International Consensus Diagnostic Criteria Research Articles

A Case of IgG 4 Seronegative Type I Autoimmune Pancreatitis

Introduction IgG related diseases (IgG4-RD) are rather distinct autoimmune gastrointestinal conditions including autoimmune pancreatitis (AIP) and sclerosing cholangitis. Patients present with organomegaly or mass, lymphadenopathy, obstructive jaundice and weight loss. The most common extra-pancreatic finding of Type 1 AIP is IgG4 Sclerosing Cholangitis which resembles Primary Sclerosing Cholangitis or cholangiocarcinoma. Case 67 y.o male with PMH of GERD, presented with 2 wk H/O generalized abdominal discomfort, weight loss, fatigue and painless jaundice. Physical Exam: Vitals WNL and positive scleral icterus. Elevated LFTs, bilirubin and Ca 19-9 were detected with normal CEA. Total IgG: 12.9 and IgG4: 0.67. Autoantibody screen negative. CT Abd/pelvis showed mediastinal lymphadenopathy, bulky pancreatic head along with tiny foci of calcifications throughout and evidence of intra and extra-hepatic biliary dilatation. MRCP showed widespread intra-hepatic duct dilatation suggestive of PSC. ERCP showed 3cm stricture in CBD and biliary stricture involving both right and left hepatic ducts. Biopsy ruled out malignancy. Patient showed clinical and lab normalization after steroid therapy which was confirmed by normal internal MRCP. Based on this clinical response and radiological evidence, a seronegative AIP with extra-pancreatic IgG4 related SC was diagnosed. Discussion Type 1 AIP, the prototype of IgG4RD is prevalent worldwide, typically affecting middle aged and older men. Sensitivity and specificity of seropositive AIP have been found to be as low as 62% and 59% respectively and studies show IgG4 seronegativity in as many as 24% cases. Despite lack of serological and histological evidence, AIP with IgG4 related SC can still be diagnosed based on history, imaging and therapeutic response as also suggested by International Consensus Diagnostic Criteria (ICDC). Conclusion: This case stresses the advantage of timely identification and treatment of seronegative IgG4 AIP and SC. Normal IgG4 levels and lack of definite histology shouldn't exclude the diagnosis when there are characteristic clinical findings and extra-pancreatic manifestations, along with distinctive imaging results. It is imperative to treat patients with steroid trial and close clinical monitoring to avoid unnecessary pancreatobiliary procedures.

Microscopic findings in EUS-guided fine needle (SharkCore) biopsies with type 1 and type 2 autoimmune pancreatitis.

The International Consensus Diagnostic Criteria (ICDC) for the diagnosis of autoimmune pancreatitis (AIP) include the histological criterion that is based on either pancreatic core needle biopsies (CNBs) or surgical specimens. However, CNBs are difficult to obtain by endoscopic ultrasound (EUS). EUS fine-needle aspiration (EUS-FNA) cytology is usually not sufficient for the diagnosis of AIP, but may sometimes contain tissue microfragments. Another approach is EUS-guided histological fine-needle biopsy (EUS-FNB), using needles such as the SharkCore or ProCore needle. Published data regarding EUS-guided SharkCore FNB for the diagnosis of AIP are lacking. We aimed to describe our histological findings in one type 1 and two type 2 AIP patients who underwent EUS SharkCore FNB. The EUS-FNBs of two patients fulfilled the histological level 2 ICDC for type 1 AIP or type 2 AIP. The EUS-FNB of one patient fulfilled the histological level 1 ICDC for type 2 AIP. The tissue cylinders and fragments measured 55, 28 and 17 mm in total. At least histological level 2 ICDC were fulfilled in all cases, and our findings regarding the utility of EUS SharkCore FNB for the diagnosis of AIP are therefore promising, but further studies based on larger numbers of patients are warranted.

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases

Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features ofpatients with IBD with and without AIP in a case-control analysis, using multivariate analysis. We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P= .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P= .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P=.023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P= .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P= .0029). In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.

Diagnosis of Autoimmune Pancreatitis: The Evolution of Diagnostic Criteria for a Rare Disease

Diagnosis of Autoimmune Pancreatitis: The Evolution of Diagnostic Criteria for a Rare Disease

Type 1 (IgG4‐related) autoimmune pancreatitis: Experiences in a medical center in southern Taiwan within the past 10 years

SummaryBackgroundsAutoimmune pancreatitis (AIP) is a relatively rare disease and has similar presentations to pancreatic cancer. There are limited reports about this disease in Taiwan.MethodsWe retrospectively reviewed 14 cases of type 1 AIP from March 2007 to March 2016 in Kaohsiung Veterans General Hospital. The diagnosis was made according to the international consensus diagnostic criteria (ICDC) for AIP.ResultsThere were 12 male and two female patients diagnosed with type 1 AIP, with a mean age of 63.6 (33 – 88) years. The rates of DM and HTN were 28.5% and 35.7%, respectively. The clinical presentations were mainly weight loss, epigastric pain, and obstructive jaundice. Most patients didn't have the habits of cigarette smoking or drinking alcohol. Minority of these patients had leukocytosis but the majority of them had anemia. All patients had a normal range of platelet count. Most patients had elevation of alanine transaminase, alkaline phosphatase or lipase. Serum immunoglobulin G (IgG) or IgG4 tests were done in most cases, and high‐up levels were seen in most of them. Six of them had an upraised CA 19‐9. All patients had a normal range of coagulation profiles (prothrombin time and activated partial thromboplastin time). Diffuse or focal swellings of the pancreas were observed from CT or MRI among different patients. Six of them had pathology evidence. Three of them received Whipple's operation. Seven of them underwent ERCP. Four of them received PTCD. Two of them received PTGBD. Corticosteroids were prescribed to all patients after the diagnosis of AIP except of that one lost to follow‐up. There were eight patients taking steroid only and five taking steroid in combination with another immunomodulator.ConclusionsType 1 AIP has several common features with pancreatic cancer so accurate diagnosis is important to avoid unnecessary operation. The diagnosis involves clinician's alertness and several diagnostic modalities, including serology, radiology and pathology. Though steroid is effective for type 1 AIP, the relapse rate is high. longterm follow‐up is required. Several clinical features in this study are different from those in other reports and further study is still required for investigation.Copyright © 2017, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.

A Comparison of DSM-IV and international expert consensus diagnostic criteria for N.M.S

IntroductionNeuroleptic malignant syndrome (NMS) requires prompt recognition for effective management, but there are no established diagnostic criteria.ObjectivesTo validate the recently published international expert consensus (IEC) diagnostic criteria for NMS, which assign priority points based on the relative importance of each criterion for diagnosing NMS.AimsDetermine optimal diagnostic cutoff for priority point score.MethodsData were extracted from 221 archived telephone contact reports of clinician-initiated calls to a national telephone consultation service from 1997–2009; each case was given a total priority point score based on the IEC criteria. DSM-IV-TR research criteria, in original form and modified to accept less than ‘severe’ rigidity, served as the primary diagnostic reference standard. Consultants’ diagnoses served as an additional reference standard. The optimal priority point cutoff score was determined using receiver operating characteristic (ROC) curve analysis.ResultsArea under the ROC curve ranged from 0.715 (95% CI = 0.645–0.785, P < 0.001) for consultant diagnoses to 0.857 (95% CI = 0.808–0.907, P < 0.001) for modified DSM-IV-TR criteria. The latter was associated with 69.6% sensitivity and 90.7% specificity.ConclusionsAgreement was best between IEC criteria with a cutoff score of 74 and modified DSM-IV-TR criteria (sensitivity 69.6%, specificity 90.7%); this cutoff score demonstrated the highest agreement in all comparisons. Consultant diagnoses showed much better agreement with modified, compared to original, DSM-IV-TR criteria, suggesting that the DSM-IV-TR criterion of “severe” rigidity may be more restrictive than what most knowledgeable clinicians use in practice.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria

Background/ObjectivesWe had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. MethodsFrom 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). ResultsOverall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p < 0.05, McNemar test). In the Pancreas-Outpatient-Clinic-Cohort, seven patients were diagnosed with AiP (n = 6 by U-AIP, n = 1 by Asian-criteria). International-Consensus-Diagnostic-Criteria confirmed the diagnosis in these individuals. Based on partial fulfillment of U-AIP, AiP was initially suspected in 13% (n = 10/77) of remaining patients from the Pancreas-Outpatient-Clinic-Cohort. In the Surgical-cohort, we identified one patient with AiP by U-AIP and ICDC. ConclusionsUnifying-Autoimmune-Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP.

Neuromyelitis Optica Spectrum Disorders.

Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and transverse myelitis, but recent studies with anti-aquaporin-4-antibody specific to NMO have revealed that the clinical spectrum is wider than previously thought. International consensus diagnostic criteria propose NMO spectrum disorders (NMOSD) as the term to define the entire spectrum including typical NMO, optic neuritis, acute myelitis, brain syndrome, and their combinations. NMOSD is now divided into anti-aquaporin-4-antibody-seropositive NMOSD and -seronegative NMOSD (or unknown serostatus). MR imaging and optical coherence tomography are indispensable in the diagnosis and evaluation of NMOSD. This article reviews the clinical and MR imaging findings of anti-aquaporin-4-antibody-seropositive and anti-myelin oligodendrocyte glycoprotein-antibody-seropositive NMOSD.

A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome.

Neuroleptic malignant syndrome requires prompt recognition for effective management, but there are no established diagnostic criteria. This is the first validation study of recently published international expert consensus (IEC) diagnostic criteria, which include priority points assigned on the basis of the importance of each criterion for making a diagnosis of neuroleptic malignant syndrome. Data were extracted from 221 archived telephone contact reports of clinician-initiated calls to a national telephone consultation service from 1997 to 2009; each case was given a total priority point score on the basis of the IEC criteria. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, (DSM-IV-TR) research criteria, in original form and modified to accept less than "severe" rigidity, served as the primary diagnostic reference standard. Consultants' diagnostic impressions were used as a secondary reference standard. Receiver operating characteristic curve analysis was used to optimize the priority point cutoff score with respect to the reference standards. Area under the receiver operating characteristic curve ranged from 0.715 (95% confidence interval, 0.645-0.785; P = 1.62 × 10) for consultant diagnoses to 0.857 (95% confidence interval, 0.808-0.907; P < 5 × 10) for modified DSM-IV-TR criteria. The latter was associated with 69.6% sensitivity and 90.7% specificity. Agreement was best between IEC criteria with a cutoff score of 74 and modified DSM-IV-TR criteria (sensitivity, 69.6%; specificity, 90.7%); this cutoff score demonstrated the highest agreement in all comparisons. Consultant diagnoses showed much better agreement with modified, compared with original, DSM-IV-TR criteria, suggesting that the DSM-IV-TR criterion of "severe" rigidity may be more restrictive than what most knowledgeable clinicians use in practice.

Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia.

BackgroundMicroRNAs (miRs) are small non‐coding RNAs that regulate gene (mRNA) expression. Although the pathological role of miRs have been studied in muscle wasting conditions such as myotonic and muscular dystrophy, their roles in cancer cachexia (CC) are still emerging.ObjectivesThe objectives are (i) to profile human skeletal muscle expressed miRs; (ii) to identify differentially expressed (DE) miRs between cachectic and non‐cachectic cancer patients; (iii) to identify mRNA targets for the DE miRs to gain mechanistic insights; and (iv) to investigate if miRs show potential prognostic and predictive value.MethodsStudy subjects were classified based on the international consensus diagnostic criteria for CC. Forty‐two cancer patients were included, of which 22 were cachectic cases and 20 were non‐cachectic cancer controls. Total RNA isolated from muscle biopsies were subjected to next‐generation sequencing.ResultsA total of 777 miRs were profiled, and 82 miRs with read counts of ≥5 in 80% of samples were retained for analysis. We identified eight DE miRs (up‐regulated, fold change of ≥1.4 at P < 0.05). A total of 191 potential mRNA targets were identified for the DE miRs using previously described human skeletal muscle mRNA expression data (n = 90), and a majority of them were also confirmed in an independent mRNA transcriptome dataset. Ingenuity pathway analysis identified pathways related to myogenesis and inflammation. qRT‐PCR analysis of representative miRs showed similar direction of effect (P < 0.05), as observed in next‐generation sequencing. The identified miRs also showed prognostic and predictive value.ConclusionsIn all, we identified eight novel miRs associated with CC.

Clinical significance of hypoechoic submandibular gland lesions in type 1 autoimmune pancreatitis.

AIMTo assess the role of ultrasonography of submandibular glands (SGs) in the diagnosis of type 1 autoimmune pancreatitis (AIP).METHODSThirty-seven patients who were definitively diagnosed with type 1 AIP according to the international consensus diagnostic criteria (ICDC) for AIP at our institution between December 1990 and April 2016 were retrospectively reviewed. Findings by physical examination, ultrasonography, and scintigraphy of SGs were analyzed to reach a diagnosis based on the ICDC for AIP. The efficacy of corticosteroid treatment in the resolution of hypoechoic lesions in SGs was also evaluated by assessment with ultrasonography before and after treatment in 18 cases.RESULTSThe sensitivity of multiple hypoechoic lesions in SGs by ultrasonography for the diagnosis of sialadenitis in type 1 AIP (84%) was higher than that of physical examination (46%), scintigraphy (28%), and SGs thickness (49%). Ultrasonographic evidence of hypoechoic lesions in SGs improved the definitive diagnosis of sialadenitis and type 1 AIP by the ICDC criteria in 11 (30%) and 2 (5.4%) cases, respectively. Multiple hypoechoic lesions in SGs were resolved or disappear by corticosteroid administration in 14 of 16 cases with hypoechoic lesions in SGs, whereas the ultrasonographic findings in the remaining 2 cases with hypoechoic lesions in SGs and the 2 cases with homogenous SG parenchyma remained unchanged after corticosteroid administration.CONCLUSIONSG ultrasonography to detect multiple hypoechoic lesions might be useful for type 1 AIP diagnosis by improving diagnostic accuracy together with the ICDC sialadenitis criteria.

From Pathogenesis, Clinical Manifestation, and Diagnosis to Treatment: An Overview on Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis which is autoimmune mediated. The international consensus diagnostic criteria (ICDC) 2011 proposed two types of AIP: type I is associated with histological pattern of lymphoplasmacytic sclerosing pancreatitis (LPSP), characterized by serum IgG4 elevation, whereas type 2 is named idiopathic duct-centric pancreatitis (IDCP), with granulocytic epithelial lesion (GEL) and immunoglobulin G4 (IgG4) negative. The pathogenic mechanism is unclear now; based on genetic factors, disease specific or related antigens, innate and adaptive immunity may be involved. The most common clinical manifestations of AIP are obstructive jaundice and upper abdominal pain. The diagnosis can be made by a combination of parenchymal and ductal imaging, serum IgG4 concentrations, pancreatic histology, extrapancreatic disease, and glucocorticoid responsiveness according to ICDC 2011. Because of the clinical and imaging similarities with pancreatic cancer, general work-up should be done carefully to exclude pancreatic malignant tumor before empirical trial of glucocorticoid treatment. Glucocorticoid is the most common drug for AIP to induce remission, while there still exists controversy on steroid maintenance and treatment for relapse. Further studies should be done to identify more specific serum biomarkers for AIP, the pathogenic mechanisms, and the treatment for relapse.

There is less MRI brain lesions and no characteristic MRI Brain findings in IIDDs patients with positive AQP4 serology among Malaysians

Background and objectiveThe recently introduced International Consensus diagnostic criteria for diagnosis of neuromyelitis spectrum disorder include patients who are seronegative for AQP4 antibody. The criteria are dependent on typical MRI changes in the spinal cord, optic nerve and brain. This study aims to determine whether there are significant differences in the MRI brain images between AQP4 positive and negative patients with IIDDs. MethodMRI brain of patients with a diagnosis of IIDDs presented to the Hospital from 2010 to 2015 was analysed. The MRI was assessed by 2 radiologists blinded to the AQP4 status, on features said to be typical of NMOSD and MS. ResultsThirty nine patients fulfilled the criteria and were included in the study. They consisted of 19 AQP4 seropositive and 20 AQP4 seronegative patients. The mean age was older (37.0 vs. 28.8 years) among the AQP4 positive group. The majority of the patients were ethnic Chinese (72%), followed by the Malays and Indians. Those with AQP4 seropositive status generally has less brain lesions, and significantly less fulfilling the McDonald DIS criteria as compared to those with AQP4 seronegative status (15.8% vs. 60.0%, p=0.005).None of the seven cerebral MRI features highlighted in NMOSD 2015 diagnostic criteria, said to be characteristic of NMOSD was more common among the AQP4 positive patients. These features were in fact seen less frequently among the AQP4 seropositive patients. An example was the extensive hemispheric lesion seen in 10.5% of AQP4 seropositive patients vs. 45% of that AQP4 seronegative group. ConclusionThere was no characteristic MRI brain features in the Malaysian AQP4 seropositive IIDD patients versus those who are seronegative. This could be a reflection of ethnical difference.

International consensus for the treatment of autoimmune pancreatitis

Background and aimsThe International Consensus Diagnostic Criteria (ICDC) for AIP has proposed two distinctive type of AIP, type 1 and type 2, and enabled us first to differentiate two types of AIP each other. By initial steroid treatment for induction of remission, remission can be successfully induced in almost all subjects with type 1 and type 2 AIP. As relapse rate in type 1 AIP is significantly higher than in type 2 AIP, there has been ongoing debate on how to treat effectively relapse of type 1 AIP. MethodsBy a modified Delphi approach, a panel of international experts has proposed an international consensus on the treatment of AIP after intense discussion and deliberation during an international consensus symposium of the International Association of Pancreatology (IAP) 2016. ResultsIndividual statements for nine clinical questions with recommendation levels and the therapeutic strategy have been proposed. ConclusionThe recommendations are based on the available evidence, and eastern and western experts' opinions to find standard treatment of AIP worldwide. These recommendations can be tailored according to the local expertise and context in the management of individual patients.

Evolution of MRI abnormalities in paediatric acute disseminated encephalomyelitis.

Acute disseminating encephalomyelitis (ADEM) is an inflammatory demyelinating disease affecting the central nervous system and mainly occurs in young children. Children who initially presented with ADEM can be diagnosed with multiple sclerosis (MS) in case new non-encephalopathic clinical symptoms occur with new lesions on MRI at least three months after onset of ADEM. We aim to study the timing of MRI abnormalities related to the evolution of clinical symptoms in our Dutch paediatric ADEM cohort. The Dutch database for acquired demyelinating syndromes (ADS) was screened for children under age eighteen fulfilling the international consensus diagnostic criteria for ADEM. Children were eligible when the first MRI was performed within the first three months after onset of clinical symptoms and at least one brain follow-up MRI was available for evaluation. Forty-two children with ADEM were included (median age four years two months). All available MRIs and medical records were assessed and categorised as 'improved', 'deteriorated' and 'unchanged'. We found that during clinical recovery, new lesions and enlargement of existing MRI lesions occurred in the first three months in about 50% of the performed MRIs. In contrast, this was rarely seen more than three months after first onset of ADEM. We recommend to perform a brain MRI as a reference scan three months after onset. Follow-up imaging should be compared with this scan in order to prevent an incorrect diagnosis of MS after ADEM.

Resonancia magnética de la pancreatitis autoinmune: una revisión de la literatura

Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis caused by an autoimmune pathogenetic mechanism. It affects males (60%) slightly more frequently, and generally occurs between 40 to 60 years, although the possible range is much wider (14-80 years). Histologically AIP is characterised by the presence of a dense inflammatory infiltrate, with variable extension. It can be focal or diffuse throughout the whole pancreas. Clinical presentation in most cases is non-specific, with patients presenting with mild abdominal pain, rarely, acute pancreatitis symptoms, weight loss, and jaundice. Several studies reported multiple organ involvement due to the autoimmune process, suggesting a systemic nature of the disease.In 2011 the International Consensus Diagnostic Criteria for autoimmune pancreatitis (ICDC) defined the guidelines, and magnetic resonance imaging (MRI) and MR-cholangiopancreatography (MRCP) became the reference diagnostic technique in the diagnosis of the disease.This paper will review the imaging characteristics, the differential diagnosis, and the imaging features after treatment and follow up. Furthermore, our experience in this uncommon and challenging disease is reviewed

Current Concepts and Diagnosis of IgG4-Related Pancreatitis (Type 1 AIP).

Although now considered to be a member of the systemic entity of immunoglobulin G4- (IgG4-) related disease, IgG4-related pancreatitis is generally referred to as type 1 autoimmune pancreatitis (AIP). Type 1 AIP was established based on a pathological background of lymphoplasmacytic sclerosing pancreatitis, high serum IgG4 concentration, and abundant IgG4-bearing plasma cell infiltration. The characteristic clinical features of type 1 AIP, such as elderly male preponderance, obstructive jaundice, and mass-forming lesions in the pancreas, often mimic those of pancreatic cancer. However, because AIP responds favorably to corticosteroid treatment, careful differentiation from pancreatic cancer is required. An AIP diagnosis is currently based on the 2011 International Consensus Diagnostic Criteria for AIP, which are based on high sensitivity, selectivity, and accuracy. Over the long term, AIP can progress to a chronic condition, with pancreatic stone formation and atrophy resembling that of chronic pancreatitis. Although AIP has been linked to the complication of malignancies, it remains controversial whether an association exists between the disease and tumor formation.

Autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids.

Diagnosis of autoimmune pancreatitis by EUS-guided FNA using a 22-gauge needle: a prospective multicenter study.

Histopathologic examination is critical for diagnosing autoimmune pancreatitis (AIP). However, specimens obtained using EUS-guided FNA (EUS-FNA) are not recommended for histopathologic diagnosis because of inadequate sample size volume. We evaluated EUS-FNA efficacy for AIP diagnosis using a 22G needle. Seventy-eight patients exhibiting the imaging characteristics indicative of AIP in the pancreatic parenchyma and pancreatic duct underwent EUS-FNA with a 22G needle at 12 institutions between February 2013 and March 2014. Samples were evaluated for tissue sampling conditions, CD38- and IgG4-positive plasma cell counts, storiform fibrosis (SF), and obliterative phlebitis (OP). Tissue specimens containing >10, 5 to 10, and 1 to 4 high-power fields (HPFs) were obtained from 29(37.2%), 18 (23.1%), and 15 (19.2%) of 78 patients, respectively. The mean ± standard deviation (SD) CD38- and IgG4-positive plasma cell counts were 23.2 ± 18.8/HPF and 5.1 ± 6.7/HPF, respectively. SF was detected in 49 of 78 patients (62.8%) and OP in 38 of 78 patients (48.7%). According to the International Consensus Diagnostic Criteria (ICDC), histopathologic levels corresponded to level 1 in 32, level 2 in 13, and unclassifiable in 17 patients. Hence, 45 of 78 patients (57.7%) could be diagnosed with lymphoplasmacytic sclerosing pancreatitis according to ICDC. Pancreatic tissues with at least 1 HPF were obtained by EUS-FNA from approximately 80% of patients, and nearly 60% of patients were diagnosed with ICDC level 2 or higher. Our findings indicate that EUS-FNA with a 22G needle may be useful for the histopathologic diagnosis of AIP. (Clinical trial registration number: UMIN000010097.).

Outcome of Long-term Maintenance Steroid Therapy Cessation in Patients With Autoimmune Pancreatitis: A Prospective Study.

To predict the duration of steroid maintenance therapy required to achieve good prognosis in patients with autoimmune pancreatitis. The study sample comprised 21 patients with autoimmune pancreatitis who met the following criteria: (1) they received steroid therapy (ST) for at least 3 years without clinical relapse; and (2) immunoglobulin (Ig) G<1600 mg/dL was observed in the past year with a prednisolone maintenance dose ≤5 mg. All patients could be diagnosed with international consensus diagnostic criteria. Patients were prospectively followed up after tapering and cessation of steroids. Clinical relapse was defined as the need to resume ST. Serological relapse was defined as having an IgG level of >1600 mg/dL. During the 43-month (range, 19 to 48 mo) follow-up period, clinical relapse occurred in 10 patients: pancreatic lesion in 4; coronary lesion in 2; submandibular lesion in 1; both pulmonary and renal lesions in 1; pulmonary, retroperitoneal, and submandibular lesions in 1; and bronchial asthma in 1. Serological relapse was observed in 12 patients. Although clinical and serological relapse occurred concomitantly in 3 patients, serological relapse preceded clinical relapse in 4 patients. Five patients experienced serological relapse alone, and no clinical or serological relapse occurred in 6 patients. According to Cox proportional hazard analysis, the duration of ST before tapering was a significant predictive parameter (hazard ratio, 0.969/month; 95% confidence interval, 0.940-0.998; P=0.038). ST cessation resulted in a high rate of clinical relapses, even in patients with long-term maintenance therapy. Therefore, it appears desirable to continue steroid maintenance therapy for a period >3 years to prevent relapse.