The Joint Vasculitis Registry in German-speaking countries (GeVas): subgroup analysis of 266 AAV-patients.

OBJECTIVES: Prospective long-term observational data on the disease course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were missing in Germany to date. Therefore, the Joint Vasculitis Registry in German-speaking countries (GeVas) has been established to follow the course of patients with AAV. The aim of this study is to present baseline data of patients with newly diagnosed and relapsing AAV enrolled in the GeVas registry. METHODS: GeVas is a prospective, web-based, multicentre, clinician-driven registry for the documentation of organ manifestations, damage, long-term outcomes, and therapy regimens in various types of vasculitis. Recruitment started in June 2019. RESULTS: Between June 2019 and October 2022, 266 patients with AAV were included in the GeVas registry, hereof 173 (65%) with new-onset and 93 (35%) with relapsing AAV. One hundred and sixty-two (61%) patients were classified as granulomatosis with polyangiitis (GPA), 66 (25%) as microscopic polyangiitis (MPA), 36 (13%) as eosinophilic granulomatosis with polyangiitis (EGPA), and 2 (1%) as renal limited AAV. The median age was 59 years (51-70 years, IQR), 130 (51%) patients were female. Most patients were ANCA positive (177; 67%) and affected by general symptoms, pulmonary, ear nose throat (ENT), renal and neurological involvement. For induction of remission, the majority of patients received glucocorticoids (247, 93%) in combination with either rituximab (118, 45%) or cyclophosphamide (112, 42%). CONCLUSIONS: Demographic characteristics are comparable to those in other European countries. Differences were found regarding ANCA status, frequencies of organ manifestations, and therapeutic regimens. The GeVas registry will allow longitudinal observations and prospective outcome measures in AAV.

[Fever in rheumatological diseases]. / Fieber bei rheumatologischen Erkrankungen.

Fever is a frequent and important symptom in patients with rheumatological diseases and can be an expression of activity of the underlying rheumatological disease. There is great variability in the incidence of fever as a symptom of the disease between individual diseases. The growing understanding of the molecular signatures of the diseases can help to explain these discrepancies: A genetic overactivation of potently pyrogenic cytokines is the reason why fever is nearly always present in autoinflammatory syndromes. In contrast, fever is less common in polyarthritis and myositis and mostly limited to severe courses of disease. In the diagnostic work-up of fever, frequent differential diagnoses, such as infections, malignancies, side effects of drugs and hypersensitivity reactions should be considered. This article provides an overview of the physiology of the development of fever, describes the relevance of fever in individual rheumatological diseases and proposes a workflow for the clinical clarification of rheumatological patients who present with fever.

[Hemophagocytic lymphohistiocytosis and macrophage activation syndrome : A multidisciplinary challenge]. / Hämophagozytische Lymphohistiozytose und Makrophagenaktivierungssyndrom : Eine multidisziplinäre Herausforderung.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that is characterized by hyperferritinemia, cytopenia, disseminated intravascular coagulopathy and functional disorders of the liver and the central nervous system. The term macrophage activation syndrome is predominantly used for secondary HLH in the context of autoimmune diseases (e.g., systemic juvenile idiopathic arthritis). In addition, malignancies and genetic inborn errors of immunity can predispose to the development of HLH. Infections (e.g., Epstein-Barr virus) in turn represent possible triggers of an acute episode. Due to the unspecific manifestation of the disease, a systematic evaluation of the organ systems is recommended in the clinical and laboratory analytical clarification of hyperinflammatory syndromes. In general, the treatment should be carried out by a multidisciplinary team with expertise in rheumatology, hematological oncology, infectious diseases and intensive care medicine. The primary treatment of HLH usually consists of glucocorticoids and in cases of a rapid deterioration of the condition anakinra (interleukin 1 block) and intravenous immunoglobulins can be employed. Treatment of the underlying disease should be consequently carried out in parallel, together with antimicrobial treatment.

The value of non-enhanced MRI in the evaluation of patients with suspected idiopathic inflammatory myopathy.

INTRODUCTION/AIMS: The performance of magnetic resonance imaging (MRI) for diagnosing suspected idiopathic inflammatory myopathy (IIM) remains controversial. Furthermore, the role of contrast-enhanced magnetic resonance imaging (CE-MRI) sequences is unclear. The aim of this study was to evaluate the sensitivity and specificity of a non-enhanced magnetic resonance imaging (NE-MRI) protocol compared to a CE-MRI protocol in adult patients with confirmed IIM. METHODS: This study retrospectively enrolled patients with suspected IIM who underwent MRI of the upper thigh between 2008 and 2020. The protocol consisted of a T1-weighted (T1w) sequence, a turbo inversion recovery magnitude (TIRM) sequence and a contrast-enhanced T1-weighted sequence (CE-T1w). After randomly stratifying patients into a group with only the T1w and TIRM sequences available and another group with additional availability of CE-T1w, three blinded readers assessed the presence of IIM based on characteristic imaging features. Confirmation of the diagnosis was determined based on the 2017 ACR/EULAR criteria. RESULTS: Of the 80 patients (mean age 49.0 ± 21.1 years; 42 female, 38 male) included, 54 (67.5%) had a positive diagnosis of IIM. Cumulated sensitivity and specificity for MRI to detect IIM was 87.1% and 83.3% in the NE-MRI group versus 87.0% and 63.0% in the CE-MRI group. The group differences for sensitivity and specificity were non-significant for each of the three readers, respectively (p ≥ .081). DISCUSSION: NE-MRI detects suspected IIM with high diagnostic accuracy and performs equivalently to CE-MRI. Therefore, it may be appropriate to omit the use of contrast agents in MRI scans performed for suspected IIM.

Diagnostic accuracy of a large language model in rheumatology: comparison of physician and ChatGPT-4.

Pre-clinical studies suggest that large language models (i.e., ChatGPT) could be used in the diagnostic process to distinguish inflammatory rheumatic (IRD) from other diseases. We therefore aimed to assess the diagnostic accuracy of ChatGPT-4 in comparison to rheumatologists. For the analysis, the data set of Gräf et al. (2022) was used. Previous patient assessments were analyzed using ChatGPT-4 and compared to rheumatologists' assessments. ChatGPT-4 listed the correct diagnosis comparable often to rheumatologists as the top diagnosis 35% vs 39% (p = 0.30); as well as among the top 3 diagnoses, 60% vs 55%, (p = 0.38). In IRD-positive cases, ChatGPT-4 provided the top diagnosis in 71% vs 62% in the rheumatologists' analysis. Correct diagnosis was among the top 3 in 86% (ChatGPT-4) vs 74% (rheumatologists). In non-IRD cases, ChatGPT-4 provided the correct top diagnosis in 15% vs 27% in the rheumatologists' analysis. Correct diagnosis was among the top 3 in non-IRD cases in 46% of the ChatGPT-4 group vs 45% in the rheumatologists group. If only the first suggestion for diagnosis was considered, ChatGPT-4 correctly classified 58% of cases as IRD compared to 56% of the rheumatologists (p = 0.52). ChatGPT-4 showed a slightly higher accuracy for the top 3 overall diagnoses compared to rheumatologist's assessment. ChatGPT-4 was able to provide the correct differential diagnosis in a relevant number of cases and achieved better sensitivity to detect IRDs than rheumatologist, at the cost of lower specificity. The pilot results highlight the potential of this new technology as a triage tool for the diagnosis of IRD.

Survey on the working, training, and research conditions of resident physicians in internistic and rheumatological continuing education-BEWUSST.

BACKGROUND: Data on the training and continuing education situation of residents in the field of internal medicine and rheumatology are not available for Germany. For this reason, the Commission for Education and Training of the German Society of Rheumatology (DGRh) initiated the BEWUSST survey on the working, training and research conditions of residents in rheumatology. METHODS: A total of 102 questions on the topics of working conditions in everyday professional life, continuing medical education and training, compatibility of career and family, compatibility of work and research, perspectives as a rheumatologist and practical activities were included in an online questionnaire. RESULTS: A total of 102 participants took part in the survey. Of the respondents 48.1% were satisfied with their professional situation, 40.2% of the participants were supervised by a specialist mentor and 54.9% were working as scientists during their work as a physician. A compatibility of family and career was possible for 34.7%. After completion of the residency 52.9% of the respondents aspired to a combined clinical and outpatient activity. CONCLUSION: Half of the trainee rheumatologists are satisfied with their professional activities, although mentoring of the assistants in training should be further improved. With respect to the desired combined clinical and outpatient activity, the existing options should be expanded or new professional fields of activity should be established, so that the specialty remains attractive for the upcoming generations.

Clinical presentation and genetic variants in patients with autoinflammatory diseases: results from the German GARROD registry.

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.

Daratumumab for autoimmune diseases: a systematic review.

OBJECTIVE: Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing reported data on the CD38-targeting antibody daratumumab as a new therapeutic approach in autoantibody-mediated autoimmune diseases. METHODS: A protocolised systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases (Medline and Embase) were searched for suitable studies. Usage of daratumumab in non-oncological or non-transplantation associated diseases with autoimmune pathophysiology was analysed including patient characteristics, therapeutic regimen, adverse events and patient outcome. RESULTS: 38 publications reporting the clinical course of 83 patients met the inclusion criteria. Daratumumab usage was reported in therapy-refractory cases (median of 5 different previous therapies) in 24 different autoimmune diseases. The median number of applications of daratumumab was 4, mainly via intravenous applications (87%). Concomitant treatment included glucocorticoids in 64% of patients, intravenous immunoglobulins (33%) and rituximab (17%). Remission or improvement of disease was reported in 81% of patients. Autoantibody depletion or reduction was stated in 52% of patients. Death occurred in three patients (3%). Adverse events were reported in 45% of patients including application-associated reaction (20%), infection (19%) and hypogammaglobulinaemia (33%). CONCLUSION: Targeting CD38 via daratumumab is a new promising therapeutic option in therapy refractory autoimmune diseases. Efficacy as well as optimal therapeutic regimen and management or prevention of adverse events require further investigation. Therefore, systematic clinical trials of this therapeutic approach are needed.

[Autoinflammatory syndromes]. / Autoinflammatorische Syndrome.

The concept of autoinflammation includes a heterogeneous group of monogenic and polygenic diseases. These are characterized by excessive activation of the innate immune system without antigen-specific T cells or autoantibodies. The diseases are characterized by periodic episodes of fever and increased inflammation parameters. Monogenic diseases include familial Mediterranean fever (FMF) and the newly described VEXAS (vacuoles, E1 enzyme, X­linked, autoinflammatory, somatic) syndrome. Heterogeneous diseases include adult-onset Still's disease and Schnitzler syndrome. Treatment is aimed at preventing the excessive inflammatory reaction in order to avoid long-term damage, such as amyloid A (AA) amyloidosis.

Systemic sclerosis and primary biliary cholangitis: Longitudinal data to determine the outcomes.

Background: Several studies described the cross-sectional characteristics of systemic sclerosis patients and coexisting primary biliary cholangitis, but longitudinal prognostic data are lacking. Aims: To describe the systemic sclerosis-primary biliary cholangitis phenotype, including baseline characteristics and outcomes. Methods: We performed a multicentre the European Scleroderma Trials and Research Group study of systemic sclerosis patients with primary biliary cholangitis or with primary biliary cholangitis-specific antibodies, matched with systemic sclerosis controls free from hepatobiliary involvement matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit. Results: A total of 261 patients were enrolled (115 primary biliary cholangitis-systemic sclerosis, 161 systemic sclerosis). At baseline, systemic sclerosis-primary biliary cholangitis patients had a higher prevalence of anti-centromere antibodies (p = 0.0023) and a lower prevalence of complete absence of digital ulcers. The milder vascular involvement was confirmed at follow-up when crucial differences emerged in the percentage of patients experiencing digital ulcers; a significantly higher number of patients who never experienced digital ulcers were observed among primary biliary cholangitis-systemic sclerosis patients (p = 0.0015). Moreover, a greater incidence of pulmonary arterial hypertension (p < 0.001) and of conduction blocks (p = 0.0256) was observed in systemic sclerosis patients without primary biliary cholangitis. Patients with primary biliary cholangitis had higher levels of liver enzymes at baseline than systemic sclerosis patients; a significant decrease in liver enzymes was observed at follow-up. Out of 18 patients with cholangitis, one received a liver transplant at follow-up. Conclusion: Our data show that systemic sclerosis-primary biliary cholangitis exhibit a mild systemic sclerosis and primary biliary cholangitis phenotype with outcomes being in general favourable.

VEXAS syndrome: a diagnostic puzzle.

The VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an adult-onset systemic autoinflammatory condition that is caused by an acquired deficiency of the UBA1 gene in hematopoietic progenitor cells. The clinical spectrum of the VEXAS syndrome currently comprises a broad range of phenotypes such as vasculitis, relapsing polychondritis and Sweet's syndrome. In the past, VEXAS patients have left clinicians puzzled and the true nature of this disease has not been captured until late 2020. This viewpoint describes the relevant clinical features of the VEXAS syndrome and reviews different approaches to establish the diagnosis. Finally, future directions within the field of systemic inflammatory diseases caused by somatic mutations are being discussed.

[Survey on the working, training, and research conditions of resident physicians in internistic and rheumatological continuing education-BEWUSST]. / Befragung zu den Arbeits-, Weiterbildungs- und Forschungsbedingungen von Assistenzärztinnen und -ärzten in der internistisch-rheumatologischen Weiterbildung ­ BEWUSST.

BACKGROUND: Data on the training and continuing education situation of residents in the field of internal medicine and rheumatology are not available for Germany. For this reason, the Commission for Education and Training of the German Society of Rheumatology (DGRh) initiated the BEWUSST survey on the working, training and research conditions of residents in rheumatology. METHODS: A total of 102 questions on the topics of working conditions in everyday professional life, continuing medical education and training, compatibility of career and family, compatibility of work and research, perspectives as a rheumatologist and practical activities were included in an online questionnaire. RESULTS: A total of 102 participants took part in the survey. Of the respondents 48.1% were satisfied with their professional situation, 40.2% of the participants were supervised by a specialist mentor and 54.9% were working as scientists during their work as a physician. A compatibility of family and career was possible for 34.7%. After completion of the residency 52.9% of the respondents aspired to a combined clinical and outpatient activity. CONCLUSION: Half of the trainee rheumatologists are satisfied with their professional activities, although mentoring of the assistants in training should be further improved. With respect to the desired combined clinical and outpatient activity, the existing options should be expanded or new professional fields of activity should be established, so that the specialty remains attractive for the upcoming generations.

'Status Quo' on Different Aspects of Gender Distribution in Rheumatology in Germany-Results from a Nationwide Online Survey among Physicians.

OBJECTIVES: Despite the increasing number of female medical students and fellows in Europe, women are still under-represented in higher academic careers and positions in medicine. The aim of this survey was to assess the 'status quo' on gender distribution among rheumatologists in Germany. METHODS: A web-based anonymous survey (21 questions with multiple answers and free text) using QuestionPro® was distributed among rheumatologists in Germany via newsletters, social media and personal contact, including questions regarding hierarchical positions and work characteristics. RESULTS: Among the total of 170 respondents (72% women, 28% men, 1% diverse), 48% were rheumatologists in training, 35% were trained rheumatologists and 7% were heads of rheumatology departments. Regarding the gender ratio at different hierarchical levels, 74% of respondents reported more men than women in leadership positions. Part-time work was possible in the departments of 86% of respondents, with more women working part-time (56%) compared to men (29%). Most respondents stated their impression that employees working part-time did not have the same career chances as full-time workers in their departments. In total, 66% agreed that activities to improve gender equity are necessary. The highest need was seen in reconciling work and family through, e.g., part-time models, flexible childcare options at work and a higher acceptance of part-time work in leadership positions. CONCLUSIONS: According to our results, a gender imbalance is prevalent among rheumatologists in Germany, with lower numbers of women evident at higher hierarchical levels. Traditional role assignments are still represented by a higher proportion of part-time work in women. The establishment of structural changes to achieve better gender equity is needed.

[Hughes-Stovin syndrome: a life-threatening manifestation of Behçet's syndrome]. / Hughes-Stovin-Syndrom: eine lebensbedrohliche Manifestation des Behçet-Syndroms.

Hughes-Stovin syndrome (HSS) is a systemic inflammatory condition of unknown origin that is considered to be part of the Behçet's syndrome (BS) spectrum. Recurrent venous thrombosis and superficial thrombophlebitis in combination with bilateral pulmonary artery aneurysms (PAA) represent the hallmark of HSS. The diagnostic evaluation includes computed tomography pulmonary angiography to detect signs of pulmonary vasculitis. The management of HSS is based on the European Alliance of Associations for Rheumatology (EULAR) recommendations for BS and mainly comprises immunosuppressive therapy with glucocorticoids and cyclophosphamide. In addition to drug therapy, PAA should be evaluated for interventional treatment. Spontaneous PAA rupture due to fragile vessel architecture can occur even in cases of remission and/or PAA regression.

[Wearables in rheumatology]. / Wearables in der Rheumatologie.

As a result of digitalization in medicine wearable computing devices (wearables) are becoming increasingly more important. Wearables are small portable electronic devices with which the user can record data relevant to health, such as number of steps, activity profile, electrocardiogram (ECG), heart and breathing frequency or oxygen saturation. Initial studies on the use of wearables in patients with rheumatological diseases show the opening up of new possibilities for prevention, disease monitoring and treatment. This study provides the current data situation and the implementation of wearables in the discipline of rheumatology. Additionally, future potential fields of application as well as challenges and limits of the implementation of wearables are illustrated.