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.

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.

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.

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.

[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.

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.

INFLAMMATORY ABDOMINAL AORTIC ANEURYSM--A FORM OF CHRONIC PERIAORTITIS.

Chronic periaortitis represents a unique pathogenic concept for three entities: Inflammatory Abdominal Aortic Aneurysm, Idiopathic Retroperitoneal Fibrosis and Perianeurysmal Retroperitoneal Fibrosis. The fundamental meaning of an inflammatory reaction to advanced atherosclerosis has been developed on the bottom of clinical and histological features. The triad of abdominal pain, weight loss and elevated inflammatory markers: erythrocyte sedimentation rate/C-reactive protein in patients with abdominal aortic aneurysms revealed on contrast-enhanced computer tomography is highly suggestive for inflammatory aneurysm. We report a case of a heavy-smoker adult male presented with suddenly abdominal symptoms suggestive for mesenteric ischemia which have proved to be due to inflammatory abdominal aortic aneurysm. The most favorable management of patients with inflammatory aneurysm is ambiguous. Surgical approach seems reasonable even supposing inflammatory aneurysm emerges less likely to rupture than the atherosclerotic variant. Corticosteroids are used in inoperable inflammatory aneurysm, even if is well known that this treatment does not change the long-term outcome of the disease. Surgical-open or Endovascular Repair of the aneurysm is the elective treatment.

Retroperitoneal disorders associated with IgG4-related autoimmune pancreatitis.

IgG4-related autoimmune pancreatitis is frequently accompanied by relevant lesions in the genitourinary tract and retroperitoneal organs, which cause various clinical problems, ranging from non-specific back pain or bladder outlet obstruction to renal failure. The diagnosis of IgG4-related retroperitoneal fibrosis requires a multidisciplinary approach, including serological tests, histological examination, imaging analysis, and susceptibility to steroid therapy. Radiological examinations are helpful to diagnose this condition, but surgical resection is occasionally unavoidable to exclude malignancy, particularly for patients with isolated retroperitoneal involvement. Steroid therapy is the treatment of choice for this condition, the same as for other manifestations of IgG4-related disease. For patients with severe ureteral obstruction, additional ureteral stenting needs to be considered prior to steroid therapy to preserve the renal function. Some papers have suggested that IgG4-related disease can affect male reproductive organs including the prostate and testis. IgG4-related prostatitis usually causes lower urinary tract symptoms, such as dysuria and pollakisuria. Patients sometimes state that corticosteroids given for IgG4-related disease at other sites relieve their lower urinary tract symptoms, which leads us to suspect prostatic involvement in this condition. Because of the limited number of publications available, further studies are warranted to better characterize IgG4-related disease in male reproductive organs.

Diffusion-weighted MRI findings of treated and untreated retroperitoneal fibrosis.

PURPOSE: We aimed to evaluate diffusion-weighted imaging (DWI) findings in patients with treated and untreated retroperitoneal fibrosis (RPF). METHODS: We analyzed magnetic resonance imaging examinations of 44 RPF patients (36 male, 8 female), of which 15 were untreated and 29 were under therapy. Qualitative DWI and T1 postcontrast signal intensities and the largest perivascular extent of RPF were compared between treated and untreated groups and correlated to erythrocyte sedimentation rate and C-reactive protein values. Quantitative DWI signal intensities and apparent-diffusion-coefficients were calculated in regions-of-interest, together with a relative index between signal intensities of RPF and psoas muscle in 15 untreated patients and 14 patients under treatment with remaining perivascular fibrosis of more than 5 mm. RESULTS: The extent of RPF in untreated patients was significantly larger compared with the extent of RPF in treated patients (P <0.0001). DWI signal intensities were significantly higher in untreated patients than in patients under therapy (mean, 27 s/mm2 vs. 20 s/mm2; P = 0.009). The calculated DWI-index was significantly higher in untreated patients than in patients under therapy (P = 0.003). CONCLUSION: Our data show significant differences in the DWI findings (b800 signal intensities and relative DWI-index) of patients with treated and untreated RPF. DWI is a promising technique in the assessment of disease activity and the selection of patients suitable for medical therapy.

[IgG4-related chronic periaortitis with retroperitoneal fibrosis].

The paper describes a case of IgG4-related chronic periaortitis in a 56-year-old man. Computed tomography revealed stenosis of the abdominal aorta and both common iliac arteries due to calcified atherosclerotic plaques, in this connection, bifurcation aorta-common femoral bypass surgery was performed. Intraoperatively, a solid retroperitoneal mass intimately connected with the walls of vessels was revealed in the retroperitoneal space around the aorta and iliac arteries. Histological examination ascertained rough fibrous connective tissue growth, a marked lymphoplasmacytic infiltration with an admixture of eosinophils, and formation of lymphoid follicles with germinal centers. Immunohistochemical examination revealed the plasma cell expression of CD20, IgG, IgG4, and kappa and lambda light chains in the inflammatory infiltrate. Because of active immune inflammation, further conservative therapy was recommended.

Serum immunoglobulin G4 level is a poor predictor of immunoglobulin G4-related disease.

OBJECTIVES: Immunoglobulin G4-related disease (IgG4-RD) is characterized by elevation in serum IgG4 levels, typical multiorgan involvement and dramatic response to steroid therapy. We determined the predictive value of an elevated serum IgG4 for the diagnosis of IgG4-RD. We also sought to identify novel conditions, which have characteristic features of IgG4-RD. METHODS: We identified all Mayo Clinic Rochester patients with serum IgG4 levels measured between January 2008 and December 2011 (n = 6014). Those with elevated serum IgG4 levels (reference range, 121-140 mg/dL) were included in the analysis and were classified as "definite," "probable," or "no" IgG4-RD. RESULTS: Serum IgG4 levels were elevated in 390 subjects (6.5%) of whom only 39 (10%) had IgG4-RD (29 "definite," 10 "probable"). The positive predictive value of an elevated serum IgG4 for IgG4-RD was poor (10%). Subjects with IgG4-RD differed from those without IgG4-RD in mean age (59.6 ± 15.2 vs 54.4 ± 18.3 years, P < 0.05), % males (90% vs 58%, P < 0.05), mean serum IgG4 level (437 ± 471 vs 223 ± 194 mg/dL, P < 0.05), and presence of chronic rhinosinusitis (7/39 vs 29/351, P = 0.05). CONCLUSIONS: Elevated serum IgG4 levels are not specific for IgG4-RD and are likely to be a false-positive. Chronic rhinosinusitis is likely an as yet underrecognized manifestation of IgG4-RD.

Concomitant occurrence of IgG4-related pleuritis and periaortitis: a case report with review of the literature.

IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Some recent reports have demonstrated that this disease can occur in the respiratory system including the pleura. Herein, we describe the first documented case of concomitant occurrence of IgG4-related pleuritis and periaortitis. A 71-year-old Japanese female with a history of essential thrombocythemia presented with persistent cough and difficulty in breathing. Computed tomography demonstrated thickening of the right parietal pleura, pericardium, and periaortic tissue and pleural and cardiac effusions. Histopathological study of the surgical biopsy specimen of the parietal pleura revealed marked fibrous thickening with lymphoplasmacytic infiltration. Phlebitis was noted, however, only a few eosinophils had infiltrated. Immunohistochemical study revealed abundant IgG4-positive plasma cell infiltration and high ratio of IgG4-/IgG-positive plasma cells (84%). Therefore, a diagnosis of IgG4-related pleuritis was made with consideration of the elevated serum IgG4 level (684 mg/dL). Recently, the spectrum of IgG4-related sclerosing disease has expanded, and this disease can occur in the pleura, pericardium, and periaortic tissue. Although histopathological analysis of the pericardium and periaortic tissue was not performed in the present case, it was suspected that thickening of the pericardium and periaortic tissue was clinically due to IgG4-related sclerosing disease. Our clinicopathological analyses of IgG4-related pleuritis and pericarditis reveal that this disease can present as dyspnea and pleural and pericardial effusion as seen in the present case, therefore, it is important to recognize that IgG4-related sclerosing disease can occur in these organs for accurate diagnosis and treatment.

Interleukin-6 as an inflammatory mediator and target of therapy in chronic periaortitis.

OBJECTIVE: Chronic periaortitis (CP) usually responds to glucocorticoids, but some patients have glucocorticoid-refractory disease or contraindications to glucocorticoid therapy. This study was undertaken to evaluate treatment with the anti-interleukin-6 receptor (anti-IL-6R) antibody tocilizumab in 2 patients with CP, one with refractory disease and the other with contraindications to glucocorticoids, and to assess IL-6 levels in an additional cohort of patients with CP. METHODS: Both patients were given intravenous tocilizumab (8 mg/kg) once every 4 weeks for 6 months. Serum IL-6 was measured in 22 patients with active CP and 16 healthy controls. Tissue IL-6 expression was assessed by confocal microscopy in biopsy specimens obtained from 6 patients with CP. RESULTS: In the first patient, whose disease was refractory to various immunosuppressive treatments, tocilizumab added to ongoing therapy with prednisone and methotrexate allowed prednisone withdrawal and induced resolution of symptoms, acute-phase reactant normalization, and reduction in (18) F-fluorodeoxyglucose ((18) F-FDG) uptake on positron emission tomography. The patient experienced a relapse 7 months later and was successfully retreated with tocilizumab. In the second patient, who was unable to tolerate glucocorticoids because of psychiatric side effects, tocilizumab monotherapy induced sustained clinical and laboratory remission, (18) F-FDG uptake disappearance, and CP shrinkage. Serum IL-6 levels were significantly higher in patients with active CP than in controls (P < 0.0001), and IL-6 was abundantly expressed in biopsy specimens from CP patients, particularly by T cells, B cells, histiocytes, fibroblasts, and vascular smooth muscle cells. CONCLUSION: Tocilizumab may be a therapeutic option for CP. The systemic and tissue up-regulation of IL-6 in CP, together with the clinical benefit of IL-6R blockade observed in our 2 patients, suggest that IL-6 may contribute to CP pathogenesis.

High serum immunoglobulin G4-related retrosternal fibrosclerosis.

A 65-year-old man with a history of exposure to asbestos complained of left leg edema. Computed tomography showed a flat, symmetrical, and longitudinal retrosternal thickening in addition to a presacral tumor. Retroperitoneal fibrosis was suspected. Serum immunoglobulin G4 (IgG4) levels were elevated (213 mg/dL). Thoracoscopic biopsy was performed. Histopathologic findings showed fibrotic tissue accompanied by proliferation of IgG4-positive plasma cells (proportion of IgG4/IgG-positive plasma cells ≥70%) indicative of multifocal fibrosclerosis.

Idiopathic retroperitoneal fibrosis: a retrospective review of clinical presentation, treatment, and outcomes.

OBJECTIVE: To describe the clinical manifestations, laboratory results, imaging findings, and treatments in patients with idiopathic retroperitoneal fibrosis (IRF) seen at Mayo Clinic in Rochester, MN. PATIENTS AND METHODS: In this retrospective study, we used International Classification of Diseases, Ninth Revision codes to identify all patients evaluated for IRF between January 1, 1996, and December 31, 2006, at Mayo Clinic in Rochester, MN. Medical records were reviewed, and clinical information was abstracted. Idiopathic retroperitoneal fibrosis was diagnosed on the basis of compatible imaging findings. Patients were followed up until their last visit at Mayo Clinic, death, or December 31, 2008, whichever came first. RESULTS: Of the 185 patients identified as having IRF, 113 (61%) were men and 72 (39%) were women. Mean ± SD age at diagnosis was 57.6 ± 11.8 years. Biopsy specimens were obtained in 142 cases (77%). The most common presenting symptoms were back pain (38%) and abdominal pain (40%). Baseline erythrocyte sedimentation rate and/or C-reactive protein levels were elevated in 88 (58%) of the 151 patients tested. The median creatinine level at diagnosis was 1.3 mg/dL (interquartile range, 1.1-2.1 mg/dL). Fifteen patients (8%) were treated with ureteral procedures only, 58 patients (31%) with medications only, and 105 patients (57%) with a combination of medical and surgical therapies. Seven patients (4%) were not treated. Corticosteroids were initiated in 116 patients (63%), and tamoxifen was used in 120 patients (65%). Follow-up was available for 151 patients (82%). Creatinine levels were normal at last visit in 102 (68%) of the 151 patients with follow-up. No patient developed end-stage renal disease. Relapses occurred in 18 (12%) of the 151 patients. Eleven patients died. CONCLUSION: In this cohort, outcomes such as end-stage renal disease or death from renal failure were not observed. Relapses may occur, and patients with IRF warrant long-term follow-up.