Elevated Serum IgG4 Levels Research Articles

1273 IgG4 Related Cholangiopathy Masquerading as Cholangiocarcinoma

INTRODUCTION: IgG4 related diseases can involve multiple organs, best described in cases of autoimmune pancreatitis (AIP). IgG4-related cholangiopathy is difficult to distinguish from other forms of biliary ductal disorders including primary biliary cholangitis, primary sclerosing cholangitis (PSC), and cholangiocarcinoma (ChCA). Specifically, IgG4 cholangiopathy and ChCA share many clinical and imaging findings which make it difficult to distinguish these entities. We report a rare case of IgG4 cholangiopathy mimicking a ChCA. CASE DESCRIPTION/METHODS: A 69-year-old male presented with nausea/vomiting, weight loss, painless jaundice, and CT suggestion of a malignant hilar mass. ERCP with cytology and EUS with FNA from the hilar mass were negative for malignancy. Two further ERCPs with Spyscope hepatic duct bifurcation biopsies showed severe stenosis of the right hepatic ducts and diffuse biliary stricturing suggestive of PSC. Brushings for cytology and fluorescence in situ hybridization (FISH) were obtained, balloon dilation and stenting performed. MRCP noted multifocal intrahepatic biliary strictures, suggestive of PSC; a hilar mass, as seen on CT, was not seen. The MR suggested a solid pancreatic uncinate process mass. A repeat EUS showed changes of chronic pancreatitis but no mass. A comprehensive review of the combination of intrahepatic strictures, pancreatic atrophy and uncinate mass suggested a diagnosis of IgG4 disease; an ANA was positive at 1:160 and IgG4 was elevated at 1,250 mg/dL (normal < 123). The patient was started on prednisone and had complete resolution of abnormal liver tests, clinical symptoms, MR biliary ductal dilatation, and MR pancreatic mass within 3 weeks. DISCUSSION: While described in AIP, IgG-4 related diseases can affect multiple organs, including kidneys, liver, salivary gland, orbit, breast, pericardium, aorta, skin, lungs, prostate, meninges, and the pituitary gland. IgG4-related cholangiopathy is a distinct yet rare etiology, characterized by elevated serum IgG4 levels and IgG4-positive plasma cell infiltration with storiform fibrosis/obliterative phlebitis of the bile duct wall. It has been identified in patients with concomitant AIP and is steroid responsive. Early diagnosis of IgG4 cholangiopathy avoids prolonged hospitalizations, unnecessary repeated procedures, and morbidity/mortality due to treatment delay We describe a rare case of IgG4 autoimmune cholangiopathy with delayed diagnosis due to concern for ChCA.

IgG4-related disease (IgG4-RD) in developmental age — diagnostic and therapeutic problems

The IgG4-related disease (IgG4-RD) is a type of a Hypergammaglobulinemia with elevated class IgG4 of unknown aetiology. It is still rarely diagnosed due to lack of clear diagnostic criteria and uncertain ethiopathogenesis. The most characteristic features are lymphocytes and plasmocytes IgG4+ inflammatory infiltrations located in various tissues and organs with elevated blood serum levels of IgG4. It mostly affects lacrimal glands, salivary glands and pancreas, therefore the clinical picture may suggest the Sjogren syndrome. The inflammatory process that is chronic and reccurent finally leads to fibrosis and sclerosis of affected tissues and organs function deterioration. The clinical picture of IgG4-RD is highly variable depending on which organs are affected. Most patients may be treated with glycocortykosteroids, however some of them develop recrudescence. The article consists of case report of the 11-yearsold boy diagnosed with the IgG4-RD. The authors showed the diagnostic and therapeutic process paying particular attention to avoid diagnostic traps. They discussed the diagnostic criteria and differential diagnostics. The IgG4-RD among pediatric population is still barely known by paediatricians. Only isolated cases are described so far. Forum Reumatol. 2019, tom 5, nr 3: 149–153

Assessment of the immunogenicity of the leptospiral LipL32, LigAni, and LigBrep recombinant proteins in the sheep model

Veterinary leptospirosis vaccines are composed of bacterins and present limitations, for example, the need for bacteriological culture and serovar-dependent immunity. Recombinant antigens represent a promising alternative. LigAni, LigBrep, and LipL32 proteins have been shown to promote a protective immune response against the homologous challenge in hamsters. Therefore, the next step is to evaluate the immunological properties of these immunogens in the actual hosts, as ruminants, which has never been performed before. The objective of this study was to evaluate the immunogenicity and potential adverse effects of the recombinant proteins LigAni, LigBrep, and LipL32 in the ovine model. For this, 16 Santa Inês sheep were allocated into three groups: two experimental (Groups A and B) and one control group (Group C). Group A was inoculated with a formulation containing the recombinant proteins in combination with the aluminum hydroxide adjuvant; Group B was inoculated with a formulation containing the recombinant proteins in combination with the Montanide adjuvant; and Group C was inoculated with adjuvants only. The results revealed that formulations containing the recombinant proteins induced total IgG seroconversion and led to a significant increase in antibody titers in the sheep model. Besides, there were no clinical changes or adverse effects. Thus, LigAni, LigBrep, and LipL32 proteins elicited a significant humoral immune response with elevated serum IgG levels, demonstrating that they possess the immunogenic and safety characteristics necessary to sustain their potential use as leptospirosis vaccines in the ruminant model.

Abdominal aortic aneurysm as an IgG4-related disease

SummaryThe objectives of this study were to evaluate patients with aortic abdominal aneurysm (AAA) with regard to immunoglobulin (Ig)G4‐related disease (IgG4‐RD). IgG4‐RD represents a recently defined condition comprised of a collection of disorders characterized by IgG4 hypergammaglobulinemia, the presence of IgG4‐positive plasma cells in organs affected with fibrotic or sclerotizing changes and typical histopathological features. It was identified as a possible cause of vasculitis in large vessels. Studies have been published on a possible association between inflammatory aortic or cardiovascular disease and IgG4‐RD. We examined 114 patients with AAA requiring surgery in order to identify findings which are characteristic of IgG4‐RD. Aneurysm samples from seven patients showed histopathological features consistent with IgG4‐RD and the presence of IgG4+ plasma cells. Only two of these seven patients showed elevated IgG4 serum levels higher 1·35 g/l. In five of the patients, the concentration of serum IgG4 was lower than 1·20 g/l, with the number of IgG4+ plasma cells being higher than 50/high‐power field. These findings were consistent with AAA being a heterogeneous group of inflammatory diseases with different pathogenesis.

IgG4 Related Disease of Epididymis, Mimicking Testicular Malignancy – A Rare Entity

Immunoglobulin G4 related disease (IgG4-RD) is a systemic fibro inflammatory condition that usually presents with multiorgan involvement. We present a rare case of 54 year old male with an isolated IgG4-RD of epididymis. The patient presented with a progressive swelling of the left testicle. A clinical diagnosis of tuberculosis was made. Ultrasound scrotum showed a relatively hetero-echoic mass lesion involving the left epididymis in close proximity to the left testis. There was a focal spindle cell proliferation and an increase in number of plasma cells and keloid like collagen. Immunohistochemistry was positive for vimentin and IgG4 and negative for CD34. Serum level of IgG4 was elevated (165 mg per dL). Computed tomography of abdomen and thorax did not show any systemic involvement. HE was posted for excision of the epididymal mass. Intraoperatively, the mass was found to be densely adherent to left testicle and inseparable from it, necessitating left total orchiectomy. Histopathology and immunohistochemistry with elevated serum IgG4 levels confirmed the diagnosis of IgG4-RD of the epididymis. To the best of our knowledge, this condition is an extremely rare entity, with only very few cases of isolated IgG4-RD of epididymis reported in medical literature, with no other systemic manifestations.

Elevated Serum IgG Levels Positively Correlated with IL-27 May Indicate Poor Outcome in Patients with HBV-Related Acute-On-Chronic Liver Failure.

Background and Aims Serum immunoglobulins are frequently increased in patients with chronic liver disease, but little is known about the role of serum immunoglobulins and their correlations with interleukin-27 (IL-27) in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). This study was aimed at determining the role of serum immunoglobulin (IgG, IgA, and IgM) levels and their associations with IL-27 in noncirrhotic patients with HBV-ACLF. Methods Samples were assessed from thirty patients with HBV-ACLF, twenty-four chronic hepatitis B (CHB) subjects, and eighteen normal controls. Disease severity of HBV-ACLF was evaluated. Serum IL-27 levels were examined by enzyme-linked immunosorbent assay. Immunoglobulin levels were assessed using immunoturbidimetric assay. Correlations between immunoglobulin levels and IL-27 were analyzed. Receiver operating characteristic (ROC) curves were used to predict the 3-month mortality. Results 25 (83.3%) HBV-ACLF patients had elevated serum IgG levels (>1 ULN), 14 (46.7%) patients had elevated IgA, and 15 (50%) had raised IgM. IgG, IgA, and IgM levels were higher in HBV-ACLF patients than in CHB patients and normal controls. Moreover, IgG, IgA, and IgM levels were positively correlated with Tbil levels but negatively correlated with prothrombin time activity (PTA) levels. Additionally, IgG levels were significantly increased in nonsurviving patients than in surviving HBV-ACLF patients (P = 0.007) and positively correlated with MELD score (r = 0.401, P = 0.028). Also, IgG levels were positively correlated with IL-27 levels in HBV-ACLF patients (r = 0.398, P = 0.029). Furthermore, ROC curve showed that IgG levels could predict the 3-month mortality in HBV-ACLF patients (the area under the ROC curve: 0.752, P = 0.005). Conclusions Our findings demonstrated that serum immunoglobulins were preferentially elevated in HBV-ACLF patients. IgG levels were positively correlated with IL-27 and may predict prognosis in HBV-ACLF patients.

Urological manifestations of the disease related to immunoglobulin G4.

Immunoglobulin G4 related disease (IgG4-RD) is a fibro-inflammatory disease of unknown etiology, characterized by lesions in the form of tumors, elevated serum IgG4 levels, plasma cells with significant IgG4 infiltration, accompanied by phlebitis obliterans and fibrosis. This disease usually has multiorgan disease, including pancreas, biliary tract, salivary glands, peri orbital tissues, kidneys, lungs, lymph nodes and retro peritoneum. IgG4-RD mainly affects men with a predominance of age by young adults until old age. The clinical manifestations of IgG4-RD, depend mainly on the organs affected and the response to steroids. His forecast is not yet clear. Within the affected urogenital organs can be observed kidney, retroperitoneum, ureter, bladder, urachus, testis/epididymis, paratesticular region, prostate and urethra.

Urological manifestations of the disease related to immunoglobulin G4

Immunoglobulin G4 related disease (IgG4-RD) is a fibro-inflammatory disease of unknown etiology, characterized by lesions in the form of tumors, elevated serum IgG4 levels, plasma cells with significant IgG4 infiltration, accompanied by phlebitis obliterans and fibrosis. This disease usually has multiorgan disease, including pancreas, biliary tract, salivary glands, peri orbital tissues, kidneys, lungs, lymph nodes and retro peritoneum. IgG4-RD mainly affects men with a predominance of age by young adults until old age. The clinical manifestations of IgG4-RD, depend mainly on the organs affected and the response to steroids. His forecast is not yet clear. Within the affected urogenital organs can be observed kidney, retroperitoneum, ureter, bladder, urachus, testis/epididymis, paratesticular region, prostate and urethra.

Clinical manifestations and risk factors of arthropathy in cystic fibrosis.

Recurrent joint pain is frequently observed in patients with CF and can lead to reduced activity and quality of life. We conducted this observational study to assess the clinical manifestations, frequency, and risk factors of CF associated arthropathy. Clinical data were collected using a digital quality management system, medical records, and by conducting structured interviews. Univariate and multivariate statistical analysis were performed for statistical interpretation. retrospective observational study including 186 patients. Of 186 patients (Demographics: Mean age 27 years, female gender 104/186 (57%), CFTR F508del homozygous 82/186 (44%) included in the study, 54/186 (29%) had experienced joint symptoms. Joint pain and swelling were the most frequent symptoms. The joints of the hands (JOH) followed by the joints of the feet were most affected. No specific pattern of autoantibodies was discovered. The level of total serum IgG, age, female gender, and pulmonary exacerbations per year were significant risk factors for arthropathy in the study cohort. Joint symptoms in CF are a frequent and clinically relevant phenomenon with a distinct clinical pattern. Pulmonary exacerbations and elevated levels of total serum IgG may reflect chronic inflammation in patients with CF and may lead to a specific arthropathy associated with this condition.

Immunophenotype involved in IgG4-related disease

As stated in the comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), IgG4-RD is characterized by elevated serum IgG4 level and pathological findings, characterized by infiltration of IgG4-positive plasma cells. In addition to fibrotic changes, dysregulated activation of lymphocytes is considered as one of major pathogenic events in IgG4-RD. Among lymphocytes, the importance of plasmablast, T follicular helper (Tfh) cells, T type 2 helper (Th2) cells, T regulatory (Treg) cells, and CD4 positive T cells with cytotoxic activity has been reported. Conversely, comprehensive immunophenotyping in patients with IgG4-RD revealed that there are two different axes consisting plasmablast-Tfh cells and Treg cells. There is need for research to seek out molecules associated with these immunocompetent cell interactions. It is believed that this will contribute to the future application to disease-specific treatment for IgG4-RD.

IgG4-related disease in the head and neck.

To summarize current evidence regarding the pathophysiology, diagnostic criteria, and management of IgG4 disease in the head and neck. The anti-CD20 antibody, rituximab is being used increasingly as a primary treatment modality in cases with a definitive diagnosis. Despite the favorable prognosis, it is now recognized that the incidence of cancer development within 3 years of diagnosis is higher than that of the general population. IgG4-related disease is a sclerosing, chronic inflammatory disease, that is benign, and usually occurs in middle-aged to elderly individuals. Definitive diagnosis of IgG4-related disease requires radiological confirmation of enlargement of the affected organ, elevated serum IgG4 levels, and characteristic histopathological findings. Treatment is primarily with systemic corticosteroids or the monoclonal anti-CD20 antibody rituximab, surgical excision, or a combination of treatment modalities. Prognosis is good with complete remission in up to 90% of patients.

IgG4-associated sclerosing cholangitis: a diagnosis that may change the course of events (review of the literature and a clinical case)

Immunoglobulin G4-associated sclerosing cholangitis (IgG4-SC) can mimic primary sclerosing cholangitis, cholangiocarcinoma, and pancreatic adenocarcinoma. Its proper diagnosis allows for an adequate therapy and an improvement of the outcomes. The article presents a short literature review with an emphasis on the challenging diagnostic and therapeutic aspects, illustrated by a clinical case. The diagnosis of IgG4-SC is based on a combination of biochemical, radiological and histological signs and symptoms, including elevated levels of serum IgG4, intra- and extrahepatic biliary strictures detected by magnetic resonance cholangiography, and multifocal IgG4-lymphoplasmic infiltrations, sclerosing fibrosis of the bile ducts, seen at morphological assessment. Glucocorticoids (GCS) are the first line agents to achieve remission in patients with IgG4-SC. Most patients respond well to the systemic GCS. However, about 20% of patients (mostly those with extensive sclerotic intra- and/or extrahepatic abnormalities and signs of advanced disease / cirrhosis) show an insufficient or no response from the beginning of the treatment. The clinical case illustrates that timely verification of the IgG4-SC diagnosis may have an important prognostic value. The case history of a 62-year old female patient confirms the difficulties of the early diagnosis of the disease: for a relatively long time, the patient had the diagnosis of primary sclerosing cholangitis. Delay with GCS prescription (the treatment was initiated only at the stage of liver cirrhosis) had led to the lack of clinical efficacy and development of complications, such as relapsing cholangitis with advanced biliary strictures. In patients with suspected primary sclerosing cholangitis, timely differential diagnosis with IgG4-SC is relevant, because early GCS administration can slow the progression of the disease.

Multivisceral IgG4-related disease presenting as recurrent massive gastrointestinal bleeding: a case report and literature review

BackgroundIgG4-related disease (IgG4-RD) is a newly recognized autoimmune systemic disorder characterized by elevated levels of serum IgG4 and abundant infiltration of IgG4-positive plasmacytes in the affected organs. The liver, biliary system and pancreas are the most commonly affected organs. However, involvement of the digestive tract is very rare. To date, only a few cases of isolated gastric IgG4-RD have been reported.Case presentationWe present a case of IgG4-RD of the liver, gallbladder, pancreas and duodenum, which was clinically misinterpreted and thereafter over-treated. A 52-year-old male presented with obstructive jaundice for 3 years, melena for 5 months and hematemesis for 10 days. Three years prior, the patient had undergone biopsies of pancreatic lesions, liver lesions, cholecystectomy and choledochojejunostomy. Histopathology showed chronic inflammatory changes. Endoscopy at admission revealed a duodenal ulcer with active bleeding. Despite medical management, the patient presented with repeated gastrointestinal bleeding. Upon evaluation, serum IgG4 levels were found to be elevated. Histopathology of the duodenal ulcer biopsy and repeated examination of the gallbladder and pancreatic and liver biopsies confirmed IgG4 positive plasma cell infiltration. A definitive diagnosis of IgG4-RD was made and steroid administration was initiated. At last follow up, 11 months to-the-day after initiating steroid treatment, the patient was asymptomatic.ConclusionsNotably, IgG4-RD of multiple digestive organs is still very rare. As a systemic disease, it is characterized by the infiltration of IgG4-bearing plasma cells and raised IgG4 levels. Histopathology findings remain the diagnostic gold standard for this disorder.

Efficacy and safety of low dose Mycophenolate mofetil treatment for immunoglobulin G4-related disease: a randomized clinical trial.

This randomized, controlled clinical trial aims to compare the efficacy and safety of glucocorticoid combined with MMF and glucocorticoid monotherapy for patients with IgG4-related disease. Sixty-nine patients newly diagnosed with IgG4-related disease were randomly divided into two groups (35 patients in Group I and 34 patients in Group II). Patients in Group I received glucocorticoid monotherapy (0.6-0.8 mg/(kg·day) and tapered gradually); patients in Group II received glucocorticoid combined with MMF therapy (1-1.5 g/day). All the patients were followed up at 1, 3, 6 and 12 months. The primary endpoint was response rate in 12 months and the secondary endpoints were relapse, remission rate and adverse reactions. Group I and Group II shared almost the same efficacy at the 1 month treatment, but during the follow-up, the complete response rate in Group II was much higher than that in Group I at different time points, and the cumulative relapse rate during 1 year of therapy was much higher in Group I than that in Group II (40.00 vs 20.59%). The remission rate was lower in Group I (51.42 vs 76.47%). Relapses were more likely to happen in lung, lacrimal gland, salivary gland, paranasal sinus and kidney. MMF could reduce relapse, especially organs recurrence. No serious adverse reactions occurred in the two groups. Combination treatment with glucocorticoid and MMF was more effective than the monotherapy, and the relapse of IgG4-related disease might be associated with the elevated levels of serum IgG4 and the low glucocorticoid maintenance dose. ClinicalTrials.gov, www.clinicaltrials.gov, NCT02458196.

High level of IgG4 as a biomarker for a new subset of inflammatory bowel disease

The roles of B and plasma cells in the pathogenesis of inflammatory bowel disease (IBD) are largely unrevealed. Data on the characteristics of IgG4 in patients with IBD are scarce. In this case-control study, serum IgG4 levels were comparable between patients with IBD and healthy individuals, whereas patients with IBD had dramatically higher mucosal IgG4 counts than healthy individuals. In patients with UC, mucosal IgG4 counts were positively correlated with serum IgG4 levels, serum IgG4/IgG ratios, and the Mayo Index; serum IgG4 levels and IgG4/IgG ratios were associated with a history of intestinal surgery and medications. A significant mucosal IgG4 count was found in 33.3% of patients with IBD, whereas, elevated serum IgG4 levels were found in only 9.9% of patients with IBD. Lesions were more severe and extensive in IBD patients with high levels of serum and mucosal IgG4. High levels of serum and mucosal IgG4 decreased after treatment with glucocorticoids or other immunosuppressants. High IgG4 level may be a biomarker for a new subset of IBD. More studies are warranted to explore this new subset of IBD for personalized therapy in the future.

Research status and challenges in immunoglobulin G4-related hepatobiliary disease

IgG4-associated hepatobiliary diseases are group of autoimmune diseases characterized by lymphoplasmacytic infiltrates with an elevated serum IgG4 levels, affecting pancreas and biliary tract. In addition, it mainly includes IgG4-related sclerosing cholangitis, IgG4-related autoimmune pancreatitis and IgG4-related autoimmune hepatitis. An accurate diagnosis helps to avoid unnecessary surgery. Notably, an early diagnosis and treatment can improve the prognosis and enhance the quality of life. This review will focus on research advances and difficulties encountered in the study of IgG4 related hepatobiliary diseases.

Interleukin-4 contributes to the shift of balance of IgG subclasses toward IgG4 in IgG4-related disease

IgG4-related disease (IgG4-RD) is a systemic disorder characterized by elevated serum IgG4 level, which is mediated by T follicular helper 2 (Tfh2) cell. However, the cytokines responsible for enhancing IgG4 production remain unclear in IgG4-RD. The aim of this study was to identify responsible Tfh2-related cytokines (interleukin (IL)-4 and IL-21) for enhancing IgG4 production in IgG4-RD. Peripheral blood mononuclear cells obtained from consecutive patients with active, untreated IgG4-RD and healthy controls were examined. The production of both IgG and IgG4 were significantly increased by stimulation with IL-4 alone as well as IL-21 alone compared to background stimulation with anti-CD40 antibody in IgG4-RD. On the other hand, the IgG4/IgG ratio was statistically higher by stimulation with IL-4 alone compared to the other Tfh2-related cytokines including IL-21 in IgG4-RD. IgG4 production was not increased by stimulation with IL-4 in healthy controls. These results suggest that IL-4 can contribute to the shift of balance of IgG subclasses toward IgG4 compared to the other Tfh2-related cytokines in IgG4-RD.

Multiple solid pancreatic lesions: Prevalence and features of non-malignancies on dynamic enhanced CT

ObjectiveTo determine the prevalence of multiple solid pancreatic lesions on dynamic enhanced CT performed for suspected pancreatic diseases, and to identify CT features of non-malignancies. MethodsWe investigated 8096 consecutive patients who underwent dynamic enhanced CT pancreas protocol at a tertiary center over 40 months. The final clinical /pathological diagnosis served as reference standard. The diagnostic accuracy of dynamic enhanced CT for non-malignancies was calculated. A univariate and multivariate analysis was conducted to identify features that predict non-malignancies. ResultsMultiple solid pancreatic lesions were identified in 121 patients. The prevalence of non-malignancies was 19.8% (24/121). The most common non-malignancy was autoimmune pancreatitis (n = 21; 17.4%). Common lesions with malignant potential included neuroendocrine neoplasia (n = 62; 51.2%), ductal adenocarcinoma (n = 15; 12.4%), metastasis (n = 9; 7.4%), and lymphoma (n = 7; 5.8%). Dynamic enhanced CT had a sensitivity of 79.2% and a specificity of 92.8% for diagnosing non-malignancies. Elevated serum IgG4 level (p < 0.001), hypo-enhancement in arterial phase (p = 0.001), hyper-enhancement in equilibrium phase (p = 0.009) and location in both proximal and distal pancreas (p = 0.036) were predictors of non-malignancies, whereas pancreatic duct morphology and vascular invasion status were not. ConclusionMultiple solid pancreatic lesions were rare, with a wide spectrum. Dynamic enhanced CT provides clues for identifying non-malignancies.

IgG4-associated cholangitis - clinical presentation of an overlooked disease entity

IgG4-associated cholangitis (IAC) is the hepatobiliary manifestation of immunoglobulin G4-related disease, which is an immune-mediated fibroinflammatory systemic disorder characterised by often elevated IgG4 serum levels and typical histopathological findings in affected tissues. IAC is frequently (>90%) accompanied by autoimmune pancreatitis type1 (AIP), which is the pancreatic manifestation of immunoglobulin G4-related disease. In 80-85% of the cases patients with IAC are male, above 50years of age and present with jaundice and weight loss. Aremarkable percentage of patients with IAC has ahistory of long-term exposure to solvents, oil products and other organic agents representing so-called "blue-collar workers". Clinical features and imaging (i. e. strictures or mass-forming lesions in the biliary tract) may mimic other biliary diseases, such as primary or secondary sclerosing cholangitis and cholangiocarinoma. The HISORt criteria are used for diagnosing IAC and comprise histologic and imaging findings, serum IgG4, organ manifestation pattern and response to immunosuppressive therapy. Serum IgG4 levels are of diagnostic value when it is above 4times the upper limit of normal. Determination of the blood IgG4/IgG mRNA ratio using quantitative polymerase chain reaction (qPCR) is an accurate diagnostic tool currently under clinical validation. The majority of patients show an excellent response to corticosteroid therapy. Symptom recurrence, however, is common making long-term treatment with low-dose prednisolone and/or azathioprine frequently necessary.

IgG4-Associated Cholangitis in Patients Resected for Presumed Perihilar Cholangiocarcinoma: a 30-Year Tertiary Care Experience.

Distinguishing perihilar cholangiocarcinoma (PHC) from benign forms of sclerosing cholangitis affecting the hilar bile ducts is challenging, since histological confirmation of PHC is difficult to obtain and accurate non-invasive diagnostic tests are not available. IgG4-associated cholangitis (IAC), an imitator of PHC, may present with clinical and radiographical signs of PHC. IAC can be accurately diagnosed with a novel qPCR test. The aim of this study was to investigate the incidence and long-term activity of IAC in patients resected for PHC in a single tertiary center over a period of 30 years. All patients with benign disease who underwent surgery for presumed PHC in our institute between 1984 and 2015 were identified. Benign liver and bile duct specimens were re-evaluated by a pathologist and scored according to international consensus pathology criteria for IgG4-related disease (IgG4-RD). Patients with benign disease still alive were followed-up and a clinical diagnosis of IAC was made using a combination of the HISORt group C (response to steroids) criteria and elevated serum IgG4 levels and/or the novel IgG4/IgG RNA ratio. Also, recurrent symptomatic disease at any time after surgery requiring immunosuppression was assessed. Out of 323 patients who underwent surgery for presumed PHC, 50 patients (15%) had benign disease. In 42% (n = 21/50) of these patients a histological (n = 17) or clinical (n = 4) diagnosis of IAC was established. The remaining patients were diagnosed with unclassified sclerosing inflammation, cystadenoma, or sclerosing hemangioma. Nine out of 12 IAC patients who were followed-up showed episodes of recurrent disease requiring immunosuppressive treatment. Liver and bile duct resections for PHC during three decades disclosed in 15% benign biliary disorders mimicking PHC of which 42% were definitely diagnosed as IAC. IgG4-RD remains active in the majority of patients with IAC years after surgery. Novel diagnostic tests for IAC might reduce misdiagnosis, unnecessary surgery, and life-threatening complications.