Immunoglobulin G4-related spinal pachymeningitis:A case report

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a complex immune-mediated condition that causes fibrotic inflammation in several organs.A significant clinical feature of IgG4-RD is hypertrophic pachymeningitis,which manifests as inflammation of the dura mater in intracranial or spinal regions.Although IgG4-RD can affect multiple areas,the spine is a relatively rare site compared to the more frequent involvement of intracranial structures.CASE SUMMARY A 70-year-old male presented to our hospital with a two-day history of fever,altered mental status,and generalized weakness.The initial brain magnetic resonance imaging(MRI)revealed multiple small infarcts across various cerebral regions.On the second day after admission,a physical examination revealed motor weakness in both lower extremities and diminished sensation in the right lower extremity.Electromyographic evaluation revealed findings consistent with acute motor sensory neuropathy.Despite initial management with intravenous immunoglobulin for presumed Guillain-Barrésyndrome,the patient exhibited progressive worsening of motor deficits.On the 45th day of hospitalization,an enhanced MRI of the entire spine,focusing specifically on the thoracic 9 to lumbar 1 vertebral level,raised the suspicion of IgG4-related spinal pachymeningitis.Subsequently,the patient was administered oral prednisolone and participated in a comprehensive rehabilitation program that included gait training and lower extremity strengthening exercises.CONCLUSION IgG4-related spinal pachymeningitis,diagnosed on MRI,was treated with corticosteroids and a structured rehabilitation regimen,leading to significant improvement.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level:A single-center,retrospective cohort study

BACKGROUND Autoimmune pancreatitis(AIP)has been linked with elevated immunoglobulin(Ig)G4 levels.The characteristics and outcomes of AIP based on serum markers have not been fully evaluated.AIM To compare clinical features,treatment efficacy,and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse.METHODS A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021.According to the serum IgG4 level,all patients were divided into two groups,the abnormal group(n=148)with a high level of IgG4[>2×upper limit of normal(ULN)]and the normal group(n=65).The t-test or Mann-Whitney U test was used to compare continuous variables.Categorical parameters were compared by theχ^(2) test or Fisher’s exact test.Kaplan-Meier curves Zhou GZ et al.Clinical characteristics and outcome of AIP WJG https://www.wjgnet.com 5126 September 21,2023 Volume 29 Issue 35 and log-rank tests were established to assess the cumulative relapse rates.Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse.RESULTS Compared with the normal group,the abnormal group had a higher average male age(60.3±10.4 vs 56.5±12.9 years,P=0.047);higher level of serum total protein(72.5±7.9 g/L vs 67.2±7.5 g/L,P<0.001),IgG4(1420.5±1110.9 mg/dL vs 252.7±106.6 mg/dL,P<0.001),and IgE(635.6±958.1 IU/mL vs 231.7±352.5 IU/mL,P=0.002);and a lower level of serum complement C3(100.6±36.2 mg/dL vs 119.0±45.7 mg/dL,P=0.050).In addition,a lower number of cases with abnormal pancreatic duct and pancreatic atrophy(23.6%vs 37.9%,P=0.045;1.6%vs 8.6%,P=0.020,respectively)and a higher rate of relapse(17.6%vs 6.2%,P=0.030)were seen in the abnormal group.Multivariate analyses revealed that serum IgG4[(>2×ULN),hazard ratio(HR):3.583;95%confidence interval(CI):1.218–10.545;P=0.020]and IgA(>1×ULN;HR:5.908;95%CI:1.199–29.120;P=0.029)and age>55 years(HR:2.383;95%CI:1.056–5.378;P=0.036)were independent risk factors of relapse.CONCLUSION AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate.Several factors,such as IgG4 and IgA,are associated with relapse.

IgG4-related sclerosing cholangitis associated with essential thrombocythemia:A case report

BACKGROUND The complexity of immunoglobulin G4(IgG4)-related diseases and their potential connection to hematologic malignancies remains unclear.This article provided a review of the diagnosis and treatment of a patient with IgG4-related sclerosing cholangitis(SC)and essential thrombocythemia(ET),along with an analysis of relevant literature to enhance comprehension of this disease.CASE SUMMARY A 56-year-old male was admitted to two hospitals with deteriorating jaundice and pruritus prior to hospitalization.Beyond our expectations,the patient was first diagnosed with IgG4-SC and ET with the Janus kinase 2 V617F mutation.Interestingly,the administration of acetate prednisone significantly resulted in improvements in both IgG4-SC and ET.Clinicians need to pay attention to immune disorders and inflammation as they contribute to the development of various disease phenotypes.CONCLUSION When IgG4-SC is suspected without histopathological evidence,diagnostic therapy and long-term regular follow-up can lead to positive treatment outcomes.Clinicians should be mindful of the potential presence of concurrent hematologic diseases in patients with immune disorders.

MOG抗体阳性和AQP4抗体阳性视神经炎治疗方法的研究进展

视神经炎是一种主要累及青年,以视神经各种炎性病变为特征的致盲性眼科疾病。近些年随着水通道蛋白-4抗体和髓鞘少突胶质细胞糖蛋白抗体在部分患者血清中的发现,越来越多的学者认为这两种抗体介导的视神经炎区别于多发性硬化相关性视神经炎,且分别具有独特的临床特征。本文对目前这两种特异性抗体相关视神经炎的治疗方法的相关研究进行综述,以期为临床工作提供帮助。

Infrequent organ involvement in immunoglobulin G4-related prostate disease: A case report

BACKGROUND Immunoglobulin G4-related prostate disease(IgG4-RPD)characterized by a high count of IgG4-positive plasma cells has distinctive serological and radiological findings.Here we report a case of a patient who was successfully treated for IgG4-RPD,which manifested as frequent micturition,dysuric,and systemic lymphadenopathy.CASE SUMMARY The patient was a 33-year-old man who was referred to our hospital because of urinary tract symptoms that had persisted for 4 years.A physical examination revealed systemic lymphadenopathy and blood tests showed hyperglobulinemia with an IgG level of 18.90 g/L and an IgG4 level of 18.40 g/L.Computed tomography(CT)revealed bilateral lacrimal gland,right parotid gland and prostatic enlargement.Based on these findings,IgG4-RD was suspected,and further pathological examination and follow-up results showed expected results.Finally,the patient was diagnosed with IgG4-RPD based on clinical symptoms,pathological examination,therapeutic effects,and follow-up results.He received 50 mg oral prednisolone(the dose was gradually reduced and a low dose was used for long-term maintenance)in combination with cyclophosphamide 1.0 g via an intravenous drip for 6 mo.One year after the treatment was initiated,he was free of urinary or other complaints and his serum IgG4 level normalized.CONCLUSION In IgG4-RPD with severe urinary tract symptoms,radiological findings should be carefully examined.IgG4-RPD prognosis is good because the disease responds well to glucocorticoids.Furthermore,it is urgent for clinicians and pathologists to improve their understanding of IgG4-RPD.

IgA、IgG、IgM及补体C3、C4对类风湿关节炎患者的诊断价值

目的分析免疫球蛋白组及补体3(complement 3,C3)、补体4(complement 4,C4)在类风湿关节炎(rheumatoid arthritis,RA)临床诊断中的应用价值。方法选择2020年3月—2022年10月赤峰市医院收治的88例初诊RA患者作为观察组,并选择同期健康人群64名作为对照组。其中RA患者依据疾病活动分数(disease activity score 28,DAS28)进行分级,高度活动组22例、中度活动组24例、低度活动组21例、缓解组21例。对每个纳入研究的RA患者及健康人群均行免疫球蛋白A(immunoglobulin A,IgA)、免疫球蛋白G(immunoglobulin G,IgG)、免疫球蛋白M(immunoglobulin M,IgM)及补体C3、C4检测。比较两组患者及不同分级RA患者间各指标的差异,并分析讨论。结果观察组患者IgA、IgG、IgM、C3、C4水平较对照组均明显升高(P<0.05)。观察组内不同活动度RA患者对比,活动度越高,对应患者IgA、IgG、IgM、C3、C4水平也明显偏高,而缓解组患者各指标水平最低(P<0.05)。结论RA患者血清免疫球蛋白及补体指标较正常人群会有所升高,且RA活动度越高,其对应指标升高程度也越明显。提示免疫球蛋白及补体可以作为RA患者早期诊断及检测的评价指标;同时,本文的研究结果也为类风湿关节炎后期诊断标准制定提供了借鉴。

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

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-αand 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.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies

In this editorial we comment on the article by Jaber et al.Autoimmune pancreatitis(AIP)represents a distinct form of pancreatitis,categorized into AIP-1 and AIP-2,characterized by obstructive jaundice,lymphoplasmacytic infiltrate,and fibrosis.AIP-1,associated with elevated immunoglobulin G4(IgG4)levels,exhibits higher relapse rates,affecting older males,while AIP-2 is less common and linked to inflammatory bowel disease.AIP is considered a manifestation of IgG4-related systemic disease,sharing characteristic histological findings.Steroids are the primary treatment,with emerging biomarkers like interferon alpha and inter-leukin-33.AIP poses an increased risk of various malignancies,and the assoc-iation with pancreatic cancer is debated.Surgery is reserved for severe cases,necessitating careful evaluation due to diagnostic challenges.AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients.Thorough diagnostic assessment,including biopsy and steroid response,is crucial for informed surgical decisions in AIP.

An aortoduodenal fistula as a complication of immunoglobulin G4-related disease

Most primary aortoduodenal fistulas occur in the presence of an aortic aneurysm,which can be part of immunoglobulin G4(IgG4)-related sclerosing disease.We present a case who underwent endovascular grafting of an aortoduodenal fistula associated with a high serum IgG4 level.A 56-year-old male underwent urgent endovascular reconstruction of an aortoduodenal fistula.The patient received antibiotics and other supportive therapy,and the postoperative course was uneventful,however,elevated levels of serum IgG,IgG4 and C-reactive protein were noted,which normalized after the introduction of steroid therapy.Control computed tomography angiography showed no endoleaks.The primary aortoduodenal fistula may have been associated with IgG4-related sclerosing disease as a possible complication of IgG4-related inflammatory aortic aneurysm.Endovascular grafting of a primary aortoduodenal fistula is an effective and minimally invasive alternative to standard surgical repair.

Immunoglobulin G4 associated autoimmune cholangitis and pancreatitis following the administration of nivolumab:A case report

BACKGROUND Immune checkpoint inhibitors have significantly improved survivals for an increasing range of malignancies but at the cost of several immune-related adverse events,the management of which can be challenging due to its mimicry of other autoimmune related disorders such as immunoglobulin G4(IgG4)related disease when the pancreaticobiliary system is affected.Nivolumab,an IgG4 monoclonal antibody,has been associated with cholangitis and pancreatitis,however its association with IgG4 related disease has not been reported to date.CASE SUMMARY We present a case of immune-related pancreatitis and cholangiopathy in a patient who completed treatment with nivolumab for anal squamous cell carcinoma.Patients IgG4 levels was normal on presentation.She responded to steroids but due to concerns for malignant biliary stricture,she opted for surgery,the pathology of which suggested IgG4 related disease.CONCLUSION We hypothesize this case of IgG4 related cholangitis and pancreatitis was likely triggered by nivolumab.

Novel mechanism of hepatobiliary system damage and immunoglobulin G4 elevation caused by Clonorchis sinensis infection

Clonorchis sinensis infection is still a major public health problem.It is estimated that more than 15 million people worldwide are infected,especially in Northeast China,Taiwan,South Korea,and North Vietnam.The detection of Clonorchis sinensis eggs in feces and bile is still the only gold standard for the diagnosis of Clonorchis sinensis infection,and new detection methods are needed to improve the detection rate.After Clonorchis sinensis invades the human body,it mainly parasitizes the hepatobiliary tract.Therefore,it is closely related to hepatobiliary diseases such as cholangitis,bile duct stones,liver fibrosis,and cholangiocarcinoma.The increase in immunoglobulin G4(IgG4)caused by Clonorchis sinensis infection is rare and there are few reports about the relevant mechanism.It may be related to the inflammatory factors interleukin(IL)-4,IL-10,and IL-13 produced by human phagocytes,T cells,B cells,and other immune cells in the process of resisting the invasion of Clonorchis sinensis.However,this finding still needs further clarification and confirmation.This article reviews the epidemiology,clinical manifestations,serology,imaging,pathogenic mechanism,and control measures of Clonorchis sinensis infection to help establish the diagnostic process for Clonorchis sinensis.We report novel mechanisms of IgG4 elevation due to Clonorchis sinensis infection to provide more experience and a theoretical basis for clinical diagnosis and treatment of this infection.

Unmet needs in biomarkers for autoimmune pancreatitis diagnosis

Autoimmune pancreatitis(AIP)is a rare chronic autoimmune disorder.The diagnosis of AIP mainly depends on histopathology,imaging and response to treatment.Serum immunoglobulin 4(IgG4)is used only as collateral evidence in diagnostic criteria for AIP because of its moderate sensitivity.Serum IgG4 levels are normal in 15%-37%of type 1 AIP and most of type 2 AIP patients.In these patients,the indeterminate imaging and histopathology may lead to the difficulty in definitive diagnosis of AIP.Therefore,discovery of new biomarkers is impor-tant for AIP diagnosis.Here,we provide some views on the progression and challenges in identifying novel serological biomarkers in AIP diagnosis.

Type one autoimmune pancreatitis based on clinical diagnosis: A case report

BACKGROUND Autoimmune pancreatitis(AIP)is a rare form of autoimmune-mediated pancrea-titis,which is easily misdiagnosed as pancreatic cancer and thus treated surgi-cally.We studied the diagnosis and treatment of a patient with type 1 AIP recent-ly admitted to our hospital,and reviewed the literature to provide a reference for clinical diagnosis of AIP.CASE SUMMARY The chief complaint was yellowing of the body,eyes and urine for 21 d.The pa-tient's clinical presentation was obstructive jaundice and imaging suggested pan-creatic swelling.It was difficult to distinguish between inflammation and tumor.Serum immunoglobulin G4(IgG4)was markedly elevated.IgG4 is an important serological marker for type 1 AIP.The patient was diagnosed with AIP,IgG4-related cholangitis,acute cholecystitis and hepatic impairment.After applying hormonal therapy,the patient's symptoms improved significantly.At the same time,imaging suggested that pancreatic swelling subsided,and liver function and other biochemical indicators decreased.The treatment was effective.CONCLUSION In patients with pancreatic swelling,the possibility of AIP should be considered.

Immunoglobulin G4-related disease involving multiple systems:A case report

BACKGROUND Ig G4-related disease(Ig G4-RD),an immune-mediated chronic progressive fibroinflammatory disease,can affect the functions of several organs.Some common characteristics can be observed in different Ig G4-RDs,such as higher prevalence in middle-aged and elderly male patients,raised serum Ig G4 levels,abundant infiltration of Ig G4-positive cells and fibrosis,diffuse or localized swelling of the affected organs,and good response to glucocorticoids treatment.CASE SUMMARY A 72-year-old man complained of left upper abdominal pain 3 mo ago,and he was diagnosed with acute onset of chronic cholecystitis and acute pancreatitis in the local hospital.Pain improved after relevant treatment.Several days ago,his abdominal pain worsened,and he was admitted to our hospital for further treatment.Doppler ultrasound showed that the pancreas presented with sausagelike swelling and the parenchymal echo was diffusely reduced.Gallbladder volume was increased,while the wall was rough and thickened with bilateral signs.Furthermore,the left submandibular gland was enlarged,accompanied with significantly increased blood flow signals.Finally,we found that the adventitia of the abdominal aorta and right iliac artery was thickened locally.Serum Ig G4 was elevated to 12600 mg/L.Therefore,the patient was diagnosed with Ig G4-RD.After treatment with methylprednisolone,he had an uneventful course and was discharged in good condition.CONCLUSION Ig G4-RD can involve almost any organs.Ultrasound has a significant role in timely and accurately diagnosis.

Immunoglobulin G4 associated autoimmune cholangitis and pancreatitis and nivolumab

This letter to editor discussing on the publication on immunoglobulin G4 associated autoimmune cholangitis and pancreatitis following the administration of nivolumab.Concerns on confounding factors are raised and discussed.

Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis:A case report

BACKGROUND A type 2b immunoglobulin G4(IgG4)-related sclerosing cholangitis(SC)without autoimmune pancreatitis is a rare condition with IgG4-SC.While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC,however,the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition.Therefore,the information of our recent case and reported cases have been summarized.CASE SUMMARY We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4,narrowing of the bile duct,its wall thickness,no complication of autoimmune pancreatitis,and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes.The cholangiogram revealed type 2b according to the classification.Corticosteroid treatment showed a favorable effect,with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness.CONCLUSION As isolated type 2b,IgG4-SC is rare,the images,histological findings,and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.

Clivus-involved immunoglobulin G4 related hypertrophic pachymeningitis mimicking meningioma:A case report

BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypertrophic pachymeningitis(Ig G4-RHP)is relatively rare and indistinguishable from other phymatoid diseases before the operation.The risk of long-term immunosuppression needs to be balanced with disease activity.CASE SUMMARY A 40-year-old man presented with headache and bilateral abducent paralysis.He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same.Before the operation and steroid therapy,the patient was suspected of having tubercular meningitis at a local hospital.A clivus lesion was found via brain magnetic resonance imaging(MRI)at this presentation.He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery.Transnasal endoscopic resection was performed to treat deterioration of nerve function.Postoperative pathologic examination suggested Ig G4-RD.Moreover,the serum Ig G4 was elevated at 1.90 g/L(reference range:0.035-1.500 g/L).After steroid therapy for 2 mo,the lesion size diminished on MRI,and the function of bilateral abducent nerves recovered.CONCLUSION Ig G4-RHP is relatively rare and indistinguishable before the operation.Elevated serum Ig G4 levels and imaging examination help in the diagnosis of Ig G4-RHP.Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.

Immunoglobulin G4-related kidney disease involving the renal pelvis and perirenal fat:A case report

BACKGROUND Immunoglobulin(Ig)G4-related disease(Ig G4-RD)is an autoimmune disease associated with chronic and progressive inflammation and fibrosis.It is difficult to differentiate Ig G4-RD involving the kidney from infectious diseases and malignancy on imaging.CASE SUMMARY We report the case of a 51-year-old Chinese man whose abdominal computed tomography scan showed diffuse bilateral enlargement of the kidneys and perirenal fat,thickening of the renal pelvic walls,and hydronephrosis of the right kidney.Relevant laboratory test results showed a serum creatinine level of 464μmol/L.The patient was diagnosed with acute renal failure and was started on intermittent hemodialysis.Further tests revealed high serum Ig G4 levels(20.8 g/L)and an enlarged right submaxillary lymph node.Biopsy and histopathological examination of the enlarged node led to the diagnosis of Ig G4-RD.After corticosteroid therapy,his serum creatinine level quickly decreased to near normal levels.CONCLUSION Ig G4-RD affecting the renal pelvis or perirenal fat is rare,with atypical imaging features.Multidisciplinary consultation is critical for accurate diagnosis and treatment of this disease.Suspected cases should undergo biopsy to avoid misdiagnosis.

Immunoglobulin G4-related disease in the sigmoid colon in patient with severe colonic fibrosis and obstruction:A case report

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is an immune-mediated condition characterized by abundant IgG4 positive plasma cells and fibrosis in the affected tissues.It affects most parts of the body;however,there are not many reports on IgG4-RD involving the colon.CASE SUMMARY A 50-year-old man complaining of intermittent fever for more than two years was referred to our hospital.Based on various investigations before surgery,we diagnosed him with chronic perforation of the sigmoid colon caused by inflammatory change or tumor.IgG blood tests before the operation suggested IgG4-RD,and postoperative pathology confirmed this prediction.CONCLUSION We present a patient with IgG4-RD with colon involvement,which is an uncommon site.This report will expand the understanding of IgG4-RD in unknown tissues.

IgG_(4)相关疾病累及腮腺1例并文献复习

目的探讨IgG_(4)相关疾病(IgG_(4)-related diseases,IgG_(4)-RD)累及腮腺的临床表现、诊断标准、治疗方案以及细针穿刺在疾病诊断中的应用,减少临床误诊漏诊。方法回顾分析华北理工大学附属医院2020年11月收治的1例累及腮腺的IgG_(4)-RD病人的病例资料,通过分析临床特点、血清学指标、影像学表现及术后病理学特征等,并复习相关文献进行分析总结。结果该66岁男性病人以右侧腮腺无痛性肿物为主要表现,行抗感染治疗后肿物无明显变化,先后两次行细针穿刺均未明确诊断,行手术切除后病理结果确诊为累及腮腺的IgG_(4)-RD,结合病人术前检查及术后病理结果,考虑病变处于非活动期,暂未给予药物治疗,密切随访,至今未见复发。结论IgG_(4)相关疾病为临床罕见疾病,缺乏典型的临床表现及特异的影像学特征,术前多不能明确诊断,病理学检查在疾病的诊断中具有重要意义,而细针穿刺在疾病的诊断中价值有限,需引起临床医生的重视。