Unnoticed Adverse Effect of Isoniazid during Childhood Tuberculosis Preventive Treatment: HyperuricemiaFunding None.
Objective Isoniazid for 6 to 9 months is the most widely used form of tuberculosis (TB) preventive treatment. We aimed to assess the adverse effects of isoniazid by using the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and uric acid (SUA) in children and adolescents receiving long-term isoniazid for latent TB infection.
Methods The study included children ≤18 years of age who underwent TB preventive treatment with isoniazid (IPT) between 2015 and 2019 at a university hospital. Serum transaminase, SUA, urea, and creatinine levels of patients were measured before the initiation of IPT, 15th day, and once a month during treatment. Patients with ALT, AST, or SUA results above cut-off levels during treatment were evaluated. The final values in follow-up were included in the data analysis.
Results A total of 141 children who underwent IPT were included. In total, 70 children had family members with confirmed TB disease, and 71 children had a positive tuberculin skin test. SUA increased above cut-off values in 16 children (11.3%), and half of them had uric acid levels over 7 mg/dL. The median duration of the development of hyperuricemia was 4.0 months. ALT or AST increased above cut-off values in 23 children (16.3%). ALT was above cut-off values in seven patients, AST was high in 20 patients. The median duration to the development of AST and/or ALT levels above cut-off was 4.0 months. Two patients had hepatotoxic transaminase levels. Three patients had both elevated transaminases and SUA levels.
Conclusion Isoniazid may also cause hyperuricemia besides elevation in transaminases in children.
Eingereicht: 20. Oktober 2020
Angenommen: 11. Januar 2021
11. März 2021 (online)
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- 1 Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health 2014; 2 (08) e453-e459
- 2 European Centre for Disease Prevention and Control/WHO Regional Office for Europe, Tuberculosis Surveillance and Monitoring in Europe. European Centre for Disease Prevention and Control/WHO Regional Office for Europe. København: Denmark; 2019 . Accessed May 19, 2020 at: http://www.ecdc.europa.eu/en/publications/Publications/Tuberculosis-surveillance-monitoring-2019.pdf
- 3 Singh M, Mynak ML, Kumar L, Mathew JL, Jindal SK. Prevalence and risk factors for transmission of infection among children in household contact with adults having pulmonary tuberculosis. Arch Dis Child 2005; 90 (06) 624-628
- 4 World Health Organisation. WHO consolidated guidelines on tuberculosis: Tuberculosis preventive treatment: Module 1: prevention. Geneva: World Health Organization; 2020 . Accessed May 22, 2020 at: https://www.who.int/publications/i/item/who-consolidated-guidelines-on-TB-module-1-prevention-TB-preventive-treatment
- 5 Marais BJ, Gie RP, Schaaf HS. et al. The clinical epidemiology of childhood pulmonary tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis 2004; 8 (03) 278-285
- 6 T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü Tüberküloz Tanı ve Tedavi Rehberi Sağlık Bakanlığı Yayın No. 1129 2nd Ed. Ankara, May 2019. Accessed May 22, 2020 at: https://hsgm.saglik.gov.tr/depo/birimler/tuberkuloz_db/haberler/Tuberkuloz_Tani_Ve_Tedavi_Rehberi_/Tuberkuloz_Tani_ve_Tedavi_Rehberi_08.07.2019_Yuksek_KB.pdf
- 7 Lancella L, Vecchio AL, Chiappini E. et al. Italian Pediatric TB Study Group. How to manage children who have come into contact with patients affected by TB. J Clin Tuberc Other Mycobact Dis 2015; 8: 1-12
- 8 Fountain FF, Tolley E, Chrisman CR, Self TH. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest 2005; 128 (01) 116-123
- 9 Chang SH, Nahid P, Eitzman SR. Hepatotoxicity in children receiving isoniazid therapy for latent tuberculosis infection. J Pediatric Infect Dis Soc 2014; 3 (03) 221-227
- 10 Chang SH, Eitzman SR, Nahid P, Finelli ML. Factors associated with failure to complete isoniazid therapy for latent tuberculosis infection in children and adolescents. J Infect Public Health 2014; 7 (02) 145-152
- 11 Şişmanlar T, Aslan AT, Budakoğlu I. Is hyperuricemia overlooked when treating pediatric tuberculosis patients with pyrazinamide?. J Trop Pediatr 2015; 61 (05) 351-356
- 12 Tsakalidis D, Pratsidou P, Hitoglou-Makedou A, Tzouvelekis G, Sofroniadis I. Intensive short course chemotherapy for treatment of Greek children with tuberculosis. Pediatr Infect Dis J 1992; 11 (12) 1036-1042
- 13 Saukkonen JJ, Cohn DL, Jasmer RM. et al; ATS (American Thoracic Society) Hepatotoxicity of Antituberculosis Therapy Subcommittee. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006; 174 (08) 935-952
- 14 Baldree LA, Stapleton FB. Uric acid metabolism in children. Pediatr Clin North Am 1990; 37 (02) 391-418
- 15 Wilcox WD. Abnormal serum uric acid levels in children. J Pediatr 1996; 128 (06) 731-741
- 16 Pokam BD, Eeteneneng EJ, Umoh A, Umoh NO, Guemdjom PW. Uric acid levels in patients on antituberculosis drugs in the Southwest region of Cameroon. Int J Mycobacteriol 2016; 5 (Suppl. 01) S116
- 17 Taki H, Ogawa K, Murakami T, Nikai T. Epidemiological survey of hyperuricemia as an adverse reaction to antituberculous therapy with pyrazinamide. Kekkaku 2008; 83 (07) 497-501
- 18 Louthrenoo W, Hongsongkiat S, Kasitanon N, Wangkaew S, Jatuworapruk K. Effect of antituberculous drugs on serum uric acid and urine uric acid excretion. J Clin Rheumatol 2015; 21 (07) 346-348
- 19 Balouch GH, Ali Shah SZ, Das T. Hepatotoxicity and hyperuricemia in patients on antituberculosis therapy (an experience at tertiary care teaching hospital). World Appl Sci J 2011; 13: 606-610
- 20 Kumar AK, Gurumurthy P. Disposition of uric acid upon administration of ofloxacin alone and in combination with other anti-tuberculosis drugs. Indian J Exp Biol 2004; 42 (03) 323-325
- 21 Rey E, Gendrel D, Treluyer JM. et al. Isoniazid pharmacokinetics in children according to acetylator phenotype. Fundam Clin Pharmacol 2001; 15 (05) 355-359
- 22 Hasan R, Malik S, Yasmeen G, Ahmad M. Isoniazid-associated uric acid retention in the lizard, uromastix hardwickii. East Cent Afr J Pharm Sci 2012; 15: 24-26
- 23 Sánchez-Albisua I, Vidal ML, Joya-Verde G, del Castillo F, de José MI, García-Hortelano J. Tolerance of pyrazinamide in short course chemotherapy for pulmonary tuberculosis in children. Pediatr Infect Dis J 1997; 16 (08) 760-763
- 24 Citak A, Kaya O, Uçsel R, Karaböcüoğlu M, Uzel N. Acute isoniazid neurotoxicity in childhood. Turk J Pediatr 2002; 44 (01) 54-57
- 25 Badrinath M, John S. Isoniazid Toxicity. StatPearls (Internet). Treasure Island, FL: StatPearls Publishing; 2020
- 26 Li N, Zhang S, Li W. et al. Prevalence of hyperuricemia and its related risk factors among preschool children from China. Sci Rep 2017; 7 (01) 9448
- 27 Rodenbach KE, Schneider MF, Furth SL. et al. Hyperuricemia and progression of CKD in children and adolescents: the chronic kidney disease in children (CKiD) cohort study. Am J Kidney Dis 2015; 66 (06) 984-992
- 28 National TB Controllers Association, Centers for Disease Control and Prevention (CDC). Guidelines for the investigation of contacts of persons with infectious tuberculosis. Recommendations from the National TB Controllers Association and CDC. MMWR Recomm Rep 2005; 54 (RR-15) 1-47
- 29 Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA 1999; 281 (11) 1014-1018
- 30 Franks AL, Binkin NJ, Snider Jr DE, Rokaw WM, Becker S. Isoniazid hepatitis among pregnant and postpartum Hispanic patients. Public Health Rep 1989; 104 (02) 151-155