Dermal connective tissue permeability in rheumatoid arthritics.

Previous studies indicate that the transfer of proteins and other substances between synovial fluid and blood is more extensive for rheumatoid arthritics than for normal persons (Harris, Millard, and Banerjee, 1958; Platt, Holley, and Pigman, 1957; Michelazzi, 1943). The protein concentration in synovial fluid is also higher for rheumatoid arthritics than for healthy individuals (Platt and others, 1957; Decker, McKenzie, McGuckin, and Slocumb, 1959; Johansen and Sylvest, 1961). These alterations suggest that a feature of this disease may be an enhanced permeability of the connective tissue. The altered permeability, in turn, could arise from a change of the physical state of the ground substance of connective tissue, particularly of the hyaluronic acid, which is especially important for the physical properties of the ground substance. This concept is in agreement with the observations that the degree of polymerization of hyaluronic acid is decreased in the synovial fluid of patients with connective tissue disease (Ragan and Meyer, 1949; Sundblad, 1953; Bollet, 1956; Stafford, Niedermeier, Holley, and Pigman, 1964), since the synovial fluid is probably derived from the ground substance. This laboratory has been engaged for some time in studying the nature of the oxidative-reductive depolymerization (ORD-reaction) of hyaluronic acid by autoxidants and the relation of this reaction to catabolic processes (Pigman, Matsumura, and Herp, 1965). Several autoxidants and antioxidants (inhibitors) which affected the in vitro oxidative-reductive depolymerization of hyaluronic acid (Pigman, Rizvi, and Holley, 1961; Pigman and Rizvi, 1959) were also found to affect in vivo skin permeability (Fabianek, Herp, and Pigman, 1963; 1965). The present paper reports data on a study of the "permeability" of human skin for groups of healthy subjects, hospitalized non-arthritic patients, and rheumatoid arthritic patients. Since most of the arthritics were on medication at the time of experimentation, the effect of oral ingestion of aspirin and other inhibitors on the skin "permeability" of rats was also investigated.