OBJECTIVES:Therapeutic management of systemic sclerosis (SSc) has evolved considerably in recent years. However, contemporary treatment patterns and prescribing determinants remain poorly characterized. METHODS:Data from the German Network for SSc (DNSS) cohort containing 6,583 patients were analyzed to describe trends in vasoactive, immunomodulatory, and antifibrotic therapy; assess variation between centers and specialties; delineate co-prescription patterns; and identify clinical predictors of treatment. RESULTS:Use of endothelin receptor antagonists and prostanoids / prostacyclin receptor agonists increased from 3.0% [95% confidence interval (CI): 1.5%-5.3%] in 2005 to 28.4% [25.5%-31.3%] in 2025, whereas prescription of calcium channel blockers and phosphodiesterase-5 inhibitors remained stable. Immunomodulatory therapy shifted away from cyclophosphamide towards mycophenolate mofetil, rituximab, and nintedanib, accompanied by a marked decline in glucocorticoid use (50.0% [31.9%-68.1%] in 2000 to 18.1% [11.8%-25.9%] in 2025). University or rheumatology centers prescribed immunomodulators and antifibrotics more frequently than non-university or dermatology centers. Co-prescription patterns showed common combination therapy with tocilizumab or rituximab and methotrexate. Nintedanib was commonly co-administered with mycophenolate, but also with cyclophosphamide or methotrexate. Rituximab was most commonly combined with mycophenolate and tocilizumab with methotrexate. Multivariable mixed models identified modified Rodnan skin score, interstitial lung disease, heart involvement, and care in a university, particularly rheumatology, center as major determinants of immunomodulatory and antifibrotic therapy. CONCLUSIONS:SSc treatment has evolved over the past 25 years, with prescribing patterns increasingly reflecting evidence and guideline recommendations. However, differences between specialties and care settings highlight the need for broader implementation of multidisciplinary, guideline-based care.

IntroductionAnifrolumab (ANI), a type I interferon receptor antagonist, has demonstrated clinical efficacy in systemic lupus erythematosus (SLE). However, its effects on serological markers commonly used to assess disease activity in clinical practice remain uncertain. This study evaluated changes in complement and autoantibody levels in SLE patients treated with ANI under routine care conditions.MethodsWe performed a single-center retrospective analysis of SLE patients receiving ≥3 ANI infusions over a 12-month period. Clinical and serological data, including complement (C3c, C4), anti-double-stranded DNA (anti-dsDNA) antibodies, prednisone dose, and SLE Disease Activity Index 2000 (SLEDAI-2K) scores, were analyzed using mixed-effects modeling (REML). Correlations between changes in clinical SLEDAI-2K (excluding serological components) and serological markers were assessed.ResultsThirteen patients (84.6% female, median age 53 years) were included. The median baseline SLEDAI-2K was 10, and 76.9% exhibited abnormal complement and/or anti-dsDNA levels. Over the treatment course (median 12 infusions), 76.9% of patients improved clinically, with a mean SLEDAI-2K reduction of 3.77 ± 2.78 points (p < 0.001). Prednisone doses decreased in 38.5% of cases. Complement (C3c, p = 0.25; C4, p = 0.10) and anti-dsDNA levels (p = 0.12) remained largely unchanged. No correlations were observed between clinical SLEDAI-2K improvement and serological parameters.DiscussionAnifrolumab therapy led to significant clinical improvement without corresponding serological changes, suggesting that traditional biomarkers may not adequately reflect therapeutic response. Monitoring under ANI should therefore emphasize clinical rather than serological parameters. These findings have implications for interpreting composite disease activity indices incorporating immunological markers in SLE management depending on the mechanism of action of a particular treatment.

In der gebietsübergreifenden Intensivmedizin und klinischen Notfallversorgung stellt die Innere Medizin mit ihren Schwerpunkten eine zentrale Säule dar. Dieses Curriculum – zusammengestellt von Mitgliedern der internistischen Fachgesellschaften (DGIIN, DGIM samt Schwerpunktgesellschaften), dem Berufsverband Deutscher Internistinnen und Internisten (BDI) sowie der Deutschen Gesellschaft für Palliativmedizin (DGP) – gibt einen umfassenden Überblick über internistische Weiterbildungsinhalte der Intensiv- und klinischen Notfallmedizin – Kenntnisse, praktische Fähigkeiten (Kompetenzgrad I–III), beruflich-professionelles Verhalten –, deren Erwerb für eine bestmögliche Versorgung der Patienten aus internistischer Sicht erforderlich scheint. Das Curriculum beschreibt zum einen die allgemeinen Aspekte der Internistischen Intensiv- und Klinischen Notfallmedizin mit den Inhalten: Struktur- und Prozessqualität, Notaufnahme: Erstdiagnostik, Initialtherapie und Indikationsstellung zur weiterführenden Behandlung, Schockraumversorgung, intensivmedizinische Syndrome, Diagnostik und Monitoring, generelle Therapieverfahren, Ethik, Hygienemaßnahmen und Pharmakotherapie. Anschließend folgen spezielle Aspekte der Internistischen Intensiv- und Klinischen Notfallmedizin: angiologische/gefäßmedizinische, endokrinologische, diabetologische und metabolische, gastroenterologische und hepatologische, geriatrische, hämatologische und medizinisch-onkologische, infektiologische, kardiologische, nephrologische, palliativmedizinische, pneumologische, rheumatologische und toxikologische. Unterlegt sind die Themen jeweils mit Verweisen auf praxisrelevante Publikationen. Primär für Internisten gedacht zeigt das Curriculum aber auch allen nichtinternistischen Intensiv- und Notfallmedizinern, mit welchen internistischen Krankheitsbildern und Komorbiditäten sie bei ihrer Tätigkeit rechnen müssen.

Implementation of Treat-to-Target (T2T) in routine clinical practice remains low in systemic lupus erythematosus (SLE). Real-world data reveal excessive use of glucocorticoids (GCs) and frequently inadequate disease control. Here, an international task force convened to develop a consensus framework for implementing T2T in routine clinical care of adult patients with SLE. This T2T task force comprised an international panel of 22 physicians involved in the care of SLE and 3 lupus patient research partners. Following a scoping review and online discussions, during which definitions and instruments available for T2T in SLE were examined, the panel developed potential framework statements for implementing T2T in SLE, which were extensively discussed before being agreed upon by Delphi consensus. Additionally, the current challenges of implementing T2T in SLE and how future research may address these issues were analyzed. The framework comprises 5 overarching principles and 11 statements. Despite the absence of formal evidence that T2T offers superiority to conventional SLE management, T2T in SLE has been recommended for over a decade. This task force offers a framework for effectively implementing T2T in SLE from a real-life perspective, informing a wide range of physicians, including those outside the limited circle of lupus specialists.

Die systemische Sklerose (Sklerodermie [SSc]) ist eine seltene Autoimmunerkrankung, die durch eine Vaskulopathie und Fibrose innerer Organe charakterisiert ist. Die interstitielle Lungenerkrankung im Rahmen der Systemsklerose (SSc-ILD) kommt bei bis zu 30

Internal medicine and its associated subspecialities represent an important cornerstone of intensive care and clinical emergency medicine. This curriculum-compiled by members of the German Society of Medical Intensive Care and Emergency Medicine (Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin), the German Society of Internal Medicine (Deutsche Gesellschaft für Innere Medizin) including subspeciality societies, the Professional Association of German Internists (Berufsverband Deutscher Internistinnen und Internisten, BDI) and the German Association for Palliative Medicine (Deutsche Gesellschaft für Palliativmedizin, DGP)-presents an overview of knowledge, skills (competence levels I-III), behaviors, and attitudes necessary for the highest treatment quality for the internal medicine aspects of intensive care and emergency medicine. It includes general aspects of intensive care and clinical emergency medicine (structure and process quality, emergency department: primary diagnostics and treatment as well as the indication for subsequent treatment, resuscitation room management, clinical syndromes in intensive care medicine, diagnostics and monitoring, general therapeutic measures, ethics, hygiene measures, and pharmacotherapy). Subsequently, specific aspects concerning angiology/vascular medicine, endocrinology, diabetology and metabolism, gastroenterology and hepatology, geriatric medicine, hematology and medical oncology, infectiology, cardiology, nephrology, palliative care, pneumology, rheumatology, and toxicology are addressed. Publications focusing on the content of advanced training are quoted to support this concept. The curriculum is written primarily for internists but may also show practicing intensivists and emergency physicians the broad spectrum of internal medicine diseases and comorbidities presented by patients admitted to the intensive care unit or the emergency department.

ZusammenfassungDas vorliegende Positionspapier (AWMF) zur Therapie der Sarkoidose der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP) wurde 2023 als deutschsprachige Ergänzung und Aktualisierung der internationalen Leitlinien der European Respiratory Society (ERS) aus dem Jahre 2021 verfasst. Sie enthält 5 im Konsensusverfahren abgestimmte Empfehlungen in Form von PICO-Fragen (Patients, Intervention, Comparison, Outcomes), die im Hintergrundtext der 4 Kapitel erläutert werden: Diagnosesicherung und Monitoring der Erkrankung unter Therapie, allgemeine Therapieempfehlungen, Therapie der Hautsarkoidose, Therapie der kardialen Sarkoidose.

Die Betreuung von Patient:innen mit komplexen Autoimmunerkrankungen erfordert eine interdisziplinäre medizinische Versorgung. In Deutschland gibt es zwar eine zunehmende Anzahl von interdisziplinär arbeitenden Zentren für Autoimmunerkrankungen, jedoch sind sie noch nicht flächendeckend vorhanden und ihre Schwerpunkte und interdisziplinären Strukturen häufig nicht nach einem allgemein konsentierten Standard organisiert. Ferner sind sie bislang nicht regelhaft in der allgemeinen Versorgungsstruktur abgebildet. Die Versorgungsstruktur für Autoimmunpatient:innen am Beispiel eines etablierten universitären Zentrums und eines klinischen Falls wird analysiert. Um exemplarisch eine Standortbestimmung interdisziplinär arbeitender Autoimmunzentren in Deutschland durchzuführen, wurden ein Universitätsklinikum für die Strukturanalyse sowie eine Fallvorstellung zur Betrachtung der klinischen Betreuung ausgewählt. In dem ausgewählten Universitätsklinikum werden Patient:innen mit Autoimmunerkrankungen durch Expert*innen verschiedener Fachdisziplinen interdisziplinär betreut. Die Strukturen sind in einem Organigramm verankert. Mithilfe standardisierter Diagnostik- und Therapiepfade („standard operating procedures“ [SOP]) werden Maßnahmen, die für eine jeweils umfassende Diagnostik und Therapie bestimmter Autoimmunerkrankungen fachübergreifend nötig sind, festgelegt. Der von uns vorgestellte Fall stellt anhand einer Patientin mit systemischer Sklerose und Lungenbeteiligung dar, wie ein standardisierter diagnostischer und therapeutischer Pfad in der Praxis umgesetzt werden kann. Wir diskutieren, welche Maßnahmen fachübergreifend für eine umfassende Diagnostik und Therapie bestimmter Autoimmunerkrankungen notwendig sind, welche Herausforderungen sich bei der Umsetzung ergeben und welche Vorteile sich gegenüber Leitlinien ergeben können – unter anderem weil sie sofort an neue Erkenntnisse angepasst werden können. Die Etablierung eines nationalen Konsenses für den Aufbau, die erforderlichen Strukturen und die Umsetzung in der Patient:innenversorgung innerhalb interdisziplinär arbeitender Zentren für Autoimmunerkrankungen in Deutschland ist wünschenswert.

Involvement of the complement system is key to the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis, but immunometabolic implications, especially on serum uric acid (UA) levels, still need to be elucidated. A total of 34 patients with biopsy-proven ANCA-associated renal vasculitis between 2015 and 2020 were retrospectively enrolled. Serum UA levels were correlated with clinical and histopathological characteristics, separated for critically ill (CI, n = 19), myeloperoxidase (MPO)-ANCA (n = 21) and proteinase 3 (PR3)-ANCA (n = 13) subgroups. We here identified inverse correlations of serum UA levels and complement C3 levels in the total cohort (p = 0.005) and the CI subgroup (p < 0.001). Intrarenal complement C4d deposition in venules correlated with serum UA levels in the total cohort (p = 0.007) and in the CI subgroup (p = 0.016). Significant associations of serum UA levels and tubulitis in areas of scarred cortex (t-IFTA) were identified in the total cohort (p = 0.008), and both subgroups of CI (p = 0.034) and MPO-ANCA (p = 0.029). In PR3-ANCA, interstitial fibrosis (ci) was observed as the strongest association with serum UA levels (p = 0.022). Our observations broaden our current understanding of contributory metabolic factors that influence the initial disease course in ANCA-associated renal vasculitis.

In Germany, physicians qualify for emergency medicine by combining a specialty medical training-e.g. internal medicine-with advanced training in emergency medicine according to the statutes of the State Chambers of Physicians largely based upon the Guideline Regulations on Specialty Training of the German Medical Association. Internal medicine and their associated subspecialities represent an important column of emergency medicine. For the internal medicine aspects of emergency medicine, this curriculum presents an overview of knowledge, skills (competence levels I-III) as well as behaviours and attitudes allowing for the best treatment of patients. These include general aspects (structure and process quality, primary diagnostics and therapy as well as indication for subsequent treatment; resuscitation room management; diagnostics and monitoring; general therapeutic measures; hygiene measures; and pharmacotherapy) and also specific aspects concerning angiology, endocrinology, diabetology and metabolism, gastroenterology, geriatric medicine, hematology and oncology, infectiology, cardiology, nephrology, palliative care, pneumology, rheumatology and toxicology. Publications focussing on contents of advanced training are quoted in order to support this concept. The curriculum has primarily been written for internists for their advanced emergency training, but it may generally show practising emergency physicians the broad spectrum of internal medicine diseases or comorbidities presented by patients attending the emergency department.

IntroductionRapidly progressive glomerulonephritis (RPGN) is characterized by a rapid loss of kidney function, affecting both renal and overall patient survival. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems including the kidney, and among most frequent causes of RPGN. We here aimed to validate a recently described scoring system for short-term treatment response to therapeutic plasma exchange (PLEX) in a well-characterized and independent cohort of severe renal AAV presenting with RPGN. Furthermore, we compared this scoring with established classification systems in renal AAV including histopathological findings.MethodsWe here directly compare the scoring system with retrospective data about PLEX treatment in our own clinical practice and according to current recommendations in a cohort of 53 patients with severe AAV presenting with RPGN confirmed by kidney biopsy.ResultsWe here confirm that PLEX scoring is capable to identify patients at risk for short-term poor outcome in severe AAV presenting with RPGN (p<0.0001). Furthermore, multiple stepwise regression analysis revealed that the PLEX score with renal biopsy performed best to predict poor outcome in this patient population (p<0.0001).ConclusionOur observations underscore the relevance of performing a kidney biopsy in this patient population that is often challenged in the setting of intensive care treatment, requirement of KRT with need for anticoagulation and bleeding risk. Therefore, validation of our observations and this recent scoring system for treatment response to PLEX in independent cohorts would be of great clinical relevance in the treatment of patients with severe AAV presenting with RPGN.

BACKGROUND:Interdisciplinary medical treatment is required to care for patients with complex autoimmune diseases. Although there are an increasing number of interdisciplinary centers for autoimmune diseases in Germany, they are not yet available throughout the country and the focuses and interdisciplinary structures are not organized according to a generally agreed standard. Furthermore, they are not regularly reflected in the general care structure. THE AIM OF THE WORK:To analyze the care structure using as an example an established center and a clinical case to demonstrate the usefulness of in-house standardized procedures. MATERIAL AND METHODS:In order to determine the status quo regarding interdisciplinary centers for autoimmune diseases in Germany, a university hospital is exemplarily presented for a structural analysis and a case presentation from another center to demonstrate the importance of an interdisciplinary patient care. RESULTS:At the selected center for autoimmune diseases of the university hospital, patients with autoimmune diseases receive interdisciplinary care from experts from various disciplines. The structures are anchored in an organizational chart. The case report demonstrates a standardized diagnostic and therapeutic pathway (standardized operating procedures, SOP) in a patient with systemic sclerosis and lung involvement. DISCUSSION:The article discusses which measures are necessary across disciplines for comprehensive diagnostics and treatment of certain autoimmune diseases, which challenges arise during implementation and which advantages can arise compared to guidelines because, among other things, they can be immediately adapted. The establishment of a national consensus for the structure, necessary settings and implementation into patient care within an interdisciplinary center for autoimmune diseases is desirable.

The present recommendations on the therapy of sarcoidosis of the German Respiratory Society (DGP) was written in 2023 as a German-language supplement and update of the international guidelines of the European Respiratory Society (ERS) from 2021. It contains 5 PICO questions (Patients, Intervention, Comparison, Outcomes) agreed in the consensus process, which are explained in the background text of the four articles: Confirmation of diagnosis and monitoring of the disease under therapy, general therapy recommendations, therapy of cutaneous sarcoidosis, therapy of cardiac sarcoidosis.

Background: Despite serum albumin levels being predictive for clinical outcome in ANCA-associated renal vasculitis, implications providing a direct link between low serum albumin levels and intrarenal lesions remain elusive. Objectives: We here aimed to systematically assess the clinical relevance of low albumin levels and scrutinize clinicopathological correlations to expand our current knowledge. Methods: We here retrospectively enrolled biopsy-proven cases of ANCA-associated renal vasculitis between 2015 till 2020 in a single-center observational study. Survival-curve analyses on long-term renal survival and short-term clinical recovery were performed. Correlative analyses between serum albumin levels, laboratory parameters, proteinuria levels, and histopathological lesions including tubulointerstitial immune cell infiltrates, lesions analogous to the Banff score and intrarenal complement deposition of C3c and C4d were performed. Results: We here show that hypoalbuminemia below the median of 2.4 g/dL impairs long-term renal survival especially in MPO-positive ANCA-associated renal vasculitis (p = 0.006, HR: 5.0, 95% CI: 1.2-21.5), while short-term clinical recovery particularly in critically ill patients is negatively affected by low serum albumin levels (p=0.0082, HR: 3.6, 95% CI: 1.1-11.7). Low albumin levels are associated with the urinary marker of tubular damage in the total cohort (β = -0.5, p = 0.01), PR3-ANCA (β = -0.5, p = 0.04) and MPO-ANCA (p = 0.002, β = -0.8), but not in critically ill patients (β = -0.5, p = 0.07) implying hypoalbuminemia to occur by extrarenal causation in the state of critical illness. We identified plasmacytic infiltrates to correlate with low albumin levels in the total cohort (β = -0.6, p = 0.004) and in the subgroup of critically ill patients (β = -0.7, p = 0.005). Banff-scored interstitial inflammation (i) was further observed to inversely correlate with albumin levels (β = -0.7, p = 0.02). Intrarenal C4d deposition showed a significant correlation with low serum albumin levels in the glomerular tuft (β = -0.4, p = 0.04) and in interstitial arteries (β = -0.7, p = 0.01). Conclusion: In conclusion, long-term renal outcome is significantly affected by low serum albumin levels especially in the setting of MPO-ANCA seropositivity. By contrast, short-term recovery was predicted by low albumin levels in critically ill patients with ANCA-associated renal vasculitis. We here provide evidence that low levels of serum albumin might directly affect tubulointerstitial inflammation as reflected by plasmacytic immune-cell infiltration, and intrarenal C4d complement deposition in ANCA-associated renal vasculitis. REFERENCES: [1] Berden, A. E., F. Ferrario, E. C. Hagen, D. R. Jayne, J. C. Jennette, K. Joh, I. Neumann, L. H. Noel, C. D. Pusey, R. Waldherr, J. A. Bruijn, and I. M. Bajema. “Histopathologic Classification of Anca-Associated Glomerulonephritis.” J Am Soc Nephrol 21, no. 10 (2010): 1628-36.[2] Flossmann, O., A. Berden, K. de Groot, C. Hagen, L. Harper, C. Heijl, P. Hoglund, D. Jayne, R. Luqmani, A. Mahr, C. Mukhtyar, C. Pusey, N. Rasmussen, C. Stegeman, M. Walsh, K. Westman, and Group European Vasculitis Study. “Long-Term Patient Survival in Anca-Associated Vasculitis.” Ann Rheum Dis 70, no. 3 (2011): 488-94.[3] Weidner, S., S. Geuss, S. Hafezi-Rachti, A. Wonka, and H. D. Rupprecht. “Anca-Associated Vasculitis with Renal Involvement: An Outcome Analysis.” Nephrol Dial Transplant 19, no. 6 (2004): 1403-11.[4] Hakroush, S., D. Tampe, P. Strobel, P. Korsten, and B. Tampe. “Comparative Histological Subtyping of Immune Cell Infiltrates in Mpo-Anca and Pr3-Anca Glomerulonephritis.” Front Immunol 12 (2021): 737708.[5] Ge, Y., G. Yang, X. Yu, B. Sun, B. Zhang, Y. Yuan, M. Zeng, N. Wang, H. Mao, and C. Xing. “Outcome Predictors of Biopsy-Proven Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis.” Front Immunol 11 (2020): 607261. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1Correlative analyses of serum albumin levels and histopathological lesions. (A) Heatmaps reflect the mean values of Spearman’s ρ, circle size represents significance level in the stepwise multivariable linear regression.