Hepatotoxicidade por Nimesulide A propósito de um caso clínico

S. Rito Nobre, J.M. Romãozinho, M. Ferreira, P. Amaro, J.E. Pina Cabral, M. C. Leitão (1)

 

 

Resumo

Doente do sexo feminino, com 44 anos de idade, residenteem ambiente rural, com um quadro inicial de leucorreia e adenopatias inguinais, pelo que foi medicada com nimesulide. Dois dias depois desenvolveu sintomas constitucionais. Na admissão hospitalar apresentava icterícia, sufusão conjuntival e hiperémia orofaríngea. Laboratorialmente destacavam-se citopenia, citólise hepática marcada, colestase, insuficiência renal e elevação da proteína C reactiva. A investigação complementar revelou anticorpos antinucleares positivos, ligeiro aumento das imunoglobulinas M e E, e espessamento da parede vesicular. O teste de transformação linfoblástica para o nimesulide foi positivo. Registou-se melhoria clínica e laboratorial após a suspensão do fármaco. Os autores discutem as principais hipóteses diagnósticas, enfatizando os critérios definidores de hepatotoxicidade e a dificuldade inerente à comprovação deste diagnóstico.

 

 

Summary

A case of a forty-four years old rural female admitted due to vaginal discharge and inguinal lymphadenopathies is presented. She took nimesulide and, after two days, started with constitutional symptoms. At hospital admission she presented with jaundice, conjunctival suffusion and pharyngeal injection. Blood tests revealed cytopenia, marked hepatic citolysis, cholestasis, renal failure and reactive C protein elevation. Complementary studies showed positive antinuclear autoantibodies, mild elevation of immunoglobulins M and E, and a thickened gallbladder wall. Lymphocyte transformation test was positive for nimesulide. There was a clinical and laboratorial improvement after cessation of the drug. The authors discuss the main diagnostic hypotheses enfatizing definition criteria for hepatotoxicity and also the difficulty in establishing this diagnosis.

 

 

Texto Completo disponível apenas em PDF

Full text only available in PDF format

 

 

Bibliografia

 

1. Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Veja MC, Lucena MI. Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists. World J Gastroenterol 2007; 13: 329-40.        [ Links ]

2. Maciá MA, Carvajal A, Pozo JG, Vera E, Pino A. Hepatotoxicity associated with nimesulide: Data from the Spanish Pharmacovigilance System. Clin Pharm Ther 2002; 72: 596-7.

3. Van Steenbergen W, Peeters P, De Bondt J, Staessen D, Buscher H, Laporta T, et al. Nimesulide-induced acute hepatitis: evidence from six cases. J Hepatol 1998; 29: 135-41.

4. Boelsterli UA. Mechanisms of NSAID-Induced Hepatotoxicity - Focus on nimesulide. Drug Safety 2002; 25: 633-48.

5. Sanford JP. Leptospirosis. In: Wilson JD et al. eds. Harrison`s Principles of Internal Medicine. 12th edition. New York: McGraw- Hill, Inc; 1991. p. 663-66.

6. Guarner J, Shieh W-J, Morgan J, Bragg SL, Bajani MD, Tappero JW, et al. Leptospirosis mimicking acute cholecystitis among athletes participating in a triathlon. Human Pathol 2001; 32: 750-2.

7. Maria V, Victorino R. Development and Validation of a Clinical Scale for the Diagnosis of Drug-Induced Hepatitis. Hepatology 1997; 26: 664-9.

8. Danan G, Benichou C. Causality assessment of adverse reactions to drugs I. A novel method based on the conclusions of International Consensus Meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993; 46: 1323-30.

9. Benichou C, Danan G, Flahault A. Causality assessment of adverse reactions to drugs II. An original model for validation of drug causality assessment methods: case reports with positive rechallenge. J Clin Epidemiol 1993; 46: 1331-36.

10. Lucena MA, Camargo R, Andrade RJ, Perez-Sanchez CJ, Sanchez De La Cuesta F. Comparison of Two Clinical Scales for Causality Assessment in Hepatotoxicity. Hepatology 2001; 33: 123-30.

11. Berg PA, Becker EW. The lymphocyte transformation test – a debated method for the evaluation of drug allergic hepatic injury. J Hepatol 1995; 22: 115-18.

12. Maria VAJ, Victorino RMM. Immunological investigation in hepatic drug reactions. Clin Exp Allergy 1998; 28: 71-7.

13. Stamm WE. Chlamydial infections. In: Fauci et al. eds. Harrison`s Principles of Internal Medicine. 14th edition. New York: Mc- Graw-Hill; 1998. p. 1058.

14. Mão de Ferro S, Ramalho F. Hepatite auto-imune. In: Tratado de Hepatologia. 1ª edição. Lisboa: Permanyer Portugal; 2006. p. 247-62.

15. Prandota J. Important role of proinflammatory cytokines/other endogenous substances in drug-induced hepatotoxicity: depression of drug metabolism during infections/inflammation states, and genetic polymorphisms of drug-metabolizing enzymes/cytokines may markedly contribute to this pathology. Am J Ther 2005; 12: 254-61.

 

 

(1)Serviço de Gastrenterologia dos Hospitais da Universidade de Coimbra

Correspondência:

Sónia Rito Nobre

Serviço de Gastrenterologia - Hospitais da Universidade de Coimbra

Avenida Bissaya Barreto e Praceta Mota Pinto

3000-075 Coimbra

Telefone: 239400483

Fax: 239701517

E-mail: soninobre@hotmail.com

 

Recebido para publicação: 27/08/2007

Aceite para publicação: 14/05/2008