Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival: A Large Cohort Study of the German Network for Systemic Sclerosis.

BACKGROUND: Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis. RESEARCH QUESTION: Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact? STUDY DESIGN AND METHODS: Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Kaplan-Meier estimates were used to compare overall survival in patients with SSc-associated ILD-PH and ILD without PH with patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival. RESULTS: Clinical data of 3,257 patients with a mean follow-up time of 3.45 ± 1.63 years have been included in our analysis. At baseline, ILD was present in 34.5%, whereas PH without ILD had a lower prevalence with 4.5%. At the end of follow-up, 47.6% of patients with SSc had ILD, 15.2% had ILD-PH, and 6.5% had PAH. ILD was more frequent in the diffuse cutaneous form (57.3%), whereas PAH did not differ significantly between SSc subtypes. Significant differences in baseline characteristics between PAH vs ILD-PH vs ILD without PH were found for age at diagnosis, sex, SSc subsets, antibody status, FVC, diffusing capacity of the lung for carbon monoxide, and therapy. Overall survival at 5 years was 96.4% for patients without pulmonary involvement and differed significantly between patients with ILD without PH, PAH, and being worst in patients with ILD-PH. Female sex (hazard ratio [HR], 0.3), higher BMI (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide values (HR, 0.98) were associated with a lower mortality risk. INTERPRETATION: ILD is the most prevalent pulmonary involvement in SSc, whereas the combination of ILD and PH is associated with the most detrimental survival.

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.

[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.

[Recommendations of the committee on complementary medicine and nutrition in ayurvedic medicine, homeopathy, nutrition and Mediterranean diet]. / Empfehlungen der Kommission Komplementäre Heilverfahren und Ernährung zu ayurvedischer Medizin, Homöopathie, Ernährung und mediterraner Kost.

Methods of complementary and alternative medicine (CAM) are appealing for many patients with rheumatic diseases. The scientific data are currently characterized by a large number of publications that stand in contrast to a remarkable shortage of valid clinical studies. The applications of CAM procedures are situated in an area of conflict between efforts for an evidence-based medicine and high-quality therapeutic concepts on the one hand and ill-founded or even dubious offers on the other hand. In 2021 the German Society of Rheumatology (DGRh) launched a committee for CAM and nutrition, which aims to collect and to evaluate the current evidence for CAM applications and nutritional medical interventions in rheumatology, in order to elaborate recommendations for the clinical practice. The current article presents recommendations for nutritional interventions in the rheumatological routine for four areas: nutrition, Mediterranean diet, ayurvedic medicine and homeopathy.

Anti-acid therapy in SSc-associated interstitial lung disease: long-term outcomes from the German Network for Systemic Sclerosis.

OBJECTIVES: Gastroesophageal reflux disease (GERD) occurs frequently in patients with SSc. We investigated whether the presence of GERD and/or the use of anti-acid therapy, specifically proton-pump inhibitors (PPIs), are associated with long-term outcomes, especially in SSc-associated interstitial lung disease (SSc-ILD). METHODS: We retrospectively analysed patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan-Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with GERD vs without GERD (SSc and SSc-ILD), and PPI vs no PPI use (SSc-ILD only). Progression was defined as a decrease in either percentage predicted forced vital capacity of ≥10% or single-breath diffusing capacity for carbon monoxide of ≥15%, or death. RESULTS: It was found that 2693/4306 (63%) registered patients with SSc and 1204/1931 (62%) with SSc-ILD had GERD. GERD was not associated with decreased OS or decreased PFS in patients in either cohort. In SSc-ILD, PPI use was associated with improved OS vs no PPI use after 1 year [98.4% (95% CI: 97.6, 99.3); n = 760 vs 90.8% (87.9-93.8); n = 290] and after 5 years [91.4% (89.2-93.8); n = 357 vs 70.9% (65.2-77.1); n = 106; P < 0.0001]. PPI use was also associated with improved PFS vs no PPI use after 1 year [95.9% (94.6-97.3); n = 745 vs 86.4% (82.9-90.1); n = 278] and after 5 years [66.8% (63.0-70.8); n = 286 vs 45.9% (39.6-53.2); n = 69; P < 0.0001]. CONCLUSION: GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD. Controlled, prospective trials are needed to confirm this finding.

[Rheumatology training positions in Germany]. / Rheumatologische Weiterbildungsstellen in Deutschland.

BACKGROUND: In the next few years many general practitioners and specialists will retire. As in other disciplines the question arises in rheumatology whether sufficient training positions are available to maintain or expand the supply of care according to demand. Therefore, the German Society of Rheumatology (DGRh) has assigned its committee for education and training to review the currently available training opportunities in Germany. The aim of this work is the quantitative survey of the training capacity to become a specialist in internal medicine and rheumatology. METHODS: Within the framework of this study, a survey was conducted via the homepages of the 17 state medical associations to determine the postgraduate medical officers, their place of work and the duration of their postgraduate training capabilities. Based on the data, a nationwide survey of training positions was conducted. RESULTS: Specialized rheumatology training is established at 229 training centers in Germany, whereby data from 187 training sites were available for analysis. The training locations are distributed as followed: 52.4% clinical sector and 47.6% outpatient sector. In total, 478.4 training positions are available in Germany (clinical sector: 391.4 and outpatient sector: 87) and 17.2% of the positions (clinical sector: 11.4% and outpatient sector: 43.1%) are not occupied. CONCLUSION: Based on this study, it can be shown that most of the continuing education positions are available in the clinical sector. In contrast, half of the training positions in the outpatient area are not filled. In order to improve the training situation, it is essential to integrate outpatient colleagues into the training program. This presupposes that further training is supported or financed by the healthcare system. In this context, optimal rheumatological care must be permanently guaranteed throughout Germany in order to provide sufficient care for the approximately 2 million patients with inflammatory rheumatic diseases.

Lifestyle Factors and Their Influence on Rheumatoid Arthritis: A Narrative Review.

In recent years, a possible association of lifestyle factors with rheumatoid arthritis (RA) has attracted increasing public interest. The aim of this review is to provide an overview of the extent and the limitations of current evidence regarding lifestyle factors and RA. The PubMed medical database was screened for epidemiological and prospective studies investigating the contribution of lifestyle factors to the development and the course of the disease. Large epidemiological studies have identified smoking, unhealthy diet and adiposity, as well as a low educational level and low socioeconomic status, as factors that increase the incidence of RA. In addition, several lifestyle habits influence the response of RA to antirheumatic drugs. Among others, smoking, obesity and poor physical activity are associated with a worse treatment outcome. Methodological problems often impair firm conclusions with respect to the causal role of these factors in the risk and the course of RA. However, current evidence is sufficient to recommend a healthy diet, the prevention of obesity, the cessation of smoking and the maintenance of a high level of physical activity to support the effectivity of modern antirheumatic medication.

Autologous hematopoietic stem cell transplantation improves long-term survival-data from a national registry.

BACKGROUND: Current recommendations on the management of systemic sclerosis (SSc) suggest that autologous hematopoietic stem cell therapy (HSCT) can be a rescue therapy for patients with rapidly progressive SSc. OBJECTIVES: To assess the safety and efficacy of HSCT for patients with SSc and to compare these with non-HSCT patients in a control cohort with adjusted risk factors. METHODS: A retrospective analysis of data from the multicentric German network for systemic scleroderma (DNSS) with 5000 patients with SSc. Control groups consisted of all patients with diffuse cutaneous (dc)-SSc (group A) and an adjusted high-risk cohort of male patients with Scl70-positive dc-SSc (group B). RESULTS: Eighty SSc patients received an HSCT 4.1 ± 4.8 years after SSc diagnosis. Among them, 86.3% had dc-SSc, 43.5% were males, and 71.3% were positive for Scl70 antibodies. The control group A (n=1513) showed a significant underrepresentation of these risk factors for mortality. When the survival of the control group B (n=240) was compared with the HSCT group, a lower mortality of the latter was observed instead. Within 5 years after HSCT, we observed an improvement of the mRSS from 17.6 ± 11.5 to 11.0 ± 8.5 (p=0.001) and a stabilization of the DLCO. We did not see differences in transplant-related mortality between patients who received HSCT within 3 years after SSc diagnosis or later. CONCLUSION: Our analysis of real-life data show that the distribution of risk factors for mortality is critical when HSCT cohorts are compared with non-HSCT control groups.

Curcumin: Useful add-on for Rheumatic Diseases?

Plant-derived nutraceuticals are proposed as new key instruments to represent a profound "back to basics" shift in medical treatment. Data accumulated over the past ten years suggest that curcumin, the major active compound of the turmeric plant, has anti-inflammatory properties. It has yet to be determined whether the anti-inflammatory profile of curcumin is potent enough to justify the application of this substance as a nutritional supplement for patients with rheumatic diseases. To address this question, the most relevant in vitro studies that investigate the mechanism of action of curcumin were reviewed in this article. In addition, a total of 18 animal and human trials were evaluated. The pleiotropic, anti-inflammatory and immunomodulatory effects of curcumin were observed in animal studies. In addition, human trials demonstrated promising findings. In these studies, curcumin was able to reduce the expression of proinflammatory cytokines, lower the level of the C-reactive protein and improve clinical parameters. A limiting factor of the application of curcumin is the inconsistent bioavailability of the substance. Therefore, new formulations have been developed to improve the pharmacodynamic profile of curcumin. The future acceptance of the substance is dependent on new controlled clinical trials with a standardised formulation of curcumin administered as well as standard of care.

Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19.

In parasite and viral infections, aberrant B cell responses can suppress germinal center reactions thereby blunting long-lived memory and may provoke immunopathology including autoimmunity. Using COVID-19 as model, we set out to identify serological, cellular, and transcriptomic imprints of pathological responses linked to autoreactive B cells at single-cell resolution. We show that excessive plasmablast expansions are prognostically adverse and correlate with autoantibody production but do not hinder the formation of neutralizing antibodies. Although plasmablasts followed interleukin-4 (IL-4) and BAFF-driven developmental trajectories, were polyclonal, and not enriched in autoreactive B cells, we identified two memory populations (CD80+/ISG15+ and CD11c+/SOX5+/T-bet+/-) with immunogenetic and transcriptional signs of autoreactivity that may be the cellular source of autoantibodies in COVID-19 and that may persist beyond recovery. Immunomodulatory interventions discouraging such adverse responses may be useful in selected patients to shift the balance from autoreactivity toward long-term memory.

[Safety aspects of the treatment with glucocorticoids for rheumatoid arthritis]. / Sicherheitsaspekte der Therapie mit Glukokortikoiden bei rheumatoider Arthritis.

Glucocorticoids (GC) are still the recommended initial treatment for rheumatoid arthritis, although the treatment should be temporary and confined to the administration of low doses. The complex mechanism of action is accompanied by side effects that particularly occur in long-term treatment exceeding 5 mg prednisolone per day. In this dosage range they promote osteoporosis, diabetes and hyperglycemia as well as cardiovascular events and infections, thereby contributing to an excess mortality. The risks of GC treatment are dependent on patient-related parameters, such as age, comorbidity and additional medication. A negative influence of very low steroid doses on overall survival is possibly due to high cumulative steroid doses; however, the data in this respect are contradictory. Recently, a validated index was developed to monitor GC-related toxicity. In the future, this index should help to describe the advantages of steroid-sparing treatment strategies. In the future, more selectively acting substances could achieve an uncoupling of desired and adverse effects.

[Gout arthritis: Pathogenesis, diagnostics and treatment]. / Die Gichtarthritis: Pathogenese, Diagnostik und Behandlung.

The initial presentation of gouty arthritis can be a dramatic event. Chronic gout may lead to the destruction of joints, invalidity and increased mortality. The incidence of this disorder is high, despite effective therapeutic measures. The treatment of refractory cases may be a challenge to the general practitioner and the specialist alike. The article presented here summarizes the current state of diagnostics and treatment of acute and chronic gout.

[Mesenchymal stem cell treatment in autoimmune diseases]. / Mesenchymale Stammzelltherapie bei Autoimmunerkrankungen.

Mesenchymal stromal or stem cells (MSC) possess strong immunomodulatory properties. Due to their impressive potential to differentiate into various cell types they are capable of inducing mechanisms of tissue repair. Experimental data have demonstrated impaired MSC function in several rheumatic diseases in vitro; however, the relevance of these phenomena for the pathogenesis of rheumatic disorders has not been convincingly demonstrated. Nevertheless, allogeneic MSC transplantation (MSCT), and possibly autologous MSCT as well, could prove to be an interesting instrument for the treatment of autoimmune rheumatic diseases. The first clinical trials have demonstrated positive effects in systemic lupus erythematosus, systemic sclerosis and Sjogren's syndrome; however, questions regarding the long-term benefits and safety as well as the best source, the optimal cultivation technique and the most effective way of application of MSC are still unanswered.

Is periodontitis a prognostic factor in order to indicate antibodies against citrullinated peptides in patients with rheumatoid arthritis?

OBJECTIVES: In this cross-sectional study we investigated antibody titres against cyclic citrullinated peptides derived from filaggrin (anti-CCP) and citrullinated α-enolase (anti-CEP-1) among patients with RA as a function of periodontal findings. METHODS: 107 patients with RA (median age 56 years, 75% females) were included. For periodontal diagnoses missing teeth, periodontal epithelial surface area, periodontal inflamed surface area and periodontal diagnosis according to the working group's guidelines of the Center for Disease Control and Prevention were determined. Subgingival bacterial DNA of five periodontopathic bacteria was assessed by PCR with sequence-specific oligonucleotides. Anti-CCP and anti-CEP-1 antibodies in plasma samples were investigated using enzyme-linked immunosorbent assays. Low resolution human leukocyte antigen (HLA) typing was carried out using PCR with sequence-specific primers. RESULTS: PESA was found associated with a low adjusted odds ratio for anti-CCP positivity (OR=1.002, p=0.040). All patients who were infected with Aggregatibacter actinomycetemcomitans were simultaneously anti-CCP positive (p=0.043). HLA-DRB1*13 lowered the adjusted odds ratio for anti-CCP (OR=0.073, p=0.002) and anti-CEP-1 (OR=0.068, p=0.018) positivity whereas HLA-DRB1*07 indicated a lower risk only for demonstrable anti-CCP antibodies (OR=0.079, p=0.004). HLA-DRB1*04 was associated with increased adjusted odds ratio for anti-CEP-1 positivity (OR=4.154, p=0.005) and the simultaneous proof of both investigated autoantibodies (OR=3.725, p=0.011). CONCLUSIONS: Among patients with RA periodontitis may be a minor risk factor for anti-CCP positivity. Our data first provide evidence that an infection with A. actinomycetemcomitans is associated with an increased formation of anti-CCP. HLA phenotype proved to be a significant risk indicator for both investigated antibodies.

Vasculitis and the ear: a literature review.

PURPOSE OF REVIEW: Systemic vasculitides as a group of inflammatory disorders of blood vessels may show clinical manifestations in the ear. This article reviews the recent literature about vasculitis of the ear or the cochleovestibular system, focusing on giant-cell arteritis, Takayasu's arteritis, polyarteritis nodosa, Kawasaki disease, microscopic polyangiitis, granulomatosis with polyangiitis (GPA), eosinophilic GPA, systemic lupus erythematosus, Cogan's syndrome and Behçet's disease. RECENT FINDINGS: In patients with vasculitis, hearing impairment is a frequent problem, followed by tinnitus and vertigo. The severity of sensorineural hearing loss can range from mild impairment to deafness. Autoimmune diseases can induce a conductive hearing loss as a result of effusions of the middle ear, the inflammation of the mucosa of the Eustachian tube, or the involvement of the ossicular chain. Vertigo may be caused by the temporary or permanent occlusion of the labyrinthine or the anterior vestibular artery. Middle ear inflammation is frequent in GPA and eosinophilic GPA. SUMMARY: The progressive sensorineural hearing loss in polyarteritis nodosa or Cogan's syndrome patients may be treated by cochlear implantation.

[Epidemiology and outcome of patients with rheumatic diseases in the intensive care unit]. / Epidemiologie und Outcome von Rheumapatienten auf der Intensivstation.

Patients with rheumatic diseases have an increased risk for admission to an intensive care unit (ICU) compared with individuals without these diseases. Besides cardiovascular events, infection complications are frequently the reason for ICU treatment. For autoimmune systemic diseases, such as systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA), it is not uncommon for the disease to be first diagnosed during intensive medical care. In addition, flares of these diseases can necessitate ICU admission of the patients. The mortality of patients with rheumatic diseases on the ICU is increased compared with control collectives, especially in patients suffering from life-threatening infections. Treatment with corticosteroids is associated with an increased risk for ICU admission as well as a poorer survival rate. In contrast, patients treated with conventional and biologic disease-modifying anti-rheumatic drugs (DMARD) are less likely to need ICU treatment, compared with rheumatism patients without these medications. Among the established scoring systems applied to estimate the prognosis of ICU patients, the APACHE II score is the best investigated system in patients suffering from rheumatic diseases. This score probably reflects the condition of these patients better than other scoring systems.