Immunoglobulin G4 -related gastrointestinal disease associated with type 1 autoimmune pancreatitis: A case report.

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

Microbe-associated molecular patterns derived from fungi and bacteria promote IgG4 antibody production in patients with type 1 autoimmune pancreatitis.

Enhanced IgG4 antibody (Ab) response is a prominent feature of type 1 autoimmune pancreatitis (AIP). Innate immune responses associated with IgG4 Ab production are poorly defined. We have previously reported that peripheral blood mononuclear cells (PBMCs) isolated from patients with type 1 AIP produce large amounts of IgG4 Abs upon stimulation with bacterial cell wall components. In addition, we showed that activation of plasmacytoid dendritic cells producing interferon (IFN)-α, interleukin (IL)-33, and B cell-activating factor (BAFF) upon sensing intestinal bacteria mediates the development of experimental AIP. In this study, we attempted to clarify the role of innate immunity against fungi in inducing enhanced IgG4 Ab responses in type 1 AIP. PBMCs isolated from healthy controls and patients with type 1 AIP were stimulated with a broad range of bacterial and fungal cell wall components. The concentrations of IgG1, IgG4, and cytokines were measured using enzyme-linked immunosorbent assays. Cell wall components derived from bacteria and fungi induced IgG1 and IgG4 Ab production in patients with type 1 AIP. Various types of microbe-associated molecular pattern motifs enhanced IgG4 Ab production in patients with type 1 AIP compared with the limited motifs in healthy controls. The enhanced IgG1 and IgG4 Ab production that followed in response to bacterial and fungal cell wall components was parallel to that of IFN-α, IFN-γ, IL-10, IL-33, and BAFF. In conclusion, cell wall components derived from fungi as well as bacteria promote IgG4 Ab responses in patients with type 1 AIP.

Plea to radiologists: Please consider Mahvash disease when encountering an enlarged pancreas.

Radiologists play a key role in establishing an early and accurate diagnosis, especially for rare diseases. Mahvash disease (OMIM 619290) is an autosomal recessive hereditary disease caused by inactivating mutations of the glucagon receptor and its main clinical consequences are pancreatic neuroendocrine tumors and in some cases, porto-sinusoidal vascular disease and portal hypertension. Untreated Mahvash disease can be lethal. The diagnosis of Mahvash disease has almost always been delayed in the past due to radiologists' unawareness of or unfamiliarity with the unique imaging features of Mahvash disease which are moderately to enormously enlarge pancreas with preserved pancreas contour and parenchyma without vascular involvement or lymphadenopathy. These features help differentiate Mahvash disease from other etiologies of diffusely enlarged pancreas such as diffuse pancreatic ductal carcinoma, diffuse pancreatic lymphoma, and autoimmune pancreatitis. Invoking Mahvash disease in the differential diagnosis of an enlarged pancreas has recently been shown to facilitate early diagnosis. To prevent missing the diagnosis of this significant disease, I sincerely ask radiologists to consider Mahvash disease in their differential diagnoses of diffusely enlarged pancreas.

New insights into predictors of autoimmune pancreatitis relapse after steroid therapy.

OBJECTIVES: While autoimmune pancreatitis (AIP) responds well to steroid therapy, the high relapse rate in type 1 AIP remains a critical problem. The present study examined predictors of relapse of type 1 AIP following steroid therapy. MATERIALS AND METHODS: Nine factors potentially predictive of relapse were analyzed in 81 AIP patients receiving steroid therapy with follow-up ≥ 12 months. The rate of serum IgG4 decrease following steroid therapy was calculated by dividing the difference between serum IgG4 values before and at two months after the start of steroid by the IgG4 value before steroid. RESULTS: A relapse occurred in 11 patients (13.5%) during a median of 38 months. Multivariate analysis revealed that the presence of IgG4-related retroperitoneal fibrosis (HR: 5.59; 95% CI: 1.42-22.0; p = 0.014) and the low rate of serum IgG4 decrease after steroid therapy (HR: 0.048; 95% CI: 0.005-0.46; p = 0.008) were significant, independent predictors of AIP relapse. The cut-off value based on receiver operating characteristic curve data for the rate of serum IgG4 decrease before and at two months after steroid therapy distinguishing patients with and without a relapse was 0.65. Using this cut-off value, the area under the curve, sensitivity, and specificity were found to be 0.63, 0.73, and 0.60, respectively. CONCLUSION: The low rate of serum IgG4 decrease after the start of steroid therapy and the presence of IgG4-related retroperitoneal fibrosis were predictive of type 1 AIP relapse. Cautious, gradual tapering of steroid dosage and longer maintenance therapy are recommended for patients with these factors.

Autoimmune Pancreatitis Mimicking Obstructive Pancreatic Neuroendocrine Tumor.

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.

Glucocorticoid therapy in pancreatic portal hypertension associated with autoimmune pancreatitis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial. CASE SUMMARY: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared. CONCLUSION: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.

Autoimmune Pancreatitis Associated With Progressive Giant Multilocular Pancreatic Pseudocyst and Steroid-Induced Diabetes.

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.

A Case with Multiple Pathologies in the Pancreatic Head.

Objectives: Autoimmune pancreatitis (AIP) type 1, paraduodenal (groove) pancreatitis, and follicular pancreatitis are rare clinical entities whose diagnosis may be challenging, given the potential imaging overlap with pancreatic cancer. Methods: We performed a retrospective analysis of the medical chart of a patient with multiple pancreas pathologies. Results: We present a case with multiple pancreas pathologies, including a poorly differentiated ductal adenocarcinoma of pancreatobiliary type, an intraductal papillary mucinous lesion (pre-existing lesion of IPMN type), and an inflammatory process with complex features, in which paraduodenal (groove) pancreatitis, follicular pancreatitis, and IgG4-related pancreatitis (AIP type 1) were also present. Conclusions: The diagnosis of AIP and paraduodenal pancreatitis is not always straightforward, and in some cases, it is not easy to differentiate them from pancreatic cancer. Surgery should be considered in patients when a suspicion of malignant/premalignant lesions cannot be excluded after a complete diagnostic work-up.

IgG4-Related Autoimmune Pancreatitis Mimicking Pancreatic Cancer: A Report of Two Cases.

IgG4-related autoimmune pancreatitis (AIP) is a rare inflammatory condition characterized by elevated IgG4-positive plasma cells and lymphoplasmacytic infiltration in the pancreas. This disease responds to steroid therapy but can be challenging to differentiate from pancreatic cancer. In this paper, we present two cases of IgG4-related AIP presenting as pancreatic masses. Our aim is to highlight the diagnostic complexities of this condition and emphasize the need for a multidisciplinary approach to avoid unnecessary surgical interventions and ensure appropriate treatment.

Prevalence of autoimmune pancreatitis in pancreatic resection for suspected malignancy: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer. METHODS: A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms 'autoimmune pancreatitis' and 'pancreatic resection' and supplemented by manual checks of reference lists in all retrieved articles. RESULTS: Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients). CONCLUSION: Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery.

IgG4-related sclerosing cholangitis associated with essential thrombocythemia: A case report.

BACKGROUND: The complexity of immunoglobulin G4 (IgG4)-related diseases and their potential connection to hematologic malignancies remains unclear. This article provided a review of the diagnosis and treatment of a patient with IgG4-related sclerosing cholangitis (SC) and essential thrombocythemia (ET), along with an analysis of relevant literature to enhance comprehension of this disease. CASE SUMMARY: A 56-year-old male was admitted to two hospitals with deteriorating jaundice and pruritus prior to hospitalization. Beyond our expectations, the patient was first diagnosed with IgG4-SC and ET with the Janus kinase 2 V617F mutation. Interestingly, the administration of acetate prednisone significantly resulted in improvements in both IgG4-SC and ET. Clinicians need to pay attention to immune disorders and inflammation as they contribute to the development of various disease phenotypes. CONCLUSION: When IgG4-SC is suspected without histopathological evidence, diagnostic therapy and long-term regular follow-up can lead to positive treatment outcomes. Clinicians should be mindful of the potential presence of concurrent hematologic diseases in patients with immune disorders.

Pancreatic infiltrative malignancy masquerading as autoimmune pancreatitis: Case report, review of radiological criteria, and literature.

We report a case of a 44-year-old male patient, who presented to the University Hospital of Salzburg, Austria with abdominal pain, persistent jaundice, and lack of appetite. Radiological work-up (CT, MRI, PET/CT) indicated a suspicious mass of the uncinate process of the pancreatic head with adjacent infiltration and regional lymphadenopathy. The differential diagnosis was between primary pancreatic cancer and focal autoimmune pancreatitis. Further laparoscopic biopsies from multiple areas, showed only fibrous scarring processes, with no malignancy. Treatment with steroids didn't give any benefits. After multiple follow-up CTs and MRs within 6 months-additional biopsies were done, which eventually demonstrated adenocarcinoma. Evidently the cancer diagnosis was much delayed and the patient started receiving chemotherapy, but radical surgery was not possible. Multiple articles and case reports can be found in the literature, that are reviewing the fact that pancreatic inflammatory processes are mimicking pancreatic tumor, but not many articles or case reports are available in the literature, where neoplastic processes are misinterpreted as inflammatory and incorrectly proven with histological examination. One of the main reasons for improper diagnosis is the desmoplastic reaction around the pancreatic malignancy. Another important aspect is the acceptance of histological diagnosis as conclusive, where no opposing arguments are specified, based on radiological criteria.

Pancreatico-renal fistula associated with pancreatic cysts caused by type 1 autoimmune pancreatitis.

To our best knowledge, the formation of a pancreatico-renal fistula and the presence of pancreatic fluid collection in the renal subcapsular space have not been reported as autoimmune pancreatitis (AIP) complications. We describe a case of a pancreatico-renal fistula associated with type 1 AIP. The patient presented with abdominal and back pain accompanied by pancreatic cystic lesions during an untreated course of AIP. The diagnosis of pancreatico-renal fistula was based on the presence of a left renal subcapsular fluid collection containing pancreatic amylase, disappearance of pancreatic cysts, and a defect in the partial anterior renal fascia observed on imaging studies. Treatment with steroids and percutaneous drainage resulted in improvement. Pancreatic pseudocysts can affect other organs owing to their digestive action. Similar symptoms may occur in patients with AIP.

A suspected case of serum IgG4-negative type 1 autoimmune pancreatitis detected due to localized pancreatic duct narrowing: a case report.

A 50-year-old woman was referred to our hospital with elevated serum amylase levels. Physical examination revealed no jaundice or abdominal tenderness. Serum IgG4 was negative. Computed tomography revealed a localized pancreatic duct narrowing in the pancreatic head, with caudal pancreatic duct dilation and an intraductal papillary mucinous neoplasm. Pancreatic enlargement was not observed. Endoscopic ultrasonography (EUS) showed a small hypoechoic mass. Although EUS-guided, fine-needle aspiration was performed, no diagnosis was established. Endoscopic retrograde pancreatography showed a localized narrowing in the main pancreatic duct of the pancreatic head. A biopsy of the narrowing was performed through the minor papilla because of difficult access from the major papilla. The specimen showed the infiltration of numerous IgG4-positive plasma cells, suggesting type 1 autoimmune pancreatitis (AIP). Six months later, magnetic resonance cholangiopancreatography revealed improvement in the narrowing without specific treatment. The patient presented with localized narrowing of the pancreatic duct and caudal duct dilation, which was distinct from pancreatic cancer. Diagnostic difficulties arose from negative serum IgG4 results, the lack of typical imaging characteristics of AIP, and failure to meet the AIP criteria according to the relevant Japanese and international guidelines. However, AIP was suspected and surgery was successfully avoided through a biopsy.

The Role of Endoscopic Ultrasound and Ancillary Techniques in the Diagnosis of Autoimmune Pancreatitis: A Comprehensive Review.

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.

A case of ulcerative colitis with a variety of autoimmune diseases including ankylosing spondylitis, type 2 autoimmune pancreatitis, and primary sclerosing cholangitis.

Ankylosing spondylitis (AS), primary sclerosing cholangitis (PSC), and autoimmune pancreatitis (AIP) are known as extraintestinal manifestations (EIMs) of ulcerative colitis (UC). A 74-year-old Japanese man visited our hospital because of white stool. He had been diagnosed with AS when he was 30 years old, and he was HLA-B27-positive. Based on various examination results, it was suspected that AIP had caused bile duct stricture. During the clinical course, he was diagnosed with UC and PSC. Then, AIP was diagnosed because he had localized pancreatic enlargement, irregular stenosis of the main pancreatic duct, PSC, and no tumor cells of pancreas. A patient with all four of these diseases, AS, AIP, PSC, and UC, is very rare. Therefore, we report a quite rare case with three EIMs (AS, PSC, and AIP) of UC.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY: The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION: In patients with pancreatic swelling, the possibility of AIP should be considered.

Diagnostic performance of F-18 FDG PET/CT in differentiating autoimmune pancreatitis from pancreatic cancer: a systemic review and meta-analysis.

OBJECTIVES: This study aims to evaluate the utility of F-18 FDG PET/CT in the non-invasive diagnosis of autoimmune pancreatitis (AIP) and differentiating it from pancreatic cancer (CaP) based on the amount and pattern of FDG uptake, as well as involvement of extra-pancreatic sites. METHODS: A systematic search was conducted using PubMed, Scopus, Cochrane Library and Google Scholar. Only those studies that compared the findings of F-18 FDG PET/CT in terms of SUVmax, pattern of FDG uptake and presence of FDG-avid extra-pancreatic sites in both AIP and CaP were included. Studies were qualitatively assessed for risk of bias and publication bias. The diagnostic performance of parameters on PET/CT was examined through pooled sensitivity, specificity, diagnostic odd's ratio (DOR) and summary receiver operator characteristic (SROC) curve analysis. RESULTS: Six studies were included with a total of 580 patients. 178 patients had AIP (Age 18-90 years, male, M: female, F ratio-8.4:1) and 402 patients had CaP (Age 22-88 years, M:F ratio-1.5:1). Type of AIP was reported in only 3 studies, with the included cases predominantly being type 1 AIP. All studies were retrospective with heterogeneity and a risk on patient selection and index test. The FDG uptake, expressed as SUVmax, was lower in AIP with a weighted mean difference of -3.11 (95% confidence interval, CI: -5.28 to -0.94). To diagnose AIP, the pooled sensitivity, specificity and DOR of diffuse pattern of FDG uptake were 0.59 (95% CI: 0.51-0.66), 0.89 (95% CI: 0.86-0.92) and 21.07 (95% CI: 5.07-88.32), respectively, with an area under curve (AUC) of 0.717 on SROC analysis. The pooled sensitivity, specificity and DOR of FDG-avid extra pancreatic sites were 0.55 (95% CI: 0.45-0.65), 0.58 (95% CI: 0.52-0.64) and 2.33 (95% CI: 1.40-3.89), respectively, with an AUC of 0.632. CONCLUSION: On F-18 FDG PET/CT, a pancreatic lesion of AIP has a lower SUVmax value than CaP. A diffuse pattern of FDG uptake and presence of an extra-pancreatic FDG-avid site are nearly 21 times and twice more likely in AIP than CaP, respectively.