Rheumatic fever is an inflammatory disease that occurs as a delayed nonsuppurative sequela of an upper respiratory tract infection by group A streptococci The clinical manifestations include the following:

polyarthritis

carditis

subcutaneous nodules

Erythema marginatum

Korea in various combinations.

In its classic form, the disorder is acute, febrile and largely self-limitantesi. However, the damage to heart valves may be chronic and progressive, leading to cardiac dysfunction is death many years after initial I'episodio.

EPIDEMIOLOGY.

The epidemiology of acute rheumatic fever mirrors that of streptococcal pharyngitis. The peak incidence is from age 5 to 15 years, but in adults there are cases both primary and recurrent. Acute rheumatic fever is rare in children under 4 years old, a fact that has led some authors to suggest that repetitive streptococcal infections are needed to prepare the host to the disease.

In the years following World War II, careful prospective studies have been conducted between the staffs of military camps suffering from exudative tonsillitis or pharyngitis caused by group A streptococci of M type In such circumstances, where cases of streptococcal pharyngitis tended to be clinically serious, and occur in epidemics, acute rheumatic fever occurs in approximately 3% of untreated patients.

Some features antecedent streptococcal infection is associated with an increased risk of acute rheumatic fever. These include raising I'entità the title of antistreptolysin O and persistence infecting organism in the pharynx. Although it is more likely to occur in acute rheumatic fever following a clinically severe exudative pharyngitis, rather than after a mild exudative disease, and over one third of cases occurs after streptococcal infections asymptomatic or so mild as to have been forgotten by the patient.

Patients with a history of acute rheumatic fever have a greatly increased risk of recurrent disease after streptococcal infection immunologically significant. Acute rheumatic fever occurs in all parts of the world, with no racial predisposition. In temperate climates, acute rheumatic fever reaches its peak incidence in the colder months, and INVEMA in early spring or just after I'apertura school in the fall. The main environmental factor that favors I'insorgenza I'affollamento seems to be, as in military barracks or similar institutions closed and families. The crowding promotes the spread of inter-group A streptococci and perhaps enhances the virulence grazte the frequent passages in man.

Acute rheumatic fever is still rampant in developing countries such as the Middle East, Indian subcontinent and many nations of Africa and South America. E 'was estimated that more than one million people suffering from rheumatic heart disease in India. Attack rates of acute rheumatic fever occur extremely high among the indigenous POPULATION as the Maori of New Zealand and Australian Aborigines. In sharp contrast, the incidence of acute rheumatic fever and prevalence of rheumatic heart disease have declined in both North America and Western Europe during the twentieth century. Rates below 2 per 100,000 children of school age have been reported in several areas of the United States. The disease has become extremely rare in affluent suburbs of many cities in the U.S. while still among the lowest group in terms of socio-economic, especially in densely populated areas of major urban centers. The highest incidence rates ripofati for African Americans than whites appear to be due to socioeconomic factors rather than genetic.
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Etiology.

The development of acute rheumatic fever requires a previous infection by a specific organism, Streptococcus group A, at a specific location of the body, usually the upper respiratory tract. Streptoccica skin infection, a precursor step of acute post-streptococcal glomerulonephritis, has never been demonstrated as the cause of rheumatic fever. A considerable collection of clinical evidence indicates that individual strains of group A streptococci, they vary in their potential reumatogenico. In separate outbreaks of acute rheumatic fever, tends to dominate a limited number of serotypes of group A streptococcal (eg., 3, 5, 18, 24 and others) and the infecting organisms are often abundant capsule as eviziato Daila their growth as mucoid colonies on plates agarsangue. Strains of the serotypes most commonly reumatogenici share a specific epitope of the M protein molecule exposed on the surface and in the majority of patients with acute rheumatic fever are high levels of IgM antibodies directed against this epitope.

Pathogenesis.

The mechanism by which group A streptococci stimulate the inflammatory response in the connective tissue characteristic of rheumatic fever remains unknown. Various theories have been suggested:

1) Toxic effects of streptococcal products, particularly the streptolysin S and O, both of which can initiate tissue injury;

2) inflammation mediated by antigen-antibody complexes probably located in sites of tissue damage;

3) autoimmune phenomena "induced by the similarity between certain antigens and human tissue.

Currently the most popular theory is that by which the tissue damage of rheumatic fever is mediated by host immune responses to their previous streptococcal infection. This theory is more credible, given the relatively long latency period between I'insorgenza of pharyngitis and acute rheumatic fever and demonstration of numerous examples of antigenic similarity between somatic constituents of group A Streptococcus and human tissues. Among these cross-reactions, the most intensively studied is that between streptococci and human heart. In a variety of experimental systems, many patients with acute rheumatic fever (as well as patients with rheumatic fever) antistreptococcal serum antibodies that develop cross-react with heart tissue. The components of streptococcal cell wall (including group A carbohydrates and protein M) and cell membrane contain epitopes that share antigenic determinants with some constituents of the human heart. Antibodies against the cytoplasm of neurons located in the caudate and subthalamic nucleus of the brain have been identified in patients with Sydenham's chorea and these antibodies cross-react with the membranes of group A streptococci Patients with acute rheumatic fever have, on average, stocks of antibodies to streptococcal extracellular somatci higher than patients with uncomplicated streptococcal infections. Data on cellular immunity is more limited. Patients with acute rheumatic fever showed an exaggerated cellular reactivity to streptococcal cell membrane antigens, as demonstrated by inhibition in vitro migration of peripheral blood lymphocytes. In the course of active rheumatic carditis, and the number of helper lymphocytes (CD4) and CD4/CD8 ratio increased to the level of the heart valves and peripheral blood. Several observations suggest that the development of rheumatic fever can be modulated, at least in part, by specific genetic constitution of the host. These observations include:

1) the tendency of rheumatic fever to hit more than one member of the same family,

2) the fact that only a small percentage of individuals who experience significant immunologically streptococcal infection develops acute rheumatic fever

3) the tendency of individuals to develop recurrent attacks of rheumatic

4) the propensity of rheumatic subjects to exhibit exaggerated immune responses to streptococcal antigens

5) the fact that some class II histocompatibility antigens are detected with a significance greater frequency in patients with acute rheumatic fever compared to controls. Recently, it was that a single non-HLA alloantigens is highly expressed on B cells of virtually all patients with acute rheumatic fever but in just under 2 °% of controls.

Pathological anatomy.

Rheumatic fever is characterized by acute exudative and proliferative inflammatory lesions in connective tissues, especially those of the heart, joints and skin. The initial lesions consist of edema of the fundamental substance, fragmentation of collagen fibers, cellular infiltration and fibrinoid degeneration. The cardiac, one can observe a widespread degeneration to necrosis of muscle cells. In a slightly more advanced stage, focal perivascular inflammatory lesions develop. These nodules, referred to Aschoff, in fact, considered pathognomonic of rheumatic fever, consisting of a central area of fibrinoid tissue surrounded by lymphocytes, plasma cells, large basophilic, some of which are multinucleated. Many of these cells have elongated nuclei with a distinctive chromatin structure, sometimes called cores "on caterpillar" or "owl's eye", according to their orientation in microscopic sections. The cells containing these nuclei are called "myocytes of Anitschkow" despite the fact that most experts consider to be of mesenchymal origin. The cardiac findings may include pericarditis, myocarditis and endocarditis. Can also be seen outbreaks of coronary arteries. Thickened and rough area (MacCallum plate) is often present in the left atrium above the mitral valve posterior cusp. The valvular lesions appear as small warts in the early stages along the line of closure. Later, with the healing, the valves can become deformed and thicker, the strings get shorter and the commissure merge. These changes lead to stenosis or regurgitation. The mitral valve is involved most frequently, followed by the aortic valve, tricuspid, and, rarely, the lung. A pathological level, I'artrite of acute rheumatic fever is characterized by a fibrinous exudate and a sterile payment without erosion of the articular surfaces or pannus formation. The subcutaneous nodules have many features in common with the histological Aschoff nodules consisting of central areas of fibrinoid necrosis surrounded by histiocytes, fibroblasts, occasional lymphocytes and rare polymorphonuclear cells. The inflammation of small arteries and arterioles can take place in all areas of the body. Despite pathologic I'evidenza a widespread vasculitis, aneurysms and thrombosis are not typical features of acute rheumatic fever.

Clinical

Rheumatic fever can affect a number of different organ systems. in particular the heart, joints, skin, subcutaneous tissue and the central nervous system. The clinical picture of the disease can be quite variable depending on the systems affected, if they are involved individually or in combination, and depending on the severity of involvement. Five clinical aspects of the disease are so characteristic that are recognized as "major events" under the revised Jones criteria for the diagnosis of acute rheumatic fever: carditis, polyarthritis, chorea, subcutaneous nodules and erythema marginatum. Other findings, which are often present, but nonspecific, were classified as "minor events". These include I'artralgia, fever, and some laboratory findings. Where it is possible to determine the latent period between streptococcal infection and I'antecedente I'insorgenza symptoms of acute rheumatic fever is between 1-5 weeks. The average latency period is 19 days for both the primary and for those attacks.

Symptoms

High fever, prostration, disabling polyarthritis

fatigue, tachycardia, heart sounds of recent onset

Acute pericarditis

Fulminant heart failure

Sydenham's chorea, without fever or toxicity

Acute abdominal pain rnimante I'appendicite

Various combinations of the above aspects

When the presenting symptom is an acute polyarthritis, I'esordio is often quite abrupt and is marked by high fever and signs of toxicity. If the initial carditis manifestezione isolated I'esordio may be insidious or subclinical. Between these two extremes, in the initial presentation of acute rheumatic fever are different grades:

1) In most of the attacks, fever and joint involvement are the earliest clinical manifestations, although occasionally may be preceded by abdominal pain localized to the periumbilical area or infraombelicale. Sometimes the seat and I'intensità of pain, as well as fleeting signs of peritoneal inflammation, may lead to a misdiagnosis of acute appendicitis. If established, the Card usually occurs within the first 3 weeks of illness. In contrast, chorea tends to appear more late in the disease, sometimes even after all other events are gone. Fortunately, no korea and poliatrite almost never occur simultaneously. Un'epistassi may be a feature of acute rheumatic fever, being able to check both the beginning durantc the acute phase of disease can be quite serious. The incidence of major events in various reported series. Overall, however, I'artrite occurs in about 75% of initial attacks of acute rheumatic fever, carditis in the 4O-50%, chorea in 15% Oei subcutaneous nodules and erythema marginatum in less than 10%. The frequency of individual events varies with I'età. The card is more common in younger age groups and is relatively rare in the initial attacks that occur in adults. Chorea occurs mainly in people between 5 years and puberty. It is observed more frequently in women and almost never occurs in adult males. Therefore, the most attacks of acute rheumatic fever occurs in adults mainly manifests with arthritis.

Arthritis.

The joint involvement varies from a simple arthralgia to acute arthritis debilitating swelling, rubor, calor, functional impotence and marked tenderness, pressure. Usually involving the major joints of the extremities - most often knees and ankles, elbows as well. The hips and small joints of the hands and feet are occasionally affected. The involvement of the shoulders and joints, low back, neck, and temporomandibular sternoclavicolari occurs in a relatively small percentage of cases. The synovial fluid contains thousands of white blood cells, with a prevalence of polymorphonuclear leukocytes. Characteristically, the joint involvement in acute rheumatic fever assumes a pattern of migrant polyarthritis. That does not mean this in a joint I'infiltrazione disappear before being hit. Rather, a number of joints involved in successive periods of involvement and overlap. Inflammation in a joint while another may begin to become symptomatic, so the process seems to be a joint misra another. In the cases treated, can be affected up to 16 joints and circra half of patients develop arthritis in multiple joints of 6. An effective anti-inflammatory therapy is administered early in the course of the disease, the involvement is monoarticular or pauciarticolare. In most cases, I'infiammazione in each joint begins to decrease spontaneously within a week and the total duration of the involvement does not exceed 2-3 weeks. The entire period of activity of polyarthritis rarely exceeds 4 weeks.

Carditis.

Rheumatic fever may involve I'endocardio, the myocardium and pericardium, and then the disease is able to induce a real pancardite. The card is the most important manifestation of acute rheumatic fever as it is the only one that can cause a significant and permanent organ damage. It is manifested clinically by:

-Puffs

Sistotico apical

Mesodiastolico apical (Carey-Coombs murmur)

Basal diastolic

Pericarditis

Cardiomegaly

Congestive heart failure

At least one of the characteristic murmur is almost always present in rheumatic carditis. Although the clinical picture may sometimes be fulminant, is more often mild or even asymptomatic and may go unnoticed in the absence of findings associated with the disease more evident as I'artrite and Korea. The diagnosis of carditis requires the presence of one of the following four events:

(L) organic recent-onset heart murmurs,

(2) cardiomegaly,

(3) pericarditis

(4) congestive heart failure.

In practice, the characteristic heart murmur of rheumatic fever are almost always present in cases of rheumatic carditis, unless it is reduced ability to hear (eg., Intense noise pericardial rub, pericardial substantial payments, low cardiac output, tachycardia severe). The diagnosis of rheumatic carditis should be made with caution in the absence of one of three puffs: systolic apical, apical meso-diastolic and systolic baseline. These puffs, if intended to develop, usually appear within the first week and almost always within the first three weeks of illness. Other finds listeners prominent in patients with active rheumatic carditis include tachycardia, which persisted during sleep rhythms of early diastolic gallop, presystolic or summation; chafing or pericardial heart sounds muffled because of a pericardial effusion. In the early stages of congestive heart failure, the rapid relaxation of the liver capsule can cause I'insorgenza hilum of the right upper quadrant pain and tenderness along I'area tegato. You can see all the clinical findings typical of the Card or 'renal failure. During the course of acute rheumatic fever may get a different variety of rhythm disturbances. By far the most common is the first degree atrioventricular block. They can also be observed other heart blocks second and third degree, a rhythm. Rle and premature contractions, atrial fibrillation usually is rather an expression of an aspect of chronic rather than acute rheumatic involvement. The conduction disturbances in itself indicate an acute carditis and their presence or absence is not related to the subsequent development of rheumatic heart disease. In cases of acute rheumatic fever with severe carditis sometimes observed focal areas of pneumonia. Many observers believe that these infiltrates represent a specific rheumatic pneumonia. However, this occurrence is difficult to prove because of the confusion caused in these patients was seriously ill and toxic, clinical entities by itself or confounding as I'edema I'embolia lung superimposed bacterial pneumonia and adult respiratory distress syndrome .



Sydenham's chorea (chorea minor, "St. Vitus Dance").

This neurological syndrome appears after a latent period varies but on average longer than that of the other manifestations of acute rheumatic fever. Often appears in "pure" form, is not accompanied by other major manifestations of the disease is, after a latent period of several months, when all other evidence of acute rheumatic activity disappeared. Chorea is caratterrzzata by involuntary movements, quick, aimless, more relevant in the extremities and face. The arms and legs move convulsively with irregular movements, jerky, uncoordinated that at times can be unilateral (emicorea). Are obvious facial tics, grimaces, contortions and grimaces. The word is usually mumbled or jerky. The tongue, when protruded, retracts involuntarily while asynchronous contractions of the lingual muscles give rise to an appearance of "bag of worms". Involuntary movements disappear during sleep and can be partially controlled by relaxation, sedation, or by will. Patients with chorea showed generalized muscle weakness and inability to maintain a tetanic muscle contraction. So when the patient is asked to tighten the examiner's fingers. occur close movements and relaxation that have been described as "taking the milker." The shutter of the knee may have a typical commuting. You do not experience any involvement of cranial nerves and pyramidal or sensory pathways are not involved. The electroencephalogram may show an abnormal slow-wave activity.

Subcutaneous nodules.

These nodules are not painful lesions of subcutaneous solid dimeisioni ranging from a few millimeters to circa2 cm. The overlying skin is freely mobile and non-flammable. The lesions tend to appear in groups on the surfaces or bony prominences and tendons. The sites include piedilette extensor surfaces of elbows, knees and wrists, I'occicipite and spinous processes of thoracic and lumbar vertebrae. The nodules are practically not I'unica event.

Erythema marginatum.

The rash begins with a macula or papule erythematosus that stretches to the extending outward. Similar nodules can be observed.

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