The Hyaluronic Acid of Synovial Fluid in Rheumatoid Arthritis.

Rheumatoid arthritis *is considered a disease which involves the connective tissue and supporting structures of the body with its primary nidus in the interfibrillar ground substance of these structures (1). The ground substances are thought to be composed of mucopolysaccharide-protein complexes. The nature of two of the polysaccharides is known-chondroitin sulfuric acid and hyaluronic acid. The latter has been isolated from skin, the vitreous of the eye and from synovial fluid (2). The synovial space has been regarded as an enlarged tissue space (3) and synovial fluid may be obtained with relative ease in many patients with rheumatoid arthritis. A study of the hyaluronic acid in the synovial fluid of patients with rheumatoid arthritis in contrast to normals seemed worthwhile as the characteristics of the hyaluronic acid thus obtained might parallel changes in other mucopolysaccharides in the smaller connective tissue spaces throughout the body. Hyaluronic acid in synovial fluid is the component of the fluid which is responsible for its high viscosity (4). A variety of quantitative viscosimetric methods have been applied to the viscous nature of synovial fluid since 1925 (5). These have yielded conflicting data but most seem to agree that normal joint fluid is a very viscous material (6). Bauer, Ropes and Waine (3) demonstrated that there is a wide range of viscosity values obtained from both normal and pathological fluids. We have shown that the viscosity of normal human knee joint fluid varies inversely with the degree of peripheral edema present (7). When joint fluid or purified hyaluronic acid is diluted with 0.85 per cent saline or distilled water an exponential curve is obtained (8, 9), and with fluids of high viscosity small increments of diluent fluid cause marked decreases in viscosity. For these reasons, viscosity alone cannot be taken as an index of the concentration of hyaluronic acid or of the extent of polymerization of the mucopolysaccharide. The concentration of hyaluronic acid may be approximated by the mucinclot method of Bauer et al. (3), but the clot thus formed contains both protein and hyaluronic acid and changes in protein concentration could cause errors in the determination of hyaluronic acid concentration. Recently a method has been described whereby the hyaluronic acid content of 1 cc. of fluid can be determined with an accuracy sufficient for a biological method (2).