Recurrent Rheumatic Fever Research Articles

Follow up study of acquired valvular heart disease.

In patients with acquired valvular heart disease detected by group cardiac examinations at school, we analyzed follow-up data obtained during school days as well as after graduation from senior high school. Of the 343 patients followed up after graduation from senior high school up to an age range of 20-38 years (mean: 29.3 years), 18 (5.2%) died, 16 (4.7%) deteriorated, 159 (46.4%) remained unchanged, 40 (11.7%) improved, 18 (5.2%) spontaneously recovered and 30 (9.7%) were treated surgically. Of patients who showed spontaneous recovery after graduation from senior high school, 16 cases (8.4%) had mitral regurgitation and 2 (3.6%) had mitral stenosis-regurgitation. In some patients, the disease type changed many years after graduation from senior high school. In particular, the appearance of stenosal lesions in the mitral or aortic valve was often delayed. The mean annual death rate for patients with acquired valvular heart disease (age range: 6-38 years) between April 1962 and March 1983 was 0.65%. The rate peaked at the 15-17 years age range. In recent years, the fatality rate has been falling and no deaths are seen in younger patients. In the past, the leading cause of death in juvenile patients with acquired valvular heart disease was the recurrence of rheumatic fever. For the past ten years, however, no death attributable to the recurrence of rheumatic fever has been registered.

Are all recurrences of “pure” Sydenham chorea true recurrences of acute rheumatic fever?

We are conducting prospective studies of patients in Santiago, Chile, who have had an attack of rheumatic fever and are receiving continuous secondary prophylaxis with monthly injections of benzathine penicillin G. Throat cultures are obtained just prior to injection each month, and serum antistreptococcal antibody titers (antistreptolysin O and antideoxyribonuclease B) are performed at least every 3 months. During the course of these studies we have observed 17 recurrences of "pure" chorea in 10 patients (six girls). In four recurrences the timing of serologic studies and onset of chorea appeared to exclude the occurrence of an immunologically significant group A streptococcal infection within the preceding 6 to 9 months. In one case the period of serologic follow-up was too brief to allow a definite determination. In the remaining 12 recurrences serologic evidence was suggestive or confirmatory of recent streptococcal infection; however, in several instances the titer elevations were quite modest. Our data suggest that in certain chorea-prone patients, Sydenham chorea may recur after streptococcal infections too weak and transient to be readily detectable or, alternatively, after stimuli other than streptococcal infection.

Recurrence of Rheumatic Fever

To the Editor.— In a case report on prophylaxis for rheumatic fever, Nordin1 expressed dismayed surprise that monthly injections of 1.2 million units of benzathine penicillin G (BPG) had failed to prevent the recurrence of rheumatic fever in a 9-year-old girl. Although BPG was clearly the best of the various antistreptococcal prophylactic regimens tested in randomized clinical trials conducted by my colleagues and me at Irvington House during the late 1950s and 1960s, BPG was not perfect.

Rheumatic Fever Article Questioned

To the Editor.— The suggestion of Nordin1 that there may be a need to re-evaluate the current recommended prophylaxis for children with rheumatic fever is valid, particularly if carefully planned and controlled studies could be carried out. However, the author's contention that "It has been assumed that the levels of penicillin [following monthly intramuscular injection of 1.2 million units of benzathine penicillin G] are adequate to prevent reinfection with group A streptococcus, and hence to prevent recurrences of rheumatic fever" has always been qualified by others.

Recurrence of Rheumatic Fever During Prophylaxis with Monthly Benzathine Penicillin G

A 9-year-old girl had apparent recurrence of rheumatic fever while receiving monthly benzathine penicillin injections. A review of pharmacokinetc studies on the subject suggests that this is a real risk. A need for review of the current recommendations for rheumatic fever prophylaxis is suggested.

Recurrences of acute rheumatic fever. A prospective study of 79 episodes.

Fifty-three patients with acute rheumatic fever and 79 recurrences were studied prospectively for six years. All the patients were examined by the same physicians during their initial attack, as well as during recurrences. Of the 27 patients with carditis in the initial attack, all had persistence of cardiac involvement during subsequent recurrences, and some additional involvement developed. Of the 26 patients without carditis in the initial attack, only two patients who initially had pure chorea also had chorea and carditis in recurrences. These data strongly support the concept that if the host escapes carditis in the initial attack, he/she will continue to do so in subsequent recurrences; however, if the heart is involved in the initial attack, recurrences can inflict further cardiac damage. In view of these findings, the current approach to prophylaxis should probably be modified.

Clinical-Echocardiographic Correlations in Acute Rheumatic Fever

Thirty-three children with acute rheumatic fever were studied using echocardiography to characterize heart involvement in this disease. Among 26 subjects with a first episode of acute rheumatic fever, 18 had a clinical diagnosis of carditis and six had heart failure. Heart failure usually resulted from valvular incompetence rather than from myocardial failure in these patients. Conversely, among seven subjects with recurrent rheumatic fever, five had a clinical diagnosis of carditis and four had heart failure. Severe left ventricular dysfunction noted on echocardiography probably contributed significantly to the appearance of heart failure in two of these four subjects. Ten patients were initially believed not to have carditis: a diagnosis of mitral valvulitis was made in two of these ten on the basis of the results of the echocardiographic examination. Echocardiography, which provides important information on the cardiac status of patients with acute rheumatic fever, may help in assessing the prognosis and may be useful in the therapy of these patients.

Clinical Immunology of the Heart

Clinical Immunology of the Heart provides an important introduction to immunologic diagnosis, cellular immunity, and immunogenetics for practicing cardiologists and others interested in cardiovascular disease. The application of the techniques and knowledge in this book will undoubtedly produce much new, valuable information and better understanding of heart disease mechanisms in the future. Chapter 1 emphasizes immunologic methods in cardiology applicable to cardiac diseases of presumed immunologic origin. Chapter 2 reveals how antibodies can be used for sensitive measurements of immunologic changes in vitro and even therapeutically. For example, purified digoxinspecific Fab fragments may be used to reverse advanced digoxin intoxication in man. Chapter 3 discusses immunologic concepts in rheumatic fever, particularly those relating group A streptococcus to the clinical and pathological events implicated in rheumatic fever and rheumatic heart disease. Evidence of a persistent genetic marker for rheumatic fever throughout life, coupled with recurrences of rheumatic fever in older people,

Follow up study of rheumatic heart disease.

The follow up study on rheumatic heart disease was carried out over a 20 year period by the questionaire method. Two hundreds and seventy-nine patients were analyzed and the following results were obtained. 1) Sixteen cases (5.5%) died, 20 cases (6.8%) showed deterioration, 155 cases (53.1%) were unchanged, 35 cases (12.0%) were improved, 12 cases (4.1%) were announced that their valvular lesions disappeared and 22 cases (7.2%) underwent cardiac surgery. The more severe the findings at the final examination under our program, the poorer the courses. 2) The cases having a severe status index showed a tendency for poor prognoses. Mitral steno-regurgitation revealed the poorest prognoses. 3) 84.3 per cent of the living cases were found to be leading normal daily lives without any restriction. 4) The average death rate was 1.0% per year during the 20 years between 1958 and 1978. The death rate for age group between 9 and 17 years old was the highest (1.34% per year). 5) The leading cause of death in every group including all the cases under our program was a recurrence of rheumatic fever. However in groups older than 18 years of age chronic congestive heart failure and unsuccessful cardiac surgery were leading causes.

Two studies of compliance with daily prophylaxis in rheumatic fever patients in Iowa.

We determined the penicillin compliance rates in school year 1974-75 for 235 children with rheumatic fever through analysis of urine specimens collected at school. Patients relatively low on compliance during the first year of sampling were divided into two equal size groups for a second year sampling study. One-half (N = 44) of these second year study patients and their parents were readvised regarding the need for penicillin prophylaxis and one-half (N = 44) served as controls. We related eductional data, behavioral ratings, and family information to compliance rates in both study years. The overall compliance for the children during the initial sampling year was 64.6 per cent. Factors found to be significantly related to compliance in year one were: 1) male sex, 2) large sibship, 3) increased number of behavior problems, 4) relatively poor academic progress, 5) lower maternal educational level, and 6) recurrence of rheumatic fever. Compliance rates for reinforced patients did not differ significantly from controls during the second year sampling.

Die Bedeutung der Röntgendiagnostik der Hände beim Systemischen Lupus erythematodes. Aus einer retrospektiven klinischröntgenologischen Studie von 124 Patienten mit Kollagenosen

40 patients with SLE were assessed, the diagnoses being made according to modified ARA-criteria; the hand films of 25 of these patients were analysed. The most important roentgenologic findings consisted of reducible deformities with mild or absent articular changes in the deformed MCP and PIP joints. As these changes often occur late in the course of SLE, a primary radiological diagnosis was possible in only three cases (8%), whereas hand films provided confirmatory evidence of disease in a further seven patients. These roentgenological characteristics of SLE were found significantly less often (p < 0.01) in patients with definite RA (3% compared to 30% of 40 SLE patients); this group tended to have positive ANF (antinuclear factors). Antibodies against DNA may be absent, especially in a less active phase of disease. ANF is non-specific, and SLE simulates RA in 10-20% of cases. It is, therefore, very important in individual cases to consider the diagnosis of SLE in the presence of deformity without corresponding articular changes. Direct comparison of both the p.a. and oblique views is essential in the evaluation of reducible deformities, although this point has not been stressed in the literature. Reducible deformities may be overlooked in physical examination, when the patient gives no history of functional disability. The main differential diagnosis is Jaccoud's arthropathy, which is rarely seen in a general hospital. Most of these patients give a history of recurrent rheumatic fever, a minority complain about joint pain or disability, approximately 90% show signs indicating a valvular lesion of the heart, over 75% have a normal ESR and a positive rheumatoid or antinuclear factor is very rarely found. The distinction from SLE or rheumatoid arthritis is therefore easily established on additional non-radiological criteria.

Streptococcal Infections That Fail to Cause Recurrences of Rheumatic Fever

Prospective studies of recurrences of streptoccal infection and acute rheumatic fever were conducted among patients attending the acute rheumatic fever prophylaxis clinic (City of Memphis Hospitals, Memphis, Tennessee) between 1965 and 1972. The patient population consisted of 124 rheumatic children and adults, two-thirds of whom had evidence of rheumatic heart disease. A total of 104 immunologically documented streptococcal infections occurred during 235 patient-years of follow-up (44.3 infections per 100 patient-years) without a single recurrence of rheumatic fever. Immune responses tended to be modest, and 80% of the infections were subclinical. The majority of our group A streptococcal isolates were obtained from routine cultures of specimens from asymptomatic individuals. Many of these strains were "pyoderma" serotypes, whereas others exhibited a characteristic (production of opacity factor) recently reported to be associated with decreased immunogenicity. Several factors may have contributed to the low recurrence rate of acute rheumatic fever, including the age range of the population under study and immunologically significant infections with strains of Streptococcus that were not group A, but a major reason may be the possibility that the group A strains prevalent in this population have diminished rheumatogenic potential.

Control of Rheumatic Fever: How Are We Doing?

The American Heart Association has recently published updated recommendations for the prevention of acute rheumatic fever.¹These recommendations are essentially the same as those first published 24 years ago²; the major differences are a consequence of the development of injectable penicillin G benzathine and of erythromycin, and the demonstration that group A streptococci frequently exhibit resistance to the tetracyclines. The similarities indicate that there have been very few changes in our approach to the control of rheumatic heart disease since it was first shown that acute rheumatic fever can be averted by appropriate treatment of the inciting streptococcal infection and that recurrent rheumatic fever can be prevented by continuous prophylaxis. We still do not know how to predict among those with streptococcal infections who are at risk for rheumatic fever, how to distinguish streptococcal carriers from those with actual infection except in retrospect, or exactly how the<i>Streptococcus</i>

Effect of long-term therapies with penicillin and sulfadiazine on Streptococcus mutans and lactobaccilli in dental plaque.

Plaque samples were obtained from 13 children receiving long-term therapy with benzathine penicillin for the prevention of rheumatic fever recurrences, 31 children receiving oral sulfadiazine for the same purpose, and 29 untreated siblings. The therapies were found to have no effect upon the proportions of Streptococcus mutans or lactobacilli in dental plaque, upon the percentage of children harboring the organisms, nor upon the susceptibility of the organisms to penicillin and sulfadiazine. Of the S. mutans strains tested, 97% had a minimal inhibitory concentration of penicillin G of less than 48 ng/ml and, of the lactobacillus strains tested, 96.8% had a minimal inhibitory concentration of less than 1,600 ng/ml. All strains of both organisms were profoundly resistant to sulfadiazine.

Repair of mitral regurgitation: An 11 year experience

One hundred thirty-three patients who underwent measured asymmetric annuloplasty for mitral regurgitation have been followed up for up to 11 years. The procedure has a very small operative risk and, for patients with rheumatic heart disease, a very low late mortality and morbidity rate. Early good results have been sustained for this follow-up period. Late breakdown of the repair has not been seen after 3 years unless infection or recurrent rheumatic fever intervened, nor has significant late stenosis been seen as a result of measured annuloplasty. These findings suggest that when the valve is repaired by this technique, competency is assured and an adequate orifice results.

Streptococcal infections. Masking by oral prophylaxis with penicillin.

When streptococcal infections with an antistreptolysin O response occur in spite of prophylaxis with penicillin administered orally, throat cultures are often falsely negative. In comparisons of rheumatic children given prophylaxis with siblings not receiving prophylaxis, cultures were negative in only 4.1% of 244 clinical infections in siblings but in 34.4% of 61 clinical infections in rheumatic children. Corresponding figures for subclinical infections were 12.8% of 384 infections in siblings and 49.5% of 95 infections in children receiving prophylaxis. Masked streptococcal infections are dangerous. Thus, 15 rheumatic fever recurrences followed 68 such infections, whereas six recurrences occurred in 88 infections with positive cultures. Although penicillin often masked throat cultures when streptococcal infection occurred in spite of prophylaxis, it did not alter the frequency with which streptococcal infections caused clinical symptoms.

Streptococcal Infections

When streptococcal infections with an antistreptolysin O response occur in spite of prophylaxis with penicillin administered orally, throat cultures are often falsely negative. In comparisons of rheumatic children given prophylaxis with siblings not receiving prophylaxis, cultures were negative in only 4.1% of 244 clinical infections in siblings but in 34.4% of 61 clinical infections in rheumatic children. Corresponding figures for subclinical infections were 12.8% of 384 infections in siblings and 49.5% of 95 infections in children receiving prophylaxis. Masked streptococcal infections are dangerous. Thus, 15 rheumatic fever recurrences followed 68 such infections, whereas six recurrences occurred in 88 infections with positive cultures. Although penicillin often masked throat cultures when streptococcal infection occurred in spite of prophylaxis, it did not alter the frequency with which streptococcal infections caused clinical symptoms.

Prevention of rheumatic fever.

To the Editor.— The development of methods for preventing recurrences of rheumatic fever by preventing group A streptococcal respiratory infections has been a major factor in the reduction of prevalence and severity of rheumatic heart disease. Although the intramuscular injection of 1.2 million units of benzathine penicillin G every four weeks is probably most effective for prophylaxis, the method has not gained wide acceptance—largely because of frequent prolonged pain at the site of injection and because of the risk of untoward reactions. For this reason, most physicians prescribe penicillin, to be taken daily by mouth, for prophylaxis in patients who have had rheumatic fever or who have rheumatic heart disease. In a long-term family study comparing patients with rheumatic fever receiving prophylaxis therapy, with siblings not receiving prophylaxis therapy, we found that orally administered penicillin (usually 200,000 units, twice a day) reduced the incidence of significant streptococcal respiratory infections by

Antistreptolysin-O titers in the course of oral penicillin administration for the prevention of recurrence of rheumatic fever

Antistreptolysin-O titers in the course of oral penicillin administration for the prevention of recurrence of rheumatic fever

Risk of rheumatic-fever recurrences after streptococcal infections. Prospective study of clinical and social factors.

Abstract The rheumatic-fever recurrence rate per streptococcal infection was studied in 393 patients in whom 711 streptococcal infections and 123 recurrences developed. Factors were evaluated for their relation to the recurrence rate by means of statistical technics that allowed testing the significance of a given factor while holding the others constant; thus, each factor was evaluated independently from the others. Symptoms of pharyngitis (sore throat and fever) were significantly associated with a high recurrence rate, whereas magnitude of rise in antistreptolysin-O titer was not. Young age and, particularly, short interval since the preceding rheumatic attack, were also significantly associated with a high rate of recurrence, as were existing rheumatic heart disease, number of previous attacks and oral (rather than parenteral) administration of drug prophylaxis. The effects of overcrowding, yearly family income, welfare status, rheumatic fever in siblings and ethnic group were not significant.