The present status of colchicine and uricosuric agents in management of primary gout.

It is conventional to divide the management of gout into the treatment of the acute attacks, the interim treatment, and treatment of the tophaceouy stage.' It is probably fair to say that, at least until 1950, virtually everything we did in the management of patients with gout was empiric. The use of colchicine developed on a purely empiric basis and has a respectable and fascinating history; the only significant clues to possible mode of action of colchicine have developed within the last few years and have been thoroughly discussed. When colchicine is given by mouth, there is quite general agreement on the dosage with 0.5 mg. or 0.6 mg. tablets, usually given one every hour, until pain is clearly relieved, or until evidence of toxicity develops, or until a total dose somewhere in the range of 71/2 to 10 mg. of the drug has been given. By intravenouy administration, the total amount of colchicine is usually limited to about 3 mg., given in divided doses. I was quite interested in Dr. Seegmiller's use of an intravenous dose as high as 5 mg. in 24 hours in some of the studies which he reported. He tells me that there were no serious side effects from a dose of this magnitude. The pattern and specificity of response to colchicine has come up for discussion. As Drs. Zuckner and Wallace have pointed out, the interpretation of the therapeutic trial with colchicine depends a great deal on what is expected of it. Most of us would agree that in the classic severe podagra, when there is a fiery red, swollen joint, with overlying skin at maximum tension, there is relatively little difficulty in evaluating the response to colchicine. With the administration of colchicine there is a subjective dicrease in the excruciating pain several hours before there is any convincing objective change. The first objective change occurs between six and twelve hours after the last dose of colchicine. This is a diminution in swelling, seen as the skin becomes a little bit wrinkled and loses the taut, shiny appearance. Within 24 hours there usually is some reduction in redness and swelling but a considerable redness may remain. Complete subsidence may not be seen for 48 to 72 hours. The real difficulty in evaluating this therapeutic trial is in more chronic situations, where redness and marked swelling are not as apparent. Under these circumstances, colchicine does not produce as dramatic results and the ability to distinguish the response to colchicine in this situation from the effect which may occur in other types of joint disease may present real difficulty. The well established attack and the polycyclic attack frequently respond incompletely to colchicine. Figures on the percentage of acute attacks which