison's 22nd Edition.

Flowchart 1

Pathogenetic pathway for acute rheumatic fever and rheumatic heart step

Caption: FIGURE 371-1 Pathogenetic pathway for acute rheumatic fever and rheumatic heart step. Interventions in parentheses are either unproven or currently unavailable.

Figures & Illustrations

Reproduced from Harrison's 22nd Edition.

Figure 1

Transthoracic echocardiographic image from a 5-year-old boy with chronic rheumatic...

Caption: FIGURE 371-2 Transthoracic echocardiographic image from a 5-year-old boy with chronic rheumatic heart disease. This diastolic image demonstrates leaflet thickening, restriction of the anterior mitral valve leaflet tip, and doming of the body of the leaflet toward the interventricular septum. This appearance (marked by the arrowhead) is commonly described as a “hockey stick” or an “elbow” deformity. • AV, aortic valve; LA, left atrium; LV, left ventricle; MV, mitral valve; RV, right ventricle. (Courtesy of Dr. Bo Remenyi, Department of Paediatric and Congenital Cardiac Services, Starship Children’s Hospital, Auckland, New Zealand.) • — 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.

Figure 2

Transthoracic echocardiographic image from a 5-year-old boy with chronic rheumatic...

Caption: Transthoracic echocardiographic image from a 5-year-old boy with chronic rheumatic heart disease. This diastolic image demonstrates leaflet thickening, restriction of the anterior mitral valve leaflet tip, and doming of the body of the leaflet toward the interventricular septum. This appearance is commonly described as a 'hockey stick' or an 'elbow' deformity.

Generated from Harrison's Principles of Internal Medicine, 22nd Edition.