allopurinol and Tuberculosis--Pulmonary

Chinese patients with arthralgia during treatment with an antituberculosis regimen containing pyrazinamide were allocated at random to 3 anti-arthralgia treatment series in a controlled double-blind study. One series (18 patients) received soluble aspirin 2.4 g daily, the second (23 patients) allopurinol 200 mg daily, and the third (19 patients) placebo only, for 8 weeks. The response was assessed both by independent assessors and by the patients themselves using a diary card. The serum uric acid concentration was measured before and during anti-arthralgia treatment. The joints most commonly affected were the shoulders, the knees and the fingers, and symptoms and signs were in general neither severe nor protracted. For most of the patients in all 3 series the joint symptoms and signs improved during the 8 weeks, but a higher proportion of patients in the aspirin and placebo series than in the allopurinol series experienced improvement, this being most rapid in the aspirin series. Only in the aspirin series was the mean serum uric acid concentration lower during treatment than before it, and this effect was related to the dose in mg per kg. It is concluded that the arthralgia was often self-limiting, that aspirin had a small beneficial effect, that allopurinol, in the dosage studied, may have had a slightly deleterious effect, but that it would be worth studying larger dosages of allopurinol because the dosage studied did not affect the serum uric acid concentration.

Topics: Adolescent; Adult; Aged; Allopurinol; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Joint Diseases; Male; Middle Aged; Pain; Pyrazinamide; Random Allocation; Time Factors; Tuberculosis, Pulmonary; Uric Acid

DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is a severe reaction triggered by drugs that manifests as pyrexia and eosinophilia with involvement of the skin and internal organs. We herein describe the case of a patient who developed hyperuricemia after receiving treatment for tuberculosis, then took allpurinol and developed DRESS syndrome with a contextual coma and right hemisyndrome. This report describes for the first time the presence of vasculitic cerebral involvement in a patient with DRESS syndrome. The cerebral vasculitis responded to treatment, showing clinical and instrumental remission. In cases such as this, allergic cerebral vasculitis should be considered in the differential diagnosis because it can be treated if recognized early, thus leading to remission without the development of any sequelae.

Topics: Adult; Allopurinol; Antitubercular Agents; Diagnosis, Differential; Drug Hypersensitivity Syndrome; Humans; Hyperuricemia; Magnetic Resonance Imaging; Male; Methylprednisolone; Tuberculosis, Pulmonary; Vasculitis, Central Nervous System

Here, we report 2 cases of drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine and allopurinol during tuberculosis treatment. Both patients also developed multiple drug hypersensitivity (MDH) to several antituberculosis drugs that were used at around the period of DIHS onset, and thus, the treatment could not be successfully completed. Our cases show that MDH can easily occur after development of DIHS. Considering that treatment for tuberculosis requires long-term management with several drugs, it is important to refrain from administering drugs that can cause DIHS during tuberculosis treatment.

Topics: Aged; Allopurinol; Antitubercular Agents; Drug Hypersensitivity Syndrome; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Pericarditis, Tuberculous; Skin; Sulfasalazine; Tuberculosis, Pulmonary

The authors describe a case of drug-induced cytolytic hepatitis probably secondary to hypersensitivity to allopurinol which was prescribed incorrectly for secondary hyperuricaemia during treatment with pyrazinamide. The diagnosis was reviewed in view of the late occurrence of hepatitis in relation to the onset of the antituberculous treatment, the absence of a viral aetiology and the presence of clinical manifestations, biological and histological features which were compatible with hypersensitivity to allopurinol. The authors recalled that the type of uricaemia induced by pyrazinamide is most often asymptomatic and does not require any treatment with uric acid lowering drugs. Cessation of pyrazinamide is justified in cases of symptomatic hyperuricaemia but when the indications for pyrazinamide are imperative, treatment with an eliminator of uric acid is indicated. Allopurinol is contra-indicated in association with pyrazinamide on account of its inhibitory reaction to xanthine oxidase. Xanthine oxidase decreases the level pyrazinoic acid, a metabolite of pyrazinamide, which is responsible for the inhibition of the tubular secretion of uric acid.

Topics: Adult; Allopurinol; Chemical and Drug Induced Liver Injury; Drug Eruptions; Drug Hypersensitivity; Drug Interactions; Humans; Male; Pyrazinamide; Tuberculosis, Pulmonary; Uric Acid

Pyrazinamide (PZA) is increasingly used with isoniazid and rifampicin, in short-course antituberculous chemotherapy in service programme conditions. Complicating arthralgias occur due to hyperuricaemia induced by the inhibition of renal tubular secretion of uric acid by pyrazinoic acid, the main PZA metabolite. Allopurinol (Al), a hypouricaemic agent, provides no substantial clinical improvement. Pharmacokinetics of PZA and its metabolites were studied in six healthy volunteers, in a cross-over design, after a single oral dose of PZA alone and, in a second trial, after the same dose together with Al. Plasma and urinary concentrations were measured by high pressure liquid chromatography with a column of cation exchange resin. Analysis of the pharmacokinetic parameters showed that Al induced marked changes in levels of PZA metabolites and accumulation of pyrazinoic acid. Despite decreasing uric acid synthesis, allopurinol increased plasma concentrations of pyrazinoic acid, which is directly responsible for the inhibition of renal urate secretion. Other drugs, which do not involve xanthine oxidase inhibition, should be used in the treatment of this side effect of chemotherapy.

Topics: Adult; Allopurinol; Drug Interactions; Drug Therapy, Combination; Humans; Joint Diseases; Male; Pain; Pyrazinamide; Tuberculosis, Pulmonary; Uric Acid