Rheumatic heart disease is the most serious complication of rheumatic fever. Acute rheumatic fever follows 0.3% of cases of group A beta-hemolytic streptococcal pharyngitis in children. As many as 39% of patients with acute rheumatic fever may develop varying degrees of pancarditis with associated valve insufficiency, heart failure, pericarditis, and even death.
With chronic rheumatic heart disease, patients develop valve stenosis with varying degrees of regurgitation, atrial dilation, arrhythmias, and ventricular dysfunction. Chronic rheumatic heart disease remains the leading cause of mitral valve stenosis and valve replacement in adults in the United States. Acute rheumatic fever and rheumatic heart disease are thought to result from an autoimmune response, but the exact pathogenesis remains unclear. Although rheumatic heart disease was the leading cause of death 100 years ago in people aged 5-20 years in the United States, incidence of this disease has decreased in developed countries, and the mortality rate has dropped to just above 0% since the 1960s. Worldwide, rheumatic heart disease remains a major health problem. Chronic rheumatic heart disease is estimated to occur in 5-30 million children and young adults; 90,000 individuals die from this disease each year. The mortality rate from this disease remains 1-10%. A comprehensive resource provided by the World Health Organization (WHO) addresses the diagnosis and treatment
Pathogenesis of rheumatic Fever
Infection by streptococci begins with the binding of bacterial surface ligands to specific receptors on host cells, and subsequently involves specific processes of adherence, colonization and invasion. The binding of bacterial surface ligands to host surface receptors is the most crucial event in the colonization of the host, and it is initiated by fibronectin and by streptococcal fibronectin-binding proteins. Enviromental factors such as crowded living conditions, with close interpersonal contacts, contribute to the rapid spread and persistence of virulent streptococcal strains. Seasonal variations in the incidence of RF closely mimic variations in streptococcal infections.2
The epidemiological association between group A b-haemolytic streptococcal infections and the subsequent development of acute rheumatic fever (RF) has been well established. RF is a delayed autoimmune response to Group A streptococcal pharyngitis, and the clinical manifestation of the response and its severity in an individual is determined by host genetic susceptibility, the virulence of the infecting organism, and a conducive environment. The precise pathogenetic mechanism of RF has not been defined. Major histocompatibiltiy antigens, potential tissue-specific antigens, and antibodies developed during and immediately after a streptococcal infection are being investigated as potential risk factors in the pathogenesis of the disease. Recent evidence suggests that T-cell lymphocytes play an important role in the pathogenesis of rheumatic carditis. It has also been postulated that particular M types of group A streptococci have rheumatogenic potential. Such serotypes are usually heavily encapsulated, and form large, mucoid colonies that are rich in M-protein. M-protein is one of the best-defined determinants of bacterial virulence. The streptococcal M-protein extends from the surface of the streptococcal cell as an alpha–helical coiled coil dimer, and shares structural homology with cardiac myosin and other alpha-helical coiled coil molecules, such as tropomyosin, keratin and laminin. Laminin is an extracellular matrix protein secreted by endothelial cells that line the heart valves and is an integral part of the valve structure. Of the more than 130 M-protein types identified, M types such as 1, 3, 5, 6, 14, 18, 19 and 24 have been associated with RF.
There is strong evidence that an autoimmune response to streptococcal antigens mediates the development of RF and RHD in a susceptible host. Genetically-programmed determinants of host susceptibility to RF have been studied extensively, in an attempt to determine why only 0.3–3% of individuals with acute streptococcal pharyngitis go on to develop RF. Further data indicate that the gene controlling the low-level response to streptococcal antigen is closely linked to the Class II human leukocyte antigen, HLA.
Diagnosis of rheumatic fever
The Jones criteria were introduced in 1944 as a set of clinical guidelines for the diagnosis of rheumatic fever (RF) and carditis. The clinical features of RF were divided into major and minor categories, based on the prevalence and specificity of manifestations. Major manifestations were least likely to lead to an improper diagnosis and included carditis, joint symptoms, subcutaneous nodules, and chorea. A history of RF or preexisting rheumatic heart disease (RHD) was considered to be a major criterion since RF tends to recur. Minor manifestations were considered to be suggestive, but not sufficient, for a diagnosis of RF. The minor manifestations comprised clinical findings (such as fever and erythema marginatum, abdominal pain, epistaxis and pulmonary findings), and laboratory markers of acute inflammation, such as leukocytosis (WBC), and elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). It was proposed that the presence of two major, or one major and two minor, manifestations offered reasonable clinical evidence of rheumatic activity. Since a previous history of definite RF or RHD was considered a major criterion, diagnosis of a recurrence of RF did not require strict application of these guidelines, and minor manifestations were considered sufficient for the diagnosis.
The Jones criteria were subsequently reviewed by the American Heart Association (AHA) and the World Health Organization (WHO) and were modified to encompass vexing clinical issues and to improve the specificity. Although the Jones criteria have been revised repeatedly, the modifications were often made without prospective studies and were based on the perceived effects of previous revision.
Management
Hospital admission may be helpful for confirming a diagnosis of rheumatic fever (RF), for instituting treatment and for educating the patients and family. Initial tests should include a throat culture (or in some circunstances rapid streptococcal detection test), a measurement of streptococcal antibody titres (eg ASO or anti DNase B), an assessment of acute-phase reactants (eg ESR or CRP), a chest X-ray, an electrocardiogram, and an echocardiogram (if facilities are available). A blood culture may help to exclude infective endocarditis.2
All patients with acute RF should be placed on bed–chair rest and monitored closely for the onset of carditis. In patients with carditis, a rest period of at least four weeks is recommended, although physicians should make this decision on an individual basis. Ambulatory restrictions may be relaxed when there is no carditis and when arthritis has subsided.
1 Antimicrobial therapy
Eradication of the pharyngeal streptococcal infection is mandatory to avoid chronic repetitive exposure to streptococcal antigens. Ideally, two throat cultures should be performed before starting antibiotics. However, antibiotic therapy is warranted even if the throat cultures are negative. Antibiotic therapy does not alter the course, frequency and severity of cardiac involvement. The eradication of pharyngeal streptococci should be followed by long-term secondary prophylaxis to guard against recurrent pharyngeal streptococcal infections.
2. Anti-inflammatory agents
It is advisable to avoid premature administration of salicylates or corticosteroids until the diagnosis of RF is confirmed.
Aspirin. Currently, 30–60 mg/kg/d is given in four divided doses. This dosage is often more than sufficient to effect dramatic relief of the arthritis and fever. In general, higher dosages carry a greater risk of side effects, and there are no proved short-term or long-term benefits of giving high doses to produce salicylate blood levels of 20–30 mg/dL. The duration of therapy must be tailored to meet the needs of the patient, but use of aspirin for 2–6 weeks, with reduction in dosage toward the end of the course, is usually sufficient. Other non-steroidal anti-inflammatory agents are commonly used because of the concerns about Reye's Syndrome, but they appear to be less effective.
Corticosteroids. Corticosteroids are rarely indicated in current therapy. However, in the unusual patient with severe carditis and manifestations of congestive heart failure, therapy may be not only effective but also lifesaving. Corticosteroid therapy may be given as follows: prednisone, 2 mg/kg/d orally for 2 weeks (or comparable doses of other corticosteroids); reduce prednisone to 1 mg/kg/d the third week, and begin aspirin, 50 mg/kg/d; stop prednisone at the end of 3 weeks, and continue aspirin for 8 weeks or until the C-reactive protein is negative and the sedimentation rate is falling.