Arthralgia was the major adverse reaction encountered in a clinical trial of the treatment
of pulmonary tuberculosis with three short-course regimens containing pyrazinamide in South
Indian patients. The first regimen was of rifampicin, streptomycin, isoniazid and pyrazinamide
given daily for three months; the second was of the same four drugs daily for three months
followed by streptomycin, isoniazid and pyrazinamide twice-weekly for two months, and the
third was the same as the second except that rifampicin was not administered. Arthralgia
was reported in 36% of 353 rifampicin patients and 66% of 179 non-rifampicin patients, a highly
significant difference (p<0.001). The onset of arthralgia was mostly during the first two
months of chemotherapy. The knees were affected in about 90% followed by the ankles in
about 50% of the patients with arthralgia, and about 60% of these patients had one or more
of the signs, swelling, tenderness and limitation of joint movement. Chemotherapy was
modified in 10 rifampicin and 15 non-rifampicin patients; the rest of the patients were managed
with symptomatic treatment with analgesics. There was a two to three fold increase in serum
uric acid concentrations by the end of the first month and the concentrations were more or
less stationary throughout the rest of the daily phase of treatment. The mean concentration
during the daily phase of treatment in patients with arthralgia (0.482 mmoles/litre) was similar
to that in those without arthralgia (0.484 mmoles/litre), while that in the rifampicin patients
(0.476 mmoles/litre) was significantly lower (p=0.03) than that in the non-rifampicin patients
(0.495 mmoles/litre)