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Acute Rheumatic Fever Workup

  • Author: Robert J Meador, Jr, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jul 19, 2016
 

Approach Considerations

Acute rheumatic fever (ARF) is diagnosed on the basis of clinical manifestations supported by laboratory tests.

Jones criteria

Guidelines for diagnosis published in 1944 by T. Duckett Jones[10] have been revised by the American Heart Association (AHA). The most recent update, published in 2015, recognizes the variability in clinical presentation in populations at different levels of risk and includes Doppler echocardiography as a tool to diagnose cardiac involvement; these changes bring the criteria into closer alignment with other international guidelines.[11]

Laboratory evidence of a preceding group A streptococcal infection is needed whenever possible. Without it, the diagnosis of ARF is in doubt, except in patients with chorea, which may be the sole initial manifestation of ARF, and rarely in patients with indolent rheumatic carditis with insidious onset and slow progression.[11]

The AHA suggests that diagnostic criteria may be applied differently, depending on rate of ARF or rheumatic heart disease (RHD) in the population. This can help avoid overdiagnosis in low-incidence populations and underdiagnosis in high-risk ones. The AHA defines low risk as an ARF incidence of <2 per 100,000 school-aged children (usually 5–14 years old) per year or an all-age prevalence of RHD of ≤1 per 1000 population per year. Children not clearly from a low-risk population are at moderate to high risk depending on their reference population.[11]

Jones criteria for the diagnosis of initial ARF are the presence of two major manifestations or one major and two minor manifestations. For recurrent ARF, the criteria are two major manifestations, one major and two minor manifestations, or three minor manifestations.

Major manifestations comprise the following:

  • Carditis, clinical and/or subclinical (ie, detected by echocardiography)
  • Arthritis
  • Chorea
  • Erythema marginatum
  • Subcutaneous nodules

In patients from low-risk populations, arthritis must be polyarthritis. For patients from moderate- and high-risk populations, either monoarthritis or polyarthritis qualifies; polyarthralgia may qualify if other causes have been excluded.

Minor manifestations in low-risk populations comprise the following:

  • Polyarthralgia
  • Fever ≥38.5°C
  • Acute phase reactions: Erythrocyte sedimentation rate (ESR) ≥60 mm in the first hour and/or C-reactive protein (CRP) level ≥3.0 mg/dL
  • Prolonged PR interval, after accounting for age variability (unless carditis is a major criterion)

Minor manifestations in moderate- and high-risk populations comprise the following:

  • Monoarthralgia
  • Fever ≥38°C
  • ESR ≥30 mm/h and/or CRP ≥3.0 mg/dL
  • Prolonged PR interval, after accounting for age variability (unless carditis is a major criterion)

Laboratory studies

According to the AHA, any one of the following can serve as evidence of preceding group A streptococcal infection[11] :

  • Elevated or rising  streptococcal antibody titer; a rise in titer is better evidence than a single titer result
  • A positive throat culture for group A β-hemolytic streptococci
  • A positive rapid group A streptococcal carbohydrate antigen test in a child whose clinical presentation suggests a high pretest probability of streptococcal pharyngitis

Rapid streptococcal tests are principally useful for prevention of ARF. Currently available tests have 90-100% specificity, permitting immediate initiation of antibiotic therapy in patients with positive results. In contrast, the sensitivity of these tests is 70-90%, lessening the value of a negative result.

Antistreptococcal antibodies usually reach a peak titer (in Todd units) at the time of onset of ARF and are more useful for diagnosis. Specific antibodies to streptococcal antigens also indicate true infection rather than mere carriage of the organism. These antibodies target extracellular products produced by streptococci.

Antistreptococcal antibodies include the following:

  • Antistreptolysin O (ASO)
  • Antideoxyribonuclease B (anti-DNAse B)
  • Antistreptokinase
  • Antihyaluronidase
  • Anti-DNAase (anti-DNPase)

Although age, geographic location, and season affect the titers, an elevated titer of at least one of these antibodies indicates streptococcal infection in 95% of patients. ASO titers are found in 80-85% of patients with ARF.

However, note that an isolated positive ASO titer is not necessarily an indication of ARF, as it may also be found in patients with certain related diseases such as rheumatoid arthritis and Takayasu arteritis. Therefore, rising ASO titers should be combined with a careful clinical evaluation and the discovery of other antistreptococcal antibodies to support the diagnosis of ARF.

The sensitivity of throat culture as evidence of recent streptococcal infection is 25-40%. For comparison, the sensitivity of ASO titer (adults with >240 Todd U and children with >320 Todd U) is 80%. The sensitivity of an elevated ASO titer in addition to anti-DNAse B or antihyaluronidase is 90%.

Acute-phase reactants such as C-reactive protein and ESR are usually elevated and helpful in monitoring disease activity.

Other laboratory tests may be helpful but not for definitive diagnosis. Synovial fluid analysis reveals a sterile inflammatory reaction, usually with fewer than 20,000 cells/μL (mainly polymorphonuclear) without crystals.

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Histologic Findings

Synovial biopsy (which is rarely performed) reveals mild inflammatory changes. The synovial membrane may be thickened, erythematous, and covered by a fibrinous exudate.

Endomyocardial biopsies have not contributed significantly to diagnosis. Focal fibrinoid lesions in the heart and histiocytic granulomas called Aschoff nodules may be late findings. Pancarditis develops with involvement of all layers of the heart.

Subcutaneous nodule histopathology reveals edema, fibrinoid necrosis, and mononuclear cell infiltrate.

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Chest Radiography

A chest radiograph may reveal cardiomegaly. See the image below.

Chest radiograph showing cardiomegaly due to cardi Chest radiograph showing cardiomegaly due to carditis of acute rheumatic fever.
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Echocardiography with Doppler

Current American Heart Association criteria recommendations regarding echocardiography are as follows:

  • Echocardiography with Doppler should be performed in all cases of confirmed and suspected ARF (class I)
  • It is reasonable to consider performing serial echocardiography/Doppler studies in any patient with diagnosed or suspected ARF, even if documented carditis is not present on diagnosis (class IIa)
  • Echocardiography/Doppler testing should be performed to assess whether carditis is present in the absence of auscultatory findings, particularly in moderate- to high-risk populations and when ARF is considered likely (class I)
  • Echocardiography/Doppler findings not consistent with carditis should exclude that diagnosis in patients with a heart murmur otherwise thought to indicate rheumatic carditis (class I)

Doppler findings in rheumatic valvulitis

To diagnose pathological mitral regurgitation by Doppler, all four of the following criteria must be met:

  • Seen in at least two views
  • Jet length ≥2 cm in at least one view
  • Peak velocity >3 m/sec
  • Pan-systolic jet in at least one envelope

To diagnose pathological aortic regurgitation by Doppler, all four of the following criteria must be met:

  • Seen in at least two views
  • Jet length ≥1 cm in at least one view
  • Peak velocity >3 m/sec
  • Pan-diastolic jet in at least one envelope

Echocardiographic findings in rheumatic valvulitis

Acute mitral valve changes include the following:

  • Annular dilation
  • Chordal elongation
  • Chordal rupture resulting in flail leaflet with severe mitral regurgitation
  • Anterior (less commonly, posterior) leaflet tip prolapse
  • Beading/nodularity of leaflet tips

Chronic mitral valve changes that are not seen in acute carditis include the following:

  • Leaflet thickening
  • Chordal thickening and fusion
  • Restricted leaflet motion
  • Calcification

Aortic valve changes in either acute or chronic carditis include the following:

  • Irregular or focal leaflet thickening
  • Coaptation defect
  • Restricted leaflet motion
  • Leaflet prolapse
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Contributor Information and Disclosures
Author

Robert J Meador, Jr, MD Rheumatologist, Dallas Diagnostic Association

Robert J Meador, Jr, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, Texas Medical Association, Dallas County Medical Society, Lupus Foundation of America, Lone Star Chapter, Sjögren’s Syndrome Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Irwin Jon Russell, MD, PhD, MS, FACR, ACR-Master Medical Director for Fibromyalgia Research and Consulting, (Retired) Faculty, Division of Clinical Immunology and Rheumatology, University of Texas Health Science Center at San Antonio

Irwin Jon Russell, MD, PhD, MS, FACR, ACR-Master is a member of the following medical societies: Alpha Omega Alpha, International Myopain Society, American College of Physicians, American College of Rheumatology, International Association for the Study of Pain

Disclosure: Received consulting fee from Daiichii Sankyo for review panel membership; Received grant/research funds from Pfizer Pharma for independent contractor; Received grant/research funds from Lilly Pharma for independent contractor.

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.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Genentech; Pfizer; Questcor.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

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Clinical manifestations and time course of acute rheumatic fever.
Chest radiograph showing cardiomegaly due to carditis of acute rheumatic fever.
Erythema marginatum, the characteristic rash of acute rheumatic fever.
 
 
 
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