Erdheim–Chester disease (ECD) is a rare inflammatory disorder characterised by organ infiltration by non-Langerhans' histiocytes. Although rare, ECD is clearly an overlooked diagnosis. No data specifically addressing the most frequent presentations of ECD at the time of onset in a large cohort of patients are currently available.
Methods
We reviewed all the published cases in the English literature of histologically-confirmed ECD. We excluded reports in which data regarding onset and diagnosis were not univocal, as well as repeated reports of the same case(s). We also included in the analysis 10 new unpublished patients from our cohort. We analysed the disease presentation with particular regard to the manifestations that induced patients to seek medical attention and their subsequent evolution.
Results
In the cumulative cohort of 259 cases, ECD predominantly presented with skeletal symptoms, diabetes insipidus, neurological and constitutional symptoms. Diabetes insipidus and constitutional symptoms, if not present at onset, seemed to only seldom develop. There were differences in ECD presentation and course among different age groups of patients.
Conclusions
Physicians should be aware of the extraordinarily heterogeneous clinical presentations and manifestations of ECD in order to include ECD in the differential diagnosis of several conditions.
An abnormal generation of reactive oxygen species (ROS) is thought to contribute to systemic sclerosis (SSc), fostering autoimmunity, fibrosis, and vascular inflammation. The function of the prototypic damage-associated molecular pattern, high mobility group box 1 (HMGB1), depends on its redox status. Here we investigate whether oxidative stress regulates the cross-talk between leukocytes and platelets via HMGB1, thus contributing to vessel inflammation in SSc.The oxidation of HMGB1 amplified its ability to activate neutrophils, as detected assessing the redistribution of primary granule molecules and the transactivation of the β2 integrin chain CD18. Activated platelets are a source of bioactive HMGB1 and via P-selectin stimulated neutrophils to generate ROS. Oxidized extracellular HMGB1, soluble or associated to platelet membrane or to platelet-derived microparticles (PDμPs), further increased leukocyte activation. Leukocyte activation abated in the presence of inhibitors of HMGB1 or of catalase, which catalyzes the dismutation of hydrogen peroxide into water and molecular oxygen. The redistribution of the content of primary granules and the transactivation of β2 integrins characterized blood leukocytes of SSc patients and membrane HMGB1 was significantly higher in patients with pulmonary hypertension or with diffuse SSc. HMGB1(+) microparticles (μPs) purified from SSc patients, but not HMGB1(-) μPs purified from control subjects, activated in vitro healthy neutrophils, and HMGB1 inhibitors reversed the effects of μPs.ROS dramatically increase the ability of extracellular HMGB1 to activate blood leukocytes. This event might contribute to maintain the microvascular injury of patients with SSc.
The immunogenic Friend-Moloney-Rauscher (FMR) virus-induced tumors have been used extensively to clarify the cellular and molecular mechanisms responsible for tumor rejection and to develop immunotherapeutic strategies. We characterize here the trimolecular complex MHC class I-antigenic determinant-T cell receptor involved in the induction of a protective CTL response against the RMA thymoma. This complex is mainly composed by the D(b) molecule interacting with a Rauscher virus antigen (Ag) determinant and the Vbeta5+ T cell receptor. We also show that the chemically induced EL-4 thymoma acquires the susceptibility to recognition by anti-RMA CTLs and the ability to elicit a protective anti-RMA CTL response only upon infection by a virus of the FMR family and that RMA and FMR virus infected EL-4 cells share tumor-associated Ag. The data strongly support the hypothesis that the high immunogenicity of virus-induced or infected tumors is determined by the expression of immunodominant virus-encoded Ag. The demonstration of a different outcome in the immune responses elicited in the presence or in the absence of viral Ag further open the contention of the molecular requirements for immunogenicity and should stimulate a more careful revision of unexpected cross-reactivity among tumors.
Apoptosis normally occurs in the human placenta. As a consequence, cell blebs, post-apoptotic debris (also referred to as syncytial knots) and membrane microparticles are released into the blood of pregnant women. These events become prominent during the best-characterized pregnancy complication, pre-eclampsia. An excessive or deregulated cell death, which results in the generation of an overwhelming burden of apoptotic material, alarms the immune system. This plays a role in the pathogenesis of systemic connective tissue diseases and possibly of small vessels vasculitis. Infiltration of leukocytes and activation of endothelial cells and platelets are hallmarks of normal pregnancy, indicating that physiologic pregnancy is a condition characterized by an activation of the innate immune system. Conversely, a failure in the physiologic termination of inflammatory events is probably a requirement for pre-eclampsia to develop. Here, we discuss recent findings suggesting a link between deregulated disposal of placental debris, the generation of endogenous pro-inflammatory signals (alarmins) and the widespread vascular inflammation that characterizes on one hand pre-eclampsia and on the other systemic autoimmune diseases.
The link between platelet activation and vascular injury in Systemic Sclerosis (SSc) is poorly characterized. Here we report that platelet activation results in i) the translocation from the cytoplasm to the surface of HMGB1, a prototypical DAMP signal associated with tissue regeneration and ii) the release of platelet derived microparticles (PDμP) expressing HMGB1. Decreased HMGB1 content (334.6 ± 21.2 vs 587.1 ± 11.1 AUF, P < 0.001) and HMGB1 translocation to the outer leaflet of the plasma membrane (17.8 ± 3.5 vs 4.5 ± 0.5%, P < 0.001) characterize circulating platelets of SSc patients (n = 29) when compared with age-matched healthy controls (HC, n = 20). Conversely, a significantly higher fraction of PDμP in the blood of SSc patients, but not of HC, consistently expose (HMGB1 (MFI 62.8 ± 3.95 vs 4.3 ± 0.7). Platelet HMGB1 depletion is significantly associated in SSc patients with degranulation and with expression of P-selectin and of tissue factor as well as with fibrinogen binding to their plasma membrane. These findings indicate that platelets represent a source of HMGB1, an ancestral signal of necrosis, in the vasculature of SSc patients, possible contributing to persistent microvascular injury and endothelial cell activation.
Abstract Blast injury is a frequent cause of injury during armed conflicts, and the force of a blast can cause closed colorectal injury and perforation. 1 After identification of a blast-related colorectal injury, the surgical options are primary repair or fecal diversion with the option for secondary repair. This structured review was conducted to determine which patients could be treated with primary repair (PR) or with fecal diversion. The review method followed the Prisma Statement method for medical systematic review. All data from the relevant articles were collected in a single database. Articles took into account wars in Bosnia, Iraq and Afghanistan from January 1993 through November 2012. The review was limited due to lack of reported data, hence qualitative analysis was the main review method. The review showed that for patients who do not have associated intra-abdominal injuries (diaphragm, stomach, pancreas, spleen, or kidney) or hemodynamic instability, PR did not result in an increase of complications or mortality. Bortolin M , Baldari L , Sabbadini MG , Roy N . Primary repair or fecal diversion for colorectal injuries after blast: a medical review . Prehosp Disaster Med . 2014 ; 29 ( 3 ): 1 - 3 .
The aim of this study was to investigate potential risk factors for Sjögren's syndrome (SS) by means of a multi-centre case-control study, focusing in particular on familial and environmental risk factors. 140 female SS patients and 109 female controls with orthopaedic problems were consecutively enrolled in seven university hospitals in Italy.Information regarding the patient's lifestyle, her medical, menstrual and pregnancy history, and any family history of autoimmune diseases (AD) was obtained through a detailed structured questionnaire. The odds ratio (OR) and 95% confidence interval (95%CI) were calculated using unconditional logistic regression, adjusting for age and family size. The probability of first-degree relatives developing an autoimmune disease was also investigated.A positive family history of AD was significantly associated with SS. Subjects with a first-degree relative (FDR) with AD showed a seven-fold increase in the risk for SS compared to controls (OR=7.4, 95%CI 2.8-20.1); the strength of this association increased with the number of relatives affected. Similarly, the FDR of SS patients had a higher risk of AD in comparison to subjects without FDR affected by SS. Women with one or more pregnancies had an increased risk of SS (OR=2.1, 95%CI 1.0-4.3).This study suggests that a family history of AD is associated with SS.
In Brief OBJECTIVE: Cell death normally occurs during pregnancy and is critical during its common complication, preeclampsia. The long pentraxin 3 (PTX3) gene is generated in tissues that cope with excessive or deregulated cell death and inhibits the cross-presentation of cell-associated antigens. We examined whether PTX3 is expressed during pregnancy and possibly involved in the development of preeclampsia. METHODS: Women with preeclampsia (n = 30), women with uncomplicated pregnancies (n = 66), age-matched healthy women (n = 50), women who developed acute bacterial infections (n = 20), and women with rheumatoid arthritis (n = 20) were studied. The concentrations of PTX3 were measured in the blood by a sandwich enzyme-linked immunosorbent assay (ELISA) and in placentas by immunohistochemistry. The concentrations of PTX3 and C-reactive protein in the various groups were compared by nonparametric tests (the Mann-Whitney U and the Kruskal-Wallis tests). The odds of developing preeclampsia were assessed using logistic regression. RESULTS: PTX3 was expressed in amniotic epithelium and chorionic mesoderm, trophoblast terminal villi, and perivascular stroma in placentas from pregnancies of uncomplicated subjects. Circulating levels steadily rose during normal gestation and peaked during labor. Serum levels of PTX3 were strikingly higher in preeclampsia compared with normal control pregnancies (5.08 ± 1.34 and 0.59 ± 0.07 ng/mL, respectively, P < .001). Sites of higher expression in the placentas from preeclamptic patients include infarcts and fibrinoid zones. CONCLUSION: Defects in the homeostatic response to cell death/remodeling events, revealed by enhanced levels of PTX3, could be implicated in preeclampsia. LEVEL OF EVIDENCE: II-2 The blood levels of the long pentraxin 3, constitutively expressed in the placenta, increase during preeclampsia, suggesting its involvement in the disease.
