[How frequent are poor prognostic markers in rheumatoid arthritis? : An estimate based on three epidemiologic cohorts]. / Wie häufig sind prognostisch ungünstige Faktoren bei Patienten mit rheumatoider Arthritis? : Eine Abschätzung anhand von 3 epidemiologischen Kohorten.

BACKGROUND: Unfavorable prognostic factors-high disease activity, early erosions, and autoantibodies-should be considered when making treatment decisions in rheumatoid arthritis (RA). There are little data on the frequency of individual poor prognostic factors among RA patients in daily care. METHODS: Disease activity (Disease Activity Score, DAS28), erosions, antibodies against citrullinated peptides or rheumatoid factor (ACPA/RF+), previous treatment failure, inflammation markers, and functional disability (FFbH < 70) were defined as prognostic factors. Different treatment decision making situations were evaluated in disease-modifying antirheumatic drug (DMARD)-naïve patients from the early RA CAPEA cohort (n = 1059), and in patients from the biologics register RABBIT after failure of one (n = 2217) or more (n = 3280) conventional synthetic (cs)DMARDs or one (n = 1134) or more (n = 795) biologic (b)DMARDs. With the national database of German arthritis centers (NDB), the frequency of these factors was analyzed according to treatment strata (no/1st/2nd/3rd DMARD; n = 5707). RESULTS: In DMARD-naïve patients (CAPEA), 50% presented with DAS28 > 5.1, 64% were ACPA/RF+, 13% had erosions, and 37% functional disability (FFbH < 70). In RABBIT, 63 (1st csDMARD failure) to 81% (≥2 bDMARD failures) were ACPA/RF+, 29 to 70% had erosions, 33 to 52% DAS28 > 5.1, and 41 to 66% had FFbH < 70, respectively. In the NDB, between 47 (DMARD-naïve) and 82% (≥2 previous DMARDs) were ACPA/RF+, 5 to 11%, had high disease activity under treatment (DAS28 > 5.1), and 26 to 50% had functional disability (FFbH < 70), respectively. CONCLUSION: With growing numbers of previous DMARD therapies, increasing proportions of patients have poor prognostic factors. This underlines the importance of these factors for a difficult-to-treat disease course.

[Medical treatment of rheumatoid arthritis in 2014 : Current data from the German Collaborative Arthritis Centers]. / Versorgung der rheumatoiden Arthritis 2014 : Aktuelle Daten aus der Kerndokumentation.

BACKGROUND: Since the introduction of biologic treatment in rheumatoid arthritis (RA), disease activity and treatment modalities have changed substantially. The current provision and developments in recent years are analyzed with annual data from the National Database of the Collaborative Arthritis Centers in Germany. METHODS: To analyze disease activity, diagnostics and treatment in RA patients in 2014 with regard to seropositivity and disease duration. Time trends from 2007-2014 are reported for disease activity (DAS28) distribution and biologic treatment. RESULTS: In 2014, a total of 8,084 RA patients were analyzed: 72 % were rheumatoid factor and/or ACPA positive, the mean age was 62 years and the mean disease duration 12 years. According to DAS28, 35.9 % were in remission, 19.2 % had low, 37.1 % moderate and 7.8 % high disease activity. An increase since 2007 was only observed in patients with a disease duration >2 years. Synthetic DMARDS were used for treatment in 78 %. Biologic treatment increased from 16 % (2007) to 27 % (2014). Especially those patients with a disease duration >5 years were treated more frequently with biologics. Seronegative patients had slightly less severe mean disease activity parameters. They were treated equally frequent with DMARDS but only half as often with biologics compared to seropositive patients. CONCLUSION: The use of biologics in RA patients has increased since 2007; however this was not observed in patients with short disease duration. Early intensive treatment adaption seems justified to improve disease activity in the large portion of patients who do not reach low disease activity under conventional DMARDs.

Quantification of periarticular demineralization and synovialitis of the hand in rheumatoid arthritis patients.

UNLABELLED: The bone mineral density (BMD) measurement of the hand in rheumatoid arthritis (RA) patients is no standard measurement method as yet. The aim was to contribute to the standardization of the hand BMD measurement, especially of periarticular regions. As results, we found best precision values for the wrist and a significant correlation between hand and spine/femur BMD depending on disease activity and disease duration. INTRODUCTION: This study was conducted to investigate (i) the precision of periarticular hand BMD measuring, (ii) the periarticular demineralization of the hand, (iii) the correlation between periarticular hand BMD and spine/femur BMD, and (iv) the correlation of hand BMD to hand synovitis. METHODS: A number of 52 RA patients were examined by BMD measurement of the femoral neck, spine, whole hand, metacarpophalangeal (MCP) joints II-V, personal identity profile (PIP) joints II-V, and wrist using dual-energy X-ray absorptiometry (DXA). Synovitis of the hand was examined by ultrasonography and magnetic resonance imaging (MRI). Three subgroups were further analyzed: early RA, established RA with moderate and with high disease activity. Early RA and established RA patients with high disease activity were Followed up after 12 months. RESULTS: We found (1) best precision of BMD measurement for the wrist, (2) BMD in RA significantly reduced if compared to normal controls, (3) a highly significant positive correlation between hand and spine/femur BMD and the power of correlation to depend on disease activity and disease duration (high correlation in RA with moderate disease activity and early RA, very high correlation in RA with high disease activity), (4) a negative correlation between hand BMD and hand synovitis in RA with high disease activity, and (5) a significant reduction of synovitis but no change in hand BMD after 12 months, respectively. CONCLUSIONS: This study shows a highly significant correlation between hand BMD and spine/femur BMD in RA patients depending on disease activity and disease duration. We conclude to measure BMD at different sites including hands in order to quantify bone loss in RA patients most properly.

Outcome of children with oligoarticular juvenile idiopathic arthritis compared to polyarthritis on methotrexate- data of the German BIKER registry.

BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligoJIA) is the most commonly diagnosed category of chronic arthritis in children. Nevertheless, there are no evidence- based guidelines for its treatment, in particular for the use of methotrexate (MTX). The primary objective of this analysis is to evaluate the outcomes in patients with persistent oligoJIA compared to those with extended oligoJIA and rheumatoid factor (RF) negative polyarthritis treated with methotrexate. METHODS: Patients with persistent or extended oligoJIA or RF negative PA recorded in the Biologics in Pediatric Rheumatology Registry (BiKeR), receiving methotrexate for the first time were included in the analyses. Efficacy was determined using the Juvenile Arthritis Disease Activity Score 10 (JADAS 10). Safety assessment included the documentation of adverse and serious adverse events. RESULTS: From 2005 through 2011, 1056 patients were included: 370 patients with persistent oligoJIA, 221 patients with extended oligoJIA and 467 patients with RF negative PA. Therapeutic efficacy was observed following the start of methotrexate. Over a period of 24 months JADAS-minimal disease activity (JADAS ≤2) was reached in 44% of patients with persistent oligoJIA, 38% with extended oligoJIA, 46% with RF negative PA, JADAS-remission defined as JADAS ≤1 was reached in 33% of patients with persistent oligoJIA, 29% with extended oligoJIA and 35% (RF negative PA). Patients with extended oligoJIA achieved JADAS remission significantly later and received additional biologic disease-modifying drugs significantly more often than patients with persistent oligoJIA or RF negative PA (p < 0.001). Tolerability was comparable. New onset uveitis occurred in 0.3 to 2.2 per 100 patient years. CONCLUSIONS: Patients with persistent oligoJIA taking methotrexate are at least as likely to enter remission as patients with extended oligo JIA or polyarticular JIA. Patients with extended oligoJIA achieved JADAS remission significantly later. Within 2 years, almost half of the patients with persistent oligoJIA achieved JADAS-minimal disease activity.

[How closely does rheumatology treatment follow the guidelines?: ambition and reality]. / Wie leitliniengerecht ist die rheumatologische Versorgung? : Anspruch und Wirklichkeit.

In 2005, the first evidence-based German guideline on the management of early rheumatoid arthritis (RA) was published. With data from the national database of the German Collaborative Arthritis Centres and other health care studies we evaluated to what extent current health care is in accordance with the guideline's recommendations.A total of 66% of all newly referred RA patients seen at the national database centers in 2008 achieved the goal of seeing a rheumatologist within 3 months of symptom onset, while 75% were seen within 6 months. Before referral, 25% of the patients had DMARD therapy and 19% glucocorticoids. Of the patients in rheumatological care, 90% received DMARDs. The availability of early arthritis clinics determines the promptness of access to a rheumatologist.After 6 years of rheumatological care, around 80% of patients continuously seen were still under treatment with a conventional or biological DMARD. The highest continuation rates were seen for methotrexate monotherapy. Biologic agents were given in 2008 to 20% of patients. Of those with "severe" or "very severe" disease, 42% received biologics and 21% DMARD combination therapy. Low-dose glucocorticoids are the standard of care; of patients in rheumatological care, 88% received dosages up to 7.5 mg/d and 74% of up to 5 mg/d.

Use of vasoactive/vasodilating drugs for systemic sclerosis (SSc)-related digital ulcers (DUs) in expert tertiary centres: results from the analysis of the observational real-life DeSScipher study.

INTRODUCTION: DeSScipher is the first European multicentre study on management of systemic sclerosis (SSc), and its observational trial 1 (OT1) evaluated the efficacy of different drugs for digital ulcer (DU) prevention and healing. The aim of this study was to assess current use of vasoactive/vasodilating agents for SSc-related DU in the expert centres by analysing the baseline data of the DeSScipher OT1. METHOD: Baseline characteristics of patients enrolled in the OT1 and data regarding DU were analysed. RESULTS: The most commonly used drugs, in both patients with and without DU, were calcium channel blockers (CCBs) (71.6%), followed by intravenous iloprost (20.8%), endothelin receptor antagonists (ERAs) (20.4%) and phosphodiesterase 5 (PDE-5) inhibitors (16.5%). Of patients, 32.6% with DU and 12.8% without DU received two drugs (p < 0.001), while 11.5% with DU and 1.9% without DU were treated with a combination of three or more agents (p < 0.001). Sixty-five percent of the patients with recurrent DU were treated with bosentan and/or sildenafil. However, 64 out of 277 patients with current DU (23.1%) and 101 (23.6%) patients with recurrent DU were on CCBs alone. CONCLUSIONS: Our study shows that CCBs are still the most commonly used agents for DU management in SSc. The proportion of patients on combination therapy was low, even in patients with recurrent DU: almost one out of four patients with current and recurrent DU was on CCBs alone. Prospective analysis is planned to investigate the efficacy of different drugs/drug combinations on DU healing and prevention. Key Points • The analysis of DeSScipher, the first European multicentre study on management of SSc, has shown that the most commonly used vasoactive/vasodilating drugs for DU were CCBs, followed by intravenous Iloprost, ERAs and PDE-5 inhibitors. • More than half of the patients with recurrent DU received bosentan and/or sildenafil. • However, the proportion of patients on combination therapy of more than one vasoactive/vasodilating drug was low and almost one out of four patients with current and recurrent DU was on CCBs alone.

Dose-related patterns of glucocorticoid-induced side effects.

OBJECTIVE: To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice. METHODS: Data from 1066 patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5-7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months. RESULTS: The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (<5 mg/day). CONCLUSION: The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.

Classification, categorization and essential items for digital ulcer evaluation in systemic sclerosis: a DeSScipher/European Scleroderma Trials and Research group (EUSTAR) survey.

BACKGROUND: A consensus on digital ulcer (DU) definition in systemic sclerosis (SSc) has been recently reached (Suliman et al., J Scleroderma Relat Disord 2:115-20, 2017), while for their evaluation, classification and categorisation, it is still missing. The aims of this study were to identify a set of essential items for digital ulcer (DU) evaluation, to assess if the existing DU classification was useful and feasible in clinical practice and to investigate if the new categorisation was preferred to the simple distinction of DU in recurrent and not recurrent, in patients with systemic sclerosis (SSc). METHODS: DeSScipher is the largest European multicentre study on SSc. It consists of five observational trials (OTs), and one of them, OT1, is focused on DU management. The DeSScipher OT1 items on DU that reached ≥ 60% of completion rate were administered to EUSTAR (European Scleroderma Trials and Research group) centres via online survey. Questions about feasibility and usefulness of the existing DU classification (DU due to digital pitting scars, to loss of tissue, derived from calcinosis and gangrene) and newly proposed categorisation (episodic, recurrent and chronic) were also asked. RESULTS: A total of 84/148 (56.8%) EUSTAR centres completed the questionnaire. DeSScipher items scored by ≥ 70% of the participants as essential and feasible for DU evaluation were the number of DU defined as a loss of tissue (level of agreement 92%), recurrent DU (84%) and number of new DU (74%). For 65% of the centres, the proposed classification of DU was considered useful and feasible in clinical practice. Moreover, 80% of the centres preferred the categorisation of DU in episodic, recurrent and chronic to simple distinction in recurrent/not recurrent DU. CONCLUSIONS: For clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered the proposed classification and categorisation as useful and feasible. The set of items needs to be validated while further implementation of DU classification and categorisation is warranted. TRIAL REGISTRATION: Observational trial on DU (OT1) is one of the five trials of the DeSScipher project (ClinicalTrials.gov; OT1 Identifier: NCT01836263 , posted on April 19, 2013).

Prevalence and clinical associations of anti-Ku antibodies in patients with systemic sclerosis: a European EUSTAR-initiated multi-centre case-control study.

OBJECTIVES: To determine the prevalence of anti-Ku antibodies in 625 patients with systemic sclerosis (SSc) from six European rheumatological centres and to evaluate their clinical and serological characteristics. METHODS: Sera of 625 consecutive patients with either limited cutaneous or diffuse cutaneous SSc were tested for antibodies to Ku antigen together with other extractable nuclear antigens by counterimmunoelectrophoresis. A case-control design with calculation of bootstrap 95% confidence intervals derived from anti-Ku negative control patients was used to evaluate clinical associations of anti-Ku antibodies. Sera from anti-Ku positive patients with SSc and a control group were additionally tested by immunofluorescence on Hep-2 cell substrates and line immunoassay. RESULTS: Anti-Ku antibodies were found in the sera of 14/625 (2.2%) patients with SSc. Of 14 anti-Ku positive patients with SSc, 10 had no other anti-extractable nuclear antigen (ENA) antibodies detected by counterimmunoelectrophoresis. Using a case-control study design, anti-Ku antibodies were significantly associated with musculoskeletal manifestations such as clinical markers of myositis, arthritis and joint contractures. In addition, a significant negative correlation of anti-Ku antibodies was found with vascular manifestation such as fingertip ulcers and teleangiectasias. There was a striking absence of anti-centromere antibodies as well as anti- polymyositis (PM)/scleroderma (Scl) antibodies in patients that were anti-Ku positive. As expected, anti-Scl70 and punctate nucleolar immunofluorescence patterns were present only in single cases. CONCLUSION: This is the largest cohort to date focusing on the prevalence of anti-Ku antibodies in patients with SSc. The case-control approach was able to demonstrate a clinically distinct subset of anti-Ku positive patients with SSc with only relative clinical differences in skeletal features. However, the notable exceptions were signs of myositis. This shows the importance of anti-Ku antibody detection for the prediction of this specific clinical subset.

Immunological characterization of the early human fracture hematoma.

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma. The early human fracture hematoma is characterized by maturation of granulocytes and migration of monocytes/macrophages and hematopoietic stem cells. Both T helper cells and cytotoxic T cells proliferate within the fracture hematoma and/or migrate to the fracture site. Humoral immunity characteristics comprise high concentration of pro-inflammatory cytokines such as IL-6, IL-8, IFNγ and TNFα, but also elevated concentration of anti-inflammatory cytokines, e.g., IL-1 receptor antagonist and IL-10. Furthermore, we found that cells of the fracture hematoma represent a source for key chemokines. Even under the bioenergetically restricted conditions that exist in the initial fracture hematoma, immune cells are not only present, but also survive, mature, function and migrate. They secrete a cytokine/chemokine cocktail that contributes to the onset of regeneration. We hypothesize that this specific microenvironment of the initial fracture hematoma is among the crucial factors that determine fracture healing.

[Pulmonary arterial hypertension in patients with congenital heart disease: current issues and health care situation]. / Pulmonalarterielle Hypertonie bei angeborenen Herzfehlern: Problemstellung und Versorgungslage.

Defects of the heart and associated large vessels (CHD) are among the most frequent congenital anomalies. Owing to improved interdisciplinary management, about 90% of CHD patients reach adulthood. Up to 10% maintain or newly develop pulmonary arterial hypertension (PAH) over time, which impairs exercise tolerance and prognosis. Data on the health care situation of patients with PAH-CHD are limited. The ongoing Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA, ClinTrials.gov Identifier NCT01347216) prospectively documents adult patients with all forms of pulmonary hypertension, if treated with PAH drugs (mean follow-up 40 months). As of 16 November 2012, 8% of the 3642 patients in the database had PAH-CHD. Of the latter, 104 were documented in great detail in specific CHD report forms. These patients were on average 39 years old, men in 39%, had a mean 6-minute walk distance of 370 ± 102 meters, and were in NYHA functional class I/II in 39%, III in 59%, und IV in 3%. Mean quality of life on the 100-point visual analogue scale (EQ-5 D) was 51. PAH-CHD patients received monotherapy in 80%, combination therapy in 9%, and no PAH drugs in 11%. Only 20% were on oral anticoagulation (OAC). Mean 4-year survival in incident patients (PAH-CHD diagnosis after start of the registry in 2007) was 79%, compared with 72% in patients with idiopathic PAH (IPAH). According to these registry data, patients with PAH-CHD have impaired exercise capacity, and substantially reduced quality of life. They receive combination therapy or OAC, respectively, less frequently than IPAH patients, however, their survival rate is higher.

[Immunoglobulins in PID, SID and neurological autoimmune disease]. / Anwendung von Immunglobulinen bei primären und sekundären Immundefekten und neurologischen Autoimmunerkrankungen.

Human immunoglobulins (IG, mostly IgG) are used as replacement therapy in patients with inherited primary immunodeficiencies, and in patients with secondary immuno-deficiencies often observed in multiple myeloma or chronic lymphocytic leukemia. Ig are also approved as immunomodulatory therapy in neurological autoimmune diseases (NAID) such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). 16 different Ig preparations for intravenous and subcutaneous use are at the moment available in Germany. The SIGNS study (Assessment of immunoglobulins in a long-term non-interventional study) investigates the clinical use of these drugs under clinical practice conditions. In this non-interventional prospective open-label cohort study, 550 patients with new or maintenance Ig therapy are observed with respect to drug utilization, effectiveness, (i. e. number of infections in PID and SID, functionality in NAID), tolerability, quality of life and costs in approximately 50 sites throughout Germany (neurologists, pediatricians, oncologists, other) for at least two years. This largest study of its kind is expected to contribute to optimization of Ig therapy in the postmarketing setting.

[International, prospective register for the documentation of first-line and maintenance therapy in patients with pulmonary hypertension (CompERA-XL)]. / Internationales, prospektives Register zur Erfassung der Initial- und Dauertherapie von Patienten mit pulmonaler Hypertonie (CompERA-XL).

In view of the manifold options for mono- and combination therapy that have now emerged for patients with pulmonary (arterial) hypertension (PAH/PH), controlled clinical trials can only provide part of the information needed for optimal management. In order to gather adequate data on PAH/PH treatment in routine clinical care, the ongoing CompERA-XL register prospectively documents consecutive patients with newly initiated treatment of PAH/PAH since May 2007. The internet-based register fulfils high quality standards through several measures (minimum centre contribution of at least 10 patients per year, automated plausibility checks of data at entry, queries, monitoring with source data verification). It can be applied, among further purposes, for quality assurance: individual centers can confidentially compare their results with the combined outcome of other centers and the recommendations from guidelines. The register, currently active in 7 countries, presently follows up 785 patients with any kind of treatment for PH/PAH (now at 626 patient years). It is expected that the register contributes to optimization of specific drug therapy for PAH and PH.

[The National Database of the German Arthritis Centres--a 12 year balance]. / Die Kerndokumentation der Rheumazentren--Bilanz nach 12 Jahren.

The National Database of the German Collaborative Arthritis Centres is the most important source for the evaluation of current health care for German rheumatology patients. Since 1993, all outpatients with inflammatory rheumatic diseases treated in one of 24 arthritis centres have been recorded once a year using a clinical record form and a patient questionnaire. The aim is to gain knowledge on the outcomes and the medical, social and economic consequences of inflammatory rheumatic diseases in the real world, and to monitor continuously the current state and trends in health care. Data from more than 200,000 patients with inflammatory rheumatic diseases from 11 years (1993-2003) are available, making it possible to analyse even very rare diseases with a sufficient numbers of cases. Selected results on the health care situation, practice variation in rheumatology and the burden of illness in various diseases are reported.

Cost of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and systemic lupus erythematosus in Germany.

OBJECTIVE: To estimate and compare the direct and indirect costs of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE), and to evaluate the effect of sex, disease duration and functional status on the various cost domains. METHODS: Data of outpatients, aged 18-65, with rheumatoid arthritis (n = 4351), ankylosing spondylitis (n = 827), PsA (n = 908) or SLE (n = 844), who were enrolled in the national database of the German collaborative arthritis centres in 2002, were analysed. Data on healthcare consumption, out-of-pocket expenses and productivity losses were derived from doctors and patients. For the calculation of indirect costs, the human capital approach (HCA) and the friction cost approach (FCA) were applied. RESULTS: Mean direct costs amounted to 4737 euros a year in rheumatoid arthritis, 3676 euros in ankylosing spondylitis, 3156 euros in PsA and 3191 euros in SLE. By using the HCA, total costs were calculated at 15,637 euros in rheumatoid arthritis, 13,513 euros in ankylosing spondylitis, 11,075 euros in PsA and 14,411 euros in SLE, whereas with the FCA the numbers were 7899 euros, 7204 euros, 5570 euros and 6518 euros, respectively. Costs increased with disease duration and were strongly dependent on functional status. In patients with the highest disability (<50% of full function), the total costs on applying the HCA were 34,915 euros in rheumatoid arthritis, 29,647 euros in alkylosing spondylitis, 37,440 euros in PsA and 32,296 euros in SLE. CONCLUSION: The costs of illness are high in all four diseases, with a strong effect of functional status on total costs. Indirect costs differ by the factor 3, based on whether the HCA or the FCA is used.

New onset or exacerbation of psoriatic skin lesions in patients with definite rheumatoid arthritis receiving tumour necrosis factor alpha antagonists.

BACKGROUND: Blockage of tumour necrosis factor alpha (TNFalpha) is highly effective in rheumatic diseases, especially in rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis. Furthermore, TNFalpha antagonists have also been shown to significantly reduce psoriatic skin lesions. CASE REPORTS: A series of nine patients with RA who were treated with different types of TNFalpha antagonists and who unexpectedly developed either a new onset or an exacerbation of psoriatic skin lesions are reported.

Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1-independent expression pathway.

BACKGROUND: Membrane-bound glucocorticoid receptors (mGCR) are up regulated on monocytes after in vitro stimulation and in patients with rheumatoid arthritis. Caveolin-1 is critical for the transport of plasma membrane oestrogen receptors to the cell surface. OBJECTIVES: To investigate the expression of mGCR in patients with systemic lupus erythematosus (SLE)-a disease with different aetiopathogenesis and treatment regimens-and to examine whether caveolin-1 is critical for the transport of mGCR to the cell surface. METHODS: Frequencies of mGCR+ peripheral blood mononuclear cells were measured using high-sensitivity immunofluorescent staining and tested for correlation with SLE disease activity and glucocorticoid treatment. Semiquantitative polymerase chain reaction, immunofluorescence, recombinant expression and confocal laser-scanning microscopy were used to search for an association of mGCR with caveolin-1. RESULTS: The frequencies of mGCR+ monocytes (CD14+) were considerably higher in patients with SLE (n = 33) than in healthy controls (n = 58), whereas B cells (CD19+) were not different in this regard. T cells (CD3+) were always mGCR-. The frequency of mGCR+ monocytes in patients with SLE did not correlate with disease activity, but did inversely correlate with glucocorticoid dosages; this inverse correlation was confirmed by corresponding in vitro experiments with stimulated monocytes. The induced up regulation of mGCR was not accompanied by an up regulation of caveolin-1, and mGCR are not colocalised with caveolin-1 in plasma membrane caveolae. CONCLUSION: mGCR are (a) up regulated in patients with SLE and by inflammatory stimuli and (b) down regulated by glucocorticoids, suggesting a negative feedback loop to control glucocorticoid action. Drugs binding selectively to mGCR may in future prove to be of therapeutic value.

[Prescription of glucocorticoids by rheumatologists in patients with rheumatoid arthritis in Germany]. / Verordnung von Glucocorticoiden bei rheumatologisch betreuten Patienten mit rheumatoider Arthritis in Deutschland.

Systemic GCs are among the most important therapeutic options in modern rheumatology. Due to their fast clinical effects and their high anti-inflammatory potential, they are indispensable in a large number of cases. This applies despite the well-known spectrum of adverse events and despite limited evidence from randomized clinical trials. In this situation, the results of observational studies gain additional importance. They provide information on therapeutic decisions of rheumatologists concerning GC therapy and their combination with other drugs as well as concerning the prevention of adverse events such as GC induced osteoporosis. The data gathered in the national database of the German Collaborative Arthritis Centers show that at the time of documentation 60% of all RA patients were under therapy with GCs, 85% of these were treated with a dosage of up to 7.5 mg/d. GCs are especially frequently used in combination with new or highly potent DMARDs. This underlines that rheumatologists take activity and severity into account in deciding both about GCs and DMARDs. However, there is high practice variation regarding the frequency of GC use among the rheumatological facilities which demonstrates the lack of good evidence.Rheumatologists are aware of various patient risks when prescribing GCs and adapt their therapies to these risks. Two thirds of all patients under GCs were receiving therapy for the prevention or treatment of osteoporosis at documentation, high risk groups such as women over 50 even more frequently. The data emphasize the high importance of GCs in modern rheumatology.