Autoimmune Pancreatitis Type Research Articles

IgG4 Related Disease Presenting as Simultaneous Pancreatic and Lung Mass Mimicking Malignancy

ABSTRACT Introduction and importance: IgG4-RD (IgG4 related disease) can be challenging as it can lead to the formation of a “mass” within organs often misdiagnosed as malignancies. Focal mass forming types of AIP (auto-immune pancreatitis) in IgG4-RD can present with obstructive jaundice and present as a pancreatic mass. IgG4-RD in the lung can also present as lung nodules mimicking carcinoma and be misdiagnosed as carcinoma of lung. Case presentation: We report a 70 years old Asian male, presented both simultaneously as a pancreatic mass with obstructive jaundice and a lung mass. the patient underwent whipple procedure and was found that the mass lesion of the pancreas is not malignancy but IgG4-RD. Then lung mass got bigger and with symptoms of coughing and weight loss, then biopsy of the lung mass also was confirmed as IgG-RD and responds well to rituximab. Clinical discussion: Malignancy is often highly suspected given the mass forming presentation of IgG4-RD in certain organs. It is very difficult to differentiate IgG4-RD from cancer. Most patients with mass formation in the pancreas often had resection done in order to exclude the malignancy. Lung involvement has been reported in IgG4-RD which presents autoimmune pancreatitis. However, a discussion on the coexistence of mass-like formation in the pancreas and lung is lacking in the literature. A thorough preoperative process aimed at ruling out differential diagnoses can avoid false diagnoses and extensive surgery. Clinicians should remain aware of various presentations of IgG4-RD to ensure the correct diagnosis. Conclusion: An awareness of these atypical presentations of IgG4-RD as both a pancreatic and a lung mass may avert unnecessary surgery. Highlight

Surgery in Autoimmune Pancreatitis

Introduction: Autoimmune pancreatitis (AIP) is a disease that may mimic malignant pancreatic lesions both in terms of symptomatology and imaging appearance. The aim of the present study is to analyze experiences of surgery in patients with AIP in one of the largest European cohorts. Patients and Methods: We performed a single-center retrospective study of patients diagnosed with AIP at the Department of Abdominal Diseases at Karolinska University Hospital in Stockholm, Sweden, between January 2001 and October 2020. Results: There were 159 patients diagnosed with AIP, and among them, 35 (22.0%) patients had surgery: 20 (57.1%) males and 15 (42.9%) females; median age at surgery was 59 years (range 37–81). Median follow-up period after surgery was 50 months (range 1–235). AIP type 1 was diagnosed in 28 (80%) patients and AIP type 2 in 7 (20%) patients. Malignant and premalignant lesions were diagnosed in 8 (22.9%) patients for whom AIP was not the primary differential diagnosis, but in all cases, it was described as a simultaneous finding and recorded in retrospective analysis in histological reports of surgical specimens. Conclusions: Diagnosis of AIP is not always straightforward, and in some cases, it is not easy to differentiate it from the malignancy. Surgery is generally not indicated for AIP but might be considered in patients when suspicion of malignant/premalignant lesions cannot be excluded after complete diagnostic workup.

Autoimmune pancreatitis: What we know so far.

Autoimmune pancreatitis (AIP) is a rare, often‐missed disease that involves inflammation of the pancreas and strictures of the pancreatic duct. Its prevalence and incidence in the United States remain scarce. The disease has a varied presentation and often mimics pancreatic malignancy, which can make the diagnosis challenging. Most patients have an excellent response to corticosteroid therapy. Immunomodulators may be used in some cases. Rituximab is an effective, emerging treatment in steroid‐refractory cases. This study aims to review the two distinct types of AIP and provide a detailed analysis of the diagnostic approach and treatment modalities.

Endoscopic ultrasound features of autoimmune pancreatitis: The typical findings and chronic pancreatitis changes

BACKGROUNDFew studies have fully described endoscopic ultrasound (EUS) features of newly diagnosed autoimmune pancreatitis (AIP) involving both typical findings and chronic pancreatitis (CP) features. The typical EUS findings are prevalent in the diffuse type AIP but may not be as common for the focal type, and the differences between the diffuse and focal AIP need to be specified.AIMTo demonstrate the EUS features of newly diagnosed AIP and the difference between diffuse and focal AIP.METHODSThis retrospective single center study included 285 patients of newly diagnosed type 1 AIP following the international consensus diagnostic criteria, with the EUS procedures accomplished before corticosteroid initiation. We explored the EUS features and compared the typical AIP and CP features between the diffuse and focal AIP cases. The Rosemont criteria were employed for CP features definition and CP change level comparison.RESULTSFor the typical AIP features, there were significantly more patients in the diffuse group with bile duct wall thickening (158 of 214 cases, 73.4% vs 37 of 71 cases, 52.1%, P = 0.001) and peripancreatic hypoechoic margin (76 of 214 cases, 35.5% vs 5 of 71 cases, 7.0%, P < 0.001). For the CP features, there were significantly more patients in the focal group with main pancreatic duct dilation (30 of 214 cases, 14.0% vs 18 of 71 cases, 25.3%, P = 0.03). The cholangitis-like changes were more prevalent in the focal cases with pancreatic head involvement. The CP change level was relatively limited for newly diagnosed AIP cases in both groups.CONCLUSIONThis study demonstrated the difference in the typical AIP and CP features between diffuse and focal AIP and indicated the limited CP change level in newly diagnosed AIP.

S1639 Type I Autoimmune Pancreatitis—A Rare Cause of Acute Pancreatitis

Introduction: IgG4-related disease (IgG4-RD) is a clinical entity characterized by multi-organ lymphoplasmacytic infiltration with IgG4 positive plasma cells that results in fibrosis. Type I autoimmune pancreatitis (AIP), one of the manifestations of IgG4-RD, is a rare cause of acute pancreatitis and it has different prognostic and therapeutic implications from other etiologies of pancreatitis. Case Description/Methods: A 27-year-old morbidly obese male presented with nausea, bilious emesis, epigastric pain and non-bloody diarrhea for 4 weeks. Exam revealed papules throughout the body, lower extremity edema and brown stool on rectal exam. Patient had severe anemia (Hg 4.6 g/dL), hyperkalemia (6.6 mmol/L), uremia (BUN 247 mg/dL), elevated creatinine (33.04 mg/dL) and lipase (1,164 U/L) levels. He also had elevated TSH (7.37 uIU/mL), decreased free T4 (0.61 ng/dL) and mildly elevated thyroid peroxidase antibody level (43.6 IU/mL). Alkaline phosphatase, total bilirubin and transaminases were normal.US and CT abdomen showed cholelithiasis without intra/extra hepatic ductal dilation and acute pancreatitis, respectively. In the absence of biliary tract obstruction, alcohol use and with normal triglyceride levels, AIP was suspected. IgG level was elevated (2305 mg/dL) with elevated IgG4 subclass (229 mg/dL) supporting the diagnosis of type 1 AIP. Diagnosis was confirmed with kidney biopsy showing diffuse TIN with lymphoplasmacytic cells positive for IgG4; other autoimmune work up including C3, C4, ANA, ds-DNA, ANCAs was negative. The patient improved with Methylprednisolone and Rituximab therapy. He was referred for kidney transplant and continues to require hemodialysis. Discussion: IgG4-RD is an autoimmune disease with multi-organ involvement and eventual fibrosis.Type I AIP can be diagnosed based on the presence of HISORt criteria; these include histologic, imaging, serologic, other organ involvement and response to glucocorticoid therapy. In our patient, elevated IgG4 level, renal biopsy and response to steroids confirmed the etiology of Type I AIP. Organs affected included kidneys (TIN), thyroid gland (Hashimoto’s thyroiditis), pancreas (AIP type I), lymphatics and skin. This case not only serves an important purpose of demonstrating the heterogeneity of IgG4-RD, but also, stresses the importance of appropriate diagnosis because AIP often can be confused with pancreatic malignancy, which, if incorrectly diagnosed, would alter the management significantly.Figure 1.: Markedly Increased Interstitial Plasma Cells Seen on H&E stain (400x) on Renal Biopsy.Figure 2.: Immunohistochemistry Stain of Renal Biopsy Staining Positive for IgG 4.

Стан IgG4-позитивних плазматичних клітин у слизовій оболонці товстої кишки при хронічних запальних захворюваннях кишечника

Мета роботи: вивчити стан IgG4-позитивних плазматичних клітин у слизовій оболонці товстої кишки в пацієнтів із встановленим морфологічним і ендоскопічним діагнозом неспецифічного виразкового коліту (НВК) та хвороби Крона (ХК). Матеріали та методи. У дослідженні був використаний біопсійний матеріал від 14 пацієнтів із встановленим морфологічним і ендоскопічним діагнозом НВК (8 хворих) і ХК (6 хворих) у стадії загострення, які проходили лікування в Інституті гастроентерології, у відділенні захворювань кишечника. Наявність автоімунного панкреатиту I і II типу була критерієм виключення. Гістологічні препарати виготовляли стандартним методом, забарвлювали гематоксиліном та еозином. Для імуногістохімічного дослідження використовували моноклональні IgG4-антитіла (Abcam, США). Результати. Отримані результати свідчать про те, що при НВК у 37,5 % випадків не були виявлені IgG4-позитивні плазматичні клітини в слизовій оболонці товстої кишки, у 25 % випадків визначені поодинокі IgG4-позитивні плазматичні клітини, у 37,5 % виявлено групи IgG4-позитивних плазматичних клітин, але не більше 5 клітин в одній групі. При ХК спостерігались групи IgG4-позитивних плазматичних клітин, що складаються з 10 або більше клітин. Висновки. При НВК IgG4-позитивні плазматичні клітини можуть бути відсутніми, а також можуть бути поодинокими або зібрані в невеликі групи до 5 клітин у кожній. При ХК спостерігаються групи, що складаються з 10 і більше IgG4-позитивних плазматичних клітин.

Efficacy and safety of rituximab in autoimmune pancreatitis type 1: our experiences and systematic review of the literature

Introduction Autoimmune pancreatitis (AIP) is a special form of pancreatitis that responds well to glucocorticoid (GC) treatment. Relapses of AIP are common. The anti-CD20 antibody rituximab (RTX) has shown promising results in GC refractory cases, but long-term data are scarce. The study aims to determine the clinical and imaging response to RTX and summarize the existing data on RTX therapy in patients with AIP type 1 in the literature. Patients and methods Retrospective analysis of electronic medical records was conducted. Additionally, we conducted a systematic review of the literature concerning RTX use in AIP type 1. Results Twelve (11.7%) of 103 patients with AIP type 1 were treated with RTX during the study period: eight (66.7%) achieved complete and four (33.3%) partial remission. RTX was discontinued in one patient who developed fever and reactivation of latent tuberculosis. None of the remaining 11 patients relapsed during a median follow-up of 17 months. No significant differences were detected in baseline clinical characteristics or history of relapse between the patients who obtained complete and partial remission. Altogether, eight studies with 110 AIP type-1 patients treated with RTX were analyzed. Adverse effects ranged from 11–43% and the relapse-free period during follow-up (range 2–173 months) ranged from 38–94%. Conclusions Our results confirm that RTX is efficacious in the treatment of AIP type 1 by inducing remission and preventing relapse. In addition, there are few adverse effects of the treatment.

Imonoglobulin G4 asociované onemocnění v gastroenterologii

IgG4-related disease is a recently defined clinical entity that can manifest itself in any organ. The most common gastrointestinal manifestations are diseases of the pancreas (autoimmune pancreatitis type 1) and biliary tree (IgG4-associated cholangitis); involvement of liver parenchyma is uncommon and the affection of tubular organs is very rare. IgG4-related pancreatitis and cholangitis can mimic malignancies in their clinical presentation. Diagnosis is often difficult and requires careful evaluation of the combination of symptoms, serology and imaging findings, while adhering to the established diagnostic criteria. The first line of treatment is the administration of corticoids and the remission is achieved in the vast majority of patients. In case of contraindication, intolerance or failure of corticotherapy, patients should receive B cell depletion therapy (rituximab). Based on the available knowledge, monotherapy with other immunosuppressants is not considered to be sufficiently effective. Some patients may benefit from maintenance treatment to prevent relapse, which is otherwise common in both IgG4-related pancreatitis and cholangitis. Recognized IgG4-related disease has a good prognosis, but some patients develop irreversible fibrotic changes in the affected organ with consequent dysfunction; the possible association of the disease with a higher risk of malignancy has not yet been reliably elucidated.

A case of recurrent pancreatitis with subclavain artery stenosis: a clinical dilemma (unrelated co-existence or IgG4 related disease?) and a clinical lesson

We report a case of a 56-year-old woman who presented with clinical features suggestive of acute pancreatitis. She had a similar episode 5 years ago. A blood pressure (BP) recording of 80/50 mmHg in the presence of acute pancreatitis led to the diagnosis of circulatory shock and vasopressors were about to be commenced. However, her overall appearance was stable and measurement of BP in the lower limbs was normal. An angiogram revealed left subclavian artery stenosis which explained the low BP reading on left arm. The patient responded to conservative management of pancreatitis, however refused further evaluation of subclavian stenosis. This case is being reported to highlight a clinical dilemma and a clinical lesson. Dilemma arises if the pancreatitis and subclavian artery stenosis is just a coincidental occurrence or it is a case of IgG4 related disease consisting of autoimmune pancreatitis (AIP) type 1 with subclavian artery stenosis a part of extra-pancreatic manifestation of the IgG4 related disease spectrum. This distinction is important in management of pancreatitis and other organ involvement. It is important to examine a patient fully and especially the vascular system - wherein all pulses are to be felt and blood pressure recorded in both sides and both limbs - whenever there is a conflict between the condition/appearance of the patient and the signs that we elicit. In this case recognising that BP was normal in the lower limbs prevented unnecessary use of vasopressors.

Pancreatic cancer in patients with autoimmune pancreatitis: A scoping review

BackgroundChronic pancreatitis is a known risk factor of pancreatic cancer (PDAC). A similar association has been suggested but not demonstrated for autoimmune pancreatitis (AIP). ObjectiveThe aim of our study was to identify and analyse all published cases of AIP and PDAC co-occurrence, focusing on the interval between the diagnoses and the cancer site within the pancreas. MethodsRelevant studies were identified through automatic searches of the MEDLINE, EMBASE, Scopus, and Web of Science databases, and supplemented by manual checks of reference lists in all retrieved articles. Missing/unpublished data were obtained from the authors of relevant publications in the form of pre-prepared questionnaires. ResultsA total of 45 cases of PDAC in AIP patients were identified, of which 12 were excluded from the analysis due to suspicions of duplicity or lack of sufficient data. Thirty-one patients (94%) had type 1 AIP. Synchronous occurrence of PDAC and AIP was reported in 11 patients (33%), metachronous in 22 patients (67%). In the metachronous group, the median period between diagnoses was 66.5 months (2–186) and a majority of cancers (86%) occurred more than two years after AIP diagnosis. In most patients (70%), the cancer originated in the part of the pancreas affected by AIP. ConclusionsIn the literature, there are reports on numerous cases of PDAC in AIP patients. PDAC is more frequent in AIP type 1 patients, typically metachronous in character, and generally found in the part of the pancreas affected by AIP.

Discriminant equation using mucosally expressed cytokines and transcription factor for making definite diagnosis of inflammatory bowel disease unclassified

BackgroundThe pathological conditions of UC and CD involved in inflammatory bowel disease-unclassified (IBD-U), UC with primary sclerosing cholangitis (PSC-UC), and UC with autoimmune pancreatitis type 2 (AIP-UC) remain unclear. Therefore, it is difficult to decide the appropriate treatments for these subtypes of UC. Our aim was to examine whether the discriminant equation using the mucosally expressed mediators designed as our previous study for IBD, could characterize IBD-U, PSC-UC, or AIP-UC.MethodsA total of 56 patients including UC (n = 24), CD (n = 15), IBD-U (n = 10), PSC-UC (n = 4), and AIP-UC (n = 3), along with 9 control patients were enrolled in this study. Mucosally expressed inflammatory mediators related to Th1, Th2, Th17, and Treg were measured using quantitative PCR in endoscopic biopsies from the inflamed intestines of the patients. The IBD-U, PSC-UC or AIP-UC were characterized using discriminant analysis and principle component analysis.ResultsThrough discriminant analyses, combinations of 3 to 7 inflammatory mediators were used to discriminate between UC and CD. Moreover, the identified 3 markers could diagnose patients with IBD-U as UC or CD with high accuracy. The distribution graph of inflammatory mediators using the principal component analysis revealed that PSC-UC and AIP-UC exhibited CD-like and UC-like features, respectively.ConclusionsThe discriminant equation using mucosally expressed mediators of IL-13, IL-21 and T-bet can be used as a universal diagnostic tool not only for IBD-U but also to assess pathological conditions in PSC-UC and AIP-UC.

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.

Diagnostic and therapeutic considerations in biopsy-proven type 2 autoimmune pancreatitis: comparative analysis with biopsy-proven type 1 autoimmune pancreatitis.

Autoimmune processes are now an increasingly recognized cause of acute and chronic pancreatitis. Autoimmune pancreatitis is a rare, benign pathology with two distinct clinicopathologic subtypes. The aim of this study was to compare the presentation, diagnostic considerations and outcomes of patients with biopsy-proven type 1 and 2 autoimmune pancreatitis (AIP). A retrospective review of the Queensland Health pathology database of histologically proven AIP was conducted. Parameters compared included demographics, diagnostic criterion and post-treatment outcomes. Twenty-three patients had a confirmed histological diagnosis of AIP (type 1=13, type 2=10). Patients with type 2 AIP were younger (median age 49 versus 59 years, P< 0.05). There was no significant difference in gender distribution of disease at presentation. Type 2 AIP presented with significant increased focal pancreatic changes on cross-sectional imaging (80% versus 54%, P< 0.05). Serum IgG4 levels were raised (>1.40 g/L) in 69% of patients with type 1 AIP and not detected in type 2 (P< 0.01). Concurrent underlying inflammatory bowel disease was present in a higher proportion of type 2 AIP (40% versus 15%, P< 0.05). A significantly increased proportion of patients with type 2 AIP underwent surgical resection (70% versus 30%, P< 0.05). Conservative management was utilized in more patients with type 1 disease (54% versus 30%). On follow-up, two patients have experienced symptomatic relapse at 6-18 months. Diagnostic challenges do exist and clinicians must suspect 2 type AIP in young, serum IgG4-negative inflammatory bowel disease patients with recurrent pancreatitis.

Role of Endoscopic Ultrasonography-Guided Fine Needle Aspiration/Biopsy in the Diagnosis of Autoimmune Pancreatitis

Type 1 autoimmune pancreatitis (AIP) is histologically characterized by lymphoplasmacytic sclerosing pancreatitis (LPSP). Recently, the diagnostic yield of endoscopic ultrasonography-guided fine needle aspiration/biopsy (EUS-FNA/B) for AIP has been reported. However, its role in the diagnostic flow of AIP is not fully elucidated. We retrospectively reviewed 53 consecutive patients who were suspected with AIP and underwent EUS-FNA/B. We evaluated the contribution of EUS-FNA/B to the diagnosis of AIP before considering response to steroid therapy among patients with diffuse enlargement of the pancreas and those with focal enlargement, respectively. Twenty-two patients showed diffuse pancreatic enlargement and 31 showed focal enlargement. The final diagnosis was definitive AIP in 32 patients, probable AIP in 2, possible AIP in 1, and mass-forming focal pancreatitis in 18. There was no change in diagnosis after EUS-FNA/B among patients with diffuse pancreatic enlargement, while diagnosis changed in 38.7% (12/31) among those with focal enlargement—there was a probable to definitive diagnosis in 4 patients, unspecified to definitive in 3, and unspecified to probable in 5. EUS-FNB provided a significantly higher sensitivity for typical pathological findings of LPSP than EUS-FNA, and 10 patients were diagnosed as pathologically definitive AIP by EUS-FNB, though none were by EUS-FNA (p = 0.002). EUS-FNA/B was useful in the diagnosis of focal type AIP, and steroid therapy could be introduced after the diagnosis was confirmed. Meanwhile, EUS-FNA/B provided no contribution to diagnosis of diffuse type AIP. EUS-FNB showed a higher diagnostic yield than FNA.

Cardiovascular and lung involvement in patients with autoimmune pancreatitis

Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated disease characterised pathologically by the infiltration of IgG4-bearing plasma cells into the involved organs. Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis with a heavy lymphocytic infiltration and two distinct histopathological subtypes, namely: lymphoplasmacytic sclerosing pancreatitis (AIP type 1) and idiopathic duct-centric pancreatitis (AIP type 2). Lung involvement and aortic involvement have been reported in 12% and 9% of patients with systemic IgG4-RD, respectively. In series including patients with AIP, both lung and aortic involvement were described in 2% of the patients. Most of the epidemiological data come from Japan, and there is a lack of information from Europe, especially the Scandinavian countries. Patients and methods: We performed a single-centre retrospective study on a prospectively collected cohort of patients diagnosed with AIP at the Department for Digestive Diseases at Karolinska University Hospital in Stockholm, Sweden, from 2004 to 2019. Demographic and clinical data were collected from the medical charts. Results: One hundred and thirty-three patients with AIP were analysed. Six patients were excluded because they lacked some of the clinical data relevant to the study. Demographic and clinical features of 127 patients were presented. There were 98 patients with AIP type 1-35 (35.7%) female and 63 (64.3%) male, with a mean age of 55.4 ± 18.2. Among them, 15 (15.3%) patients had lung and/or cardiovascular involvement-11 (11.2%) patients had lung involvement, 10 (10.2%) patients had cardiovascular involvement (six patients had both). Most of them (67.0%) had never smoked. The mean follow-up time of the patients with AIP type 1 was 49 months. Conclusions: Lung and/or cardiovascular involvement were diagnosed in 15 (15.3%) patients in our historical cohort of patients with AIP type 1. Most of the lung involvement was presented in the form of nodular lesions in the lungs, non-specific infiltrates, “ground-glass” appearance with pleura thickening, and effusion. Aortic involvement was a major form of vascular involvement in patients with AIP, as in previous published studies on patients with IgG4-RD.

Identification of serum IFN-\u03b1 and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

Prevalence of histological features resembling autoimmune pancreatitis in neoplastic pancreas resections.

Types 1 and 2 autoimmune pancreatitis (AIP) can mimic pancreatic neoplasia. Due to the small quantity of tissue in mass-targeted pancreas biopsies, inflammatory features may raise the differential of AIP. However, the frequency of AIP-like histology in neoplastic pancreas is not well characterised. Therefore, the specificity of inflammatory lesions on biopsy with respect to the diagnosis of AIP is uncertain. Neoplastic pancreas resections performed at our institution between 2008 and 2019 were retrospectively reviewed. Features of AIP types 1 and 2 were assessed in the non-neoplastic areas. If features of immunoglobulin (Ig)G4-associated AIP were seen, IgG4 immunohistochemistry was performed. We identified 163 neoplastic pancreas resections. Of these, 34 had one or more types of inflammatory lesions in non-neoplastic pancreatic tissue. Dense lymphoplasmacytic inflammation mimicking type 1 AIP was found in six cases with mild to moderately increased IgG4-positive plasma cells. Neutrophilic infiltrates in small intralobular ducts were found in 20 cases. Mild extralobular ductitis or duct microabscess was found in 10 specimens. Marked neutrophilic duct destruction that resembled granulocytic epithelial lesions was found in 12 cases. Some cases showed multiple features. Approximately 20% of neoplastic pancreas resections showed focal areas that could raise the differential of AIP. More cases showed neutrophilic predominant inflammation as seen in type 2 autoimmune pancreatitis, compared to dense lymphoplasmacytic infiltrates seen in type 1 AIP. Pathologists must be cautious when making a diagnosis of AIP on biopsy tissue based on histological findings alone.

Focal pancreatic lesions in autoimmune pancreatitis and weight loss

A 67-year-old male patient was admitted to hospital with upper abdominal pain, jaundice and pale stool for 2 weeks. Laboratory investigation showed highly elevated cholestatic parameters and transaminases but no...

Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency.

Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice. The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy. Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy. One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%. In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

Immunoglobulin G subtypes-1 and 2 differentiate immunoglobulin G4-associated sclerosing cholangitis from primary sclerosing cholangitis.

BackgroundAutoimmune pancreatitis is a special form of chronic pancreatitis with strong lymphocytic infiltration and two histopathological distinct subtypes, a lymphoplasmacytic sclerosing pancreatitis and idiopathic duct centric pancreatitis. Immunoglobulin G4-associated cholangitis may be present at the time of autoimmune pancreatitis type 1 diagnosis or occur later over the course of the disease. Immunoglobulin G4 is considered reliable but not an ideal marker for diagnosis of autoimmune pancreatitis type 1 with reported sensitivity between 71–81%. It is essential to differentiate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis as the treatment and prognosis of the two diseases are totally different. It was the aim of the study to find a marker for immunoglobulin G4-associated cholangitis that would distinguish it from primary sclerosing cholangitis.Patients and methodsWe performed a retrospective analysis of patients with autoimmune pancreatitis at our outpatient clinic. Patients from the primary sclerosing cholangitis registry were taken as a control group. Blood samples for the measurement of immunoglobulin subclasses were analysed at the time of diagnosis.ResultsPatients with autoimmune pancreatitis and immunoglobulin G4-associated cholangitis had higher values of immunoglobulin G2 when compared to autoimmune pancreatitis alone or primary sclerosing cholangitis with a high specificity (97%) and high positive predictive value (91%). In patients with normal or low immunoglobulin G2 or immunoglobulin G4, a high level of immunoglobulin G1 indicated primary sclerosing cholangitis.ConclusionImmunoglobulin G1 and immunoglobulin G2 can distinguish patients with immunoglobulin G4-associated cholangitis from those with primary sclerosing cholangitis.