Hyperuricemia and Arthralgias During Pyrazinamide Therapy in Patients With Pulmonary Tuberculosis

Background: Pyrazinamide (PZA) is used frequently in monotherapy or in combination therapy with isoniazide and rifampicin in the management of patients with pulmonary tuberculosis (TB). However, hyperuricemia, arthralgia, or symptoms of gout may occur in patients treated long-term with PZA. Typically, aspirin therapy is instituted to reduce the inflammatory pain associated with arthralgia in patients being treated with PZA. The authors determined the incidence of hyperuricemia and arthralgias in TB patients treated with combination therapy and the effect of aspirin therapy on serum uric acid levels in these patients. Methods: The authors enrolled 50 patients categorized as having active pulmonary tuberculosis based on clinical history, physical exam findings, and related investigations. Whole blood samples were obtained from these patients before, during, and after combination therapy, following discontinuation of combination therapy, and after administration of aspirin. Uric acid was quantified in serum samples from all patients using the uricase method in the Hitachi 916 chemistry analyzer. The uric acid levels during and after discontinuation of combination therapy and after initiation of aspirin therapy were determined. In addition, the authors determined the incidence of hyperuricemia and arthralgia among these patients. Results: Combination therapy resulted in progressive hyperuricemia in about 50% of the patients between the 6th and 8th weeks of treatment. Arthralgia occurred in 22% of these cases. Discontinuation of combination therapy and institution of aspirin therapy for 2 weeks resulted in the return of uric acid levels to the pretreatment levels in these patients. Conclusion: Significant hyperuricemia, with some arthralgia, can occur in TB patients treated with combination therapy. Pyrazinamide is the most likely component of combination therapy responsible for these effects. However, aspirin therapy is effective in controlling joint pain in these patients and in reducing their hyperuricemia to normouricemic levels. Combination therapy remains a useful treatment in the management of patients with pulmonary TB, despite the relatively minimal side effects caused by PZA.