Therapie der Myositiden

Zusammenfassung: Zu den idiopathischen inflammatorischen Myositiden zählen die Dermatomyositis (DM), Polymyositis (PM), die Einschlusskörperchenmyositis ("inclusion body myositis", IBM) und die nekrotisierende autoimmune Myopathie (NAM). Bei DM und PM werden initial Glukokortikosteroide empfohlen. Steroid-sparende Immunsuppressiva wie Azathioprin, Methotrexat oder CyclosporinA werden bei ungenügendem Ansprechen verabreicht, bei drohenden Steroidnebenwirkungen oder wenn die initiale Prognose ungünstig ist. Die Therapie kann auch mit intravenösen Immunglobulinen (IVIG) eskaliert werden. Tacrolimus und Mycophenolat Mofetil (MMF) waren in kleineren Fallserien effektiv. Cyclophosphamid sollte therapierefraktären Patienten vorbehalten bleiben. Auch MMF kann mit IVIG kombiniert werden, um die Therapie zu intensivieren. Die Evidenz für Rituximab ist für den Routineeinsatz ungenügend. TNF-α-Inhibitoren und Plasmapherese haben nicht überzeugt. Die kutanen Manifestationen der DM reagieren auf Sonnenschutz, Antimalariamittel, topische Glukokortikosteroide sowie Calcineurininhibitoren. Bei der NAM sollten Statine abgesetzt und Prednison mit Immunsuppressiva initiiert werden. Bei der IBM wird ein Therapieversuch mit Prednison, Methotrexat oder Azathioprin bei Kreatinkinase-Erhöhung oder entzündlichem Infiltrat empfohlen. In jedem Stadium der Myositiden ist Physiotherapie nützlic

Sklerodermie und fibrosierende Erkrankungen

Zusammenfassung: Bei der Sklerodermie und anderen fibrosierenden Erkrankungen wie den Fibromatosen, der Arthrofibrose und dem M.Ormond liegt eine Fibroblastenproliferation mit mehr oder weniger starker Begleitentzündung vor. Bei der Sklerodermie kommt es zu einer Hautfibrose mit obstruktiver Vaskulopathie. Sklerodermiforme Hautveränderungen werden auch im Rahmen der "Graft-versus-Host-Disease" nach hämatopoetischer Stammzelltransplantation, bei Malignomen und nach Applikation bestimmter Medikamente beobachtet. Die Fibromatosen werden in eine unter der Hautoberfläche gelegene Gruppe und die tief im Körper lokalisierten Desmoide unterteilt. Im Rahmen des M.Ormond findet sich eine Aortitis mit Ausdehnung der fibrosierenden Entzündung in den Retroperitonealraum. Die Bedeutung der histopathologischen Diagnostik bei fibrosierenden Erkrankungen ist unterschiedlich und reicht von einer erkrankungsbestätigenden bis hin zu einer erkankungsdefinierenden Diagnos

Oligoarthritis durch Tropheryma whipplei: "Of bugs and joints"

Zusammenfassung: Der Morbus Whipple ist eine seltene, ohne antibiotische Therapie schwer verlaufende, chronische Infektionserkrankung durch Tropheryma whipplei, ein ubiquitär vorkommendes, grampositives Bakterium. Der Erreger kann in den betroffenen Geweben und Körperflüssigkeiten durch histologischen Nachweis PAS-positiver Makrophagen, elektronenmikroskopisch und in der Polymerasekettenreaktion (PCR) nachgewiesen werden. Arthralgien und Arthritiden sind ein häufiges Primärsymptom dieser Multisystemerkrankung. Im Verlauf treten häufig Gewichtsverlust, Diarrhö und Abdominalschmerzen auf. In 10-40% der Krankheitsfälle bestehen zusätzlich neurologische Symptome. Wir berichten über einen 67-jährigen Patienten mit jahrzehntelanger Oligoarthritis, bei dem der Erreger mittels PCR ausschließlich in der Synovialflüssigkeit nachgewiesen werden konnte. Dieser Fall illustriert, dass der charakteristische Befund PAS-positiver Makrophagen und selbst die erregerspezifische PCR im Dünndarmgewebe negativ sein kann, sodass der Erregernachweis aus dem jeweils symptomatischen Organsystem angestrebt werden sollte. Die mehrmonatige bis mehrjährige Behandlung erfolgt möglichst mit liquorgängigen Antibiotika, typischerweise mit Ceftriaxon, gefolgt von Cotrimoxazol. Vor Abschluss der Therapie ist der Nachweis der Erregerfreiheit im Darm, Liquor bzw. im betroffenen Organ anzustrebe

Prospective evaluation of the capillaroscopic skin ulcer risk index in systemic sclerosis patients in clinical practice: a longitudinal, multicentre study.

Nailfold capillaroscopy (NC) is an important tool for the diagnosis of systemic sclerosis (SSc). The capillaroscopic skin ulcer risk index (CSURI) was suggested to identify patients at risk of developing digital ulcers (DUs). This study aims to assess the reliability of the CSURI across assessors, the CSURI change during follow-up and the value of the CSURI in predicting new DUs. This multicentre, longitudinal study included SSc patients with a history of DUs. NC images of all eight fingers were obtained at baseline and follow-up and were separately analysed by two trained assessors. Sixty-one patients were included (median observation time 1.0 year). In about 40% of patients (assessor 1, n = 24, 39%; assessor 2, n = 26, 43%) no megacapillary was detected in any of the baseline or follow-up images; hence the CSURI could not be calculated. In those 34 patients in whom CSURI scores were available from both assessors (26% male; median age 57 years) the median baseline CSURI was 5.3 according to assessor 1 (IQR 2.6-16.3), increasing to 5.9 (IQR 1.3-12.0) at follow-up. According to assessor 2, the CSURI diminished from 6.4 (IQR 2.4-12.5) to 5.0 (IQR 1.7-10.0). The ability of a CSURI ≥ 2.96 category to predict new DUs was low (for both assessors, positive predictive value 38% and negative predictive value 50%) and the inter-assessor agreements for CSURI categories were fair to moderate. In this study, around 40% of patients could not be evaluated with the CSURI due to the absence of megacapillaries. Clinical decisions based on the CSURI should be made with caution. Current Controlled Trials, ISRCTN04371709 . Registered on 18 March 2011

Quantification of three macrolide antibiotics in pharmaceutical lots by HPLC: Development, validation and application to a simultaneous separation

A new validated high performance liquid chromatographic (HPLC) method with rapid analysis time and high efficiency, for the analysis of erythromycin, azithromycin and spiramycin, under isocratic conditions with ODB RP18 as a stationary phase is described. Using an eluent composed of acetonitrile –2-methyl-2-propanol –hydrogenphosphate buffer, pH 6.5, with 1.5% triethylamine (33:7: up to 100, v/v/v), delivered at a flow-rate of 1.0 mL min-1. Ultra Violet (UV) detection is performed at 210 nm. The selectivity is satisfactory enough and no problematic interfering peaks are observed. The procedure is quantitatively characterized and repeatability, linearity, detection and quantification limits are very satisfactory. The method is applied successfully for the assay of the studied drugs in pharmaceutical dosage forms as tablets and powder for oral suspension. Recovery experiments revealed recovery of 97.13–100.28%

The APEX Large CO Heterodyne Orion Legacy Survey (ALCOHOLS): I. Survey overview

Context: The Orion molecular cloud complex harbours the nearest Giant Molecular Clouds (GMCs) and the nearest site of high-mass star formation. Its young star and protostar populations are thoroughly characterized. The region is therefore a prime target for the study of star formation. Aims: Here, we verify the performance of the SuperCAM 64 pixel heterodyne array on the Atacama Pathfinder Experiment (APEX). We give a descriptive overview of a set of wide-field CO(3-2) spectral line cubes obtained towards the Orion GMC complex, aimed at characterizing the dynamics and structure of the extended molecular gas in diverse regions of the clouds, ranging from very active sites of clustered star formation in Orion B to comparatively quiet regions in southern Orion A. In a future publication, we will characterize the full population of protostellar outflows and their feedback over an entire GMC. Methods: We present a 2.7 square degree (130 pc2) mapping survey in the 12CO(3-2) transition, obtained using SuperCAM on APEX at an angular resolution of 1900 (7600 AU or 0.037 pc at a distance of 400 pc), covering the main sites of star formation in the Orion B cloud (L 1622, NGC 2071, NGC 2068, Ori B9, NGC 2024, and NGC 2023), and a large patch in the southern part of the L 1641 cloud in Orion A. Results: We describe CO integrated line emission and line moment maps and position-velocity diagrams for all survey fields and discuss a few subregions in some detail. Evidence for expanding bubbles is seen with lines splitting into double components, often in areas of optical nebulosities, most prominently in the NGC 2024 H ii region, where we argue that the bulk of the molecular gas is in the foreground of the H ii region. High CO(3-2)/CO(1-0) line ratios reveal warm CO along the western edge of the Orion B cloud in the NGC 2023/NGC 2024 region facing the IC 434 H ii region. We see multiple, well separated radial velocity cloud components towards several fields and propose that L 1641-S consists of a sequence of clouds at increasingly larger distances. We find a small, seemingly spherical cloud, which we term ’Cow Nebula’ globule, north of NGC 2071. We confirm that we can trace high velocity line wings out to the ’extremely high velocity’ regime in protostellar molecular outflows for the NGC 2071-IR outflow and the NGC 2024 CO jet, and identify the protostellar dust core FIR4 (rather than FIR5) as the true driving source of the NGC 2024 monopolar outflow

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

Natural variability in the disease course of SSc-ILD: implications for treatment

Contains fulltext : 232636.pdf (Publisher’s version ) (Open Access)Interstitial lung disease (ILD) affects approximately 50% of patients with systemic sclerosis (SSc) and is the leading cause of death in SSc. Our objective was to gain insight into the progression of SSc-associated ILD (SSc-ILD). Using data from longitudinal clinical trials and observational studies, we assessed definitions and patterns of progression, risk factors for progression, and implications for treatment. SSc-ILD progression was commonly defined as exceeding specific thresholds of lung function worsening and/or increasing radiographic involvement. One definition used in several studies is decline in forced vital capacity (FVC) of ≥10%, or ≥5-10% plus a decline in diffusing capacity of the lung for carbon monoxide ≥15%. Based on these criteria, 20-30% of patients in observational cohorts develop progressive ILD, starting early in the disease course and progressing at a highly variable rate.Risk factors such as age, FVC, extent of fibrosis and presence of anti-topoisomerase I antibodies can help predict progression of SSc-ILD, though composite risk scores may offer greater predictive power. Whilst the variability of the disease course in SSc-ILD makes risk stratification of patients challenging, the decision to initiate, change or stop treatment should be based on a combination of the current disease state and the speed of progression