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Highlighting the importance of early diagnosis in progressive multi-organ involvement of igg4-related disease: A case report and review of literature

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World Journal of Clinical Cases 2018年第13期6卷 707-715页

作者： Jing Xue Xue-Mei Wang Yan Li Li Zhu Xiao-Ming Liu Juan Chen Shu-Hong Chi Department of Rheumatology General Hospital of Ningxia Medical University Institute of Human Stem Cell Research General Hospital of Ningxia Medical University Department of Radiology General Hospital of Ningxia Medical University Department of Pulmonary and Critical Care Medicine General Hospital of Ningxia Medical University

igg4-related disease(igg4-RD)is an increasingly recognized pathological entity that tends to involve multiple organs with an elevated level of serum igg4,which is easily misdiagnosed owing to sharing common clinical features with a variety of other diseases.Here,we report an interesting igg4-RD case of a woman with progressive multi-organ involvement for over 19 years,started with swollen eyelids,dry eye and mouth,and polydipsia and hydruria.Imaging diagnosis revealed diffuse enlargement of the parotid glands,enlargement of the head of the pancreas,pulmonary infection and interstitial lung.Serological tests showed a remarkable elevation of the serum igg4,and cytological analysis further revealed a large amount of lymphoplasmacytic infiltration into the focal lobule,and igg 4-positive cell infiltration in bladder mucosa.Therapeutically,the patient responded well to steroid therapy,and thus,she was diagnosed as igg 4-RD suspicious.This report highlights the importance of an early diagnosis in this autoimmune disease and suggests that patients with a clinically unclear cause of inflammation,swelling and refractory glands,rhinitis,pancreatitis,hypophysitis,and/or interstitial pneumonia should be considered for igg 4-RD.The plasma igg4 level and lymphoplasmacytic infiltration may be useful indexes for screening,and a low dose of steroid maintaining therapy may offer benefits for patients with igg4-RD.

关键词： igg4 igg4-related disease Autoimmune disease Steroid therapy

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Autoimmune hepatitis and igg4-related disease

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World Journal of Gastroenterology 2019年第19期25卷 2308-2314页

作者： Kosuke Minaga Tomohiro Watanabe Hobyung Chung Masatoshi Kudo Department of Gastroenterology and Hepatology Kindai University Faculty of Medicine Department of Gastroenterology and Hepatology Kobe City General Hospital

igg4-related disease(igg4-RD) is a chronic-fibroinflammatory disorder affecting a wide range of organs. Elevation of serum igg4 concentrations and abundant infiltration of igg4-expressing plasma cells are key diagnostic features of this autoimmune disease. Although common organ involvement of igg4-RD includes the salivary glands, pancreas, and bile duct, hepatic involvement is less well established. Recently, five studies identified a subtype of autoimmune hepatitis(AIH), called igg4-associated AIH(igg4-AIH). igg4-AIH is diagnosed based on significant accumulation of igg4-expressing plasmacytes in the liver in patients who met the diagnostic criteria for classical AIH. Although four of the five reports regarded igg4-AIH based on hepatic accumulation of igg4-positive cells alone, one report diagnosed igg4-AIH based on both hepatic accumulation of igg4-positive cells and elevated serum concentrations of igg4. igg4-AIH diagnosed based on the latter criteria may be a hepatic manifestation of igg4-RD whereas igg4-AIH diagnosed based on the former criteria may be a subtype of AIH. In this review article, we summarize and discuss clinicopathological features of igg4-AIH.

关键词： Autoimmune hepatitis igg4 igg4-related disease igg4-associated autoimmune hepatitis

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Tumor-induced osteomalacia with igg4-related lymph node disease

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Chinese Medical Journal 2019年第8期132卷 994-995页

作者： Ye Zhang Chang Xu Yan Yang Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Geriatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China

To the Editor:A 60-year-old man presented with progressively worsened limb weakness of 4 years duration,which had rendered him wheelchair-bound since May 2018.The patient also had muscle and joint pain and numbness.He had a history of type 2 diabetes,hypertension,and gout,no family history of bone disease.He took diabetic peripheral neuropathy treatment but the symptoms kept progressing.On admission,the patient was well developed and in normal body shape.Physical examination was unremarkable except for all-sided weakness.Laboratory evaluation showed hypophosphatemia with notable elevated urinary phosphorus loss.Other laboratory abnormalities were elevated alkaline phosphatase levels,mild insufficient vitamin D status,and mild elevated parathyroid hormone.After bone scintigraphy failed to localize an osseous tumor,whole-body positron emission tomography(PET)/computed tomography(CT)using 18F-fluorodeoxyglucose(18F-FDG)and the radiolabeled somatostatin analog 68Ga-DOTATATE were performed to make clear diagnosis of oncogenic hypophosphatemic osteomalacia.Both of the examinations revealed a suspicious mass in subcutaneous tissue around the umbilicus and enlarged right axillary lymph nodes[Figure 1A and 1B].

关键词： Tumor-induced osteomalacia igg4-related lymph node disease progressively worsened limb weakness

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Chinese Medical Sciences Journal 2017年第1期32卷 65-68页

作者： Xing Chen Lihua Wang Lixian Zhang Caihong Zhao Department of Urology China-Japan Friendship Hospital Department of Gastroenterology Harrison International Peace Hospital

igg4-related autoimmune pancreatitis (AIP) is themost common type of igg4-related diseases. Theobservation of a diffused and localized enlargementof the pancreas and strictures in the main pancreaticduct on radiological imaging is essential fordiagnosing AIP. The clinical features of AIP which presentas a localized pancreatic mass greatly mimic pancreaticcancer. Cases with AIP mimicking pancreatic cancer arereported numerously. However, cases of igg4-related AIPmanifesting acute pancreatitis symptoms and extensiveperipancreatic effusion are rarely observed. Meanwhile,acute pancreatitis is a common disease. If misdiagnosed asacute pancreatitis, igg4-related AIP may progressseriously. Here, we report a rare case of igg4-related AIPsuspected of acute pancreatitis because of epigastric painand extensive peripancreatic effusion on computed tomography(CT) images.

关键词： autoimmune pancreatitis igg4-related diseases computed tomography

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Diagnosis of igg4-related sclerosing cholangitis

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World Journal of Gastroenterology 2013年第43期19卷 7661-7670页

作者： Takahiro Nakazawa Itaru Naitoh Kazuki Hayashi Katsuyuki Miyabe Shuya Simizu Takashi Joh Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical SciencesNagoya 467-8601Japan

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.

关键词： igg4-related sclerosing cholangitis Primary sclerosing cholangitis igg4 Sclerosing cholangitis

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Autoimmune pancreatitis in the context of igg4-related disease:Review of imaging findings

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World Journal of Gastroenterology 2014年第41期20卷 15177-15189页

作者： Leslie K Lee Dushyant V Sahani Division of Abdominal Imaging and Intervention Department of RadiologyMassachusetts General HospitalHarvard Medical School

Current understanding of autoimmune pancreatitis(AIP) recognizes a histopathological subtype of the disease to fall within the spectrum of igg4-related disease.Along with clinical,laboratory,and histopathological data,imaging plays an important role in the diagnosis and management of AIP,and more broadly,within the spectrum of igg4-related disease.In addition to the defined role of imaging in consensus diagnostic protocols,an array of imaging modalities can provide complementary data to address specific clinical concerns.These include contrast-enhanced computed tomography(CT) and magnetic resonance(MR) imaging for pancreatic parenchymal lesion localization and characterization,endoscopic retrograde and magnetic resonance cholangiopancreatography(ERCP and MRCP) to assess for duct involvement,and more recently,positron emission tomography(PET) imaging to assess for extra-pancreatic sites of involvement.While the imaging appearance of AIP varies widely,certain imaging features are more likely to represent AIP than alternate diagnoses,such as pancreatic cancer.While nonspecific,imaging findings which favor a diagnosis of AIP rather than pancreatic cancer include:delayed enhancement of affected pancreas,mild dilatation of the main pancreatic duct over a long segment,the "capsule" and "penetrating duct" signs,and responsiveness to corticosteroid therapy.Systemic,extra-pancreatic sites of involvement are also often seen in AIP and igg4-related disease,and typically respond to corticosteroid therapy.Imaging by CT,MR,and PET also play a role in the diagnosis and monitoring after treatment of involved sites.

关键词： Autoimmune pancreatitis igg4-related disease Pancr

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World Journal of Gastroenterology 2013年第48期19卷 9490-9494页

作者： Li-Mei Qu Ya-Hui Liu David R Brigstock Xiao-Yu Wen Yong-Fang Liu Ya-Jun Li Run-Ping Gao Department of Hepatic-Biliary-Pancreatic Medicine First Hospital Jilin University Department of Hepatic-Biliary-Pancreatic Surgery First Hospital Jilin University The Research Institute at Nationwide Children’s Hospital Columbus OH 43205 United States Division of Pediatric Surgery Department of Surgery The Ohio State University Columbus OH 43205United States

Autoimmune pancreatitis(AIP)is a form of chronic pancreatitis that is categorized as type 1 or type 2according to the clinical profile.Type 1 AIP,which predominantly presents in a few Asian countries,is a hyper-igg4-related disease.We report a case of igg4-related AIP overlapping with Mikulicz’s disease and lymphadenitis,which is rare and seldom reported in literature.A 63-year male from Northeast China was admitted for abdominal distension lasting for one year.He presented symmetric swelling of the parotid and submandibular glands with slight dysfunction of salivary secretion for 6 mo.He had a 2-year history of bilateral submandibular lymphadenopathy without pain.He underwent surgical excision of the right submandibular lymph node one year prior to admission.He denied any history of alcohol,tobacco,or illicit drug use.Serological examination revealed high fasting blood sugar level(8.8 mmol/L)and high level of igg4(15.2 g/L).Anti-SSA or anti-SSB were negative.Computed tomography of the abdomen showed a diffusely enlarged pancreas with loss of lobulation.Immunohistochemical stain for igg4 demonstrated diffuse infiltration of igg4-positive plasma cells in labial salivary gland and lymph node biopsy specimens.The patient received a dose of 30 mg/d of prednisone for three weeks.At this three-week follow-up,the patient reported no discomfort and his swollen salivary glands,neck lymph node and pancreas had returned to normal size.The patient received a maintenance dose of 10mg/d of prednisone for 6 mo,after which his illness had not recurred.

关键词： igg4-related disease Type 1 autoimmune pancreatitis Mikulicz’s disease Lymphadenitis

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First case of igg4-related sclerosing cholangitis associated with autoimmune hemolytic anemia

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World Journal of Gastroenterology 2014年第26期20卷 8740-8744页

作者： Hironori Masutani Kosuke Okuwaki Mitsuhiro Kida Hiroshi Yamauchi Hiroshi Imaizumi Shiro Miyazawa Tomohisa Iwai Miyoko Takezawa Wasaburo Koizumi Department of Gastroenterology Kitasato University East Hospital

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 a73-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.

关键词： igg4-related sclerosing cholangitis Immunoglobulin

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Colovesical fistula caused by glucocorticoid therapy for igg4-related intrapelvic mass

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World Journal of Clinical Cases 2015年第12期3卷 1000-1004页

作者： Yohei Yabuuchi Hiroyuki Matsubayashi Masato Matsuzaki Akio Shiomi Michihisa Moriguchi Ichiro Kawamura Ichiro Ito Hiroyuki Ono Division of Endoscopy Shizuoka Cancer Center Division of Urology Shizuoka Cancer Center Division of Colon Surgery Shizuoka Cancer Center Division of Intervention Radiology Shizuoka Cancer Center Division of Infectious Diseases Shizuoka Cancer Center Division of Pathology Shizuoka Cancer Center

igg4-related disease(igg4-RD) is an immune-mediated fibroinflammatory disorder that can occur in almost all systemic organs and generally responds to corticosteroid treatment. We report a rare case of an igg4-related intrapelvic mass lesion that responded to steroid therapy but caused a fistula between the sigmoid colon and bladder. A 71-year-old man was followed after treatment for hepatocellular carcinoma. Follow-up computed tomography(CT) incidentally depicted left hydronephrosis with an ill-demarcated intrapelvic mass lesion. This lesion was histologically diagnosed as igg4-RD by open biopsy, and peroral steroid therapy was initiated. One month after starting steroids, a colovesical fistula was detected by follow-up CT. A colostomy and urethral catheterization were emergently performed. The patient recovered and the mass lesion was drastically minimized by the initiation of glucocorticoids; however, he still needs urethral catheterization. igg4-RD develops in various systemic organs and generally responds well to steroids. Clinicians must be watchful for the complications of responses to corticosteroids, such as fistulization, when the mass lesion of igg4-RD is adjacent to multiple luminal organs.

关键词： igg4-related disease Intrapelvic mass Steroid therapy Colovesical fistula Colostomy Urethral catheterization

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Roles of plasmablasts in igg4-related disease and various immune-based diseases

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World Journal of Rheumatology 2016年第1期6卷 16-22页

作者： Syuichi Koarada Yoshifumi Tada Department of Rheumatology Faculty of MedicineSaga University

igg4-related disease(igg4-RD) is a systemic fibroinflammatory disease with multiple organ disorders.Recently,in igg4-RD,increased circulating plasmablasts have been found.The subsets of plasmablasts are negative for RP105(CD180).A large population of B cells lacking RP105(RP105-negative B cells) are found inpatients with active with systemic lupus erythematosus and other systemic autoimmune diseases,including dermatomyositis,and Sj?gren's syndrome.In other conditions,such as neuromyelitis optica,Kawasaki's disease,primary biliary cirrhosis and aging,RP105 expression on B cells and monocytes also alters.We review the basic science and clinical significance of RP105-negative B cells including plasmablasts in various immune-based diseases.RP105-negative B cells,especially plasmablasts,play crucial roles in both systemic and organ-specific autoimmune and inflammatory disorders.

关键词： Plasmablast CD180 igg4-related disease Autoimmune disease

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