Simultaneous occurrence of autoimmune pancreatitis and sclerosing cholangitis as immune-related adverse events of pembrolizumab

2021 ◽  
Vol 14 (6) ◽  
pp. e243360
Author(s):  
Tsuyoshi Suda ◽  
Masako Kobayashi ◽  
Koji Kurokawa ◽  
Eiki Matsushita
Keyword(s):  
Bile Duct ◽  
Adverse Events ◽  
Autoimmune Pancreatitis ◽  
Sclerosing Cholangitis ◽  
Intrahepatic Bile Duct ◽  
Simultaneous Occurrence ◽  
Cd8 Cells ◽  
Igg4 Related Disease ◽  
Contrast Enhanced Ct ◽  
Serum Igg4

A 57-year-old man with lung cancer, previously treated with the programmed death-1 inhibitor pembrolizumab, was evaluated for liver injury and acute pancreatitis. Serum IgG4 levels were not elevated. Contrast-enhanced CT showed pancreatic swelling, contrast unevenness in the liver and thickening of the common bile duct and gall bladder. Magnetic resonance cholangial pancreatography revealed beads in the left intrahepatic bile duct and localised narrowing of the head and body of the central pancreatic duct. Endoscopic ultrasound-guided fine-needle and liver needle biopsy showed CD8+ and CD4+ T lymphocyte aggregates, whereas immunostaining revealed greater infiltration by CD8+ cells than CD4+ cells. IgG4-related disease was ruled out based on serum and pathological findings. The patient simultaneously presented with immune-related adverse events, autoimmune pancreatitis-like features and sclerosing cholangitis, which were ameliorated by steroid therapy. CD8+ lymphocytes were the dominant infiltrating cells in autoimmune pancreatitis and sclerosing cholangitis.

scholarly journals Cholangiocarcinoma Presenting after Eight Years of Treatment of IgG4-Related Autoimmune Pancreatitis with Steroids

2021 ◽  
pp. 154-162
Author(s):  
Hiroharu Shinozaki ◽  
Yuuichi Sasakura ◽  
Satoshi Shinozaki ◽  
Toshiaki Terauchi ◽  
Junichi Matsui ◽  
...  
Keyword(s):  
Bile Duct ◽  
Autoimmune Pancreatitis ◽  
Biliary Obstruction ◽  
Intrahepatic Bile Duct ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Steroid Treatment ◽  
Igg4 Related Disease ◽  
Lymph Node Enlargement ◽  
Serum Igg4

Autoimmune pancreatitis (AIP) is characterized by pancreatic manifestations of IgG4-related disease. Malignancies in patients with AIP have been reported, but carcinoma of the bile duct is extremely rare. We report a patient with IgG4-related AIP who developed cholangiocarcinoma after 8 years of steroid treatment. A 76-year-old male presented with fever (37.8°C) due to biliary obstruction and cholangitis. He had been treated with steroids for 8 years to control inflammation due to IgG4-related AIP. During 8 years of treatment, hepatobiliary enzyme levels were well controlled within their normal range, but serum IgG4 levels remained elevated. A computed tomography scan showed intrahepatic bile duct dilatation. Magnetic resonance cholangiopancreatography showed obstructive changes at the junction of the cystic and common ducts. To relieve biliary obstruction, endoscopic bile duct drainage using a nasobiliary tube was performed, and cytology was Class IV. Aorto-caval lymph node enlargement was found at laparotomy, intraoperatively diagnosed as adenocarcinoma, and resection was abandoned. He died 4 months postoperatively. We report a patient with IgG4-related AIP complicated by cholangiocarcinoma which developed after 8 years of steroid treatment. Even if hepatobiliary markers are well controlled, periodic follow-up with imaging studies may facilitate detection of an early cholangiocarcinoma.

scholarly journals Biliary Involvement in Type 2 Autoimmune Pancreatitis

2019 ◽  
Vol 13 (1) ◽  
pp. 200-206 ◽  
Author(s):  
Diana Ollo ◽  
Sylvain Terraz ◽  
Gregoire Arnoux ◽  
Giacomo Puppa ◽  
Jean-Louis Frossard ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Autoimmune Pancreatitis ◽  
Sclerosing Cholangitis ◽  
Hepatic Duct ◽  
Intrahepatic Bile Duct ◽  
Rare Condition ◽  
Left Hepatic Duct ◽  
Mr Cholangiography ◽  
Igg4 Related Disease

Autoimmune pancreatitis (AIP) is a rare condition classified in 2 subtypes. Their distinction relies on a combination of clinical, serological, morphological and histological features. Type 1 is a pancreatic manifestation of IgG4-related disease characterized by multiorgan infiltration by IgG4 plasmocytes. In this condition, hepatobiliary infiltration is frequent and often mimics cholangiocarcinoma or primary sclerosing cholangitis. On the other hand, type 2 is commonly limited to the pancreas. Herein, we describe the case of a patient who presented a type 2 AIP associated with cholangiopathy, a condition not described in the established criteria. He first developed a pancreatitis identified as type 2 by the typical histopathological features and lack of IgG4 in the serum and tissue. Despite a good clinical response to steroids, cholestasis persisted, identified by MR cholangiography as a stricture of the left hepatic duct with dilatation of the intrahepatic bile duct in segments 2 and 3. Biliary cytology was negative. Evolution was favorable but after steroid tapering a few months later, the patient suffered from recurrence of the pancreatitis as well as progression of biliary attempt, suspicious for cholangiocarcinoma. As the investigations again ruled out neoplastic infiltration or primary sclerosing cholangitis, azathioprine was initiated with resolution of both pancreatic and biliary attempts.

scholarly journals IgG4-Related Sclerosing Cholangitis Mimicking Cholangiocarcinoma

2021 ◽  
pp. 39-46
Author(s):  
Pham Minh Thong ◽  
Vu Dang Luu ◽  
Thieu-Thi Tra My ◽  
Nguyen Xuan Hien ◽  
Tran Anh Tuan ◽  
...  
Keyword(s):  
Bile Duct ◽  
Sclerosing Cholangitis ◽  
Wall Thickening ◽  
Systemic Involvement ◽  
Bile Duct Stenosis ◽  
Diffusion Weighted Images ◽  
Igg4 Related Disease ◽  
Imaging Characteristics ◽  
Serum Igg4 ◽  
Duct Stenosis

IgG4-related sclerosing cholangitis (IgG4-SC) is a relatively newly identified disease that is frequently associated with autoimmune pancreatitis. The differential diagnosis between cholangiocarcinoma, primary sclerosing cholangitis, and IgG4-SC can be challenging due to significant overlap among the clinical and imaging characteristics. We report the case of a 71-year-old woman who was diagnosed with IgG4-related disease based on increased serum IgG4 levels, imaging, and clinical presentation, which showed systemic involvement, including sclerosing cholangitis and kidneys. The patient presented with chronic jaundice. Magnetic resonance imaging revealed bile duct strictures and the dilatation of upstream bile ducts, smooth wall thickening with uniform enhancement in the delayed phase, and no vascular infiltration. Multiple low-density, wedge-shaped areas were identified in both kidneys, which were hypointense on T2-weighted images and hyperintense on diffusion-weighted images. The serum IgG4 levels of this patient were elevated to nearly 10-fold the normal upper limit. A diagnosis of IgG4-SC associated with IgG4-related kidney was made. Based on this case, pre-surgery IgG4 serum treatment in patients with non-malignant bile duct stenosis was recommended to exclude IgG4-SC.

scholarly journals IgG4-Seronegative Autoimmune Pancreatitis and Sclerosing Cholangitis

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Allon Kahn ◽  
Anitha D. Yadav ◽  
M. Edwyn Harrison
Keyword(s):  
Autoimmune Pancreatitis ◽  
Sclerosing Cholangitis ◽  
Clinical Presentation ◽  
Surgical Intervention ◽  
Comprehensive Evaluation ◽  
Elevated Serum ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Type 1 Autoimmune Pancreatitis

IgG4-related disease is a relatively novel clinical entity whose gastrointestinal manifestations include type 1 autoimmune pancreatitis (AIP) and IgG4-associated sclerosing cholangitis. The presence of elevated serum IgG4 is suggestive but not essential for the diagnosis of type 1 AIP and is a pervasive feature of the proposed diagnostic criteria. The differential diagnosis of type 1 AIP includes malignant conditions, emphasizing the importance of a deliberate, comprehensive evaluation. Management of patients with a suggestive clinical presentation, but without serum IgG4 elevation, is difficult. Here we present three cases of IgG4-seronegative AIP and sclerosing cholangitis that responded to empiric steroid therapy and discuss approach considerations. These cases demonstrate the value of meticulous application of existing diagnostic algorithms to achieve a clinical diagnosis and avoid surgical intervention.

scholarly journals IgG4-Related Sclerosing Cholangitis Involving the Intrahepatic Bile Ducts Diagnosed with Liver Biopsy

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Malene Theilmann Thinesen ◽  
Ove B. Schaffalitzky de Muckadell ◽  
Sönke Detlefsen
Keyword(s):  
Bile Duct ◽  
Liver Biopsy ◽  
Hot Spots ◽  
Sclerosing Cholangitis ◽  
Bile Ducts ◽  
Bile Duct Carcinoma ◽  
Duct Carcinoma ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4

IgG4-related disease is characterized by lymphoplasmacytic inflammation and fibrosis, often leading to mass-forming lesions in different organs. When IgG4-related disease affects the bile ducts, it is called IgG4-related sclerosing cholangitis. A 74-year-old male complained of dysphagia and abdominal pain. Endoscopic retrograde cholangiography and magnetic resonance cholangiography revealed bile duct changes suspicious of a bile duct carcinoma or cholangitis. Liver biopsy showed storiform fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, and a portal-based inflammatory nodule with expansion of a portal tract. Hot spots revealed 339 IgG4-positive cells per high power field (HPF) and an IgG4/IgG ratio of 72%. Eight months earlier, an inguinal lymph node had been removed, showing expanded interfollicular zones and increased plasma cells. Hot spots revealed 593 IgG4-positive cells and an IgG4/IgG ratio of 92%. The serum IgG4 of the patient was elevated nearly 10 times upper limit of normal. The diagnosis of IgG4-related sclerosing cholangitis associated with IgG4-related lymphadenopathy was made. There was good response to treatment with prednisolone and azathioprine. The differentiation of IgG4-related sclerosing cholangitis from primary sclerosing cholangitis and bile duct carcinoma is often difficult. Liver biopsy only rarely contributes to this setting, but we describe and report in detail a case where liver biopsy showed a portal-based inflammatory nodule with the characteristic features of this disease.

scholarly journals Immunoglobulin G4-related sclerosing cholangitis mimicking cholangiocarcinoma: a case report and literature review

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052095921
Author(s):  
Cheng Xu ◽  
Yongmei Han
Keyword(s):  
Sclerosing Cholangitis ◽  
Plasma Cells ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Immunoglobulin G4 ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
History Of ◽  
The Common

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a novel clinical disease that is characterized by elevated serum IgG4 concentrations and tumefaction or tissue infiltrated by IgG4+ plasma cells. The clinical manifestations of IgG4-RD depend on the type of tissues affected. IgG4-related sclerosing cholangitis is a type of IgG4-RD. We report a patient who initially visited a local hospital with a 5-month history of jaundice. He was found to have a mass in the upper part of the common bile duct that mimicked cholangiocarcinoma. He underwent surgery in our hospital and was later diagnosed with IgG4-related sclerosing cholangitis. We administered prednisolone 40 mg once a day for treatment. Taking into account the possible side effects of moderate-dose hormone therapy, we also administered teprenone, potassium chloride, and calcium carbonate. The patient did not have any recurrence of symptoms or adverse drug reactions during follow-up.

scholarly journals Intraductal Papillary Neoplasm of the Bile Duct With Invasive Adenocarcinoma Complicating IgG4-related Sclerosing Cholangitis: Report of a Case

2017 ◽  
Vol 102 (1-2) ◽  
pp. 70-76
Author(s):  
Ryo Ashida ◽  
Teiichi Sugiura ◽  
Yukiyasu Okamura ◽  
Takaaki Ito ◽  
Keiko Sasaki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Sclerosing Cholangitis ◽  
Invasive Carcinoma ◽  
Extrahepatic Bile Duct ◽  
Inflammatory Cells ◽  
Wall Thickening ◽  
Multidetector Row Computed Tomography ◽  
Intraductal Papillary Neoplasm ◽  
Serum Igg4 ◽  
Papillary Neoplasm

Although there have been many previous studies of IgG4-related SC focusing on the differential diagnosis from cholangiocarcinoma, only a few patients with cholangiocarcinoma against a background of IgG4-related SC have been reported. We herein present a case of intraductal papillary neoplasm of the bile duct (IPNB) associated with invasive carcinoma complicating IgG4-related sclerosing cholangitis. A 71-year-old female with icterus was admitted to a local hospital, where stricture of the extrahepatic bile duct were detected, and subsequently referred to our hospital for possible surgery. Abdominal multidetector-row computed tomography demonstrated marked wall thickening along the entire extrahepatic bile duct. The left lateral superior bile duct (B2) and left lateral inferior duct (B3) were individually obstructed, and percutaneous transhepatic biliary drainage catheters were placed in B2 and B3 separately. The patient was diagnosed to have diffusely spread cholangiocarcinoma and underwent right hepatic trisectionectomy with caudate lobectomy and pancreatoduodenectomy. A histological examination revealed intraductal papillary tumors composed of fibrovascular stalks covered by neoplastic epithelium. Carcinomatous invasion of the papillary tumors was observed in the fibromuscular layer, and there was abundant infiltration of inflammatory cells with fibrosis outside of the cancerous tissue. The inflammatory cells were primarily composed of plasma cells, a majority of which were positive for IgG4 (>30 cells/high-power field); the postoperative serum IgG4 level was 890 mg/dL. Therefore, a diagnosis of coexisting IPNB associated with invasive carcinoma and IgG4-related sclerosing cholangitis was made. To the best of our knowledge, this is the first report of IPNB complicating IgG4-related sclerosing cholangitis.

scholarly journals SAT0525 EFFICACY AND SAFETY OF MZR FOR IgG4-RELATED DISEASE.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1219-1220
Author(s):  
S. Kawaai ◽  
S. Fukui ◽  
T. Nakai ◽  
G. Kidoguchi ◽  
H. Ozawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Retention Rate ◽  
Case Reports ◽  
Efficacy And Safety ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Number Of Patients ◽  
Serum Igg4 ◽  
Over Time

Background:IgG4-Related Disease (IgG4RD) is known to cause multiple organ lesions with infiltration of IgG4-positive plasma cells, and patients often have relapses with tapering treatments despite an initial good response to glucocorticoids therapy. Mizoribine (MZR) is an immunosuppressant working as an inhibitor of purine synthesis, which mechanism of action is similar to mycophenolate mofetil. Data regarding the efficacy and safety of MZR on IgG4RD is limited although some previous case reports1showed effectiveness for IgG4RD.Objectives:This study aims to assess the efficacy and safety of MZR in patients with IgG4RD.Methods:We retrospectively reviewed charts of IgG4RD patients who used MZR between January 2004 and December 2019 at Immuno-Rheumatology Center in St. Luke’s International Hospital, Tokyo, Japan. We investigated basic demographics, involved organs, results of blood tests including IgG and IgG4 titer, and medications used including glucocorticoid and other immunosuppressants (IS). We followed IgG4 titer, dose of glucocorticoid, flare of disease and retention of MZR at the beginning, 6 and 12months after starting MZR. We compared changes in PSL (prednisolone) doses and IgG4 titers over time using Friedman test with Bonferroni correction. We also checked adverse events during follow up.Results:Twenty-two patients with IgG4RD who used MZR were included. Median age was 62 years old, and 15 (68.2%) patients are male. Lacrimal and salivary glands, pancreatitis and retroperitoneal fibrosis were common lesions. All patients were initially treated with glucocorticoids. Flare was observed in 5 (22.7 %) patients before initiation of MZR. The number of patients who continued MZR without flare are 19 (86.4 %) at 6 months, and 14 (73.7 %) at 12 months. IgG4 titer significantly declined at 6 and 12 months from baseline although significant consecutive decrease in PSL dose (Figure 1, 2). Liver dysfunctions are commonest adverse events (n=16, 72.7%) but mild (grade1; n=15, 68.2%) and most cases are apparently due to other reasons. Serious infection (SI) occurred in 3 (13.6%) patients in total follow up, however no SI were observed during 1 year after MZR treatment.Conclusion:MZR can be safely used in patients of IgG4RD with high retention rate, and seemed to have steroid-sparing effect. Prospective comparative studies are needed.References:[1]Nanke Y, Kobashigawa T, Yago T, Kamatani N, Kotake S. A case of Mikulicz’s disease, IgG4-related plasmacytic syndrome, successfully treated by corticosteroid and mizoribine, and then by mizoribine alone. Intern Med 49: 1449-1453, 2010.Table 1.Patient characteristics    Table 2.Disease and treatment status before and after initiation of MZR    Figure 1.Serum IgG4 level changesFigure 2.Changes in the PSL dose over timeDisclosure of Interests:None declared

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