Significance of high serum IgG4 in complete or non-full-fledged IgG4-related disease-a retrospective investigation of 845 patients and its clinical relevance.

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized heterogeneous, subacute, and usually silent autoimmune disease involving many organs with protean manifestations. However, high IgG4 in serum is not necessarily indicating an IgG4-RD. The aims of this study were to investigate the clinical relevance of high serum IgG4 level in IgG4-RD or non IgG4-RD patients, and to see if IgG4-RD in Taiwan differs from that in other parts of the world. METHODS: Eight hundred forty-five patients with high IgG4 were retrospectively reviewed from January 2002 to May 2020 in Taipei Veteran General Hospital. Two hundred sixty-seven patients fulfilled IgG4-RD criteria and were categorized into pancreato-hepato-biliary disease, retroperitoneal fibrosis and/or aortitis, head/neck-limited disease, classic Mikulicz syndrome with systemic involvement, CNS-limited disease, sclerosing vasculitis, skin-limited disease, and sensorineural hearing disease. These manifestations were correlated to smoking, atopy, hyper-IgE/eosinophilia, aging, malignancies, and hypocomplementemia. Five hundred seventy-eight patients were not fulfilling the criteria but were also analyzed for the prevalence of allergy, malignancy, connective tissue diseases, lung diseases, and infections. RESULTS: In IgG4-RD patients, 124 (46.4%) smoked. Top 4 clinical subtypes included Mikulicz syndrome with systemic involvement (33.3%), pancreato-hepatobiliary disease (31.4%), head/neck disease (19.4%), and retroperitoneal fibrosis/aortitis (12.7%). Top 4 co-morbid conditions included high serum IgE/eosinophilia (46.2%), hypocomplementemia (34%), malignancies (13.4%), and allergy (13.4%). Pancreato-biliary disease was associated with high IgE/eosinophilia (r2 = 0.380, P = 0.025) and malignancy (r2 = 0.211, P = 0.027), Miculicz syndrome with allergy (r2 = 0.396, P < 0.01) and high IgE/eosinophil (r2 = 0.396, P < 0.01), CNS diseases (r2 = 0.973, P = 0.035) and sclerosing vasculitis (r2 = 1, P < 0.01) with advanced age respectively, with the latter being also related to atopy and high IgE/eosinophilia (r2 = 1, p < 0.01). CONCLUSION: Smoking may precipitate IgG4-RD. IgG4-RD with pancreato-hepatobiliary disease is closely related to allergy and neoplasm, and those with Mikulicz syndrome may result from atopy. Elderly IgG4-RD patients tend to develop CNS pathology parallel to advancing of age. The disease may probably be originated from an unknown mechanism that may sporadically evolve into malignancies.

Association of retroperitoneal fibrosis with malignancy and its outcomes.

INTRODUCTION: Retroperitoneal fibrosis (RPF) is characterized by a highly fibrotic retroperitoneal mass and encompasses the idiopathic form and secondary to malignancies. Because we have limited knowledge whether RPF is associated with malignancy, we aimed to investigate the relationship between RPF and malignancy and to compare the characteristics and prognosis of cancers among patients with RPF. METHODS: Medical records of 111 patients diagnosed as having RPF were reviewed and 38 cases of cancer, confirmed by biopsy, were identified. Standardized incidence ratios (SIRs) were calculated for cancers and stratified according to cancer type and RPF-cancer diagnosis interval. Cancer characteristics and outcomes were compared between RPF-cancer diagnosis intervals. RESULTS: The average age at RPF diagnosis was 59.2 ± 15.0 years, and 69.4% of the patients were male. The cancer SIRs in patients with RPF relative to age- and sex-matched individuals in the general population was 2.2 (1.6-3.1). SIRs of renal pelvis cancer and multiple myeloma were significantly higher than in the general population. When stratified by RPF-cancer intervals, the SIR for cancer was 9.9 within 1 year of RPF diagnosis, while no significant increase in the SIR was found after 1 year from RPF diagnosis. Cancer stage was more advanced at the time of diagnosis in patients within a 1-year interval for RPF than those with cancer within a >5-year interval, with a correspondingly increased mortality in the former patients. CONCLUSIONS: RPF was significantly associated with malignancy, particularly those diagnosed within 1 year of RPF diagnosis. Cancer stages at diagnosis were more advanced and the mortality rate was higher in patients within a 1-year interval between RPF and cancer diagnosis than in those with a >5-year interval between diagnoses.

Characteristics and prognosis of IgG4-related periaortitis/periarteritis: A systematic literature review.

OBJECTIVE: Immunoglobulin G4 (IgG4)-related disease is a systemic chronic fibroinflammatory disease that can affect almost every organ of the body. IgG4-related periaortitis/periarteritis is a newly recognized subset of IgG4-related disease, and its characteristics and prognosis remain unclear. We investigated the clinical characteristics and prognosis of IgG4-related periaortitis/periarteritis. METHODS: We performed a systematic literature review of IgG4-related periaortitis/periarteritis. Additionally, we have summarized the characteristics and prognosis of IgG4-related coronary arteritis. RESULTS: We investigated 248 patients with IgG4-related periaortitis/periarteritis. All studies reported the condition in elderly patients, and male predominance was observed. The infra-renal abdominal aorta and iliac arteries were the most commonly affected sites. Most reports showed the serum C-reactive protein elevation in this disease entity, in contrast to non-vascular IgG4-related disease. Based on radiological findings observed in 27 patients with IgG4-related coronary arteritis, vasculitic lesions were classified into 3 types: stenotic (67% of patients), aneurysmal (42%), and diffuse wall thickening type (92%). Serum IgG4 level, but not C-reactive protein level, was associated with the number of affected organs in IgG4-related coronary arteritis. Corticosteroid treatment with or without cardiac surgery or percutaneous coronary intervention was effective in most patients with IgG4-related coronary arteritis; however, 33% of patients showed an unfavorable clinical course including disease progression, relapse, or death. Pre-treatment stenosis and/or aneurysms were associated with progression of stenosis or aneurysm after corticosteroid treatment. CONCLUSION: Most clinical characteristics were similar between the IgG4-related periaortitis/periarteritis and the non-vascular IgG4-related disease groups; however, serum C-reactive protein level elevation was observed only in the former. Although corticosteroid treatment was effective, this disease can be life-threatening secondary to myocardial infarction, aortic dissection, and aneurysmal rupture. Pre-treatment evaluation of stenosis or aneurysms is important for predicting progression of stenosis or aneurysm after corticosteroid treatment.

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.

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.

Idiopathic retroperitoneal fibrosis and its overlap with IgG4-related disease.

Retroperitoneal fibrosis (RPF) is a rare disease characterised by fibrous tissue proliferation in the retroperitoneum, with encasement of the ureters and large vessels of the abdomen as the most destructive of potentially severe complications. It can either be idiopathic, or secondary to infections, malignancies, or the use of certain drugs. The idiopathic form accounts for approximately 75% of the cases, and is usually responsive to immunosuppressive therapy. In recent years, the emergence of a new clinical entity, IgG4-related disease (IgG4-RD), shed light on many fibro-inflammatory disorders once thought to be separate clinical entities, although frequently associated in the so-called multifocal fibrosclerosis. Among these, together with sclerosing pancreatitis and cholangitis, pseudotumour of the orbit, idiopathic mediastinal fibrosis and other conditions, is idiopathic retroperitoneal fibrosis (IRF). Both IRF and IgG4-RD can be associated with a wide variety of disorders, usually governed by immune-mediated (and particularly auto-immune) mechanisms. In our review, we discuss the clinical and therapeutic challenges IRF presents to the internist, as well as the meaning of its recent inclusion in the IgG4-RD spectrum from a clinical practice standpoint.

IgG4-related retroperitoneal fibrosis: a newly characterized disease.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by chronic, nonspecific inflammatory and sclerotic or fibrotic tissue in the periaortic or periiliac retroperitoneum that encases adjacent structures. There will be a series of clinical manifestations once the proliferated fibrous tissues encase the abdominal aorta, iliac arteries and urinary duct. RPF is generally divided into two types: idiopathic retroperitoneal fibrosis (IRPF) without identified pathogenesis, making up about two-thirds of cases, and secondary retroperitoneal fibrosis. Recent studies on Immunoglobulin G4-related disease (IgG4-RD) reveal that abundant infiltration of IgG4 positive plasma cells is found in biopsies on the mass of RPF of some IRPF patients, which is identified as one spectrum of IgG4-RD and is named IgG4-related RPF. IgG4-related RPF is often misdiagnosed as retroperitoneal visceral malignancy and is treated with surgery. In addition, because of its good response to glucocorticoid, early detection and treatment is important. We review the definition, epidemiology, clinical features, diagnostic criteria, treatment and prognosis of IgG4-related RPF in this article to raise awareness of this newly characterized disease.

[Retroperitoneal fibrosis in adults: Main characteristics and relevance of the diagnostic procedures based on a retrospective multicenter study on 77 cases]. / Fibrose rétropéritonéale de l'adulte : analyse descriptive et évaluation de la pertinence des examens complémentaires réalisés à visée diagnostique à partir d'une série rétrospective multicentrique de 77 cas.

INTRODUCTION: Retroperitoneal fibrosis (RPF) is a rare disorder characterized by the sheathing of retroperitoneal structures by fibro-inflammatory process. It can be either isolated or associated with an underlying disease or condition. In the absence of consistent and consensual approach, the objective of this study was to assess the relevance of diagnostic tests performed during the diagnostic work-up of RPF. METHODS: Seventy-seven patients were included in this retrospective multicenter study. The diagnosis of RPF was defined by the presence of a thickened circumferential homogeneous tissue unsheathing the infrarenal aorta, excluding peri-aneurysmal fibrosis and a clear evidence of a cancer. RESULTS: In 62 cases (80.5%), the RPF was considered as being primary or "idiopathic". Surgical (n=31) or CT-guided (n=9) biopsies of the RPF were performed in half of the patients showing some fibrotic or non-specific inflammatory lesions in 98% of cases. A bone marrow biopsy was performed in 23 patients leading to diagnosis of low grade B cell non-Hodgkin lymphoma in a single patient who also had a monoclonal gammopathy IgM. The systematic search for autoantibodies or serum tumor markers was of no diagnostic value. CONCLUSIONS: Although the diagnostic procedure was heterogeneous, no cause or associated disease was found in the majority of cases of FRP in this series. In the absence of any clinical or paraclinical evidence suggesting an underlying disease or any atypical features at presentation, a number of non-invasive tests (autoantibodies, tumor markers, bone scintigraphy) and also more invasive diagnostic tests (bone marrow and RPF biopsies) seem of little relevance.

Drug-induced retroperitoneal fibrosis: short aetiopathogenetic note, from the past times of ergot-derivatives large use to currently applied bio-pharmacology.

Among the secondary forms of retroperitoneal fibrosis (RPF), that drug-induced shows very intriguing aspects given both the broad range of involved pharmaceuticals and the considerable interest arisen from the related pathogenetic mechanisms. The particular incidence, in the last four decades past century, of the RPF due to long-term use of ergot alkaloid derivatives (ergotamine, methysergide, pergolide, bromocriptine, cabergoline) and specific L-dopa derived agents, such as methyldopa, as well as to different analgesics, came progressively down given that their long-term use for either the prevention of migraine attacks or the therapy of chronic pathologies (Parkinson's disease, prolactinoma, pain management, etc) has been, year after year, supplanted or even made unavailable in many countries. More recently, instead, the occurrence of the RPF has been sometimes identified with the use of antitumoral chemotherapeutics, such as carboplatin and methotrexate, and, just lately, as an unusual side-effect of certain biological agents, about which it is timely to go into specific pathogenetic problems in more depth.

[Idiopathic retroperitoneal fibrosis: a multicentric retrospective study of 30 French cases and follow-up of the renal function]. / Fibrose rétropéritonéale idiopathique : évolution à long terme du pronostic rénal dans une série rétrospective multicentrique de 30 cas.

PURPOSE: Idiopathic retroperitoneal fibrosis (IRF) is an inflammatory disorder, affecting the aorta and the surrounding vessels and tissues. The prognosis is mainly driven by the risks of chronic kidney disease and relapse. Our aim was to assess the prevalence of chronic kidney disease at follow-up. METHODS: We retrospectively reviewed the medical records of patients diagnosed for IRF in Seine-Saint-Denis (France) between 1987 and 2011. We collected informations about presentation, radiologic findings and follow-up. Diagnosis of IRF was confirmed when all the following criteria were met: infiltration of the infrarenal aorta or iliac vessels, absence of aneurysmal dilation, lack of clinical suspicion of malignancy. RESULTS: Thirty patients were identified, with a male/female ratio of 4.9. Mean age was 55±13 years old. The mean creatinine clearance was 66 mL/min/1.73 m(2) and the mean CRP was 45±36 mg/L. In 24 (80%) patients, the location of IRF was periaortic and periiliac. Eleven patients (37%) underwent a diagnostic biopsy, and 14 (47%) required an ureteral procedure. A mean follow-up of 63 months was available for 29 patients: 69% relapsed, 7 developed chronic renal disease (24%), and one died of urinary sepsis. Older age (P=0.023), diabetes (P=0.007), and initial renal insufficiency (P=0.05) were associated with a risk of chronic renal insufficiency. CONCLUSION: The high frequency of relapses and chronic renal disease emphasizes the need of close follow-up in patients diagnosed with IRF.

The use of a thermoexpandable metal alloy stent in the minimally invasive management of retroperitoneal fibrosis: a single center experience from the United kingdom.

PURPOSE: To review our experience with and the effectiveness of the ureteral Memokath 051 metallic stent for the minimally invasive management of retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: We retrospectively reviewed the records of patients with RPF who were treated between April 2008 and February 2013. Success was defined as improvement of renal function and lack of complications after stent placement. Follow-up was at 6 weeks, 3 months, 6 months, and annually thereafter. RESULTS: A total of 14 patients were identified. The study included eight female and six male patients. Mean age was 60.2 years±8.4 standard deviation (SD). The majority of patients had idiopathic RPF (n=12, 85.7%). Stent placement was performed in 23 renal units in 14 patients, 9 (64.3%) of whom had bilateral disease. Ten (71.4%) patients had previously received medical treatment, while three (21.4%) presented with recurrent disease postureterolysis. The mean length of follow-up was 22.5 months (range 3-56 mos). Mean stricture length was 7.6 cm±6.2 SD on the right and 7.7 cm±5.1 SD (P=0.925) on the left. Patients tolerated the stents well with minimal discomfort. Ureteral obstruction was managed successfully in 78.6% of patients (n=11/14). All patients had improvement of renal function. CONCLUSIONS: To our knowledge, this is the first study using metal stents in patients with RPF. Retrograde placement of the ureteral Memokath 051 metal stent can be considered as a promising alternative for initial or salvage postureterolysis minimally invasive management of ureteral obstruction in RPF.

[IgG4-related disease]. / Maladie associée aux immunoglobulines G de type 4.

IgG4-related disease is an emerging pathological condition characterized by one or several fibrosing and inflammatory organ involvements. Histological findings are typical and associate storiform fibrosis with polyclonal lymphocytic and plasma-cell infiltrate, with predominant IgG4-expressing plasma cells. Sclerosing lymphoplasmocytic pancreatitis, or type 1 auto-immune pancreatitis, and other organ involvements have been reported: sclerosing cholangitis, sialadenitis, dacryoadenitis, retroperitoneal fibrosis, aortitis, interstitial nephritis, polyadenopathy and inflammatory pseudo-tumors. Serum IgG4 level is elevated in most of patients, but the histological documentation remain necessary for the diagnosis. Dramatic response to steroids is usual but relapses are frequent.

Retroperitoneal fibrosis.

Retroperitoneal fibrosis (RPF) is a condition characterized by the presence of inflammation and fibrosis in the retroperitoneal space, for which no standard diagnostic criteria exist. Historically, treatment has focused on relieving the obstruction with percutaneous or cystoscopic assisted placement of ureteral stents followed by more definitive resolution of ureteric obstruction with open or laparoscopic ureterolysis. However, over the past several years management has shifted from primarily a surgical approach to an immunosuppressive-based therapy aimed at modulation of the immune system. This review focuses on the recent advances in the classification, epidemiology, pathophysiology, pathology, imaging, and treatment of RPF.

[Long-term follow-up of a French cohort of retroperitoneal fibrosis]. / Fibrose(s) rétropéritonéale(s) : stratégie diagnostique, pathologies associées et suivi à long terme d'une cohorte française.

PURPOSE: Retroperitoneal fibrosis (RPF) is a rare disease with an expanding etiologic spectrum. We aimed to analyze non-invasive diagnosis strategy, associated disorders, monitoring, treatment and prognosis. METHODS: Retrospective cohort study in a single tertiary center. RESULTS: Eighteen RPF cases (11 males) followed between 1996 and 2009 were reviewed. Blood CRP level was high in all cases before treatment. CT scan, associated or not with MRI or 18-FDG PET-scan, confirmed the diagnosis in 15 patients. Histological analysis of a surgical biopsy specimen was performed in only three cases. Ten patients suffered retroperitoneal fibrosis secondary to systemic vasculitis (granulomatosis with polyangeitis, n=1, Takayasu aortitis, n=2), systemic fibrosis with Riedel thyroiditis (n=1) and atheromatous periaortitis (n=6). Fifteen patients were treated with corticosteroids with a mean treatment duration of 60 months (12-228). Dependency to corticosteroids was recorded in ten patients. Patients with fibrosis related to vasculitis were younger, had a higher CRP level, more frequent corticosteroid dependency and a higher relapse rate. Relapses were successfully treated with steroids. Immunosuppressive treatment was only prescribed in the setting of systemic vasculitis. No patient died, after a 6±2 years follow-up. Late relapses could occur, sometimes years after steroid therapy cessation. CONCLUSION: In our study, RPF occurred as a secondary disorder in 60% of the cases. Disease extension, relapse rate and treatment response varied according to the underlying cause of RPF, pleading for an extensive and systematic initial assessment. Since no death or end-stage renal insufficiency was observed, RPF might be considered as a steroid-sensitive and benign disorder.

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.

Vasculitis of the gastrointestinal tract in chronic periaortitis.

The term "chronic periaortitis" (CP), proposed by Mitchinson in 1984, comprises 3 main entities: idiopathic retroperitoneal fibrosis (IRF), inflammatory abdominal aortic aneurysms (IAAAs), and perianeurysmal retroperitoneal fibrosis (PRF).The presence of constitutional symptoms, high acute-phase reactants, positive autoantibodies, and associated autoimmune diseases suggests a systemic inflammatory process. Histopathologic findings show vasculitis with fibrinoid necrosis involving the aortic vasa vasorum as well as the small and medium retroperitoneal vessels.We reviewed the medical records of 608 patients with a diagnosis of vasculitis involving the gastrointestinal (GI) tract at the Mayo Clinic between January 1996 and December 2007. Only patients with biopsy-proven or typical angiographic findings of vasculitis localized to the GI tract were included.Five patients were identified with evidence of CP (1 patient with PRF, 1 with IRF, and 3 with IAAAs). Three patients were men, and the median age at diagnosis was 49 years. The diagnosis of GI vasculitis and CP was made simultaneously in 4 patients. At the time of onset, all patients had abdominal pain and constitutional manifestations; the median erythrocyte sedimentation rate was 62.5 mm/1 h (range, 20-86 mm/1 h). All patients had evidence of mesenteric vasculitis at angiography. Three patients also had associated renal artery stenoses. Abdominal computed tomography showed spleen infarcts in 2 patients, bowel wall thickening in 1, and liver infarction in 1. Two patients underwent surgical intervention for acute abdomen; there was histologic evidence of small bowel infarcts and infarction of the spleen and liver in 1. Oral prednisone was administered to all 5 patients (median starting dose, 60 mg/d; range, 25-80 mg/d). Three patients also received immunosuppressive agents, 1 tamoxifen, and 1 anti-tumor necrosis factor therapy. All patients had at least 1 relapse or recurrence of vasculitis, but at last visit, GI vasculitis and CP were in remission in all 5 patients.This study provides evidence that GI manifestations due to mesenteric vasculitis may be associated with CP. Vasculitic involvement of the renal arteries is also frequently present in these patients. Aggressive immunosuppressive treatment should be promptly initiated to forestall abdominal complications. These findings reinforce the hypothesis that a vasculitic process plays an important role in the pathogenesis of CP.

Autoantibodies against oxidized low-density lipoprotein and lipid profile in patients with chronic periaortitis: case-control study.

Chronic periaortitis is thought to result from an autoallergic reaction to oxidized low-density lipoprotein (OxLDL). No data exist on lipid profile and atherosclerotic biomarkers. We investigated circulating levels of OxLDL and of anti-OxLDL (aOxLDL) antibodies in patients with chronic periaortitis using the cross-sectional case-control study on 20 patients with chronic periaortitis. Patients were compared to 20 age- and sex-matched controls. aOxLDL antibodies were measured by ELISA and expressed as mean optical density values at 450 nm from duplicate measurements (OD(450)). aOxLDL antibody titers (median [interquartile range]) did not differ significantly between patients and controls (aOxLDL-IgM: 0.70 [0.24-1.08] vs. 0.54 [0.25-0.73] OD(450); aOxLDL-IgG: 0.59 [0.38-0.75] vs. 0.41[0.33-0.63]OD(450)). Female patients had higher aOxLDL-IgM levels than male patients (1.02 [0.46-1.38] vs. 0.29 [0.22-0.84] OD(450); P = 0.05). aOxLDL-IgM titers were lower in patients with cardiovascular disease (CVD) than in patients without CVD (0.22 [0.16-0.37] vs. 0.92 [0.70-1.30] OD(450); P = 0.003) and correlated positively with HDL-cholesterol (r = 0.47, 95% CI 0.02-0.69; P = 0.03) and inversely with diastolic blood pressure (r = -0.46, 95% CI -0.75 to -0.01; P = 0.03) and OxLDL/apoB ratio (r = -0.41, 95% CI -0.73 to 0.04; P = 0.06). No differences or associations were found between aOxLDL-IgG titers and other variables between or within patients and/or controls. In patients OxLDL levels correlated with smoking pack-years (r = 0.58, 95% CI 0.17-0.81; P = 0.007). Data suggest a differing innate immune response to OxLDL in patients with chronic periaortitis compared to controls. Whether this response is causally related to chronic periaortitis development remains to be clarified.

Associated findings and complications of retroperitoneal fibrosis in 204 patients: results of a urological registry.

PURPOSE: We studied the frequency of associated findings and complications of retroperitoneal fibrosis in a large clinical collective of urological patients. MATERIALS AND METHODS: All urology departments in Germany were invited to participate in a registry of patients with retroperitoneal fibrosis, for which a data sheet with more than 200 questions was developed. RESULTS: As of March 2010 a total of 204 patients were registered. The male-to-female ratio was 2.1:1 and the average age at onset was 55.6 years. In 123 cases (60.3%) the diagnosis was confirmed by histopathology. Coexisting autoimmune diseases were found in 9.8% of patients, consisting mainly of thyroid disorders. Coexisting fibrosis was detected in 3.4% of the patients and 73.9% of those queried were active smokers. Of 176 patients for whom data on therapy were available 123 received monotherapy and 41 received combination therapy for a mean of 12.1 months (12 received none), while 87 underwent a total of 103 operative procedures. Hydronephrosis was the most frequent complication in 95.6% of patients. Atrophic kidney from undetected hydronephrosis appeared in 46 patients (22.5%) and in 4 bilateral damage necessitated dialysis. Complications from vascular obstruction were observed in 27.5% of patients. Large bowel obstruction requiring colostomy occurred in 4 patients (2.0%). CONCLUSIONS: Patients with retroperitoneal fibrosis often first present to urology departments upon referral for hydronephrosis. In this series at least 1 kidney appeared to be irreversibly damaged in more than 20% of patients. Urologists should be mindful of the role of smoking role as a risk factor, complications arising from vascular and large bowel obstructions, and the possible association of retroperitoneal fibrosis with autoimmune disease.

Idiopathic retroperitoneal fibrosis: prospective evaluation of incidence and clinicoradiologic presentation.

Retroperitoneal fibrosis (RPF) is a rare disorder of unknown etiology. Its incidence is unknown, and the insidious and nonspecific nature of symptoms may contribute to considerable diagnostic delay. We conducted the current study to assess the incidence and clinicoradiologic characteristics of idiopathic RPF. For this, we evaluated prospectively 53 consecutive patients with a diagnosis of idiopathic RPF at our tertiary care referral center from April 1998 through January 2008.Calculated annual incidence of RPF was 1.3/100,000 inhabitants. Mean age was 64 +/- 11.1 (SD) yr; male-female ratio was 3.3:1.0. Median duration of symptoms was 6.0 mo (IQR 3.0-12.0). Abdominal, flank, and/or back pain and discomfort were the major symptoms, with visual analogue scale scores of 49 +/- 27.2 mm and 43 +/- 29.4 mm for pain and discomfort, respectively. Female patients had higher erythrocyte sedimentation rate (ESR), higher white blood cell count, and lower hemoglobin content than male patients at presentation. Computed tomography-documented maximal mass thickness amounted to 35 +/- 16.6 mm; craniocaudal length amounted to 137 +/- 48.8 mm. RPF mass extension up to or above the level of the renal vessels was noted in 3 patients (6%). Six patients (11%) presented with atypical RPF localization and/or bulky mass. Localized lymphadenopathy adjacent to the RPF mass was observed frequently (25%). Patients with hydronephrosis (56%) presented earlier than patients without hydronephrosis, with higher creatinine and greater mass thickness but similar pain severity. Patients were typically at high cardiovascular risk with increased-often aneurysmal-infrarenal aortic diameter (25.0 mm, IQR 22.0-30.0). RPF mass distribution was similar in patients with or without aneurysmal dilation. Occupational asbestos exposure (20%) and asbestos-related pleural changes (17%) were frequent among males. Previous or concurrent chronic inflammatory disease and/or autoimmune disease was noted in 8 patients (15%). Multivariate analysis revealed an independent association of ESR values with severity of pain and discomfort. Smoking was independently associated with infrarenal aortic diameter.In summary, annual RPF incidence is higher than previously assumed. Age at diagnosis and male-female ratio seem to have changed over time. RPF typically affects patients at high cardiovascular risk, including increased aortic diameter. Clinical presentation is influenced by sex, severity of inflammation and presence of hydronephrosis. Prolonged asbestos exposure and asbestos-related pleural changes were frequent among males. Localized lymphadenopathy adjacent to the RPF mass occurs frequently and should not confuse RPF diagnosis.

Retroperitoneal fibrosis: a review of clinical features and imaging findings.

OBJECTIVE: Retroperitoneal fibrosis is a rare collagen vascular disorder of unclear cause. Both benign and malignant associations have been described, rendering differentiation of these entities of paramount importance because sinister pathology alters the diagnosis. Thus, a high level of diligence is required in the investigation of this condition, particularly in patients with concomitant systemic conditions. CONCLUSION: Familiarity with the realm of imaging manifestations of retroperitoneal fibrosis is vital to ensure correct diagnosis and optimal treatment.