Delayed and prolonged cholestatic hepatitis with ductopenia after long-term ciprofloxacin therapy for Crohn's disease

Ciprofloxacin, a fluorinated quinolone, is a powerful antibiotic widely used for its broad spectrum of activity in ambulatory and long-term care setting. Until now, ciprofloxacin administration has been associated with a few cases of acute, sometimes cholestatic jaundice or fulminant hepatic failure believed mainly related to idiosyncratic hypersensitivity. We report a case of delayed and prolonged cholestatic hepatitis with ductopenia occurring after 6 months of treatment in a patient with Crohn's disease. This observation suggests the potential for the drug to induce long-term likely dose-related severe hepatotoxicity.     

Ductal regeneration in vanishing bile duct syndrome in Hodgkin's lymphoma

We present the case of a 17-year-old male patient with Hodgkin's lymphoma (nodular sclerosis) in the mediastinum. During the postoperative period treatment with erythromycin was started and the patient developed progressive jaundice and cholestasis. Treatment modified for the lymphoma was initiated, which achieved complete remission and subsequent improvement and resolution of the cholestasis. Histological study of the liver revealed massive loss of bile ducts. After resolution of the cholestasis, consecutive biopsies revealed ductal proliferation. The present report therefore illustrates a case of ductopenia or vanishing bile duct syndrome (VBDS) with ad integrum regeneration of the bile ducts simultaneous with lymphoma remission. Because the 2 possible causes, erythromycin toxicity and Hodgkin's lymphoma, occurred simultaneously, the etiology of the VBDS cannot be definitively established.     

Idiopathic adulthood ductopenia: case report and review of the literature

The clinical and pathological findings of idiopathic ductopenia were studied in a 30-year-old woman who initially manifested jaundice and pruritus. Serum biochemical tests of liver function indicated severe and progressive cholestasis. Viral hepatitis markers and circulating autoantibodies were absent. The patient had a normal cholangiogram and lacked evidence of inflammatory bowel disease. Histological examination of a liver specimen showed severe cholestasis and absence of interlobular bile ducts. Severe jaundice and intractable pruritus developed in the patient and served as the indications for liver transplantation 4 months after initial examination. Transplantation resulted in prompt and complete resolution of the jaundice and pruritus. Two types of idiopathic adulthood ductopenia associated with different prognoses are recognized. Patients with type 1 idiopathic adulthood ductopenia are asymptomatic or manifest symptoms of cholestatic liver disease. They tend to have less destruction of the intrahepatic bile ducts on liver biopsy specimens. Their clinical course ranges from spontaneous improvement to progression to biliary cirrhosis. In contrast, patients with type 2 idiopathic adulthood ductopenia generally manifest initial symptoms of decompensated biliary cirrhosis, have extensive destruction of the intrahepatic bile ducts on liver biopsy, and frequently require orthotopic liver transplantation.     

Prolonged cholestasis and ductopenia following gold salt therapy

Abstract: Hepatotoxicity, predominantly cholestatic, is a rare adverse effect of gold salt therapy, which usually completely resolves within a few months. We report the case of a female patient treated for rheumatoid arthritis, who had gold salt overdose, and in whom acute cholestatic hepatitis occurred three weeks after beginning of therapy. Evolution of gold concentration was followed in plasma and urine, as well as in cutaneous and liver dry tissue. Liver biopsy showed marked inflammatory changes of interlobular bile ducts that evolved towards ductopenia, which was responsible for prolonged cholestasis still present 15 months later. In addition, sialadenitis with sicca syndrome was noted six months after onset of the disease. The mechanism of hepatotoxicity was probably immunoallergic since liver lesions were associated with hypersensitivity syndrome including dermatitis and blood and tissue eosinophilia. This is the first report of gold salt hepatotoxicity with histological demonstration of cholangitis followed by ductopenia.     

Prolonged cholestasis and ductopenia associated with tenoxicam

Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.     

Ductopenia related liver sarcoidosis

Sarcoidosis is a systemic granulomatous disease which may involve many organs.In approximately 95% of patients there is liver involvement,with noncaseating hepatic granulomas occurring in 21 to 99% of patients with sarcoidosis.Liver involvement is usually asymptomatic and limited to mild to moderate abnormalities in liver biochemistry.The occurrence of jaundice in sarcoidosis is rare;extensive imaging procedures and the examination of liver biopsies permit a precise diagnostic.Ductopenia associated with sarcoidosis has been reported in less than 20 cases and can lead to biliary cirrhosis and liver-related death.We report here on a case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded.The patient follow up was 8 years.Although ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis.A review of the literature of reported cases of ductopenia related to sarcoidosis is provided.     

Fulminant hepatic failure as a presenting paraneoplastic manifestation of Hodgkin's disease.

Malignancies may uncommonly present as fulminant hepatic failure and, due to the rarity of such an occurrence, they may easily be overlooked as one of its possible causes. An unusual case of Hodgkin's disease presenting as a fulminant hepatic failure is reported. A 34-year-old man presented with an acute onset of liver failure characterized by jaundice, ascites, encephalopathy and bleeding diathesis. Chemotherapy was initiated, resulting in a dramatic improvement not only in the patient's level of consciousness, but also in prothrombin time. Unfortunately, he succumbed shortly after to disseminated candidiasis. A post-mortem needle liver sample revealed massive hepatocellular necrosis, but no liver infiltration by the neoplastic disease. We conclude that in Hodgkin's disease, involvement of the liver can be manifested as a syndrome of paraneoplastic fulminant hepatic failure. In such cases, liver transplantation is an absolute contraindication but urgent chemotherapy under antifungal surveillance can be life saving.     

Reversible methotrexate associated lymphoproliferative disease evolving into Hodgkin's disease

We describe a case of nodular sclerosing Hodgkin's disease (NSHD) developing in a 61-year-old woman with seropositive rheumatoid arthritis treated with oral methotrexate (MTX) 5 to 15 mg/week for 5 years. Computed tomography (CT) of the abdomen revealed splenomegaly and marked abdominal and retroperitoneal lymphadenopathy. MTX was discontinued; several weeks later prednisone 10 mg/day was added to control worsening polyarthralgia. Repeat CT at 3 months showed almost complete regression of the splenomegaly and lymphadenopathy. However, CT studies at 10 months showed asymptomatic progression of lymphadenopathy, which on biopsy revealed NSHD. Patients with apparently reversible MTX associated lymphoproliferative disorder require periodic monitoring for asymptomatic development of malignant lymphoma.     

Obstructive Jaundice Secondary to Primary Biliary Involvement with Hodgkin''s Disease

A 41-yr-old man presented with jaundice, night sweats, and weight loss. The patient had been on phenytoin for seizure disorder. The drug was discontinued, and a diminution of bilirubin and transaminases occurred over several weeks. Percutaneous liver biopsy revaled cholestasis at the time of maximal hyperbilirubinemia. Recurrent jaundice ensued several weeks later, and an ERCP revealed a common bile duct lesion. Laparotomy revealed Hodgkin's disease involving the common bile duct and periportal node. This cause represents the first report of extrahepatic biliary obstruction from Hodgkin's disease.     

Hodgkin's disease presenting with progressive liver failure

We report an unusual case of a 70-year-old man with a diagnosis of Hodgkin's disease, who presented with fever and liver dysfunction. A few cervical lymph nodes, less than 1 cm in diameter were palpable, but other lymph nodes were not detected even by CT scan. Blood cell counts showed thrombocytopenia (platelet counts 6.8 x 10(4)/microliter), and some values for liver enzymes were out of the normal range (AST 56 U/l, ALT 87 U/l, LDH 347 U/l, ALP 1,529 U/l, and gamma-GTP 190 U/l). Abdominal CT scan showed diffuse enlargement of the liver and spleen. Endoscopic retrograde biliary cholangiopancreatography was performed because of progressive jaundice, but no abnormality was found in the biliary tract. A few granulomas were observed in bone marrow clot specimens, but tumor cells were not detected. A diagnosis of Hodgkin's disease was established by a cervical lymph node biopsy. Chemotherapy was immediately instituted, and both the jaundice and fever improved dramatically. Because cervical lymph nodes were not detected at one month after the onset and liver dysfunction appeared before cytopenia, it is suggested that the site of the primary lesion in this case was the liver.     

Acquired infundibular pulmonary stenosis. Possible late complication following radiotherapy of Hodgkin disease

A case of infundibular pulmonary stenosis occurring years after a mediastinal radiation for Hodgkin's disease is reported. As far as the literature is known to us, a similar case has not yet been described. It is most likely that the development of the stenosis is due to the radiation therapy, since a murmur was not heard before radiation and a mild stenosis was proved several years after radiation. Now, a high gradient with the typical signs of an infundibular pulmonary stenosis was present. Unfortunately the patient refused the operation. Further possibilities for acquired pulmonary stenosis and cardial complications after mediastinal radiation for Hodgkin's disease will be discussed.     

Role of bone marrow examination in staging Hodgkin's disease: experience in México

We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.).     

Familial idiopathic adulthood ductopenia: a report of five cases in three generations

BACKGROUND/AIMS: Idiopathic adulthood ductopenia is a cholestatic liver disease of unknown etiology. Although most cases are sporadic, familial cases do occur. METHODS: We describe a series of adult-onset bile duct depletion involving five members of an extended family spanning three generations. The proband, a 49-year-old man, presented in 1989 with asymptomatic elevation of liver enzyme tests. Investigations for chronic liver disease, including endoscopic retrograde cholangiopancreatography, were negative. Findings on liver biopsy progressed from normal in 1989 to striking loss of interlobular bile ducts in 1992. Ursodeoxycholic acid has resulted in improvement of liver enzyme tests. The proband's brother required a liver transplant at age 35 for cryptogenic cirrhosis. The proband's sister, age 42, has had intermittent jaundice and elevation of liver enzyme tests since 1971. Her liver biopsy findings progressed from normal in 1975, to striking bile duct damage by 1997. The proband's 21-year-old son has elevated liver enzyme tests and a liver biopsy consistent with idiopathic adulthood ductopenia. The proband's father had a liver biopsy at age 70 for investigation of a liver mass. It revealed extensive fibrosis and striking bile duct destruction. RESULTS/CONCLUSIONS: This is the largest series of familial idiopathic adulthood ductopenia reported, and the first with multiple generations described. Genetics appears to play a role in some cases of adulthood ductopenia. Ursodeoxycholic acid may be beneficial in the treatment of this condition.     

Successful treatment of steroid-resistant Weber-Christian disease with biliary ductopenia using cyclosporin A

SIR, Weber–Christian disease (WCD) is an unusual idiopathicdisorder characterized by non-suppurative nodular panniculitiswith fever and cutaneous lesions [1]. The aetiology of WCD remainsunknown, and systemic WCD, associated with severe liver damage,is often fatal [2]. Hepatic injury associated with WCD is characterizedby steatohepatitis [3, 4]. To our knowledge, however, WCD withbiliary ductopenia has not yet been reported. We report thefirst case of systemic WCD with biliary ductopenia that wassuccessfully treated with cyclosporin A (CyA). The patient was a 27-yr-old Japanese     

Hodgkin's disease diagnosed by endoscopic ultrasound-guided fine needle aspiration of a periduodenal lymph node

Hodgkin's disease rarely presents as obstructive jaundice. We report a case of Hodgkin's disease arising in periduodenal lymph nodes, presenting with biliary obstruction, definitively diagnosed on cytologic material obtained by endosonographically-guided real-time fine needle aspiration biopsy and confirmed at laparotomy. The medical literature pertaining to the use of endosonography and fine needle aspiration biopsy for pancreatic lesions and abdominal lymphoma is reviewed. Currently available data support the use of fine needle aspiration biopsy in establishing the diagnosis of lymphoma. This case highlights the utility of endoscopic ultrasonography with endosonographically guided real-time fine needle aspiration biopsy in diagnosing and managing patients with extrahepatic biliary obstruction or suspected abdominal lymphoma. Pairing endosonographically guided real-time fine needle aspiration biopsy with on-site cytologic assessment and immediate specimen triage can lead to definitive diagnosis of abdominal lymphoma, avoiding surgical intervention in many cases.     

Vanishing Bile Duct Syndrome in a Hodgkin's Lymphoma Patient with Fatal Outcome Despite Lymphoma Remission

Vanishing bile duct syndrome (VBDS) is a condition resulting from severe bile duct injury, progressive destruction, and disappearance of intrahepatic bile ducts (ductopenia) leading to cholestasis, biliary cirrhosis, and liver failure. VBDS can be associated with a variety of disorders, including Hodgkin''s lymphoma (HL). We describe a 33-year-old male patient who presented with lymphadenopathy and jaundice, and was diagnosed to have HL. Serum bilirubin worsened progressively despite chemotherapy, with a cholestatic pattern of liver enzymes. Diagnosis of VBDS was established on liver biopsy. Although remission from HL was achieved, the patient died of liver failure. Presence of jaundice in HL patients should raise the possibility of VBDS. This report discusses the difficulties of delivering chemotherapy in patients with liver dysfunction. HL-associated VBDS carries a high mortality but lymphoma remission can be achieved in some patients. Therefore, liver transplantation should be considered early in these patients.     

Spontaneous regression of Hodgkin's disease: two case reports and a review of the literature

We present two cases of patients with Hodgkin's lymphoma who experienced spontaneous regressions of their disease. The first case was a 31-year-old man diagnosed with stage IIIA lymphocyte predominant Hodgkin's disease in 1994, who elected to be followed without any treatment. Over the subsequent 3 years, he experienced significant regression in his lymphadenopathy, and still remains asymptomatic of his disease 70 months after diagnosis. The second case was a 47-year-old man with a bulky anterior mediastinal mass found on a thoracic CT scan, ultimately diagnosed with stage IIB Nodular Sclerosing Hodgkin's Lymphoma. Repeat imaging of the chest performed two months later, just prior to initiating treatment, revealed that the mass had spontaneously decreased by >75% of its original size. Spontaneous regressions of Hodgkin's lymphoma are exceedingly rare. A review of the literature regarding spontaneous regressions of lymphoma and cancer in general is discussed.     

Manifestation late in life of idiopathic adulthood ductopenia

Abstract: Idiopathic adulthood ductopenia is a chronic cholestasic liver disease of unknown etiology characterized by the loss of interlobular bile ducts. We describe three patients who fulfilled the diagnostic criteria of idiopathic adulthood ductopenia, but differed from the cases reported so far in late manifestation of the disease and a benign clinical course despite histologic evidence of ongoing cholangitis. Treatment with ursodeoxycholic acid in one patient resulted in improvement of biochemical markers of cholestasis, suggesting that chronic cholestasis in idiopathic adulthood ductopenia can be influenced beneficially.     

Effect of plasma exchange on the circulating IL-6 levels in a patient with fatal hemophagocytic syndrome associated with bile ductopenia

We report here the case of a patient suffering from hemophagocytic syndrome (HPS) associated with bile ductopenia. A 24-year old man was admitted after suffering fever, sore throat and general malaise for 7 days and jaundice for 2 days. Clinical studies showed hepatic dysfunction with hyperbilirubinemia. Epstein-Barr viral DNA from two bone marrow samples was detected. Bone marrow aspiration disclosed findings of HPS. Liver biopsy showed centrilobular cholestasis with lack of interlobular bile duct. Repeated therapeutic plasma exchange was effective for decreasing serum bilirubin and interleukin-6 levels. The patient received liver transplantation, however, he finally died of alveolar hemorrhage resulting from disseminated intravascular coagulation and acute rejection.