title: Intrahepatic cholestasis and phospholipidosis associated with the use of trimethoprim-sulfamethoxazole.
abstract: Although liver injury after administration of the trimethoprim-sulfamethoxazole combination is rare, hepatocellular necrosis and cholestasis have developed in a few cases. We describe a patient who developed a severe, prolonged cholestatic reaction after trimethoprim-sulfamethoxazole administration. The findings from serial liver biopsy samples showed characteristic abnormalities of phospholipidosis that have not been previously described for trimethoprim-sulfamethoxazole-related hepatic injury. The most prominent finding on electron microscopic evaluation of the liver was the presence of prominent hepatocyte lysosomal inclusions characterized by concentric arrangements of membranous and lamellated structures. The patient improved after several courses of exchange plasmapheresis, which may have assisted in the removal of toxic drug-lipid complexes. The pathogenesis of this acquired secondary phospholipidosis is unknown. Possible mechanisms include generation of highly lipid-soluble metabolites and inhibition of the lysosomal enzyme phospholipase A1.
authors.affiliation: Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
authors.forename: S J
authors.initials: SJ
authors.lastname: Muñoz
authors.forename: A
authors.initials: A
authors.lastname: Martinez-Hernandez
authors.forename: W C
authors.initials: WC
authors.lastname: Maddrey
mesh_terms: D056486:Chemical and Drug Induced Liver Injury; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy; D004338:Drug Combinations; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008107:Liver Diseases / Q000378:metabolism; D008247:Lysosomes / Q000648:ultrastructure; D008854:Microscopy, Electron; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism*; D010956:Plasmapheresis; D011537:Pruritus / Q000139:chemically induced / Q000628:therapy; D013420:Sulfamethoxazole / Q000009:adverse effects*; D014295:Trimethoprim / Q000009:adverse effects*; D014552:Urinary Tract Infections / Q000188:drug therapy
chemical_list: D004338:Drug Combinations; D010743:Phospholipids; D014295:Trimethoprim; D013420:Sulfamethoxazole