Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages.

Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR-/- macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients.

Clinical characteristics of IgG4-related retroperitoneal fibrosis versus idiopathic retroperitoneal fibrosis.

Retroperitoneal fibrosis (RPF) is an uncommon condition characterized by inflammation and fibrosis in the retroperitoneal space. More than two-thirds of RPF are idiopathic, with the remaining stemed from a variety of secondary causes. It was suggested that IgG4-related RPF is a secondary form of RPF. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-related RPF and IRPF in a large Chinese cohort. We retrospectively reviewed the medical records of 132 RPF patients diagnosed at Peking University People's Hospital between March 2010 and March 2018. Among the 132 patients, the mean age at disease onset was 54.8 years. IgG4-related RPF group showed greater male predominance compared to IRPF group. IgG4-related RPF patients showed a longer interval between symptom onset and diagnosis, and allergic diseases were more common in this group. Sixty-four patients (48.4%) had lower back pain, which was more common in IRPF group than that in IgG4-related RPF patients. In terms of organ involvement, although 42 of 47 patients (89.3%) with IgG4-related RPF had other organ involvement, there were no patients in the IRPF group with other organ involvement. In addition, the serum IgG4 level, elevated eosinophils counts and IgE level were significantly higher in IgG4-related RPF patients. We described the demographic, clinical and laboratory differences between IgG4-related RPF and IRPF patients, indicating their potential differences in pathogenesis, which was of great importance to diagnose and manage the two phenotypes.

18F-FDG PET/MRI compared with clinical and serological markers for monitoring disease activity in patients with aortitis and chronic periaortitis.

OBJECTIVES: We compared the diagnostic value of fully integrated 18F-FDG PET/MRI to that of clinical and serological markers for monitoring disease activity in patients with aortitis/chronic periaortitis (A/CPA) during immunosuppressive therapy. METHODS: Patients positive for A/CPA at the initial and at least 2 consecutive PET/MRI studies were included for retrospective analysis. Imaging (qualitative and quantitative analysis), clinical, and serologic (C-reactive protein, erythrocyte sedimentation rate) assessments were determined at each visit, and their findings compared. Differences in various PET/MRI parameters, clinical symptoms, and serologic markers during therapy between first and second visits were tested for statistical significance. Spearman's rank correlation coefficient was calculated to relate imaging to serologic marker changes between the first 2 visits. RESULTS: Serial assessments were performed in 12 patients with A/CPA, over 34 visits. PET/MRI suggested active disease in 22/34 (64.7%) studies, whereas clinical assessment and serological analysis were positive in only 18/34 (52.9%) and 17/34 (50%) cases, respectively. Disease activity assessment differed between PET/MRI, and clinical and serological markers, in 8/34 (23.5%) and 9/34 (26.5%) cases, respectively. Imaging and serologic parameters (p < 0.009) and clinical symptoms (p = 0.063) predominantly improved at the second visit. Changes from the first to the second visit were not correlated between PET/MRI and serologic markers. CONCLUSIONS: Fully integrated 18F-FDG PET/MRI provides a comprehensive imaging approach with data on vascular/perivascular inflammation that is complementary to clinical and laboratory assessments. This highlights the potential value of imaging-based disease activity monitoring, which might have a crucial impact on clinical management in patients with A/CPA.

IgG4-related disease in patients with newly diagnosed idiopathic retroperitoneal fibrosis: a population-based Danish study.

Objectives: IgG4-related disease (IgG4-RD) may present as 'idiopathic' retroperitoneal fibrosis (IRPF). We aimed to determine the occurrence of IgG4-retroperitoneal fibrosis (IgG4-RPF) in a nationwide study on patients with newly diagnosed IRPF, and to compare histopathological, imaging, and clinical features in the IgG4-RPF and non-IgG4-RPF subsets. Method: The National Danish Pathology Register was searched for biopsy codes relating to retroperitoneal tissue from 1 January 2004 to 31 December 2013. Secondary causes of RPF were excluded. Among 724 candidate cases, 68 were identified with IRPF. Clinical, laboratory, and imaging recordings were reviewed, and tissue blocks were scrutinized for IgG4-RPF features according to international consensus. Results: Forty-two patients (28 males), median age 56 (25-74) years were included. Nineteen (45%) met the criteria for IgG4-RPF, seven with definite and 12 with possible IgG4-RPF, while 23 had non-IgG4-RPF. Local manifestations and laboratory measures did not differ between RPF subsets. Arterial hypertension (p = 0.037) and periaortic fibrosis (p = 0.024) were more common in IgG4-RPF vs non-IgG4-RPF. Plasma cell IgG4/total IgG ratios ≥ 40% were associated more with core histopathological features of IgG4-RD compared to ratios < 40% (p < 0.001). There was a positive correlation between tissue IgG4-positive plasma cells and eosinophil cell count in patients with IgG4-RPF (rho = 0.50, p = 0.043). Conclusion: Forty-five per cent of this nationwide study population with newly diagnosed IRPF could be reclassified with IgG4-RPF. The association between high numbers of IgG4-bearing plasma cells and histopathological features of IgG4-RPF supports IgG4-bearing plasma cells with a perturbed distribution between IgG4 and total IgG being implicated in the pathogenesis of IgG4-RPF.

Clinical and Prognostic Significance of Serum IgG4 in Chronic Periaortitis. An Analysis of 113 Patients.

Objective: Chronic periaortitis (CP) is a rare fibro-inflammatory disorder that incorporates idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysms, and perianeurysmal retroperitoneal fibrosis. CP is included in the spectrum of IgG4-related disease. Since CP patients rarely undergo diagnostic biopsies, serum IgG4 levels are often used to classify CP as IgG4-related. However, the clinical and prognostic significance of serum IgG4 in CP is unknown. Methods: We measured serum IgG4 in active CP patients and compared the clinical characteristics, response to therapy and outcome of patients with high and normal levels. We also tested the diagnostic significance of IgG4 by comparing its levels in CP patients, healthy and disease controls (malignancies, Erdheim-Chester disease, large-, and small-vessel vasculitis). Results: We studied 113 consecutive patients with active CP. Twenty-four (21.2%) had high serum IgG4 (>135 mg/dL). The demographic, laboratory, and clinical characteristics of patients with high and normal IgG4 were similar, and so were the rates of ureteral obstruction and the disease characteristics on CT, MRI, and 18F-FDG-PET. Patients with high IgG4 only had a higher frequency of extra-retroperitoneal fibro-inflammatory lesions (p = 0.005). There were no significant differences in response to therapy and relapses between the two groups. Serum IgG4 levels did not discriminate CP from controls. Conclusions: Serum IgG4 levels are high in a minority of CP patients and do not identify specific clinical or prognostic subgroups; only a higher frequency of extra-retroperitoneal lesions is found in high-IgG4 patients. Serum IgG4 levels do not help in the differential diagnosis between CP and its mimics.

Long-term outcomes and predictors of a large cohort of idiopathic retroperitoneal fibrosis patients: a retrospective study.

OBJECTIVES: Idiopathic retroperitoneal fibrosis (iRPF) is an uncommon disease with inflammatory features. Most patients have good prognosis but some may relapse or even progress to chronic renal failure. The aims of the study were to investigate the prognosis of a large cohort of iRPF patients and explore the risk factors for poor outcomes. METHODS: All patients with a definite diagnosis of iRPF in Peking University First Hospital between 1 January 2003 and 31 December 2016 were enrolled. Their clinical and laboratory data at diagnosis and subsequent follow-up visits were collected. The endpoint of follow-up was defined as disease relapse or the last follow-up. RESULTS: In total, 155 iRPF patients (45 females, 110 males) with a mean ± sd age of 55.1 ± 12 years at diagnosis were enrolled. The median duration of follow-up was 45.3 (0.1-169.2) months. During the whole follow-up, 27/153 (17.6%) patients encountered at least one relapse. Higher baseline erythrocyte sedimentation rate (ESR) was associated with a higher risk of relapse [p = 0.021, odds ratio (OR) = 1.016, 95% confidence interval (CI) 1.002-1.029]. A longer course of glucocorticoid treatment was associated with a lower risk of relapse (p = 0.030, OR = 0.948, 95% CI 0.904-0.995). Patients with a permanent presence of hydronephrosis were more likely to develop renal atrophy (33/154 vs 19/51, χ2 = 5.069, p = 0.024). CONCLUSIONS: Higher baseline ESR and a shorter course of glucocorticoid treatment seemed to be predictors of relapse in iRPF patients. Prompt release of hydronephrosis to prevent kidney atrophy is very important for preserving renal function and improving the prognosis.

Comparison of two subsets of Chinese patients with retroperitoneal fibrosis in terms of IgG4 immunohistochemical staining.

OBJECTIVE: To identify clinical and pathological differences between IgG4-related retroperitoneal fibrosis (IgG4-RPF) and idiopathic RPF (iRPF) in a Chinese population. METHOD: Clinical and pathological data of 50 RPF patients from 2006 to 2016 were retrospectively analysed. The presence of at least one characteristic histopathological feature, >30 IgG4+ plasma cells per high power field, and an IgG4+/IgG+ plasma cells ratio cutoff of >40% were used to define IgG4-RPF. RESULTS: Patients with IgG4-RPF were significantly more likely to have pain (94.1 vs 68.8%, P = 0.048), elevated serum IgE concentration (166.1 vs 40.2 IU/ml, P = 0.029) and tissue eosinophilia (47.1 vs 12.5%, P = 0.018), compared with patients with iRPF. In the IgG4-RPF subgroup, patients with tissue eosinophilia demonstrated higher levels of CRP (4.3 vs 1.9 mg/dl, P = 0.027) and ESR (62.1 vs 22.8 mm/h, P = 0.001). Among the 50 patients with RPF, the average number of tissue IgG4+ plasma cells was positively correlated with the number of tissue eosinophils (r = 0.37, P = 0.009). Moreover, serum IgG4 concentration and serum IgE concentration showed positive correlation (r = 0.834, P = 0.000). CONCLUSION: The distinct serological and histopathological features of Chinese patients with IgG4-RPF were elevated serum IgE concentration and tissue eosinophilia, which potentially can aid and support the diagnosis. As serum IgG4 concentration may be normal in patients with IgG4-RPF, serum IgE may represent a useful serological marker in distinguishing IgG4-RPF from iRPF.

Diffusion-weighted MRI and PET-CT in the follow up of chronic periaortitis.

Aim of the present study is to compare magnetic resonance imaging (MRI) and positron emission tomography (PET) parameters in the follow up of chronic periaortitis (CP), with a focus on changes in the apparent diffusion coefficient (ADC) and standardized uptake values (SUV). 127 patients with CP were treated in our urology between 2007 and 2017. We identified 14 patients with parallel abdominal MRI and PET-CT examinations before therapy and in the follow up resulting in a total of 56 examinations. Relative contrast uptake and diffusion-weighted MRI parameters were compared to SUV in the corresponding PET-CT examinationsand laboratory infection markers. All examined MRI and PET-CT parameters showed significant changes between basis and follow-up examinations. Median ADC values increased significantly (p < 0.001) in the follow up. SUVmax and the other MR parameter (contrast uptake, DWI-signal) declined significantly. We observed a strong negative correlation between ADC and SUVmax (rho: - 0.61; p < 0.001). In addition, we found an inverse correlation of ADC with the inflammation markers ESR (rho: - 0.64; p < 0.001) and CRP (rho: - 0.54; p = 0.001). MRI and PET-CT showed comparable results in the individual follow up of CP and compared to laboratory inflammation markers. Our data support MRI as first imaging modality due to absent radiation and the necessity of repetitive follow-up examinations in patients with CP.

Idiopathic retroperitoneal fibrosis: a cross-sectional study of 142 Chinese patients.

OBJECTIVE: To investigate the epidemiological, clinicolaboratory, imaging, and therapeutic characteristics of idiopathic retroperitoneal fibrosis (iRPF) in China. METHOD: All patients presenting to the Chinese People's Liberation Army General Hospital from October 1996 to July 2016 diagnosed with iRPF were included. Data were collected from medical records and the smoking index was calculated. Scheel radiological classification was used to assess the extent of soft-tissue density. RESULTS: The study included 142 patients (120 men, 22 women). The mean age was 54.3 years. Disease duration ranged from 0.23 to 109.5 months (median 2.7). Current smoking rate was 53.5%. Flank pain was more common in males (p = 0.041) and in the high smoking index group (p = 0.03). C-reactive protein level ranged from 0.08 to 8.9 mg/dL (median 1.9). Serum immunoglobulin G4 (IgG4) was elevated in 31/63 patients (49.2%), and males had higher IgG4 concentrations (p = 0.017) at presentation. Respectively, 44.4%, 5.6%, and 22.5% of cases were classified into Scheel classes I, II, and III. Eight patients (5.6%) had atypical RPF localization and 103 (72.5%) presented with hydronephrosis, which was more common in class III patients (p = 0.04). Nine patients (6.3%) received no treatment; the others received medical (34.5%) or surgical treatment (14.8%), or both (44.4%). CONCLUSIONS: There was a higher rate in males and younger age at disease onset in these Chinese iRPF patients than in other populations. Acute-phase reactants and serum IgG4 were elevated in some patients. Tobacco use may be a risk factor for iRPF in Chinese populations.

Clinical characteristics and outcomes of 61 patients with chronic periaortitis including IgG4-related and non-IgG4-related cases.

AIM: Chronic periaortitis (CP) is a disease characterized by a fibro-inflammatory periaortic cuff and adventitia-predominant fibrosis. CP encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (AAA), and recent studies have documented overlap between CP and immunoglobulin G4-related disease (IgG4-RD). This study aimed to investigate clinical characteristics and treatment outcomes of patients with CP. METHOD: CP patients were identified by retrospective review of 1245 patients with International Classification of Diseases 10th edition code of aortitis or aortic disease. Patients were further classified into IgG4-related and non-IgG4-related CP according to the criteria proposed by a Japanese study. RESULTS: A total of 61 CP patients were identified. Patients showed a male predominance (70%) with median age of 61 at diagnosis. The abdominal aorta was most commonly involved (84%), while the thoracic aorta was affected in 46% of patients. Twenty-three (38%) patients had accompanying aortic aneurysm. Approximately 60% of patients achieved remission without further relapse during the course. Ten patients were classified as IgG4-related and 25 as non-IgG4-related. There was no significant difference in clinical features and outcomes between groups, with the exception of older age and greater pancreas involvement in IgG4-related patients. CONCLUSION: We documented 61 CP patients including 10 IgG4-related cases. CP involved the abdominal aorta in most patients and the thoracic aorta in approximately 50% of patients. IgG4-related CP patients were older and had greater pancreas involvement, but disease outcomes appeared to be similar between IgG4-related and non-IgG4-related CP.

Retroperitoneal fibrosis-clinical presentation and outcome analysis from urological perspective.

PURPOSE: To study clinical presentation, laboratory results, imaging findings and treatment options and outcomes of retroperitoneal fibrosis (RPF). To determine whether it follows the same natural course and response to treatment in the Asian population as in the Western world. MATERIALS AND METHODS: Medical records of patients diagnosed with RPF on imaging and histopathology between February 2010 and April 2016 were reviewed. RESULTS: Of the 21 patients analyzed, mean age at presentation was 50.81 years. The male to female ratio was 0.9:1. Pain was most common presenting complaint (95.23% cases), almost 85% cases were idiopathic and rests were postradiation induced. The median creatinine level was 1.8 mg/dL. The mean erythrocyte sedimentation rate (ESR) was 53.2 mm/h. Hydronephrosis was present in all patients and 47.6% had atrophic kidneys. Diffuse retroperitoneal mass was present in 61.1%. Ureterolysis with lateralization, omental wrapping or gonadal pedicle wrap was done in 17 cases. Two patients underwent uretero-ureterostomy. One patient underwent ileal replacement of ureter, and one ileal conduit. Eighteen patients received concurrent medical treatment, 11 were given tamoxifen, 2 steroids (Prednisolone), and five were given both. Of the 20 patients with follow-up, 70% had complete symptomatic relief; ESR improvement was seen in 77.8%. Follow-up ultrasound showed resolved and decreased hydronephrosis in 20% and 55% respectively. One patient had treatment failure and 17.65% had disease recurrence. CONCLUSIONS: RPF is a rare disease with varied presentation and outcomes. The male to female ratio may be equal in Asians and smoking could be lesser contributing factor. More Asian cohort studies are required to support same.

Elevated serum IgG4 levels in diagnosis and treatment response in patients with idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (iRPF) may be a manifestation of IgG4-related disease. Measuring serum IgG4 (sIgG4) may be of value in monitoring iRPF, but this has scarcely been evaluated. It is unknown if tamoxifen (TMX) affects sIgG4 levels. We performed a prospective inception cohort study of 59 patients with untreated (re)active iRPF stratified by elevated (>1.4 g/L) or normal sIgG4 level. Changes in sIgG4 levels following TMX initiation and, if treatment failed, during subsequent corticosteroid (CS) treatment were analyzed. The median sIgG4 level was 1.1 g/L (interquartile range (IQR) 0.4-2.2); 24 patients (40%) had elevated sIgG4 level. Patients with elevated sIgG4 tended to present with higher ESR (46 vs. 34 mm/h; P = 0.08) and more frequent locoregional lymphadenopathy adjacent to the mass (41.7 vs. 20.0%; P = 0.08). sIgG4 also correlated with ESR (ρ = 0.26; P = 0.05) and serum creatinine (SC) (ρ = 0.26; P = 0.04). Following TMX initiation, sIgG4 level decreased, particularly when achieving treatment success (P < 0.01). Odds ratio for TMX treatment success in patients with elevated sIgG4 level was 0.77 (95% CI 0.53-1.14; P = 0.19). After adjusting for age, sex, and SC, the odds ratio was 0.78 (95% CI 0.51-1.18; P = 0.24). ROC curve analyses of sIgG4 on a continuous scale and treatment success showed an AUC of 0.62. Treatment success and concurrent sIgG4 decrease (P < 0.01) were achieved in 78% of patients who converted to CS therapy. Patients with elevated sIgG4 level may be more inflammatory than patients with normal sIgG4 level, but this needs further study. TMX affects sIgG4 levels, but to a lesser extent than CSs. sIgG4 cannot be used as an outcome prediction tool, irrespective of which cutoff value was chosen.

Disease activity and vascular involvement in retroperitoneal fibrosis: first experience with fully integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging compared to clinical and laboratory parameters.

OBJECTIVES: The aim of this study was to evaluate the value of fully integrated [18F]-FDG PET/MRI in the assessment of retroperitoneal fibrosis with regard to disease activity, extent and vascular involvement compared to clinical and laboratory parameters. METHODS: Seventeen [18F]-FDG PET/MRI examinations were performed in fourteen patients. Qualitative (visual 4-point scale) and quantitative PET parameters (maximum standardised uptake value, SUVmax; target-background ratio, TBR) as well as RF thickness and volume were correlated to clinical and inflammatory parameters and compared between therapy-naïve patients and patients under immunosuppression. Evidence for associated large-vessel vasculitis was examined. Magnetic resonance angiography (MRA) was performed to detect aneurysms or stenoses. RESULTS: Clinical parameters, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) only incompletely displayed inflammatory activity and did not correlate with PET/MRI parameters. In 29% (4/17) resp. 50% (8/16) of PET/MRI examinations active disease was detected although CRP resp. ESR were in the normal range. SUVmax, TBR and volume of the retroperitoneal mass differed significantly between therapy-naïve patients and patients under therapy (SUVmax p=0.004, TBR p=0.015, volume p=0.015), whereas thickness of the retroperitoneal mass did not (p=0.406). Large-vessel vasculitis was detected in 21% (3/14) and aortic aneurysms in 14% (2/14) of patients. Vasculitis occurred apart from the site of RF in two patients. CONCLUSIONS: Whole body hybrid [18F]-FDG-PET/MRI is superior to clinical and inflammatory parameters in disease activity assessment of RF. There may be substantial disease activity despite inflammatory parameters in the normal range. Associated large-vessel vasculitis and aneurysms may occur apart from the site of RF.

[18F]-Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis, Treatment Stratification, and Monitoring of Patients with Retroperitoneal Fibrosis: A Prospective Clinical Study.

BACKGROUND: The ability to distinguish malignant from benign retroperitoneal fibrosis (RPF) and to select patients who are likely to respond to steroid treatment using a noninvasive test would be a major step forward in the management of patients with RPF. OBJECTIVE: To prospectively evaluate the potential of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) to improve clinical decision-making and management of RPF. DESIGN, SETTING, AND PARTICIPANTS: A total of 122 RPF patients were assessed and managed by a multidisciplinary RPF service between January 2012 and December 2015. Of these, 78 patients underwent 101 FDG-PET scans, as well as computed tomography and blood tests. Management was based on the findings from these investigations. Median follow-up was 16 mo. RESULTS AND LIMITATIONS: Of the 24 patients with negative [18F]-FDG-PET, none (0%) had malignancy on biopsy (negative predictive value 100%). [18F]-FDG-PET identified malignancy in 4/4 patients (100%) before biopsy. All four patients had highly avid PET (maximum standardised uptake value ≥4) with atypical avidity distribution. [18F]-FDG-PET revealed avidity in 19/38 patients (50%) with normal inflammatory markers and no avidity in 10/63 patients (16%) with raised marker levels. Patients with highly avid PET were significantly more likely to respond to steroids compared to those with low avidity (9/11 [82%] vs 3/24 [12%]; p<0.01) or negative PET (9/11 [82%] vs 0/14 [0%]; p<0.01). Limitations include the small number of patients and the predominance of tertiary referrals, which may represent patients with particularly problematic RPF. CONCLUSIONS: This study has established a promising role for [18F]-FDG-PET in optimising and individualising the treatment of RPF. PATIENT SUMMARY: This study shows that [18F]-fluorodeoxyglucose positron emission tomography scans could reduce the need for biopsy in patients with retroperitoneal fibrosis (RPF). This technique can distinguish cancer from noncancerous RPF, and may be better than blood tests in assessing and monitoring RPF. It also appears to predict a patient's response to steroids, which should allow more individualised treatment.

Critical review of IgG4-related hypophysitis.

PURPOSE: IgG4-related hypophysitis is a rare disease, with only 34 cases published in English (2015). Available short reviews may not present complete details of IgG4-related hypophysitis. We aimed to survey case reports of IgG4-related hypophysitis, including abstracts of scientific meetings, in English and Japanese. METHODS: We searched for information about IgG4-related hypophysitis in PubMed and Igakuchuozasshi (Japan Medical Abstracts Society). Among 104 case reports found, we reviewed 84 fulfilling Leporati's diagnostic criteria. RESULTS: The mean ±  SD age of onset was 64.2  ±  13.9, 67.5  ±  9.8, and 56.4  ±  18.6 years for all subjects, men, and women, respectively. Men:women was 2.4:1. On magnetic resonance imaging, pituitary, stalk, and pituitary-stalk mass were observed at frequencies of 14.3, 21.4, and 64.3%, respectively. Manifestations were anterior hypopituitarism in 26.2% (22 cases), central diabetes insipidus in 17.9% (15 cases), and panhypopituitarism in 52.4% (44 cases). The median level of serum IgG4 was 264.5 mg/dL for all subjects, 405 mg/dL for men, and 226 mg/dL for women. The mean number of IgG4-related systemic diseases was 2.7  ±  1.5 in all subjects, 3.0  ±  1.5 in men, and 1.8  ±  1.1 in women. Among the IgG4-related diseases, retroperitoneal fibrosis was the most frequent (26.2%), followed by salivary gland diseases (25%). Glucocorticoid therapy was generally effective, except for two cases that received replacement doses. There were significant differences between sexes in terms of age, serum IgG4 levels, and number of IgG4-related diseases. CONCLUSION: IgG4-related hypophysitis may have different clinical characteristics between genders. This survey may lack some information because the Japanese abstracts did not contain certain details.

Non-IgG4-related Multifocal Fibrosclerosis.

Multifocal fibrosclerosis (MFS), which causes systemic and chronic connective tissue inflammation, has been associated with IgG4 and regarded as an identical entity with "IgG4-related disease (IgG4-RD)". Although a few cases of MFS mimicking IgG4-RD histopathologically, despite the absence of a serum IgG4 elevation and IgG4-positive plasma cell infiltration, have been reported, there is, so far, little information regarding such exceptional cases. We herein demonstrate a case of non-IgG4-related MFS presenting with periaortitis and parotiditis, whose histological findings were consistent with IgG4-RD despite the absence of elevated serum and tissue IgG4 levels.

Perfusion-based assessment of disease activity in untreated and treated patients with aortitis and chronic periaortitis: correlation with CT morphological, clinical and serological data.

OBJECTIVE: To evaluate the role of perfusion-based assessment of inflammatory activity in patients with treated and untreated aortitis and chronic periaortitis as compared with clinical and serological markers. METHODS: 35 patients (20 females; median age 66 years) with (peri) aortitis were retrospectively evaluated. All patients had clinical symptoms prompting at the time of imaging. All patients first underwent whole-body contrast-enhanced CT and subsequently segmental volume perfusion CT for assessment of the degree of vascularization of (peri) aortitis as a surrogate marker for inflammatory activity. Blood flow, blood volume, volume transfer constant (k-trans), time to peak and mean transit time were determined. The thickness of the increased connective tissue formation was measured. Perfusion data were correlated with clinical symptoms and acute-phase inflammatory parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leukocyte number. RESULTS: 21 of 35 patients were untreated and 14 of 35 had previous/ongoing immunosuppression. The interobserver agreement was good (κ = 0.78) for all perfusion parameters. Average values of perfusion parameters were higher in untreated patients but remained abnormally elevated in treated patients as well. Perfusion data and ESR and CRP correlated well both in aortitis (p < 0.05) and in periaortitis (p < 0.05). In periaortitis, perfusion parameters agreed well with ESR and CRP values (p < 0.05) only in untreated patients. CONCLUSION: Perfusion CT parameters in untreated aortitis and chronic periaortitis correlate well with serological markers with respect to disease activity assessment. However, in treated periaortitis, correlations were weak, suggesting an increased role for (perfusion-based) imaging. ADVANCES IN KNOWLEDGE: Volume perfusion CT may be used for diagnosis of aortitis/periaortitis.

Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan.

Riedel's thyroiditis (RT) is a rare chronic fibrosing disorder characterized by a hard, infiltrative lesion in the thyroid gland, which is often associated with multifocal fibrosclerosis. Immunoglobulin G4-related disease (IgG4-RD) is typified by infiltration of IgG4-positive plasma cells into multiple organs, resulting in tissue fibrosis and organ dysfunction. In order to evaluate the clinicopathological features of RT and its relationship with IgG4-RD, we performed a Japanese literature search using the keywords "Riedel" and "Riedel's thyroiditis." We used the electronic databases Medline and Igaku Chuo Zasshi, the latter of which is the largest medical literature database in Japan. The diagnosis of RT was based on the presence of a fibroinflammatory process with extension into surrounding tissues. Only 10 patients in Japan fulfilled RT diagnostic criteria during the 25-year period between 1988 and 2012. Two patients with confirmed IgG4/IgG immunohistochemical findings demonstrated 43 and 13 IgG4-positive plasma cells per high-power field, respectively, and the IgG4-positive/IgG-positive plasma cell ratios of 20% and less than 5%. Of the 10 patients with RT, two received glucocorticoids, one of whom experienced marked shrinkage of the thyroid lesion. One patient had extra-thyroid involvement in the form of retroperitoneal fibrosis. Although the clinicopathological features of RT suggest that IgG4-RD may be the underlying condition in some cases, further investigation is needed to clarify the etiology of RT in relation to IgG4-RD.

Retroperitoneal fibrosis: a retrospective clinical data analysis of 30 patients in a 10-year period.

BACKGROUND: Retroperitoneal fibrosis (RPF) is an uncommon disease that is characterized by development of fibrosclerotic tissues involving retroperitoneal structures. This study aimed to investigate the clinical features of 30 patients with RPF in a single center in Beijing in a 10-year period. METHODS: We retrospectively analyzed clinical data on demographic characteristics, clinical manifestations, laboratory findings, radiological findings, modalities of treatments, outcomes and prognosis of 30 patients with RPF. Patients were treated in Beijing Chao-Yang Hospital between January 2003 and December 2013. RESULTS: The mean age of patients with RPF was 56.7 ± 14.4 years. Twenty-three patients were men and seven patients were women. Acute phase reactants were elevated in most patients. Rheumatic factor was positive in 4/25 (16.0%) patients, and antinuclear antibody was positive in 6/22 (27.3%) patients. Elevation of IgG4 was observed in 9/22 (40.9%) patients. The most common type was I + III (n = 13), followed by I + II + III (n = 12). Five patients undertook an 18 F-fluoro-deoxy-D-glucose positron emission tomography examination and increased uptake was detected in four patients. Eight patients received combination therapy with glucocorticoids and tamoxifen. Surgical intervention treatments included intraureteral double-J stent implantation (n = 26), percutaneous nephrostomy (n = 2), open ureterolysis and intraperitonealization of the ureters (n = 5) and laparoscopic ureterolysis and intraperitonealization of the ureters (n = 5). Three patients underwent hemodialysis because of renal failure. CONCLUSIONS: Clinical characteristics of RPF patients in our study are similar to those previously reported. Steroids and immunosuppressive therapy combined with ureterolysis could be a viable choice of treatment for RPF. More prospective, multi-center studies with a longer follow-up are warranted.