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Rheumatic Fever Workup

  • Author: Mark R Wallace, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
Updated: Oct 08, 2015

Laboratory Studies

No single specific laboratory test can confirm the diagnosis of acute rheumatic fever (ARF). Evidence of preceding group A streptococcal infection is an integral part of the Jones criteria for ARF diagnosis unless the patient has chorea (which may occur months after the inciting infection) or indolent rheumatic heart disease (see Diagnosis).[6]

Throat culture

Throat culture remains the criterion standard for confirmation of group A streptococcal infection. Rapid antigen detection tests are not as sensitive.

If a rapid antigen detection test result is negative, obtain a throat culture in patients with suspected rheumatic fever.

On the other hand, because of the high specificity of these tests, a positive rapid antigen test confirms a streptococcal infection.

Antibody titer tests

Antibody titer tests used include ASO test, antistreptococcal DNAse B (ADB) test, and the antistreptococcal hyaluronidase (AH) test.

ASO is a test used to detect streptococcal antibodies directed against streptococcal lysin O. An elevated titer is proof of a previous streptococcal infection. It is usually more elevated after a pharyngeal than skin infection, while the ADB is typically elevated regardless of the site of the infection.[26]

Acute and convalescent sera, if available, are helpful for proving recent streptococcal infection.

The antibody tests must be interpreted with caution in areas with high rates of streptococcal infection and ARF, as relatively high titers are commonly encountered in the population. These tests are of greater utility in areas with lower prevalence (eg, in most Western countries).[27]

Acute-phase reactants, erythrocyte sedimentation rate, and C-reactive protein

Acute-phase reactants, the erythrocyte sedimentation rate (ESR), and C-reactive protein levels (CRP) are usually elevated at the onset of ARF and serve as a minor manifestation in the Jones criteria. These tests are nonspecific, but they may be useful in monitoring disease activity.

Blood cultures

Blood cultures are obtained to help rule out infective endocarditis, bacteremia, and disseminated gonococcal infection.


Imaging Studies

Chest radiography

Chest radiography can reveal cardiomegaly and CHF in patients with carditis.


Echocardiography may demonstrate valvular regurgitant lesions in patients with ARF who do not have clinical manifestations of carditis. This does not qualify as carditis in the most recent Jones diagnostic criteria, as the clinical implications of subclinical carditis remain unclear, but some experts believe the diagnostic criteria for ARF should be modified to allow for specific abnormalities found only on echocardiograms to be included.

The diagnostic criteria used in New Zealand and Australia allow for the use of echocardiography to prove carditis; this is a controversial topic (see Physical),[21, 20, 19, 23, 24, 17] as it helps detect 16-47% more cases of carditis[28, 29] ; however, the clinical importance is unclear. Some data suggest such subclinical carditis cases should receive long-term penicillin prophylaxis as if they had more classic clinical carditis.[22]

Valvular stenotic lesions, especially of the mitral valve, can be observed in rheumatic heart disease.

In the absence of mitral valve disease involvement, isolated echocardiographic disease of the aortic valve is uncommon in patients with rheumatic heart disease.


Other Tests

The most common finding on electrocardiography is a prolongation of the PR interval, which is a nonspecific finding, but counts as a minor manifestation in the Jones diagnostic criteria. It does not count as proof of carditis. On rare occasions, second- or third-degree heart block is present. In patients with chronic rheumatic heart disease, electrocardiography may show left atrial enlargement secondary to mitral stenosis.

Various other studies may be needed to rule out other illnesses in the differential diagnoses. Common tests would include rheumatoid factor, antinuclear antibody (ANA), Lyme serology, blood cultures, and evaluation for gonorrhea.



Arthrocentesis can be performed to rule out septic arthritis but is usually unnecessary.


Histologic Findings

Rheumatic fever is characterized pathologically by exudative and proliferative inflammatory lesions of the connective tissue in the heart, joints, blood vessels, and subcutaneous tissue.

In the early stage, fragmentation of collagen fibers, cellular infiltration that is predominantly lymphocytic, and fibrinoid deposition followed by the appearance of a myocardial Aschoff nodule (a perivascular focus of inflammation that has an area of central necrosis surrounded by a rosette of large mononuclear and giant multinuclear cells) occur. The nuclei of these cells resemble owl eyes and are called Anichkov cells.

Subcutaneous nodules histologically resemble Aschoff nodules. The brain may show scattered areas of arteritis and petechial hemorrhages, which have an uncertain relationship to Sydenham chorea.



Because acute rheumatic fever (ARF) can have diverse manifestations and because no specific diagnostic test for the disease exists, arriving at the correct diagnosis is particularly important. This is essential not only in terms of prescribing appropriate therapy for the acute attack but also because of the necessity for prescribing continuous antistreptococcal prophylaxis to prevent subsequent attacks and additional damage.

The Jones criteria were first established in 1944 and have been modified or updated several times, most recently in 1992. In general, the changes have tended to make the criteria more specific and less sensitive. This makes sense in the developed world, where the incidence of ARF continues to fall, but cases may be missed in high-prevalence areas. The main controversies now are about the use of echocardiography alone to confirm carditis (currently not allowed in Jones criteria), the need to show evidence of a current or recent streptococcal infection (with exceptions for chorea and indolent rheumatic heart disease), and the development of monoarticular arthritis if anti-inflammatory agents were used early and may have aborted the development of polyarthritis.[6, 24, 23]

If echocardiography alone were adequate for confirmation of carditis, the requirement for proof of prior streptococcal infection dropped, and monoarticular arthritis allowed, the Jones criteria would be more inclusive but less specific.[30] The New Zealand criteria allow for subclinical diagnosis of carditis and the inclusion of some cases of monoarticular arthritis[17] ; with these more liberal standards, they discover about 16% more carditis cases.[28] Studies in developing countries have suggested that using echocardiography could increase the carditis diagnosis rate by 47%.[29]

Jones criteria

Major criteria are as follows:

  • Carditis (based on clinical criteria)
  • Polyarthritis
  • Chorea (rare in adults)
  • Erythema marginatum (uncommon; rare in adults)
  • Subcutaneous nodules (uncommon; rare in adults)

Minor criteria are as follows:

  • Arthralgia (cannot count arthritis as a major criterion and arthralgia as a minor criterion)
  • Fever
  • Elevated ESR or CRP level
  • Prolonged PR interval

Evidence of group A streptococcal disease is required except when rheumatic fever is first discovered after a long latent period (eg, Sydenham chorea, indolent carditis), as follows:

  • Evidence of preceding group A streptococcal infection - Positive throat culture or rapid antigen test result
  • Elevated or rising streptococcal antibody titer

If supported by evidence of preceding group A streptococcal infection, the presence of two major manifestations or one major and two minor manifestations indicates a high probability of ARF. Failure to fulfill the Jones criteria makes the diagnosis unlikely but not impossible. Clinical judgment is required.

The World Health Organization (WHO) follows the Jones criteria for the diagnosis of ARF, but possible recurrences require only two minor criteria plus evidence of recent streptococcal infection.[6]

Contributor Information and Disclosures

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.


Larry I Lutwick, MD Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Jayashree Ravishankar, MD, MRCP Medical Director, STAR Health Center, State University of New York Downstate Medical Center

Jayashree Ravishankar, MD, MRCP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Thomas J Marrie, MD Dean of Faculty of Medicine, Dalhousie University Faculty of Medicine, Canada

Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Association of Medical Microbiology and Infectious Disease Canada, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

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Clinical manifestations and time course.
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