a Intensive Care Unit, Hôtel-Dieu Hospital, 69288 Lyon, France b Hepato-gastroenterology and AIDS Unit, Hôtel-Dieu Hospital, 69288 Lyon, France
Sir,
Didanosine (ddI) is a member of the nucleoside analogue class (29,39-dideoxyinosine) which inhibits the reverse transcriptase of the human immunodeficiency virus (HIV) in vitro and improves surrogate markers of HIV infection in vivo. Major clinical adverse effects are nowadays well known: pancreatitis, painful neuropathic syndrome, fulminant hepatic failure. 1 Chattha et al., 2 Freiman et al., 3 and Lai et al. 4 have reported an uncommon but potentially fatal adverse effect similar to Reye's syndrome with hepatic steatosis and aerobic (type B) lactic acidosis during the course of ddI therapy. We report the case of acute pancreatitis with severe lactic acidosis in an HIV-infected patient on ddI therapy.
A 58-year-old HIV-1 infected homosexual man had been diagnosed with AIDS 8 months earlier after he had presented with Kaposi's sarcoma. He had been treated with ddI (400 mg/day), d4T (80 mg/day) and indinavir (1200 mg/day). He had no past history of liver or biliary disease, blood transfusion, drug addiction or alcohol abuse. He had been admitted to the hospital with a 10 day history of abdominal pain. Admission laboratory values were significantly increased for amylase (1059 IU/L), bilirubin (124 µmol/L), aspartate aminotransferase (107 IU/L), alanine aminotransferase (75 IU/L), alkaline phosphatase (172 IU/L), >-glutamyl transpeptidase (453 IU/L) and arterial blood lactate concentration (13 mmol/L). There was no sign of hepatic failure. Abdominal computed tomography confirmed the pancreatitis and showed vesicular sludge in the gall bladder. Abdominal ultrasound did not show biliary tract abnormalities and revealed hepatomegaly. Endoscopic ultrasonography of the biliary tract did not show abnormalities. A liver biopsy showed inflammation without necrosis or fibrosis. All microbial cultures of blood, bone marrow and cerebrospinal fluid were negative. There were no other obvious causes of lactic acidosis such as diabetic ketoacidosis, malignancy, sepsis, uraemia, thyrotoxicosis, exogenous intoxication, 2 myopathy or thiamine deficiency. 5 Therefore, ddI, d4T and indinavir were stopped. Amylase levels decreased and returned to normal within 10 days and lactate levels within 3 weeks.
DdI's adverse effects such as pancreatitis or liver steatosis are well known whereas lactic acidosis is misappreciated. 6 An extensive search of literature showed only one case of a patient dying of a similar syndrome (acute pancreatitis- lactic acidosis). 6
References
1 . Bissuel, F., Bruneel, F., Habersetzer, F., Chassard, P., Cotte, L., Chevallier, M. et al. (1994). Fulminant hepatitis with severe lactate acidosis in HIV-infected patients on didanosine therapy. Journal of Internal Medicine 235, 36771.[ISI][Medline]
2
.
Chattha, G., Arieff, A. I., Cummings, C. & Tierney, L. M.
(1993). Lactic acidosis complicating the acquired immunodeficiency syndrome. Annals of Internal Medicine 118, 379.
3 . Freiman, J. P., Helfert, K. E., Hamrell, M. R. & Stein, D. S. (1993). Hepatomegaly with severe steatosis in HIV-seropositive patients. AIDS 7, 37985.[ISI][Medline]
4 . Lai, K. K., Gang, D. L., Zawacki, J. K. & Cooley, T. P. (1991). Fulminant hepatic failure associated with 29,39-dideoxyinosine. Annals of Internal Medicine 115 , 2834.[ISI][Medline]
5 . Fulop, M. (1993). Lactic acidosis and AIDS. Annals of Internal Medicine 119, 344.
6 . Yarchoan, R., Lietzau, J. A., Nguyen, B. Y., Brawley, O. W., Pluda, J. M., Saville, M. W. et al. (1994). A randomized pilot study of alternating or simultaneous zidovudine and didanosine therapy in patients with symptomatic human immunodeficiency virus infection. Journal of Infectious Diseases 169, 917.[ISI][Medline]