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Introduction: 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). Methods: 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. Results: Severe 25-OH D ³ 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 %). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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.

Background: Multimodal rheumatologic complex treatment (MRCT, operation and procedures classification system, OPS code 8‑983) is a specific concept of acute inpatient care (DRG I97Z) for treatment of patients with rheumatic diseases, degenerative diseases and/or chronic pain syndromes suffering from exacerbated pain and functional impairment., Objective: A monocentric retrospective analysis of the effects of MRCT on pain and functional status in patients with rheumatoid arthritis (RA) was conducted., Methods: A total of 103 treatment episodes in 75 patients with proven RA who received MRCT between 2014 and 2017 were included in the analysis. The changes in pain intensity were evaluated using a numerical rating scale (NRS), the functional limitations as assessed by the Hanover function questionnaire (FFbH) and the health assessment questionnaire (HAQ) and the disease activity (disease activity score of 28 joints, DAS28) before and after MRCT episodes. In addition, the patient characteristics and the course of the disease were documented and a univariate analysis of the influence of these factors on the parameters activity and function was performed., Results: In patients with RA, the MRCT resulted in a significant amelioration of pain (p < 0.0001), a significant improvement of functional capacity (FFbH p = 0.0013, HAQ p = 0.1396) and a significant reduction of disease activity (DAS28 p < 0.0001). Different aspects of the disease and its previous course (e. g. disease duration, type and number of previous anti-rheumatic drugs, current medication) did not have a significant effect on the response., Conclusion: This retrospective monocentric analysis proved the efficacy of MRCT with respect to the inpatient treatment period in a large cohort of RA patients. This treatment concept not only improved pain and function (FFbH) but also significantly reduced the disease activity.

Whipple's disease (WD) is a rare, chronic multiorgan disease which can caused by Tropheryma whipplei, a ubiquitous gram positive bacterium. Detection of T. whipplei is mostly performed histologically using periodic acid-Schiff (PAS) staining in affected tissues to visualize characteristic PAS-positive macrophages and by the polymerase chain reaction (PCR). Clinically, WD is often characterized by gastrointestinal symptoms (diarrhea, colic-like abdominal pain and weight loss). Arthritis is a common presentation of WS, often leading to a misdiagnosis of seronegative rheumatoid arthritis and as a consequence to immunosuppressive therapy. The clinical presentation of WD is highly polymorphic affecting different organ systems (e. g. cardiac or neurological manifestation) and making an appropriate clinical diagnosis and even the diagnostic process itself difficult. This article reports on three cases presenting with completely different leading symptoms (initially misdiagnosed as seronegative rheumatoid arthritis, spondyloarthritis and adult onset of Still's disease, respectively) that illustrate the rich diversity of WD. The cases were chosen to draw attention to the fact that although WD is mainly associated with the field of gastroenterology and gastrointestinal (GI) involvement is common, it may appear without GI symptoms. In cases of a clinical suspicion of WD, diagnostic efforts should be made to detect the bacterium in the affected organ. The German S2k guidelines on GI infections and WD published in January 2015 summarized the current state of the art for WD. The currently recommended primary treatment is antibiotics that can infiltrate the cerebrospinal fluid, e. g. ceftriaxone, followed by cotrimoxazole, which should be maintained over several months.

Modern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.

The term modern disease-modifying antirheumatic drugs (DMARD) includes not only the constantly growing family of DMARDs for chronic inflammatory rheumatic diseases but also the repositioning of established drugs in updated and novel algorithms of the different entities. The usual precursor for these developments is rheumatoid arthritis for which completely revised and updated guidelines have been published not only in Germany but also on the European level. In addition, label extensions to existing drugs have been granted for connective tissue diseases and vasculitides, e.g. anti-CD20 antibodies for antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides and belimumab for systemic lupus erythematosus. Moreover, several novel drugs, especially of the biologics class, have been either introduced in clinical rheumatology or are close to being licensed and include ustekinumab for psoriatic arthritis, granulocyte growth inhibitors and janus kinase inhibitors for rheumatoid arthritis and atacicept for systemic lupus erythematosus. With the termination of the patent for several biologics, a new momentum also took place: the approval of the so-called biosimilars which has already initiated intensive discussions not only with respect to "similar" effects and side effects but also with respect to their potential impact on economical aspects.

Introduction: Peripheral arthritis is the most common presenting complaint in clinical rheumatology. Unequivocal identification of the underlying entity can be difficult, particularly at an early stage. Such cases are commonly referred to as undifferentiated peripheral inflammatory arthritis (UPIA). Since evidence-based recommendations for the clinical management of UPIA are lacking, this international 3e initiative convened 697 rheumatologists from 17 countries to develop appropriate recommendations., Methods: Based on a systematic literature research in Medline, EMBASE, Cochrane Library, and the ACR/EULAR abstracts of 2007/2008, 10 multinational recommendations were developed by 3 rounds of a Delphi process. In Germany, a national group of experts worked on 3 additional recommendations using the same method. The recommendations were discussed among the members of the 3e initiative and the degree of consensus was analyzed as well as the potential impact of the recommendations on clinical practice., Results: A total of 39,756 references were identified, of which 250 were systematically reviewed for the development of 10 multinational recommendations concerning differential diagnosis, diagnostic and prognostic value of clinical assessments, laboratory tests and imaging techniques, and monitoring of UPIA. In addition, 3 national recommendations on the diagnostic and prognostic value of a response to anti-inflammatory therapy on the analysis of synovial fluid and on enthesitis were developed by the German experts based on 35 out of 5542 references., Conclusions: The article translates the 2011 published original paper of the international 3e initiative (Machado et al., Ann Rheum Dis 70:15-24, 2011) and reports the methods and results of the national vote and the additional 3 national recommendations.

Surgical synovectomy is a useful therapeutic option for rheumatoid arthritis patients with ongoing active synovitis despite optimal medical therapy. The present experimental study evaluated the novel, minimally invasive surgical technique of hydro-jet cutting in vitro using synovial biopsies. Depending on the selected water pressure (30-100 bar) it is possible to achieve precise and selective dissection of the synovial membrane. It was found that application of a water jet at 60 bar for 15 s is ideal for dissecting the stratum synoviale from the stratum fibrosum without any alteration of the joint capsule. This finding was confirmed by histological analyses. This novel and precise dissection technique promises to be an excellent alternative to the established techniques of synovectomy in the near future.

Objective: To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc)., Methods: A list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores., Results: Physicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting., Conclusion: The three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.

Over the course of the last decade, biologic response modifiers (biologics) have significantly broadened the therapeutic armamentarium in clinical rheumatology. In addition to their impressive efficacy, they have also received considerable attention regarding their adverse effects. In contrast to the risk of severe infections and malignancies, the cardiovascular risk of these drugs has provoked less vigilance. This article reviews the current data on the cardiovascular effects and adverse effects of biologics.

Rheumatic disease can affect and severely damage vital organs and thus cause acute emergencies and life-threatening complications. As systemic diseases they can cause any presenting complaint commonly encountered in emergency medicine. Because of their relative rarity in general practice, a high level of vigilance is required in order to recognize an emergency caused by an underlying rheumatic disease in individual cases. The most important rheumatological emergencies comprise septic arthritis, gout, atlantoaxial subluxation, renal crisis and digital ulcers in systemic sclerosis, amaurosis fugax in giant cell arteritis, the catastrophic anti-phospholipid antibody syndrome and the pulmonary-renal syndrome. This article provides an overview over these rheumatological emergencies in order to aid recognition of these entities in individual cases and to thus facilitate immediate and adequate treatment, which is of vital importance for affected patients., (Georg Thieme Verlag KG Stuttgart, New York.)

The clinical success of B-cell depletion using the anti-CD20 antibody rituximab has sparked a new era in the therapy of rheumatic diseases. A large variety of novel B-cell directed biologic agents has been developed recently. The new strategies not only aim at depleting B-cells (ocrelizumab, veltuzumab, ofatumumab, TRU-015) but also target essential survival and proliferation factors such as BAFF (belimumab, atacicept, briobacept), and are directed at modulating B-cell function via CD22 (epratuzumab), inhibition of costimulation (abatacept) and induction of tolerance (abetimus). Thus far, clinical trials indicate high efficacy comparable to rituximab as well as a good safety profile. This review summarizes the therapeutic mechanisms of the novel B-cell directed agents and the current status of clinical trials in rheumatic diseases.