Contributor: John M. Kissane and John D. Pfeifer
Rheumatic fever is an acute inflammatory process that involves the heart, joints, skin and central nervous system. The disease follows infections by Group A beta hemolytic streptococci in susceptible individuals, and the relevant streptococcal infection is practically always acute tonsillopharyngitis. The tissues involved are not infected by streptococci, and the latent period of two to three weeks between the infection and the onset of acute rheumatic fever suggests that immunologic events are responsible for acute rheumatism. The attack rate for acute rheumatic fever is about 3% of those with streptococcal tonsillopharyngitis, and the disease recurs with increasing frequency after each successive infection by appropriate streptococci.
The inflammatory process in tissues involved by acute rheumatic fever is thought to be immunologically mediated either as a response to soluble antigen-antibody complexes or as cytotoxic autoimmunity directed against human tissues that share antigens with streptococci; an enormous literature beyond the scope of this discussion has accumulated relating to this hypothesis. The rheumatigenicity of various capsular serotypes of Group A streptococci has recently attracted particular attention; type 18, 3, and to a lesser extent 5, are more prone than others to be followed by acute rheumatic fever.
The very wide use of antibiotics, particularly penicillins, in the treatment of acute tonsillopharyngitis has sharply reduced the frequency of acute rheumatic fever in developed countries. The disease remains by far the most common cause of acquired heart disease in young patients in developing countries; even the United States, there have been recent outbreaks in several localities.
Several factors may have contributed to this re-emergence of rheumatic fever, including diminished clinical use of throat cultures, lack of patient compliance in completing their courses of antibiotic treatment, and possibly even genetic changes in the infecting streptococcus.
Rheumatic carditis is a specific granulomatous inflammation of all layers of the heart. Grossly, the process causes the development of a row of small tan-pink warty excrescences (verruca) along the line of closure of any or all the cardiac valves), and less conspicuously on chordae tendinae or mural endocardium. This process begins as microscopic foci of edema, swelling, and eosinophilia of the cardiac interstitium. These foci of fibrinoid necrosis are initially infiltrated by lymphocytes and plasma cells, and soon by cardiac histiocytes. Some of these histiocytes become enlarged, ameboid cells with bean shaped nuclei containing prominent nucleoli (that depending upon the plane at which they are sectioned, are described as owl-eye or caterpillar-shaped), and it is these modified cardiac macrophages that are the classically recognized Anitchkoff cells.
These foci of fibrinoid necrosis are initially infiltrated by lymphocytes and plasma cells, and soon by characteristic Anitchkoff cells. Depending upon the plane of section some of these enlarged histiocytes may have the shape of an owl eye or a caterpillar. Anitchkoff cells, although characteristic of the carditis of acute rheumatic fever, may be seen in many forms of cardiac injury, not all of them inflammatory. After a few weeks Anitchkoff cells fuse and form multinucleated Aschoff cells. Healing of this process, ultimately with fibrosis, scars the myocardium and epicardium, but most importantly distorts the cardiac valves leading to chronic valvular heart disease. A single valve, several valves, or all valves may be involved. Vascularization of valve leaflets in this healing process predisposes the damaged valve to lodgement of bacteria and development of bacterial endocarditis [endocarditis - bacterial].
Periarticular tissues are seldom examined in cases of acute rheumatic fever, but in a few instances have revealed chronic inflammation by lymphocytes, plasma cells and histiocytes sometimes arranged in perivascular palisades indistinguishable from those of rheumatoid arthritis. Unlike rheumatoid arthritis, however, the arthritis of acute rheumatic fever resolves completely between attacks (the dissimilar resolution of articular and cardiac lesions in rheumatic fever underlies the clinical adage, "It licks the joints, but gnaws at the heart").
In subcutaneous but rarely other tissues, rheumatic fever may give rise to rheumatoid nodules, pea-sized slightly tender nodules that consist of flame-shaped foci of fibrinoid necrosis mantled by lymphocytes, plasma cells, and histiocytes.
Central nervous system lesions cause Sydenham chorea.
In subcutaneous but rarely other tissues, rheumatic fever may give rise to rheumatoid nodules, pea-sized slightly tender nodules that consist of flame-shaped foci of fibrinoid necrosis mantled by lymphocytes, plasma cells, and histiocytes. Rheumatoid nodules are thus histologically very like the soft tissue lesions of active rheumatoid arthritis, and the differential diagnosis also includes other necrobioses such as erythema nodosum and necrobiosis lipoidica diabeticorum.