Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies.

In this editorial we comment on the article by Jaber et al. Autoimmune pancreatitis (AIP) represents a distinct form of pancreatitis, categorized into AIP-1 and AIP-2, characterized by obstructive jaundice, lymphoplasmacytic infiltrate, and fibrosis. AIP-1, associated with elevated immunoglobulin G4 (IgG4) levels, exhibits higher relapse rates, affecting older males, while AIP-2 is less common and linked to inflammatory bowel disease. AIP is considered a manifestation of IgG4-related systemic disease, sharing characteristic histological findings. Steroids are the primary treatment, with emerging biomarkers like interferon alpha and interleukin-33. AIP poses an increased risk of various malignancies, and the association with pancreatic cancer is debated. Surgery is reserved for severe cases, necessitating careful evaluation due to diagnostic challenges. AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients. Thorough diagnostic assessment, including biopsy and steroid response, is crucial for informed surgical decisions in AIP.

Recent advances in the management of autoimmune pancreatitis in the era of artificial intelligence.

Autoimmune pancreatitis (AIP) is a type of immune-mediated pancreatitis subdivided into two subtypes, type 1 and type 2 AIP. Furthermore, type 1 AIP is considered to be the pancreatic manifestation of the immunoglobulin G4 (IgG4)-related disease. Nowadays, AIP is increasingly researched and recognized, although its diagnosis represents a challenge for several reasons: False positive ultrasound-guided cytological samples for a neoplastic process, difficult to interpret levels of IgG4, the absence of biological markers to diagnose type 2 AIP, and the challenging clinical identification of atypical forms. Furthermore, 60% and 78% of type 1 and type 2 AIP, respectively, are retrospectively diagnosed on surgical specimens of resected pancreas for suspected cancer. As distinguishing AIP from pancreatic ductal adenocarcinoma can be challenging, obtaining a definitive diagnosis can therefore prove difficult, since endoscopic ultrasound fine-needle aspiration or biopsy of the pancreas are suboptimal. This paper focuses on recent innovations in the management of AIP with regard to the use of artificial intelligence, new serum markers, and new therapeutic approaches, while it also outlines the current management recommendations. A better knowledge of AIP can reduce the recourse to surgery and avoid its overuse, although such an approach requires close collaboration between gastroenterologists, surgeons and radiologists. Better knowledge on AIP and IgG4-related disease remains necessary to diagnose and manage patients.

Pancreatitis in Children.

Pediatric pancreatitis describes a spectrum covering acute pancreatitis, acute recurrent pancreatitis, and chronic pancreatitis, each with varying clinical manifestations and risk factors requiring a tailored diagnostic approach. We emphasize management strategies based on age, risk factors, recurrence, and complications. A discussion of the role of therapeutic endoscopy is reviewed and highlights the growing role of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography in children with pancreatitis. Particular diagnostic challenges in autoimmune pancreatitis are reviewed with an emphasis on differentiating this entity from alternate pancreaticobiliary pathologies. Finally, we explore a multidisciplinary approach to acute recurrent and chronic pancreatitis.

Plasmacytoid Dendritic Cells as a New Therapeutic Target for Autoimmune Pancreatitis and IgG4-Related Disease.

Although plasmacytoid dendritic cells (pDCs) able to produce large amounts of type 1 interferons (IFN-I) play beneficial roles in host defense against viral infections, excessive activation of pDCs, followed by robust production of IFN-I, causes autoimmune disorders including systemic lupus erythematosus (SLE) and psoriasis. Autoimmune pancreatitis (AIP), which is recognized as a pancreatic manifestation of systemic immunoglobulin G4-related disease (IgG4-RD), is a chronic fibroinflammatory disorder driven by autoimmunity. IgG4-RD is a multi-organ autoimmune disorder characterized by elevated serum concentrations of IgG4 antibody and infiltration of IgG4-expressing plasmacytes in the affected organs. Although the immunopathogenesis of IgG4-RD and AIP has been poorly elucidated, recently, we found that activation of pDCs mediates the development of murine experimental AIP and human AIP/IgG4-RD via the production of IFN-I and interleukin-33 (IL-33). Depletion of pDCs or neutralization of signaling pathways mediated by IFN-I and IL-33 efficiently inhibited the development of experimental AIP. Furthermore, enhanced expression of IFN-I and IL-33 was observed in the pancreas and serum of human AIP/IgG4-RD. Thus, AIP and IgG4-RD share their immunopathogenesis with SLE and psoriasis because in all these conditions, IFN-I production by pDCs contributes to the pathogenesis. Because the enhanced production of IFN-I and IL-33 by pDCs promotes chronic inflammation and fibrosis characteristic for AIP and IgG4-RD, neutralization of IFN-I and IL-33 could be a new therapeutic option for these disorders. In this Mini Review, we discuss the pathogenic roles played by the pDC-IFN-I-IL-33 axis and the development of a new treatment targeting this axis in AIP and IgG4-RD.

Pancreatitis autoinmune en pediatría. Caso clínico / Autoimmune pancreatitis in children. Clinical case

La pancreatitis recurrente ocurre en el 15-35% en la edad pediátrica. Se define como 2 o más episodios distintos de pancreatitis aguda con normalización de enzimas pancreáticas entre cada episodio. Una de sus causas es la pancreatitis autoinmune. En los últimos 10 años se controlaron, en el Hospital Garrahan, 10 pacientes con diagnóstico de pancreatitis recurrente, de los cuales solo uno tuvo diagnóstico de pancreatitis autoinmune. Se describe el caso clínico de una paciente, que, inicialmente, tenía estudios normales de función y anatomía pancreática y, en la evolución, luego de un episodio de pancreatitis aguda, desarrolló estenosis del conducto de Wirsung sugestiva de pancreatitis autoinmune. Se considera importante describir esta patología infrecuente en pediatría, pero que se encuentra en auge.

Introduction. Recurrent pancreatitis occurs in children between 15 and 35% of the cases. It is defined as two or more separate episodes of acute pancreatitis with normalization of the pancreatic enzymes between episodes. One of the causes is autoimmune pancreatitis. Over the last 10 years, 10 patients with recurrent pancreatitis were sent at our center. Only one was considered to have autoimmune pancreatitis. We described a clinical case about a patient, who had, at the beginning, normal functional and anatomical studies, and then was finally diagnosed with autoimmune disease based on findings on the magnetic resonance cholangiopancreatography with a duct of Wirsung abnormality. We considered important to describe this uncommon disorder in childhood, in spite of having an increasing incidence.

Mesenchymal stromal cells and their derivatives - putative therapeutics in the management of autoimmune pancreatitis.

Autoimmune pancreatitis, a derivative of chronic pancreatitis, frequently causes acute episodes with clinical symptoms parallel to those of acute pancreatitis. Corticosteroids are effective in the treatment of 90% of autoimmune pancreatitis cases, but for the remaining 10%, options are limited. Due to their significant immunomodulatory capabilities, mesenchymal stromal cells (MSCs) have been proposed as a novel treatment strategy for various immune and inflammatory pathologies including those with autoimmune origins. Here, we not only highlight the most recent MSC live-cell experiments to address acute pancreatitis, but also discuss the opportunities afforded by the emergence of the newly identified field of MSC necrobiology. We conclude that the putative employment of MSC derivatives provides a newer and simpler therapeutic approach that could have significant advantages over the use of cells themselves.

Pancreatitis autoinmune: desafío diagnóstico y tratamiento actual / Autoimmune pancreatitis: diagnostic challenges and current treatment

Autoimmune pancreatitis (AIP) is an inflammatory disease of the pancreas. The mechanism of the disease is not completely known. However, AIP shows cellular and humoral immunity elements, the most important being helper and regulatory T lymphocytes as well as B-lymphocytes and plasmocytes, participating in the fibroinflammatory process. Two histologic types have been described with different clinical characteristics. Type 1 AIP is part of a systemic condition associated with an increase of IgG4, while type 2 is a pancreatic disease, frequently associated with inflammatory bowel disease. From the clinical point of view, a third category is described when the classification is not possible at the moment of the diagnosis. The most important differential diagnosis of AIP is pancreatic cancer and it can be difficult, because current diagnostic methods used, including biopsy, have low specificity and sensitivity. AIP patients recover rapidly after steroid therapy, which can be useful even in differential diagnosis. Long-term prognosis is good: more than half of type 1 and almost all cases of type 2 patients have favorable outcome without recurrence and without severe consequences.

La pancreatitis autoinmune (PAI) es una enfermedad inflamatoria del páncreas. El mecanismo fisiopatológico no es completamente conocido. Sin embargo, presenta elementos de inmunidad celular y humoral, siendo de mayor importancia los linfocitos T-helper, T-reguladores, linfocitos B y plasmocitos, que participan en el desarrollo de la enfermedad. Se reconocen dos tipos histológicos con características clínicas también distintas. El tipo 1 forma parte de una enfermedad sistémica relacionada a aumento de IgG4, mientras el tipo 2 es una enfermedad pancreática, aunque con frecuencia asociada a enfermedad inflamatoria intestinal. Desde el punto de vista clínico, existe una tercera categoría, que se presenta cuando en el momento del diagnóstico de PAI la tipificación clínicamente no es posible. El diagnóstico diferencial más importante de la PAI es el cáncer de páncreas y puede ser clínicamente difícil. Los métodos actuales de diagnóstico incluyen la biopsia pero tienen un rendimiento bajo. La PAI responde rápidamente al tratamiento con esteroides, hecho que puede ser útil aún en el diagnóstico diferencial. Su pronóstico a largo plazo es bueno: más de la mitad de los casos tipo 1 y casi todos los casos tipo 2 evolucionan sin recaída y sin consecuencias graves a largo plazo.