Used to describe ductopenia related to drugs but not specific term
Etiology/Pathogenesis
• Many medication classes implicated
Antiinflammatory, antibiotics, antiepileptics, psychiatric drugs, tranquilizers, hypoglycemics, and others
• Also occurs with herbal or toxin exposure or genetic disposition
Clinical Issues
• Jaundice
Temporal relationship between drug administration and onset of signs and symptoms
Most patients recover fully with discontinuation of drug
Few cases develop chronic cholestatic injury
Microscopic
• Generally, no specific features indicating injury is drug related
Cholestasis, usually zone 3
Bile duct epithelial cell injury
– Cytoplasmic eosinophilia &/or vacuolization
– Nuclear pleomorphism and uneven nuclear spacing
– Apoptosis and atrophy of ductal epithelium
Bile ductular proliferation
Lymphocytic or mixed cell cholangitis
• Some cases show changes of progression/chronicity
Progressive ductopenia
Periportal hepatocyte swelling and copper accumulation
Bile Duct Injury Secondary to ACE Inhibitor This example of drug-induced cholangitis due to an ACE inhibitor shows a damaged duct with eosinophilic cytoplasm, irregular spaces between nuclei, and variation in nuclear size and shape.
Cholangitis With Neutrophils and Eosinophils This example of drug-related cholangitis due to antibiotics shows a duct with cholangitis surrounded by portal edema and an infiltrate that is rich in eosinophils.
Drug-Related Bile Duct Injury This severely injured duct shows marked cytoplasmic vacuolization and eosinophilia as well as irregularly spaced nuclei.
Ductular Reaction Numerous proliferating bile duct profiles are seen at the edge of this portal tract in a case of drug-related cholangitis. The native bile duct is distinct from these proliferating bile duct profiles.
TERMINOLOGY
Synonyms
• Cholangiodestructive cholestasis
• Vanishing bile duct syndrome: Ductopenia related to drugs but not specific entity, ductopenia in graft-vs.-host disease and chronic ductopenic rejection
• Stevens-Johnson syndrome
Drug reaction associated with severe mucocutaneous manifestations and vanishing bile duct syndrome
Definitions
• Bile duct injury, cholangitis, &/or ductopenia related to adverse drug reactions
Often accompanied by cholestasis
ETIOLOGY/PATHOGENESIS
2 Categories of Injury
• Predictable: Dose related, reproducible, and related to intrinsic toxicity of drug or its metabolites
• Idiosyncratic: Unpredictable, unrelated to dose, not reproducible in animal models
Allergic or autoimmune responses to drug or its metabolite may be involved
with eosinophilic cytoplasm, irregular spaces between nuclei, and variation in nuclear size and shape.
shows marked cytoplasmic vacuolization and eosinophilia as well as irregularly spaced nuclei.
are seen at the edge of this portal tract in a case of drug-related cholangitis. The native bile duct is distinct 
from these proliferating bile duct profiles.
Antibiotics: Amoxicillin-clavulanic acid, ampicillin, clindamycin, erythromycin, tetracycline, trimethoprim/sulfamethoxazole
