Autoimmune pancreatitis: Current perspectives.

Over the last two decades, our knowledge and understanding regarding the pathogenesis and biology of autoimmune pancreatitis (AIP) have improved tremendously. Type 1 AIP or IgG4-related pancreatitis (IgG4-RP) is now believed to be the prototype of the multisystemic IgG4-related disease. In view of clinical features like obstructive jaundice and mass-forming lesions in the pancreas in elderly men, type 1 AIP often mimics pancreatic cancer. IgG4-related sclerosing cholangitis concomitantly involving the extrahepatic and intrahepatic biliary tree is the most common extrapancreatic involvement seen in up to 80% of these patients, which needs to distinguish from cholangiocarcinoma. Histology is characterised by lymphoplasmacytic inflammation, abundant IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. Apart from histology, high serum IgG4 levels, pancreatic parenchymal and duct imaging findings and other organ involvement aid in diagnosis especially in cases where definitive histology is not evident. Also, these parameters lay the foundation of various diagnostic criteria proposed over last few years. On the contrary, histology alone is the mainstay for establishing diagnosis of idiopathic duct-centric pancreatitis (IDCP) as it lacks any specific serological marker or imaging. Since both types of AIP respond dramatically to corticosteroid treatment, a biopsy is crucial to establish the preoperative diagnosis and to exclude malignancy so as to avoid unnecessary surgery. This review discusses the morphologic spectrum, treatment and prognosis of IgG4-RP and IDCP with an emphasis on approach to diagnosis with relevant histologic features, differential diagnoses and the challenges faced during biopsy interpretation.

[Type 1 autoimmune pancreatitis: a case report]. / Pancreatitis autoinmune tipo 1: reporte de caso.

Autoimmune pancreatitis (PAI) is a rare pathology and an entity to consider in the differential diagnosis of obstructive jaundice and pancreatic mass. It is a chronic inflammatory disease of the pancreas with established clinical, radiological, serological and histopathological characteristics. The treatment is based on the use of corticosteroids and usually has a good response, with complete resolution of clinical, analytical and radiological parameters. We present the case of a 62-year-old woman with abdominal pain in the right hypochondrium and epigastrium associated with low weight. Normal laboratory tests. Abdominal TEM: pancreas increased in volume diffusely with peripancreatic halo. EUS: extensive heterogeneous lesion involving the head and body, FNA is performed. AP: lympho-plasmocitary infiltrate. IgG4: 520 mg / dL. It is determined that it is a probable type I autoimmune pancreatitis and it is decided to perform a therapeutic trial with corticosteroids. Tomographic control is performed at 4 weeks with adequate response.

Risk factors and treatment of relapses in autoimmune pancreatitis: Rituximab is safe and effective.

Background and aims: Steroid therapy is the first-line treatment for autoimmune pancreatitis but relapses are frequent. The aims were to assess the efficacy and the safety of immunomodulator treatments for relapsing autoimmune pancreatitis and rituximab in particular and to identify relapsing risk factors. Methods: Patients followed for autoimmune pancreatitis from 2000 to 2016 were included. Data were retrospectively analysed regarding autoimmune pancreatitis treatment. Results: In total, 162 patients with autoimmune pancreatitis type 1 (n = 92) and type 2 (n = 70) were included (median follow-up: 3 years (0.5-14). Relapse occurred in 46.5% of patients with autoimmune pancreatitis type 1 (vs 19.3% in autoimmune pancreatitis 2; p < 0.001). Risk factors of relapse were cholangitis, initial use of steroids, other organ involvement and chronic pancreatitis in autoimmune pancreatitis type 1 and initial use of steroids, tobacco consumption and chronic pancreatitis for autoimmune pancreatitis type 2. Overall, 21 patients were treated with immunomodulators (azathioprine, n = 19, or methotrexate, n = 2) for relapses. The efficiency rate was 67%. A total of 17 patients were treated with rituximab, with two perfusions at 15 days apart. The efficacy was 94% (16/17), significantly better than immunomodulator drugs (p = 0.03), with a median follow-up of 20 months (11-44). Only two patients needed two supplementary perfusions. Conclusion: In relapsing autoimmune pancreatitis, rituximab is more efficient than immunomodulator drugs and shows better tolerance.

Autoimmune Pancreatitis and IgG4-Related Disease: The Storiform Discovery to Treatment.

Autoimmune pancreatitis (AIP) is an entity that has been recognized since 1961. Prior to the discovery of elevated serum IgG4 as a useful biomarker for its diagnosis, Dr. Yoshida in 1995 first described the entity of AIP, which in retrospect closely resembles the current concept of type 1 AIP. Since the discovery of IgG4 as a biomarker (the IgG4-era), a novel concept of IgG4-related disease (IgG4-RD) has been accepted as being comprised of two subtypes of AIP: type 1 defined as the pancreatic manifestation of IgG4-RD, and type 2 characterized by granulocytic epithelial lesions. The characteristic features of type 1 AIP are increased serum IgG4 levels, lymphoplasmacytic sclerosing pancreatitis (abundant infiltration of IgG4+ plasmocytes and lymphocytes, storiform fibrosis, and obliterative phlebitis), extrapancreatic manifestations of IgG4-RD (e.g., sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis), and steroid responsiveness. These entities can be differentiated from mimickers by a combination of serum IgG4 level, imaging features, and histopathological findings. The current first-line therapy is corticosteroids, or rituximab in high-risk patients with steroid intolerance. Although relapse rates are high, treatment of relapsed disease remains experimental.

The Challenge of Autoimmune Pancreatitis: A Portrayal From the Pediatric Perspective.

Autoimmune pancreatitis (AIP) is a rare disorder characterized by prompt clinical response to corticosteroids. Lost tolerance to a variety of pancreatic antigens and subsequent development of autoantibodies are presumably involved in the initiation of AIP. Even pediatric patients have been reported with features of AIP, and awareness of this disorder is increasing among different clinicians. The terms lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis refer to the different histologic patterns of AIP, named type 1 and type 2, respectively. A combination of serologic, radiologic, and histologic investigations is needed to assess diagnosis of AIP and rule out neoplastic disorders. In addition, type 1 AIP can be distinguished by raised levels of serum immunoglobulin G4 and should be considered as part of systemic immunoglobulin G4-related disease. Conversely, type 2 AIP is frequently reported in younger patients and has less clear immune-mediated pathogenetic mechanisms. The natural history of pediatric AIP is obscure, and the diagnostic usefulness of different autoimmune abnormalities found in adults with AIP is limited for children. Tips to manage pediatric patients with AIP have been recently drafted through a set of recommendation statements. This review describes the current data about AIP and the pathogenic contribution of specific autoantibodies expressly in the pediatric population.

Steroid Therapy and Steroid Response in Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP), a unique subtype of pancreatitis, is often accompanied by systemic inflammatory disorders. AIP is classified into two distinct subtypes on the basis of the histological subtype: immunoglobulin G4 (IgG4)-related lymphoplasmacytic sclerosing pancreatitis (type 1) and idiopathic duct-centric pancreatitis (type 2). Type 1 AIP is often accompanied by systemic lesions, biliary strictures, hepatic inflammatory pseudotumors, interstitial pneumonia and nephritis, dacryoadenitis, and sialadenitis. Type 2 AIP is associated with inflammatory bowel diseases in approximately 30% of cases. Standard therapy for AIP is oral corticosteroid administration. Steroid treatment is generally indicated for symptomatic cases and is exceptionally applied for cases with diagnostic difficulty (diagnostic steroid trial) after a negative workup for malignancy. More than 90% of patients respond to steroid treatment within 1 month, and most within 2 weeks. The steroid response can be confirmed on clinical images (computed tomography, ultrasonography, endoscopic ultrasonography, magnetic resonance imaging, and 18F-fluorodeoxyglucose-positron emission tomography). Hence, the steroid response is included as an optional diagnostic item of AIP. Steroid treatment results in normalization of serological markers, including IgG4. Short- and long-term corticosteroid treatment may induce adverse events, including chronic glycometabolism, obesity, an immunocompromised status against infection, cataracts, glaucoma, osteoporosis, and myopathy. AIP is common in old age and is often associated with diabetes mellitus (33-78%). Thus, there is an argument for corticosteroid therapy in diabetes patients with no symptoms. With low-dose steroid treatment or treatment withdrawal, there is a high incidence of AIP recurrence (24-52%). Therefore, there is a need for long-term steroid maintenance therapy and/or steroid-sparing agents (immunomodulators and rituximab). Corticosteroids play a critical role in the diagnosis and treatment of AIP.