Dimitrios Vassilopoulos

Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease

Objectives Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is characterised by neutrophil activation. An elevated prevalence of venous thromboembolic events has been reported in AAV. Because of the critical role of neutrophils in inflammation associated thrombosis, we asked whether neutrophil tissue factor (TF) may be implicated in the thrombotic diathesis in AAV. Methods Neutrophils from four patients and sera from 17 patients with ANCA associated vasculitis with active disease and remission were studied. TF expression was assessed by immunoblotting and confocal microscopy. Circulating DNA levels were evaluated. TF expressing microparticles (MPs) were measured by flow cytometry and thrombin–antithrombin complex levels by ELISA. Results Peripheral blood neutrophils from four patients with active disease expressed elevated TF levels and released TF expressing neutrophil extracellular traps (NETs) and MPs. TF positive NETs were released by neutrophils isolated from the bronchoalveolar lavage and were detected in nasal and renal biopsy specimens. Elevated levels of circulating DNA and TF expressing neutrophil derived MPs were further observed in sera from patients with active disease. Induction of remission attenuated the aforementioned effects. Control neutrophils treated with sera from patients with active disease released TF bearing NETs and MPs which were abolished after IgG depletion. Treatment of control neutrophils with isolated IgG from sera from patients with active disease also resulted in the release of TF bearing NETs. TF implication in MP dependent thrombin generation was demonstrated by antibody neutralisation studies. Conclusions Expression of TF in NETs and neutrophil derived MPs proposes a novel mechanism for the induction of thrombosis and inflammation in active AAV.

Plasma testosterone in male patients with Huntington's disease: Relations to severity of illness and dementia

Huntingtons disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive loss among other, of dopaminergic receptors in striatum, cortex, and hypothalamus. Central dopaminergic activity has been implicated in the regulation of sex hormones. Several features of testosterone deficiency, such as reduced muscle mass, depressive mood, and cognitive impairment, are often present in HD patients, but data on their testosterone levels are lacking. We assessed plasma levels of testosterone, LH, and FSH in 42 male patients with HD, confirmed by molecular genetic analysis, and searched for differences from age‐matched healthy male subjects and for relations to CAG repeat number, age, age range, 26 to 76 (mean, 50.7 ± 12.3) years; duration of illness range, 1 to 23 (mean, 6.7 ± 6.3) years; and CAG repeat numbers from 40 to 65 (45.1 ± 3.8). Disease symptomatology was assessed using the Unified Huntingtons Disease Rating Scale. Testosterone and LH levels of the patients were significantly lower compared to the levels of 44 age‐matched (mean age, 48.9 ± 13.0, range, 26–76 years) healthy men. Severity of illness was negatively related to plasma testosterone levels. Further, low testosterone levels were associated with dementia but not with depression or psychotic features. Clinical studies with selected HD patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well‐being, and, eventually, neuroprotective effects. Ann Neurol 2005;57:520–525

Influence of sleep disturbance on quality of life of patients with epilepsy

The frequency of sleep disturbances in patients with epilepsy and their impact on quality of life (QoL) have been documented in a few reports, and the results are conflicting. We identified 124 consecutive epilepsy out-patients who visited the epilepsy out-patient clinics at the University Hospital of Alexandroupolis, the AHEPA Hospital in Thessaloniki and the Aeginitio Hospital in Athens. We measured excessive daytime sleepiness (EDS) with the Epworth Sleepiness Scale (ESS), obstructive sleep apnea (OSA) with the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ), and insomnia with the Athens Insomnia Scale (AIS). We evaluated quality of life by the Quality of Life in Epilepsy Inventory (QOLIE-31). EDS was found in 16.9% (21/124) of epileptic patients, OSA in 28.2% (35/124), and insomnia in 24.6% (30/122). In multivariate analysis, we found that insomnia was an independent negative factor for Total score (p<0.001), Overall QoL (p=0.002), Emotional well-being (p<0.001), Energy/fatigue (p<0.001), Cognitive functioning (p=0.04) and Social functioning (p=0.03), and OSA only for Cognitive functioning (p=0.01). According to our findings, EDS, OSA, and insomnia are frequent in epileptic patients. Epileptic patients with sleep disturbance, mainly insomnia, have significant QoL impairment.

Virally associated arthritis 2008: clinical, epidemiologic, and pathophysiologic considerations

Several viruses have been associated with the development of inflammatory arthritis, including the hepatitis viruses (hepatitis B virus and hepatitis C virus), HIV, the parvovirus B19, the human T-cell lymphotropic virus-I, and the alphaviruses. Here, we review the epidemiology, the pathophysiological mechanisms, the pertinent clinical and laboratory findings as well as the principles of therapy of the most common virus-associated arthritides. We believe that the knowledge of these key diagnostic and therapeutic features of virus-associated arthritides is important for the rheumatologist of the 21st century.

Immunopathogenesis of hepatitis B e antigen negative chronic hepatitis B infection

Hepatitis B e antigen (HBeAg) negative chronic hepatitis B represents currently the predominant form of chronic hepatitis due to the hepatitis B virus (HBV) in several parts of the world. In this review, recent data regarding the process of HBeAg negative HBV strain selection during the course of chronic HBV infection are presented and the potential virus and/or host-mediated mechanisms that lead to chronic liver necroinflammation, i.e. chronic hepatitis are outlined.

Comparison of Two Gamma Interferon Release Assays and Tuberculin Skin Testing for Tuberculosis Screening in a Cohort of Patients with Rheumatic Diseases Starting Anti-Tumor Necrosis Factor Therapy

ABSTRACT Gamma interferon release assays (IGRAs) are increasingly used for latent Mycobacterium tuberculosis infection (LTBI) screening in patients with rheumatic diseases starting anti-tumor necrosis factor (anti-TNF) therapies. We compared the performances of two IGRAs, an enzyme-linked immunospot release assay (T-SPOT.TB) and an enzyme-linked immunosorbent assay (QuantiFERON-TB Gold In Tube [QFT-GIT]), to that of tuberculin skin testing (TST) for LTBI screening of 157 consecutive rheumatic patients starting anti-TNF therapies. Among 155 patients with valid results, 58 (37%) were positive by TST, 39 (25%) by T-SPOT.TB assay, and 32 (21%) by QFT-GIT assay. IGRAs were associated more strongly with at least one risk factor for tuberculosis (TB) than TST. Risk factors for a positive assay included chest X-ray findings of old TB (TST), advanced age (both IGRAs), origin from a country with a high TB prevalence, and a positive TST (T-SPOT.TB assay). Steroid use was negatively associated with a positive QFT-GIT assay. The agreement rate between IGRAs was 81% (kappa rate = 0.47), which was much higher than that observed between an IGRA and TST. If positivity by either TST or an IGRA was required for LTBI diagnosis, then the rate of LTBI would have been 46 to 47%, while if an IGRA was performed only for TST-positive patients, the respective rate would have been 11 to 17%. In conclusion, IGRAs appear to correlate better with TB risk than TST and should be included in TB screening of patients starting anti-TNF therapies. In view of the high risk of TB in these patients, a combination of one IGRA and TST is probably more appropriate for LTBI diagnosis.

Long-term safety of rituximab in patients with rheumatic diseases and chronic or resolved hepatitis B virus infection

Patients with rheumatic diseases and chronic, or less frequently, resolved hepatitis B virus (HBV) infection, can develop viral reactivation during antitumor necrosis factor therapy.1–3 Treatment with chemotherapeutic regimens that includes rituximab (RTX) without prophylactic antiviral therapy, has been linked to HBV reactivation in lymphoma patients with chronic (27%–80%), or resolved (3%–25%) HBV infection.1 ,4 Since there are no data available for rheumatic patients, we studied the safety of RTX in such patients with chronic or resolved HBV infection. Forty-one consecutive patients with various rheumatic diseases (rheumatoid arthritis/RA: n=34, other: n=7) who had received ≥1 cycle of RTX and had ≥6 months of follow-up were included in this prospective study. Patients were treated with the standard dose of RTX (1 gm intravenous at days 1 and 15, table 1). Patients were screened for HBV at baseline (HBsAg, anti-HBc, anti-HBs); those found …

Successful treatment of adult patients with idiopathic recurrent pericarditis with an interleukin-1 receptor antagonist (anakinra)

Idiopathic recurrent pericarditis (IRP) is observed in 10–30% of cases after a first episode of acute pericarditis, whereas a second recurrence appears in anevenhigher rate (~50%) [1,2]. Although severalmechanisms have been suggested to explain recurrence, most of them appear simply contributory. Today, there is increasing evidence that autoimmune and autoinflammatory pathways aremainly involved in its pathogenesis [3,4]. The optimal regimen for treating IRP has not been established [1]. Several medications either alone or in combination have been tested including nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin, colchicine, corticosteroids, and immunosuppressive agents. To date, the only available medication proved in randomized trials to decrease the recurrence rate is colchicine [2]. However, even with colchicine, a substantial proportion of patients experience recurrences [2]. Recently, Picco and et al. reported the successful use of an interleukin1β receptor antagonist anakinra in three children with resistant IRP [4]. Here, we present our experience in three adults with drug resistant or intolerant IRP. All patients were informed in detail regarding the management with anakinra and gave informed consent. Case#1: A 26-year-oldmale had suffered 8 episodes of IRP since 2004. He has received various regimens including NSAIDs, colchicine, steroids and azathioprine (Fig. 2A). In October 2006 treatment with prednisone was instituted but his symptoms recurred every time the dose was tapered below 15mg/day. Unfortunately, the patient developed steroidrelated complications including glaucoma, osteopenia and proximal myopathy of the lower extremities. In his latest admission inMarch 2010, the patient was started on anakinra (150 mg/day subcutaneously, SC) as monotherapy for 3 months and steroidswere tapered off. Administration of anakinrawas followed byan immediate and dramatic clinical response International Journal of Cardiology 160 (2012) 66–77

Is There a Place for Cardiovascular Magnetic Resonance Imaging in the Evaluation of Cardiovascular Involvement in Rheumatic Diseases

Cardiovascular magnetic resonance (CMR) is a noninvasive, nonradiating imaging technique, which provides novel information for the evaluation of cardiovascular diseases. Until now it has been successfully used for the evaluation of congenital and acquired heart diseases, cardiac tumors-mass, iron overload, and myocardial fibrosis detection. Recently, its diagnostic capabilities have been extended to the evaluation of myocardial inflammation and myocardial perfusion. Currently, it is considered the gold standard for the evaluation of volumes, mass, ejection fraction of atriums and ventricles, quantification of iron overload in different organs, detection and follow-up of myocardial inflammation, myocardial infarction and its complications, evaluation of the aorta, detection of anomalous coronary arteries, and ectatic or aneurysmatic coronary arteries. All the above applications and mainly the CMR ability to detect myocardial inflammation, perfusion defects, fibrosis, coronary and great arteries aneurysms make it a valuable tool for cardiovascular system assessment, commonly affected during the course of rheumatic diseases. The technique has been already successfully used in the evaluation of vasculitides, systemic lupus erythematosus, myositis, and scleroderma. However, further studies are needed to evaluate its usefulness as a diagnostic and monitoring tool of cardiovascular involvement in rheumatic patients.

Hashimoto Encephalopathy with Pegylated Interferon Alfa-2b and Ribavirin:

OBJECTIVE: To report an instance of Hashimoto encephalopathy probably resulting from pegylated interferon alfa-2b and ribavirin. CASE SUMMARY: A 36-year-old woman with a 10-year history of autoimmune thyroiditis presented with symptoms and signs consistent with Hashimoto encephalopathy during therapy with pegylated interferon alfa-2b and ribavirin for chronic hepatitis C. DISCUSSION: Hashimoto encephalopathy is a rare autoimmune condition that occurs in patients with Hashimoto thyroiditis and high titers of antithyroid antibodies. It is characterized by a variety of nonspecific neuropsychiatric symptoms, increased cerebrospinal fluid protein level, and abnormal brain imaging and electroencephalogram. Prompt response to corticosteroids is observed in most cases. As of August 29, 2005, this is the first report of such an association. An objective causality assessment revealed that the Hashimoto encephalopathy was probably caused by the patients medications. CONCLUSIONS: Hashimoto encephalopathy may rarely be triggered by interferon alfa therapy in susceptible patients.