trimethoprim--sulfamethoxazole-drug-combination and Cholestasis--Intrahepatic

A 22-year-old woman was given trimethoprim plus sulphamethoxazole for a urinary infection (160 and 800 mg, respectively, daily), drugs she had not previously taken. After 2 weeks she noticed a rash of small spots on her trunk. In addition she had nausea and vomiting. The rash faded within 2 days of stopping the drug, but progressive jaundice developed.. SGPT and SGOT concentrations rose to maximally 328 and 83 U/l, total bilirubin to maximally 5.9 mg/dl. There was no evidence for viral hepatitis (B or C, cytomegalovirus, Epstein-Barr), autoimmune hepatitis or primary biliary hepatitis. Liver biopsy showed central acinar cholestasis, which suggested drug-induced liver damage.. The patient's symptoms regressed over several weeks without any specific treatment and 8 weeks after onset of the rash the laboratory tests also became normal. The allergic cause of the cholestatic hepatitis was confirmed by a lymphocyte transformation test.. Clinical suspicion of drug allergy as cause of a cholestatic hepatitis can be confirmed reliably and without any risk to the patient with the lymphocyte transformation test.

Topics: Adult; Anti-Infective Agents, Urinary; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Diagnosis, Differential; Drug Hypersensitivity; Female; Humans; Lymphocyte Activation; Remission, Spontaneous; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim/sulfamethoxazole is well known to cause intra-hepatic cholestasis which in rare instances can be prolonged and lead to vanishing bile duct syndrome. The risk regarding the potential for cross-reactivity between structurally related molecules such as dapsone and trimethoprim/sulfamethoxazole in causing hepatotoxicity is scarce. Herein, we report a case of vanishing bile duct syndrome following dapsone use in a patient with HIV infection and a recent history of trimethoprim/sulfamethoxazole-induced cholestasis. The patient had severe and protracted cholestasis during 2 years of follow-up and eventually died of liver failure.

Topics: Anti-Infective Agents; Cholestasis, Intrahepatic; Dapsone; Drug Interactions; Drug Therapy, Combination; Fatal Outcome; HIV Infections; Humans; Male; Middle Aged; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Cholestasis, Intrahepatic; Humans; Immunocompromised Host; Magnetic Resonance Imaging; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Topics: Anti-Infective Agents; Bile Duct Diseases; Cholestasis, Intrahepatic; Humans; Liver Failure; Liver Transplantation; Male; Middle Aged; Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

Two patients who developed cholestatic liver disease after exposure to antibiotics are described. One patient who received clindamycin had liver biopsy findings of marked cholestasis, portal inflammation, bile duct injury and bile duct paucity (ductopenia). A second biopsy after clinical improvement showed resolution of cholestasis but persistence of duct paucity. Three years later, treatment with ampicillin caused another episode of cholestatic hepatitis with cholestasis and duct paucity on rebiopsy. The second patient, who developed cholestasis after receiving trimethoprim-sulfamethoxazole, had marked duct paucity in the liver biopsy. This is the first description, to our knowledge, of ductopenia apparently caused by clindamycin. Cross-reactivity between clindamycin and ampicillin is also demonstrated in one patient. This report documents that duct paucity may occur within 10 days of onset of jaundice and appears to be confined to ducts less than 0.03 mm in diameter.

Topics: Abscess; Adult; Aged; Ampicillin; Bile Ducts, Intrahepatic; Biopsy; Cholestasis, Intrahepatic; Clindamycin; Cross Reactions; Humans; Male; Respiratory Tract Infections; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Biopsy; Celiac Artery; Cholestasis, Intrahepatic; Humans; Hyperbilirubinemia; Liver; Male; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Combinations; Humans; Male; Recurrence; Respiratory Tract Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Cholestasis, Intrahepatic; Drug Combinations; Humans; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Combinations; Drug Hypersensitivity; Female; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Trimethoprim-sulfamethoxazole is known to produce hepatitis. We report a case involving the inadvertent rechallenge with trimethoprim-sulfamethoxazole (Bactrim) in a patient with a previous episode of drug-induced hepatitis. A liver biopsy specimen showed both cholestatic and cytotoxic changes consistent with drug-induced damage. Comparison with existing cases is presented and an immunologic cause is considered.

Topics: Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Drug Combinations; Humans; Liver; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Child, Preschool; Cholestasis, Intrahepatic; Drug Combinations; Female; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections