Type 1 autoimmune pancreatitis is a common manifestation of IgG4-related disease (IgG4-RD). However, there is a paucity of literature characterizing pancreatic damage and symptom burden in IgG4-RD.

We performed a cross-sectional analysis of patients who fulfilled the ACR/EULAR IgG4-RD Classification Criteria. Disease features and complications were collected by medical record review. A survey regarding symptoms and disease history was distributed to all patients. Characteristics were compared between patients with and without autoimmune pancreatitis.

Of 303 patients who fulfilled Classification Criteria at the time of the chart review, 118 (39 %) had evidence of autoimmune pancreatitis. Overt indicators of acute pancreatitis (e.g., abdominal pain, nausea/emesis, elevated serum lipase) each occurred in fewer than 50 % of patients with autoimmune pancreatitis. Diabetes mellitus (DM), exocrine pancreatic insufficiency (EPI), or both were present in 47 %, 48 %, and 21 % of the autoimmune pancreatitis patients, respectively. After encouraging all patients to have fecal elastase measured, 40/49 (82 %) stool samples had low elastase concentrations. 9/118 (8 %) had undergone pancreatic resections before the diagnosis was established. 162/325 (50 %) completed surveys (n = 81 [50 %] with autoimmune pancreatitis). Patients with autoimmune pancreatitis reported a higher burden of abdominal pain, weight loss, and changes in stool than those without (all p < 0.05).

Despite an often subclinical presentation, autoimmune pancreatitis is associated with EPI, DM, or both in a high percentage of patients with IgG4-RD. While symptomatic acute pancreatitis may not be common, patient-reported symptom burden due to IgG4-related autoimmune pancreatitis or its complications is greater than previously appreciated.

Current diagnosis of autoimmune pancreatitis (AIP) is challenging and often requires combining multiple dimensions. There is a need to explore new methods for diagnosing AIP. The development of artificial intelligence (AI) is evident, and it is believed to have potential in the clinical diagnosis of AIP. This article aims to list the current diagnostic difficulties of AIP, describe existing AI applications, and suggest directions for future AI usages in AIP diagnosis.

Autoimmune pancreatitis (AIP) is a steroid-responsive fibroinflammatory disorder with 2 clinically distinct subtypes known as type 1 autoimmune and type 2 autoimmune pancreatitis. Type 1 AIP is considered the pancreatic manifestation of immunoglobulin G4-related disease, a systemic disease often presenting with other organ involvement. Advances in understanding the unique clinical presentation, imaging findings, histopathology, and clinical course of this relatively uncommon disease have led to international consensus regarding diagnosis and treatment. While corticosteroids remain the mainstay of treatment, several emerging novel therapies have been explored primarily in the context or relapsing and refractory cases.

Autoimmune pancreatitis (AIP) is an inflammatory disease that may be mistaken for pancreatic cancer, especially when there is a focal lesion in the pancreatic head. It often involves biliary strictures and occasional tumor marker elevations, causing confusion with malignancy. An incomplete assessment might lead to unwarranted surgery for what is actually an inflammatory process. By combining imaging, histopathology, IgG4 measurement, and the clinical response to steroids, physicians can reach the correct diagnosis more reliably. We describe four adults, ages 64 to 84, who had obstructive jaundice, biliary dilation, and imaging findings suggesting a possible pancreatic head tumor. Tumor marker levels varied; some were elevated, while others were unremarkable. In two instances, imaging raised concerns about vascular involvement. Endoscopic ultrasound-guided biopsies showed lymphoplasmacytic inflammation without malignant cells, and all patients had elevated IgG4 levels that decreased with steroid therapy. Each individual underwent endoscopic biliary stenting and began a course of prednisone, leading to a return of normal liver function and improvement in imaging findings. Two required short-term additional stent management for persistent strictures, and three underwent gallbladder removal due to associated disease. All four avoided major pancreatic surgery and had a favorable clinical course. These cases show the importance of a methodical workup that includes IgG4 assessment and biopsy confirmation. Steroid therapy can resolve clinical and radiologic abnormalities once AIP is recognized. This approach spares many patients from extensive operations when their presumed neoplasm is, in reality, an autoimmune condition.

Autoimmune pancreatitis (AIP) is a rare chronic pancreatitis subtype that often mimics pancreatic cancer due to the overlapping clinical and radiological features, posing significant diagnostic challenges. Similarly, distinguishing AIP from pancreatic neuroendocrine neoplasms (PanNENs), which present with nonspecific symptoms, adds complexity to clinical evaluations. We present the case of a 46-year-old male with recurrent acute idiopathic pancreatitis. Abdominal computed tomography (CT) revealed a 25 mm hypodense mass in the pancreatic tail with mild arterial contrast enhancement. Magnetic resonance imaging (MRI) showed the mass to be hypointense on T2-weighted sequences, with no diffusion restriction and an enhancement pattern akin to normal pancreatic tissue. The endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) was inconclusive. Gallium-68 DOTATATE positron emission tomography-CT (Ga-68 DOTATATE PET-CT) showed an increased tracer uptake, leading to a distal pancreatectomy with a splenectomy. Histopathology demonstrated chronic sclerotic pancreatitis with inflammatory infiltrates. Elevated serum IgG4 levels confirmed the diagnosis of type 1 AIP Differentiating AIP from pancreatic malignancies, including PanNENs, is both critical and complex. This case highlights a misdiagnosis of PanNENs in a patient with focal AIP, where neuroendocrine hyperplasia and islet cell clusters within fibrotic areas mimicked PanNENs, even on Ga-68 PET-CT. The findings emphasize the potential for false positives with Ga-68 DOTATATE PET-CT and the importance of integrating clinical, radiological, and histological data for an accurate diagnosis.

Elevated serum IgG4 (sIgG4) is a useful diagnostic marker of type 1 autoimmune pancreatitis (AIP). This study aimed to clarify the clinicopathological characteristics of the type 1 AIP patients without elevated sIgG4 levels.

We analyzed the clinical data of patients registered in a nationwide epidemiological survey in Japan. AIP was diagnosed according to the International Consensus Diagnostic Criteria. Patients with sIgG4 levels ≥135 mg/dl at the diagnosis were classified as sIgG4-positive AIP, and those with sIgG4 levels <135 mg/dl were as sIgG4-negative AIP.

A total of 1285 patients with AIP were enrolled in this study; 1128 (87.8 %) had sIgG4-positive AIP and 157 (12.2 %) had sIgG4-negative AIP. Compared to patients with sIgG4-positive AIP, those with sIgG4-negative AIP more frequently experienced inflammatory bowel diseases (3.8 % vs. 0.4 %), and less frequently developed extrapancreatic lesions (53.5 % vs. 72.3 %), including sclerosing cholangitis (30.6 % vs. 40.7 %) and sialadenitis/dacryoadenitis (5.1 % vs. 24.7 %). Histopathological examinations were performed more frequently in patients with sIgG4-negative AIP. The criterion of abundant IgG4-positive plasma cells was less frequently fulfilled by patients with sIgG4-negative AIP (28.0 % vs. 43.1 %). A Kaplan-Meier analysis showed that relapse occurred less frequently in patients with sIgG4-negative AIP (P = 0.006). Results were similar even if the patients with AIP-not otherwise specified (n = 45) were excluded.

Patients with sIgG4-negative type 1 AIP and those with sIgG4-positive type 1 AIP present with different clinicopathological features which suggests heterogeneity of patients with type 1 AIP. Low serum IgG4 levels could indicate low disease activity in type 1 AIP.

Autoimmune pancreatitis is an increasingly recognized inflammatory type of subacute pancreatitis; two subtypes of autoimmune pancreatitis have been identified so far: the "lymphoplasmacytic" type 1 variant and the "neutrophilic" type 2 variant. Type 1 autoimmune pancreatitis represents the most common manifestation of IgG4-related disease, a fibro-inflammatory disorder characterized by elevated IgG4 levels in the serum and affected tissues. Type 2 autoimmune pancreatitis is a pancreas-specific disorder that frequently occurs in the context of inflammatory bowel diseases. Due to the complexity of both diseases, a comprehensive work up with imaging, laboratory, and histological studies is required to achieve a diagnosis and rule out malignancies. Glucocorticoids represent the cornerstone of the treatment, often supported by other immunosuppressive drugs in case of steroid intolerance or aggressive disease. Maintenance treatment is often employed in type 1 autoimmune pancreatitis because of the higher relapse rate compared with type 2 autoimmune pancreatitis. In this review, we summarize the key concept of autoimmune pancreatitis, delve into the differential diagnosis between the two subtypes, and cover the recent relevant research findings and pressing unmet needs.

Autoimmune pancreatitis (AIP) is a rare and complex condition that can be difficult to identify due to its resemblance to malignancies. This case report presents a unique instance of AIP in a 9-year-old male patient who presented with painless jaundice and elevated liver function test results. His symptoms were persistent even after previous common bile duct stent placement, requiring additional investigation. The possibility of AIP was raised by further serological tests and imaging examinations. The diagnosis was then confirmed by multiple characteristic findings revealed through history, imaging, clinical examination, histology, and lab results. Treatment was initiated with corticosteroids, which resulted in a complete resolution of symptoms and remarkable recovery. This case emphasizes the significance of including AIP in the differential diagnosis of pancreatic disorders, even in pediatric patients.

Autoimmune and immune-mediated biliary diseases represent a small proportion of biliary disorders, but owing to their progressive nature, lead to end-stage liver disease, necessitating liver transplantation for definitive management.

IgG4-related sclerosing cholangitis (IgG4-SC) is a unique, steroid-responsive, fibroinflammatory condition that is more commonly found in older men and is strongly associated with autoimmune pancreatitis (AIP). It may pose a diagnostic challenge at times due to closely mimicking hepatobiliary diseases such as primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and cholangiocarcinoma. IgG4-SC has an excellent prognosis when promptly diagnosed and treated with steroids. Literature search strategy: The authors searched PubMed and Google Scholar, for articles with the search terms "autoimmune cholangiopathy" and "IgG4 cholangiopathy."

Rare pancreatic tumors and non-neoplastic tumor-like lesions present a diagnostic challenge due to their uncommon occurrence and overlapping imaging characteristics with more prevalent pancreatic neoplasms. Advances in imaging technologies and diagnostic criteria have contributed to increased detection of these rare entities in clinical practice. This pictorial review focuses on the radiologic-pathologic correlation of rare pancreatic tumors, including colloid carcinoma, acinar cell carcinoma, pancreatoblastoma, primary pancreatic lymphoma, and non-neoplastic tumor-like lesions such as hamartomas and inflammatory pseudotumors. Detailed imaging features, such as signal intensities on MRI and enhancement patterns on CT, are correlated with pathological findings to assist in the differential diagnosis. Familiarity with these characteristics is crucial for radiologists to ensure accurate diagnosis and guide appropriate treatment strategies, as management and prognosis significantly differ from common pancreatic neoplasms.

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of 'idiopathic hyalinizing fibrosclerosis' for this under-recognized, rare, systemic condition.

Autoimmune pancreatitis (AIP), otherwise known as non-alcoholic destructive pancreatitis or sclerosing pancreatitis, is a rare form of chronic pancreatitis that is clinically significant due to its potential to mimic pancreatic cancer. In our case, we present a 64-year-old male with a past medical history of type 2 diabetes and epigastric abdominal pain for one year who presented with worsening epigastric abdominal pain, 12-pound weight loss, and vomiting and was found to have a neuroendocrine tumor on a preliminary pathology report, while official pathology later came back stating AIP. Distinguishing between autoimmune pancreatitis (AIP) and pancreatic cancer is vital, given the stark contrast in their treatment and prognosis. In our case, preliminary pathology suggested a neuroendocrine tumor, prompting consultation with oncology. Utilizing invasive testing like EUS-FNA, we obtained an official diagnosis and prevented the patient from undergoing unnecessary treatments and interventions. Our case shows the importance of further testing when a patient presents with a fast-growing obstructive pancreatic mass. While searching the literature, there are no previously documented cases of an AIP mass as large as our patients and as fast-growing.

IgG4-related disease is an immune-mediated disease that can lead to substantial morbidity and organ damage. Capable of affecting nearly any organ system or anatomic site, and showing considerable overlap in clinical presentation with various other diseases, IgG4-related disease often poses a diagnostic challenge for clinicians. Furthermore, there are no diagnostic biomarkers with high specificity for IgG4-related disease, and histopathological examination is nuanced and requires clinical correlation for accurate diagnosis. Therefore, it is crucial for clinicians to recognise the clinical phenotypes of IgG4-related disease. The disease is generally considered to have predominantly fibrotic and proliferative (or inflammatory) manifestations, with distinct clinical, serological and histopathological findings associated with each manifestation. However, the fibrotic and proliferative manifestations of this disease frequently occur together, thereby blurring this dichotomous distinction. In this Series paper, we provide a detailed overview of the clinical manifestations typical of the proliferative features of IgG4-related disease, with an emphasis on the diagnostic evaluation and differential diagnosis of each proliferative disease manifestation. In addition, we summarise the immune mechanisms underlying IgG4-related disease, suggest a framework for how to approach management and monitoring after the diagnosis is established, and highlight current unmet needs for patient care surrounding this disease.

Autoimmune pancreatitis (AIP) is acknowledged as a benign ailment with swift responsivity to corticosteroid treatment (CST). Though past assumptions dismissed its connection to cyst formation, a few instances of AIP-linked pancreatic cysts (PCs) have been documented. While some cases responded positively to CST, others demonstrated resistance, necessitating intervention. Our case is a 50-year-old male with a known diagnosis of type 1 AIP. This case presents a specific adverse drug reaction of glucocorticoid that causes diabetes mellitus. Glucocorticoid was tapered due to clinical improvement and diabetes complications but also caused multiple flares. Additionally, in several months, CT showed progressive enlarging multi-cystic pancreatic head lesions, which cause constriction at the distal duodenal outlet and biliary ductal dilation. This case presents a specific adverse drug reaction of glucocorticoid that causes diabetes mellitus. Meanwhile, the fast-growing multi-cysts in the pancreatic head after treatment of type 1 AIP were very rare.

Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis with a multifactorial pathogenesis. Historically, it has been classified as type 1 and type 2, according to its clinical and histological features. The diagnosis of AIP is challenging and relies on a combination of clinical, histopathologic, serologic, and imaging characteristics. In the available guidelines, the imaging hallmarks of AIP are based on cross-sectional imaging and cholangiopancreatography retrograde endoscopic findings. Endoscopic ultrasound (EUS) is generally used for pancreatic tissue acquisition to rule out pancreatic cancer and diagnose AIP with limited accuracy. Several papers reported the reliability of EUS for providing informative morphologic features of AIP. Nowadays, the improvement in the resolution of EUS conventional images and the development of new ancillary technologies have further increased the diagnostic yield of EUS: contrast-enhanced EUS and EUS elastography are non-invasive and real-time techniques that strongly support the diagnosis and management of pancreatic diseases. In this review article, we will present the role of conventional EUS and ancillary diagnostic techniques in the diagnosis of AIP to support clinicians and endosonographers in managing this condition.

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma.

A 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor.

It is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.

Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens.

We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP.

We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose.

Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased. It is of great importance to summarize and discuss the latest progress regarding IgG4-AIP disease.

Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.

Immunoglobulins are an essential part of the humoral immune response. IgG4 antibodies are the least prevalent subclass and have unique structural and functional properties. In this review, we discuss IgG4 class switch and B cell production. We review the importance of IgG4 antibodies in the context of allergic responses, helminth infections and malignancy. We discuss their anti-inflammatory and tolerogenic effects in allergen-specific immunotherapy, and ability to evade the immune system in parasitic infection and tumour cells. We then focus on the role of IgG4 autoantibodies and autoantigens in IgG4-autoimmune diseases and IgG4-related disease, highlighting important parallels and differences between them. In IgG4-autoimmune diseases, pathogenesis is based on a direct role of IgG4 antibodies binding to self-antigens and disturbing homeostasis. In IgG4-related disease, where affected organs are infiltrated with IgG4-expressing plasma cells, IgG4 antibodies may also directly target a number of self-antigens or be overexpressed as an epiphenomenon of the disease. These antigen-driven processes require critical T and B cell interaction. Lastly, we explore the current gaps in our knowledge and how these may be addressed.

Recurrent acute pancreatitis is beginning to be recognized as an intermediary stage in the continuous spectrum between acute and chronic pancreatitis. It is crucial to identify this disease stage and intervene with diagnostic and therapeutic modalities to prevent the painful and irreversible condition of chronic pancreatitis. We review the recent advances in diagnosing and managing this important 'call for action' condition.

Autoimmune pancreatitis (AIP) is classified as a distinct form of pancreatitis according to the guidelines. It is characterized by imaging morphologic and histologic features and is associated with extrapancreatic manifestations in type 1 IgG 4-associated disease. Symptoms and findings almost always improve with administration of steroids. Differentiation from pancreatic ductal adenocarcinoma is required, particularly in the presence of AIP with focal parenchymal involvement.

If AIP is suspected, abdominal ultrasound and/or endosonography, computed tomography (CT), and preferably magnetic resonance imaging (MRI) are indicated. A distinction is made between parenchymal and ductal changes that specifically indicate the presence of AIP.

The diagnosis of autoimmune pancreatitis should be made based on the International Consensus Criteria (ICDC), in which the five main features (imaging, serology, histology, other organ involvement, response to steroid medication) are assessed. In type 1 AIP, typical imaging changes are sufficient to establish the diagnosis even with negative histology, whereas for type 2 AIP, histologic evidence is required. Imaging changes help in the differential diagnosis from pancreatic cancer.

The following article addresses and evaluates crucial imaging diagnostic CT and MRI criteria for correct classification of findings, description of results, and differentiation of autoimmune pancreatitis from pancreatic cancer.

IgG4-related cholangitis (IRC) is the major hepatobiliary manifestation of IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder. The pathogenesis of IgG4-RD and IRC is currently viewed as multifactorial, as there is evidence of a genetic predisposition while environmental factors, such as blue-collar work, are major risk factors. Various autoantigens have been described in IgG4-RD, including annexin A11 and laminin 511-E8, proteins which may exert a partially protective function in cholangiocytes by enhancing secretion and barrier function, respectively. For the other recently described autoantigens, galectin-3 and prohibitin 1, a distinct role in cholangiocytes appears less apparent. In relation to these autoantigens, oligoclonal expansions of IgG4+ plasmablasts are present in patients with IRC and disappear upon successful treatment. More recently, specific T-cell subtypes including regulatory T cells, follicular T helper 2 cells, peripheral T helper cells and cytotoxic CD8+ and CD4+ SLAMF7+ T cells have been implicated in the pathogenesis of IgG4-RD. The clinical presentation of IRC often mimics other biliary diseases such as primary sclerosing cholangitis or cholangiocarcinoma, which may lead to inappropriate medical and potentially invalidating surgical interventions. As specific biomarkers are lacking, diagnosis is made according to the HISORt criteria comprising histopathology, imaging, serology, other organ manifestations and response to therapy. Treatment of IRC aims to prevent or alleviate organ damage and to improve symptoms and consists of (i) remission induction, (ii) remission maintenance and (iii) long-term management. Glucocorticosteroids are highly effective for remission induction, after which immunomodulators can be introduced for maintenance of remission as glucocorticosteroid-sparing alternatives. Increased insight into the pathogenesis of IRC will lead to improved diagnosis and novel therapeutic strategies in the future.

Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported.

An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD.

We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred.

In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity.

A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted.

The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement.

This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab.

Obstructive jaundice is a joint clinical presentation with many etiologies, including pancreatic cancer and autoimmune pancreatitis (AIP). Differentiating between these two conditions is pivotal due to the divergent management approaches and prognoses. In this case report, we present a case of a 49-year-old female patient who presented with weight loss, intermittent chronic abdominal pain, and jaundice. She was initially suspected of having pancreatic cancer because of clinical presentation and imaging findings. However, she was ultimately diagnosed with Type 1 AIP due to histopathology findings and elevated immunoglobulin G4. This case highlights the complexities in diagnosis, the role of advanced imaging techniques and tissue sampling, and the lessons learned regarding managing this challenging clinical scenario.

Autoimmune pancreatitis (AIP) usually responds dramatically to steroid therapy. Occasionally, however, misdiagnosed patients have undergone pancreaticoduodenectomy. This study is aimed at providing useful information to improve the accuracy of diagnosis before surgery and thus avoid unnecessary resections in patients with AIP.

From January 2015 to February 2020, a series of patients were enrolled, having undergone pancreaticoduodenectomy for presumed malignancy. AIP diagnoses were confirmed by postoperative pathology. The demographic and clinical data of the AIP patients were evaluated. The main diagnostic criteria (HISORt, Asian, and ICDC) for AIP were applied to assess whether and how unnecessary surgery could have been avoided.

A total of 124 cases of pancreaticoduodenectomy were performed for presumed malignancy. Six patients were diagnosed with benign disease and five with AIP. The prevalences of benign disease and AIP were 4.8% and 4%, respectively. Four patients were female and 1 male, with a mean age of 60.0 years old. Jaundice, pain, and weight loss were observed in 100%, 20%, and 40% of AIP patients, respectively. The radiologic features of the AIP patients were a diffusely enlarged gland (40.0%), a focally enlarged gland (40.0%), pancreatic ductal dilatation (60.0%), upstream parenchymal atrophy (20.0%), bile duct thickening (66.0%), and bile duct stricture (40.0%). Based on the diagnostic criteria for AIP, surgery could have been avoided in two cases.

IgG4 measurement and integrated use of major diagnostic criteria should be emphasized in every patient eligible for pancreaticoduodenectomies.

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is considered a biliary manifestation of IgG4-related diseases. However, there has been a controversy on the clinical outcomes according to the location of the involved bile duct. We therefore compared the clinical outcomes and long-term prognosis of IgG4-SC with proximal bile duct involvement (proximal IgG4-SC) and IgG4-SC with distal bile duct involvement (distal IgG4-SC).

We reviewed the data of patients with IgG4-SC that were prospectively collected at 10 tertiary centers between March 2002 and October 2020. Clinical manifestations, outcomes, association with autoimmune pancreatitis (AIP), steroid-responsiveness, and relapse of IgG4-SC were evaluated.

A total of 148 patients (proximal IgG4-SC, n = 59; distal IgG4-SC, n = 89) were analyzed. The median age was 65 years (IQR, 56.25-71), and 86% were male. The two groups were similar in terms of jaundice at initial presentation (51% vs 65%; P = 0.082) and presence of elevated serum IgG4 (66% vs 70%; P = 0.649). The two groups showed significant differences in terms of steroid-responsiveness (91% vs 100%; P = 0.008), association with AIP (75% vs 99%; P = 0.001), and occurrence of liver cirrhosis (9% vs 1%; P = 0.034). During a median follow-up of 64 months (IQR, 21.9-84.7), the cumulative relapse-free survival was significantly different between the two groups (67% vs 79% at 5 years; P = 0.035).

Relapse of IgG4-SC frequently occurred during follow-up. Proximal IgG4-SC and distal IgG4-SC had different long-term outcomes in terms of steroid-responsiveness, occurrence of liver cirrhosis, and recurrence. It may be advantageous to determine the therapeutic and follow-up strategies according to the location of bile duct involvement.

Diagnosis and management of autoimmune pancreatitis during pregnancy. Autoimmune pancreatitis is a rare and life-threatening condition with increased maternal and fetal morbidity and mortality. Autoimmune pancreatitis may result in a mass-forming lesion in the pancreas resembling pancreatic cancer; therefore, meticulous and careful investigations must be done to avoid misdiagnosing autoimmune pancreatitis as pancreatic cancer. Since autoimmune pancreatitis improves dramatically to steroid therapy, accurate diagnosis of autoimmune pancreatitis can avoid unnecessary procedures, surgeries, and pancreatic resection. A case of a pregnant lady in her third trimester was presented with abdominal pain, nausea, and vomiting. On examination, there was tenderness in both epigastric and right hypochondrium associated with elevated serum amylase, liver transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase, and immunoglobulin G4. Both abdominal ultrasound and magnetic resonance cholangiopancreatography showed a pancreatic head lesion with dilation in both pancreatic duct and common bile duct. Steroid was initiated that resulted in rapid and dramatic responsiveness. Acute pancreatitis is uncommon during pregnancy, and autoimmune pancreatitis is a very rare form of acute pancreatitis; therefore, a clear and rapid assessment, diagnosis, and management plan are necessary to avoid maternal and fetal morbidity and mortality.

Autoimmune pancreatitis (AIP) is a rare form of a chronic, immune-mediated, inflammatory pancreatic condition. There is limited data regarding presentation and outcome in the pediatric population. We described a single-center case series of 4 pediatric patients with AIP to better understand the presentation, symptoms, and outcomes of this rare condition.

Data collected included demographics, serology markers, symptoms at presentation, imaging, additional organ involvement, histology, treatment methods, and outcomes. The diagnosis of AIP was made by a combination of serology, pancreatic imaging, histology, extrapancreatic manifestations, and steroid response.

All patients were diagnosed with type 2 AIP. Abdominal pain, emesis, and obstructive jaundice were the most common symptoms at presentation. Autoimmune markers were negative. Cross-sectional abdominal imaging showed diffuse/focal pancreatic gland enlargement and common bile duct stricture universally and main pancreatic duct irregularity in half of the patients. Biopsies showed lymphoplasmacytic infiltration with associated pancreatic fibrosis and atrophy. Treatment with an 8-week tapering course of prednisone showed prompt response with resolution of symptoms and normalization of laboratory test results.

Our case series shows that AIP in children is a rare entity with a distinct clinical presentation, classical radiographic and histological features with good long-term prognosis.

Autoimmune pancreatitis (AIP) is a distinct form of pancreatic inflammatory disease that responds well to glucocorticoid therapy. Knowledge on AIP has rapidly evolved over the past two decades. Based on bibliometric analysis, this study aimed to assess the research status of AIP over the past two decades and determine the research focus and emerging topics.

AIP-related publications published between January 1, 2002, and June 6, 2022, were retrieved from the Web of Science Core Collection. Bibliometric data were analyzed using HisCite, VOSviewer, CiteSpace, and bibliometrix package. Annual output, leading countries/regions, active institutions and authors, core journals and references, and keywords of AIP were evaluated.

Overall, 1,772 publications were retrieved from 501 journals by 6,767 authors from 63 countries/regions. Japan published articles on AIP the most (n=728, 41.1%), followed by the United States (n=336, 19%), Germany (n=147, 8.3%), China (n=127, 7%), and Italy (n=107, 6%). The top three most prolific authors were Terumi Kamisawa from Tokyo Metropolitan Komagome Hospital (n=117), Kazuichi Okazaki from Kansai Medical University (n=103), and Shigeyuki Kawa from Matsumoto Dental University (n=94). Pancreas was the most productive journal regarding AIP research (n=95), followed by the Journal of Gastroenterology (n=67), Internal Medicine (n=66), Pancreatology (n=63), and World Journal of Gastroenterology (n=62). "Diagnosis" was the most mentioned keyword. "Risk," "malignancy," "outcome," "22-gauge needle," and "fine-needle aspiration" were recognized as emerging topics.

Japan was the leading country in AIP research. Research papers were mainly published in specialized journals. Diagnosis was the research focus. Long-term outcomes and pancreatic tissue acquisition were recognized as research frontiers for AIP.

Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disorder usually involving the abdominal aorta and surrounding structures. It is divided into primary (idiopathic) and secondary RPF. Primary RPF can be immunoglobulin (Ig) G4-related disease or non-IgG4-related disease. Recently, there has been a rise in case reports regarding the topic, but awareness about the disease is still far from ideal. Hence, we present the case of a 49-year-old female who had repeated admissions for chronic abdominal pain attributed to chronic alcoholic pancreatitis. She had a medical history significant for psoriasis and surgical history significant for cholecystectomy. Her computed tomography (CT) scans on each admission for the last year showed some signs of RPF, but it was never considered the primary etiology of her chronic symptoms. We also obtained magnetic resonance imaging (MRI) which did not show any underlying malignancy but showed the progression of her RPF. She was started on a steroid regimen, which significantly improved her symptoms. She was diagnosed with idiopathic RPF due to unclear etiology, although her underlying risk factors, including psoriasis, past surgeries, and pancreatitis-associated inflammation, were considered predisposing factors. Idiopathic RPF accounts for more than two-thirds of total cases of RPF. Patients with autoimmune diseases can overlap with other autoimmune disorders. For non-malignant RPF, medical management with 1mg/kg/day steroids is deemed effective. Still, there is a lack of prospective trials and consensus for guidelines on treating RPF. The follow-up involves laboratory tests, including erythrocyte sedimentation rate, C-reactive protein, and CT or MRI in an outpatient setting to identify treatment response and relapse. There is a need for more streamlined guidelines to diagnose and manage this disease.

Proper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP.

We retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment.

MAAS (median, 8 points) at the start of the initial treatment was reduced after treatment (median, 4 points; P < 0.001). A MAAS ≥11 points at the start of the initial treatment was associated with relapse. The initial treatment-induced reduction of MAAS<60% was more frequent in patients with relapse (75.0%) than in patients without relapse (37.6%; P = 0.007). MAAS at the start of maintenance treatment was higher for patients with relapse (median, 5 points) than that for patients without relapse (median, 4 points; P = 0.007). MAAS ≥4 points at the start of maintenance treatment was associated with subsequent relapse.

MAAS is useful for predicting relapse in patients with type 1 AIP undergoing maintenance therapy.

Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.