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


Lab Med. 2007;38(8):495-497. 

In This Article

Abstract and Introduction


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.


(PZA) has become an important component of short-term, multiple-drug therapy of tuberculosis (TB).[1] It is a synthetic analogue of nicotinamide that is only weakly bactericidal against extracellular Mycobacterium tuberculosis organisms, but it has potent intracellular bactericidal activity, particularly in the relatively acidic intracellular environment of macrophages and areas of acute inflammation. This drug is highly effective during the initial 2 months of treatment, in which acute inflammatory changes persist, and its use has enabled shorter treatment regimens and has reduced the risk of relapse. It is mainly metabolized in the liver and is excreted largely in the urine.[1,2]

Pyrazinamide inhibits renal tubular excretion of urate by inhibiting its renal tubular secretion, resulting in some degree of hyperuricemia that is often asymptomatic. Occasionally, however, acute episodes of gout can occur in patients treated with PZA. In addition, arthralgia may occur in these patients, unrelated to their uric acid level, that is responsive to treatment with analgesics such as aspirin.[1,2,3] Moreover, aspirin is known to prevent hyperuricemia and the arthralgia associated with PZA therapy.[4,5,6] To further validate these findings, 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.


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