Local anti-rheumatic effectiveness of higher esters and analogues of hydrocortisone.

During the past 31 years we have given more than 17,000 intrasynovial injections of hydrocortisone (Compound F) into the joints, bursae, or tendon sheaths of nearly 1,300 patients for various forms of rheumatic disease (Hollander and others, 1951a, 1954; Brown and others, 1953; Hollander, 1953a,b). Numerous confirmatory and supplementary reports in the world medical literature have shown that this method has now been widely accepted as an adjunct in the local management of arthritis and related conditions (See Bibliography). While we have found that intra-articular hydrocortisone acetate (F a) produces a temporary alleviating effect in over 80 per cent. of all joints injected, the transitory nature of this effect limits its practical value as therapy in about one-third of our cases. Obviously, joint injections cannot be repeated every few days, even on hospitalized patients. Since the method has proved of value mainly in helping to preserve normal joint function in ambulatory patients who would otherwise be disabled by some local rheumatic inflammation, a search has been conducted to find an agent capable of prolonging the local palliative effect. Investigations into the disappearance of hydrocortisone from the synovial fluid, which revealed the absorption of the injected hormone by the cells of the synovial fluid and particularly by the lining membrane of the synovium, were reported by us a year ago (Hollander, 1953c, Zacco and others, 1954). The most significant finding was that the hydrocortisone acetate was apparently absorbed and retained by the lining of the synovium without splitting the ester, whereas unabsorbed hormone remaining in the joint fluid was rapidly hydrolysed and broken down. We therefore assumed that higher, and less