Autoimmune pancreatitis with retroperitoneal fibrosis which responded to steroid therapy but was complicated with refractory renal dysfunction

A 58-year-old male had been diagnosed as having autoimmune pancreatitis (AIP) from the results of serological examinations and image findings. He was treated with prednisolone (PSL) for 3.5 months. Fifteen months later, follow-up CT revealed the main pancreatic duct (MPD) dilatation in the pancreas body to tail and right hydronephrosis caused by complicated retroperitoneal mass. We diagnosed him as having recurrent AIP with retroperitoneal fibrosis, and restarted PSL treatment. After one month, Examinations indicated amelioration of the MPD dilatation and right hydronephrosis, but not the right renal failure. This case indicates the importance of maintenance of PSL treatment.     

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis

The standard treatment for autoimmune pancreatitis (AIP) is steroid therapy, although some patients improve spontaneously. Indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, back pain, and the presence of symptomatic extrapancreatic lesions. Prior to steroid therapy, obstructive jaundice should be managed by biliary drainage, and blood glucose levels should be controlled in patients with diabetes mellitus. The recommended initial oral prednisolone dose for induction of remission is 0.6 mg/kg/day, which is administered for 2–4 weeks. The dose is then tapered by 5 mg every 1–2 weeks, based on changes in clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5–5 mg/day) over a period of 2–3 months. Cessation of steroid therapy should be based on the disease activity in each case. Termination of maintenance therapy should be planned within 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapse. Application of immunomodulatory drugs is considered for AIP patients who prove resistant to steroid therapy. The prognosis of AIP appears to be good over the short-term with steroid therapy. The long-term outcome is less clear, as there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy.     

Autoimmune pancreatitis with multifocal lesions

Two cases of a focal type of autoimmune pancreatitis (AIP) with distinct double mass lesions within the pancreas are described. In both patients, computed tomography (CT) showed localized pancreatic masses with delayed enhancement, and magnetic resonance cholangiopancreatography (MRCP) revealed localized stenoses of the main pancreatic duct (MPD) with mild upstream dilatation. Fluorodeoxyglucose positron emission tomography (FDG-PET) examination, performed in one patient, showed intense uptake concordant with tumors. Both patients received pancreatic resection with a presumptive diagnosis of pancreatic carcinoma. Histologic evaluation of the tumors showed marked lymphoplasmacytic infiltration and fibrosis around the large and medium pancreatic ducts, without any evidence of malignancy. Serum IgG4 concentration, measured postoperatively, was elevated in both patients. The characteristic morphological features of AIP are diffuse swelling of the pancreatic parenchyma and diffuse narrowing of the MPD. Recently, a focal type of AIP, which mimics pancreatic carcinoma, has been recognized. Considering the favorable response of AIP to steroid therapy, it is clinically important to differentiate the focal type of AIP from pancreatic carcinoma and to know that AIP sometimes exhibits multiple lesions within the pancreas.     

Incidence and outcome of lung involvement in IgG4‐related autoimmune pancreatitis

We evaluated the incidence and outcome of lung involvement in 35 patients with autoimmune pancreatitis (AIP). Our results indicate that lung involvement is commonly observed in AIP (40%). In addition, corticosteroid treatment improved the lung lesions and appeared to reduce the probability of relapse compared with pancreatic lesions (0% vs 36%). This is the first report to assess the long‐term outcome of lung involvement in AIP (52 ± 33 months).     

Autoimmune pancreatitis

The purpose of this review is to provide a concise view of the existing knowledge of autoimmune pancreatitis (AIP) for practicing clinicians. AIP is a rare disease whose recognition and understanding are evolving. It is a type of chronic pancreatitis that often presents as obstructive jaundice, has a distinctive histology, and is exquisitely sensitive to steroid therapy. This form of chronic pancreatitis has a unique clinical, biochemical, and radiological profile. The term "AIP" encompasses two subtypes: types 1 and 2. Type 1 AIP is the pancreatic manifestation of a systemic fibro-inflammatory disease called immunoglobulin G4-associated systemic diseases. Type 2 AIP has been shown to be associated with inflammatory bowel disease. Existing criteria are geared towards the diagnosis of type 1 AIP. At present, pancreatic histology is a requirement for the definitive diagnosis of type 2 AIP. AIP can mimic most other pancreatic diseases in its presentation, but in clinical practice, it often has to be differentiated from pancreatic cancer. There are established criteria and algorithms not only to diagnose AIP, but also to differentiate it from pancreatic cancer. The utility of these algorithms and the approach to management are discussed here.     

Autoimmune hemolysis associated with primary biliary cirrhosis responding to ursodeoxycholic acid as sole treatment

Coombs' positive autoimmune hemolytic anemia (AIHA) has been rarely described in association with primary biliary cirrhosis (PBC). The previously reported cases have responded to treatment with a combination of corticosteroids and ursodeoxycholic acid (UDCA). We report a case of AIHA occurring in association with PBC, which has responded to treatment with UDCA alone. Possible mechanisms of autoimmune hemolysis in this patient include bile salt induced immune dysregulation and direct damage to red cell membranes by bile salts leading to exposure of neoantigens and development of red cell autoantibodies. A trial of UDCA as a single agent should be considered as initial treatment in this rare disorder.     

Autoimmune Pancreatitis with Gastric Cancer: Some IgG4-related Diseases May Be Paraneoplastic Syndrome

A 70-year-old man was referred to our department for the treatment of early gastric cancer. Contrast-enhanced computed tomography (CT) incidentally showed diffuse enlargement of the pancreas with a capsule-like rim, and blood tests showed elevated serum IgG4 levels, leading to a diagnosis of autoimmune pancreatitis (AIP). Endoscopic treatment for gastric cancer was performed, and pathological findings showed adenocarcinoma with abundant IgG4-positive plasma cell infiltration. Thereafter, the serum IgG4 levels normalized, and the findings of AIP disappeared on CT without steroid treatment. These findings suggest that the gastric cancer activated an IgG4-related immune response, resulting in the development of AIP.     

Autoimmune pancreatitis diagnosed after pancreatoduodenectomy and successfully treated with low-dose steroid

A 69‐year‐old woman presented with obstructive jaundice and a 30‐mm hypoechoic mass in the pancreatic head on ultrasonography. Magnetic resonance imaging (MRI) revealed enlargement of the pancreatic head with dilatation of the upstream main pancreatic duct and no dilatation of the proximal biliary tree. Endoscopic retrograde pancreatography showed a localized irregular narrowing of the main pancreatic duct in the head of the pancreas. Pylorus‐preserving pancreatoduodenectomy (PPPD) was performed under the diagnosis of pancreatic head cancer. Histopathological examination showed fibrosis with lymphoplasmacytic infiltration, suggesting the diagnosis of autoimmune pancreatitis (AIP). Serum IgG concentration was within normal limits immediately after the operation but was elevated 4 months later, when MRI showed enlargement of the remnant pancreas, with a peripheral rim of low intensity. Oral administration of prednisolone was initiated, at a dose of 5 mg/day. The serum IgG concentration declined and MRI showed improvement of the pancreatic enlargement and the disappearance of the peripheral rim. AIP has not relapsed for 1 year so far, with the patient being kept on 5 mg/day prednisolone. This communication reports a patient with AIP showing an interesting clinical course.     

Autoimmune pancreatitis in Japan: overview and perspective

Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren’s syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren’s syndrome or PSC. Now the concept of “IgG4-related sclerosing disease” has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called “idiopathic duct-centric chronic pancreatitis (IDCP)” and “AIP with granulocyte epithelial lesion (GEL)” and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.     

Autoimmune pancreatitis mimicking an intra-ductal papillary mucinous neoplasm of the pancreas: an original case

In recent years, autoimmune pancreatitis (AIP) has been increasingly recognized. It can be associated with diabetes mellitus and other systemic autoimmune diseases, or with bile ducts lesions, which are also responsive to steroid therapy as pancreatic lesions. We report the case of a 34-year-old man with a history of a first acute pancreatitis, attributed to an intraductal papillary-mucinous neoplasm of the pancreas (IPMN) with segmental involvement of the main pancreatic duct. A spleno-pancreatectomy was performed, and pathological examination of the specimen diagnosed autoimmune pancreatitis. A treatment with corticosteroids was carried out. To our knowledge, this is the first reported case of AIP mimicking IPMN of the main pancreatic duct.     

Risk factors associated with relapse of type 1 autoimmune hepatitis in Japan

Aim: Patients receiving corticosteroid therapy on a tapered schedule occasionally suffer autoimmune hepatitis (AIH) relapses. The aim of this study was to assess the frequency and features of relapses, explore risk factors associated with relapses, and evaluate the effectiveness of azathioprine (AZP) therapy against relapses in Japanese patients with type 1 AIH. Methods: We assessed clinical characteristics and therapeutic processes in 67 patients diagnosed with AIH. Results: Twenty patients (29.9%) suffered from relapses during tapering of corticosteroid therapy. The remaining 47 patients sustained their remission. At the onset of disease, risk factors associated with relapse were: age of 50 years or older; total bilirubin of 1.5 mg/dL or more; aspartate aminotransferase levels of 250 IU/L or more; alanine aminotransferase levels of 250 IU/L or more; prothrombin activity of 80% or more; γ‐globulin levels of 3.4 g/dL or more; and International Autoimmune Hepatitis Group (IAIHG) score of 17 or more in univariate analysis. Grading of histological interface hepatitis is not significantly associated with relapse. Multivariate analysis revealed that IAIHG scores of 17 or more were significantly associated with relapse (odds ratio = 6.57, 95% confidence interval = 1.19–36.33). Seven patients who relapsed were treated with AZP and prednisolone (PSL), and all sustained remission (100%). Of the remaining 13 relapse patients who received only PSL, eight (61.5%) suffered additional relapses. Conclusion: Our results demonstrate the risk factors associated with relapse of AIH. We also show that early administration of AZP after the first relapse may help to prevent additional relapses.     

Autoimmune pancreatitis:report of two cases and literature review

BACKGROUND:Autoimmune pancreatitis(AIP)is a unique chronic inflammation of the pancreas in which autoimmune mechanisms are involved in the pathogenesis.It is characterized by clinical,histopathological,radiographic,serologic and therapeutic features.Since it was first described in 1995,increasing numbers of AIP patients have been diagnosed.METHODS:In this study,the data from 2 patients with AIP who had elevation of serum immunoglobulin G,positive autoantibody,swelling of the pancreas and narrowing of the ma...     

Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP

Steroid therapy appeared to be a standard treatment for autoimmune pancreatitis (AIP), although some AIP patients improve spontaneously. The indications for steroid therapy in AIP patients are symptoms such as obstructive jaundice, abdominal pain, and back pain, and the presence of symptomatic extrapancreatic lesions. Before steroid therapy, jaundice should be managed by biliary drainage in patients with obstructive jaundice, and blood glucose levels should be controlled in patients with diabetes mellitus. For the initial oral prednisolone dose for induction of remission, 0.6 mg/kg/day is recommended. The initial dose is administered for 2–4 weeks, and the dose is tapered by 5 mg every 1–2 weeks, based on changes in the clinical manifestations, biochemical blood tests (such as liver enzymes and IgG or IgG4 levels), and repeated imaging findings (US, CT, MRCP, ERCP, etc.). The dose is tapered to a maintenance dose (2.5–5 mg/day) over a period of 2–3 months. Steroid therapy should be stopped based on the disease activity in each case. Stopping of maintenance therapy should be planned within at least 3 years in cases with radiological and serological improvement. Re-administration or dose-up of steroid is effective for treating AIP relapses. The prognosis of AIP appears to be good over the short-term with steroid therapy. It is unclear whether the long-term outcome is good because there are many unknown factors, such as relapse, pancreatic exocrine or endocrine dysfunction, and associated malignancy.     

Autoimmune hepatitis in Singapore: a rare syndrome affecting middle-aged women

BACKGROUND AND AIM: The prevalence of autoimmune hepatitis in Singapore is unknown. Over a period of 7 years, 24 cases were diagnosed in a district general hospital in Singapore (Toa Payoh Hospital) by using the scoring system proposed by the International Autoimmune Hepatitis Group in 1993. The aims of our study were to determine the prevalence of autoimmune hepatitis in Singapore, and to investigate the characteristics and prognosis in the mainly Chinese population. METHODS: The case records of all 24 patients were reviewed, and the following parameters were recorded: age at presentation, sex, symptoms and signs at presentation, past exposure to hepatotoxic drugs, alcohol intake, blood transfusion laboratory and histological tests used to determine autoimmune hepatitis, response to treatment, complications, and survival. RESULTS: The mean age of patients was 57 years old. There was a female-male ratio of 11:1. Forty-two percent of the patients were cirrhotic at presentation. The prevalence of autoimmune hepatitis was four per 100 000, with no significant difference between Chinese, Malay and Indian patients (Odds ratio of 0.38 by the chi-squared test). Eighty-nine percent of the patients responded to treatment with the induction of prednisolone, but the relapse rate was 61%. Treatment failure occurred in one patient. The mortality rate during the 7 years of follow up was 21%, and all were caused by complications of cirrhosis. The survival at 5 years was 71%, with a standard error of 0.13. CONCLUSION: Autoimmune hepatitis in Singapore is mainly a disease in older women. The response to steroid treatment is good, with a 5-year survival rate of 71%.     

Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease

Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. Many new clinical aspects of AIP have been clarified during the past 10 years, and AIP has become a distinct entity recognized worldwide. However, its precise pathogenesis or pathophysiology remains unclear. As AIP dramatically responds to steroid therapy, accurate diagnosis of AIP is necessary to avoid unnecessary surgery. Characteristic dense lymphoplasmacytic infiltration and fibrosis in the pancreas may prove to be the gold standard for diagnosis of AIP. However, since it is difficult to obtain sufficient pancreatic tissue, AIP should be diagnosed currently based on the characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevation of serum γ-globulin, IgG, or IgG4, along with the presence of autoantibodies), clinical findings (elderly male preponderance, fluctuating obstructive jaundice without pain, occasional extrapancreatic lesions, and favorable response to steroid therapy), and histopathological findings (dense infiltration of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative phlebitis in various organs). It is apparent that elevation of serum IgG4 levels and infiltration of abundant IgG4-positive plasma cells into various organs are rather specific to AIP patients. We propose a new clinicopathological entity, “IgG4-related sclerosing disease”, and suggest that AIP is a pancreatic lesion reflecting this systemic disease.     

Autoimmune pancreatitis with pseudocysts

A 47-year-old woman was admitted to our hospital with complaints of fever, upper abdominal pain, and back pain. The serum amylase, C-reactive protein (CRP), and IgG (especially IgG₄) were elevated, and abdominal computed tomography (CT) revealed diffuse enlargement of the pancreas and pseudocysts. Endoscopic retrograde pancreatography (ERP) revealed diffuse irregular narrowing of the main pancreatic duct. Histopathological examination of the pancreatic tissue showed fibrotic change with lymphocytic infiltration. Based on these findings, we diagnosed this case as a case of autoimmune pancreatitis. This case also fully satisfied the diagnostic criteria for autoimmune pancreatitis established by the Japan Pancreas Society in 2002. Few reports have been published on cases of autoimmune pancreatitis complicated by the formation of pseudocysts in the pancreas. We, therefore, report this case here to emphasize that cases of autoimmune pancreatitis can be complicated by the development of pseudocysts.     

Coexisting Type 1 Autoimmune Pancreatitis and Mixed-type Intraductal Papillary Mucinous Neoplasm

An 84-year-old man was referred to our hospital for a cystic lesion of the pancreatic head, swelling of the pancreatic tail and hilar biliary stricture, resulting in elevated liver enzyme levels. We suspected branch duct-type intraductal papillary mucinous neoplasm (IPMN) and type I autoimmune pancreatitis (AIP) associated with sclerosing cholangitis because of the high serum IgG4 levels. The main pancreatic duct on the tail side of the AIP lesion was moderately dilated. Although the biliary stricture and pancreatic swelling improved after prednisolone treatment, the pancreatic enzyme levels increased rapidly. The entire main pancreatic duct exhibited remarkable dilatation, which led to the diagnosis of mixed-type IPMN. The clinical characteristics of IPMN in the main pancreatic duct appear to have been initially masked by AIP.     

Liver atrophy and portal stenosis in two cases of sclerosing cholangitis associated with autoimmune pancreatitis

Sclerosing cholangitis with autoimmune pancreatitis (SC with AIP) takes a better clinical course than primary sclerosing cholangitis due to the effectiveness of steroid therapy. However, the morphological and functional changes in SC with AIP during long-term observation have not yet been reported. We encountered two cases of SC with AIP that resulted in liver atrophy and portal obstruction during long-term observation. One case was followed up without steroid therapy. The other case was treated with endoscopic biliary drainage initially. These cases may provide further information regarding steroid therapy for SC with AIP.     

Autoimmune pancreatitis and cholangitis

Autoimmune pancreatitis(AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4(Ig G4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreaticmanifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG 4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG 4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.     

Autoimmune pancreatitis complicated by an infected pseudocyst

A 53-year-old man was admitted due to upper abdominal pain. He had been diagnosed with autoimmune pancreatitis (AIP) 4 years previously and had been taking steroids for maintenance therapy since that time. Abdominal computed tomography revealed multiple pseudocysts in the head of the pancreas and a dilated pancreatic duct with mottled calcifications around the pseudocyst. Despite the continuation of steroid therapy for 4 months, the size of the pseudocyst increased further and diffuse calcifications developed throughout the pancreas. He was readmitted due to severe abdominal pain and a high fever, and endoscopic drainage of the pancreatic pseudocyst was performed. Two months after the internal drainage, the pseudocyst disappeared and his symptoms subsided. There are few reports concerning AIP complicated by the formation of pseudocysts. We report this case to emphasize that AIP can be complicated by the development of pseudocysts with progression to chronic pancreatitis, accompanied by multiple calcifications.