Vanishing bile duct syndrome following pembrolizumab infusion: case report and review of the literature

PD-1/PD-L1 inhibitors demonstrate high efficacy in non-small-cell lung cancer and are now routinely used in clinical practice. Severe immune-related adverse events are reported in about 5% of patients, requiring hospitalization and possibly leading to death. We present a rare case of vanishing bile duct syndrome that arose a few days after the first pembrolizumab infusion. Laboratory tests and radiological imaging studies were performed to orient diagnosis and monitor the disease, while the evidence of ductal loss on the histological sample was pathognomonic for vanishing bile duct syndrome. High-dose steroid therapy and immunosuppressors were administered, resulting in scarce efficacy. Prompt recognition and management of similar conditions is crucial to avoid fatal events. Further studies are needed to investigate new drugs for steroid-refractory conditions.

Vanishing Bile Duct Syndrome and Hodgkin’s Lymphoma: Case Report and Thorough Review of the Literature

Vanishing Bile Duct Syndrome (VBDS) is a rare, acquired disorder, characterized by progressive destruction and loss of intrahepatic bile ducts. The main clinical manifestations are jaundice and pruritus, caused by intralobular cholestasis. Although the pathogenic mechanism is poorly understood, VBDS has been associated with numerous etiologies such as medications, malignancies, infections and autoimmune diseases. This syndrome can appear as a paraneoplastic phenomenon in patients with Hodgkin’s Lymphoma (HL). Diagnosis is based on clinical evaluation and confirmed via liver biopsy, while treating the underlying cause is the main therapeutic target. If bile duct regeneration does not occur, possible outcomes include cirrhosis, hepatic failure and death, with liver transplantation being the only curative option. In this paper, we describe a case of HL-related VBDS in a 31-year-old female patient, who presented with jaundice, pruritus and cervical lymphadenopathy. The stage of HL was determined as IIA and a liver biopsy was performed, which confirmed the degeneration of bile ducts. The patient was treated with the ABVD regimen and dexamethasone. Follow-up tests were normal and supported the full remission hypothesis. We conducted an analytical literature review and collected the available data from 38 confirmed cases, regarding the epidemiology, viral infections, clinical findings, therapeutic options and outcome.

Drug-Induced Vanishing Bile Duct Syndrome: From Pathogenesis to Diagnosis and Therapeutics

The most concerned issue in the context of drug/herb-induced chronic cholestasis is vanishing bile duct syndrome. The progressive destruction of intrahepatic bile ducts leading to ductopenia is usually not dose dependent, and has a delayed onset that should be suspected when abnormal serum cholestasis enzyme levels persist despite drug withdrawal. Immune-mediated cholangiocyte injury, direct cholangiocyte damage by drugs or their metabolites once in bile, and sustained exposure to toxic bile salts when biliary epithelium protective defenses are impaired are the main mechanisms of cholangiolar damage. Current therapeutic alternatives are scarce and have not shown consistent beneficial effects so far. This review will summarize the current literature on the main diagnostic tools of ductopenia and its histological features, and the differential diagnostic with other ductopenic diseases. In addition, pathomechanisms will be addressed, as well as the connection between them and the supportive and curative strategies for ductopenia management.

Hodgkin-lymphomához társult eltűnőepeút-szindróma

Összefoglaló. Az eltűnőepeút-szindróma ritka, rossz prognózisú kórkép. Az epeutak progresszív destrukciójával, az intrahepaticus epeutak eltűnésével jár, epepangáshoz, biliaris cirrhosishoz, végül májelégtelenséghez vezet. A háttérben álló kiváltó okok között infekciók, ischaemia, gyógyszermellékhatások, illetve daganatos megbetegedések szerepelhetnek. A malignitások közül a leggyakrabban a Hodgkin-lymphomához társult formájával találkozhatunk. Cikkünkben egy fiatal, Hodgkin-lymphomás betegünk esetét szeretnénk bemutatni, akinél az icterus hátterében eltűnőepeút-szindróma igazolódott, melyet egyéb okok kizárását követően szövettani mintavétellel igazoltunk. A két ciklus ABVD-protokoll szerinti kezelést követő PET/CT az alapbetegség tekintetében komplett metabolikus remissziót igazolt. A klinikai javuláshoz azonban hosszú hónapokra volt szükség. Végül az epeúteltűnés esetünkben reverzibilis folyamatnak bizonyult, az alapbetegség tekintetében a komplett metabolikus remisszió elérésével az epeút-károsodás megállítható volt. Orv Hetil. 2021; 162(22): 884–888. Summary. destruction and loss of the intrahepatic bile ducts leading to cholestatis, biliar chirrosis and finally liver failure. It has been described in different pathologic conditions including infections, ischemia, adverse drug reactions and malignancies. The Hodgkin’s lymphoma-associated type occurs most frequently among the forms of the disease of malignant origin. In this report, we introduce the case of a 32-year-old male patient with Hodgkin’s lymphoma, diagnosed with vanishing bile duct syndrome upon liver biopsy as a root cause behind his icterus. The PET/CT has proven complete metabolic remission after 2 cycles of ABVD chemoterapy. Clinical improvement, however, occurred only after several months. Finally the loss of bile ducts proved to be a reversible process, the complete metabolic remission of Hodgkin’s lymphoma resulted in the regeneration of the bile ducts. Orv Hetil. 2021; 162(22): 884–888.

A fatal case of toxic epidermal necrolysis combined with vanishing bile duct syndrome and hemophagocytic lymphohistiocytosis

This case report describes a case of fatal Toxic Epidermal Necrolysis complicated by both vanishing bile duct syndrome and hemophagocytic lymphohistiocytosis due to Influenza B infection. Here we highlight the potential for complex morbidity secondary to underlying autoimmune hypersensitivity. Furthermore, the stepwise progression of these pathologies is noted, with the initial epidermal lesions first progressing to cholestatic injury and then subsequently to the hematologic manifestations.