Natural History Of Rheumatic Fever Research Articles

Rheumatic Fever and Long-term Sequelae in Children.

Rheumatic fever and rheumatic heart disease continue unabated, affecting young individuals in most of the developing nations. Focal outbreaks of smaller magnitude have also been reported since the mid-1980s from industrialized western nations, where this disease had almost disappeared. The introduction of penicillin in the mid-1940s has markedly changed the natural history of rheumatic fever, although the incidence of rheumatic fever declined in developed nations even before that, mainly due to better living conditions. Treatment of rheumatic fever chiefly involves the use of antibiotics (penicillin) and anti-inflammatory drugs, like salicylates or corticosteroids, to eradicate Streptococci. Patients with severe carditis, congestive heart failure, or pericarditis are best treated with corticosteroids because these are more potent anti-inflammatory agents than salicylates. Salicylates may be sufficient for cases with mild or no carditis. The treatment must be continued for 12 weeks. Several studies have shown that valvular regurgitation, and not myocarditis, is the cause of congestive heart failure in active rheumatic carditis. Therefore, surgery with mitral valve replacement or repair is indicated in cases with intractable hemodynamics due to mitral regurgitation. The development of chronic valvular lesion after an episode of rheumatic fever is dependent upon the presence or absence of carditis in the previous attack and compliance with secondary prophylaxis. Recurrences due to inadequate penicillin prophylaxis are responsible for hemodynamically significant chronic valvular lesions requiring surgery. Primary prevention of rheumatic fever is fraught with difficulties and may not be feasible in most of the countries where the disease is rampant. Secondary prevention, ie, preventing recurrence of rheumatic fever, is the appropriate strategy with proven efficacy. A repository form of penicillin, benzathine penicillin G, given as an intramuscular injection at 3 weekly intervals in the dose of 1,200,000 U, remains the treatment of choice for secondary prevention of rheumatic fever. Alternative antibiotics may be used in those allergic to penicillin. An effective and safe vaccine against rheumatic fever is not yet available.

Treatment of rheumatic carditis.

Rheumatic fever and rheumatic heart disease continue unabated in most of the developing nations, affecting young individuals. Focal outbreaks of smaller magnitude have also been reported since mid 1980s from industrialized western nations, where this disease had almost disappeared. Introduction of penicillin in mid 1940s had markedly changed the natural history of rheumatic fever, although the incidence of rheumatic fever declined in developed nations before that, due to better living conditions. Treatment of rheumatic fever chiefly involves use of antibiotics (penicillin) to eradicate streptococci, and anti-inflammatory drugs like salicylates or corticosteroids. Patients with severe carditis, congestive heart failure and/or pericarditis are best treated with corticosteroids as these are more potent anti-inflammatory agents than salicylates. Salicylates may be sufficient for cases with mild or no carditis. The treatment must be continued for 12 weeks. Several studies have shown that valvular regurgitation, and not myocarditis, is the cause of congestive heart failure in active rheumatic carditis. Therefore surgery with mitral valve replacement or repair is indicated in cases with intractable hemodynamics due to mitral regurgitation. Development of chronic valvular lesion after an episode of rheumatic fever is dependent upon presence or absence of carditis in the previous attack and compliance with secondary prophylaxis. Recurrences due to inadequate penicillin prophylaxis are responsible for hemodynamically significant chronic valvular lesions requiring surgery.

A Clinicoepidemiologic Study of Heart Disease in Schoolchildren of Menoufia, Egypt

This study was conducted to determine the prevalence of rheumatic heart disease (RHD) and congenital heart disease (CHD) in primary schoolchildren of Menoufia, Egypt and to study the relationship between these two problems and socioeconomic conditions. A total of 8000 children were screened for cardiac disease in their schools. Children with confirmed RHD and CHD in addition to 200 healthy children (controls) were visited at their homes to assess their social environment and other factors according to a designed questionnaire. We found prevalence rates of 3.4/1000 and 2.6/1000 for the RHD and CHD respectively. The most common cardiac defects were double mitral and pulmonary stenosis in the RHD and CHD groups respectively. Nineteen (39.6%) of the patients were diagnosed for the first time during the study. Penicillin prophylaxis was received by only four (14.8%) of the RHD children and none of the CHD children. The number of other affected siblings, increased multiparity, repeated abortion, and intake of contraceptives by mothers were significantly higher in families of the children with CHD. The proportion of illiterate, unskilled, and heavy smoking fathers was higher in the two patient groups. Family income was lowest in the RHD group, while increased crowding index and low whole social environment were significantly related to both RHD and CHD. Effective programs at the community and health service levels are needed in Menoufia to solve the problem of heart disease in schoolchildren in the immediate future.

The Natural History of Rheumatic Fever and Rheumatic Heart Disease in the Orient

Studies published in the past 10 years suggest that group A streptococcal infections are frequent in the Orient and lead to a high incidence of rheumatic fever (RF) and rheumatic heart disease (RHD). In the present study, streptococcal infections were found to be more prevalent in Japan and Taiwan, whereas RF and RHD were more common and severe in the Philippines, Thailand, and Indonesia, particularly among the socioeconomically less privileged populations. The pattern of childhood RF varied: Carditis was the most common manifestation, occurring in 57% to 94% of the patients; polyarthritis was generally atypical and less common in the tropics; chorea minor and erythema marginatum were much more common in Japan, less common in Taiwan and rare in the tropics. RF recurrences were quite common and led to the development of new carditis, and deterioration or persistence of the pre-existing heart disease. The 5 year mortality rates differed greatly, ranging from zero to 42%. There was disappearance of the heart murmur in 16.5% to 37.5% of patients. Such apparent recovery was related to adherence to chemoprophylaxis. The major risk factors adversely affecting survival were the severity of carditis, inadequacy of medical service, non-compliance to chemoprophylaxis, RF recurrence, poor socioeconomic status, and high prevalence of group A streptococci. It is concluded that there is no uniform "Oriental-type" of natural history of RF and RHD. The natural history varies greatly among countries as is true in other parts of the world.

3. Social Problem of Rheumatic Heart Disease

Although there are many social problems in patients with rheumatic heart disease (RHD) due to chronic physical disability, the prophylaxis of RHD in the adult has not been established. Some reasons are that the natural history of rheumatic fever (RF) and RHD is not known in adults as in children, and that studies on adult RF are few in the world1)-6). From the point of prophylaxis, it is important to make clear what kind of disadvantages will such patients and their families have in social life. And it is necessary to clarify the character of acute RF and RHD in the adult.

The Natural History of Rheumatic Fever

RECENT REPORTS from Puerto Rico emphasize that rheumatic fever occurs among the children 1 and adults 2,3 of this tropical island. Furthermore, the manifestations now being observed are similar to those seen in colder climates. Moreover carditis seemed to have been at least as frequent and severe in this series as in those reported from temperate zones. 1 Whereas rheumatic fever was known to be both severe and prevalent at high altitudes, it has long been a rarity at sea level in tropical areas of the Carribean. This matter was summarized in 1886 by Hirsch 4 as follows: Of the area and frequency of rheumatic fever in North America we are unable to judge, owing to the extreme scantiness of our geographical information; but, if we may infer from the number of communications made about it to medical societies, particularly in the Northern and Central United States, it should be

Rheumatic Fever: Diagnosis, Management and Prevention

Rheumatic fever has been intensively studied clinically over the last half-century. Because of the sequelae of heart valvular scarring and because children are so prominently affected, the disease has commanded exceptional attention from clinical investigators. Since streptococcal infections are important in the pathogenesis of rheumatic fever, microbiologists have joined the effort in recent years. From this intensive clinical and microbiological research has emerged a remarkably complete documentation of the natural history of rheumatic fever, with statistical-clinical correlation of events from the onset of the inciting streptococcal pharyngitis to the progress of the valvular heart disease. Drs. Markowitz and Kuttner have done a remarkable job of synthesizing from many publications a composite picture of rheumatic fever. Their work is not simply scholarly but reflects their years of clinical experience, contemplation and research in rheumatic fever and poststreptococcal disease states. The writing is that of the seasoned and experienced physician, answering the

NATURAL HISTORY OF RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE. TEN-YEAR REPORT OF A CO-OPERATIVE CLINICAL TRIAL OF A.C.T.H., CORTISONE, AND ASPIRIN.

NATURAL HISTORY OF RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE. TEN-YEAR REPORT OF A CO-OPERATIVE CLINICAL TRIAL OF A.C.T.H., CORTISONE, AND ASPIRIN.

The Natural History of Rheumatic Fever and Rheumatic Heart Disease

1. A study has been made 10 years after the end of treatment of the 497 children who were admitted to the U.K./U.S. cooperative clinical trial of the relative merits of ACTH, cortisone, and aspirin in the treatment of acute rheumatic fever. 2. Three hundred and ninety-seven of the cases (79.9 per cent) were known to be alive at 10 years and the status of the heart was known for 347 of them. In addition, 23 (4.6 per cent) had died, 19 from rheumatic fever and rheumatic heart disease, and 77 (15.5 per cent) were untraced. The very low fatality rate is striking. 3. At the end of 10 years, there is no evidence that, on the treatment schedule used in this study, the prognosis has been influenced more by one treatment than another. This confirms the findings reported at 1 year and at 5 years. 4. The most important factor in determining the prevalance of rheumatic heart disease at the end of 10 years is the status of the heart at the time treatment was begun. For cases initially without carditis the prognosis was excellent, since in 94 per cent there was no residual heart disease. In cases initially with carditis but without pre-existing heart disease, the proportion without residual heart disease was 70 per cent for those with only a grade I apical systolic murmur, and 74 per cent for those with only a grade II or III apical systolic murmur. The proportion without heart disease decreased to 32 per cent for those initially with failure and/or pericarditis. In cases with pre-existing heart disease, the prognosis was poor. Forty per cent of those initially without pericarditis or failure and only 11 per cent of those with pericarditis and/or failure were without heart disease at 10 years. 5. Mitral stenosis, uncommon at 5 years, was definitely diagnosed in 18 of the 347 cases examined at 10 years and in 7 of the 19 deaths from rheumatic fever and rheumatic heart disease. The prevalence of this complication increased with the severity of the cardiac status at start of treatment and was greater in females than in males. 6. Retreated recurrences of rheumatic fever in cases without pre-existing heart disease worsened the prognosis but did not increase the prevalence of mitral stenosis. Patients surviving an initial attack of rheumatic fever without residual heart disease do develop heart disease following a retreated recurrence. The effect of initial cardiac status on, the recurrence rate could not be determined. 7. Sex affected the outcome at 10 years. Rheumatic fever in its milder grades had a worse prognosis, and mitral stenosis was more common in females than in males. 8. These results make clear that the status of the heart of the patients at the start of treatment, the rate of recurrence of acute rheumatic fever, and the sex of the subjects must all be taken closely into account in the evaluation of any treatment of acute rheumatic fever.

Experimental reactivation of subsiding rheumatic fever.

When anti-inflammatory therapy is reduced or discontinued in patients with acute rheumatic fever, a flare-up of disease activity frequently occurs, manifested by clinical abnormalities or by changes only in laboratory tests. The nature of this rebound phenomenon was recently analyzed in a retrospective survey of 265 patients with acute rheumatic fever (1, 2). The results indicated that most clinical rebounds were not due to any of the three possible causes to which they have been attributed in the past: 1) polycyclic rheumatic activity, 2) an insufficient duration of therapy or 3) relative hypoadrenalism. Instead, the data strongly suggested that these rebounds represented the appearance of the inflammation that had been suppressed during the antirheumatic therapy. This hypothesis was based on the findings that the incidence of clinical rebounds increased with greater severity of cardiac involvement, that rebounds were more frequent in patients treated with steroids alone than in those treated with salicylates, that rebounds were more likely to occur after long courses of steroid therapy than after short courses, that they were rare after long courses of salicylates, and finally, that the incidence of post-steroid rebounds could be reduced by adding salicylates when the steroid reduction began, and by continuing salicylates for several weeks after steroids were stopped. This new hypothesis has important implications regarding the natural history of rheumatic fever and has practical significance for its treatment. One of the implications has been used in the present study to provide a method of testing the validity of the theory. If the hypothesis is correct, it should be possible to create a rebound by giving anti-inflammatory therapy at a time when the convalescent rheumatic patient has no clinical abnormalities but is still in a subclinical inflammatory

The effect of mitral commissurotomy on the natural history of rheumatic heart disease

Dr. Nicholas P. Christy: This exercise points out some common misconceptions concerning the natural history of rheumatic heart disease, emphasizing the relative rarity of valvular disease following an attack of acute rheumatic fever, and showing that only a small proportion of patients who have valvular involvement are likely to become ideal candidates for mitral commissurotomy. An attempt was made to assess the effect of this operative procedure upon the natural history of rheumatic heart disease, an assessment difficult to make in the absence of a truly comparable untreated control group. Of 130 patients subjected to commissurotomy who were followed up for periods as long as eight years after surgery, careful direct clinical study showed improvement in 44 per cent, no change in 21 per cent; 11 per cent were worse and 24 per cent died. The changes in objective findings were less striking than the changes in symptoms. The incidence of hemoptysis was sharply reduced and congestive heart failure and dyspnea were improved in over half the patients; on the other hand, murmurs and cardiac size tended either to remain the same or to change in an adverse direction. Operative deaths were chiefly caused by emboli, congestive heart failure and bacterial endocarditis. The operative outcome seemed to be adversely affected by the preexistence of severe, long-standing heart failure, calcification of the mitral valve, and a cardiac classification of IV. All observers believed that present criteria for selection of patients for commissurotomy are far from perfect, but the participants agreed that youth, a small heart in regular sinus rhythm, and recent deterioration predisposed to a good operative result. Objective observations of the effect of the operation upon the natural history of rheumatic heart disease are recorded. Right heart catheterization showed early physiologic improvement following commissurotomy, and demonstrated that such improvement could be sustained for years. The value of left heart catheterization in selected patients (those with associated mitral insufficiency or aortic valvular disease, patients suspected of restenosis of the valve after commissurotomy) was indicated as a measure of the degree of mitral block. It was suggested that the spectrum of patients with rheumatic heart disease can be roughly arranged in groups in terms of myocardial versus mechanical (mitral block) lesions, a classification which may lend further aid in evaluating the suitability of patients for operation. The surgical problem was discussed in relation to the mechanical changes that may conduce to restenosis of the valve after operation, e.g., increasing stiffness of the valve itself, and shortening and fixation of the chordae tendineae. It is hoped that the insertion of prosthetic mitral valves may offer hope for the future. The somewhat pessimistic operative results here recorded are at variance with certain earlier, more enthusiastic reports. The discrepancies depend upon several factors: duration and objectivity of medical follow-up; additional changes in the natural history of rheumatic fever superimposed by other therapy, especially prophylaxis; and differences of opinion about what is the true natural history of this disorder. Certainly the natural history is changing, and mitral commissurotomy, in a very small group of the total number of rheumatic subjects, appears to be contributing to the change.

The appearance of new cardiac murmurs in patients having rheumatic heart disease with no concomitant evidence of rheumatic activity

In four children who had had rheumatic fever a new cardiac murmur was observed in the course of routine examination at a time when the disease had been regarded as in a quiescent stage. This was taken as evidence of activity of the rheumatic process. The values of three acute phase reactants (the erythrocyte sedimentation rate, C-reactive protein and serum mucoprotein) and of antibodies to two hemolytic streptococcal antigens (antistreptolysin and antihyaluronidase) were found to be within normal limits in these patients at the time the evidence of extension of the rheumatic process was observed, and to have shown only minor variations during the preceding months. The values of these three acute phase reactants were also within normal limits in two other patients in whom the activity of the rheumatic process was doubtful or at a barely detectable level. The results of serial determinations of these values are presented in some of these patients, as well as in a group with long continued overt activity of rheumatic fever, and of other patients in whom a single episode of this disease was followed by a prolonged quiescent period. The significance of these findings in relation to variants in the natural history of rheumatic fever is discussed.

Rheumatic heart disease in the Framingham study.

THE pattern of distribution of rheumatic heart disease in the general population is of particular interest not only to those studying the natural history of rheumatic fever but also to those concerned with the pre-eminence of heart disease as a cause of disability and death. Studies of the epidemiology of rheumatic fever have helped to establish the association between that disease and streptococcal infections as well as to describe the familial aggregation of cases of rheumatic fever1 , 2 and its predilection for northern latitudes.3 However, data on the epidemiology of the late cardiac sequelae of rheumatic fever have been largely restricted . . .

Aschoff bodies in left auricular appendages of patients with mitral stenosis; clinicopathologic study, including postoperative follow-up.

IN RECENT years surgical valvulotomy for mitral stenosis has made it possible to examine microscopically the left auricular appendage and observe histologically the rheumatic process in a part of the heart during life. Since this is a phase in the natural history of rheumatic fever, it may be possible to correlate the incidence and degree of activity with the clinical events of rheumatic cardiac disease. Although the lesions of rheumatic fever have been described in the left auricle proper,* the auricular appendage has escaped more critical examination. Von Glahn, 8 in a study of rheumatic auricular endocarditis, concluded that the changes observed may extend into the first portion of the auricular appendage. He did not, however, record Aschoff bodies in this location. Similarly, Gross, 9 in an exhaustive review of rheumatic auricular lesions, made no reference to the auricular appendage. Unusual circumstances have on occasion prompted the making of sections of this

Sequelae of rheumatic fever in men: four to eight year follow-up study.

Although the natural history of rheumatic fever in children is well documented, the literature contains few such studies of the disease in adults. 1 Knowledge of the course and late effects of rheumatic fever in adults could be of value for comparison with other studies in evaluating the results of new methods of treatment; in establishing physical standards for selection and utilization of men for military service; and in determining candidacy for discharge from the armed forces once the disease has occurred. The present report is based on a study of male veterans of World War II who had had an attack of rheumatic fever during military service and who were observed four to eight years after that attack. In evaluating the sequelae of rheumatic fever in our series of veterans, the following aims were considered important: (1) to determine to what extent rheumatic heart disease is a sequel to

RELATION OF THE HEMOLYTIC STREPTOCOCCUS TO RHEUMATIC FEVER

IN THE natural history of rheumatic fever, there are two sets of observations, the epidemiologic 1 and the immunologic, 2 which bear some implication as to a specific etiologic agent. The data in both these fields of observation point to the hemolytic streptococcus as having some causal relation to the disease, although they offer no hint of a possible mechanism by which the hemolytic streptococcus might cause the phenomena of rheumatic fever. In the immunologic field, earlier analytic work on this question, as well as current work in these laboratories, 3 has been reviewed elsewhere. Among the biochemical effects which might be caused by the streptococcus, the possible role of streptococcic hyaluronidase in the pathogenesis of rheumatic fever has been the subject of recent speculation. 4 This speculation has been based on three propositions: ( 1) Rheumatic fever is a disease of hyaline connective tissue; (2) hyaluronic acid, which characterizes hyalin,

THE NATURAL HISTORY OF RHEUMATIC CARDIAC DISEASE: A STATISTICAL STUDY

We are approaching the end of a study which has occupied us continuously for fifteen years. The task that was set was an attempt to describe the natural history of rheumatic fever, presumably a single disease. The results have been accomplished through the cooperation of many persons of good will.¹The brief descriptions and the generalizations now possible could not have been made without the great labor or the continued reflection which have been devoted to this task. It is not too much to say that we know the behavior of rheumatic fever, at least in this locality and at this time. It is possible now toseparate knowledge which is complete and definitive from information which is partial and tentative. It is possible, furthermore, to interpret the latter in terms of the former. The length of time during which we have been familiar with this subject has made it

The natural history of rheumatic fever in the first three decades

Summary An analysis of the clinical course exhibited by 225 rheumatic subjects who have lived to their present ages of sixteen to thirty years, and 112 individuals who have succumbed to the disease during a twenty-year period of observation, has been presented. The onset of the disease from childhood is characterized by protean manifestations of activity and by a varied number of years of freedom from recurrence or continuous years of manifestations of active infection. After puberty, about the age of sixteen years, the majority of the subjects (66 per cent) were free from recurrence of symptoms, compared with 13 per cent before this age period. The practical importance of consideration of the age factor in this disease has been discussed. From a comparison of the course of the disease in the living and in the deceased series of subjects, it appears that the disease is self-limited, death being due in most instances to fatal active carditis. While the first attack of carditis may be severe and fatal, the majority of the deceased subjects survived subsequent recurrent active carditis. The average age of death was 12.6 years, and the greatest incidence was in the age group of twelve to sixteen years, inclusive, for the series. The care and management of these patients during the period of observation is not within the scope of this report. It is, however, of some interest to note that the children who experienced several intercurrent years of freedom from manifestations of rheumatic activity, remained in the same environment. Those who succumbed to the disease and those who survived with minimal degree of cardiac damage received comparable medical supervision. It is difficult to reconcile some current etiologic hypotheses with the observed course of the disease in these subjects. The type of rheumatic manifestation, exclusive of active carditis, did not appear to be of prognostic significance. The incidence of heart disease was comparable whether patients exhibited joint pains alone or chorea or polyarthritis with or without joint pains. All of the subjects presented evidence of cardiac involvement, although in only 39 per cent were the symptoms of carditis above the clinical horizon and capable of recognition. When the symptoms of active carditis were of sufficient degree to be diagnosed, the subsequent amount of cardiac damage, that is the multiple valvular lesions and marked cardiac enlargement, was greater and the mortality higher. During the course of the disease physical signs of valvular involvement may disappear, may be inconstant or uncharacteristic, leading to the erroneous opinion that the heart is left unscathed. The presence of considerable cardiac enlargement, established by adequate roentgenologic examination in a large series of these children who were under continuous careful observation, indicates the limitations of a diagnosis of the absence of cardiac involvement in rheumatic individuals based on physical examination alone. It is of some prognostic importance to note that the majority of these rheumatic individuals who survived were able to carry on their work and play without circulatory symptoms, particularly after puberty. The future course of the disease in these individuals must await a further period of continued observation for final comment. It would seem likely, however, that the usual unfavorable prognostic opinion that the majority succumb during the third and fourth decades is influenced by observations which are limited to adult patients who are under observation because of symptoms or by postmortem statistics. There may well be in the general population a considerable number of rheumatic individuals in whom the disease has been mild or unrecognized and the presence of heart disease unknown. Our own observations, as well as the frequent accidental discovery of mitral stenosis during routine physical examination or postmortem examination, favor this view. Accumulation of adequate data as to the true incidence, morbidity, and mortality of this disease is a vital need. Such information can only be collated from studies of representative series of subjects under continuous observation from the onset of the disease throughout its course to its end. An adequate comprehension of the natural history of rheumatic fever is the only reliable criterion available at the present time for considering critically current etiologic hypotheses and for evaluating various therapeutic measures.

INTRAVENOUS VACCINATION WITH HEMOLYTIC STREPTOCOCCI

The natural history of rheumatic fever in children is characterized by the repeated recurrence of its many and varied manifestations of activity over a period of years. From the onset until the patient is about 12 years of age there is apparent an increasing susceptibility and after this age a diminishing susceptibility.¹ If the conception of rheumatic fever is accepted as an allergic or hyperergic phenomenon, and if it is assumed that the many manifestations of activity are due to a state of hypersensitivity of the tissues to some component of streptococci, the period before 12 years may be considered one of predominant hypersensitiveness to streptococci and the period after 12 years as one of gradually increasing hyposensitiveness, possibly due to autodesensitization. It would then seem reasonable to attempt to induce a state of hyposensitiveness during the period of increasing susceptibility. Therefore it was considered worthwhile to attempt to

Natural History of Rheumatic Fever

Natural History of Rheumatic Fever