Die Rheumatologie ist ein Fachgebiet voller Differenzialdiagnosen. So klar auch selbst klassische Krankheitsbilder wie die rheumatoide Arthritis als die häufigste chronisch entzündlich verlaufende Gelenkerkrankung in Lehrbüchern beschrieben sein mögen, in der klinischen Praxis stellen sie nicht selten eine diagnostische Herausforderung dar. Dies bezieht sich sowohl auf die arthritische Gelenkbeteiligung als auch auf die häufig assoziierten extraartikulären Manifestationen. Grundlegend sind Anamnese und klinischer Befund, aber zur sicheren Diagnosefindung tragen Labor und Bildgebung insbesondere in der Frühphase der Erkrankung oft entscheidend bei. In diesem Beitrag, der keinen Anspruch auf Vollständigkeit haben kann, wird der Schwerpunkt auf die aus Autorensicht häufigsten Krankheitsbilder gelegt, die vom ähnlichen Gelenk- und Organbefund her eine rheumatoide Arthritis imitieren können. Dies schließt sowohl metabolische, entzündliche nichtinfektiöse und infektiöse Erkrankungen als auch tumoröse Erkrankungen mit ein. Eine Verwechslung mit einer rheumatoiden Arthritis hat in der Regel langfristige und schwere Konsequenzen für die betroffenen Patienten. Deshalb sollte bei ungewöhnlichen Begleitsymptomen, atypischem Verlauf und fehlendem Ansprechen auf übliche Behandlungsansätze die Diagnose einer rheumatoiden Arthritis hinterfragt und geprüft werden.

Etablierung einer offenen rheumatologischen Sprechstunde zur Früherkennung von Patienten mit entzündlich rheumatischen Erkrankungen und Einleitung einer weiteren Diagnostik und Therapie.

AIM OF THE PROJECT: To establish an open rheumatological outpatient consultation service for early diagnosis of inflammatory rheumatic diseases and initiation of further diagnostics and treatment. METHODS: In 2015 an open consultation service was initiated for patients with signs of an early rheumatic disease after referral by primary care physicians. Patients could attend once a week without the need for a prior appointment if they fulfilled at least one of the following criteria: positive rheumatoid factor, increased CRP, anti-CCP antibody or antinuclear antibody, joint pain or back pain for over 3 months, swollen joints, fever of unknown origin or acute muscle pain with or without headache of unknown origin. This article presents the results of the retrospective descriptive data analysis of the first 2 years of this project. RESULTS: A total of 1262 patients were treated with an average of approximately 20 patients per consultation. In nearly half of the patients an inflammatory rheumatological disease could be diagnosed and immediate diagnostic and treatment measures could be initiated. The diagnostic delay for patients with rheumatoid arthritis was 12 weeks, for patients with polymyalgia rheumatica 11 weeks and for patients with psoriatic arthritis or axial spondylarthritis 18 and 44 weeks, respectively. The time expenditure was a total of 4-5 h per week for an experienced rheumatologist and a specialized rheumatology nurse. CONCLUSION: Through this open rheumatological outpatient consultation a low threshold opportunity for the early diagnosis of rheumatologic diseases could be established. The diagnostic delay for many rheumatological diseases could be considerably shortened. Cooperation with rheumatologists in private practice guaranteed the subsequent specialized rheumatological care of the identified patients in the early stages of their illness.

Im Allgemeinen manifestiert sich die Arthritis urica (Gicht) klinisch als akute Gelenkentzündung, Bursitis oder Uratkristallablagerung in Form von Tophi. Manifestationen am Achsenskelett sind ebenfalls bekannt und beschrieben, kommen aber selten vor und spielen aus diesem Grund im Bewusstsein von Rheumatologen eine untergeordnete Rolle. Mithilfe der Dual-energy-Computertomographie (CT) lassen sich Gichttophi auch in ungewöhnlichen oder für Punktionen schwer zugänglichen Regionen nachweisen. Wir berichten über zwei seltene Fälle einer Achsenskelettbeteiligung der Gicht bei einem 76-jährigen Patienten mit Beteiligung der Halswirbelsäule und einer 53-jährigen Patientin mit Beteiligung der Sakroiliakalgelenke. In beiden Fällen gelang die Diagnose auf Basis einer Dual-energy-CT.

Clinical manifestations of gouty arthropathy are usually acute inflammatory arthritis, bursitis and accumulation of urate crystals in the form of tophi. Manifestations on the axial skeleton are also known and have been described but occur infrequently and for this reason play a subordinate role in the awareness of rheumatologists. With dual energy computed tomography (CT) gout tophi can be detected even in unusual regions or regions that are difficult to access for puncturing. We describe two rare cases of gouty arthropathy of the axial skeleton in a 76-year-old male patient with spinal involvement and in a 53-year-old female patient with involvement of the sacroiliac joint. In both cases the diagnosis was achieved with dual energy CT.

OBJECTIVES To compare sleep quality, disease activity and patient-reported outcomes such as fatigue and immune parameters in patients with rheumatoid arthritis treated with etanercept (ETA) or methotrexate (MTX). METHODS Of 36 patients (28-joint Disease Activity Score, DAS28CRP≥3.2) in this 16-week (w), open, prospective study, 19 (11 women) received MTX 12.5-17 mg/w, and 17 (14 women) received ETA 25 mg x 2/w, alone or in combination with MTX. Clinical (DAS28CRP, visual analogue scale), laboratory (C-reactive protein [CRP]), sleep (polysomnography), functional (Multidimensional Fatigue Inventory; Health Assessment Questionnaire-Disability Index (HAQ-DI); 36-item Short-Form Health Survey (SF-36), immunological (humoral/cellular) and neuroendocrine (hormonal) parameters were recorded at baseline (BL), w8 and w16. RESULTS BL characteristics did not differ significantly between the ETA and MTX groups except disease duration: mean age (years): 48.6±8.8 vs. 49.4±16.6; mean disease duration (months): 19.6±46.3 vs. 81.2±79.2; and DAS28CRP: 4.4±0.9 vs. 4.4±1.7, respectively. DAS28CRP, SF-36, and HAQ-DI improved significantly in both groups from BL to w16 (p≤0.05). The DAS28CRP improvements at w16 (mean changes -1.8 in the ETA group, and -1.4 in MTX group), were not statistically significant from each other. The absolute values of sleep efficiency, total sleep time, and stage 2 sleep duration increased significantly in the ETA group, but no significant changes were reported in the MTX group. CONCLUSIONS Both therapies improved disease activity, CRP, SF-36 and HAQ-DI, with faster, more pronounced changes in DAS28CRP in the ETA group, which alone had significantly improved sleep parameters.

Background In patients with rheumatoid arthritis (RA), seropositivity for either rheumatoid factor or anti-CCP antibodies has been identified as a predictive marker for treatment response to rituximab (RTX) in different studies. However, it is unclear, whether analysis of fine-reactivity against certain epitopes of citrullinated antigens or immunoglobulin subclass reactivity can contribute to the prediction of treatment response to RTX. Objectives To investigate whether reactivity patterns against epitopes of the mutated citrullinated vimentin (MCV) antigen and/or anti-MCV subclass reactivities can contribute to differentiation of responders to RTX. Methods Fine-reactivity against MCV was investigated in anti-MCV antibody positive patients with RA (n=34) under treatment with RTX. According to EULAR response criteria, 23 patients were classified as responders by reaching remission as defined by DAS28 <2.6 or low disease activity as defined by DAS28 <3.2. Follow-up analyses of anti-MCV response were performed using 88 synthetic overlapping MCV peptides in ELISA. The peptides used contained all known modifications of vimentin by mutation and citrullination1. In addition, influence of RTX treatment on anti-MCV IgG, IgM and IgA antibody reactivities was investigated by ELISA. Results At baseline or during follow-up, none of the responders showed an anti-MCV IgA antibody response. In contrast, non-responders were positive for anti-MCV IgA in 50% of the cases at baseline and showed no reduction of antibody subclass reactivities in the follow-up. Furthermore, anti-MCV antibody subclass reactivities showed that RTX-responders were characterized by a reduction of anti-MCV IgG antibody titers, and by a normalization of anti-MCV IgM titers in all initially positive cases. At baseline, subsequent responders to RTX treatment were characterized by only a minor different epitope recognition pattern compared to non-responders. Remarkably upon treatment, a reduction of the number of recognized MCV epitopes was observed in 16 out of 23 responders (69.6%) in contrast to 3 out of 11 (27.3%) non-responders in follow-up analyses. Conclusions Responders to RTX were characterized by a restricted immunoglobulin subclass reactivity against MCV lacking IgA anti-MCV antibodies at baseline, and a reduction of anti-MCV antibody titers as well as the epitope recognition pattern under treatment. Fine-reactivity against the MCV antigen can potentially contribute as a useful marker to predict response to RTX in anti-MCV positive RA patients. References Bang H, Egerer K, Gauliard A, Luthke K, Rudolph PE, Fredenhagen G, Berg W, Feist E, Burmester GR. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 2007 Jul 30;56(8):2503-2511 Disclosure of Interest L. Naumann Grant/Research support from: Roche Pharma AG, H. Bang Employee of: Orgentec, K. Egerer: None Declared, D. Meyer zum Büschenfelde: None Declared, B. Lehmann: None Declared, G. Fredenhagen Employee of: Orgentec, H. Bastian: None Declared, E. Wittenborn Employee of: Roche Pharma AG, G.-R. Burmester: None Declared, E. Feist: None Declared

Background To study the prolonged effect on disease activity by an early induction therapy with adalimumab (ADA) plus methotrexate (MTX) versus MTX alone in DMARD naïve patients (pts) with early RA (designated HIT HARD, funded by the German Ministry of Science). Methods In a double-blind randomized controlled trial, RA pts (disease duration of ≤12 months, ≥6 swollen, ≥6 tender joints, and CRP≥10 mg/l) were randomized into two groups: placebo (PBO) plus MTX (n=85), given s.c. at 15 mg/week (w) versus MTX 15 mg/w s.c. plus 40 mg ADA s.c. eow over 24w (n=87). After w24, both groups were treated only with MTX up to w48. The primary outcome measure was the DAS28-response at w48. Secondary outcomes was the pts in remission (DAS28<2.6), ACR responses, HAQ, SF36 and radiographic progression. Statistical analysis was based on the ITT population. To improve power, analysis of covariance (ANCOVA) with baseline (BL) status as covariable was applied to compare DAS28, HAQ between groups. Non-parametric ANCOVA was used to compare van der Heijde modified Sharp (Sharp vdH) scores. Multiple imputation method was used to replace missing data. Results Mean disease duration at BL was 1.7 years, 91 (53%) were ACPA positive and 114 (63%) IgM RF positive. DAS28 was 6.2±0.8 (ADA/MTX) and 6.3±0.9 (PBO/MTX) (p=0.60). Outcome parameters at w24 and w48 are presented in tables 1. During the induction phase, ADA/MTX reduced disease activity to a significantly greater extent than PBO/MTX (Table 1). After termination of ADA or PBO and continuation with MTX alone, the differences between both groups in clinical outcome parameters (DAS28, remission, ACR50 response, HAQ, SF36 mental score) decreased at w24/48 and did not reach statistical significance at w48. Nevertheless, combination therapy significantly reduced radiographic progression as demonstrated by the Sharp vdH erosion score (p=0.010) as compared to the combination group, joint space narrowing score (p=0.035) and Sharp vdH total score (p=0.003); Ratingen score (p=0.012) compared to MTX alone when analyzed after w48. Conclusions Superiority in reduction of radiographic progression after initial combination therapy with ADA and MTX was seen at w 48, even after discontinuation of ADA treatment at w 24. Such a sustained effect was not found regarding the primary endpoint (DAS28 reduction). Disclosure of Interest J. Detert Grant/Research support from: Abbott & Co GmbH, Speakers Bureau: Abbott & Co GmbH, H. Bastian Speakers Bureau: Abbott & Co GmbH, J. Listing: None Declared, A. Weiss: None Declared, S. Wassenberg: None Declared, A. Liebhaber: None Declared, K. Rockwitz: None Declared, R. Alten: None Declared, K. Krüger: None Declared, R. Rau: None Declared, C. Simon: None Declared, E. Gremmelsbacher: None Declared, T. Braun: None Declared, B. Marsmann: None Declared, V. Höhne-Zimmer: None Declared, K. Egerer: None Declared, F. Buttgereit: None Declared, G.-R. Burmester Grant/Research support from: Abbott & Co GmbH, Consultant for: Abbott & Co GmbH, Speakers Bureau: Abbott & Co GmbH

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA.

OBJECTIVE:Recently, new classification criteria for rheumatoid arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative approach (consensus; based on paper patients), and finally a common sense-based approach (evaluation of the former phases). Now the individual items that make up these criteria are being evaluated. This study was undertaken to analyze the item "autoantibodies," in particular rheumatoid factor (RF) level.METHODS:Three separate cohorts comprising a total of 972 patients with undifferentiated arthritis were studied for RA development (according to the 1987 American College of Rheumatology criteria) and arthritis persistence. The positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were compared between different levels of RF and the presence of anti-citrullinated protein antibody (ACPA). A similar comparison was made in 686 RA patients for the rate of joint destruction and achievement of sustained disease-modifying antirheumatic drug-free remission during 7 years of followup. The variation in RF levels obtained by different measurement methods in the same RF-positive sera was explored.RESULTS:Compared to high RF levels, presence of ACPA had a better balance between positive LR and negative LR and between PPV and NPV for RA development. The additive value of ACPA assessment after testing for RF level was higher than vice versa. The association between high RF level and RA severity was not as strong as that between ACPA antibodies and RA severity. The RF level obtained by different methods in the same patients' sera varied considerably.CONCLUSION:Our findings indicate that determination of RF level is subject to large variation; high RF level has limited additive prognostic value compared to ACPA positivity. Thus, omitting RF level and using RF presence, ACPA presence, and ACPA level may improve the 2010 criteria for RA.

Die rheumatoide Arthritis ist die häufigste chronisch-entzündliche rheumatische Gelenkerkrankung, die unbehandelt zu radiologisch erfassbaren progredienten Gelenkdestruktionen führt. Die Erkrankung hat eine wesentliche sozialökonomische Bedeutung, da es bei einem Großteil der betroffenen Patienten zur Manifestation im berufsfähigen Alter kommt, mit resultierender Arbeitsunfähigkeit sowie möglicher Invalidität. Für die Prognose spielt eine frühzeitige adäquate antirheumatische Basistherapie sowie ergo- und physiotherapeutische Maßnahmen eine entscheidende Rolle. In den letzten Jahren haben sich die Möglichkeiten der medikamentösen Behandlung deutlich verbessert. Dieser Fortschritt war die Grundlage für neue Therapiestrategien mit einer dem individuellen Krankheitsverlauf eng angepassten medikamentösen Behandlung mit dem Ziel einer Krankheitsremission.

Biologika haben die Therapie von entzündlich-rheumatischen Erkrankungen in den letzten 10 Jahren revolutioniert. Durch die gezielte Inhibition von inflammatorischen Zytokinen sowie der Blockade von zentralen Zellen, die an einer Entzündungsreaktion beteiligt sind, konnte ein Ausmaß der Entzündungshemmung erreicht werden, das vor der Einführung der Biologika undenkbar war. Die Notwendigkeit, die heutigen Biologika weiter zu entwickeln, basiert vor allem darauf, dass 1. der klinische Effekt zwar bei jedem zugelassenen Biologikum bei der großen Mehrzahl, aber durchaus nicht bei allen Patienten eintritt, dass 2. durch die Blockade wichtiger Mediatoren des Immunsystems Risiken für die Entstehung von Infektionen oder bösartigen Neubildungen bestehen und dass 3. die heutigen Biologika allesamt parenteral verabreicht werden müssen. In der vorliegenden Übersicht portraitieren wir eine Reihe von innovativen Biologika und niedermolekularen Molekülen, die im Moment in klinischen Studien bei Patienten mit entzündlich-rheumatischen Erkrankungen untersucht werden und von denen einige in nächster Zeit das Armamentarium der verfügbaren Biologika in der Rheumatologie erweitern werden.

Biologics have revolutionized the treatment of inflammatory joint disease in the last decade. By precisely targeting and inhibiting inflammatory cytokines as well as the blockade of cells centrally integrated in the immune system, inhibition of inflammation has become possible which had been unthinkable before. The medical need to improve our current approach with biologics even more is based on three observations: (1) even though the clinical effect of a given biologic is evident in the majority of patients, not all show a satisfactory response, (2) the blockade of important mediators of the immune system bears the risk of infection and potentially malignant events and (3) all current biologics need to be administered parenterally. The present review describes several innovative biologics and low molecular weight compounds which are currently being investigated in clinical trials in patients suffering from inflammatory rheumatic conditions. Some of them may become a part of our growing armamentarium to treat these diseases which still represent a major burden to the patients and society.

Tumor necrosis factor (TNF)-alpha blocking agents play an important role in rheumatology. For this reason, questions about the pathogenic characteristics of TNF in carcinogenesis are of the utmost importance. The observation that TNF leads to necrosis in tumor tissue gave rise to the hope that an agent had been identified for the treatment of malignant tumors. However, this expectation remained unfulfilled, not the least due to the toxicity of systemically applied TNF. In addition, TNF is produced by many tumor cells. There is evidence that for some tumors TNF promotes tumor growth, invasiveness and metastasis. It is quite possible, therefore, that the inhibition of TNF-alpha has an inhibitive effect on carcinogenesis and/or tumor progression. In 2009 the US Food and Drug Administration (FDA) issued a cancer warning for the use of TNF inhibitors in children and adolescents. There is still some controversy as to whether TNF blocking therapy, co-medication or the rheumatic disease itself leads to an increased cancer risk in these young patients. In adults, safety information so far available suggests a favorable risk-benefit profile for the long-term use of TNF inhibitors. However, many questions remain unanswered as to the role TNF itself plays in the pathogenesis of solid tumors.

Tumor-Nekrose-Faktor- (TNF-)α-blockierende Substanzen spielen eine wichtige Rolle in der Rheumatologie. Deshalb ist die Frage nach den pathogenetischen Eigenschaften von TNF bei der Tumorgenese von enormer Bedeutung. Die Beobachtung, dass TNF zu Nekrosen im Tumorgewebe führte, nährte seinerzeit die Hoffnung, eine Substanz zur Behandlung von Malignomen identifiziert zu haben. Diese Erwartung blieb jedoch nicht zuletzt aufgrund der Toxizität von systemisch angewandtem TNF unerfüllt. Zudem wird TNF auch von vielen Tumorzellen produziert. Bei einigen Tumoren gibt es Hinweise dafür, dass sich TNF fördernd auf Tumorwachstum, -invasivität und -metastasierung auswirkt. Es ist daher durchaus vorstellbar, dass die Inhibition von TNF-α hemmende Effekte auf Karzinomgenese und/oder Tumorprogression hat. Im Jahr 2009 hat die amerikanische „Food and Drug Administration“ (FDA) die Malignomwarnung für alle Anti-TNF-Präparate in der Kinder- und Jugendmedizin ausgeweitet. Die Frage, ob eine Anti-TNF-Therapie, Komedikation oder die rheumatologische Grunderkrankung zu einem erhöhten Krebsrisiko führen, wird weiterhin kontrovers diskutiert. Die bisher ermittelten Sicherheitsdaten legen in der Erwachsenenmedizin ein günstiges Risiko-Nutzen-Profil von Anti-TNF-Präparaten in der Langzeitanwendung nahe. Bezüglich der Rolle von TNF selbst in der Pathogenese solider Tumoren bleiben auch heute noch viele Fragen ungeklärt.

Objective. To assess if electrostimulation of lower limbs relieves lower limbs venous insufficiency-related symptoms during pregnancy.Patients and methods.- A two-step study was conducted. First, a monocentric prospective preliminary study including 30 pregnant women was conducted to assess the effects of electrostimulation on fetal monitoring and uterine contractions. Then, a multicentric prospective non-randomised study including. 58 pregnant women with a gestational age between 23 and 33 weeks of amenorrhoea was conducted to evaluate the electrostimulation treatment. This evaluation was based on a clinical examination performed pre- and post-treatment, a CIVIQ questionnaire filled out pre- and post-treatment. and a daily diary filled out by the patient during treatment duration. Treatment duration was 21 days including two daily treatment sequences of 20 min. Three groups of patients were identified based on initial intensity of venous insufficiency-related symptoms (group 1 minor symptoms, group 2 moderate symptoms, group 3 severe symptoms).Results.- Preliminary study showed no interferences between electrostimulation and fetal cardiac rhythm, uterine contractions and maternal uterine tint( fetal umbilical arteries Doppler. Concerning the evaluation of the electrostimulation: in group 1, electrostimulation significantly reduced heavy legs sensation (p < 0,001) and calves pain (p = 0,02) between the beginning and the end of the treatment. The four scores calculated with the CIVIQ questionnaire decreased after treatment and a significant reduction was noted for generalised pain feeling (p = 0,04) and psychological impact (p = 0,03). In group 2, a significant decrease was noted for tiredness (p < 0,001), heavy legs sensation (p < 0,001), calves pain (p < 0,001) and edema (p = 0,02) between the beginning and the end of the treatment. The four scores calculated with the CIVIQ questionnaire significantly decrease after 21 days of treatment. In group 3, a significant decrease of heavy legs sensation (p = 0,03) and calves and malleoli perimeters (p < 0,05) was noted. After 21 days of treatment, the four scores calculated with the CIVIQ questionnaire significantly decrease (p < 0,05). When comparing the three groups, beneficial effects of the treatment are most marked in group 2 regarding subjective symptoms, CIVIQ questionnaire scores and leg pain. According to the patients, effectiveness and tolerance of the treatment ranged from good to excellent in the three groups.Discussion and conclusion.- Electrostimulation is an effective and well-tolerated treatment of lower limbs venous insufficiency-related symptoms in pregnant women. It, use during pregnancy did not show any effects on fetus and pregnancy. (C) 2008 Elsevier Masson SAS. All rights reserved.