Chemotherapy of tuberculosis of bones and joints.

The assessment of therapeutic remedies for tuberculosis is notoriously difficult : many remedies in the past have enjoyed popular favour but have been forgotten ; many papers have been written on calcium or tuberculin or gold, but who now refers to them? These thoughts must have been in the minds of the Medical Research Council in 1946 when they undertook to plan trials of streptomycin in pulmonary tuberculosis (Medical Research Council 1948), because they determined to use for the test only patients having a similar type of disease and that a type not suitable for other forms of therapy, and that for controls there should be a parallel series of patients treated only by bed rest. They were able to draw on the large pulmonary tuberculosis population of the London County Council and the Middlesex County Council but found after three months that there were not enough suitable patients in these areas and so extended their recruitment into Scotland and Wales and the Midlands. No such method is possible for the solitary investigator working from material in a single hospital. In the absence of any such method, considerable difficulties present themselves. The variety of lesions in skeletal is much greater than that in pulmonary tuberculosis, not only as each joint is affected but according to the degree that associated lesions are present. In pulmonary tuberculosis the radiographic appearance gives early information about onset of disease, about healing, and accurate information about the extent. This is not true of skeletal tuberculosis, in which radiographic changes lag behind clinical : the degree of disease is not faithfully represented in the radiograph of a tuberculous joint and as the processes of disease and repair are slow it is difficult to find critical criteria of the time of healing. It has seemed best to the author therefore not to attempt too fine a review of his patients but to compare different groups of patients in bulk, and to assess what changes in treatment have been made possible by the introduction of chemotherapy and antibiotics. It is hoped to show that this method has given valuable information. In addition, evidence is available of the appearance of joints at operation of patients who have received courses of antibiotics. The principal antibiotic studied in this essay is streptomycin sulphate. This was given to adults in doses of one gramme intramuscularly every day for ninety days. Proportionately smaller doses were given to children. In the early stages of its use intra-articular injections of 200 miffigrams at weekly or biweekly intervals were also given, but this method was abandoned as the repeated trauma to the joint seemed to cause synovitis to persist. The use of para-amino-salicylates (P.A.S.) in combination with streptomycin was limited to adult patients who had associated pulmonary tuberculosis because it is known that tubercie bacilli in pulmonary lesions develop resistance to streptomycin unless P.A.S. is also given. Those who had no associated pulmonary tuberculosis were not given P.A.S. because evidence was lacking that the tubercle bacilli in skeletal lesions developed resistance, and the amount of benefit derived from the addition of P.A.S. did not seem to warrant the long course needed of a drug which, in the early days at any rate, was unpleasant to take. In addition to a study of the effects of streptomycin in skeletal tuberculosis a short series of patients treated with iso-nicotinic acid hydrazide has been studied and the results will be described. At present it is the author’s practice to prescribe a combination of streptomycin and iso-nicotinic acid hydrazide as advocated by Joiner et al. (1952) in their treatment of pulmonary lesions.