Therapy satisfaction and health literacy are key factors to improve medication adherence in systemic sclerosis.

OBJECTIVE: Although medication adherence (MA) contributes to therapeutic outcome in systemic sclerosis (SSc), research data are scarce. Factors influencing MA in SSc are hardly known. METHOD: We conducted a monocentric, cross-sectional study on 85 patients with SSc at the University of Lübeck, Germany, using the Compliance Questionnaire of Rheumatology as the main measurement tool of MA. We also used the Scleroderma Health Assessment Questionnaire, Illness Perception Questionnaire - Revised, Health Literacy Questionnaire, Lübeck Medication Satisfaction Questionnaire (a novel instrument created for this study), and patients' demographic and clinical data, to find factors contributing to MA. RESULTS: Good MA was seen in 51.8% of patients. MA was positively associated with therapy satisfaction (p < 0.001), modified Rodnan Skin Score (p = 0.032), age (p = 0.025), intake of micronutrients (p = 0.033), number of prescribed drugs (p = 0.014), and some dimensions of health literacy. Negative associations were found for patients with weight loss attributed to SSc (p = 0.009) and the perception that the disease is caused by the patient's personality (p = 0.011) or emotional state (p = 0.037). CONCLUSION: Although most SSc patients display good MA, non-adherence remains a major problem. Patients should be assessed for non-adherence. The factors affecting MA identified herein could help to improve therapeutic outcomes.

[The unusual mimicker of a polymyositis]. / Der außergewöhnliche Nachahmer einer Polymyositis.

This article describes a hantavirus-associated pronounced myositis as a rare differential diagnosis to polymyositis. The literature on the pathogenesis of hantavirus disease discusses less a direct viral cytopathology but more a secondary immune dysregulation with induction of a capillary leak. This article describes for the first time a case of successful treatment of protracted hantavirus myositis using high-dose glucocorticoids and cyclophosphamide, followed by ciclosporin and MTX.

The first composite score predicting Digital Ulcers in systemic sclerosis patients using Clinical data, Imaging and Patient history-CIP-DUS.

BACKGROUND: Digital ulcers (DU) present a challenging complication in systemic sclerosis (SSc). The aim of this study was to combine clinical characteristics and imaging methods to a composite score for the prediction of DU in SSc patients. METHODS: Seventy-nine SSc patients received clinical examination, their patient history was taken and nailfold capillaroscopy (NC), colour Doppler ultrasonography (CDUS) and fluorescence optical imaging (FOI) of the hands were performed at baseline. Newly developed DU over a period of approximately 12 months were registered. We used criteria with area under the curve (AUC) of at least 0.6 in regard to the development of these new DU to create the score (CIP-DUS, clinical features, imaging, patient history-digital ulcer score). RESULTS: Twenty-nine percent of all SSc patients developed new DU during follow-up (48.1% diffuse, 18.4% limited SSc). Based on the cross-validated (cv) AUC, a weight (cvAUC > 0.6 and ≤ 0.65: 1; cvAUC > 0.65 and ≤ 0.7: 2; cvAUC > 0.7: 3) was assigned to each selected parameter. The performance of the final CIP-DUS was assessed with and without the CDUS/FOI component. For the scleroderma patterns in NC, three points were appointed to late, two to active and one point to early capillaroscopy pattern according to Cutolo et al. The CIP-DUS including the CDUS and FOI parameters resulted in a good diagnostic performance (AUC after cross-validation: 0.83, 95%CI 0.74 to 0.92) and was well calibrated (chi-square = 12.3, p = 0.58). The cut-off associated with the maximum of sensitivity and specificity was estimated at ≥ 10 points resulting in a sensitivity of 100% and specificity of 74% for new DU during follow-up. Excluding CDUS and FOI parameters leads to a non-statistically significant lower performance (AUC after cross-validation: 0.81, 95%CI 0.72 to 0.91). However, including CDUS and FOI resulted in a better classification of patients in respect to the outcome new DU in follow-up due to significantly better reclassification performance (NRI = 62.1, p = 0.001) and discrimination improvement (IDI = 9.7, p = 0.01). CONCLUSION: A new score was introduced with the aim to predict digital ulcers. If applied correctly and with the new imaging techniques proposed, all patients at risk of digital ulcers throughout 12 months could be identified.

ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis-a EUSTAR analysis.

OBJECTIVES: To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). METHODS: SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). RESULTS: Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06-4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65-3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29-3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32-2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC-mostly in daily dosages below 15 mg of prednisolone-did not influence the hazard for SRC. CONCLUSIONS: ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

[Reality of inpatient vasoactive treatment with prostacyclin derivatives in patients with acral circulation disorders due to systemic sclerosis in Germany]. / Versorgungsrealität der stationären vasoaktiven Therapie mit Prostazyklinderivaten bei Patienten mit akralen Durchblutungsstörungen bei systemischer Sklerose in Deutschland.

BACKGROUND: Raynaud's phenomenon and the frequently ensuing digital ulcerations represent an early and very distressing symptom in patients with systemic sclerosis (scleroderma, SSc) causing significant limitations in the ability to work and quality of life. The use of vasoactive drugs (especially intravenous prostacyclin derivatives) is recommended to reduce the risk of hypoxic tissue damage up to the loss of fingers. METHODS: In order to obtain information about the current state of treatment of patients with prostacyclin derivatives in routine clinical life in Germany, a survey was conducted among the centers affiliated to the German Network for Systemic Scleroderma (DNSS). In addition, a separate patient survey was conducted by the schleroderma self-help group (Sklerodermie Selbsthilfe e. V.), which only covered the symptoms Raynaud's syndrome, digital ulcers and the use of intravenous prostacyclin derivatives. RESULTS: Of the 433 patients surveyed 56% stated that they had already been treated with prostacyclin derivatives (iloprost/alprostadil) because of their illness and symptoms. A total of 61% received the treatment for severe Raynaud's phenomenon and 39% for digital ulcerations. Most respondents not only experienced an improvement in Raynaud's phenomenon and digital ulcers but also a significant improvement of limitations in everyday life. They also needed significantly less outside help and absenteeism from work was much lower. CONCLUSION: Patients consistently reported a positive effect of treatment with prostacyclin derivatives on Raynaud's phenomenon, acral ulcerations, pain and daily restrictions and felt well and safely cared for during inpatient treatment. These positive effects in the patients' perceptions provide crucial information supporting and confirming the current European and international treatment recommendations.

Evaluation of choroidal substructure perfusion in patients affected by systemic sclerosis: an optical coherence tomography angiography study.

Objective: Vasculopathy in systemic sclerosis (SSc) is characterized by the obliteration of arterioles and a reduced capillary density in various tissues. In SSc, atrophic alterations of the choroid have been suggested based on morphological data acquired by optical coherence tomography (OCT). In this study, we aimed to assess the choroid in eyes of patients with SSc from a microcirculatory, dynamic point of view by adding optical coherence tomography angiography (OCTA) to the diagnostic spectrum.Method: SSc patients were enrolled, and age- and gender-matched healthy subjects were used as controls. In addition to basic ophthalmological and rheumatological examinations, individuals underwent enhanced-depth imaging OCT and OCTA. Subfoveal thicknesses of the choroid as well as all three choroidal vascular sublayers were measured and submacular perfusion values were evaluated.Results: In total, 12 patients with SSc and 12 matched controls were included. The median age of participants was 64 years. Submacular perfusion was significantly lower in the choriocapillaris (Δ = 0.72%; p = 0.045), Sattler's layer (Δ = 2.87%; p = 0.001), and Haller's layer (Δ = 2.69%; p = 0.018) of SSc patients compared to controls. Subfoveal thicknesses of Sattler's layer (Δ = 15 µm; p = 0.026) and Haller's layer (Δ = 41 µm; p = 0.045) were also significantly smaller in the SSc group.Conclusion: Choroidal microcirculation is impaired in SSc, even in patients without ophthalmological symptoms. Choroidal OCT and OCTA may offer additional biomarkers for SSc activity.

Large Variability of Frequency and Type of Physical Therapy in Patients in the German Network for Systemic Sclerosis.

OBJECTIVE: To determine the type and frequency of physical therapy (PT) prescribed by physicians for patients in the registry of the German Network for Systemic Sclerosis. METHODS: The data for 4,252 patients were analyzed using descriptive statistics, chi-square tests, and odds ratios (ORs). RESULTS: Overall, 37.4% of patients (1,590 of 4,252) received PT at the end of a yearly follow-up. The most frequently used type of PT was lymphatic drainage (n = 1,061, 36.8%), followed by exercise therapy (n = 1,047, 36.3%) and heat therapy (n = 689, 23.9%). More than three-fourths of treated patients (82%) received 1 or 2 different forms of PT simultaneously. The prescription of PT was associated with the extent of skin fibrosis as measured by the modified Rodnan skin thickness score (<10 [41.8% of patients], 11-20 [55.8% of patients], and >21 [63.9% of patients]; P < 0.001). Patients with musculoskeletal involvement (e.g., arthritis, muscle weakness, joint contractures, tendon friction rubs) had a higher chance of receiving PT than patients without these symptoms, with corresponding ORs ranging from 1.96 (95% confidence interval [95% CI] 1.69-2.28) for joint contractures to 3.83 (95% CI 2.89-5.08) for arthritis. When comparing the type of PT prescription across the initial and all follow-up visits from 2003 to 2017, significant alterations with a decreasing frequency of patients receiving PT could be observed (P = 0.001). CONCLUSION: To our knowledge, this is the first study reporting the use of PT in patients with systemic sclerosis (SSc) in a large cohort. Although SSc is characterized by considerable disability and restriction of motion, <40% of patients received PT.

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.

Association between baseline clinical and imaging findings and the development of digital ulcers in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) can lead to ischemic complications such as digital ulcers (DUs). The aim of the study was to find predictors of DUs by clinical and new imaging methods. PATIENTS AND METHODS: All 79 SSc patients included in the study received a clinical, colour Doppler ultrasound (CDUS), fluorescence optical imaging (FOI) and capillaroscopy examination at baseline, and their capacity to predict new DU development was analysed in 76 patients at 12 months follow-up. RESULTS: Twenty-two of 76 patients (28.9%) developed new ulcers during follow-up (diffuse SSc 48.1%; limited SSc 18.4%). Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 0.7576 for DU development, with a specificity of 87% and a sensitivity of 54.6% (p = 0.0003, OR = 8.1 [95%CI 2.5-25.6]) at a cut-off of ≥ 21 points (ACR/EULAR classification criteria for SSc). Capillaroscopy and CDUS had high sensitivity (100% and 95.5%) but low specificity (28.9% and 22.2%) for ulcer occurrence when used alone, but better specificity (46.3%) when combined (OR = 18.1 [95%CI 2.3-144.4]; p = 0.0004). Using FOI, fingers with pathologic staining had a higher risk for new ulcer development in the same finger (p = 0.0153). General future DU (i.e. DU also in other fingers) was associated with a missing FOI signal in the right digit III at baseline (p = 0.048). CONCLUSION: New imaging modalities can predict digital ulcer development in SSc patients with high sensitivity for capillaroscopy and CDUS and enhanced specificity when combined. A missing signal of FOI in the right digit III at baseline was associated with general future DU.

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).

Differences associated with age at onset in early systemic sclerosis patients: a report from the EULAR Scleroderma Trials and Research Group (EUSTAR) database.

OBJECTIVE: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years' duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets. METHOD: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud's SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud's phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31-59, and ≥ 60 years. We performed descriptive and bivariate analyses. RESULTS: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud's. CONCLUSION: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice.

[Mimetics of systemic sclerosis]. / Imitatoren der systemischen Sklerose.

BACKGROUND: Systemic sclerosis (SSc) is characterized by heterogeneous clinical symptoms. Peripheral skin fibrosis can be a common symptom. Nevertheless, a variety of diseases with different etiologies are associated with a thickening of the skin and make the initial diagnosis of systemic sclerosis more difficult. OBJECTIVE: The different disease entities that can lead to dermal fibrosis should be differentiated. An earlier diagnosis of SSc would therefore be facilitated. METHODS: A literature search was carried out for clinical pictures that can be associated with skin fibrosis. The clinical picture, the etiology and the treatment of the individual diseases are described. RESULTS: Diseases that can mimic the cutaneous symptoms of SSc include morphea, scleroderma, diabetic cheirarthritis, scleromyxedema, nephrogenic systemic fibrosis and eosinophilic fasciitis. The characteristic pronounced skin involvement, an accompanying Raynaud's phenomenon, capillary microscopy, histopathology and antinuclear antibodies help to enable a differentiation of SSc from its mimics. CONCLUSION: An early differential diagnostic distinction between SSc and other sclerosing diseases is important due to SSc-associated and potentially life-threatening systemic organ involvement. If a diagnosis of SSc has been made, a critical and organ-specific evaluation with respect to pulmonary, gastrointestinal, renal and cardiac involvement is mandatory and should be repeated at regular intervals.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

Interstitial lung disease increases mortality in systemic sclerosis patients with pulmonary arterial hypertension without affecting hemodynamics and exercise capacity.

Published data suggest that coexisting interstitial lung disease (ILD) has an impact on mortality in patients with systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), but there is scarce knowledge if this is reflected by hemodynamics, exercise capacity, autoantibody profile, or pulmonary function. In this partially retrospective study, 27 SSc-PAH patients were compared to 24 SSc-PAH patients with coexisting ILD respecting to survival, pulmonary function, hemodynamics, exercise capacity, and laboratory parameters. Survival was significantly worse in SSc-PAH-ILD patients than in SSc patients with isolated PAH (1, 5, and 10-year survival rates 86, 54, and 54% versus 96, 92, and 82%, p = 0.013). Compared to isolated SSc-PAH patients, patients with SSc-PAH-ILD revealed lower forced expiratory volume after 1 s (FEV1) values at the time of PAH diagnosis as well as 1 and 2 years later (p = 0.002) without significant decrease in the PAH course in both groups. At PAH diagnosis, diffusion capacity for carbon monoxide (DLCO) values were lower in the ILD-PAH group. Coexisting ILD was not associated with lower exercise capacity, different FEV1/forced vital capacity (FVC) ratio, higher WHO functional class, or reduced hemodynamics. Higher levels of antibodies against angiotensin and endothelin receptors predict mortality in all SSc-PAH patients but could not differentiate between PAH patients with and without ILD. Our study confirmed an impact of ILD on mortality in SSc-PAH patients. Pulmonary function parameters can be used to distinguish PAH from PAH-ILD. The higher mortality rate cannot be explained by differences in hemodynamics, exercise capacity, or autoantibody levels. Mechanisms of mortality remain to be studied.

[De-escalation of therapy in ANCA-associated vasculitides]. / Therapiedeeskalation bei ANCA-assoziierten Vaskulitiden.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) require a differentiated therapeutic approach depending on the degree of organ dysfunction and disease activity. In organ dysfunction and life-threatening AAV cyclophosphamide and rituximab are recommended for the induction of remission. For remission induction with a lack of organ dysfunction and non-life-threatening AAV, methotrexate or mycophenolate mofetil are recommended. For remission maintenance therapy azathioprine or methotrexate are used. In the case of contraindications, intolerance or previous failure of azathioprine and methotrexate treatment, rituximab, leflunomide or mycophenolate mofetil may be used as alternatives. Maintenance therapy is usually continued for at least 2 years. De-escalation of therapy requires continuous clinical monitoring while the glucocorticoid medication and immunosuppressive therapy is tapered; however, every de-escalation of therapy carries a risk of relapse.

[Digital ulcers in systemic sclerosis : A retrospective heath service study analysing treatment with bosentan and other vasoactive therapies]. / Digitale Ulzerationen bei systemischer Sklerose : Eine Versorgungsforschungsstudie über den Einsatz von Bosentan und anderen vasoaktiven Therapien.

BACKGROUND: Digital ulcers (DU) affect up to 60 % of patients with systemic sclerosis (SSc) and have a considerable impact on quality of life and morbidity. It is unclear to what extent authorised medicines are used, and if therapy guidelines are implemented in everyday practice. METHOD: This retrospective health care study examined current standards of treatment for therapy and prevention of SSc-associated DU in an online survey with 83 physicians. Additionally, data from 161 case studies of SSc patients with DU were analysed, and the effect of DU treatment on the course of the disease determined. RESULTS: For treatment and prevention of active DU, physicians predominantly indicated topical therapies, calcium channel blockers, iloprost and endothelin receptor antagonists. According to the case studies, 90 % of episodes with acute DU were treated with bosentan and iloprost in mono- or combination therapy. Preventive treatment was only administered during 50 % of episodes without DU, even after three or more phases with active DU. For the prevention of new DU, bosentan was used in mono- or combination therapy in 57 % of episodes without DU. Bosentan therapy during prevention shortened the following acute phase by 32 %. Additionally, continuous treatment with bosentan in acute and prevention phases reduced the duration of the following acute phase and increased the time to onset of new DU by 16 %. Moreover, bosentan stabilised the number of new DU. CONCLUSION: In summary, these data confirm the efficacy of bosentan in preventing new DU when used in DU-free episodes and possibly also in phases of acute DU. Therapy recommendations for the treatment of DU are currently not fully implemented. In the future, even more attention should be paid to DU therapy.

[Risk stratification and follow-up assessment of patients with pulmonary arterial hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Risikostratifizierung und Verlaufskontrollen bei PAH-Patienten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to risk stratification and follow-up assessment of patients with PAH. This manuscript summarizes the results and recommendations of this working group.

[Rheumatology - Integration into student training (RISA) : Current structure of clinical rheumatology in German universities (RISA III)]. / Rheumatologie - Integration in die studentische Ausbildung (RISA) : Zur aktuellen Struktur der internistischen Rheumatologie an deutschen Hochschulen (RISA III).

The German Society of Rheumatology and the Committee for Student Training investigated what effects the structures in university medicine have on student teaching. In February 2014 a questionnaire was sent to the teaching staff and Deans of each of the 37 medical faculties. Of the locations seven were classified as being independent rheumatological university hospitals and nine universities had a W2/W3/C3 grade professor as head of a department of clinical rheumatology but answerable to superiors. In the 37 faculties in Germany the proportion of lecture hours, the proportion of obligatory lecture hours, the number of hours for practical exercises and the number of hours for bedside teaching were distributed very differently and as a rule higher in universities with academic freedom. Not all medical faculties have obligatory teaching in the field of clinical rheumatology. On average medical students see five patients with rheumatological symptoms during their studies. In summary, over the past years it has not been possible to successfully utilize the great importance of rheumatology for society and the innovation potential of this discipline in order to improve the integration of clinical rheumatology into universities.