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, 24]
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. [33]
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). [34]
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
Echocardiography may demonstrate valvular regurgitant lesions in patients with ARF who do not have overt clinical manifestations of carditis. This is now considered an integral part of the evaluation of proven or suspected ARF everywhere. [24, 29, 20] Echocardiography was used as a diagnostic criterion in New Zealand and Australia before being advocated universally, [23, 26, 27, 28, 31, 32] and reveals 16%-47% more cases of carditis [35, 36] than clinical criteria alone. Patients with echocardiographically diagnosed subclinical carditis cases should receive the same long-term penicillin prophylaxis as those with the more classic clinical carditis, [24, 30] since they are also at risk for poor outcomes due to recurrent rheumatic heart disease. [20]
Valvular stenotic lesions, especially of the mitral valve, can be observed in rheumatic heart disease. Pathological mitral and/or aortic regurgitation are also frequently encountered, [20] though isolated echocardiographic disease of the aortic valve is uncommon 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 often 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 since 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 need for 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 2015. The 2015 revision, for the first time, uses slightly different, more specific, diagnostic criteria in areas of low endemicity than the more sensitive criteria for moderate- to high-risk areas. Low-risk areas, by this definition, have an ARF incidence of less than 2 per 100,000 school-aged children or an all-age rheumatic heart prevalence of less than 1 per 1000 persons. Medium- to high-risk countries exceed these thresholds. Additional major changes include the recommended use of echocardiography and the inclusion of subclinical carditis as a major criterion, as well as the inclusion of monoarthritis in higher-risk areas. [24, 35, 36, 37]
Jones Criteria, 2015 revision, low-risk populations (United States, Europe, other high-income areas)
Major criteria are as follows:
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Carditis (clinical or echocardiographic diagnosis)
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Polyarthritis (not monoarthritis)
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Chorea (rare in adults)
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Erythema marginatum (uncommon; rare in adults)
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Subcutaneous nodules (uncommon; rare in adults)
Minor criteria are as follows:
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Polyarthralgia (cannot count arthritis as a major criterion and arthralgia as a minor criterion)
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Fever exceeding 38.5°C
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Elevated ESR (>60 mm/hr) or CRP level (>3 mg/L)
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Prolonged PR interval
Jones criteria, 2015 revision, high-risk populations (Oceania, Africa, South Asia, other lower-income areas)
Major criteria are as follows:
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Carditis (clinical or echocardiographic diagnosis)
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Polyarthritis or monoarthritis: Polyarthralgias can also be considered but only after careful consideration of the differential diagnoses.
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Chorea (rare in adults)
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Erythema marginatum (uncommon; rare in adults)
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Subcutaneous nodules (uncommon; rare in adults)
Minor criteria are as follows:
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Polyarthralgia (cannot count arthritis as a major criterion and arthralgia as a minor criterion)
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Fever exceeding 38°C (note lower cutoff)
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Elevated ESR (>30 mm/hr; note lower ESR standard) or CRP level (>3 mg/L)
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Prolonged PR interval
Universal criteria
In both higher- and lower-risk settings, evidence of group A streptococcal disease is required for diagnosis, except when rheumatic fever is first discovered after a long latent period (eg, Sydenham chorea, indolent carditis), as follows:
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Evidence of preceding group A streptococcal infection - Positive throat culture or rapid antigen test result
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Elevated or rising streptococcal antibody titer
Scoring
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.
Recurrent ARF can be diagnosed based on 2 major, 1 major plus 2 minor, or 3 minor criteria.
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Clinical manifestations and time course.
