Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis. For steroid-dependent disease, azathioprine has been used for maintenance of remission. Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis; however, there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis. A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil, which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production. Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events. The patient was managed without a biliary stent. However, there was a return of symptoms, jaundice, increase in transaminases, and hyperbilirubinemia when the prednisone dose reached 11 mg per day. In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis, the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events, but it did not enable discontinuation of the steroids. Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.     

Overlap syndrome of autoimmune pancreatitis and cholangitis associated with secondary Sjögren's syndrome

In approximately 25% of patients with acute or chronic pancreatitis the cause remains unclear. Despite progress in understanding so-called idiopathic pancreatitis, more diagnostic criteria are needed. We report on a patient who presented with jaundice, but without pain or fever. Under the assumption of pancreatic cancer the patient underwent hemipancreatoduodenectomy. Histological examination showed chronic sclerosing inflammation of the pancreas and bile ducts without any signs of malignancy. Ten weeks later he developed bilateral parotid swelling and recurrent bouts of fever. Again liver enzymes were elevated and unsuccessfully treated with antibiotics for bacterial cholangitis. Further biopsies from submandibular gland, lymph nodes and liver again showed chronic sclerosing inflammation with lymphoplasmacytic infiltration. For sicca symptoms the diagnosis of a primary Sjogren's syndrome was proposed. However, with corticosteroid treatment the patient improved remarkably but after tapering he relapsed. On the basis of established criteria, we diagnosed autoimmune pancreatitis with (1) diffuse swelling of the pancreas, (2) irregularities of the pancreatic duct, (3) lymphoplasmacytic infiltration, (4) response to corticosteroids, (5) hypergammaglobulinaemia, and (6) disproportionately raised IgG4. In addition, the patient fulfilled the criteria for secondary Sjogren's syndrome. Autoimmune pancreatitis may present as an isolated or syndromic disease. It is an autoimmune disorder of unknown cause and should be included in the differential diagnosis of pancreatic disorders.     

Atteintes extrapancréatiques au cours de la pancréatite auto-immune: particularités et apport diagnostique

Autoimmune pancreatitis is a rare entity. It represents 2 to 5% of chronic pancreatitis. With clinical, biological, and radiological particularities, extra pancreatic features of autoimmune pancreatitis have a great value for diagnosis. Our study concerns 3 cases of autoimmune panreatitis. We will study the extrapancreatic features particularities and their diagnosic value. We report 3 cases (two men and a woman 55, 28 and 24 years-old) with autoimmune pancreatitis with jaundice or epigastrium pain, synchronous and metachronous extrapancreatic features. In 2 cases, these extra-pancreatic features included cholangitis with renal atrophy and retroperitoneal fibrosis in one case. In the last case, we found Crohn’s disease and Gougerot-Sjogren disease. IGG4 level was high in the three cases. The diagnosis was made radiologically (CT scan, MRI) in two cases and histologically after duodenopanreatectomy in one case. Corticoid therapy had constituted a diagnosis and therapeutic test in two cases and treatment for extra-pancreatic features in one case. The presence of synchronous or metachronous inflammatory lesions of the biliary tract, kidney, intestine or other during the auto-immune pancreatitis can guide the diagnosis of this rare and often misunderstood disease. Their knowledge can save the patient a surgical procedure allowing medical treatment with corticosteroids.     

A case of autoimmune pancreatitis effectively treated with an immunosuppressant (azathioprine)

The patient was a 42-year-old man who presented at our hospital with obstructive jaundice. Although antinuclear antibody test results were negative, and immunoglobulin G4 (IgG4) was not elevated, endoscopic ultrasound revealed a mixed internal hyperechoic and diffuse hypoechoic pattern, a finding consistent with autoimmune pancreatitis. Endoscopic retrograde cholangiopancreatography further revealed irregular narrowing of the main pancreatic duct and sclerosing cholangitis with distal biliary stricture. In addition, endoscopic ultrasound with fine needle aspiration cytology resulted in a diagnosis of type 1 autoimmune pancreatitis. Oral prednisolone treatment was initiated at 30 mg/day, and the dosage was gradually decreased. However, in accordance with the patient’s wishes, maintenance treatment was discontinued once dosage reached 5 mg/day. Despite this, relapse of obstructive jaundice occurred 1 month post discontinuation, and was treated with methyl-prednisolone pulse therapy (500 mg/day) followed by oral prednisolone. However, computed tomography, magnetic resonance imaging, and endoscopic ultrasound did not reveal sufficient improvement after 6 months of treatment. Therefore, an immunosuppressant (azathioprine) was introduced. Subsequent imaging analyses and endoscopic ultrasound fine needle aspiration revealed clear improvements in pathology.     

Autoimmune-related Pancreatitis

Opinion statement The treatment of patients with autoimmune pancreatitis poses a challenge to the clinician. Prednisone, in an initial dosage of 30 to 40 mg/d, is used in patients with moderate abdominal and back pain, obstructive jaundice, or sclerosing cholangitis. Antacid or anticholinergic agents may be used to minimize stimulation of pancreatic exocrine function. Patients with quiescent disease may not need pharmacologic medication. In patients with complications such as obstructive jaundice and infection, biliary drainage and administration of antibiotics are recommended prior to steroid therapy. Steroid therapy occasionally ameliorates diabetes mellitus associated with autoimmune pancreatitis.     

Sclerosing cholangitis associated with autoimmune pancreatitis

Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by irregular narrowing of the pancreatic duct, pancreatic swelling, and a favorable response to corticosteroids, in which the autoimmune mechanism is postulated in the pathogenesis. High serum immunoglobulin (Ig)G4 concentrations and various types of extrapancreatic involvement are prominent features of this disease. Sclerosing cholangitis is a major extrapancreatic lesion of autoimmune pancreatitis that has been regarded as primary sclerosing cholangitis (PSC) complicating chronic pancreatitis. Because sclerosing cholangitis associated with autoimmune pancreatitis (SC-AIP) also favorably responds to corticosteroid therapy, it should be differentiated from PSC. Useful points regarding the differentiation between SC-AIP and PSC are as follows: (i) PSC occurs in younger and SC-AIP in older individuals; (ii) obstructive jaundice is more frequently seen in SC-AIP; (iii) PSC is complicated with inflammatory bowel disease, whereas SC-AIP is complicated with so called extrapancreatic lesions of AIP; (iv) high serum IgG4 concentrations are frequently seen in SC-AIP; (v) a cholangiogram may differentiate the two conditions to some extent; (vi) abundant IgG4-bearing plasma cell infiltration is seen in SC-AIP; and (vii) steroid therapy is effective for SC-AIP. IgG4-related sclerosing cholangitis without pancreatic lesion may be a metachronous phenotype of SC-AIP, and also should be differentiated from PSC. The pathogenesis of AIP and SC-AIP remains unclear. The complement activation system of the classical pathway may be contributing in some cases.     

Endoscopic ultrasound-guided biliary drainage performed for refractory bile duct stenosis due to chronic pancreatitis: a case report

We report a case of the patient who underwent endoscopic ultrasound-guided biliary drainage (EUS-BD) for refractory bile duct stenosis due to chronic pancreatitis. The patient had repeatedly undergone endoscopic biliary stenting for bile duct stenosis due to chronic pancreatitis. Because of repeated relapses of cholangitis and jaundice, transpapillary treatment was judged to have reached its limits. Surgical bypass was attempted but had to be abandoned due to adhesions. Thus, EUS-BD was performed. The procedure was successful, and placement of a covered expandable metallic stent (C-EMS) relieved cholangitis. Two months after placement, the C-EMS was removed, and the patient became stent-free but closure of the fistula subsequently occurred.     

Recurrent liver failure caused by IgG4 associated cholangitis

Immunoglobulin G4 associated cholangitis (IAC) is an autoimmune disease associated with autoimmune pancreatitis (AIP). It presents with clinical and radiographic findings similar to primary sclerosing cholangitis (PSC). IAC commonly has a faster, more progressive onset of symptoms and it is more common to see obstructive jaundice in IAC patients compared to those with PSC. One of the hallmarks of IAC is its responsiveness to steroid therapy. Current recommendations for treatment of AIP demonstrate excellent remission of the disease and associated symptoms with initiation of steroid therapy followed by steroid tapering. If untreated, it can progress to irreversible liver failure. This report describes a 59 year-old female with undiagnosed IAC who previously had undergone a pancreaticoduodenectomy for a suspected pancreatic cancer and later developed liver failure from presumed PSC. The patient underwent an uncomplicated liver transplantation at our institution, but experienced allograft failure within five years due to progressive and irreversible bile duct injury. Radiology and histology suggested recurrence of PSC, but the diagnosis of IAC was suspected based on her past history and confirmed when IgG4 positive cells were found within the intrahepatic bile duct walls on a liver biopsy. A successful liver retransplantation was performed and the patient is currently on triple immunosuppressive therapy. Our experience in this case and review of the current literature regarding IAC management suggest that patients with suspected or recurrent PSC with atypical features including history of pancreatitis should undergo testing for IAC as this entity is highly responsive to steroid therapy.     

Autoimmune pancreatitis mimicking cancer of the head of pancreas: report of two cases

Autoimmune pancreatitis has been characterised in 1995, but only a few cases have been published since then, most of them from Japan. This report describes the cases of two Belgian male patients who presented with isolated obstructive jaundice. Radiological imaging studies were highly suggestive of carcinoma of the head of pancreas and both patients underwent uneventful cephalic pancreaticoduodenectomy with portal vein resection. Pathological analysis of the removed tissues suggested an autoimmune process in both cases. Both patients had hyper-gammaglobulinemia and antinuclear antibodies, but failed to show evidence of any other autoimmune disease or cause of chronic pancreatitis. In both cases final diagnosis was autoimmune pancreatitis. Preoperative clinical suspicion of this diagnosis is mandatory and may avoid unnecessary surgery in future cases.     

Laparoscopic Pancreatic Biopsy in Autoimmune Pancreatitis—Report of TWO Cases

Two cases of autoimmune pancreatitis that were diagnosed by laparoscopic pancreatic biopsy are reported. Patient 1 was a 71–year-old woman with obstructive jaundice and dry eyes. Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis of the distal common bile duct and proximal main pancreatic duct. Only the head of the pancreas was enlarged. The patient had associated Sjogren's syndrome and sclerosing cholangitis. Patient 2 was a 65–year-old man with obstructive jaundice that occurred after laparoscopic cholecystectomy. ERCP revealed a diffusely irregular and narrowed pancreatic duct and stenosis of the distal common bile duct. The whole pancreas was enlarged. Both patients underwent laparoscopic pancreatic biopsy to rule out pancreatic cancer. The definitive diagnosis in each case was autoimmune pancreatitis. The postoperative course in both cases was uneventful. Both patients recovered quickly with steroid therapy undertaken soon after the biopsy. In summary, a laparoscopic approach for the pancreatic biopsy in autoimmune pancreatitis appears to be feasible and useful in determining the therapeutic strategy. (Dig Endosc 1999; 11: 250–254)     

Diagnostic challenges of Wilson’s disease presenting as acute pancreatitis,cholangitis, and jaundice

Wilson’s disease is a rare disorder of copper transport in hepatic cells, and may present as cholestatic liver disease; pancreatitis and cholangitis are rarely associated with Wilsons’s disease. Moreover, cases of Wilson’s disease presenting as pigmented gallstone pancreatitis have not been reported in the literature. In the present report, we describe a case of a 37-year-old man who was admitted with jaundice and abdominal pain. The patient was diagnosed with acute pancreatitis, cholangitis, and obstructive jaundice caused by pigmented gallstones that were detected during retrograde cholangiopancreatography. However, because of his long-term jaundice and the presence of pigmented gallstones, the patient underwent further evaluation for Wilson’s disease, which was subsequently confirmed. This patient’s unique presentation exemplifies the overlap in the clinical and laboratory parameters of Wilson’s disease and cholestasis, and the difficulties associated with their differentiation. It suggests that Wilson’s disease should be considered in patients with pancreatitis, cholangitis, and severe protracted jaundice caused by pigmented gallstones.     

Characteristic Pancreatic Duct Appearance in Autoimmune Chronic Pancreatitis: A Case Report and Review of the Japanese Literature

We report a case demonstrating the progressive narrowing of the pancreatic duct, which is presumed to be characteristic of autoimmune pancreatitis, and we review the 37 cases of chronic pancreatitis in which autoimmunity was suggested as an etiological factor in the Japanese literature. A 55-year-old man presented with abdominal discomfort, jaundice, and diffuse swelling of the pancreas on ultrasonography. Serial endoscopic retrograde pancreatography demonstrated the progression of an irregular narrowing of the main pancreatic duct forming diffusely over the course of 2 months. Because the patient had hyperglobulinemia and tested positive for autoantibodies, he was diagnosed as a case of autoimmune chronic pancreatitis. Steroid therapy was carried out with excellent success.     

A pancreatic abscess 7 years after a pancreatojejunostomy for calcifying chronic pancreatitis

We present herein a case of a 75-year-old Japanese man who had developed a pancreatic abscess 7 years after a longitudinal pancreatojejunostomy for chronic pancreatitis. The patient, a heavy drinker of alcohol, underwent surgical decompression of a ductal obstruction to relieve persistent abdominal pain due to severely calcifying chronic pancreatitis. After the surgery, he stopped drinking alcohol and was treated with insulin to control secondary diabetes mellitus. Thereafter, his symptoms disappeared. Seven years after the surgery, however, he was hospitalized due to obstructive jaundice, high-grade fever, and right hypochondria pain. Ultrasound and computed tomographic scans of the abdomen both disclosed a cystic mass, approximately 6 cm in size, in the pancreatic head. Magnetic resonance imaging strongly suggested a pancreatic abscess with necrotic fluid and debris. First, percutaneous transhepatic cholangiodrainage (PTCD) was done to treat the progressively obstructive jaundice. Subsequently, fine-needle aspiration of the pancreatic abscess was performed under ultrasound guidance. Enterococcus avium and Klebsiella oxytoca were revealed by culture of abscess aspirates. He was successfully cured by treatment with both appropriate antibiotic and continuous PTCD for the obstructive jaundice. Received: April 3, 2001 / Accepted: August 10, 2001     

Complete obstruction of the lower common bile duct caused by autoimmune pancreatitis: is biliary reconstruction really necessary?

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63‐year‐old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patient's high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30 mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.     

Management of common bile duct stricture caused by chronic pancreatitis with metal mesh self expandable stents.

Twenty patients with chronic pancreatitis and signs of biliary obstruction were treated by endoscopic placement of self expandable metal mesh stents, and followed up prospectively. Eleven had been treated previously with plastic endoprostheses. All had persistent cholestasis, seven patients had jaundice, and three overt cholangitis. Endoscopic stent placement was successful in all cases. No early clinical complication was seen and cholestasis, jaundice or cholangitis rapidly resolved in all patients. Mean follow up was 33 months (range 24 to 42) and consisted of clinical evaluation, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP). In 18 patients, successive ERCPs and cholangioscopies have shown that the metal mesh initially embeds in the bile duct wall and is rapidly covered by a continuous tissue by three months. The stent lumen remained patent and functional throughout the follow up period except in two patients who developed epithelial hyperplasia within the stent resulting in recurrent biliary obstruction, three and six months after placement. They were treated endoscopically with standard plastic stents with one of these patients ultimately requiring surgical drainage. No patient free of clinical or radiological signs of epithelial hyperplasia after six months developed obstruction later. This new treatment could become an effective alternative to surgical biliary diversion if further controlled follow up studies confirm the initial impression that self expandable metal mesh stents offer a low morbidity alternative for longterm biliary drainage in chronic pancreatitis without the inconvenience associated with plastic stents.     

Cholangiocarcinoma due to postradiation therapy cholangitis and chronic pancreatitis

There are no reports of cholangiocarcinoma complicating post radiotherapy cholangitis. We report the case of a 40 year old patient who had undergone thoracoabdominal radiotherapy for Hodgkin's disease, 22 years ago. This radiotherapy was complicated, many years later, by chronic pancreatitis and cholangitis. Recurrent angiocholangitis led us to schedule a biliodigestive anastomosis. During surgery, cholangiocarcinoma was discovered. The patient died from his carcinoma some months later.     

Autoimmune pancreatitis starting as a localized form

Ultrasonography showed a hypoechoic mass in the head of the pancreas, and endoscopic retrograde pancreatography (ERP) showed localized stenosis of the pancreatic duct in the head of the pancreas. Computed tomography (CT) showed enlargement, with a capsule-like rim, in the head of the pancreas. Internal biliary tube drainage was performed to relieve the obstructive jaundice. The patient was followed-up under the tentative diagnosis of localized "mass-forming" pancreatitis. Four months after the drainage, CT showed diffuse swelling of the pancreas, with a capsule-like rim, and ERP demonstrated diffuse irregular narrowing of the pancreatic duct. Glucose intolerance was noted for the first time. Steroid was given as a diagnostic treatment for autoimmune pancreatitis. Two months after initiation of the steroid treatment, the ERP findings were normal, and CT showed a normal pancreas. The biliary tube was removed, and the glucose intolerance was subsequently alleviated. To summarize, we report a case of autoimmune pancreatitis starting as localized "mass-forming" pancreatitis with a peripheral rim on imagings. It is very important to be well aware of the presence of the localized form of autoimmune pancreatitis. Received: July 4, 2000 / Accepted: February 2, 2001     

Autoimmune pancreatitis

Autoimmune pancreatitis is a form of chronic pancreatitis of presumed autoimmune aetiology. The disease is characterised with clinical, serological, histomorphological and imaging features. Autoimmune pancreatitis is recognised as a T-cell-mediated specific disease with lymphoplasmatic infiltration of pancreatic tissue and pancreatic parenchyma fibrosis. Serum immunoglobulin IgG or IgG4 and antibodies (rheumatoid factor, lactoferrin antibodies, carbonic anhydrase II, etc) are usually increased. But the lack of specific biochemical markers is a major drawback in the diagnosis of autoimmune pancreatitis. The Japan Pancreas Society proposed diagnostic criteria for autoimmune pancreatitis as the presence antibodies, pancreas enlargement and pancreatic duct narrowing, lymphoplasmatic infiltration, response to corticosteroid therapy, and association with other autoimmune diseases such as autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, sialoadenitis, inflammatory bowel disease and Sj?gren syndrome. New criteria (HISORt Criteria) incorporate imaging changes, organ involvement, specific elevation of IgG4 subclass and histopathological markers. Autoimmune pancreatitis could be associated with diabetes mellitus and exocrine pancreatic dysfunction. Clinically, autoimmune pancreatitis is a disease with mild symptoms; severe attacks of abdominal pain are not typical. Typically, pancreatic calcifications and pseudocyst are absent; on the other hand jaundice and/or pancreatic mass are frequent signs, and both make differential diagnosis with pancreatic cancer difficult. From a practical point of view, in an elderly male presenting with obstructive jaundice and pancreatic mass, autoimmune pancreatitis is one of the differential diagnoses to avoid unnecessary surgical therapy.     

Idiopathic fibrosing pancreatitis associated with ulcerative colitis

Idiopathic fibrosing pancreatitis has been associated with Sjögren''s syndrome, primary biliary cirrhosis and primary sclerosing cholangitis. This condition frequently develops in childhood and youth, and has also been related to ulcerative colitis and pericholangitis. Pancreatic complications have been rarely described as systemic complications of ulcerative colitis. A 25-year-old man presented with epigastric pain and jaundice. Abdominal ultrasonography, computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) revealed a diffuse enlargement of the pancreas, filiform distal stenosis of the common bile duct and intrahepatic bile ducts, and pancreatic duct dilatation. At operation, a rock-hard and nodular pancreas was noted. Cholecystectomy and Roux-en-Y hepaticojejunostomy, with an access loop, was successfully performed. Idiopathic fibrosing pancreatitis should be considered in young patients with obstructive jaundice, especially those affected with chronic inflammatory or autoimmune diseases. Glucocorticoid therapy would be the first-line treatment, although many patients require operation.