Rheumatic fever: biochemical and histopathological aspects.

In rheumatic fever, lesions occur in the connective tissue-of the heart, of the synovial and serous membranes, and of the subcutaneous tissue. While these lesions are sufficiently characteristic to allow confident recognition on histological grounds alone, purely morphological studies have so far revealed little of the essential nature of the lesion, or its possible origins. Aetiologically, the implication of haemolytic streptococcal respiratory infections rests on sound inference from numerous bacteriological studies. Further, lesions more or less closely resembling those of the human disease have been produced in laboratory animals by techniques involving immunization or infection with streptococci, and also by non-specific sensitization to various foreign proteins. But whether or not immunologically determined, the primary lesion of the connective tissue in rheumatic fever, as distinct from the inflammatory reaction to it, remains undefined. The recent tendency to include rheumatic fever in the group of ' collagen diseases,' along with rheumatoid arthritis, peri-arteritis nodosa, disseminated lupus erythematosus and a number of other conditions affecting connective tissue, is based on relatively slender evidence that collagen is, in fact, primarily affected. Apart from collagen fibres, connective tissue contains other extracellular elements-the elastic fibres and the interfibrillar ground substance. Although the latter has the appearance of an amorphous matrix, the work of Day (1950, 1952) suggests that it, no less than the fibrillar elements, has organized structural form. It is this framework of structurally organized connective tissue that is modified by the rheumatic lesion. Inflammation, as Ungar has recently re-emphasised (Ungar, 1952), is a response to a direct physical or chemical stimulation of the tissues. It is, perhaps, a reasonable working hypothesis, that this stimulus arises in rheumatic fever from changes occurring in the structural elements of the connective tissue. We know little of the nature of the changes occurring in fibrils or ground substance because we know ul