Showing papers by "Ulf Müller-Ladner published in 2012"

Update on the profile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database

Abstract: The EUSTAR database provides an abundance of information on the true clinical face of SSc that will be helpful in improving the classification of SSc and its subsets and for developing more specific therapeutic recommendations

Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative

Abstract: Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA).

S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012

Abstract: Auf Basis der 2010 publizierten EULAR-Empfehlungen ist von der DGRh eine S1-Leitlinie fur die sequenzielle medikamentose Therapie der rheumatoiden Arthritis erstellt und der Therapiealgorithmus uberarbeitet worden. Die Neufassung erfolgte auf der Grundlage einer aktualisierten systematischen Literaturrecherche und eines Expertenkonsensus. Bei Diagnosestellung ist Methotrexat die Standardbasistherapie und wird in der Regel mit niedrig dosiertem Prednisolon kombiniert. Bei nicht ausreichendem Ansprechen sollte nach 12 Wochen eine klassische DMARD-Kombinationstherapie eingesetzt werden. Bei anhaltend hoher Krankheitsaktivitat wird spatestens nach 6 Monaten der Einsatz eines Biologikums empfohlen, in Sondersituationen (z. B. fruhe Destruktionen, ungunstige Prognose) ggf. fruher. Falls sich das zuerst angewendete Biologikum in einem Zeitraum von 3 bis 6 Monaten als nicht ausreichend effektiv erweist, sollte der Wechsel auf ein anderes Biologikum erfolgen. Bei lang anhaltender Remission kann eine kontrollierte Reduktion der Basistherapie versucht werden.

Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis?

Abstract: Objectives Several clinical studies have suggested the adipocytokine adiponectin is involved in the progression of rheumatoid arthritis (RA). From this point of view, adiponectin might present a new therapeutic target. However, as adiponectin also exerts beneficial effects in the human organism, a strategy that would allow its detrimental effects to be abolished while maintaining the positive effects would be highly favourable. To elucidate such a strategy, the authors analysed whether the different adiponectin isoforms induce diverging effects, especially with regard to rheumatoid arthritis synovial fibroblasts (RASF), a central cell type in RA pathogenesis capable of invading into and destroying cartilage. Methods Affymetrix microarrays were used to screen for changes in gene expression of RASF. Messenger RNA levels were quantified by real-time PCR, protein levels by immunoassay. The migration of RASF and primary human lymphocytes was analysed using a two-chamber migration assay. Results In RASF, the individual adiponectin isoforms induced numerous genes/proteins relevant in RA pathogenesis to clearly different extents. In general, the most potent isoforms were the high molecular weight/middle molecular weight isoforms and the globular isoform, while the least potent isoform was the adiponectin trimer. The chemokines secreted by RASF upon adiponectin stimulation resulted in an increased migration of RASF and lymphocytes. Conclusion The results clearly suggest a pro-inflammatory and joint-destructive role of all adiponectin isoforms in RA pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.

Measuring Pain and Efficacy of Pain Treatment in Inflammatory Arthritis: A Systematic Literature Review

Abstract: Objective. To systematically review the available literature on measuring pain and the efficacy of pain treatment in inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations. Methods. A systematic literature search was performed in Medline, Embase, Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism 2008/2009 meeting abstracts, searching for studies evaluating clinimetric properties of pain measurement tools in IA (convergent validity, internal consistency, retest reliability, responsiveness, feasibility, and standardization). Studies that presented information on these properties were reviewed and their data were integrated into the pool of results available for pain measures in IA. Results. In total, 51 articles were included in the review. Validated information on pain was available for tools covering different facets such as overall pain, anatomically specific pain, or a mixture of both. Data from these studies showed that single pain-related items such as the visual analog scale (VAS), numeric rating scale (NRS), or verbal rating scale (VRS) provide sufficient clinimetric information. Similar results were obtained for the pain subscales of the Arthritis Impact Measurement Scales (AIMS/AIMS2) and the bodily pain subscale of the Medical Outcome Study Short-Form Survey 36. Most clinimetric coefficients showed acceptable results with respect to validity, reliability, and sensitivity to change, while the degree of standardization and feasibility mostly filled at least 2 of 3 predefined criteria. Conclusion. A variety of pain measures are available to cover different aspects of pain such as intensity, frequency, or location. Single-item tools such as VAS, NRS, or VRS can be recommended to measure overall pain in clinical practice. If more specific issues need to be addressed, more sophisticated tools should be taken into account.

Profile of gastrointestinal involvement in patients with systemic sclerosis

Abstract: Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.

Juvenile and young adult-onset systemic sclerosis share the same organ involvement in adulthood: data from the EUSTAR database

Abstract: Objective. The aim of the present study was to explore the long-term outcome and clinical characteristics of adult patients with juvenile onset in the EULAR Scleroderma Trials and Research (EUSTAR) cohort and compare them with adult patients with onset between 20 and 40 years of age. Methods. From the EUSTAR SSc cohort two patient groups were analysed: patients with juvenile SSc (jSSc) who are adults at present, and patients diagnosed between the age of 20 and 40 years (aSSc). Demographic data of the patients, organ involvement and outcome of the disease were examined using the Minimal Essential Data Set database system. Results. From 5000 patients in the EUSTAR cohort, 60 patients (1.2%) with jSSc and 910 patients (18%) with aSSc were selected according the inclusion criteria. In the jSSc group, the mean age of disease onset was 12.4 years (range 215.9 years), and in the aSSc group, the mean age was 32 years (range 2040 years). Disease subsets were similar. The antibody profile was also comparable except for ACAs, which were positive in 5% of the jSSc group and 26.9% of the aSSc group (P < 0.005). Organ involvement (lung, kidney, joint, muscle and heart) was similar in the two groups of patients at the time of the last follow-up. Conclusion. The subset distribution in the jSSc and aSSc cohorts was found to be similar. Only the frequency of ACAs was significantly lower in the jSSc, which supports the hypothesis that the SSc patients with paediatric onset in the adult cohort may represent a distinct subgroup of the complete cohort of paediatric patients.

Comparison of qualitative and quantitative analysis of capillaroscopic findings in patients with rheumatic diseases

Abstract: No guidelines for the application of qualitative and quantitative analysis of the capillaroscopic examination in the rheumatologic practice exist. The aims of the study were to compare qualitative and quantitative analysis of key capillaroscopic parameters in patients with common rheumatic diseases and to assess the reproducibility of the qualitative evaluation of the capillaroscopic parameters, performed by two different investigators. Two hundred capillaroscopic images from 93 patients with different rheumatic diseases were analysed quantitatively and qualitatively by two different investigators. The distribution of the images according to the diagnosis and the microvascular abnormalities was as follows—group 1: 73 images from systemic sclerosis patients (“scleroderma” type pattern), group 2: 10 images from dermatomyositis (“scleroderma-like” pattern), group 3: 25 images from undifferentiated connective tissue disease and different forms of overlap (24 “scleroderma-like”), group 4: 26 images from systemic lupus erythematosus patients, group 5: 46 images from rheumatoid arthritis and group 6: 20 images from primary Raynaud’s phenomenon patients. All the images were mixed and blindly presented to both investigators. For comparison of the quantitative and qualitative method, investigator 1 assessed presence of dilated, giant capillaries and avascular areas quantitatively by the available software programme and his estimates were compared with the results of investigator 2, who assessed the parameters qualitatively. In addition, the capillaroscopic images were evaluated qualitatively by the investigator 1 and 2 for presence of dilated, giant capillaries, avascular areas and haemorrhages. The comparison of the quantitative and qualitative assessment of the two investigators demonstrated statistically significant difference between the two methods for the detection of dilated and giant capillaries (P 0.05). As we further analysed the results for the capillaroscopic images, demonstrating a “scleroderma” and a “scleroderma-like” pattern (170/200), analogous results were found for the evaluated parameters. Among the 20 capillaroscopic images from patients with primary RP, the estimates for the absence of giant capillaries and avascular areas were equal in 100% (P > 0.05). Comparing the qualitative assessment of the two investigators, a statistically significant difference between estimates of the two investigators was found for the presence of dilated capillaries (P 0.05). The results of the study have shown that qualitative assessment of capillaroscopic parameters in patients with rheumatic diseases is an adequate method for the everyday rheumatologic practice, especially in cases with primary RP for exclusion presence of microangiopathy. No significant difference between qualitative and quantitative methods of assessment was found for the detection of avascular areas. However, the quantitative analysis is more precise especially for the detection of capillary dilation. A good reproducibility of the qualitative evaluation, performed by two different investigators was also found.

TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients

Abstract: Introduction Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH. Objective To explore the genetic bases of SSc–PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. Materials and methods TGFβ receptor genes, BMPR2, ALK1 , TGFR2 and ENG , were sequenced in 10 SSc–PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc–PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc–PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. Results No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc–PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc–PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. Conclusions This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc–PAH using both sequencing and genotyping methods.

Sensitivity and specificity of ultrasonography and low-field magnetic resonance imaging for diagnosing arthritis

Abstract: Objectives To evaluate the value of grey-scale ultrasonography (US) including power Doppler ultrasonography (PDUS) and low-field magnetic resonance imaging (MRI) for the diagnosis of arthritis in a diagnostic phase III study. Methods Fifty consecutive patients with suspected arthritis were included in the study. Following a standardised protocol, US of the carpus and the metacarpophalangeal (MCP) joints of the dominant hand was performed. Subsequently, low-field MRI was done using standard sequences, with contrast agent (Gadolinium DTPA) administered to 29 patients. Results In 32 out of 50 patients a clinical diagnosis of arthritis was established. In grey-scale ultrasonography including PDUS, sensitivity and specificity were determined as 0.94 and 0.5, respectively, for synovitis (effusion and hypertrophy), 0.72 and 0.94, respectively, for Doppler signals, and 0.38 and 1.0, respectively, for bone erosions. In low-field MRI, sensitivity and specificity values were 0.77 and 0.75, respectively, for synovitis (when using contrast agent), 0.48 and 0.78, respectively, for bone marrow oedema, and 0.58 and 0.83, respectively, for bone erosion. Conclusions Both grey-scale ultrasonography including PDUS and low-field MRI are suitable imaging methods for diagnosing arthritis at an early stage. However, PDUS displays a higher specificity and almost the same sensitivity as compared to contrast-enhanced MRI, while being a much simpler and less costly procedure.

[Gout as a systemic disease. Manifestations, complications and comorbidities of hyperuricaemia].

Abstract: Of all inflammatory rheumatic diseases gout has the highest prevalence. Patients with intermittent acute gout attacks are usually treated by primary care physicians. However, in cases of insufficient long-term control of serum uric acid levels, complications or atypical clinical manifestations may necessitate consultation with a rheumatologist in the further course of the disease. An oligoarticular or polyarticular presentation can give rise to the initial suspicion of rheumatoid or psoriatic arthritis. In these cases a careful clinical work-up supported by laboratory and imaging investigations is necessary and synovial fluid analysis is usually required. As in other rheumatic diseases extra-articular manifestations are of utmost importance for morbidity and mortality. Gout is a complex metabolic and inflammatory disease and besides articular symptoms the renal and cardiovascular effects of hyperuricemia are particularly relevant for the overall prognosis.

Die Gicht als Systemerkrankung

Abstract: Die Gicht ist die haufigste entzundliche Erkrankung des rheumatischen Formenkreises. In der Regel werden Patienten mit akuten Gichtanfallen hausarztlich versorgt. Leider erfolgt die konsequente, langfristige Harnsauresenkung bei manifester Gicht oft ungenugend, so dass erst unklare, komplizierende Verlaufe zur Vorstellung beim Rheumatologen fuhren. Haufig besteht bei oligo- oder polyartikularen Arthritiden als Uberweisungsgrund die Verdachtsdiagnose einer rheumatoiden Arthritis oder Psoriasisarthritis. In diesen Fallen ist rheumatologisch eine rationale Differenzialdiagnostik gefragt, die klinische, laborchemische und bildgebende Untersuchungen umfasst. Nicht selten wird eine Gelenkpunktion erforderlich. Wie bei anderen entzundlichen Erkrankungen ist die rheumatologische Kompetenz nicht nur auf die Manifestationen der Gicht am Bewegungsapparat beschrankt. Vor dem Hintergrund, dass der Gichterkrankung eine komplexe metabolisch-inflammatorische Storung zugrunde liegt, scheint es bedeutsam, neben den moglichen Folgen am Gelenksystem auch assoziierte renale und kardiovaskulare Effekte der Hyperurikamie zu berucksichtigen, da diese letztlich prognosebestimmend sind.

Die Gicht als Systemerkrankung Manifestationen, Begleit- und Folgeerkrankungen der Hyperurikämie

Abstract: ZusammenfassungDie Gicht ist die häufigste entzündliche Erkrankung des rheumatischen Formenkreises. In der Regel werden Patienten mit akuten Gichtanfällen hausärztlich versorgt. Leider erfolgt die konsequente, langfristige Harnsäuresenkung bei manifester Gicht oft ungenügend, so dass erst unklare, komplizierende Verläufe zur Vorstellung beim Rheumatologen führen. Häufig besteht bei oligo- oder polyartikulären Arthritiden als Überweisungsgrund die Verdachtsdiagnose einer rheumatoiden Arthritis oder Psoriasisarthritis. In diesen Fällen ist rheumatologisch eine rationale Differenzialdiagnostik gefragt, die klinische, laborchemische und bildgebende Untersuchungen umfasst. Nicht selten wird eine Gelenkpunktion erforderlich. Wie bei anderen entzündlichen Erkrankungen ist die rheumatologische Kompetenz nicht nur auf die Manifestationen der Gicht am Bewegungsapparat beschränkt. Vor dem Hintergrund, dass der Gichterkrankung eine komplexe metabolisch-inflammatorische Störung zugrunde liegt, scheint es bedeutsam, neben den möglichen Folgen am Gelenksystem auch assoziierte renale und kardiovaskuläre Effekte der Hyperurikämie zu berücksichtigen, da diese letztlich prognosebestimmend sind.AbstractOf all inflammatory rheumatic diseases gout has the highest prevalence. Patients with intermittent acute gout attacks are usually treated by primary care physicians. However, in cases of insufficient long-term control of serum uric acid levels, complications or atypical clinical manifestations may necessitate consultation with a rheumatologist in the further course of the disease. An oligoarticular or polyarticular presentation can give rise to the initial suspicion of rheumatoid or psoriatic arthritis. In these cases a careful clinical work-up supported by laboratory and imaging investigations is necessary and synovial fluid analysis is usually required. As in other rheumatic diseases extra-articular manifestations are of utmost importance for morbidity and mortality. Gout is a complex metabolic and inflammatory disease and besides articular symptoms the renal and cardiovascular effects of hyperuricemia are particularly relevant for the overall prognosis.

Comparison of patient satisfaction with two different etanercept delivery systems

Abstract: The objective of this study was to investigate patients’ perceptions of the acceptability of two devices delivering etanercept for rheumatoid arthritis (RA) treatment and to explore whether specific patients’ attributes are associated with device preferences Two similar multicenter, open-label, randomised, parallel-design studies were conducted in a total of 13 European countries A total of 640 adult patients with RA were randomised to receive etanercept 50 mg once-weekly subcutaneously for 12 weeks in either a pre-filled syringe (PFS) or a pre-filled pen (PFP) Patient satisfaction at week 12 was measured on a 0- to 10-point Likert scale (primary endpoint) The study was powered to demonstrate non-inferiority of a PFP over PFS for the primary endpoint At week 12, mean patient satisfaction was 83 (± 24) points in the pen group and 72 (± 26) points in the syringe group Non-inferiority and even superiority of the pen over the syringe was demonstrated In conclusion, this study showed higher patient satisfaction in the group of patients injecting etanercept with a PFP compared with the group of patients using a PFS

Osteometabolic and Osteogenetic Pattern of Turkish Immigrants in Germany

Abstract: The etiology of osteoporosis comprises environmental and genetic factors. This study investigated vitamin D deficiency and specific genetic alterations of bone metabolism in a group of 183 Turkish immigrants in Germany in comparison with 46 age and sex matched healthy German controls (females in both groups were pre-menopausal). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Serum levels of osteologic parameters were determined after overnight fasting. Polymorphisms of the vitamin D receptor (VDR) and lactase genes were genotyped using genomic DNA from peripheral leukocytes. Statistical analysis comprised student’s t-test, Mann-Whitney rank sum test, Chi-square analysis and Fisher’s exact test. Severe 25-OH D3 hypovitaminosis (83.1%) and elevated parathyroid hormone (82%) were common among immigrants. Osteoporosis but not osteopenia was more prevalent in immigrants. Among immigrants with osteoporosis, TRAP5b was elevated in 26.7%, and β-crosslaps in 13.3%. Only the FokI FF VDR-gene-polymorphism was significantly more prevalent among immigrants. In contrast, Ff-genotyped Turkish women exhibited significantly decreased BMD. Lactase polymorphisms were significantly more common among immigrants (84.2% vs. 30.4%) and the CC genotype was commonly associated with reduced BMD (41.6%) but rarely osteoporosis (8.4%). Vitamin D deficiency, secondary hyperparathyroidism and osteoporosis are common among Turkish immigrants in Germany. Thus, in this population osteologic parameters and BMD should be analyzed and deficiencies be treated. Specifically, the VDR gene polymorphism FokI Ff is of clinical value in identifying females at risk of osteoporosis. In contrast, LCT polymorphisms, though common, do not appear to be a risk factor.

The Role of Corticosteroids for Pain Relief in Persistent Pain of Inflammatory Arthritis: A Systematic Literature Review

Abstract: Objective. To conduct a systematic review of the available literature addressing the effectiveness, safety, and role of corticosteroids for pain relief in persistent pain of inflammatory arthritis (IA), as part of the international 3e (Evidence, Expertise, Exchange) Initiative. Methods. A systematic literature research (SLR) was carried out in Medline, Embase, the Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism meeting abstracts, searching for studies evaluating the use of steroids for the treatment of residual pain in IA despite adequate antiinflammatory therapy. Results. Of 3887 references retrieved by SLR, 2 randomized controlled studies and 35 review articles underwent full-text review. No article was found to adequately address the research question. Conclusion. No data on the efficacy and safety of systemic corticosteroids in residual pain in IA could be identified from the literature.

Einfluss einer seriellen niedrig dosierten Radonstollen-Hyperthermie auf zentrale Zytokine des Knochen­metabolismus bei ankylosierender Spondylitis

Abstract: Eine sekundare Osteoporose stellt eine haufige und komplizierende Begleiterkrankung bei Patienten mit ankylosierender Spondylitis dar. Die Abnahme der Knochendichte ist Ausdruck eines zugunsten des Knochenabbaus verschobenen Gleichgewichts von osteokatabolen und osteoanabolen knochenphysiologischen Stoffwechselprozessen, die durch diverse Faktoren beeinflusst werden. Bei Patienten mit gesicherter ankylosierender Spondylitis (AS) im chronischen Stadium (n=24, Altersdurchschnitt 58 Jahre) und einer altersvergleichbaren Patientengruppe mit Osteoarthrose (OA, n=24) wurde der Einfluss einer seriellen Radonstollen-Hyperthermie (12 Anwendungen in 3 Wochen) auf die Serumspiegel der Zytokine Osteoprotegerin (OPG), receptor activator of NF kappa-B ligand (RANKL) und Tumornekrosefaktor alpha (TNF-alpha) sowie auf den RANKL/OPG-Quotienten als Marker zur Quantifizierung des Knochenmetabolismus untersucht. Die Messungen erfolgten vor und nach serieller Radonstollen-Hyperthermie. Die Medikation in beiden Gruppen umfasste lediglich eine bedarfsabhangige Einnahme nicht-steroidaler Antiphlogistika (NSAR). Eine TNF-Hemmer-Therapie sowie Medikation mit moglichem Einfluss auf den Knochenstoffwechsel bestand nicht. Nach der seriellen Radonstollen-Hyperthermie zeigte sich bei den AS-Patienten ein tendenzieller, bei den OA-Patienten ein signifikanter Abfall der TNF-alpha Spiegel (p Die serielle Radonstollen-Hyperthermie bewirkte bei Patienten mit chronischer AS einen Anstieg der knochenanabolen und einen Ruckgang der knochenkatabolen Zytokine, was der molekularen Grundlage fur eine Verminderung des osteoklastaren Knochenabbaus im Rahmen der entzundlich bedingten sekundaren Osteoporose entspricht. Somit kommt der Radonstollen-Hyperthermie ein wichtiger Stellenwert im multimodalen Therapiekonzept der AS zu.

Clinical correlations of hypocomplementaemia in systemic sclerosis: an analysis of the EULAR Scleroderma Trial and Research group (EUSTAR) database

Abstract: Endothelial cells, fibroblasts, and lymphocytes play a role in the pathogenesis of systemic sclerosis (SSc) (1). Autoantibody-mediated tissue injury seems not to be paramount, although serum immune...

Ambulante Physiotherapie bei Osteoporose

Abstract: Analysiert wurden anhand der Vorschriften der deutschen gesetzlichen Krankenversicherung die existierende und explizit angeforderte Ruckmeldungsquote, Kooperation und Verordnungstreue von ambulanten Physiotherapeuten gegenuber dem verordnenden Arzt im Bereich einer ambulanten osteologischen und rheumatologischen Schwerpunktpraxis und die Frage nach der Beurteilbarkeit der Effizienz der jeweiligen Therapie. Hierzu wurden prospektiv 475 Heilmittelverordnungen in einem uberregionalen Einzugsgebiet bezuglich der verpflichtend angeforderten Therapieberichte (Ruckmeldungsquote), dem Informationsgehalt der Therapieberichte sowie der laut Patienten durchgefuhrten Therapie beurteilt. Zudem wurde die Quote angeforderter Folgeverordnungen wie auch die Fahigkeit der Patienten, die zu erlernenden Ubungen eigenstandig durchzufuhren, analysiert. Abschliesend sollte die Effizienz der Heilmittelverordnung beurteilt werden. Es zeigte sich eine Ruckmeldequote von 9,7%. Je nach Heilmittelverordnung schwankte diese erheblich (von klassische Massage 6,8%, Warmetherapie 12,8%, KG ohne oder mit Geraten oder im UWB 9,1–20,4% bis Elektrotherapie 20%). Selbsterlernte Ubungen, die den Patienten bei den 141 verordneten Ubungsbehandlungen zu vermitteln waren, konnten lediglich von 38 (27%) adaquat demonstriert werden. Von den 46 Therapieberichten wurden vier mit hilfreichen Informationen fur den Arzt versehen. Bei 38 der 46 Ruckmeldungen (82,6%) wurden Folgeverordnungen empfohlen. Die Daten belegen, dass im ambulanten Bereich keine suffiziente Kooperation zwischen verordnendem Arzt und behandelndem Physiotherapeuten besteht. Die geringe Ruckmeldequote erschwert die valide Beurteilung der Effizienz der Heilmittelverordnungen. Daher ist dringend – neben einer Verbesserung der Aus-, Fort- oder Weiterbildung – ein Kontrollmechanismus zur Verordnung von physikalischen Therapiemasnahmen zu implementieren.

Systematische Literaturrecherche für die S1-Leitlinie zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis

Abstract: Ausgangspunkt der neuen S1-Leitlinie waren die 2010 erschienenen EULAR Recommendations zum Management der rheumatoiden Arthritis (RA), die nach umfangreichen systematischen Literaturrecherchen (SLR) evidenzbasiert erstellt worden sind. Die SLR wurde fur die deutschen Empfehlungen aktualisiert und wird in ihrer Methodik vorgestellt. Die SLR wurde fur den Zeitraum von Januar 2009 bis Ende August 2011 durchgefuhrt. Es wurden alle kontrollierten Studien eingeschlossen, die die krankheitsmodifizierende Therapie der RA hinsichtlich ihrer Wirksamkeit auf Klinik, Funktion und Struktur untersucht haben. Von 6869 gesichteten Arbeiten wurden 138 Artikel und 56 Abstracts fur die Erstellung der Leitlinie berucksichtigt. Auf einem Konsensustreffen wurden die Ergebnisse der SLR vorgestellt. Auf dieser Grundlage formulierte das Expertengremium modifizierte Empfehlungen und verabschiedete diese mittels Konsensus. Mithilfe der aktualisierten SLR konnten wesentliche neue Daten im Entscheidungsprozess fur die neue S1-Leitlinie zur medikamentosen Therapie der RA berucksichtigt werden.

Klinische Präsentationen der Tuberkulose im Alltag

Abstract: Seit Beginn der Ara der biologischen Praparate weis man, dass Tuberkulose eine potenziell lebensbedrohliche Komplikation bei der Behandlung von Patienten mit rheumatischen Erkrankungen darstellt Nationale und internationale Gesellschaften haben Empfehlungen fur das Tuberkulosescreening herausgegeben und fur die Behandlung von Tuberkuloserisikopatienten Aufgrund der relativen Seltenheit offener Tuberkulose bei Patienten mit rheumatischen Erkrankungen ist die Erfahrung einzelner Rheumatologen mit dieser Komplikation begrenzt Daher haben wir die Tuberkulosefalle in unserem Rheumazentrum (mit Behandlung von uber 1500 stationaren und 8000 ambulanten Fallen pro Jahr) von 2006–2011 ausgewertet, um mehr als 10 Jahre nach Beginn der ersten Anwendung von Biologika auserhalb kontrollierter klinischer Studien ein lebensnahes Bild zu erhalten Wir fanden 4 Falle, anhand derer sich die Schwierigkeiten von Diagnose und Therapie zeigen

Is nailfold videocapillaroscopy a valuable diagnostic tool in pulmonary hypertension

Abstract: Background: Pulmonary hypertension (PH) can be based on idiopathic pulmonary arterial hypertension (iPAH), connective tissue diseases such as systemic sclerosis (SSc-PAH), left heart disease (LHD-PH), chronic obstructive pulmonary disease (COPD-PH), or chronic thromboembolic events (CTEPH). Objectives: Analysis of microvascular patterns of patients with PH has been performed using nailfold videocapillaroscopy (NVC). The benefit of NVC in PH was evaluated with focus on SSc patients. Methods: NVC was performed in 81 patients. 2nd-5th fingers were bilaterally analyzed. Pictures were scored for capillary density (CD, capillaries/mm), and dimensions. Parameters such as hemorrhages and neoangiogenesis or capillary alterations such as ectasia (>20µm) and giant shape (>50µm) were qualitatively assessed. Results: 14.8% had iPAH, 14.8% LHD-PH, 7.4% COPD-PH and 17.2% CTEPH. 45.7% had SSc and 12.3% SSc-PAH. The CD in SSc-PAH was significantly lower compared to all other PH forms (4.9 vs. 10.2, 10.0, 11.7 and 9.47 in iPAH, LHD-PH, COPD-PH and CTEPH; p Conclusions: Assessing capillary density in PH is a powerful tool to discriminate between SSc-PAH and other forms of PH. In this respect, NVC should be considered, besides checking for antinuclear antibodies, if the underlying cause of PH is unclear to determine SSc-PAH.

Expression of extracellular RNA in synovial tissue and RNase activity in synovial fluid of rheumatoid arthritis patients

Abstract: Background RNA is required for protein biosynthesis. However, extracellular RNA (exRNA) is also present within tissues and actively secreted by cells. Examples for the exRNA-activity are a pro-coagulative effect and an enhanced permeability of the blood-brain-barrier by exRNA. Furthermore, specific exRNAs are accumulated in the serum in cancer and these exRNA have actually been identified as tumour-markers. A pro-inflammatory effect of extracellular DNA due to tissue damage has been described in rheumatoid arthritis (RA). Therefore, the authors analysed the presence and the expression pattern of exRNA in the joint as well as the activity of RNase in the synovial fluid of RA patients. Methods Synovium from RA and OA patients (n=3 each) were stained with 4′,6-diamidin-2-phenylindole (DAPI) to locate DNA and SYTO RNASelect Green Fluorescent Stain to locate RNA in the tissue. A serial tissue section was stained with HE OA: n=3 and psoriatic arthritis (PsA): n=5) was measured using the Quant-iT RNA Assay Kit. Results RNA and DNA signals were detectable in all areas of the synovium. Merging the RNA and DNA signals showed a co-localisation of the signals within the nucleus of the cell. Interestingly, an intensive cytoplasmatic and exRNA signal could be observed in the lining layer of RA and OA patients with stronger signal intensity in the RA lining. Due to the increased thickness of the lining layer in RA patients, an increased amount of exRNA in RA patients when compared to OA was detectable. This signal was not co-localised with the DNA. A reduced RNase activity was measured in the synovial fluid of patients with RA (20.1±3.61) and PsA (21.3±2.5) in comparison to OA patients (35.8±4.5), reaching statistical significance when comparing PsA to OA patients (p=0,033). In addition, RNase activity was inversely correlated to CRP serum level (r=−0.43). Conclusion In OA and especially RA patients, exRNA is present in the synovial lining layer. RNase activity in the synovial fluid seems to be reduced in patients with chronic inflammation (RA and PSA) in contrast to OA. The increased amounts of exRNA could demonstrate a new pro-inflammatory mechanism active in chronic inflamed tissue that could be important for the perpetuation and chronification of inflammation.

19. Cortisol-induced adhesion of synovial fibroblasts is mediated by the endocannabinoid system

Abstract: Background In rheumatoid arthritis, glucocorticoid secretion in relation to inflammation is inadequate. Besides their direct effects on inflammation, glucocorticoids induce indirect effects by modulation of the endocannabinoid system. Therefore, we hypothesize that some actions of cortisol in the periphery are also mediated by the endocannabinoid system. We inhibited FAAH, the major enzyme for endocannabinoid degradation, and blocked cannabinoid receptors (CBrs) to study the role of endocannabinoids in cortisol-mediated effects. Methods We performed immunofluorescence analysis to detect all components of the endocannabinoid system in synovial fibroblasts (SFs). Adhesion was assessed using the Xcelligence system by Roche. Mass spectrometry was used to detect anandamide in tissue culture supernatants. Results Cortisol increased the adhesion of synovial fibroblasts to fibronectin in a dose dependent manner with a maximum at 10–8 M. This increase was blocked by a CB1r and a GPR18 antagonist but also by an inhibitor of FAAH. The latter effect could be reversed in SFs from osteoarthritic (OA) patients by nimesulide, a selective cox-2 inhibitor and O-1918, a GPR18 antagonist. Conclusion The effect of cortisol on SF adhesion is dependent on the production and degradation of anandamide. This endocannabinoid binds a plethora of receptors, but all with different affinities. Due to FAAH inhibition, anandamide concentrations are altered within the cytoplasm. This might shift the cellular response from one receptor type to another explaining the observed effects.