Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease.

BACKGROUND: In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version.Methods and Results: Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively. CONCLUSIONS: Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

Improved Renal Function in Initial Treatment Improves Patient Survival, Renal Outcomes, and Glucocorticoid-Related Complications in IgG4-Related Kidney Disease in Japan.

Introduction: We aimed to clarify long-term renal prognosis, complications of malignancy, glucocorticoid (GC) toxicity, and mortality in immunoglobulin G4 (IgG4)-related kidney disease (IgG4-RKD). Methods: Reviewing the medical records of 95 patients with IgG4-RKD, we investigated clinical and pathologic features at baseline, the course of renal function, complications of malignancy, GC toxicity, and mortality during follow-up (median 71 months). The standardized incidence ratio (SIR) of malignancy and standardized mortality ratio were calculated using national statistics. Factors related to outcomes were assessed by Cox regression analyses. Results: At diagnosis, the median estimated glomerular infiltration rate (eGFR) was 46 ml/min per 1.73 m2. GC achieved initial improvement. Additional renal function recovery within 3-months of initial treatment occurred in patients with highly elevated serum IgG and IgG4 levels and hypocomplementemia. During follow-up, 68%, 17%, and 3% of the patients had chronic kidney disease (CKD), >30% eGFR decline, and end-stage renal disease (ESRD), respectively. Age-adjusted and sex-adjusted Cox regression analyses indicated that eGFR (hazard ratio [HR], 0.71) and extensive fibrosis (HR, 2.58) at treatment initiation had a significant impact on the time to CKD. Ten patients died, and the standardized mortality ratio was 0.94. The SIR of malignancy was 1.52. The incidence rate (IR) of severe infection was 1.80/100 person-years. Cox regression analyses showed that the best eGFR within 3 months after treatment initiation were associated with lower mortality (HR 0.67) and fewer severe infections (HR 0.63). Conclusion: This study suggests that more renal function recovery through early treatment initiation may improve patient survival, renal outcomes, and some GC-related complications in IgG4-RKD.

A case of subarachnoid haemorrhage associated with MPO-ANCA-positive eosinophilic granulomatosis with polyangiitis, successfully treated with glucocorticoid, cyclophosphamide, and mepolizumab.

Subarachnoid haemorrhage (SAH) is a quite rare but serious central nervous system complication of eosinophilic granulomatosis with polyangiitis (EGPA). We report a case of myeloperoxidase antineutrophil cytoplasmic antibody-positive EGPA in which SAH developed during glucocorticoid induction pulse therapy for skin purpura, peripheral neuropathy, and rapidly progressive glomerulonephritis. In addition to high-dose glucocorticoid and intravenous cyclophosphamide, we administered mepolizumab, a humanised anti-interleukin-5 monoclonal antibody, and this resulted in remission of the SAH. Although the pathogenesis of SAH in EGPA is not fully understood, both necrotising vasculitis and eosinophilic inflammation are thought to be involved. In addition to prompt intensive immunosuppressive therapy, mepolizumab should be considered for SAH associated with EGPA.

Successful Rituximab Therapy for Skin Sclerosis and Myositis in a Patient With Systemic Sclerosis, Myositis and Sjögren's Syndrome Associated With Autoimmune Polyendocrine Syndrome Type 2.

Autoimmune polyendocrine (or polyglandular) syndrome (APS) is a relatively rare clinical condition characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance. APS is broadly categorized as rare monogenic forms, such as autoimmune polyendocrine syndrome type 1 (APS-1), and a more common polygenic variety, autoimmune polyendocrine syndrome type 2 (APS-2). Although many autoimmune conditions including autoimmune rheumatic diseases can develop in APS-2, systemic sclerosis or myositis as a complication is quite rare and no treatment strategy has yet been established. A 25-year-old man who had been diagnosed as having type 1 diabetes developed finger stiffness. Although the subjective symptoms were relatively mild, extensive examinations including various autoantibodies, hormones and biopsy of the skin and minor salivary glands revealed that he had APS-2 (type 1 diabetes and autoimmune thyroid disease) accompanied by systemic sclerosis, myositis and Sjögren's syndrome. Rituximab therapy was initiated for the progressive skin sclerosis, and this resulted in significant alleviation of both the sclerosis and the myositis. In APS, early diagnosis and immunomodulatory therapy may arrest the autoimmune process before irreversible organ damage has occurred. This case report suggests that rituximab may be a promising therapy for autoimmune rheumatic diseases associated with APS-2.

Recent advances in IgG4-related kidney disease.

Recent advances in the management and understanding of immunoglobulin (Ig)G4-related kidney disease (RKD) have emphasized the importance of urgent treatment in IgG4-related tubulointerstitial nephritis. On the other hand, to avoid long-term glucocorticoid toxicity, strategies for early withdrawal of steroids or combination of immunosuppressants, such as rituximab, and the minimum dose of steroids have been pursued. However, disease recurrence after reducing or stopping steroid therapy hampers early withdrawal of glucocorticoid maintenance therapy. In addition, knowledge has accumulated in diagnostic approaches including differential diagnosis of anti-neutrophil cytoplasmic antibodies-associated vasculitis, idiopathic multicentric Castleman's disease, and Rosai-Dorfman disease with kidney lesion, which leads to earlier and precise diagnosis of IgG4-RKD. This review summarizes recent progress in the differential diagnosis of IgG4-RKD and related treatment strategies and recent topics of hypocomplementaemia, membranous glomerulonephritis, and IgG4-related pyelitis and periureteral lesion.

Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG4-related disease and Kimura disease.

BACKGROUND: How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T-cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs in patients with elevated tissue expression levels of IgE (Kimura disease, KD) and those of IgG4 (IgG4-related disease, IgG4-RD) can provide important insights regarding cytokine expression by Tfh cells. OBJECTIVE: We sought to identify disease-specific Tfh cell subsets in secondary and tertiary lymphoid organs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in 2 distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes). METHODS: Single-cell RNA sequencing, in situ sequencing, and multicolor immunofluorescence analysis were used to investigate B cells, Tfh cells, and infiltrating type 2 cells in lesion tissues from patients with KD or IgG4-RD. RESULTS: Infiltrating Tfh cells in tertiary lymphoid organs from IgG4-RD were divided into 6 main clusters. We encountered abundant infiltrating IL-10-expressing LAG3+ Tfh cells in patients with IgG4-RD. Furthermore, we found that infiltrating AICDA+CD19+ B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG4 expression. In contrast, we found that infiltrating IL-13-expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13-expressing Tfh cells in tissues from patients with IgG4-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG4-RD; in contrast, type 2 immune cells were abundant in KD. CONCLUSIONS: Our analysis revealed a novel subset of IL-10+LAG3+ Tfh cells infiltrating the affected organs of IgG4-RD patients. In contrast, IL-13+ Tfh cells and type 2 immune cells infiltrated those of KD patients.

Nationwide epidemiological survey of immunoglobulin G4-related disease with malignancy in Japan.

BACKGROUND AND AIM: To clarify the clinicoepidemiological characteristics of immunoglobulin G4 (IgG4)-related disease (IgG4-RD) with malignancy, a nationwide epidemiological survey was conducted. METHODS: Immunoglobulin G4-related disease patients with malignancy who had visited selected hospitals in Japan were surveyed. The study consisted of two stages: the number of IgG4-RD patients with malignancy was estimated by the first questionnaire and their clinicoepidemiological characteristics were assessed by the second questionnaire. RESULTS: The frequencies of autoimmune pancreatitis (AIP), IgG4-related sialadenitis, IgG4-related eye disease, IgG4-related kidney disease, and IgG4-related retroperitoneal fibrosis were 44.7%, 20.8%, 14.0%, 5.16%, and 5.12%, respectively. The overall prevalence of malignant disease in IgG4-RD cases was estimated to be 10 900 per 100 000 cases, which was significantly higher than that of malignant disease in the general population. The prevalence of malignant lymphoma in IgG4-RD cases was the highest and was estimated to be 1985 per 100 000 cases. IgG4-related kidney disease had the highest frequency of malignant disease (17.1%). In data from 200 patients, 61 (30.5%) cases of cancer were found 2 years or more before the IgG4-RD diagnosis, 92 cases (46%) during the 1 year preceding or following IgG4-RD diagnosis, and 62 cases of cancer (31%) 2 or more years following IgG4-RD diagnosis. CONCLUSIONS: The nationwide survey for IgG4-RD with malignancy in Japan showed that IgG4-RD may be related with malignant diseases.

Validation of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD) 2011, and proposal of a new 2020 version.

BACKGROUND: In 2011, the IgG4-related kidney disease (IgG4-RKD) working group of the Japanese Society of Nephrology proposed diagnostic criteria for IgG4-RKD. The aim of the present study was to validate those criteria and develop a revised version. METHODS: Between April 2012 and May 2019, we retrospectively collected Japanese patients with kidney disease, for whom data on serum IgG4 values and/or immunohistological staining for IgG4 in renal biopsy samples were available. These patients were classified as IgG4-RKD or non-IgG4-RKD based on the diagnostic criteria for IgG4-RKD 2011, and the results were evaluated by expert opinion. Accordingly, we developed some revised versions of the criteria, and the version showing the best performance in the present cohort was proposed as the IgG4-RKD criteria for 2020. RESULTS: Of 105 included patients, the expert panel diagnosed 55 as having true IgG4-RKD and 50 as mimickers. The diagnostic criteria for IgG4-RKD 2011 had a sensitivity of 72.7% and a specificity of 90.0% in this cohort. Of the 15 patients with true IgG4-RKD who were classified as non-IgG4-RKD, all lacked biopsy-proven extra-renal lesions, although many had clinical findings highly suggestive of IgG4-RD. The revised version to which "bilateral lacrimal, submandibular or parotid swelling, imaging findings compatible with type 1 autoimmune pancreatitis or retroperitoneal fibrosis" was added as an item pertaining to extra-renal organ(s) improved the sensitivity to 90.9% while the specificity remained at 90.0%. CONCLUSION: The revised version has considerably improved test performance after addition of the new extra-renal organ item (imaging and clinical findings).

Hypocomplementemia is related to elevated serum levels of IgG subclasses other than IgG4 in IgG4-related kidney disease.

OBJECTIVES: This study investigated the clinical features of IgG4-RKD patients with hypocomplementemia compared with those without it, so as to clarify the factors related to hypocomplementemia. METHODS: In this single-center retrospective study, we analyzed the clinical features of 25 patients with IgG4-RKD according to the presence/absence of hypocomplementemia. Additionally, we validated the results of a single-center study in a separate large multicenter cohort of 328 patients with IgG4-RD, and searched for factors related to hypocomplementemia. RESULTS: Serum IgG levels (p < .001), non-IgG4 IgG levels, calculated as the total IgG minus IgG4 (p < .001), serum IgG1 levels (p = .017), and the number of involved organs (p = .018) were significantly higher in the hypocomplementemia group. At relapse of renal lesions in four patients, all had serum IgG4 re-elevation, with the three with hypocomplementemia presenting worsening of hypocomplementemia and re-elevation of non-IgG4 IgG levels. In a validation cohort of 328 patients with IgG4-RD, multivariate logistic regression analysis indicated elevation of non-IgG4 IgG levels to be an independent factor related to hypocomplementemia in the patients with IgG4-RKD. CONCLUSION: The present study suggests that hypocomplementemia is associated with elevation of IgG subclasses other than IgG4 including IgG1 in IgG4-RKD.

Effect of sucroferric oxyhydroxide on gastrointestinal microbiome and uremic toxins in patients with chronic kidney disease undergoing hemodialysis.

BACKGROUND: In patients with chronic kidney disease (CKD), dysbiosis in the gastrointestinal microbiome is thought to be associated with increased production of uremic toxins, such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Sucroferric oxyhydroxide (SFO), an iron-based phosphate binder, may affect the gastrointestinal microbiome and the production of uremic toxins. We aimed to examine whether SFO administration affected distribution of gastrointestinal microbiome and serum uremic toxin levels in CKD patients undergoing hemodialysis. METHODS: In this single-center, open-label, interventional study, 18 maintenance hemodialysis patients with hyperphosphatemia were prescribed with SFO. We collected serum samples before and after 3 months of administration, and serum levels of IS and PCS were measured. A control group of 20 hemodialysis patients without SFO was evaluated. We evaluated gastrointestinal microbiome of patients pre- and post-SFO administration by 16S rDNA sequencing and bioinformatics analysis. RESULTS: Serum IS and PCS levels were significantly elevated after administration of SFO (IS before 2.52 ± 1.60 mg/dl vs. after 3.13 ± 1.51 mg/dl, P = 0.008; PCS before 2.32 ± 2.44 mg/dl vs. after 3.45 ± 2.11 mg/dl, P = 0.002), while serum IS and PCS levels did not change in the control group. Microbiome analysis in the SFO group showed no significant change in diversity and major components in phylum, class, order, family, gene, and species. CONCLUSION: Administration of SFO increased the serum levels of IS and PCS with no change of major components of gastrointestinal microbiome.

Changes in the incidence of cervical lesions owing to the development of rheumatoid arthritis treatment and the impact of cervical lesions on patients' quality of life.

Objectives: To clarify changes in the incidence of cervical lesions in rheumatoid arthritis (RA) patients with advanced treatment and the impact of cervical lesions on the patients' quality of life (QOL).Methods: Incidence of radiographic cervical lesions in 1333 RA patients in 2015 was compared with that in our 1999 survey. The association between cervical lesions and QOL evaluated using three different patient-based questionnaires was also analyzed.Results: The incidence of atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS) in 2015 decreased by 50%, 75%, and 5%, respectively, compared to the 1999 survey. Although QOL, evaluated using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ; specific to myelopathy), deteriorated as the cervical lesion progressed, there was no association between cervical lesion progression and QOL evaluated using the Short Form-8™ (SF-8™; comprehensive health-related QOL). Cervical lesion progression was also associated with QOL deterioration evaluated using the Health Assessment Questionnaire Disability Index (HAQ-DI; specific to RA), but age and disease duration had stronger influences.Conclusion: The incidence of cervical lesions decreased in 2015 compared to 1999. Cervical lesion progression may be associated with QOL deterioration due to myelopathy. Age and disease duration have more impact on disease-specific QOL.

Impaired expression of innate immunity-related genes in IgG4-related disease: A possible mechanism in the pathogenesis of IgG4-RD.

Background: IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. The pathogenesis of this disease is not clear. Transcriptome analysis was performed to identify genes over- and under-expressed in patients with IgG4-RD.Method: DNA microarray analysis was performed using RNA from peripheral blood mononuclear cells of two patients with IgG4-RD and four healthy individuals. Genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy were identified. Four genes related to innate immunity such as transcobalamin I (TCN1), secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability-increasing protein (BPI) and lactotransferrin (LTF) were assessed by real-time PCR in 15 IgG4-RD patients and 13 healthy individuals.Result: DNA microarray analysis identified 30 genes showing a greater than threefold change in expression in IgG4-RD patients following steroid therapy. Real-time RT-PCR showed that the levels of mRNAs encoding TCNI and SLPI, except for BPI and LTF, were significantly lower in patients with IgG4-RD than in healthy people. The levels of all four mRNAs in patients with IgG4-RD were significantly increased after steroid treatment.Conclusion: These results indicate that reduction in expression of innate immunity-related genes may participate in the pathogenesis of IgG4-RD that steroid treatment may rectify impaired innate immunity as well as acquired immunity.

The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease.

IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serological, radiological and pathological data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD. An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises; existing literature; derivation and validation cohorts of 1879 subjects (1086 cases, 793 mimickers); and multicriterion decision analysis to identify, weight and test potential classification criteria. Two independent validation cohorts were included. A three-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least one of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serological, radiological and pathological items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, eight weighted inclusion criteria domains, addressing clinical findings, serological results, radiological assessments and pathological interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% CI 97.2% to 99.8%) and a sensitivity of 85.5% (95% CI 81.9% to 88.5%). In the second, the specificity was 97.8% (95% CI 93.7% to 99.2%) and the sensitivity was 82.0% (95% CI 77.0% to 86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiological and basic science investigations.

The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease.

OBJECTIVE: IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serologic, radiologic, and pathologic data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD. METHODS: An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises, existing literature, derivation and validation cohorts of 1,879 subjects (1,086 cases, 793 mimickers), and multicriterion decision analysis to identify, weight, and test potential classification criteria. Two independent validation cohorts were included. RESULTS: A 3-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least 1 of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serologic, radiologic, and pathologic items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, 8 weighted inclusion criteria domains, addressing clinical findings, serologic results, radiology assessments, and pathology interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% confidence interval [95% CI] 97.2-99.8%) and a sensitivity of 85.5% (95% CI 81.9-88.5%). In the second, the specificity was 97.8% (95% CI 93.7-99.2%) and the sensitivity was 82.0% (95% CI 77.0-86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. CONCLUSION: ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiologic, and basic science investigations.

Tubulointerstitial nephritis with monotypic lympho-plasmacytic infiltrates in a patient with primary Sjögren's syndrome accompanied by IgA-type monoclonal gammopathy.

BACKGROUND: Although most cases of tubulointerstitial nephritis in paraproteinemia are monoclonal light chain deposition-mediated, interstitial nephritis as neoplastic interstitial cell infiltration has rarely been described. On the other hand, lympho-plasma-cell-rich tubulointerstitial nephritis, in which the infiltrative cells are usually polytypic, is often evident in primary Sjögren's syndrome (pSS). Herein we present a rare case of pSS in a patient who had been diagnosed as having IgA kappa-type monoclonal gammopathy of undetermined significance (MGUS) and developed tubulointerstitial nephritis with monotypic (IgA kappa) lympho-plasmacytic infiltrates. CASE PRESENTATION: A 74-year-old Japanese woman with pSS who had been diagnosed as having IgA kappa-type MGUS developed progressive renal dysfunction. Renal biopsy revealed tubulointerstitial nephritis with abundant plasma cell-rich mononuclear cell infiltrates without atypia. Immunohistochemical staining for immunoglobulins and light chains showed that most infiltrates were positive for IgA and kappa. Most of the infiltrative cells were positive for CD38 and CD138, and cells positive for CD 19 and CD 45 were also widely evident. Electron microscopy and immunofluorescence studies revealed no apparent immunological deposits in the glomeruli and tubules. Bone marrow and whole-body radiological examinations revealed no findings suggestive of multiple myeloma or lymphoma. Renal function improved rapidly with prednisolone 40 mg daily and has been maintained at the same level on low-dose prednisolone and azathioprine for 18 months. CONCLUSION: Tubulointerstitial nephritis with monotypic cell infiltrates, without immunological deposits, is a quite rare histological picture in MGUS, and might be a unique renal manifestation in patients with pSS.

Enormous Aneurysm in Coronary Artery Fistula With Immunoglobulin G4-Related Disease.

We report the first case of coronary artery fistula with aneurysmal change in a patient with immunoglobulin G4-related disease (IgG4-RD). This case revealed concomitant coronary artery dilation, pericardial inflammatory nodules, and coronary-pulmonary fistula aneurysm in addition to several IgG4-RD lesions. Each of these features was located in close proximity to the thickened pericardium. These lesions might result from inflammation of the pericardial space, which extended to the coronary-pulmonary artery vessels, leading to aneurysmal formation. This case will enhance our understanding of the pathological mechanisms of IgG4-RD inflammation.

Clinical and Pathological Characteristics of IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis Diagnosed Based on Experts' Diagnosis.

IgG4-related disease is a systemic disease, characterized by elevation of serum IgG4 and, histopathologically, massive infiltration of IgG4+ lymphocyte and plasma cell infiltration, storiform fibrosis, causing enlargement, nodules or thickening. It may affect various organs simultaneously or metachronously. Here we analyzed the clinical and pathological characteristics of 99 patients diagnosed with IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis. Of 99 patients (women/men, 15/84; mean age 67.3±9.5 years), 33 were diagnosed based on the histopathological findings of perivascular/retroperitoneal lesions, 50 were diagnosed based on the characteristic imaging findings of perivascular/retroperitoneal lesions and the presence of definitive IgG4-related disease in other organ(s), and the remaining 16 patients were diagnosed by experts based on the characteristic imaging findings of perivascular/retroperitoneal legions, serological findings, response to glucocorticoid treatment, and/or the presence of suspected IgG4-related disease in other organ(s). According to the new organ-specific criteria proposed by experts, 73 (73.7%) diagnoses were categorized to be definitive, and 6 (6.1%) and 17 (17.2%) diagnoses were categorized to be probable and possible, respectively. Further analyses are needed to clarify the optimal diagnostic and therapeutic strategy of IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis. (This is a translation of J Jpn Coll Angiol 2018; 58: 117-129.).