Population-based epidemiological projections of rheumatoid arthritis in Germany until 2040.

OBJECTIVES: Our aim was to conduct a population-based projection to estimate the number of rheumatoid arthritis (RA) cases in Germany until 2040. METHOD: Data obtained from a report published in 2017 (doi:10.20364/VA-17.08) were used for future prediction analysis. The data were originally collected by the German Central Institute for Statutory Health Insurance. We used the illness-death model to estimate future numbers of RA cases, considering nine possible scenarios based on different incidence and mortality rates. RESULTS: In the baseline scenario, the number of women with RA is projected to increase by 417 000 cases and men by 179 000 cases by 2040, compared with 2015. Peak numbers of cases are concentrated in the 70-80-year-old age group, particularly among women. In the most favourable scenario (scenario 2), assuming a decreasing incidence, the total number of RA cases is projected to rise by 284 000 by 2040, reflecting a 38% relative increase from 2015 to 2040. The least favourable scenario (scenario 9), assuming an increasing incidence, projects a significant burden on the healthcare system. The total number of RA cases is expected to rise by 1.16 million by 2040, marking a substantial 158% relative increase from 2015 to 2040. CONCLUSIONS: Our research emphasizes a discernible trend: with an ageing society, improving treatment effectiveness, and declining all-cause mortality, we anticipate a rise in the absolute numbers of RA cases in Germany in the coming years. Our models robustly support this viewpoint, underscoring impending challenges for healthcare systems. Addressing these challenges demands multifaceted interventions.

[Determinants of health-related quality of life in systemic lupus erythematosus: a monocentric, retrospective long-term observational study in Germany]. / Determinanten gesundheitsbezogener Lebensqualität bei systemischem Lupus erythematodes: eine monozentrische, retrospektive Langzeitobservationsstudie in Deutschland.

BACKGROUND: Improvement of health-related quality of life (HRQoL) is a prioritized treatment target in systemic lupus erythematosus (SLE). A retrospective chart review of patients with repeated HRQoL measurements from the outpatient department was conducted in order to better understand which factors drive HRQoL in established SLE. Of particular interest was the association between HRQoL and disease activity. METHODS: The medical outcomes study short form 36 (SF-36), systemic lupus activity measure (SLAM) and routine clinical data of 169 patients (83% female, mean age 40.3 ± 13 years, disease duration 9.4 ± 7 years) over an average of 7.1 ± 4.2 years were available for analysis by linear mixed modelling. Factors associated with the physical component summary (PCS) and mental component summary (MCS) of the SF-36 were assessed. The proportion of HRQoL which could be explained by the variables was estimated by marginal R2 (mR2) and conditional R2 (cR2). RESULTS: At baseline, SLE patients showed a reduced HRQoL in all subscales of the SF-36 including PCS and MCS with the exception of vitality. A higher PCS over time was significantly associated with concurrent parameters, such as intake of antimalarial drugs, no glucocorticoid use, less fatigue, lower disease activity as well as to the baseline parameters of younger age and higher PCS (mR2 54.7%, cR2 59.9%). A higher MCS was associated with concurrent use of glucocorticoids and a higher baseline MCS (mR2 21.7%, cR2 25.1%). CONCLUSION: The use of antimalarial drugs and no glucocorticoid intake as well as low current disease activity are modifiable factors associated with a better physical HRQoL. The mental component of HRQoL was poorly represented by conventional parameters and not associated with parameters of disease activity in the present study cohort.

Multiparametric detection of autoantibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous disease with respect to disease manifestations, disease progression and treatment response. Therefore, strategies to identify biomarkers that help distinguishing SLE subgroups are a major focus of biomarker research. We reasoned that a multiparametric autoantibody profiling approach combined with data mining tools could be applied to identify SLE patient clusters. We used a bead-based array containing 86 antigens including diverse nuclear and immune defense pathway proteins. Sixty-four autoantibodies were significantly (p < 0.05) increased in SLE (n = 69) compared to healthy controls (HC, n = 59). Using binary cut-off thresholds (95% quantile of HC), hierarchical clustering of SLE patients yields five clusters, which differ qualitatively and in their total number of autoantibodies. In two patient clusters the overall accumulated autoantibody reactivity of all antigens tested was 31% and 48%, respectively. We observed a positive association between the autoantibody signature present in these two patient clusters and the clinical manifestation of glomerulonephritis (GLMN). In addition, groups of autoantibodies directed against distinct intracellular compartments and/or biological motifs characterize the different SLE subgroups. Our findings highlight the relevant potential of multiparametric autoantibody detection and may contribute to a deeper understanding of the clinical and serological diversity of SLE.

[Eosinophilic granulomatosis with polyangiitis presenting as livedo racemosa]. / Livedo racemosa als kutane Manifestation bei eosinophiler Granulomatose mit Polyangiitis.

As a rare antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is characterized by asthma, severe peripheral eosinophilia and the presence of extravascular granulomas. Cutaneous involvement usually includes palpable purpura or cutaneous to subcutaneous nodes. We present the case of a 43-year-old woman with EPGA and the unusual cutaneous manifestation of livedo racemosa.

HLA-A2 phenotype may be protective against Graves' disease but not against Hashimoto's thyroiditis in Caucasians.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are the most common autoimmune thyroid diseases (AITDs) affecting up to 5% of the general population. In Caucasians HT has a prevalence of up to 4.60% and GD a prevalence of 1-2%. The aim of this study was to investigate the association between HLA-A2 and the AITDs GD and HT among Caucasians. HLA alleles of 33 patients with GD and 75 patients with HT were determined by serological typing. The frequency of HLA A2 was significantly reduced in GD (p=0.033) but not in HT (p=n.s.) as compared to control samples. In individuals positive for HLA-A2 odds ratio for protection from GD was found to be 2.8. This study supports the hypothesis that genetic predisposition to GD is not restricted to MHC class II molecules. The significant negative association between HLA A2 and GD supports the hypothesis that MHC class I genes may be relevant for the protection from GD. In contrast the nonsignificant results for HT indicate that this association may not apply to AITDs in general.

Validation and evaluation of the German Brief Index of Lupus Damage (BILD)--a self-reported instrument to record damage in systemic lupus erythematosus.

INTRODUCTION: Damage is a very important predictor for outcome in systemic lupus erythematosus (SLE) and should be routinely documented. Patient-reported assessments for damage are rare and neither the Lupus Damage Index Questionnaire (LDIQ) nor the Brief Index of Lupus Damage (BILD) is validated in German language. Our aim was to validate the BILD in German language and evaluate its use as a patient-administered instrument. METHOD: We translated and adapted the BILD questionnaire to use it as a self-administered questionnaire for German-speaking SLE patients. It was applied to SLE outpatients at an academic centre and compared to the SLICC/SDI and other lupus outcome parameters. RESULTS: The German BILD showed as strong a correlation with the SLICC/SDI as the original version of the BILD and a superior correlation compared to the LDIQ. It scored significantly higher with an increase of age, disease duration or disease activity, with a lower functional status or overall health and a higher probability of receiving an incapacity pension. CONCLUSION: The German version of the BILD shows a comparable validity to the original BILD with even higher correlation to physician-reported damage even when used as a self-administered questionnaire. Hence it represents a promising instrument to survey damage in clinical routine as well as in clinical and epidemiological studies.

Cardiovascular disease and serum defensin levels in systemic lupus erythematosus.

OBJECTIVES: To analyse if defensins, immunomodulatory peptides involved in angiogenesis and elevated in the sera of systemic lupus erythematosus (SLE) patients, relate to cardiovascular disease in SLE. METHODS: Serum levels of the defensins human beta defensin 2 (hBD2) and human neutrophil peptide (HNP) of 72 SLE patients were determined by ELISA at baseline. Cardiovascular risk factors and the occurrence of cardiovascular events (CVE: stroke, claudication, angina pectoris, myocardial infarction) were recorded over 6 years. Intima media thickness of the carotid arteries (CIMT) was measured by ultrasound in 42 patients at baseline and at 4 years. Normally distributed log-transformed defensin levels (log-hBD2 and log-HNP) were used for statistical analysis. RESULTS: SLE patients who experienced a CVE had significantly higher log-hBD2 values and a likelihood-ratio for CVE of 2.23 when levels increased above 3.3 log(ng/ml). Using binary logistic regression analysis, log-hBD2 significantly contributed to a model also incorporating the number of traditional cardiovascular risk factors (dyslipidemia, hypertension, positive family history, age, smoking) as explanatory variables for the incidence of cardiovascular events. Moreover, SLE patients with progressive CIMT showed increased log-hBD2 and log-HNP values. Both defensin-levels also showed some correlation to the plaque stadium at baseline (hBD2: r2 0.10; HNP r2 0.12). Neither log-hBD2 nor log-HNP were correlated to traditional cardiovascular risk factors. CONCLUSIONS: HNP and especially hBD2 may be indicators of progressive cardiovascular disease in SLE.

Elevated levels of human beta-defensin 2 and human neutrophil peptides in systemic lupus erythematosus.

OBJECTIVE: Defensins are immunomodulatory peptides and components of the innate immune response. They have been shown to be modulated in various disease states and in response to inflammatory stimuli. Recently, alpha-defensins have been implicated in the pathogenesis of autoimmune diseases. In order to explore whether these defensins may have a role in the pathogenesis of systemic lupus erythematosus (SLE), we sought to determine whether altered expression can be found in SLE patients. MATERIAL AND METHODS: Serum and EDTA-blood of 50 SLE patients who fulfilled the American College of Rheumatology (ACR) criteria (aged 41.4 ± 13.3 years) and 28 age- and sex-matched healthy controls were collected. Real-time polymerase chain reaction with gene-specific primers for human neutrophil peptides (HNPs), human beta-defensin 2 and 3 (hBD2, 3) in isolated polymorphonuclear cells and enzyme-linked immunosorbent assay (ELISA) in serum samples were performed. Results of SLE patients were compared with the control group and correlated to routine laboratory parameters, clinical data and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: SLE patients were predominantly female (90%) with a mean SLEDAI of 5.7 ± 6.1. In sera, patients displayed higher amounts of hBD2 and HNPs when compared with healthy controls. Furthermore, hBD2 correlated with levels of anti-dsDNA antibodies, erythrocyte count and the SLEDAI. Elevated values were observed in patients with myositis (n = 4). Serum HNPs on the other hand correlated with the neutrophil count and was elevated in patients with a rash (n = 7). Lupus patients suffering from transverse myelitis (n = 3) had raised serum-values of both HNPs and hBD2. While no mRNA of hBD2 or hBD3 was detected in polymorphonuclear cells, HNP mRNA was found in both healthy controls and patients without significant difference. Lupus nephritis and rash were associated with higher amounts of HNP mRNA, and the relative amount of copies correlated positively with the SLEDAI and negatively with C3 measurements. CONCLUSIONS: Serum levels of hBD2 and HNPs are elevated in SLE. The correlations of hBD2 and HNPs to established disease activity parameters and distinct clinical situations suggest that innate immune mechanisms are activated. Defensins may be involved in SLE pathogenesis.

[Therapy of dyslipidemia in rheumatic diseases]. / Therapie der Dyslipidämie bei entzündlich-rheumatischen Erkrankungen.

Cardiovascular diseases are the main cause of death worldwide and dyslipidemia constitutes a substantial risk factor. Patients with rheumatic diseases, especially active inflammatory arthritis and systemic lupus erythematosus, show unfavorable lipid profiles, which, however, do not account for the total excess cardiovascular morbidity. Effective disease management, life-style changes and cholesterol-lowering agents can ameliorate the lipid profile and lower cardiovascular mortality. Due to their anti-inflammatory and potent cholesterol-lowering properties, statins are the pharmacological agents of first choice. National and international guidelines on cardiovascular risk prevention differ concerning appraisal of the individual risk and lipid targets. The EULAR recently released recommendations for cardiovascular risk management in patients with inflammatory arthritis.