Pediatric Rheumatic Fever Workup

The following studies are indicated in patients with rheumatic fever (RF):

• Throat culture

  • The appropriate technique includes vigorous swabbing of both tonsils and the posterior pharynx. The sample is grown on sheep blood agar to demonstrate the presence of beta-hemolytic streptococci infection. Colonies that grow on the agar can be tested with latex agglutination, fluorescent antibody assay, coagglutination, or precipitation techniques to demonstrate group A beta hemolytic streptococci (GABHS) infection.

  • Throat cultures for GABHS infections usually are negative by the time symptoms of rheumatic fever or rheumatic heart disease (RHD) appear.

  • Make attempts to isolate the organism prior to the initiation of antibiotic therapy to help confirm a diagnosis of streptococcal pharyngitis and to allow typing of the organism if it is isolated successfully.

• Rapid antigen detection test

  • This test allows rapid detection of group A streptococci (GAS) antigen, allowing the diagnosis of streptococcal pharyngitis to be made and antibiotic therapy to be initiated while the patient is still in the physician's office.

  • This test reportedly has a specificity of greater than 95% but a sensitivity of only 60-90%. Thus, obtain a throat culture in conjunction with the rapid antigen detection test.

• Antistreptococcal antibodies

  • Clinical features of rheumatic fever begin when antistreptococcal antibody levels are at their peak. Thus, these tests are useful for confirming previous GAS infection. Antistreptococcal antibodies are particularly useful in patients who present with chorea as the only diagnostic criterion.

  • Sensitivity for recent infections can be improved by testing for several antibodies. Check antibody titers 2 weeks apart to detect a rising titer. The most common extracellular antistreptococcal antibodies tested include antistreptolysin O (ASO) and anti-DNase B, antihyaluronidase, antistreptokinase, antistreptococcal esterase, and anti–nicotinamide adenine dinucleotide (anti-NAD). Antibody tests for cellular components of GAS antigens include antistreptococcal polysaccharide, antiteichoic acid antibody, and anti-M protein antibody.

  • In general, the antibodies to extracellular streptococcal antigens rise during the first month after infection and then plateau for 3-6 months before returning to normal levels after 6-12 months. When the ASO titer peaks (2-3 wk after onset of rheumatic fever), the sensitivity of this test is 80-85%.

  • The anti-DNase B has a slightly higher sensitivity (90%) for revealing rheumatic fever or acute glomerulonephritis. Antihyaluronidase frequently is abnormal in patients with rheumatic fever with a normal ASO titer, may rise earlier, and persists longer than elevated ASO titers during incidents of rheumatic fever.

• Acute-phase reactants: C-reactive protein and erythrocyte sedimentation rate are elevated in individuals with rheumatic fever due to the inflammatory nature of the disease. Both tests have high sensitivity but low specificity for rheumatic fever.

• Heart reactive antibodies: Tropomyosin is elevated in persons with acute rheumatic fever.

• Rapid detection test for D8/17: This immunofluorescence technique for identifying the B-cell marker D8/17 is positive in 90% of patients with rheumatic fever and may be useful for identifying patients who are at risk of developing rheumatic fever.

The following imaging studies have been used in the workup:

• Chest radiography

  • Cardiomegaly, pulmonary congestion, and other findings consistent with heart failure may be observed on chest radiograph in individuals with rheumatic fever (as is shown on the image below).

    Chest radiograph showing cardiomegaly due to carditis of acute rheumatic fever.

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  • When the patient has fever and respiratory distress, the chest radiograph helps differentiate between congestive heart failure (CHF) and rheumatic pneumonia.

• Echocardiography

  • In individuals with acute RHD, echocardiography identified and quantitated valve insufficiency and ventricular dysfunction. Studies in Cambodia and Mozambique demonstrated a 10-fold increase in the prevalence of RHD when echocardiography is used for clinical screening compared with strictly clinical findings. ^[16]

  • Handheld echocardiography was investigated as a screening tool and found to be 90% sensitive and 92% specific for identifying patients with rheumatic heart disease in Ugandan children. ^[17]

  • A study by Godown et al. assessed the value of handheld echocardiography over auscultation to identify rheumatic heart disease. The study found that auscultation alone was a poor screening test for rheumatic heart disease and that handheld echocardiography significantly improved detection of rheumatic heart disease and was a cost-effective screening strategy for rheumatic heart disease in resource-limited settings. ^[18]

  • The World Heart Federation has published guidelines for identifying individuals with rheumatic heard disease without a clear history of acute rheumatic fever. Based on 2-dimensional (2D) imaging and pulsed and color Doppler interrogation, patients are divided into 3 categories: definite rheumatic heart disease, borderline rheumatic heart disease, and normal. For pediatric patients (defined as age < 20 y), definite echo features include pathologic mitral regurgitation (MR) and at least 2 morphological features of rheumatic heart disease of the mitral valve, mitral stenosis mean gradient of more than 4 mm Hg, pathological aortic regurgitation and at least 2 morphological features of rheumatic heart disease of the aortic valve, or borderline disease of both the aortic valve and mitral valve. ^[19]

  • The revised criteria by the American Heart Association for the diagnosis of acute rheumatic fever was based on the findings above, as well as to align with the World Heart Federation guidelines. In the newest version of the revised Jones Criteria morphologic and Doppler findings on echocardiogram may supersede auscultatory findings for carditis. Acute morphologic changes in the mitral valve  may include annular dilation, chordal elongation, chordal rupture resulting in flail leaflet with severe mitral regurgitation, or prolapse or beading/nodularity of the leaflet tips.  Chronic changes in the mitral valve should show leaflet thickening and calcification, with restricted motion. There may also be evidence of chordal thickening and fusion. Changes in the aortic valve  may include prolapse, coaptation defect, and thickening of the leaflets, with restricted motion.  Doppler findings for the mitral and aortic valves mirrored the recommendations of the World Heart Federation. ^[14]

  • In persons with mild carditis, Doppler evidence of mitral regurgitation may be present during the acute phase of disease but resolves in weeks to months.

  • In contrast, patients with moderate-to-severe carditis have persistent mitral and/or aortic regurgitation. The most important echocardiographic features of mitral regurgitation from acute rheumatic valvulitis are annular dilatation, elongation of the chordae to the anterior leaflet, and a posterolaterally directed mitral regurgitation jet.

  • During acute rheumatic fever, the left ventricle frequently is dilated in association with a normal or increased fractional shortening. Thus, some cardiologists believe that valve insufficiency (eg, from endocarditis), rather than myocardial dysfunction (eg, from myocarditis), is the dominant cause of heart failure in individuals with acute rheumatic fever.

  • In individuals with chronic RHD, echocardiography tracks the progression of valve stenosis and may help determine the time for surgical intervention. The leaflets of affected valves become thickened diffusely, with fusion of the commissures and chordae tendineae. Increased echodensity of the mitral valve may signify calcification.

ECG findings include the following:

• Sinus tachycardia most frequently accompanies acute RHD. Alternatively, some children develop sinus bradycardia from increased vagal tone. No correlation between bradycardia and severity of carditis is observed.

• First-degree atrioventricular (AV) block (prolongation of PR interval) is observed in some patients with RHD. This abnormality may be related to localized myocardial inflammation involving the AV node or to vasculitis involving the AV nodal artery. First-degree AV block is a nonspecific finding and should not be used as a criterion for the diagnosis of RHD. Its presence does not correlate with the development of chronic RHD.

• Second-degree (ie, intermittent) and third-degree (ie, complete) AV block with progression to ventricular standstill have been described. However, heart block in the setting of rheumatic fever typically resolves with the rest of the disease process.

• In individuals with acute pericarditis, ST segment elevation may be present, most marked in leads II, III, aVF, and V₄ through V₆.

• Finally, patients with RHD may develop atrial flutter, multifocal atrial tachycardia, or atrial fibrillation from chronic mitral valve disease and atrial dilation.

Cardiac catheterization is not indicated in acute rheumatic fever.

Pathologic examination of the insufficient valves may reveal verrucous lesions at the line of closure.

Aschoff bodies (ie, perivascular foci of eosinophilic collagen surrounded by lymphocytes, plasma cells, and macrophages) are found in the pericardium, perivascular regions of the myocardium, and endocardium. The Aschoff bodies assume a granulomatous appearance with a central fibrinoid focus and eventually are replaced by nodules of scar tissue. Anitschkow cells are plump macrophages within Aschoff bodies.

In the pericardium, fibrinous and serofibrinous exudates may produce an appearance of "bread and butter" pericarditis.