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