ARF is a disease that has a specific etiologic agent yet has some similarities to the rheumatoid-collagen-vascular group. The etiologic agent is the beta-hemolytic Lancefield group A Streptococcus. Apparent hypersensitivity or other effect of this organism causes connective tissue changes manifested by focal necrosis of collagen and the development of peculiar aggregates of histiocytes called “Aschoff bodies.” Symptoms of ARF include fever, a migratory type of polyarthritis, and frequently cardiac damage manifested by symptoms or only by electrocardiogram (ECG) changes. Diagnosis or confirmation of diagnosis often rests on appropriate laboratory tests.

Culture. Throat culture should be attempted; the finding of beta-hemolytic streptococci, Lancefield group A, is a strong point in favor of the diagnosis if the clinical picture is highly suggestive. However, throat cultures often show negative results by the time ARF symptoms develop, and a positive throat culture is not diagnostic of ARF (since group A streptococci may be present in 15%-20% of clinically normal children). Blood culture findings are almost always negative.

Streptolysin-O tests. Beta streptococci produce an enzyme known as streptolysin-O. About 7-10 days after infection, antibodies to this material begin to appear. The highest incidence of positive results is during the third week after onset of ARF. At this time, 80%-85% (range, 45%-95%) abnormal results are obtained; thereafter the antibody titer drops steadily. At the end of 2 months only 70%-75% of test results are positive; at 6 months, 35%; and at 12 months, 20%. Therefore, since the Streptococcus most often cannot be isolated, antistreptolysin-O (ASO) titers of more than 200 Todd units may be helpful evidence of a recent infection. However, this does not actually prove that the disease in question is ARF. Group A streptococcal infections are fairly frequent, so that occasionally a group A infection or the serologic effects of such an infection may coexist with some other arthritic disease. Another problem with ASO elevation is that the elevation persists for varying periods of time, raising the question whether the streptococcal infection that produced the antibodies was recent enough to cause the present symptoms. Commercial tests vary somewhat in reliability, and variations of 1 or 2 dilutions in titer on the same specimen tested by different laboratories are not uncommon.

Antibodies against other streptococcal enzymes. Commercial slide latex agglutination tests that simultaneously detect ASO plus several other streptococcal antibodies, such as antideoxyribonuclease-B (AND-B) are available. The best known of these multiantibody tests is called Streptozyme. Theoretically, these tests ought to be more sensitive for detection of group A beta-hemolytic streptococcal infections than the streptolysin-O test alone, since patients who develop acute glomerulonephritis are more apt to produce antibodies against AND-B than streptolysin-O, and the antibodies against streptococcal enzymes may be stimulated unequally in individual patients. However, there is considerable debate in the literature on the merits of the combination-antibody tests versus the single-antibody tests. The American Heart Association Committee on Rheumatic Fever published their opinion in 1988 that Streptozyme gave more variable results than the ASO method and therefore was not recommended. If both the streptolysin-O test plus the AND-B test are performed, the combined results are better than either test alone and even a little better than the single combination-antibody slide test. However, relatively few laboratories perform the AND-B test, and even fewer routinely set up both the ASO test plus the AND-B test in response to the usual order for an ASO titer.

Diagnosis. When a patient has an acute-onset sore throat and the question involves etiology (group A Streptococcus vs. some other infectious agent), throat culture is the procedure of choice, because it takes 7-10 days before ASO antibody elevation begins to occur. On the other hand, ARF and acute glomerulonephritis develop some time after the onset of the initiating streptococcal infection. The average latent period for ARF is 19 days, with a reported range of 1-35 days. Therefore, the ASO (or Streptozyme and its equivalents) is more useful than throat culture to demonstrate recent group A streptococcal infection in possible ARF or acute glomerulonephritis.

Other tests. The ESR is usually elevated during the clinical course of ARF and is a useful indication of current activity of the disease. However, the ESR is very nonspecific and indicates only that there is an active inflammatory process somewhere in the body. In a minority of ARF patients, peculiar subcutaneous nodules develop, most often near the elbows. These consist of focal collagen necrosis surrounded by palisading of histiocytes. In some cases, therefore, biopsy of these nodules may help confirm the diagnosis of ARF. However, biopsy is not usually done if other methods make the diagnosis reasonably certain. Also, the nodules are histologically similar to those of RA. During the acute phase of the disease there usually is moderate leukocytosis, and most often there is mild to moderate anemia.