Diagnosis of IgG4-related sclerosing cholangitis

IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis(PSC),and the presence of segmental stenosis suggests cholangiocarcinoma(CC).IgG4-SC responds well to steroid therapy,whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention.Since IgG4-SC was first described,it has become a third distinct clinical entity of sclerosing cholangitis.The aim of this review was to introduce the diagnostic methods for IgG4-SC.IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical,serological,morphological,and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis.When intrapancreatic stenosis is detected,pancreatic cancer or CC should be ruled out.If multiple intrahepatic stenoses are evident,PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining.Associated inflammatory bowel disease is suggestive of PSC.If stenosis is demonstrated in the hepatic hilar region,CC should be discriminated by ultrasonography,intraductal ultrasonography,bile duct biopsy,and a higher cutoff serum IgG4 level of 182 mg/dL.     

Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012

Background

IgG4-sclerosing cholangitis (IgG4-SC) patients have an increased level of serum IgG4, dense infiltration of IgG4-positive plasma cells with extensive fibrosis in the bile duct wall, and a good response to steroid therapy. However, it is not easy to distinguish IgG4-SC from primary sclerosing cholangitis, pancreatic cancer, and cholangiocarcinoma on the basis of cholangiographic findings alone because various cholangiographic features of IgG4-SC are similar to those of the above progressive or malignant diseases.

Methods

The Research Committee of IgG4-related Diseases and the Research Committee of Intractable Diseases of Liver and Biliary Tract in association with the Ministry of Health, Labor and Welfare, Japan and the Japan Biliary Association have set up a working group consisting of researchers specializing in IgG4-SC, and established the new clinical diagnostic criteria of IgG4-SC 2012.

Results

The diagnosis of IgG4-SC is based on the combination of the following 4 criteria: (1) characteristic biliary imaging findings, (2) elevation of serum IgG4 concentrations, (3) the coexistence of IgG4-related diseases except those of the biliary tract, and (4) characteristic histopathological features. Furthermore, the effectiveness of steroid therapy is an optional extra diagnostic criterion to confirm accurate diagnosis of IgG4-SC.

Conclusion

These diagnostic criteria for IgG4-SC are useful in practice for general physicians and other nonspecialists.     

Diagnostic procedures for IgG4-related sclerosing cholangitis

Background/purpose

IgG4-related sclerosing cholangitis (IgG4-SC) is one of several diseases associated with autoimmune pancreatitis (AIP). However, diffuse cholangraphic abnormalities seen in association with AIP may resemble those seen in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma. IgG4-SC responds well to steroid therapy, whereas in contrast, liver transplantation is the only effective therapy for PSC, and surgical intervention is also needed for cholangiocarcinoma. The aim of this review was to establish the diagnostic procedures for IgG4-SC.

Methods

A literature search was conducted, covering English-language articles dealing with IgG4-SC published between 1991 and March 2010. As clinical data on IgG4-SC are limited, the author also took into consideration his own clinical experience with the treatment of IgG4-SC over a period of more than 19 years.

Results

When intrapancreatic stenosis is detected, pancreatic cancer should be ruled out. If multiple intrahepatic stenosis is evident, PSC should be discriminated on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. An association with inflammatory bowel disease (IBD) is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, cholangiocarcinoma should be discriminated by US, EUS, IDUS, and bile duct biopsy.

Conclusion

For diagnosis of IgG4-SC, coexistence of AIP is the most useful finding. However, the most important consideration for clinicians is to be aware of IgG4-SC when encountering patients with obstructive jaundice.     

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.     

Diagnostic criteria for IgG4-related sclerosing cholangitis based on cholangiographic classification

Background  

IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from pancreatic cancer (PCa), primary sclerosing cholangitis (PSC), and cholangiocarcinoma (CC). We attempted to establish diagnostic criteria for IgG4-SC based on cholangiographic classification by comparison with several diagnostic modalities.     

IgG4相关硬化性胆管炎的研究进展

免疫球蛋白G4相关硬化性胆管炎(immunoglob-ulin G4-related sclerosing cholangitis,IgG4-SC)是一种新近认识的以血清IgG4升高、慢性进行性阻塞性黄疸、弥漫性或局限性IgG4阳性浆细胞和淋巴细胞组织浸润、纤维化及闭塞性静脉炎为特征的慢性炎症性疾病,常并发自身免疫性胰腺炎(autoimmune pancreatitis,AIP),其临床、生化及影像学特征与原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)或胆管癌(cholangiocarcinoma,CC)相似.类固醇激素是IgG4-SC的主要治疗手段,而肝移植是PSC唯一的有效治疗方法,CC则需外科手术治疗.因此,IgG4-SC与PSC或CC间的准确鉴别是目前面临的一个十分重要的课题.本文详尽地阐述了免疫球蛋白G4(immunoglobulin G4,IgG4)的特征和功能,IgG4-SC的诊断和治疗,IgG4-SC与AIP、PSC及CC之间关系等研究进展,为IgG4-SC的精确诊断和治疗提供了新的思路.     

Usefulness of laparoscopy and intraductal ultrasonography in a patient with isolated immunoglobulin G4-related sclerosing cholangitis

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is often associated with type 1 autoimmune pancreatitis, and the frequency of isolated IgG4-SC seems to be quite low, making the diagnosis of isolated IgG4-SC challenging. A 63-year-old male was admitted to our hospital for frequent fever. Abdominal magnetic resonance cholangiopancreatography showed diffuse narrowing of the common bile duct and post-stenotic dilatation of the right posterior bile duct. Laboratory tests showed abnormalities in the levels of hepatobiliary enzymes and serum IgG4 levels. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing of intrahepatic bile ducts and post-stenotic dilatation of the right posterior bile duct but no abnormalities in the pancreas. Intraductal ultrasonography showed symmetric circumferentially thickened walls of both narrowed and non-narrowed common bile ducts. Histologic examination of the common bile duct mucosa showed infiltration of IgG4-positive plasma cells. Laparoscopic observations showed discoloration with red lobular markings and multiple small depressed lesions. Liver histology showed mild cholangitis with infiltration of IgG4-positive plasma cells around the bile ducts. From these findings, the patient was diagnosed with isolated IgG4-SC. After treatment with a steroid, bile duct dilatations improved. Laparoscopy and intraductal ultrasonography were useful to diagnose isolated IgG4-SC.     

IgG4相关性硬化性胆管炎100例临床特征分析

目的 由于临床和影像学表现的相似及临床医生认知不足,IgG4相关性硬化性胆管炎(IgG4-SC)常被误诊为原发性硬化性胆管炎(PSC)或胆管癌(CC)等胆汁淤积性疾病,而采取了不必要的手术治疗,因此对IgG4-SC的准确认识非常重要。目前,对IgG4-SC的临床研究比较缺乏,文献多为零星的临床病例报道,缺乏系统总结。我们通过汇总分析国内报道的病例,探讨了IgG4-SC患者的临床特点和误诊原因,以提高对该病的认识和诊断水平。方法 以“IgG4相关性硬化性胆管炎”为关键词在中国知网数据库、万方数据库和维普数据库检索2019年9月前公开发表的文献,并提取相关病例的一般资料、临床表现、实验室检查、影像学表现、病理学特征、误诊情况、治疗和预后等信息进行汇总分析。结果 纳入25篇文献,包括100例患者,男女比例为4∶1,平均发病年龄为(58.8±12.3)岁;最常见的临床表现为黄疸(85%)和腹痛(53%); 94.2%(81/86)患者血清IgG4水平增高,33%患者血清CA19-9升高;影像学表现为胆总管下段狭窄57例,肝门区胆管狭窄伴肝内胆管扩张15例;34例肝组织检查发现胆囊壁/胆管壁纤维组织增生伴大量淋巴细胞和浆细胞浸润,可见闭塞性静脉炎或席纹状硬化;免疫组化检测,15例显示IgG4⁺浆细胞>10/HPF;在100例中,12例因误诊为胆管癌而实施手术治疗,61例应用糖皮质激素治疗,58例(95%)病情缓解。结论 IgG4-SC患者多以梗阻性黄疸和腹痛为主要表现,在临床和影像学表现上与原发性硬化性胆管炎和胆管癌十分相似,需注意鉴别诊断。     

Endoscopic transpapillary intraductal ultrasonography and biopsy in the diagnosis of IgG4-related sclerosing cholangitis

Purpose  

IgG4-related sclerosing cholangitis (IgG4-SC) is one of the diseases associated with autoimmune pancreatitis. Several cases of IgG4-SC showed no pancreas abnormalities and it was difficult to distinguish cholangiocarcinoma. We aimed to clarify the findings of transpapillary intraductal ultrasonography (IDUS) and bile duct biopsy in the patients with IgG4-SC.     

Inflammatory bowel disease of primary sclerosing cholangitis: A distinct entity?

This is a review of the characteristic findings of inflammatory bowel disease(IBD)associated with primary sclerosing cholangitis(PSC)and their usefulness in the diagnosis of sclerosing cholangitis.PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD.IBDassociated with PSC(PSC-IBD)shows an increased incidence of pancolitis,mild symptoms,and colorectal malignancy.Although an increased incidence of pancolitis is a characteristic finding,some cases are endoscopically diagnosed as right-sided ulcerative colitis.Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon.The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition.The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)are similar to those of PSC.The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.     

Role of endoscopy in the diagnosis of autoimmune pancreatitis and immunoglobulin G4‐related sclerosing cholangitis

Autoimmune pancreatitis (AIP) must be differentiated from pancreatic carcinoma, and immunoglobulin (Ig)G4‐related sclerosing cholangitis (SC) from cholangiocarcinoma and primary sclerosing cholangitis (PSC). Pancreatographic findings such as a long narrowing of the main pancreatic duct, lack of upstream dilatation, skipped narrowed lesions, and side branches arising from the narrowed portion suggest AIP rather than pancreatic carcinoma. Cholangiographic findings for PSC, including band‐like stricture, beaded or pruned‐tree appearance, or diverticulum‐like outpouching are rarely observed in IgG4‐SC patients, whereas dilatation after a long stricture of the bile duct is common in IgG4‐SC. Transpapillary biopsy for bile duct stricture is useful to rule out cholangiocarcinoma and to support the diagnosis of IgG4‐SC with IgG4‐immunostaining. IgG4‐immunostaining of biopsy specimens from the major papilla advances a diagnosis of AIP. Contrast‐enhanced endoscopic ultrasonography (EUS) and EUS elastography have the potential to predict the histological nature of the lesions. Intraductal ultrasonographic finding of wall thickening in the non‐stenotic bile duct on cholangiography is useful for distinguishing IgG4‐SC from cholangiocarcinoma. Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is widely used to exclude pancreatic carcinoma. To obtain adequate tissue samples for the histological diagnosis of AIP, EUS‐Tru‐cut biopsy or EUS‐FNA using a 19‐gauge needle is recommended, but EUS‐FNA with a 22‐gauge needle can also provide sufficient histological samples with careful sample processing after collection and rapid motion of the FNA needles within the pancreas. Validation of endoscopic imaging criteria and new techniques or devices to increase the diagnostic yield of endoscopic tissue sampling should be developed.     

First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia

To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.     

Sclerosing cholangitis associated with autoimmune pancreatitis differs from primary sclerosing cholangitis

AIM： To clarify the characteristic features of biliary lesions in patients with autoimmune pancreatitis （AIP） and compare them with those of primary sclerosing cholangitis （PSC）.METHODS： The clinicopathological characteristics of 34 patients with sclerosing cholangitis （SC） associated with AIP were compared with those of 4 patients with PSC.RESULTS： SC with AIP occurred predominantly in elderly men. Obstructive jaundice was the most frequent initial symptom in SC with AIP. Only SC patients with AIP had elevated serum IgG4 levels, and sclerosing diseases were more frequent in these patients. SC patients with AIP responded well to steroid therapy. Segmental stenosis of the lower bile duct was observed only in SC patients with AIP, but a beaded and prunedtree appearance was detected only in PSC patients.Dense infiltration of IgG4-positive plasma cells was detected in the bile duct wall and the periportal area, as well as in the pancreas, of SC patients with AIP.CONCLUSION： SC with AIP is distinctly different from PSC. The two diseases can be discriminated based on cholangiopancreatographic findings and serum IgG4 levels.     

Pathology and immunopathology of immunoglobulin G4-related sclerosing cholangitis: The latest addition to the sclerosing cholangitis family

Sclerosing cholangitis is heterogeneous in its etiopathogenesis. Recently, sclerosing cholangitis showing abundant immunoglobulin (Ig)G4+ plasma cell infiltration was added to the sclerosing cholangitis group. This form was frequently associated with sclerosing pancreatitis (autoimmune pancreatitis) and also occasionally with other diseases such as chronic sclerosing sialadenitis, all of which falls within IgG4-related sclerosing disease. Herein, this new member, called IgG4-related sclerosing cholangitis (IgG4-SC), is reviewed. IgG4-SC shows grossly medullary and fleshy lesions along the biliary tree, and histologically marked lymphoplasmacytic infiltration with extensive fibrosis, and obliterative phlebitis, sharing histopathological features with sclerosing pancreatitis. Peribiliary glands are also severely affected. Interestingly, hepatic inflammatory pseudotumor (HIP) is not infrequently associated with IgG4-SC, and is thought as a local exaggeration of IgG4-SC. Immunohistochemically, many IgG4+ plasma cells and CD4+/CD25+ regulatory T cells are found around the affected bile ducts and portal tracts. Incontrast, these cells are scarce in the affected bile ducts of primary sclerosing cholangitis (PSC), a prototype of sclerosing cholangitis. Biliary lining epithelia are relatively spared in IgG4-SC in comparison with those of PSC showing degeneration and ulceration. In some cases of IgG4-SC, IgG4+ plasma cells are also found considerably in small portal tracts, so needle liver biopsy is useful for the diagnosis of IgG4-SC. Therapeutically, IgG4-SC responds well to steroid therapy, while such character is not reported in PSC. Taken together, IgG4-SC may be etiologically different from PSC, and immunopathological processes relating to IgG4 and regulatory T cells may be involved in the pathogenesis of IgG4-SC. Further studies are needed to clarify the etiopathogenesis of IgG4-SC and its related disorders.     

A case of sclerosing cholangitis without pancreatic involvement thought to be associated with autoimmunity

Sclerosing cholangitis (SC) is one of the lesions frequently seen in IgG4-related systemic diseases, causing biliary stricture and mimicking bile duct carcinoma and primary sclerosing cholangitis (PSC). Although it often accompanies autoimmune pancreatitis (AIP), autoimmune-related SC without a pancreatic lesion is very rare. A 79-year-old woman was referred to our institution with suspected diagnosis of bile duct carcinoma in the previous hospital. The patient was not icteric and fever free, but with an elevated level of serum biliary enzyme, which lead us to detect this disease. Clinical images including computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP) and intraductal ultrasonography (IDUS) demonstrated multiple strictures at the intrahepatic bile duct and enhanced wall thickness at the upper common bile duct, however her pancreas was normal. Repeated endoscopic procedures with multiple biopsies from the biliary strictures demonstrated fibrous ductal tissues with lymph-plasma cell infiltration (>10 IgG4(+) cells/HPF). By positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET), the uptake of FDG was not remarkable in areas other than the biliary lesions. Additional laboratory tests showed elevated levels of serum IgG (2,571 mg/dL), and γ-globulin (29%), and positive autoantibodies, but normal IgG4 (53.2 mg/dL). Together with clinical images, laboratory and histological findings, we diagnosed this patient as sclerosing cholangitis which was thought to be associated with autoimmunity. After one year of follow-up without steroid therapy, idiopathic thrombocytopenic purpura (ITP) developed with an increased level of serological markers. We encountered a rare case of sclerosing cholangitis expected to be associated with autoimmunity, which showed biliary strictures mimicking bile duct carcinoma and needed careful diagnosis. Unlike the typical AIP, the current case demonstrated distinct serological findings and no other organ involvement. Further study is needed to clarify the characteristics of sclerosing cholangitis associated with autoimmunity with a large number of cases.     

Autoimmune pancreatitis and IgG-positive sclerosing cholangitis

Sclerosing cholangitis is a heterogenous disease. Sclerosing cholangitis with an unknown cause is abbreviated PSC. PSC affects extra- as well as intra-hepatic bile ducts and since this is a permanently progressing fibrous condition, it leads to liver cirrhosis. The disease is often associated with a development of cholangocarcinoma and idiopathic intestinal inflammation. Causal therapy does not exist; liver transplantation is indicated. IgG4 cholangitis differs from PSC in a number of features. This form is, unlike PSC, linked to autoimmune pancreatitis (AIP) as well as other IgG4 sclerosing diseases. Anatomically, distal region of ductus choledochus is most frequently involved. Icterus is, unlike in PSC, a frequent symptom of AIP. There also is a distinctive histological picture--significant lymphoplasmatic infiltration of the bile duct wall with abundance of IgG4 has been described, lymphoplasmatic infiltration with fibrosis in the periportal area and the presence of obliterating phlebitis is also typical. However, intact biliary epithelium is a typical feature. IgG4 can be diagnosed even without concurrent presence of AIP. IgG4 sclerosing cholangitis is a condition sensitive to steroid therapy. At present, there is no doubt that IgG4 sclerosing cholangitis is a completely different condition to primary sclerosing cholangitis. From the clinical perspective, these diseases should be differentiated in every clinician's mind as (a) AIP is treated with corticosteroids and not with an unnecessary surgery, (b) IgG4 sclerosing cholangitis is mostly successfully treated with corticosteroids and the disease is not, unlike PSC, a risk factor for the development of cholangiocarcinoma.     

Small bile duct involvement in IgG4-related sclerosing cholangitis: liver biopsy and cholangiography correlation

Background

IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from primary sclerosing cholangitis (PSC). In this study, we performed a retrospective study to reveal cases in which liver needle biopsy was useful for differential diagnosis.

Methods

Nineteen patients with IgG4-SC and 22 patients with PSC were studied. All patients underwent endoscopic retrograde cholangiography and liver needle biopsy. We defined small bile duct involvement of IgG4-SC histologically as damage to the small bile duct associated with infiltration of ??10 IgG4+ plasma cells per high power field (HPF). Clinicopathological characteristics were compared between IgG4-SC patients with and without small bile duct involvement.

Results

Small bile duct involvement was observed in 5 (26%) of the patients with IgG4-SC. Patients with small bile duct involvement showed a higher incidence of intrahepatic biliary strictures on cholangiography (80 vs. 21%, p?=?0.038). Conversely, 4 of 7 (57%) patients with intrahepatic biliary strictures on cholangiography had histologically evident small duct involvement. The number of IgG4+ plasma cells was significantly correlated with the site of the most proximal stricture on cholangiograms (p?=?0.021). The number of IgG4+ plasma cells per HPF was significantly higher in IgG4-SC patients with intrahepatic biliary strictures than in those with PSC (13.4 vs. 0.4?cells/HPF, p?<?0.001).

Conclusions

Involvement of small bile ducts is more frequent in patients with intrahepatic biliary strictures on cholangiography, and liver needle biopsy is especially useful for these patients.     

Analysis of regulatory T cells and IgG4-positive plasma cells among patients of IgG4-related sclerosing cholangitis and autoimmune liver diseases

Objectives

Patients with autoimmune pancreatitis (AIP) characteristically show elevated serum levels of immunoglobulin G4 (IgG4) and abundant infiltration of IgG4-positive plasmacytes in the involved organs. The most common involved organ showing extrapancreatic lesions is the bile duct, which exhibits sclerosing cholangitis (SC). However, the role of IgG4 in the development of IgG4-related SC (IgG4-SC) remains unclear. To clarify the role of IgG4 in IgG4-SC, we have performed an immunohistochemical analysis of the bile duct.

Methods

Laboratory and immunohistochemical findings of liver biopsy specimens obtained from patients with IgG4-SC, primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cirrhosis (PBC) were compared. The biopsy specimens were first stained with anti-IgG1, anti-IgG4, and anti-Foxp3 (forkhead box P3) antibodies, and the ratio of IgG4-, IgG1-, and Foxp3-positive cells, respectively, to infiltrated mononuclear cells (IgG4/Mono, IgG1/Mono, Foxp3/Mono) was assessed.

Results

The ratio of IgG4/IgG1-positive plasma cells was significantly higher in specimens obtained from patients with IgG4-SC than in those from patients with PSC, AIH, and PBC. The Foxp3/Mono ratio in patients with PBC was significantly higher than that in patients with IgG4-SC and PSC. In patients with IgG4-SC, the number of Foxp3-positive cells was significantly correlated with the number of IgG4-positive cells; in the other patient groups, there was no correlation.

Conclusions

The IgG4/IgG1 ratio in the liver may be a useful marker for differential diagnosis of IgG4-SC and PSC. In IgG4-SC, abundant infiltration of regulatory T cells (Tregs) may affect the switching of B cells to IgG4-producing plasmacytes, and there is a possibility that the function of Tregs is different in IgG4-SC and other liver diseases (PSC, AIH, and PBC).     

Isolated intrapancreatic Ig G4-related sclerosing cholangitis

Immunoglobulin G4-related sclerosing cholangitis(Ig G4-SC) is frequently associated with type 1 autoimmune pancreatitis(AIP). Association with AIP can be utilized in the diagnosis of Ig G4-SC. However, some cases of Ig G4-SC are isolated from AIP, which complicates the diagnosis. Most of the reported cases of isolated Ig G4-SC displayed hilar biliary strictures, whereas isolated Ig G4-SC with intrapancreatic biliary stricture is very rare. Recently, we have encountered 5 isolated intrapancreatic Ig G4-SC cases that were not associated with AIP, three of which were pathologically investigated after surgical operation. They all were males with a mean age of 74.2 years. The pancreas was not enlarged in any of these cases. No irregular narrowing of the main pancreatic duct was found. Bile duct wall thickening in lesions without luminal stenosis was detected by abdominal computed tomography in all five cases, by endoscopic ultrasonography in two out of four cases and by intraductal ultrasonography in all three cases. In three cases, serum Ig G4 levels were within the normal limits. The mean serum Ig G4 level measured before surgery was 202.1 mg/d L(4 cases). Isolated intrapancreatic Ig G4-SC is difficult to diagnose, especially if the Ig G4 level remains normal. Thus, this type of Ig G4-SC should be suspected in addition to cholangiocarcinoma and pancreatic cancer if stenosis of intrapancreatic bile duct is present.     

Differentiating Immunoglobulin G4-Related Sclerosing Cholangitis from Hilar Cholangiocarcinoma

Background/Aims

Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC.

Methods

We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC.

Results

In patients with hilar CC, obstructive jaundice was more frequent (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were significantly higher and frequently elevated. The pancreas was enlarged in all IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01). Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC patients (p<0.01). Bile duct wall thickening in areas without stenosis was more frequent in IgG4-SC patients (p<0.01).

Conclusions

An integrated diagnostic approach based on clinical, serological, imaging, and histological findings is necessary to differentiate IgG4-SC from hilar CC.