Clinical and pathophysiological issues associated with type 1 autoimmune pancreatitis

In 1995, Yoshida and colleagues proposed the concept of ‘autoimmune pancreatitis’ (AIP). Recently, it is accepted that the existence of two subtypes of AIP—type 1, which involves immunoglobulin G4 (IgG4) as the pancreatic manifestation of IgG4-related disease (IgG4-RD), and type 2, which is characterized by granulocytic epithelial lesions. Type 2 AIP is thought to be rare in Japan. In 2011, the International Consensus Diagnostic Criteria (ICDC) for autoimmune pancreatitis was proposed. In Japan, the clinical diagnostic criteria of AIP 2011 was proposed by the Japan Pancreas Society (JPS) and the Research Committee of Intractable Diseases of the Pancreas. The JPS 2011 is based on ICDC and a simplified checklist of items to diagnose type 1 AIP. Although recent progress in type 1 AIP has resolved clinical features, diagnosis, treatment, and pathogenesis, many clinical and basic issues still remain unclear. Here, we provide an overview of the recent clinical and basic issues associated with type 1 AIP.     

The role of EUS-guided fine needle aspiration in autoimmune pancreatitis: a single center prospective study

Abstract

Objectives: Histopathological examination is pivotal in diagnosing autoimmune pancreatitis (AIP). The usefulness of EUS-guided fine needle aspiration (EUS-FNA) in diagnosing AIP remains controversial worldwide. The authors conducted this study to evaluate the efficacy of EUS-FNA for AIP diagnosis using a 22-gauge needle.

Methods: Between January 2013 and May 2017, 37 patients had imaging studies suggestive of AIP at Tongji Hospital, and 27 patients of them were enrolled in this study. Tissue specimens acquired through EUS-FNA were analyzed for periductal lymphoplasmacytic infiltrate (LPI), storiform fibrosis (SF), obliterative phlebitis (OP) and immunoglobulin G4 (IgG4)-positive plasma cell counts. Clinical Trials.gov no: TJ-C20121220.

Results: LPI and SF were present in 18 (66.67%) and 18 (66.67%) of 27 patients, respectively. Abundant IgG4-positive plasmacyte infiltration >10/high-power field (HPF) was detected in 8 of 27 patients (29.63%). OP and the characteristic findings of idiopathic duct-centric chronic pancreatitis (IDCP) and granulocytic epithelial lesion (GEL) were not detected in this study. According to the International Consensus Diagnostic Criteria (ICDC) for AIP, 5 and 12 of 27 patients were assessed as having level 1 and level 2 histological findings, respectively, suggesting that 17 of 27 patients (62.96%) had lymphoplasmacytic sclerosing pancreatitis (LPSP) based on the ICDC.

Conclusions: In 92.6% of patients, pancreatic tissues with >5 HPFs were obtained by EUS-FNA using a 22-G needle. In 63% of patients, histology was evaluated to be?≥?level 2 according to the ICDC. The study indicates that EUS-FNA with a 22-G needle is valuable in the histopathological diagnosis of AIP.     

Intraductal papillary mucinous neoplasm of the pancreas and IgG4-related disease: A coincidental association

Background/aimsCoexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates.MethodsSerum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant.ResultsSerum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN.ConclusionsIn a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.     

A proposal of a diagnostic algorithm with validation of International Consensus Diagnostic Criteria for autoimmune pancreatitis in a Japanese cohort

BackgroundAmong many diagnostic criteria for autoimmune pancreatitis (AIP), the International Consensus Diagnostic Criteria (ICDC) first enabled us to diagnose and compare type 1 and type 2 AIP, which permitted tailoring individual diagnostic algorithms depending on local expertise. We compared them and validated ICDC with special reference to levels 1 and 2, and proposed a diagnostic algorithm for AIP in Japan.MethodsThe diagnostic sensitivity of 5 major criteria (ICDC, Korean, Japanese-2011, Asian, and HISORt criteria) was compared, using 61 patients with AIP. Fifty six patients with pancreatic cancer served as a control. Pancreas imaging on computed tomography (CT) and endoscopic retrograde pancreatography (ERP) were independently evaluated by 3 pancreatologists (5, 10, and 20 years of career experience) and each diagnostic criterion of ICDC was validated with special reference to levels 1 and 2.ResultsThe sensitivities of 5 major criteria were 95.1% (ICDC), 90.2% (Korean), 86.9% (Japanese), 83.6% (Asian), and 83.6% (HISORt) with 100% of specificity in each. In the evaluation of pancreas imaging, diagnostic sensitivities of combination with CT and ERP in segmental/focal type AIP were significantly higher than single imaging (26% in CT (P < 0.01) or 35% in ERP (P < 0.05) vs 63% in CT + ERP), but not significantly different in the diffuse type.ConclusionsOf the 5 criteria, ICDC is the most sensitive and useful for diagnosing AIP. We have proposed a diagnostic algorithm with CT for the diffuse type of AIP, and combination with CT + ERP followed by EUS-FNA for the segmental/focal type.     

Diagnosis,treatment and long-term outcomes of autoimmune pancreatitis in Spain based on the International Consensus Diagnostic Criteria: A multi-centre study

ObjectivesAutoimmune pancreatitis (AIP) is a form of chronic pancreatitis that has been reported worldwide for the last two decades. The aim of this study is to analyse the clinical profile of patients from Spain with AIP, as well as treatments, relapses and long-term outcomes.MethodsData from 59 patients with suspected AIP that had been diagnosed in 15 institutions are retrospectively analysed. Subjects are classified according to the International Consensus Diagnostic Criteria (ICDC). Patients with type 1 AIP (AIP1) and type 2 AIP (AIP2) are compared. Kaplan–Meier methodology is used to estimate the overall survival without relapses.ResultsFifty-two patients met ICDC, 45 patients were AIP1 (86.5%). Common manifestations included abdominal pain (65.4%) and obstructive jaundice (51.9%). Diffuse enlargement of pancreas was present in 51.0%; other organ involvement was present in 61.5%. Serum IgG4 increased in 76.7% of AIP1 patients vs. 20.0% in AIP2 (p = 0.028). Tissue specimens were obtained in 76.9%. Initial successful treatment with steroids or surgery was achieved in 79.8% and 17.3%, respectively. Maintenance treatment was given in 59.6%. Relapses were present in 40.4% of AIP1, with a median of 483 days. Successful long-term remission was achieved in 86.4%.ConclusionsAIP1 is the most frequent form of AIP in Spain in our dataset. Regularly, ICDC allows AIP diagnosis without the need for surgery. Steroid and chirurgic treatments were effective and safe in most patients with AIP, although maintenance was required many times because of their tendency to relapse. Long-term serious consequences were uncommon.     

Clinical features and relapse rates after surgery in type 1 autoimmune pancreatitis differ from type 2: A study of 114 surgically treated European patients

BackgroundAt the recent consensus conference on autoimmune pancreatitis (AIP) in Honolulu, we presented preliminary data from our study of surgically treated AIP patients. Our data strongly supported the separation of AIP into type 1 and type 2. Our study is based on a total of 114 surgically treated European AIP patients. Our aims were to elucidate serum IgG4 elevation, other organ involvement, relapse of disease, steroid treatment and diabetes after surgery in 114 surgically treated European AIP patients.Methods88 pancreaticoduodenectomies, 22 left-sided resections and 4 total pancreatectomies were examined. All cases were graded for granulocytic epithelial lesions, IgG4-positive cells, storiform fibrosis, phlebitis and eosinophilic granulocytes. Follow-up data were obtained from 102/114 patients, mean follow-up was 5.3 years.ResultsHistologically, 63 (55.3%) of the 114 patients fulfilled the criteria of type 1 AIP, while 51 (44.7%) patients fulfilled the criteria of type 2 AIP. Type 1 AIP patients were older and more often males than type 2 AIP patients. Elevation of serum IgG4, involvement of extrapancreatic organs, disease relapse, systemic steroid treatment and diabetes after surgery were noted more often in type 1 AIP, while inflammatory bowel disease (IBD) was observed mainly in type 2 AIP.ConclusionsHistological typing of AIP is clinically important because type 1 AIP is part of the IgG4-related disease and type 2 AIP is associated with IBD. Our data also show that relapse of disease and steroid treatment after surgery occur more frequently in type 1 than in type 2 AIP.     

Comparison of five-phase computed tomography images of type 1 autoimmune pancreatitis and pancreatic cancer: Emphasis on cases with atypical images

Background/objectivesInternational consensus diagnostic criteria (ICDC) include characteristic images of autoimmune pancreatitis (AIP); however, reports on atypical cases are increasing. The aims of this study were to compare CT findings between AIP and pancreatic cancer (PC), and to analyze type 1 AIPs showing atypical images.MethodsFive-phase CT images were compared between 80 type 1-AIP lesions and 80 size- and location-matched PCs in the case-control study. Atypical AIPs were diagnosed based on the four ICDC items.ResultsICDC items were recognized in most AIP lesions; pancreatic enlargement (87.7%), narrowing of the main pancreatic duct (98.8%), delayed enhancement (100%), and no marked upstream-duct dilation (97.5%). CT values of AIPs increased rapidly until the pancreatic phase and decreased afterward, while those of PCs gradually increased until the delayed phase (P < 0.0001). Atypical images were recognized in 14.8% of AIPs, commonly without pancreatic enlargement (18.5 mm) and sometimes mimicking intraductal neoplasms. The CT values and their ratios were different between atypical AIPs and size-matched PCs most significantly in the pancreatic phase, but similar in the delayed phase.ConclusionsOrdinary type 1 AIPs can be diagnosed with the ICDC, but atypical AIPs represented a small fraction. “Delayed enhancement” is characteristic to ordinary AIPs, however, “pancreatic-phase enhancement” is more diagnostic for atypical AIPs.     

The clinical utility of immunoglobulin G4 in the evaluation of autoimmune pancreatitis and pancreatic adenocarcinoma

Background

Elevation in the serum immunoglobulin-G4 (IgG4) level has been used as a diagnostic marker to distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), but its true utility is ill-defined. This study evaluates the clinical utility of IgG4 in differentiating AIP from PDAC.

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.     

A comparison of the diagnostic efficacy in type 1 autoimmune pancreatitis based on biopsy specimens from various organs

BackgroundComprehensive immunostaining evaluation of the biopsy specimens from various organs with type 1 autoimmune pancreatitis (AIP) has not been elucidated. Our aim was to clarify which of these biopsy specimens and counting method could be a useful tool for supporting the diagnosis of AIP.MethodsWe retrospectively evaluated biopsy specimens from pancreas (n = 19), stomach (n = 28), duodenum (n = 27), duodenal papilla (n = 25), colon (n = 19), liver (n = 11), bile duct (n = 24), and minor salivary gland (n = 13) in 36 patients with AIP. Positive IgG4 immunostaining (>10 plasma cells/high-power field [HPF]) and positive IgG4/IgG ratio (>40%) of biopsy specimens from 8 sites of 6 organs in one HPF and an average from 3 HPFs were compared between AIP and controls.ResultsThe sensitivity of IgG4 immunostaining for AIP in one HPF were 16% in pancreas, 14% in stomach, 15% in duodenum, 52% in duodenal papilla, 11% in colon, 27% in liver, 21% in bile duct and 8% in minor salivary gland, respectively. The positive IgG4 immunostaining of the duodenal papilla in one HPF showed the highest sensitivity (52%) and accuracy (73%) among the 8 sites. It also showed the highest sensitivity among 4 different counting methods (IgG4 immunostaining in one HPF and 3 HPFs, both IgG4 immunostaining and IgG/IgG4 ratio in one HPF and 3 HPFs), but there were no significant differences with respect to specificity and accuracy.ConclusionsIgG4 immunostaining of swollen duodenal papilla with more than 10 IgG4-positive plasma cells in at least one HPF is useful for supporting the diagnosis of AIP.     

Clinical characteristics of immunoglobulin IgG4-related sclerosing cholangitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort

BackgroundThe clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort.AimsTo clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP.MethodsWe retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP.ResultsAIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI.ConclusionsThe clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.     

Gene expression profiling of morphologic subtypes of pancreatic ductal adenocarcinoma using surgical and EUS-FNB specimens

Background/objectivesVarious classifications of pancreatic ductal adenocarcinoma (PDAC) based on RNA profiling resulted in two main subtypes. Kalimuthu and coworkers proposed a morphology-based classification that concurred with these subtypes. Immune therapy approaches in PDAC were so far disappointing. Morphologic PDAC subtypes may differ regarding key immune-oncology pathways. We aimed to examine the reproducibility and prognostic value of Kalimuthu’s morphologic classification, and to evaluate differences between subtypes regarding gene expression related to tumor biology and immune-oncology.MethodsPDAC specimens from 196 patients were included, 108 consecutive chemotherapy-naïve surgical specimens and 88 endoscopic ultrasound-guided fine needle biopsies (EUS-FNBs). The specimens were evaluated as per Kalimuthu by two pancreatic pathologists, resulting in Group A and Group B tumors. Digital mRNA expression profiling was performed, on the surgical specimens using the NanoString IO360 panel of 770 key tumor biology related and 30 custom-genes, and on the EUS-FNBs using a targeted panel of 123 genes.ResultsMorphologic subtyping reached substantial interobserver agreement between the two pathologists. In the surgical and EUS-FNB cohorts, 44.4% and 38.6% were Group A tumors, which were associated with improved survival. Group A showed higher expression of immune-related genes and cytokine/chemokine/interleukin signaling and Group B of genes related to cancer cell proliferation and cell cycle regulation. Hierarchical clustering based on significant differences in gene expression levels between Groups A and B revealed clusters with prognostic value.ConclusionsMorphologic subtyping according to Kalimuthu is reproducible and holds prognostic value, in surgical as well as EUS-FNB specimens. As upregulation of immune-related genes was found in Group A, future studies should evaluate the potential of immune therapy approaches with special emphasis on this subtype of PDAC.     

Ulcerative Colitis and Immunoglobulin G4

Background/Aims

Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4.

Methods

Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients.

Results

UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05).

Conclusions

UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.     

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

AIM To assess the role of ultrasonography of submandibular glands(SGs) in the diagnosis of type 1 autoimmune pancreatitis(AIP). METHODS Thirty-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.RESULTS The 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 ICDCcriteria 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.CONCLUSION SG ultrasonography to detect multiple hypoechoic lesions might be useful for type 1 AIP diagnosis by improving diagnostic accuracy together with the ICDC sialadenitis criteria.     

The role of CD19+CD24highCD38high and CD19+CD24highCD27+ regulatory B cells in patients with type 1 autoimmune pancreatitis

BackgroundPatients with type 1 autoimmune pancreatitis (AIP) have several immunologic and histologic abnormalities. It is known that depletion of B cells by rituximab is effective for treatment of IgG4-related disease (IgG4-RD) such as type 1 AIP, suggesting that B cells may be a key player in IgG4-RD. However, the role of regulatory B cells (Bregs) in type 1 AIP is unclear, and the objective of this paper is to clarify the role of Bregs in the pathophysiology of type 1 AIP by analyzing circulating Bregs.MethodWe recruited 21 patients with type 1 AIP as determined by the International Consensus Diagnostic Criteria for AIP (ICDC). No patients received corticosteroid treatments. For comparison, we recruited 14 patients with chronic pancreatitis (CP), 20 patients with pancreatic cancer, and 25 healthy subjects as controls. We analyzed Bregs as CD19⁺CD24^highCD38^high and CD19⁺CD24^highCD27⁺ from peripheral blood by flow cytometry.ResultsIn peripheral blood, CD19⁺CD24^highCD38^high Bregs were significantly increased in type 1 AIP patients compared with CP, pancreatic cancer, and healthy controls. Although not significant different, CD19⁺CD24^highCD27⁺ Bregs of type 1 AIP were decreased compared to those of other groups. IL-10⁺ B cells were not significantly different from type 1 AIP patients and healthy controls. In untreated type 1 AIP patients, the number of CD19⁺CD24^highCD38^high Bregs and IgG4 were not correlated.ConclusionsOur data suggested that CD19⁺CD24^highCD38^high Bregs seemed to increase reactively to suppress the disease activity, and are consistent with the hypothesis that CD19⁺CD24^highCD27⁺ Bregs might be involved in the development of type 1 AIP, although it still remains unclear whether the decrease of CD19⁺CD24^highCD27⁺ cells is cause or effect of AIP.     

Relationship between autoimmune pancreatitis and pancreatic cancer: A single-center experience

ObjectivesOrdinary chronic pancreatitis (CP), such as alcoholic CP, is well established to have the increased risk for pancreatic cancer (PaC), nevertheless an association between autoimmune pancreatitis (AIP) and PaC is still unknown. The aims of this study are to examine the frequency of patients who developed PaC during follow-up after being diagnosed with type 1 AIP and to compare the incidence rate of PaC between patients with type 1 AIP and CP.MethodsSixty-three patients with type 1 AIP and 41 patients with CP were enrolled. We examined development of PaC during follow-up from their clinical records.ResultsThe mean follow-up period was 62.4 months in AIP group and 49.2 months in CP group. The occurrence of PaC was observed in 3 patients with AIP during the mean follow-up period of 94.7 months (range, 31–186), whereas a single CP patient developed PaC 38 months after CP diagnosis. The incident rate of PaC during follow-up was comparable between the 2 groups [4.8% (3/63) in type 1 AIP group vs. 2.4% (1/41) in CP group]. In all of 3 AIP patients who developed accompanying PaC, the clinical remission of AIP was achieved with maintenance steroid therapy, when tumors were discovered. In the histological examination of one surgical patient with PaC, lymphoplasmacytic infiltration in storiform fibrosis with abundant IgG4-positive cell infiltration was observed around the PaC area.ConclusionsSimilar to patients with ordinary CP, surveillance for development of PaC is needed at regular interval during follow-up in AIP patients.     

Ⅰ型自身免疫性胰腺炎的研究

自身免疫性胰腺炎（AIP）是自身免疫介导的一种慢性胰腺炎.Ⅰ型AIP是AIP最主要的类型,在慢性胰腺炎患者中约占2％,好发于成年男性.胰腺癌是AIP最主要的鉴别诊断,两者的鉴别依赖于血清学、影像学和组织学检查.血清IgG4水平的升高是最敏感和特异的指标.影像学特征包括胰管不规则狭窄,胰腺弥漫性或局限性肿大,胰腺周围包膜样边缘（capsule-like rim）,动态增强扫描晚期可见强化.胰腺的活检或手术切除标本显示弥漫性淋巴细胞、浆细胞浸润,席纹样纤维化,闭塞性静脉炎.     

Current concept and diagnosis of IgG4-related disease in the hepato-bilio-pancreatic system

Recently, IgG4-related disease (IgG4-RD) has been recognized as a novel clinical entity with multiorgan involvement and unknown origin, associated with abundant infiltration of IgG4-positive cells. The Japanese research committee, supported by the Ministry of Health, Labor and Welfare of Japan, unified many synonyms for these conditions to the term “IgG4-RD” in 2009. The international symposium on IgG4-RD endorsed the comprehensive nomenclature as IgG4-RD, and proposed the individual nomenclatures for each organ system manifestations in 2011. Although the criteria for diagnosing IgG4-RD have not yet been established, proposals include the International Pathological Consensus (IPC) and the Comprehensive Diagnostic Criteria (CDC) for IgG4-RD for general use, and several organ-specific criteria for organ-specialized physicians, e.g., the International Consensus Diagnostic Criteria (ICDC) and the revised clinical diagnostic criteria in 2011 by the Japan Pancreas Society (JPS-2011) for type1 AIP; the Clinical Diagnostic Criteria 2012 for IgG4-sclerosing cholangitis (IgG4-SC-2012); the diagnostic criteria for IgG4-positive Mikulicz’s disease by the Japanese Society for Sjogren’s syndrome; and diagnostic criteria for IgG4-related kidney disease by the Japanese Society of Nephrology. In cases of probable or possible IgG4-RD diagnosed by the CDC, organ-specific diagnostic criteria should be concurrently used according to a diagnosis algorithm for IgG4-RD, with referral to a specialist.     

Evaluation of submandibular versus labial salivary gland fibrosis in IgG4-related disease

Abstract

The newly comprehensive diagnostic criteria in 2011 emphasize the importance of IgG4-positive plasmacyte infiltration along with storiform or swirling fibrosis and obliterative phlebitis in diagnosing IgG4-related disease(RD). Although labial salivary gland (LSG) biopsy is a minimally invasive and convenient procedure for obtaining tissues, LSG fibrosis is thought to be inconspicuous or absent in IgG4-RD cases. In this study we evaluated 15 patients with IgG4-RD, in whom both submandibular gland (SMG) and LSG biopsies were performed at the same time. Histological evaluation revealed fibrosis in all the SMG specimens but in only one LSG specimen (6.7%). The diagnosis of IgG4-RD is primarily based on its morphological appearance on biopsy. The results of this study demonstrated that although more invasive than LSG biopsy, SMG biopsy is recommended for accurate diagnosis of IgG4-related MD and to exclude malignant diseases.     

Demystifying seronegative autoimmune pancreatitis

BackgroundAutoimmune pancreatitis (AIP) has been classified into type 1 and type 2 subtypes. Serum immunoglobulin G4 (IgG4) elevation characterizes type 1 AIP. Type 2 AIP and a subset of type 1 AIP are seronegative, i.e., have normal serum IgG4 levels.AimWe compared the profiles of the three subsets of AIP to identify the unique characteristics of seronegative type 1 AIP and type 2 AIP.MethodsWe compared the clinical profiles of 69 seropositive type 1 AIP patients, 21 seronegative type 1 AIP patients and 22 type 2 AIP patients.ResultsAmong type 1 AIP, seronegative group had similar clinical profiles when compared to seropositive group except that they were more likely to undergo surgical resection than seropositive patients (p = 0.001). Seronegative type I AIP patients were older (61.9 ± 13.7 vs 45.3 ± 17.4; p = 0.004), and differed in the occurrence of other organ involvement (OOI) (71.4% vs 0%; p < 0.001) and disease relapse (33.3% vs 0%; p = 0.005) when compared with type 2 AIP. All seronegative type 1 AIP patients had at least one of the following –OOI, disease relapse, and age >50 years while none of the type 2 AIP had OOI or disease relapse.ConclusionsSeronegative and seropositive type 1 AIP patients have similar clinical profiles, which are distinct from that of type 2 AIP. Among the seronegative AIP group, patients are more likely to have type 1 AIP rather than type 2 AIP if they are older than 50 years or have OOI or disease relapse.