Serum uric acid estimation and arthralgia in patient receiving regimen containing pyrazinamide

Introduction

Pyrazinamide was normally reserve regimen drug used for the treatment of patient who has failed as p[primary chemotherapy. Today Pyrazinamide is at the forefront of the chemotherapeutic armamentarium along with Rifampicin and INH as one of the pillars of SCC. A not infrequent reaction to Pyrazinamide is hyperuricemia and arthralgia which is probably due to inhibition of renal excretion of uric acid. However the exact mechanism of arthralgia is yet to be established on firmer grounds. The current study was undertaken to determine the incidence of hyperuricemia and arthralgia in regimens containing Pyrazinamide.1, 2, 3, 4, 5, 6

Materials and Methods

This study was carried out in patients attending the tertiary health care center. 91 patients diagnosed to have Tuberculosis both Pulmonary and extra Pulmonary were taken up for the study. This included sputum positive and sputum negative Pulmonary Tuberculosis patients. Patients with Pleural effusion and Tuberculosis lymphadenopathy were also part of the study. S. Uric acid levels were estimated for all patients by Phosphotungstate method before treatment and at the end of 2 months.

Discussion

The incidence of hyperuricemia and arthralgia observed in the Pyrazinamide containing regimens was similar to those observed by other workers. The overall incidence of arthralgia in the various studies varies from nil (Zierski and Bek 1980) to as high as 67% has been reported by Iyer and Sreenivasan1978. Tolerance of Pyrazinamide in SCC for Pulmonary tuberculosis in children (upto 15 years). This prospective study from Dept. of Paediatrics, Hospital Infantal la paz, Madrid, Spain (1985-95). Studies showed increased S. Uric acid in 92.2% of children (total of 114 children) and significant fell again one month after Pyrazinamide stopped. There was no sign of arthralgia.9, 10, 11, 12

Conclusion

The addition of Pyrazinamide in chemotherapy for Pulmonary Tuberculosis in children was found to be safe.

Renal excretion of uric acid is suppressed by Pyrazinamide being less than 40% at fire hours. The excretion of uric acid increases thereafter and returns to pre-treatment value at 24 hours. The serum concentration shows little or no change suggesting that the serum is probably saturated at this concentration and any further uric acid must be deposited in the joints or eliminated by uricolysis. The sustained level of uric acid increases at 24 hours after drug administration despite the urinary excretion returning to the pre-treatment levels may be due to the dynamic equilibrium between the deposited uric acid and the.Serum uric acid by mobilising uric acid from tissues and this could be responsible for the lack of association between arthralgia and serum uric acid concentration.

In the present study the incidence of hyperuricemia and arthralgia with pyrazinamide therapy was 63.7% (58 out of 91) and 20.8% (19 out of 91) respectively. The onset of arthralgia was within 15 days of starting therapy in the majority of cases. However none of the patient had to be discontinuing treatment because of arthralgia. In this study all of the arthralgic patients were hyperuricemic. However 1/3 rd of hyperuricemics had arthralgia indicating that hyperuricemia and arthralgia were not synonymous. In other words hyperuricemia associated with Pyrazinamide was mostly asymptomatic. It was also noticed that there was a statistically significant reduction in the incidence of hyperuricemia with advancing age.

Further work on this association is indicated tyherewas no correlation between the degree of hyperuricemia and severity of arthralgia symptoms. There was no incidence of acute Gout in our study. There was no relationship between the dosage of Pyrazinamide and development of hyperuricemia and arthralgia. Hyperuricemia and arthralgia had no statistically significant association with sex. Multiple joint involvements were seen in 4 cases. There was no involvement of small joint in our study. In contrast in gout involvement of small joints like toes is usual and simultaneous involvement of 2 or more joints is uncommon. There is only circumstantial evidence to implicate hyperuricemia in Pyrazinamide arthropathy. As pointed out of Horse fall et al on account of difference in the types of joints involved between Pyrazinamide arthropathy and Gout it is possible that different mechanisms may be operative in the two diseases. The reduction of arthralgia was purely a subjective phenomenon. No leading questions were asked and any spontaneous complaint was noted followed by examination of the affected joint. This could depend on various factors like patient’s willingness to be forthcoming with his problems, awareness of the patient.

In contrast to the weight bearing joints like knee it which was involved in our study. Finally as far as the incidence of arthralgia is concerned it is unlikely that subjective error in the diagnosis of arthralgia would entirely account for the large geographical variation observed. Whether this is due to genetic, nutritional or some other factor remains to be determined. The susceptibility to arthralgia might depend on factors like concentration of urate binding proteins in individuals.

Result of the study

As shown in the above table 61 % of male and 69 % of female were hyperuricemic. There was no statistically significant assosciation between incidence of hyperuricemia, sex and Pyrazinamide therapy.

17 % of male, 27 % of female had arthralgia, again no statistically significant assosciation was found.

Conclusions

From the study we have arrived at the following conclusions.

Source of Funding

No financial support was received for the work within this manuscript.

Conflict of Interest

The authors declare they have no conflict of interest.