Hyperuricemia and Arthralgias During Pyrazinamide Therapy in Patients With Pulmonary Tuberculosis

W. Qureshi, MD; G. Hassan, MD; S. M. Kadri, MPH, WHOFETP; G. Q. Khan, MD; Bensson Samuel, CT(ASCP); Ali Arshad, MBBS

Disclosures

Lab Med. 2007;38(8):495-497. 

In This Article

Discussion

The trend the authors observed between increasing serum UA levels and the number of weeks on combination therapy ( Table 1 ) is consistent with the studies by Sharma and colleagues,[7] Zierski and colleagures,[8] Khana and colleagues,[9] and Inoue and colleagues[10] in which the incidence of hyperuricemia was 43.4%, 56.0%, 73.7%, and 86.3%, respectively, in patients treated with combination therapy or PZA alone. In similar studies by others, the incidence of hyperuricemia following PZA therapy alone was as high as 100%.[4,11] Such differences in the the prevalence of hyperuricemia following combination therapy is probably attributable to rifampicin. Raghupati and colleagues[12] have shown previously that rifampicin enhances the renal excretion of UA regardless of the presence or absence of PZA as a component of the combination therapy used in the treatment of patients with TB. In the authors' study, the relatively lower prevalence (48.0%) of hyperuricemia was probably related to the uricosuric effect of rifampicin. Exclusion of ethambutol in the authors' study might also have been responsible for the lower frequency of hyperuricemia, since this drug is known to increase serum UA levels.[13]

Among a subset of patients (n = 11) who developed hyperuricemia, the joints most affected were the knees, shoulders, and ankles ( Table 2 ); however, radiologic studies did not reveal any abnormality. This finding suggests that the arthralgia reported by these patients was non-deforming and non-erosive. Similar findings were observed in the studies by Khana and colleagues[9] and Sharma and colleagues.[7] In these studies, the severity of arthalgias was not severe enough to warrant termination of therapy and none of their patients developed frank arthritis. Horsefall and Plummer[14] also noted involvement of big joints during PZA therapy; however, Zierski and colleagues[8] and Cullen and Levine[15] did not observe any joint involvement despite development of hyperuricemia in their patients.[12] The frequency of arthralgias reported among studies of patients undergoing combination therapy or therapy with PZA alone varies widely from 13.0% to 66.6%.[7,10,16,17]

The authors' study demonstrated no direct relationship between the level of serum UA concentration and the severity of arthralgia in patients undergoing combination therapy. Similarly, the results of the Hong Kong study demonstrated that joint symptoms are not directly related to serum UA levels in patients with TB undergoing combination therapy.[12] In the present study, serum UA levels returned to normal in all patients who were given 2 weeks of aspirin therapy ( Table 3 ) or in those in whom PZA therapy was discontinued ( Table 4 ). Moreover, similar to the findings reported by Sherma and colleagues,[7] all of these patients reported relief of their joint symptoms. These observations suggest that aspirin therapy has beneficial effects associated with a reduction in serum UA concentration and an improvement of the signs and symptoms of arthralgia. Because PZA therapy does not lead to either severe intolerable joint manifestations or irreversible sequelae, and aspirin is effective in reducing the pain associated with arthralgia in patients undergoing this therapy, discontinuation of PZA therapy, either alone or as part of combination therapy, does not seem warranted.

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