Pediatric Rheumatic Heart Disease Clinical Presentation
- Author: Thomas K Chin, MD; Chief Editor: P Syamasundar Rao, MD more...
A diagnosis of rheumatic heart disease is made after confirming antecedent rheumatic fever. The modified Jones criteria (revised in 1992) provide guidelines for the diagnosis of rheumatic fever.
The Jones criteria require the presence of 2 major or 1 major and 2 minor criteria for the diagnosis of rheumatic fever. The major diagnostic criteria include carditis, polyarthritis, chorea, subcutaneous nodules, and erythema marginatum. The minor diagnostic criteria include fever, arthralgia, prolonged PR interval on ECG, elevated acute phase reactants (increased erythrocyte sedimentation rate [ESR]), presence of C-reactive protein, and leukocytosis.
Additional evidence of previous group A streptococcal pharyngitis is required to diagnose rheumatic fever. One of the following must be present:
Positive throat culture or rapid streptococcal antigen test result
Elevated or rising streptococcal antibody titer
History of previous rheumatic fever or rheumatic heart disease
These criteria are not absolute; the diagnosis of rheumatic fever can be made in a patient with chorea alone if the patient has had documented group A streptococcal pharyngitis.
After a diagnosis of rheumatic fever is made, symptoms consistent with heart failure, such as difficulty breathing, exercise intolerance, and a rapid heart rate out of proportion to fever, may be indications of carditis and rheumatic heart disease.
Physical findings in a patient with rheumatic heart disease include cardiac and noncardiac manifestations of acute rheumatic fever. Some patients develop cardiac manifestations of chronic rheumatic heart disease.
Cardiac manifestations of acute rheumatic fever
Pancarditis is the most serious and second most common complication of rheumatic fever (50%). In advanced cases, patients may complain of dyspnea, mild-to-moderate chest discomfort, pleuritic chest pain, edema, cough, or orthopnea. For a graph illustrating the time course for the carditis relative to the other clinical manifestations of rheumatic fever, see the Medscape Reference article Pediatric Rheumatic Fever.
Upon physical examination, carditis is most commonly detected by a new murmur and tachycardia out of proportion to fever. New or changing murmurs are considered necessary for a diagnosis of rheumatic valvulitis.
Some cardiologists have proposed that echo-Doppler evidence of mitral insufficiency, particularly in association with aortic insufficiency, may be sufficient for a diagnosis of carditis (even in the absence of accompanying auscultatory findings) ; however, given the sensitivity of modern Doppler devices, this remains controversial.
Other cardiac manifestations include congestive heart failure and pericarditis.
Patients in whom the diagnosis of acute rheumatic fever is made should be frequently examined because of the progressive nature of the disease.
New or changing murmurs
The murmurs of acute rheumatic fever are typically due to valve insufficiency.
The following murmurs are most commonly observed during acute rheumatic fever:
Apical pansystolic murmur is a high-pitched, blowing-quality murmur of mitral regurgitation that radiates to the left axilla. The murmur is unaffected by respiration or position. Intensity varies but is grade 2/6 or greater. The mitral insufficiency is related to dysfunction of the valve, chordae, and papillary muscles.
Apical diastolic murmur (also known as a Carey-Coombs murmur) is heard with active carditis and accompanies severe mitral insufficiency. The mechanism for this murmur is relative mitral stenosis, as the large volume of regurgitant flow traverses the mitral valve during ventricular filling. It is heard best with the bell of the stethoscope, while the patient is in the left lateral position and the breath held in expiration.
Basal diastolic murmur is an early diastolic murmur of aortic regurgitation and is high-pitched, blowing, decrescendo, and heard best along the right upper and mid-left sternal border after deep expiration while the patient is leaning forward.
Congestive heart failure
Heart failure may develop secondary to severe valve insufficiency or myocarditis.
The physical findings associated with heart failure include tachypnea, orthopnea, jugular venous distention, rales, hepatomegaly, a gallop rhythm, edema, and swelling of the peripheral extremities.
A pericardial friction rub indicates that pericarditis is present.
Increased cardiac dullness to percussion and muffled heart sounds are consistent with pericardial effusion.
A paradoxical pulse (and accentuated fall in systolic blood pressure with inspiration) with decreased systemic pressure and perfusion and evidence of diastolic indentation of the right ventricle on echocardiogram reflect impending pericardial tamponade. In this clinical emergency, the pericardial effusion should be evacuated by pericardiocentesis.
Common noncardiac (and diagnostic) manifestations of acute rheumatic fever include polyarthritis, chorea, erythema marginatum, and subcutaneous nodules.
Other clinical, noncardiac manifestations include abdominal pain, arthralgias, epistaxis, fever, and rheumatic pneumonia.
Polyarthritis is the most common symptom and is frequently the earliest manifestation of acute rheumatic fever (70-75%). Characteristically, the arthritis begins in the large joints of the lower extremities (knees and ankles) and migrates to other large joints in the lower or upper extremities (elbows and wrists). Affected joints are painful, swollen, warm, erythematous, and limited in their range of motion. The pain is out of proportion to clinical findings.
The arthritis reaches maximum severity in 12-24 hours, persists for 2-6 days (rarely more than 3 wk) at each site, and rapidly responds to aspirin. Aspirin improves symptoms in affected joints and prevents further migration of the arthritis.
Polyarthritis is more common and more severe in teenagers and young adults than in younger children.
Sydenham chorea occurs in 10-30% of patients with rheumatic fever. Patients present with difficulty writing, involuntary grimacing, purposeless (choreiform) movements of the arms and legs, speech impairment, generalized weakness, and emotional lability. Physical findings include hyperextended joints, hypotonia, diminished deep tendon reflexes, tongue fasciculations ("bag of worms"), and a "milk sign" or relapsing grip demonstrated by alternate increases and decreases in tension when the patient grips the examiner's hand.
In the absence of a family history of Huntington chorea, the diagnosis of acute rheumatic fever is almost certain. A long latency period (1-6 mo) between streptococcal pharyngitis and the onset of chorea is observed; a history of an antecedent sore throat is frequently not obtained. Patients with chorea often do not demonstrate other Jones criteria. Chorea is slightly more common in females than males. It is also known as rheumatic chorea, Sydenham chorea, chorea minor, and St Vitus dance. Daily handwriting samples can be used as an indicator of progression or resolution of disease. Complete resolution of the symptoms typically occurs with improvement in 1-2 weeks and full recovery in 2-3 months. However, cases have been reported in which symptoms wax and wane for several years.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) may be associated with chorea. Children have been identified in whom group A streptococcal infection appears to have triggered a relapsing-remitting symptom complex characterized by obsessive-compulsive disorder (somatic obsessions and checking, cleaning, and repeating compulsions), and neurologic abnormalities, such as cognitive defects and motoric hyperactivity. The symptoms are prepubertal in onset and may include emotional lability, separation anxiety, and oppositional behaviors.
Streptococcal infection has been proposed to trigger the formation of antibodies that cross-react with the basal ganglia of genetically susceptible hosts in a manner similar to the proposed mechanism for Sydenham chorea, thus causing the symptom complex.
Erythema marginatum, also known as erythema annulare, is a characteristic rash that occurs in 5-13% of patients with acute rheumatic fever. It begins as 1-3 cm in diameter, pink-to-red nonpruritic macules or papules located on the trunk and proximal limbs but never on the face. The lesions spread outward to form a serpiginous ring with erythematous raised margins and central clearing. The rash may fade and reappear within hours and is exacerbated by heat. Thus, if the lesions are not well visualized, they can be accentuated by the application of warm towels, a hot bath, or the use of tangential lighting. The rash occurs early in the course of the disease and remains long past the resolution of other symptoms.
Erythema marginatum also has been reported in association with sepsis, drug reactions, and glomerulonephritis. For an example of the typical rash of erythema marginatum, see the Medscape Reference article Pediatric Rheumatic Fever.
Subcutaneous nodules are currently an infrequent manifestation of rheumatic fever. The frequency has declined over the past several years to 0-8% of patients with rheumatic fever. When present, the nodules appear over the extensor surfaces of the elbows, knees, ankles, knuckles, and on the scalp and spinous processes of the lumbar and thoracic vertebrae where they are attached to the tendon sheath. They are firm, nontender, and free from attachments to the overlying skin and range in size from a few mm to 1-2 cm. They vary in number from one to dozens (mean 3-4). Histologically, they contain areas resembling the Aschoff bodies seen in the heart.
Subcutaneous nodules generally occur several weeks into the disease and resolve within a month. These nodules are strongly associated with severe rheumatic carditis, and, in the absence of carditis, the diagnosis of subcutaneous nodules should be questioned.
Abdominal pain usually occurs at the onset of acute rheumatic fever. This pain resembles abdominal pain from other conditions with acute microvascular mesenteric inflammation and may mimic acute appendicitis. Patients may complain of arthralgias on presentation.
Determine if the patient has taken aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) because these may suppress the full manifestations of the disease. Epistaxis may be associated with severe protracted rheumatic carditis. Fevers above 39°C with no characteristic pattern are initially present in almost every case of acute rheumatic fever. Fever may be low-grade in children with mild carditis or absent in patients with pure chorea. It decreases without antipyretic therapy in about 1 week, but low-grade fevers persist for 2-3 weeks. Patients with rheumatic pneumonia present with the same signs as patients with infectious pneumonia. Rheumatic pneumonia should be differentiated from respiratory distress related to congestive heart failure.
Cardiac manifestations of chronic rheumatic heart disease
Valve deformities, thromboembolism, cardiac hemolytic anemia, and atrial arrhythmias are the most common cardiac manifestations of chronic rheumatic heart disease.
Mitral stenosis occurs in 25% of patients with chronic rheumatic heart disease and in association with mitral insufficiency in another 40%. Progressive fibrosis (ie, thickening and calcification of the valve) takes place over time, resulting in enlargement of the left atrium and formation of mural thrombi in that chamber. The stenotic valve is funnel-shaped, with a "fish mouth" resemblance. Upon auscultation, S1 is initially accentuated but becomes reduced as the leaflets thicken. P2 becomes accentuated, and the splitting of S2 decreases as pulmonary hypertension develops. An opening snap of the mitral valve often is heard at the apex, where a diastolic filling murmur also is heard.
Aortic stenosis from chronic rheumatic heart disease is typically associated with aortic insufficiency. The valve commissures and cusps become adherent and fused, and the valve orifice becomes small with a round or triangular shape. Upon auscultation, S2 may be single because the aortic leaflets are immobile and do not produce an aortic closure sound. The systolic and diastolic murmurs of aortic valve stenosis and insufficiency are heard best at the base of the heart.
Thromboembolism occurs as a complication of mitral stenosis. It is more likely to occur when the left atrium is dilated, cardiac output is decreased, and the patient is in atrial fibrillation. The frequency of this complication has decreased with the use of anticoagulation and the development of surgical repair for the valve abnormality.
Cardiac hemolytic anemia is related to disruption of the RBCs by a deformed valve. Increased destruction and replacement of platelets also may occur.
Atrial arrhythmias are typically related to a chronically enlarged left atrium (from a mitral valve abnormality). Successful cardioversion of atrial fibrillation to sinus rhythm is more likely to be successful if the left atrium is not markedly enlarged, the mitral stenosis is mild, and the patient has been in atrial fibrillation for less than 6 months. Patients should be anticoagulated before cardioversion to decrease the risk of systemic embolization.
Rheumatic fever is thought to result from an inflammatory autoimmune response. Rheumatic fever only develops in children and adolescents following group A beta-hemolytic streptococcal pharyngitis, and only streptococcal infections of the pharynx initiate or reactivate rheumatic fever.
Genetic studies show strong correlation between progression to rheumatic heart disease and human leukocyte antigen (HLA)-DR class II alleles and the inflammatory protein-encoding genes MBL2 and TNFA. Furthermore, both clones of heart tissue–infiltrating T cells and antibodies have been found to be cross-reactive with beta-hemolytic streptococcus. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10-(+) cells are consistently predominant in valvular tissue, whereas IL-4 regulatory cytokine expression is consistently low.
Decreased levels of regulatory T cells have also been associated with rheumatic heart disease and with increased severity. In utero precursors predisposing to rheumatic heart disease have also been proposed[11, 12] ; Eriksson et al suggest increased spiraling of the umbilical cord may increase risk of developing rheumatic heart disease secondary to presumed change in hemodynamic conditions during formation of the mitral valve.
The proposed pathophysiology for development of rheumatic heart disease is as follows: Cross-reactive antibodies bind to cardiac tissue facilitating infiltration of streptococcal-primed CD4+ T cells, which then trigger an autoimmune reaction releasing inflammatory cytokines (including TNF-alpha and IFN-gamma). Because few IL-4–producing cells are present in valvular tissue, inflammation persists, leading to valvular lesions.
WHO. Rheumatic Fever and Rheumatic Heart Disease. 2004. Available at http://www.who.int/cardiovascular_diseases/resources/en/cvd_trs923.pdf.
Parks T, Smeesters PR, Steer AC. Streptococcal skin infection and rheumatic heart disease. Curr Opin Infect Dis. 2012 Apr. 25(2):145-53. [Medline].
Pickering LK, et al. 2009 Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009. 616-628.
Veasy LG, Wiedmeier SE, Orsmond GS, et al. 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].
Breda L, Marzetti V, Gaspari S, Del Torto M, Chiarelli F, Altobelli E. Population-based study of incidence and clinical characteristics of rheumatic Fever in abruzzo, central Italy, 2000-2009. J Pediatr. 2012 May. 160(5):832-836.e1. [Medline].
Marijon E, Ou P, Celermajer DS, et al. Prevalence of rheumatic heart disease detected by echocardiographic screening. N Engl J Med. 2007 Aug 2. 357(5):470-6. [Medline].
AHA. Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council. on Cardiovascular Disease in the Young, the American Heart Association. JAMA 1992 Oct 21; 268(15):2069-73. [Medline].
Minich LL, Tani LY, Pagotto LT, Shaddy RE, Veasy LG. Doppler echocardiography distinguishes between physiologic and pathologic "silent" mitral regurgitation in patients with rheumatic fever. Clin Cardiol. 1997 Nov. 20(11):924-6. [Medline].
Mukhopadhyay S, Varma S, Gade S, Yusuf J, Trehan V, Tyagi S. Regulatory T-cell deficiency in rheumatic heart disease: a preliminary observational study. J Heart Valve Dis. 2013 Jan. 22(1):118-25. [Medline].
Bas HD, Baser K, Yavuz E, Bolayir HA, Yaman B, Unlu S. A shift in the balance of regulatory T and T helper 17 cells in rheumatic heart disease. J Investig Med. 2014 Jan. 62(1):78-83. [Medline].
Eriksson JG, Kajantie E, Phillips DI, Osmond C, Thornburg KL, Barker DJ. The developmental origins of chronic rheumatic heart disease. Am J Hum Biol. 2013 Sep-Oct. 25(5):655-8. [Medline].
Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. J Am Dent Assoc. 2008 Jan. 139 Suppl:3S-24S. [Medline]. [Full Text].
[Guideline] Remenyi B, Wilson N, Steer A, Ferreira B, Kado J, Kumar K. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease--an evidence-based guideline. Nat Rev Cardiol. 2011. 9(5):297-309. [Medline].
Beaton A, Aliku T, Okello E, Lubega S, McCarter R, Lwabi P. The utility of handheld echocardiography for early diagnosis of rheumatic heart disease. J Am Soc Echocardiogr. 2014 Jan. 27(1):42-9. [Medline].
Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007 Oct 9. 116(15):1736-54. [Medline]. [Full Text].
Yakub MA, Dillon J, Krishna Moorthy PS, Pau KK, Nordin MN. Is rheumatic aetiology a predictor of poor outcome in the current era of mitral valve repair? Contemporary long-term results of mitral valve repair in rheumatic heart disease. Eur J Cardiothorac Surg. 2013 Oct. 44(4):673-81. [Medline].
Abernethy M, Bass N, Sharpe N, et al. Doppler echocardiography and the early diagnosis of carditis in acute rheumatic fever. Aust N Z J Med. 1994 Oct. 24(5):530-5. [Medline].
Asbahr FR, Garvey MA, Snider LA, et al. Obsessive-compulsive symptoms among patients with Sydenham chorea. Biol Psychiatry. 2005 May 1. 57(9):1073-6. [Medline].
Braunwald E. Rheumatic fever. Heart Disease: A Textbook of Cardiovascular Medicine. 5th ed. Philadelphia, Pa: WB Saunders Co; 1997.
Carapetis JR, McDonald M, Wilson NJ. Acute rheumatic fever. Lancet. 2005 Jul 9-15. 366(9480):155-68. [Medline].
Cilliers AM, Manyemba J, Saloojee H. Anti-inflammatory treatment for carditis in acute rheumatic fever. Cochrane Database Syst Rev. 2003. CD003176. [Medline].
Clinical trial. The natural history of rheumatic fever and rheumatic heart disease. Ten-year report of a cooperative clinical trial of ACTH, cortisone, and aspirin. Circulation. 1965 Sep. 32(3):457-76. [Medline].
Cotran RS, Kumar V, Collins T, Robbins SL. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia, Pa: WB Saunders Co; 1999.
Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council. on Cardiovascular Disease in the Young, the American Heart Association. Pediatrics 1995 Oct; 96(4 Pt 1):758-64. [Medline].
Doshi H, Shukla V, Korula RJ. Emergency valve replacement in rheumatic heart disease. J Heart Valve Dis. 2003 Jul. 12(4):516-9. [Medline].
Ellis NM, Li Y, Hildebrand W, Cunningham MW. T cell mimicry and epitope specificity of cross-reactive T cell clones from rheumatic heart disease. J Immunol. 2005 Oct 15. 175(8):5448-56. [Medline].
Fae KC, Oshiro SE, Toubert A, et al. How an autoimmune reaction triggered by molecular mimicry between streptococcal M protein and cardiac tissue proteins leads to heart lesions in rheumatic heart disease. J Autoimmun. 2005 Mar. 24(2):101-9. [Medline].
Guilherme L, Fae K, Oshiro SE, Kalil J. Molecular pathogenesis of rheumatic fever and rheumatic heart disease. Expert Rev Mol Med. 2005 Dec 8. 7(28):1-15. [Medline].
Massell BF, Fyler DC, Roy SB. The clinical picture of rheumatic fever: diagnosis, immediate prognosis, course, and therapeutic implications. Am J Cardiol. 1958 Apr. 1(4):436-49. [Medline].
Narula J, Virmani R, Reddy KS, Tandon R. Rheumatic Fever. Washington DC: American Registry of Pathology; 1999.
Orün UA, Ceylan O, Bilici M, Karademir S, Ocal B, Senocak F. Acute rheumatic fever in the Central Anatolia Region of Turkey: a 30-year experience in a single center. Eur J Pediatr. 2012 Feb. 171(2):361-8. [Medline].
Rimoin AW, Hamza HS, Vince A, et al. Evaluation of the WHO clinical decision rule for streptococcal pharyngitis. Arch Dis Child. 2005 Oct. 90(10):1066-70. [Medline].
Robertson KA, Volmink JA, Mayosi BM. Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis. BMC Cardiovasc Disord. 2005 May 31. 5(1):11. [Medline].
Sampaio RO, Grinberg M, Leite JJ, et al. Effect of enalapril on left ventricular diameters and exercise capacity in asymptomatic or mildly symptomatic patients with regurgitation secondary to mitral valve prolapse or rheumatic heart disease. Am J Cardiol. 2005 Jul 1. 96(1):117-21. [Medline].
Shrivastava S, Dev V, Vasan RS, et al. Percutaneous balloon mitral valvuloplasty in juvenile rheumatic mitral stenosis. Am J Cardiol. 1991 Apr 15. 67(9):892-4. [Medline].
Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases [published erratum appears in Am J Psychiatry 1998 Apr;155(4):578]. Am J Psychiatry. 1998 Feb. 155(2):264-71. [Medline].
Talwar S, Rajesh MR, Subramanian A, et al. Mitral valve repair in children with rheumatic heart disease. J Thorac Cardiovasc Surg. 2005 Apr. 129(4):875-9. [Medline].
Walker KG, Lawrenson J, Wilmshurst JM. Neuropsychiatric movement disorders following streptococcal infection. Dev Med Child Neurol. 2005 Nov. 47(11):771-5. [Medline].