Consensus Diagnostic Criteria For Autoimmune Pancreatitis Research Articles

S1630 Chronic Autoimmune Pancreatitis Presenting With Exocrine Deficiency and Type 3c Diabetes Mellitus

Introduction: Unexplained pancreatic exo/endocrine insufficiency should prompt evaluation for autoimmune pancreatitis. Case Description/Methods: 54-year-old African-American male with past medical history significant for prior DVT was admitted for initial episode of Hyperosmolar Hyperglycemic state (HHS) after complaining of general malaise and polydipsia. Further history taking revealed acute on chronic steathorea and a subacute weight loss of fifteen pounds. Patient's HHS was managed with fluid resuscitation and an insulin infusion. Work-up of his steathorea revealed an undetectable fecal elastase level. His labs were significant for AST 94 U/L, ALT/143 U/L ALP of 144 U/L. A CT of his abdomen and pelvis with contrast demonstrated an atrophic pancreas with diffuse calcifications (Figure 1A,B). Follow up MRCP demonstrated irregular pancreatic duct with strictures and dilated side branches with mild dilation of the common bile duct. Initial etiology of the patient's presentation with HHS was thought to be secondary to new diagnosis of Latent Autoimmune diabetes (LADA), given the presence of positive Glutamic Acid Decarboxylase-65 antibodies, and low C-peptide levels in the context of hyperglycemia. However, in view the of the symptoms of steatorhea, additional investigations were sent which demonstrated elevated IgG4 at 106.40 mg/dL concerning for Autoimmune Pancreatitis (AIP) and Type 3c (pancreatogenic) diabetes mellitus. He denied any history tobacco/alcohol abuse. The patient was treated with pancrealipase and insulin therapy which resulted in an improvement in symptoms. Discussion: The 2011 International Consensus Diagnostic Criteria for AIP confirms an acute state of the disease. However, literature had validated that approximately 40% of patients with AIP experienced pancreatic stone formation, pancreatic atrophy, and/or irregular dilatation of the main pancreatic duct over a long-term course. Patients with AIP generally respond favorably to Prednisolone therapy in the acute setting and utilized to prevent pancreatic stone formation with progression to chronic pancreatitis and subsequent endo/exocrine deficiency. Our patients clinical and radiologic findings were more consistent with an advanced disease state limiting the utility of steroid administration. Undifferentiated pancreatitis without typical risk factor exposures should prompt Gastroenterologist's suspicion of AIP to prevent progression to advanced disease states as exemplified in our patient with pancreatogenic Type 3c Diabetes mellitus.Figure 1.: A: Coronal section of a CT Abdomen and Pelvis with IV contrast demonstrating an atrophic pancreas with diffuse calcifications (demarcated by the red outline) consistent with chronic pancreatitis and no acute stigmata. B: Sagittal section of a CT Abdomen and Pelvis with IV contrast demonstrating an atrophic pancreas diffuse pancreatic calcifications (demarcated by the red outline) consistent with chronic pancreatitis and no acute stigmata. Incidental finding of a large stool ball within the rectum.

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases

Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features ofpatients with IBD with and without AIP in a case-control analysis, using multivariate analysis. We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P= .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P= .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P=.023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P= .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P= .0029). In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.

Diagnosis of Autoimmune Pancreatitis: The Evolution of Diagnostic Criteria for a Rare Disease

Diagnosis of Autoimmune Pancreatitis: The Evolution of Diagnostic Criteria for a Rare Disease

Current Concepts and Diagnosis of IgG4-Related Pancreatitis (Type 1 AIP).

Although now considered to be a member of the systemic entity of immunoglobulin G4- (IgG4-) related disease, IgG4-related pancreatitis is generally referred to as type 1 autoimmune pancreatitis (AIP). Type 1 AIP was established based on a pathological background of lymphoplasmacytic sclerosing pancreatitis, high serum IgG4 concentration, and abundant IgG4-bearing plasma cell infiltration. The characteristic clinical features of type 1 AIP, such as elderly male preponderance, obstructive jaundice, and mass-forming lesions in the pancreas, often mimic those of pancreatic cancer. However, because AIP responds favorably to corticosteroid treatment, careful differentiation from pancreatic cancer is required. An AIP diagnosis is currently based on the 2011 International Consensus Diagnostic Criteria for AIP, which are based on high sensitivity, selectivity, and accuracy. Over the long term, AIP can progress to a chronic condition, with pancreatic stone formation and atrophy resembling that of chronic pancreatitis. Although AIP has been linked to the complication of malignancies, it remains controversial whether an association exists between the disease and tumor formation.

Recent developments in steroid-responsive pancreatitides (autoimmune pancreatitis).

There are two distinct steroid responsive chronic fibro-inflammatory diseases of the pancreas, called type 1 and type 2 autoimmune pancreatitis (AIP). We review recent progress in this field. It has recently been suggested that the term AIP be used to describe type 1 AIP and the term idiopathic duct-centric chronic pancreatitis (IDCP) be used for type 2 AIP. Clinical features and long-term outcomes of AIP and IDCP are well characterized and prognosis of both diseases is excellent. Diagnostic strategies tailored to regional practice patterns have emerged with the application of International Consensus Diagnostic Criteria for AIP. Although corticosteroids remain the mainstay of treatment, management of relapses and strategies for preventing multiple relapses are better understood, including the role of maintenance therapy and B-cell depletion therapy with rituximab. Association studies with malignancies have yielded conflicting results regarding risk of cancer in AIP. The treatment, follow-up guidelines and associations continue to evolve with our increasing experience with both AIP and IDCP. In AIP, rituximab can be used for both induction and maintenance of remission. IDCP responds to steroids without need for maintenance therapy. Both AIP and IDCP have excellent prognosis.

The role of CD19+CD24highCD38high and CD19+CD24highCD27+ regulatory B cells in patients with type 1 autoimmune pancreatitis

BackgroundPatients with type 1 autoimmune pancreatitis (AIP) have several immunologic and histologic abnormalities. It is known that depletion of B cells by rituximab is effective for treatment of IgG4-related disease (IgG4-RD) such as type 1 AIP, suggesting that B cells may be a key player in IgG4-RD. However, the role of regulatory B cells (Bregs) in type 1 AIP is unclear, and the objective of this paper is to clarify the role of Bregs in the pathophysiology of type 1 AIP by analyzing circulating Bregs. MethodWe recruited 21 patients with type 1 AIP as determined by the International Consensus Diagnostic Criteria for AIP (ICDC). No patients received corticosteroid treatments. For comparison, we recruited 14 patients with chronic pancreatitis (CP), 20 patients with pancreatic cancer, and 25 healthy subjects as controls. We analyzed Bregs as CD19+CD24highCD38high and CD19+CD24highCD27+ from peripheral blood by flow cytometry. ResultsIn peripheral blood, CD19+CD24highCD38high Bregs were significantly increased in type 1 AIP patients compared with CP, pancreatic cancer, and healthy controls. Although not significant different, CD19+CD24highCD27+ Bregs of type 1 AIP were decreased compared to those of other groups. IL-10+ B cells were not significantly different from type 1 AIP patients and healthy controls. In untreated type 1 AIP patients, the number of CD19+CD24highCD38high Bregs and IgG4 were not correlated. ConclusionsOur data suggested that CD19+CD24highCD38high Bregs seemed to increase reactively to suppress the disease activity, and are consistent with the hypothesis that CD19+CD24highCD27+ Bregs might be involved in the development of type 1 AIP, although it still remains unclear whether the decrease of CD19+CD24highCD27+ cells is cause or effect of AIP.

Diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP).

Taking Care of Pancreatitis, Not So Simple: IgG4-related Multiorgan Disease Presenting as Pancreatitis

Introduction: Autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related sclerosing disease. In type 1 AIP, extrapancreatic organs may be involved synchronously or metachronously. One hallmark of type 1 AIP is elevated serum IgG4 level. We report a patient presenting with pancreatitis found to have multiorgan involvement with IgG4-related disease in the setting of normal serum IgG4. Case: A 59-year-old male was seen in the gastroenterology clinic for complaint of abdominal pain for 4-5 months, worse with meals, associated with nausea, night sweats, and 20-pound weight loss in 3 months. He denied vomiting, diarrhea, hematemesis, melena, hematochezia. He quit smoking 3 years ago, alcohol 10 years ago. Past history: skin vasculitis treated with oral steroids 3 years ago. Two CT scan abdomen/pelvis in the last 4 months were unremarkable. Physical exam: tenderness in epigastrium, right upper quadrant. Laboratory value: lipase 1,322, amylase 384, BUN/creat 25/1.7, HB 12.2, alk phos 298, ESR >140, C-reactive protein 87.3, serum triglyceride 151. The patient was not on medication known to cause pancreatitis. He was treated with IV fluids, bowel rest, pain medication. MRI abdomen: diffuse pancreatic body enlargement, bilateral renal enlargement and enhancement. Further work up revealed ANA titer 1:80, positive rheumatoid factor, rest of autoimmune panel was negative. Total IgG 3359, IgM 79, IgA 183, IgE 40. IgG subclass levels were: IgG1 1,420, IgG2 953, IgG3 182, IgG4 40. At this point, considering multiorgan involvement with elevated total IgG, a kidney biopsy was obtained to confirm IgG4-related disease. Biopsy revealed lymphoplasmacytic infiltrate involving tubules with plasma cell staining for IgG4. Patient was started on oral prednisone with symptomatic improvement. Discussion: The prevalence of type 1 AIP is 2-11% in patients with chronic pancreatitis. International consensus diagnostic criteria for AIP involves five features: imaging of pancreatic parenchyma and duct, serology, other organ involvement, histology of pancreas, response to steroid therapy. The number of IgG4+ plasma cells is more sensitive and specific than serum IgG4. Not all patients with type I AIP exhibit elevated serum IgG4 levels as demonstrated in our patient.Figure: MRI: abnormal foci of ill-defined signal and enhancement in both kidneys, and pancreas.

Recent Advances in the Diagnosis and Management of Autoimmune Pancreatitis: Similarities and Differences in Japan and Korea

Two subtypes (types 1 and 2) of autoimmune pancreatitis (AIP) are currently recognized. Type 1 AIP is related to immunoglobulin G4 (lymphoplasmacytic sclerosing pancreatitis), and type 2 AIP is characterized by neutrophilic infiltration into the epithelium of the pancreatic duct (idiopathic duct-centric pancreatitis). Although type 2 AIP is sometimes observed in the United States and Europe, most cases of AIP in Japan and Korea are type 1. The international consensus diagnostic criteria for AIP were created to be applicable worldwide and to distinguish between the two types of AIP. AIP is diagnosed based on the presence of at least one of the five cardinal features (i.e., imaging, serology, other organ involvement, histology, and response to steroid therapy). Oral steroids are the standard therapy for AIP, but immunomodulatory drugs or rituximab have been successfully used for patients with relapsed AIP in the United States and Europe. Generally, the clinical manifestations and demography of AIP are similar between Japan and Korea. However, there are differences in some aspects of the disease, including the proportion of other organ involvement, the prevalence of type 2 AIP, diagnostic criteria and maintenance therapy between the two countries.

Republished: Recent advances in autoimmune pancreatitis: type 1 and type 2

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterised clinically by frequent presentation with obstructive jaundice, histologically by a lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response...

Recent advances in autoimmune pancreatitis: type 1 and type 2

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterised clinically by frequent presentation with obstructive jaundice, histologically by a lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response...

Peripancreatic vascular involvements of autoimmune pancreatitis

Although peripancreatic vascular lesions are occasionally encountered in autoimmune pancreatitis (AIP), there are few reports focusing on these involvements. We aimed to investigate the peripancreatic vascular involvements associated with AIP. We retrospectively analyzed 54 AIP patients who met the International Consensus Diagnostic Criteria for AIP between July 2003 and October 2010. All of the 54 patients were subjected to multiphasic multidetector computed tomography, and the prevalence, location and prognosis of peripancreatic vascular involvements were investigated. Of the 54 AIP patients, 24 (44.4%) exhibited involvements in the form of peripancreatic vascular lesions (stenoses of the splenic vein in 22 and of the superior mesenteric-portal vein in 13, development of perigastric collateral circulation in 18, gastric varices with a red color sign in one and thrombosis inside the portal vein in one). Diffuse-type AIP was associated with a significantly higher prevalence of vascular involvements compared with focal-type AIP (P = 0.033). A total of 14 out of 16 patients who underwent corticosteroid treatment showed improvement in vascular lesions. One case followed up without corticosteroid treatment and presenting an obstruction of the splenic vein exhibited involvements in the form of an infarction and hemorrhagic cysts of the spleen and ultimately underwent distal pancreatectomy and splenectomy. Autoimmune pancreatitis patients show a high prevalence of peripancreatic vascular involvements. Thus, patients with vascular involvements are suitable candidates for steroid therapy with evaluation of its potential merits and demerits, even if they are asymptomatic.

Diagnosis of autoimmune pancreatitis by EUS-FNA by using a 22-gauge needle based on the International Consensus Diagnostic Criteria

It is controversial whether EUS-guided FNA by using 22-gauge (G) needles is useful for the diagnosis or evaluation of autoimmune pancreatitis (AIP). To evaluate the usefulness of EUS-FNA by 22-G needles for the histopathological diagnosis of AIP. A retrospective study. Single academic center. A total of 273 patients, including 25 with AIP, underwent EUS-FNA and histological examinations. EUS-FNA by using 22-G needles provided adequate tissue samples for histopathological evaluation because more than 10 high-power fields were available for evaluation in 20 of 25 patients (80%). The mean immunoglobulin G4-positive plasma cell count was 13.7/high-power field. Obliterative phlebitis was observed in 10 of 25 patients (40%). In the context of the International Consensus Diagnostic Criteria for AIP, 14 and 6 of 25 patients were judged to have level 1 (positive for 3 or 4 items) and level 2 (positive for 2 items) histological findings, respectively, meaning that 20 of 25 patients were suggested to have lymphoplasmacytic sclerosing pancreatitis based on the International Consensus Diagnostic Criteria. The diagnosis in 1 patient was type 2 AIP because a granulocytic epithelial lesion was identified in this patient. A retrospective study with a small number of patients. The results of this study suggest that EUS-FNA by using 22-G needles provides tissue samples adequate for histopathological evaluation and greatly contributes to the histological diagnosis of AIP.

Regulatory T Cells in Type 1 Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is a newly recognized pancreatic disorder. Recently, International Consensus Diagnostic Criteria for AIP (ICDC) was published. In this ICDC, AIP was classified into Type 1 and Type 2. Patients with Type 1 AIP have several immunologic and histologic abnormalities specific to the disease, including increased levels of serum IgG4 and storiform fibrosis with infiltration of lymphocytes and IgG4-positive plasmacytes in the involved organs. Among the involved organs showing extrapancreatic lesions, the bile duct is the most common, exhibiting sclerosing cholangitis (IgG4-SC). However, the role of IgG4 is unclear. Recently, it has been reported that regulatory T cells (Tregs) are involved in both the development of various autoimmune diseases and the shift of B cells toward IgG4, producing plasmacytes. Our study showed that Tregs were increased in the pancreas with Type 1 AIP and IgG4-SC compared with control. In the patients with Type 1 AIP and IgG4-SC, the numbers of infiltrated Tregs were significantly positively correlated with IgG4-positive plasma cells. In Type 1 AIP, inducible costimulatory molecule (ICOS)+ and IL-10+ Tregs significantly increased compared with control groups. Our data suggest that increased quantities of ICOS+ Tregs may influence IgG4 production via IL-10 in Type 1 AIP.

Recent advances in autoimmune pancreatitis

It is now clear that are two histological types (Type-1 and Type-2) of autoimmune pancreatitis (AIP). The histological pattern of Type-1 AIP, or traditional AIP, is called lymphoplasmacytic sclerosing pancreatitis (LPSP). The histological pattern of Type-2 AIP is characterized by neutrophilic infiltration in the epithelium of the pancreatic duct. In general, Type-2 AIP patients are younger, may not have a male preponderance, and rarely show elevation of serum IgG4 compared with Type-1 AIP patients. Unlike Type-1 AIP patients, Type-2 AIP patients rarely have associated sclerosing diseases, but they are more likely to have acute pancreatitis and ulcerative colitis. Although Type-2 AIP is sometimes observed in the USA and Europe, most AIP cases in Japan and Korea are Type-1. The international consensus diagnostic criteria for AIP comprise 5 cardinal features, and combinations of one or more of these features provide the basis for diagnoses of both Type-1 and Type-2 AIP. Due to the fact that steroid therapy is clinically, morphologically, and serologically effective in AIP patients, it is the standard therapy for AIP. The indications for steroid therapy in AIP include symptoms such as obstructive jaundice and the presence of symptomatic extrapancreatic lesions. Oral prednisolone (0.6 mg/kg/day) is administered for 2–4 weeks and gradually tapered to a maintenance dose of 2.5–5 mg/day over a period of 2–3 months. Maintenance therapy by low-dose prednisolone is usually performed for 1–3 years to prevent relapse of AIP.