eMedicine Specialties > Infectious Diseases > Cardiovascular and Intravascular Infections

Rheumatic Fever: Differential Diagnoses & Workup

Author: Mark Raymond Wallace, MD, Infectious Disease Fellowship Director, Orlando Regional Healthcare; Clinical Professor of Medicine, Florida State University
Coauthor(s): 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; Jayashree Ravishankar, MD, Fellow, Department of Medicine, Division of Infectious Diseases, State University of New York Health Science Center at Brooklyn
Contributor Information and Disclosures

Updated: Apr 13, 2009

Differential Diagnoses

Other Problems to Be Considered

Gout
Bacterial endocarditis
Disseminated gonococcal infection
Systemic vasculitis
Acute hepatitis B or C
Poststreptococcal arthritis
Still disease
Arthralgias and elevated antistreptolysin-O (ASO) titers²⁰
Sarcoidosis

Workup

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 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 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.²¹
  • 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).²²
• 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 are obtained to help rule out infective endocarditis, bacteremia, and disseminated gonococcal infection.

Imaging Studies

• 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. This is a controversial topic (see Physical).^{17,16,15,18,19}
  • 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.

Procedures

• 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.

Diagnosis

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 center around the use of echocardiography alone to confirm carditis (currently not allowed) and the need to show evidence of a current or recent streptococcal infection (with exceptions for chorea and indolent rheumatic heart disease).^6,19,18 If echocardiography alone were adequate for confirmation of carditis and the requirement for proof of prior streptococcal infection dropped, the Jones criteria would be much more inclusive but less specific.²³

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

• 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

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