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Autoimmune pancreatitis (AIP) is a disease concept that originated in Japan. It is characterized by diffuse pancreatic enlargement and irregular narrowing of the main pancreatic duct. Although the usefulness of the histological diagnosis of AIP using endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) and EUS-guided fine-needle biopsy (FNB) has been reported, enhanced diagnostic performance is expected with improvements in tissue collection methods and fine-needle techniques. Guidance for establishing the tissue diagnosis of AIP has been developed and is useful for histological evaluation. Histopathological diagnosis by EUS-FNA/FNB is expected to play a central role in AIP diagnosis in the future.

To evaluate the accuracy of the lesion-to-erector spinae signal intensity ratio (SIR) on magnetic resonance imaging (MRI) for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDA).The MRI data of 21 patients with AIP and 27 patients with PDA were analysed retrospectively, and the signal intensity in pancreatic lesions and erector spinae muscles at the same level on T2-weighted imaging (T2WI), arterial phase (AP) imaging, and delayed phase (DP) imaging was measured for calculation of SIRs.The mean SIRs of the pancreatic lesions and erector spinae from T2WI, AP, and DP images of AIP patients were 0.96, 1.27, and 1.42, respectively, while those of PDA patients were 1.35, 0.80, and 0.91, respectively. The differences in the SIRs between the AIP and PDA groups were statistically significant (p0.001), with corresponding area under curve (AUC) values of 0.925, 0.906, and 0.961, respectively. The optimal cut-off values for the SIRs on T2WI, AP and DP images were 1.21, 1.01, and 1.08, respectively. SIR values 1.21 on T2WI,1.01 on AP imaging, and1.08 on DP imaging identified AIP with sensitivities of 85.7%, 90.5%, and 90.5%, respectively, and specificities of 81.5%, 74.6%, and 81.5%, respectively. The AUC values for SIRs did not differ significantly between T2WI and DP imaging or AP and DP imaging (Z = 0.778, p=0.436; Z = 1.279, p=0.201).The SIRs of pancreatic lesions and erector spinae on T2WI, AP, and DP images can be used to differentiate AIP from PDA.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss’ к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

The diagnosis of the rare disease autoimmune pancreatitis (AIP) is demonstrated in the case of a patient who underwent a series of examinations that were unable to unequivocally prove the diagnosis of benignity. The disease as a form of chronic pancreatitis, and the most important and first objective of the examination is to exclude malignant disease of the pancreas and biliary tract. While imaging led to suspicion of malignancy, repeated histological examinations did not confirm it. After we were able to exclude suspected carcinoma according to the available diagnostic criteria, AIP was confirmed, and a diagnosis of type I was made, which belongs to the group of diseases characterized by high levels of immunoglobulin G4 (IgG4) in the blood serum. Successful treatment with glucocorticoids was initiated with induction of disease remission. However, AIP shows frequent relapses and this should also be borne in mind during treatment. Our case report also describes such a case.

BACKGROUND The survival rate of pancreatic ductal adenocarcinoma (PDAC) is very poor because early detection is difficult. Extracellular vesicles (EVs) are released from cells associating with the cellular condition and circulated in the blood. We aimed to identify EV proteins from endoscopic ultrasound-fine needle aspiration (EUS-FNA) biopsy samples in order to develop novel biomarkers for PDAC. METHODS Extracellular vesicles were isolated from EUS-FNA samples of 40 PDAC patients and six autoimmune pancreatitis (AIP) patients to be used as a control. EV proteins were identified using nanoLC-MS/MS. RESULTS Intact EVs approximately 200 nm in diameter were detected from EUS-FNA samples. We identified 2059 or 1032 EV proteins in PDAC or AIP, respectively, and 1071 EV proteins were detected only in PDAC. One hundred and fifty-three EV proteins were significantly different between PDAC and AIP: 64 proteins were down-regulated in PDAC whereas 89 EV proteins were up-regulated in PDAC including mucins, keratins, Ras-related proteins, and olfactomedin-4, which proteins have been reported to be elevated in PDAC tissue/blood, or cultured pancreatic cancer cell lines. Notably, in the 89 up-regulated PDAC EV proteins we identified novel proteins including ADP-ribosylation factor 3, CD55, pyruvate kinase, and lipopolysaccharide-induced tumor necrosis factor. Out of 89 proteins, a total of 13 proteins including Ras-related proteins were significantly elevated in PDAC stages II-IV compared to PDAC stage I, including Ras-related proteins, moesin, and CD55. CONCLUSIONS The EV proteins obtained from EUS-FNA samples contain a PDAC-specific protein barcode. The EV proteins identified from EUS-FNA samples include promising biomarkers for the diagnosis and clinical staging of PDAC.

The diagnosis of autoimmune pancreatitis (AIP) is challenging and should be achieved through the comprehensive evaluation of clinical, radiological, serological, and pathological evidence, as there is currently no single reliable diagnostic modality. Endoscopic ultrasonography (EUS) can reveal pancreatic parenchymal and ductal features in much more detail than any other existing imaging modality. In this article, we focused on three applications of EUS, i.e., conventional EUS imaging, EUS elastography (EUS-EG), and contrast-enhanced harmonic EUS (CEH-EUS), for the diagnosis of AIP. Diffuse hypoechoic areas, diffuse enlargement, bile duct wall thickening, and peripancreatic hypoechoic margins on conventional EUS are characteristic features of AIP, and the frequencies of these findings are significantly higher in AIP than in pancreatic cancer (PC). EUS-EG of the pancreatic parenchyma in AIP showed homogenous stiffness and that the elasticity of the pancreas may change after steroid therapy. CEH-EUS revealed focal or diffuse iso-enhancement in most AIP cases and hypo-enhancement in most PC cases. However, some AIP cases show a contrast enhancement pattern similar to that of PC. It should be noted that EUS findings of AIP may differ depending on its stage or disease activity. Differentiation from PC has become an increasingly important issue in the process of diagnosing AIP, and EUS, including elastography and contrast enhancement, could be a promising imaging modality for this purpose.

Background Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment. Methods The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates. Results Seven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5–93.9) with no heterogeneity (I2 = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5–40.3) with moderate heterogeneity (I2 = 51%). A higher rate of relapse (35.9%, 95%CI 17.3–60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8–53) with substantial heterogeneity (I2 = 73.6%). No publication bias was observed. Conclusion Treatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We 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. Results AIP 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. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Background. The diagnosis of IgG4-associated sclerosing disease, IgG4-associatied condition, is based on a comprehensive evaluation of characteristic clinical, radiographic, serologic, histological and immunohistochemical features. The histopathological is the main examination in the diagnosis of IgG4-associatied diseases. The purpose of the study was to evaluate the state of IgG4-positive plasma cells in the mucosa of the colon in patients with established morphological and endoscopic diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD). Materials and methods . The study used biopsies material from 14 patients treated at the Institute of Gastroenterology, in the department intestine diseases, with established morphological and endoscope diagnosis of UC (8) and CD (6) in the acute stage. All patients had no evidence of autoimmune pancreatitis type I and II. Biopsy were fixed in 10.0% neutral formalin, dehydrated in alcohols of increasing concentration and embedded in paraffin for histological studies. Histological sections of 3–5 µm were colored with hematoxylin and eosin. There were used monoclonal IgG4 antibodies for immunohistochemical studies (Abcam, USA). Results . Our results show that with ulcerative colitis in 37.5 % of cases IgG4-positive plasma cells in the colon mucosa have not been identified. In 25 % of cases, sporadic IgG4-positive plasma cells were identified. In 37.5 % of cases, the groups of IgG4-positive plasma cells not exceeding 5 cells in one group were found. In Crohn’s disease, groups of IgG4-positive plasma cells were observed in all cases, in addition it should be noted that the group included 10 or more cells. Conclusions. It is shown that in UC, IgG4-positive plasma cells may be absent, solitary or gathered in small groups to 5 cells, and in CD, the groups consisting of 10 or more cells are observed.

The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (p = 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00535-021-01817-9.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition of unknown etiology, with presumed autoimmune mechanisms. It is characterized by high levels of IgG4 and variable clinical manifestations. It can involve one or multiple organs. Herein, we reported the case of a 62-year-old man with three organs involvement. He initially presented with recurrent jaundice. Laboratory analysis revealed cholestasis, high gamma-globulin levels, renal failure, and proteinuria. Abdominal Magnetic Resonance Imaging (MRI) showed segmental strictures of the left intrahepatic bile ducts and the wirsung duct with an increased volume of the pancreas and diffuse bilateral enlargement of the kidneys. Laboratory tests revealed high IgG4 levels (770 mg/dL). Based on the biological and radiological findings, we have suggested the diagnosis of systemic IgG4-related disease involving bile ducts, the pancreas, and probably the kidneys. Renal biopsy revealed lymphoplasmacytic infiltrate and fibrosis, but no IgG4-positive cell. The patient received corticosteroid therapy with a complete resolution of all symptoms and a rapid normalization of all blood tests. The present case underlines the complexity of IgG4-RD because of its variable clinical presentation. The diagnosis is challenging and should be carefully assessed for possible multi-organ involvement.

Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody. While an effective treatment for a variety of tumors, immune checkpoint inhibitors (ICI) can cause immune-related adverse events such as ICI-pancreatic injury (ICI-PI). Here we present a case of a 60-year-old man with metastatic acral melanoma treated with nivolumab and ipilimumab who developed ICI-PI. Changes in positron emission tomography images preceded symptom onset. However, this case is unique in that the patient presented with cholestatic liver disease. Magnetic resonance cholangiopancreatography showed a dilated extrahepatic bile duct that resolved with steroid therapy, similar to the clinical course of autoimmune pancreatitis. ICI-PI has variable presentations including obstructive jaundice with a clinical course mimicking autoimmune pancreatitis and prompt awareness and treatment of ICI-PI is clinically significant given increasing use of ICIs.

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.

Background Chronic pancreatitis is a known risk factor of pancreatic cancer (PDAC). A similar association has been suggested but not demonstrated for autoimmune pancreatitis (AIP). Objective The 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. Methods Relevant 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. Results A 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. Conclusions In 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.

Pancreatitis is as common in children as it is in adults, though causes and accepted imaging strategies differ in children. In this narrative review we discuss the epidemiology of childhood pancreatitis and key imaging features for pediatric acute, acute recurrent, and chronic pancreatitis. We rely heavily on our collective experience in discussing advantages and disadvantages of different imaging modalities; practical tips for optimization of ultrasound, CT, and MRI with MRCP in children; and image interpretation pearls. Challenges and considerations unique to imaging pediatric pancreatitis are discussed, including timing of imaging, role of secretin-enhanced MRCP, utility of urgent MRI, severity prediction, autoimmune pancreatitis, and best methods for serial imaging. We suggest a methodical approach to pancreatic MRI interpretation in children and have included a sample structured report, and we provide consensus statements according to our experience imaging children with pancreatitis.

The diagnosis of autoimmune pancreatitis (AIP) is often difficult as the main differential diagnosis is pancreatic head adenocarcinoma. Some clinical, radiological, serological and histological criteria help in guiding the diagnosis. The serum gamma-globulin IgG4 dosage is the most sensitive and specific marker. The shape of the ductal stenosis in AIP is characteristic. The treatment is based on corticosteroids. We report the case of a 53-year-old woman, presenting with pancreatic head mass mimicking an adenocarcinoma.

Purpose Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are malignancies with poor prognoses that can be difficult to distinguish preoperatively. Thrombospondin-2 has been proposed as a novel diagnostic biomarker for early pancreatic ductal adenocarcinoma. The aim of the present study was to evaluate thrombospondin-2 as a diagnostic and prognostic biomarker in combination with current biomarker CA 19-9 for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. Methods Thrombospondin-2 was measured in prospectively collected serum samples from patients who underwent surgery with a histopathological diagnosis of distal cholangiocarcinoma (N = 51), pancreatic ductal adenocarcinoma (N = 52) and benign pancreatic diseases (N = 27) as well as healthy blood donors (N = 52) using an enzyme-linked immunosorbent assay. Results Thrombospondin-2 levels (ng/ml) were similar in distal cholangiocarcinoma 55 (41–77) and pancreatic ductal adenocarcinoma 48 (35–80) (P = 0.221). Thrombospondin-2 + CA 19-9 had an area under the curve of 0.92 (95% CI 0.88–0.97) in differentiating distal cholangiocarcinoma and pancreatic ductal adenocarcinoma from healthy donors which was superior to CA 19-9 alone (P Conclusions Serum thrombospondin-2 in combination with CA 19-9 has potential as a biomarker for distal cholangiocarcinoma and pancreatic cancer.

Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer, whereas such an association with autoimmune pancreatitis (AIP) is widely debated. Due to the rarity of the latter disorder, there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer, which do not seem to support it. However, these studies are affected by several limitations and, therefore, a link between AIP (and, specifically, type 1 AIP) and pancreatic cancer cannot be ruled out definitively on this basis. Moreover, several immunopathological aspects of type 1 AIP and, in general, immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression. In detail, Th2 immunological dominance, type 2 macrophage polarization and basophil infiltration observed in type 1 AIP, may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis, in addition to the immunosuppressive therapies that can be used in these patients.

Purpose of review Approximately 20-30% of children who experience one episode of acute pancreatitis will have at least one additional episode. For some children, pancreatitis recurs multiple times and in a few years is followed by the diagnosis of chronic pancreatitis. Identifying risk factors for recurrent episodes and disease progression is critical to developing therapeutic interventions. Recent findings Obesity is driving an increase in biliary stone disease and severe acute pancreatitis. Recurrent acute pancreatitis (RAP) may lead to the development of diabetes through autoimmune mechanisms. Cystic fibrosis or CFTR-related disorders may present as RAP and CFTR modulator therapy can increase or decrease the risk of acute pancreatitis in these populations. Children with Crohn disease have a three-fold risk of acute pancreatitis over the general population while children with ulcerative colitis are at increased risk for pediatric autoimmune pancreatitis, a disorder that may be distinct from autoimmune pancreatitis described in adults. Obstructive jaundice in the absence of identified mechanical factors may be a presenting sign of pediatric autoimmune pancreatitis. Summary Pediatric RAP is a painful condition that leads to gland destruction and functional insufficiency. Risk factors are being clarified but preventive treatments remain elusive.

A 71-year-old man with obstructive jaundice was referred to our department. He underwent cholangiojejunostomy 15 years ago for palliative drainage. At that time, he had obstructive jaundice caused by an unresectable pancreatic head tumor. Contrast-enhanced computed tomography (CE-CT) now revealed a mass with low enhancement in the hepatic hilum that occluded the hilar bile duct and infiltrated extensively along the portal vein and hepatic artery. CE-CT also showed marked atrophy of the left hepatic lobe. No swelling or tumors were observed in the pancreas. Serum immunoglobulin G4 (IgG4) levels were as high as 465 mg/dL. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed targeting the hepatic hilar lesion. Immunohistological results of the biopsy specimens suggested that the lesion was an IgG4-related hepatic inflammatory pseudotumor (IPT) with no atypical cells. Steroid treatment resulted in rapid clinical improvement. This case suggested the usefulness of EUS-FNB for diagnosing IgG4-related hepatic hilar IPT.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thorough histologic examination with attention to certain morphologic features can assist in deciphering neoplastic from reactive, however small biopsies often remain a challenge. Variable histologic patterns in conventional PDAC may also confound the diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such as adenosquamous and squamous cell carcinoma, colloid carcinoma, medullary carcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitate excluding metastasis from other sites prior to rendering the diagnosis of pancreatic carcinoma. The use of immunohistochemical staining and molecular markers can aid in separating benign from malignant and PDAC from metastasis. PDAC expresses a few non-specific epithelial and mucin immunomarkers such as CK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemical marker that is specific for PDAC in the right clinical context is SMAD4. Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDAC in a limited sample. Unfortunately, this finding is seen only in 50% of PDAC cases. The identification of certain mutations can help support a diagnosis of PDAC when benign conditions are in the differential. At the molecular level, KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequent neoplastic progression is driven by additional mutations of tumor suppressor genes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also provide an insight to the prognosis. For instance, the loss of SMAD4 is associated with a poor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associated with improved survival.

Solitary organ autoimmune disorders, formerly known as autoimmune pancreatitis (AIP), autoimmune sialadenitis, and autoimmune sclerosing cholangitis, are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease (IgG4-RD). AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody (Ab), accumulation of IgG4-expressing plasmacytes in the affected organs, and involvement of multiple organs. It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity. However, a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype. In addition, disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone. Therefore, it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD. Recently, we found that activation of plasmacytoid dendritic cells producing both interferon-α (IFN-α) and interleukin-33 (IL-33) mediate murine AIP and human IgG4-RD. More importantly, we provided evidence that serum concentrations of IFN-α and IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders. In this Frontier article, we have summarized and discussed biomarkers of AIP and IgG4-RD, including Igs, autoAbs, and cytokines to provide useful information not only for clinicians but also for researchers.

Inflammatory bowel diseases (IBD), which is a term for two conditions (ulcerative colitis and Crohn’s disease), are chronic inflammatory diseases of the gastrointestinal tract that are the subject of many studies and much discussion around the world. The global prevalence of IBD is 20.4 per 100 thousand for ulcerative colitis and 3.7 per 100 thousand for Crohn’s disease. Every year the number of patients is increasing, which may indicate improvement in diagnosis of IBD, but at the same time demonstrates certain disadvantages and difficulties in the diagnosis and treatment of this group of patients. However, despite the fact that IBD has been exercising the minds of scientists around the world for many decades, many issues of diagnosis and treatment of this pathology appear relevant. Due to the paucisymptomatic condition of patients at early stages and the similarity of its symptoms with other gastroenterological diseases, the diagnosis of IBD involves certain difficulties in many cases. Advanced forms of the disease, as well as complications of IBD, result from late diagnosis. Endoscopic ultrasound (EUS, endo-ultrasound), which includes endoscopic and ultrasound examinations, is a modern imaging technique for the diagnosis of gastrointestinal diseases. The article discusses various international and Russian studies on the use of EUS in various pathologies of the gastrointestinal tract. Despite the absence of EUS in the formal guidelines for IBD, the technique appears promising for diagnosis, differential diagnosis of ulcerative colitis and Crohn’s disease, as well as complications of these diseases, such as primary sclerosing cholangitis, chronic and autoimmune pancreatitis, autoimmune hepatitis, pancreatic cancer, etc.

Background The fecal microbiota in pancreatic ductal adenocarcinoma (PDAC) and in autoimmune pancreatitis (AIP) patients remains largely unknown. We aimed to characterize the fecal microbiota in patients with PDAC and AIP, and explore the possibility of fecal microbial biomarkers for distinguishing PDAC and AIP. Methods 32 patients with PDAC, 32 patients with AIP and 32 age- and sex-matched healthy controls (HC) were recruited and the fecal microbiotas were analyzed through high-throughput metagenomic sequencing. Alterations of fecal short-chain fatty acids were measured using gas chromatographic method. Results Principal coordinate analysis (PCoA) revealed that microbial compositions differed significantly between PDAC and HC samples; whereas, AIP and HC individuals tended to cluster together. Significant reduction of phylum Firmicutes (especially butyrate-producing bacteria, including Eubacterium rectale, Faecalibacterium prausnitzii and Roseburia intestinalis) and significant increase of phylum Proteobacteria (especially Gammaproteobacteria) were observed only among PDAC samples. At species level, when compared with HC samples, we revealed 24 and 12 differently enriched bacteria in PDAC and AIP, respectively. Functional analysis showed a depletion of short-chain fatty acids synthesis associated KO modules (e.g. Wood-Ljungdahl pathway) and an increase of KO modules associated with bacterial virulence (e.g. type II general secretion pathway). Consistent with the downregulation of butyrate-producing bacteria, gas chromatographic analysis showed fecal butyrate content was significantly decreased in PDAC group. Eubacterium rectale, Eubacterium ventrisum and Odoribacter splanchnicus were among the most important biomarkers in distinguishing PDAC from HC and from AIP individuals. Receiver Operating Characteristic analysis showed areas under the curve of 90.74% (95% confidence interval [CI] 86.47–100%), 88.89% (95% CI 73.49–100%), and 76.54% (95% CI 52.5–100%) for PDAC/HC, PDAC/AIP and AIP/HC, respectively. Conclusions In conclusion, alterations in fecal microbiota and butyrate of patients with PDAC suggest an underlying role of gut microbiota for the pathogenesis of PDAC. Fecal microbial and butyrate as potential biomarkers may facilitate to distinguish patients with PDAC from patients with AIP and HCs which worth further validation.

Background There is currently no S3 guideline that contains statements on the diagnosis and treatment of acute, chronic and autoimmune pancreatitis in a single guideline. Objectives This article presents the most relevant recommendations relating to radiological imaging from the new "S3 guideline for pancreatitis". Materials and methods The guideline was developed by the DGVS (German Society for Digestive and Metabolic Diseases). After an online-based Delphi survey, the statements were discussed by an interdisciplinary expert team at a 3-day consensus conference and then agreed upon. The level of evidence scheme (version 2) of the Oxford Centre for Evidence-based Medicine was used. Results The new German "S3 guideline pancreatitis" comprises for the first time all entities of pancreatitis, acute, chronic and autoimmune pancreatitis and contains a large number of innovations with regard to diagnostic imaging and therapy. In addition to the evidence-based recommendations for diagnosis and therapy, a German-language glossary of the revised Atlanta classification on acute pancreatitis was adopted by consensus of the interdisciplinary guideline expert team. Furthermore, protocol recommendations for the performance of computed tomography (CT) are provided for the first time. In this article we introduce the key recommendations and innovations in the field of diagnostic radiologic imaging for acute, chronic and autoimmune pancreatitis. Conclusions In the future, every radiologist should have deep knowledge of the recommended time intervals for radiological imaging in acute pancreatitis and know the German terms for the description of acute pancreatitis; furthermore they should be able to classify the morphologies to the appropriate stages.

Introduction Autoimmune hepatitis (AIH) is an immune mediated, inflammatory disease affecting the liver as a result of environmental triggers in susceptible individuals leading to loss of self-tolerance. The immunopathogenesis of AIH is not fully understood which limits targeted therapeutic options. Areas covered In this review, the authors provide an overview of current practice in the management of AIH which include induction therapy with corticosteroids (+/- thiopurines), followed by maintenance therapy. Lack of early response to treatment may serve as a predictor of those at risk of requiring treatment escalation to second- and third-line agents such as mycophenolate mofetil (MMF), calcineurin inhibitors or biologics. Evidence for third-line agents from small retrospective studies or individual centres are reviewed. The nuances of AIH treatment in pregnancy, overlap syndromes and drug induced liver injury (DILI) warrant further consideration. Expert opinion Augmenting the balance of regulatory T cells (Treg) and effector T cells is an appealing therapeutic target with a multitude of agents in development. Many of the challenges in AIH research are due to its rarity and lack of randomised data. Management of AIH should strive towards individualised care through risk stratification and use of the best therapeutic modality for each patient.

Die im Jahr 1992 veröffentlichte Atlanta-Klassifikation zur Beurteilung von Schweregraden und Komplikationen der akuten Pankreatitis sollte ursprünglich eine einheitliche Terminologie für Kliniker und Forscher etablieren. Nach einer kontinuierlichen Weiterentwicklung wurde dann 2012 die revidierte Atlanta-Klassifikation publiziert, um die Aspekte der Bildgebung besser zu integrieren sowie Unschärfen in der Terminologie zu optimieren. Diese Begrifflichkeiten bezüglich der Krankheitseinteilung, -phasen, Schweregradbeurteilung und lokaler Komplikationen lagen bisher lediglich als englische Ausdrücke vor. Dies verhinderte eine weitere Verbreitung und Anwendung im klinischen Alltag im deutschsprachigen Raum. Um eine Anpassung in der deutschsprachigen Medizin zu erreichen, wurden die Termini der revidierten Atlanta-Klassifikation durch ein Expertenteam der Deutschen Röntgengesellschaft basierend auf aktueller Literatur übersetzt und im Rahmen der Konsensuskonferenz der neu erstellten S3-Leitlinie Pankreatitis im Februar 2020 mit einer Zustimmung von 97,3 % als Teil der Leitlinienempfehlung angenommen. Im folgenden Text mit Glossar werden die übersetzten und konsentierten Begrifflichkeiten anhand von Bildbeispielen erläutert. Kernaussagen

Pancreatic ductal adenocarcinoma (PDAC) and autoimmune pancreatitis (AIP) are diseases with a highly analogous visual presentation that are difficult to distinguish by imaging. The purpose of this research was to create a radiomics-based prediction model using dual-time PET/CT imaging for the noninvasive classification of PDAC and AIP lesions. This retrospective study was performed on 112 patients (48 patients with AIP and 64 patients with PDAC). All cases were confirmed by imaging and clinical follow-up, and/or pathology. A total of 502 radiomics features were extracted from the dual-time PET/CT images to develop a radiomics decision model. An additional 12 maximum intensity projection (MIP) features were also calculated to further improve the radiomics model. The optimal radiomics feature set was selected by support vector machine recursive feature elimination (SVM-RFE), and the final classifier was built using a linear SVM. The performance of the proposed dual-time model was evaluated using nested cross-validation for accuracy, sensitivity, specificity, and area under the curve (AUC). The final prediction model was developed from a combination of the SVM-RFE and linear SVM with the required quantitative features. The multimodal and multidimensional features performed well for classification (average AUC: 0.9668, accuracy: 89.91%, sensitivity: 85.31%, specificity: 96.04%). The radiomics model based on 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT dual-time images provided promising performance for discriminating between patients with benign AIP and malignant PDAC lesions, which shows its potential for use as a diagnostic tool for clinical decision-making. • The clinical symptoms and imaging visual presentations of PDAC and AIP are highly similar, and accurate differentiation of PDAC and AIP lesions is difficult. • Radiomics features provided a potential noninvasive method for differentiation of AIP from PDAC. • The diagnostic performance of the proposed radiomics model indicates its potential to assist doctors in making treatment decisions.

An 84-year-old man was referred to our hospital for a cystic lesion of the pancreatic head, swelling of the pancreatic tail and hilar biliary stricture, resulting in elevated liver enzyme levels. We suspected branch duct-type intraductal papillary mucinous neoplasm (IPMN) and type I autoimmune pancreatitis (AIP) associated with sclerosing cholangitis because of the high serum IgG4 levels. The main pancreatic duct on the tail side of the AIP lesion was moderately dilated. Although the biliary stricture and pancreatic swelling improved after prednisolone treatment, the pancreatic enzyme levels increased rapidly. The entire main pancreatic duct exhibited remarkable dilatation, which led to the diagnosis of mixed-type IPMN. The clinical characteristics of IPMN in the main pancreatic duct appear to have been initially masked by AIP.

Autoimmune pancreatitis is a rare, distinct and increasingly recognized form of chronic inflammatory pancreatic disease secondary to an underlying autoimmune mechanism. We report on a 14-year-old boy who developed autoimmune pancreatitis, while he was under treatment with eltrombopag for chronic immune thrombocytopenia. Therapy with corticosteroids resulted in complete remission of both. This is the first report on the co-occurrence of autoimmune pancreatitis and chronic immune thrombocytopenia in childhood, and clinicians should be aware of this rare association, because early diagnosis and therapy of autoimmune pancreatitis may prevent severe complications.

IgG4-related disease (ER-IgG4) is a recognised systemic disease. It was described after patients diagnosed with autoimmune pancreatitis showed signs of extra-pancreatic disease. The clinical manifestation of these patients is subacute and is manifested by the appearance of pseudotumoral lesions, or inflammatory or fibrous tumours. Sometimes it can be serious as in the case of patients with cholangitis or large vessel vasculitis. Diagnostic criteria include, among others, serum IgG4 elevation and/or histological parameters. The 18F-FDG-PET/CT is useful in the initial diagnosis, biopsy guidance as well as in the assessment of response to therapy. It usually responds to steroid therapy.

Video Video 1 Pursuit of a pancreatic mass: autoimmune pancreatitis mimicking pancreatic cancer. EUS features of autoimmune pancreatitis in an older man who presented with obstructive jaundice and pancreatic mass.

A 65-year-old man with ulcerative colitis presented with aggravated diabetes. Computed tomography showed two masses in the body and tail of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed, with histopathological findings suggesting autoimmune pancreatitis (AIP). Type-2 AIP was suspected, and administration of prednisolone was initiated. The pancreatic masses had disappeared after the treatment. In this case, EUS-FNA was effective for the diagnosis of type-2 AIP. The two-lesion mass formation observed here is a rare presentation of the disease. In patients with a history of ulcerative colitis, the possibility of late-onset type-2 AIP should be kept in mind.

In this case report, we present a case of autoimmune pancreatitis (AIP) diagnosis in a patient after a 7-year history of suspicious pancreatic cancer. Kim's and Japanese criteria were used to diagnose AIP. Our case avoided undesirable invasive procedures and recovered thanks to the proper diagnosis and timely treatment with prednisone. Early and accurate diagnosis of AIP, in this case, had a significant impact on the treatment and prognosis process. (C) 2021 The Author(s) Published by S. Karger AG, Basel

IgG4-related disease is a systemic disorder characterised by diffuse or tumoural inflammatory lesions. It can mimic pancreatic cancer, leading to errors in diagnosis and treatment increasing rates of morbidity and mortality in patients. The aim of this review is to take a differential diagnostic approach to these two entities using epidemiology, clinical and laboratory findings, imaging and histopathology.

IgG4-related sclerosing cholangitis (IgG4-SC) is a relatively newly identified disease that is frequently associated with autoimmune pancreatitis. The differential diagnosis between cholangiocarcinoma, primary sclerosing cholangitis, and IgG4-SC can be challenging due to significant overlap among the clinical and imaging characteristics. We report the case of a 71-year-old woman who was diagnosed with IgG4-related disease based on increased serum IgG4 levels, imaging, and clinical presentation, which showed systemic involvement, including sclerosing cholangitis and kidneys. The patient presented with chronic jaundice. Magnetic resonance imaging revealed bile duct strictures and the dilatation of upstream bile ducts, smooth wall thickening with uniform enhancement in the delayed phase, and no vascular infiltration. Multiple low-density, wedge-shaped areas were identified in both kidneys, which were hypointense on T2-weighted images and hyperintense on diffusion-weighted images. The serum IgG4 levels of this patient were elevated to nearly 10-fold the normal upper limit. A diagnosis of IgG4-SC associated with IgG4-related kidney was made. Based on this case, pre-surgery IgG4 serum treatment in patients with non-malignant bile duct stenosis was recommended to exclude IgG4-SC.

Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step-up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non-opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner.

Chronic pancreatitis is a complex chronic inflammatory condition that results in pancreas fibrosis and calcification with subsequent exocrine and endocrine insufficiency. Alcohol and nicotine are the most prevalent risk factors, however, recent studies have increasingly discovered genetic associations that increase the risk to develop chronic pancreatitis. Here, we discuss different etiologies of the disease including autoimmune pancreatitis, and present evidence-based diagnostic and therapeutic approaches. In particular, we highlight the interdisciplinary and interventional management of local complications such as pseudocysts, pancreatic duct stones, biliary duct and pancreatic duct stenosis and persistent pain.

Autoimmune pancreatitis (AIP) is characterized by pancreatic manifestations of IgG4-related disease. Malignancies in patients with AIP have been reported, but carcinoma of the bile duct is extremely rare. We report a patient with IgG4-related AIP who developed cholangiocarcinoma after 8 years of steroid treatment. A 76-year-old male presented with fever (37.8°C) due to biliary obstruction and cholangitis. He had been treated with steroids for 8 years to control inflammation due to IgG4-related AIP. During 8 years of treatment, hepatobiliary enzyme levels were well controlled within their normal range, but serum IgG4 levels remained elevated. A computed tomography scan showed intrahepatic bile duct dilatation. Magnetic resonance cholangiopancreatography showed obstructive changes at the junction of the cystic and common ducts. To relieve biliary obstruction, endoscopic bile duct drainage using a nasobiliary tube was performed, and cytology was Class IV. Aorto-caval lymph node enlargement was found at laparotomy, intraoperatively diagnosed as adenocarcinoma, and resection was abandoned. He died 4 months postoperatively. We report a patient with IgG4-related AIP complicated by cholangiocarcinoma which developed after 8 years of steroid treatment. Even if hepatobiliary markers are well controlled, periodic follow-up with imaging studies may facilitate detection of an early cholangiocarcinoma.

We herein report a 67-year-old woman with malignant lymphomas of the bile duct that developed after regression of a pancreatic head mass. Computed tomography suggested the mass was pancreatic head cancer. Endoscopic ultrasonography showed a low-echoic mass with hyperechoic strands resembling autoimmune pancreatitis. Her serum IgG4 concentration was elevated to 674 mg/dL. After the pancreatic head mass spontaneously diminished, three masses were detected in the common bile duct. A biopsy of the major papilla revealed high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangement. Systemic chemotherapy with rituximab plus etoposide, prednisolone, vincristine, cyclophosphamide and doxorubicin resulted in complete remission.

IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.

Immunoglobulin G4 related-disease (IgG4-RD) is a multisystemic immune-mediated fibroinflammatory disease, with a strong predilection for salivary and lacrimal glands, pancreas, biliary tree, lungs, kidneys, aorta, and retroperitoneum. In the case of pancreatic involvement, it manifests as autoimmune pancreatitis. Patients with IgG4-RD usually have mild to moderate eosinophilia in the peripheral blood, however, they may present a secondary hypereosinophilic syndrome (HES). Although there are cases described with severe eosinophilia (> 5,000/µL), the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD considers peripheral eosinophilia above 3,000/µL as an exclusion criterion, although stating that assessment for the presence of exclusion criteria should be individualized depending on a patient’s clinical scenario. Here, we describe the clinical case of a 30-year-old woman who presented with chronic diarrhea and abdominal pain. The diagnostic workup revealed eosinophilic ascites, severe peripheral blood eosinophilia (> 5,000/µL), IgG4 elevation (> 2 × upper normal limit), and also diffuse swelling in the body and pancreatic tail (computed tomography (CT) scan). There was a prompt response to corticosteroid therapy with clinical resolution and continued remission under therapy. The patient was diagnosed with IgG4-RD with secondary HES, explaining the gastrointestinal tract and peritoneum damage in the form of enterocolitis and ascites. Exclusion of alternative diagnosis was made.

BackgroundIgG4-related kidney disease (IgG4-RKD) can affect multiple organs, which was first reported as a complication or extra-organ manifestation of autoimmune pancreatitis in 2004. It is characterized by abundant IgG4-positive plasma cells infiltration in tissues involved.Case presentationA 69-year-old man presented with cough and renal dysfunction with medical history of hypertension and diabetes. Pathological findings revealed interstitial nephritis and he was initially diagnosed with IgG4-RKD. Prednisone helped the patient to get a remission of cough and an obvious decrease of IgG4 level. However, he developed invasive pulmonary fungal infection while steroid theatment. Anti-fungal therapy was initiated after lung puncture (around cavitary lung lesion). Hemodialysis had been conducted because of renal failure and he got rid of it 2 months later. Methylprednisolone was decreased to 8 mg/day for maintenance therapy. Anti-fungal infection continued for 4 months after discharge home. On the 4th month of follow-up, Chest CT revealed no progression of lung lesions.ConclusionsThe corticosteroids are the first-line therapy of IgG4-RD and a rapid response helps to confirm the diagnosis. This case should inspire clinicians to identify IgG4-related lung disease and secondary pulmonary infection, pay attention to the complications during immunosuppressive therapy for primary disease control.