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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.

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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 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.

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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.

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Procedures

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

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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.

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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 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]

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Contributor Information and Disclosures
Author

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.

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

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.

References
  1. Cilliers AM. Rheumatic fever and its management. BMJ. 2006 Dec 2. 333(7579):1153-6. [Medline].

  2. Stollerman GH. Rheumatic fever. Lancet. 1997 Mar 29. 349(9056):935-42. [Medline].

  3. Bisno AL, Pearce IA, Stollerman GH. Streptococcal infections that fail to cause recurrences of rheumatic fever. J Infect Dis. 1977 Aug. 136(2):278-85. [Medline].

  4. Shulman ST. Rheumatic heart disease in developing countries. N Engl J Med. 2007 Nov 15. 357(20):2089; author reply 2089. [Medline].

  5. McDonald M, Currie BJ, Carapetis JR. Acute rheumatic fever: a chink in the chain that links the heart to the throat?. Lancet Infect Dis. 2004 Apr. 4(4):240-5. [Medline].

  6. Carapetis JR, McDonald M, Wilson NJ. Acute rheumatic fever. Lancet. 2005. 366:155-68. [Medline].

  7. Erdem G, Mizumoto C, Esaki D, Reddy V, Kurahara D, Yamaga K, et al. Group A streptococcal isolates temporally associated with acute rheumatic fever in Hawaii: differences from the continental United States. Clin Infect Dis. 2007 Aug 1. 45(3):e20-4. [Medline].

  8. Guilherme L, Kalil J, Cunningham M. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006 Feb. 39(1):31-9. [Medline].

  9. Guilherme L, Kalil J. Rheumatic Heart Disease: Molecules Involved in Valve Tissue Inflammation Leading to the Autoimmune Process and Anti-S. pyogenes Vaccine. Front Immunol. 2013. 4:352. [Medline].

  10. Veasy LG, Wiedmeier SE, Orsmond GS. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med. 1987 Feb 19. 316(8):421-7. [Medline].

  11. Wallace MR, Garst PD, Papadimos TJ, Oldfield EC 3rd. The return of acute rheumatic fever in young adults. JAMA. 1989 Nov 10. 262(18):2557-61. [Medline].

  12. Erdem G, Dodd A, Tuua A, Sinclair S, I'atala TF, Marrone JR, et al. Acute rheumatic fever in American Samoa. Pediatr Infect Dis J. 2007 Dec. 26(12):1158-9. [Medline].

  13. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005 Nov. 5(11):685-94. [Medline].

  14. Carapetis JR. Rheumatic heart disease in developing countries. N Engl J Med. 2007 Aug 2. 357(5):439-41. [Medline].

  15. Joseph N, Madi D, Kumar GS, Nelliyanil M, Saralaya V, Rai S. Clinical spectrum of rheumatic Fever and rheumatic heart disease: a 10 year experience in an urban area of South India. N Am J Med Sci. 2013 Nov. 5(11):647-52. [Medline].

  16. Casey JD, Solomon DH, Gaziano TA, Miller AL, Loscalzo J. Clinical problem-solving. A patient with migrating polyarthralgias. N Engl J Med. 2013 Jul 4. 369(1):75-80. [Medline].

  17. Atatoa-Carr P, Lennon D, Wilson N,. Rheumatic fever diagnosis, management, and secondary prevention: a New Zealand guideline. N Z Med J. 2008 Apr 4. 121(1271):59-69. [Medline].

  18. Weiner SG, Normandin PA. Sydenham chorea: a case report and review of the literature. Pediatr Emerg Care. 2007 Jan. 23(1):20-4. [Medline].

  19. Marijon E, Ou P, Celermajer DS, Ferreira B, Mocumbi AO, Jani D, et al. Prevalence of rheumatic heart disease detected by echocardiographic screening. N Engl J Med. 2007 Aug 2. 357(5):470-6. [Medline].

  20. Marijon E, Ou P, Celermajer DS, Ferreira B, Mocumbi AO, Sidi D, et al. Echocardiographic screening for rheumatic heart disease. Bull World Health Organ. 2008 Feb. 86(2):84. [Medline].

  21. Vijayalakshmi IB, Vishnuprabhu RO, Chitra N, Rajasri R, Anuradha TV. The efficacy of echocardiographic criterions for the diagnosis of carditis in acute rheumatic fever. Cardiol Young. 2008 Oct 10. 1-7. [Medline].

  22. Sahin M, Yildirim I, Ozkutlu S, Alehan D, Ozer S, Karagöz T. Clinical features and mid- and long-term outcomes of pediatric patients with subclinical carditis. Turk J Pediatr. 2012 Sep-Oct. 54(5):486-92. [Medline].

  23. Narula J, Kaplan EL. Echocardiographic diagnosis of rheumatic fever. Lancet. 2001 Dec 8. 358(9297):2000. [Medline].

  24. Tubridy-Clark M, Carapetis JR. Subclinical carditis in rheumatic fever: a systematic review. Int J Cardiol. 2007 Jun 25. 119(1):54-8. [Medline].

  25. Lopez-Benitez JM, Miller LC, Schaller JG, Moreno LM, de Canata ME. Erroneous diagnoses in children referred with acute rheumatic fever. Pediatr Infect Dis J. 2008 Feb. 27(2):181-2. [Medline].

  26. Kaplan EL, Anthony BF, Chapman SS, Ayoub EM, Wannamaker LW. The influence of the site of infection on the immune response to group A streptococci. J Clin Invest. 1970 Jul. 49(7):1405-14. [Medline].

  27. Ayoub EM, Nelson B, Shulman ST, Barrett DJ, Campbell JD, Armstrong G. Group A streptococcal antibodies in subjects with or without rheumatic fever in areas with high or low incidences of rheumatic fever. Clin Diagn Lab Immunol. 2003 Sep. 10(5):886-90. [Medline].

  28. Wilson NJ, Voss L, Morreau J, Stewart J, Lennon D. New Zealand guidelines for the diagnosis of acute rheumatic fever: small increase in the incidence of definite cases compared to the American Heart Association Jones criteria. N Z Med J. 2013 Aug 2. 126(1379):50-9. [Medline].

  29. Shivaram P, Ahmed MI, Kariyanna PT, Sabbineni H, Avula UM. Doppler echocardiography imaging in detecting multi-valvular lesions: a clinical evaluation in children with acute rheumatic fever. PLoS One. 2013. 8(9):e74114. [Medline].

  30. Pereira BA, da Silva NA, Andrade LE, Lima FS, Gurian FC, de Almeida Netto JC. Jones criteria and underdiagnosis of rheumatic fever. Indian J Pediatr. 2007 Feb. 74(2):117-21. [Medline].

  31. Voss LM, Wilson NJ, Neutze JM, Whitlock RM, Ameratunga RV, Cairns LM. Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial. Circulation. 2001 Jan 23. 103(3):401-6. [Medline].

  32. Bilavsky E, Eliahou R, Keller N, Yarden-Bilavsky H, Harel L, Amir J. Effect of benzathine penicillin treatment on antibiotic susceptibility of viridans streptococci in oral flora of patients receiving secondary prophylaxis after rheumatic fever. J Infect. 2008 Apr. 56(4):244-8. [Medline].

  33. Dale JB. Current status of group A streptococcal vaccine development. Adv Exp Med Biol. 2008. 609:53-63. [Medline].

  34. Veasy LG. Time to take soundings in acute rheumatic fever. Lancet. 2001 Jun 23. 357(9273):1994-5. [Medline].

  35. Ragupathi L, Herman J, Mather P. Late Recurrence of Rheumatic Fever. Am J Med Sci. 2015 Oct. 350 (4):342-3. [Medline].

 
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