Cardiovascular risk in axial spondyloarthritis-a systematic review.

Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of this important aspect of axial spondyloarthritis, we conducted a systematic literature search of all articles published between January 2000 and 25 May 2023 on cardiovascular manifestations. Using PubMed and SCOPUS, 123 out of 6792 articles were identified and included in this review. Non-radiographic axial spondyloarthritis seems to be underrepresented in studies; thus, more evidence for ankylosing spondylitis exists. All in all, we found some traditional risk factors that led to higher cardiovascular disease burden or major cardiovascular events. These specific risk factors seem to be more aggressive in patients with spondyloarthropathies and have a strong connection to high or long-standing disease activity. Since disease activity is a major driver of morbidity, diagnostic, therapeutic, and lifestyle interventions are crucial for better outcomes. Key Points • Several studies on axial spondyloarthritis and associated cardiovascular diseases have been conducted in the last few years addressing risk stratification of these patients including artificial intelligence. • Recent data suggest distinct manifestations of cardiovascular disease entities among men and women which the treating physician needs to be aware of. • Rheumatologists need to screen axial spondyloarthritis patients for emerging cardiovascular disease and should aim at reducing traditional risk factors like hyperlipidemia, hypertension, and smoking as well as disease activity.

[National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic DMARDS (disease modifying antirheumatic drugs)]. / Consensus Statement der Österreichischen Gesellschaften für Rheumatologie und Rehabilitation, Pneumologie, Infektiologie, Dermatologie und Gastroenterologie zum Umgang mit latenter Tuberkulose bei Therapien mit biologischen oder "targeted synthetic" DMARDs ("disease modifying antirheumatic drugs").

This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated.

National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic disease modifying antirheumatic drugs (DMARDs).

This publication provides a thorough analysis of the most relevant topics concerning the management of latent tuberculosis when using biologic and targeted synthetic Disease Modifying Antirheumatic Drugs (DMARDs) by a multidisciplinary, select committee of Austrian physicians. The committee includes members of the Austrian Societies for Rheumatology and Rehabilitation, Pulmonology, Infectiology, Dermatology and Gastroenterology. Consensus was reached on issues regarding screening and treatment of latent tuberculosis and includes separate recommendations for each biologic and targeted synthetic DMARD.

Computed Tomography Findings as Determinants of Local and Systemic Inflammation Biomarkers in Interstitial Lung Diseases: A Retrospective Registry-Based Descriptive Study.

PURPOSE: To evaluate the association of peripheral blood (PBL) and broncho-alveolar lavage (BAL) biomarkers with inflammatory versus fibrotic high-resolution computed tomography (HRCT) findings in interstitial lung disease (ILD) patients. METHODS: HRCT findings of 127 consecutive ILD-board patients were semi-quantitatively evaluated: reticulation/honeycombing (RET), traction bronchiectasis (TBR) and emphysema (EMP) were classified as non-inflammatory/fibrotic; consolidations (CON), ground glass opacities (GGO), parenchymal nodules (NDL) and mosaic attenuation (MOS) as active inflammatory. Each HRCT finding was assessed in six distinct lung regions, resulting scores were graded as minimal (0-1 regions involved), medium (2-4) or extensive (5-6). Associations of routinely assessed PBL/BAL biomarkers with these HRCT scores were evaluated using Spearman correlation coefficients and graphical presentation; significance was tested by applying Kruskal-Wallis tests. RESULTS: Blood neutrophil, lymphocyte and eosinophil fraction, neutrophil to lymphocyte ratio (NLR) and BAL lymphocyte fraction consistently showed opposite correlations with inflammatory versus non-inflammatory/fibrotic HRCT finding scores. Blood lymphocyte fraction significantly differed by graded GGO (p = 0.032) and CON (p = 0.027) extent, eosinophil fraction by TBR (p = 0.006) and NLR by CON (p = 0.009). C-reactive protein was significantly related to GGO (p = 0.023) and CON (p = 0.004), BAL lymphocyte fraction to GGO (p = 0.017) extent. CONCLUSION: Blood lymphocyte and eosinophil fraction, NLR, CRP and BAL lymphocyte fraction may aid to differentiate inflammatory from non-inflammatory/fibrotic ILD patterns. TRIAL REGISTRATION: This evaluation was based on data from the ILD registry of Kepler University Hospital Linz, as approved by the ethics committee of the Federal State of Upper-Austria (EK Number. I-26-17).

Computed tomography findings as determinants of pulmonary function tests in fibrotic interstitial lung diseases-Network-analyses and multivariate models.

The aim was to evaluate the impact of multiple high-resolution computed tomography (HRCT) features on pulmonary function test (PFT) biomarkers in fibrotic interstitial lung disease (FILD) patients. HRCT of subsequently ILD-board-discussed FILD patients were semi-quantitatively evaluated in a standardized approach: 18 distinct lung regions were scored for noduli, reticulation, honeycombing, consolidations, ground glass opacities (GGO), traction bronchiectasis (BRK) and emphysema. Total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC, diffusion capacity for carbon monoxide (DLCO) and transfer coefficient (KCO) were assessed. Interactions between each PFT biomarker and all HRCT scores were visualized by network analyses, modeled according to the Schwarz Bayesian Information Criterion and incorporated in uni- and multivariate stepwise regression analyses. Among 108 FILD patients (mean age 67 years, 77% male), BRK extent was a major significant uni- or multivariate determinant of all PFT analyzed. Besides that, diffusion-based variables DLCO and KCO showed a larger dependency on reticulation, emphysema and GGO, while forced expiratory volume-based measures FEV1, FVC and FEV1/FVC were more closely associated with consolidations. For TLC, the only significant multivariate determinant was reticulation. In conclusion, PFT biomarkers derived from spirometry, body plethysmography and diffusion capacity in FILD patients are differentially influenced by semi-quantified HRCT findings.

The Supply of Rheumatology Specialist Care in Real Life. Results of a Nationwide Survey and Analysis of Supply and Needs.

Objectives: To study the balance between the supply and need for rheumatology care in Austria. In addition, to investigate rheumatologists' work-hours, the amount of time rheumatologists dedicate to care for patients with rheumatic and musculoskeletal diseases (RMD), with non-RMD problems, and other professional activities such as research, teaching, and administration. Methods: A questionnaire covering aspects of professional activities was sent to all 215 rheumatologists registered with the Austrian Medical Association. The data collected was set in relation to the need calculated on the basis of recommendations put forward by the German society of rheumatology. Results: 149 of the 215 rheumatologists (69.0%) responded. Median weekly working time was 50 h (IQR 45-60). 47.4% of the working time was spent for care of patients with RMD. The remaining time was dedicated to patients with non-rheumatic diseases (19.6%), research and teaching (8.4%), and administration (24.5%). The number of full-time equivalents (FTE, based on a 40-h work-week) available for rheumatology care, thus, was calculated to be 178.5. Based on disease prevalence/incidence estimates and on the time allocation results of this survey, our study resulted in a need of 4.29 rheumatologists per 100.000 adult inhabitants (301.79 for an adult population of 7.03 × 106). Conclusion: The study demonstrated a substantial mismatch between the available supply and the need for rheumatology care. The results of our study are a conservative estimate, which should be taken into consideration for future healthcare workforce planning. In particular, the rising need for rheumatologists should be met by increasing the numbers of those specialists.

Depression: a common comorbidity in women with rheumatoid arthritis-results from an Austrian cross-sectional study.

OBJECTIVES: Previous research showed that depression is common in rheumatoid arthritis (RA). However, the prevalence very much depends on different assessment tools and sociocultural differences, respectively. The main study aim and research question was to investigate the proportion of depressive symptoms in Austrian female patients with RA. SETTING: A nationwide multicentre study with seven secondary care centres all over Austria (hospital-based rheumatological outpatient clinics and private practices). PARTICIPANTS: 319 patients with RA and 306 healthy controls (HCO), all female Caucasians, were asked to complete a Beck's Depression Inventory-Fast Screen (BDI-FS). Patients and HCO were ≥18 years. Patients had to fulfil the 2010 classification criteria for RA. In addition, disease activity, disability, medication, drinking of alcoholic beverages, smoking and occupational status were evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES: A BDI-FS cut-off value of ≥4, per definition, indicates the presence of a depressive symptomatology. RESULTS: The return rate of questionnaires was high: 235/319 (73.7%) in patients with RA and 180/306 (58.8%), ending up with 392 complete questionnaires from 223 patients with RA (69.9%) and 169 HCO (55.2%). The BDI-FS was significantly higher in patients with RA (median BDI-FS 2 (IQR 0-4) vs median 1 (IQR 0-2) in HCO, p<0.001). BDI-FS scores from ≥4, which by definition indicate depression, were found in 29.6% of patients with RA and 12.4% of HCO (p<0.001). Depressive symptoms were strongly associated with disease activity (Clinical Disease Activity Index, p<0.001) and disability (Health Assessment Questionnaire, p<0.005). No association of depressive symptoms with age, alcohol consumption, smoking, occupational status or use of medication was found. CONCLUSIONS: One-third of female patients with RA showed depressive symptoms. Depression was significantly higher in female patients with RA than in female HCO and was strongly associated with disease activity and disability. It would be of interest to address the same question in male participants.

High Burden of Sexual Dysfunction in Female Patients with Rheumatoid Arthritis: Results of a Cross-sectional Study.

OBJECTIVE: To evaluate the effect of rheumatoid arthritis (RA) on impairing women's sexuality regarding motivation, activity, and satisfaction, and to assess the correlation of disease-related physical impairment within sexual functioning. METHODS: An anonymous survey among women with RA and healthy controls (HC) using standardized questionnaires, predominantly the Changes in Sexual Functioning Questionnaire-short form (CSFQ-14). In addition, disease activity, depression, and disability were evaluated. RESULTS: There were 319 questionnaires distributed to patients and 306 to HC. Of these, 235 patient questionnaires (73.7%) and 180 HC questionnaires (58.8%) were returned, of which 203 and 169 were completed, respectively. Of the patients with RA, 47.8% had a total CSFQ-14 score of ≤ 41, indicating female sexual dysfunction (FSD), as compared to 14.2% of HC (p < 0.0001). The median CSFQ-14 score was lower in patients with RA [42 points, interquartile range (IQR) 36-48] than in HC (49 points, IQR 44-54; p < 0.0001), resulting in an OR of 5.53 (95% CI 3.19-9.57; p < 0.0001). After adjustment for confounders, given a higher mean age of patients (55.2 ± 11.3 yrs) than HC (47.4 ± 11.8 yrs; p < 0.0001), the OR for FSD in patients with RA was still 3.04 (95% CI 1.61-5.75; p = 0.001). Neither the Health Assessment Questionnaire-Disability Index nor the Clinical Disease Activity Index was associated with FSD after adjustment. CONCLUSION: FSD apparently is highly prevalent in female patients with RA, affects all subdomains of sexual function, and is most likely underestimated in daily clinical practice. Of note, FSD could not be linked to disability or RA disease activity.

Cardiovascular disease in patients with autoinflammatory syndromes.

Autoinflammatory syndromes (AIS) are characterized by recurring events of inflammation, leading to a variety of organ manifestations and fever attacks. A subgroup of AIS is commonly referred to as hereditary periodic fever syndromes (HPFS). There is substantial evidence that autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus are strongly associated with cardiovascular morbidity and mortality. The link between AIS and cardiovascular disease is not that clear, even if the concept of continuous inflammation as a risk factor for cardiovascular disease is widely accepted. Research on the association of AIS and cardiovascular disease is increasing within the last years. In this review, we will discuss the association of several AIS with cardiovascular disease. Based on the rarity of some entities, lack of data, however, led to exclusion of some rare AIS. Especially, for Behcet's disease (BD), adult-onset Still's disease (AOSD), and Familial Mediterranean fever (FMF), there is an association with a number of cardiovascular abnormalities. BD is the AIS, which is most strongly associated with manifestation in the arterial and venous system. AOSD is strongly associated with cardiac inflammation (peri-/myocarditis). FMF patients are likely to suffer from serositis. Of note, there seems to be a link between variants of AOSD as well as FMF and idiopathic recurrent acute pericarditis.

Association of vascular function and estimated cardiovascular risk in patients with rheumatoid arthritis / Associação entre a função vascular e o risco cardiovascular estimado em pacientes com artrite reumatoide

Abstract Objectives: Rheumatoid arthritis (RA) patients should receive cardiovascular (CV) risk assessment. For this purpose CV risk calculators are available. In addition, parameters of vascular function can be measured and used for risk prediction. Aim of the present study was to assess the association of these two concepts. Methods: 287 RA patients (58.4 ± 12.6 years) and 232 controls (49.9 ± 13.4 years) were included in this cross-sectional study. We calculated 10 year CV risk with SCORE and QRISK2. For SCORE we used the recommended multiplier of 1.5 in eligible RA patients and estimated the risk also in patients younger than 40 years (mSCORE (0-65)). Augmentation index (AIx) and central pulse pressure (PP), markers of vascular integrity and CV risk, were assessed by pulse wave analysis (PWA). Primary endpoint was the correlation of AIx and the estimated CV risk using mSCORE (0-65). Results: In RA patients AIx showed a statistically significant correlation with mSCORE (0-65) (rho = 0.3374; p < 0.0001) and QRISK2 (rho = 0.3307; p < 0.0001). The correlations of central PP with mSCORE (0-65) (rho = 0.4692; p < 0.0001) and QRISK2 (rho = 0.5828; p < 0.0001) were also statistically significant. Increasing quartiles of central PP were associated with an increased odds of being in the "high risk"category according to SCORE (OR 2.18; 95% CI 1.58-3.01) or QRISK2 (OR 2.18; 95% CI 1.75-2.72). In control patients we also found a correlation of AIx and central PP with SCORE (0-65) and QRISK2. Conclusions: Parameters of central haemodynamics correlate with calculated CV risk. However, both do not give exactly the same information. The question arises whether a combination of both concepts would result in an improved CV risk prediction.

Resumo Objetivos: Os pacientes com artrite reumatoide (AR) devem receber uma avaliação do risco cardiovascular (CV). Para esse fim, existem as calculadoras de risco CV. Além disso, parâmetros da função vascular podem ser medidos e usados para predição do risco. O objetivo deste estudo foi avaliar a associação entre esses dois conceitos. Métodos: Foram incluídos neste estudo transversal 287 pacientes com AR (58,4 ± 12,6 anos) e 232 controles (49,9 ± 13,4 anos). Calculou-se o risco CV em 10 anos com o Score e o QRISK2. No Score, usou-se o multiplicador recomendado de 1,5 em pacientes com AR elegíveis e estimou-se também o risco em pacientes com menos de 40 anos [mScore (0-65)]. O índice de aumento (AIx) e a pressão de pulso (PP) central, marcadores da integridade vascular e risco CV, foram avaliados pela análise de onda de pulso (PWA). O desfecho primário foi a correlação entre o AIx e o risco CV estimado com o mScore (0-65). Resultados: Em pacientes com AR, o AIx mostrou correlação estatisticamente significativa com o mScore (0-65) (rho = 0,3374; p < 0,0001). A correlação entre o AIx e o QRISK2 também foi significativa (rho = 0,3307, p < 0,0001). As correlações entre a PP central e o mScore (0-65) (rho = 0,4692; p < 0,0001) e QRISK2 (rho = 0,5828; p < 0,0001) também foram estatisticamente significativas. Os quartis incrementais da PP central estiveram associados a uma maior probabilidade de estar na categoria de "alto risco"de acordo com o Score (OR 2,18; IC 95% 1,58 a 3,01) ou QRISK2 (OR 2,18; IC 95% 1,75-2,72). Nos pacientes do grupo controle também se encontrou uma correlação entre o AIx e a PP central no Score (0-65) e no QRISK2. Conclusões: Os parâmetros de hemodinâmica central se correlacionam com o risco CV calculado. No entanto, ambos não fornecem exatamente as mesmas informações. Pergunta-se se uma combinação de ambos os conceitos resultaria em uma melhor predição do risco CV.

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3-3.2) as compared to controls (1.3; IQR 0.8-2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15-0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92-4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10-7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00-129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46-4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.

Association of vascular function and estimated cardiovascular risk in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) patients should receive cardiovascular (CV) risk assessment. For this purpose CV risk calculators are available. In addition, parameters of vascular function can be measured and used for risk prediction. Aim of the present study was to assess the association of these two concepts. METHODS: 287 RA patients (58.4±12.6 years) and 232 controls (49.9±13.4 years) were included in this cross-sectional study. We calculated 10 year CV risk with SCORE and QRISK2. For SCORE we used the recommended multiplier of 1.5 in eligible RA patients and estimated the risk also in patients younger than 40 years (mSCORE (0-65)). Augmentation index (AIx) and central pulse pressure (PP), markers of vascular integrity and CV risk, were assessed by pulse wave analysis (PWA). Primary endpoint was the correlation of AIx and the estimated CV risk using mSCORE (0-65). RESULTS: In RA patients AIx showed a statistically significant correlation with mSCORE (0-65) (rho=0.3374; p<0.0001) and QRISK2 (rho=0.3307; p<0.0001). The correlations of central PP with mSCORE (0-65) (rho=0.4692; p<0.0001) and QRISK2 (rho=0.5828; p<0.0001) were also statistically significant. Increasing quartiles of central PP were associated with an increased odds of being in the "high risk" category according to SCORE (OR 2.18; 95% CI 1.58-3.01) or QRISK2 (OR 2.18; 95% CI 1.75-2.72). In control patients we also found a correlation of AIx and central PP with SCORE (0-65) and QRISK2. CONCLUSIONS: Parameters of central haemodynamics correlate with calculated CV risk. However, both do not give exactly the same information. The question arises whether a combination of both concepts would result in an improved CV risk prediction.

Rituximab for immunologic renal disease: What the nephrologist needs to know.

Rituximab (RTX), a chimeric, monoclonal anti-CD20 antibody, is increasingly used in immune-mediated renal diseases. While licensed in the induction treatment of ANCA-associated vasculitis, it represents one of the most commonly prescribed off-label drugs. Much of the information regarding its safety has been drawn from experience in hematology and rheumatology. Ample evidence illustrates the safety of RTX, however, rare but serious adverse events have emerged that include progressive multifocal leucoencephalopathy and hepatitis B reactivation. Moderate to severe hypogammaglobulinemia and late-onset neutropenia following RTX therapy confer an increased infectious risk and factors predicting these side effects (i.e. a genetic basis) need to be identified. Nephrologists initiating RTX need to bear in mind that long-term risks and optimal dosing for many renal indications remain unclear. Special considerations must be given when RTX is used in women of childbearing age. We summarize practical aspects concerning the use of RTX. This review will provide nephrologists with information to guide their use of RTX alerting them to safety risks and the need for patient counselling.

Relapsing polychondritis: a chameleon among orphan diseases.

Relapsing polychondritis (RPC) is a rare disease with recurrent episodes of inflammation of cartilage tissue leading to fibrosis and organ damage. Despite unknown etiology, there is some evidence of a genetic predisposition. The clinical presentation is heterogeneous and an association with other autoimmune disorders such as rheumatoid arthritis or different forms of vasculitis has been described. All organ systems containing cartilage can be affected, such as ear, nose, joints, trachea, aorta, and coronary arteries. Given the broad spectrum of potential manifestations, a variety of medical specialists may be involved in the management of RPC patients. As establishing the diagnosis of RPC may be difficult, an interdisciplinary approach may be preferable. Treatment options include glucocorticoids, dapsone, disease-modifying antirheumatic drugs, and biologics. Prognosis is as heterogeneous as the clinical picture, depending on the severity of organ damage. In this paper we give an overview of the current knowledge with regard to pathogenesis, clinical picture, diagnosis, and therapy of RPC.

Urinary albumin excretion in patients with rheumatoid arthritis in a large cross-sectional study.

While there is a lot of evidence published on the association of cardiovascular (CV) disease and rheumatoid arthritis (RA), little is known about urinary albumin excretion (UAE)-a marker of CV risk-in this particular high-risk population. Therefore, we investigated UAE in a large cross-sectional study. We used data from the US National Health and Nutrition Examination Survey (NHANES), including the years 2007-2012. Primary outcome was the proportion of patients with a urinary albumin-creatinine ratio (ACR) >30 mg/g. A total of 14,648 study participants (representing a population size of 174,663,008) with available ACR were included in the study (14,179 without RA and 469 with RA). In the RA group, the proportion of patients with an ACR >30 mg/g was 10.46 % (95 % CI 7.47-14.45 %) and in the non-RA group this proportion was 13.39 % (95 % CI 12.65-14.16 %; p = 0.09). There was a strong association between RA and DM (OR 5.84; 95 % CI 4.48-7.62). In the RA group, significantly more patients had a former CV event (OR 3.01; 95 % CI 2.28-3.97). Adjustments for DM, smoking status, former CV event, age, systolic blood pressure, and gender did not substantially alter the association between RA and ACR >30 mg/g (OR 0.82; 95 % CI 0.51-1.33). We did not find evidence for a difference in UAE in patients with or without RA, despite the fact that RA was associated with DM and, in addition, RA patients more often had a previous CV event. These findings may support the assumption that despite an increased CV risk, UAE does not play a major role in RA patients.

IgG4-related disease: current challenges and future prospects.

Immunoglobulin G4-related disease (IgG4-RD) represents an immune-mediated fibroinflammatory condition with a characteristic histopathological appearance that can affect various organs. Although numerous single-organ manifestations have been described more than a century ago, its systemic nature and unique features were only discovered in the last 2 decades, when IgG4-RD emerged as a new entity of disease. IgG4-RD is usually considered a rare disease, but its true epidemiology has not yet been fully clarified. Also, despite recent advances in the identification of the underlying immunological processes, its pathophysiology is only incompletely understood till now. The diagnostic workup of IgG4-RD is complex and usually requires a combination of clinical examination, imaging, histological, and serological analyses. However, no finding alone is specific for IgG4-RD. Therefore, its diagnosis requires careful interpretation of examination results in context with the patient's clinical appearance as well as the exclusion of a broad variety of differential diagnoses. The past years brought rapid advances concerning this novel disease entity: diagnostic criteria, further insights into the underlying immunological processes, new biomarkers, and novel therapeutic approaches were proposed and widened the knowledge in the field of IgG4-RD. Still, a greater number of questions remain unanswered, and many recent developments require further discussion and proof from clinical trials. This review should give an overview on current knowledge and future perspectives in epidemiology, pathophysiology, diagnosis, and therapy of IgG4-RD.

Urinary Albumin Excretion and Vascular Function in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with significant cardiovascular (CV) morbidity and mortality. Increased urinary albumin excretion is a marker of CV risk. There are only few data on urinary albumin excretion in RA patients. Aim of the present study was to investigate urinary albumin excretion in RA patients and analyze, whether there is an association between urinary albumin excretion and vascular function as measured by the augmentation index (AIx). In a total of 341 participants (215 with RA, 126 without RA) urinary albumin-creatinine ratio (ACR) was determined and the AIx was measured. The Kolmogorov-Smirnov-test was used to cluster patient groups whose distributions of ACR can be considered to be equal. A crude analysis showed a median ACR of 6.6 mg/g in the RA group and 5.7 mg/g in patients without RA (P > 0.05). In order to account for diabetes (DM) we formed 4 distinct patient groups. Group 1: RA-/DM- (n = 74); group 2: RA+/DM- (n = 195); group 3: RA-/DM+ (n = 52); group 4: RA+/DM+ (n = 20). Clustering of these groups revealed two distinct patient groups: those without RA and DM, and those with either RA or DM or both. The latter group showed statistically significant higher ACR (median 8.1 mg/g) as the former (median 4.5 mg/g). We found no significant correlation between AIx and ACR. Urinary albumin excretion in patients with RA or DM or both is higher than in subjects without RA and DM. This can be seen as a sign of vascular alteration and increased CV risk in these patients.

Power of national economy, disease control and employment status in patients with RA-an analytical multi-site ecological study.

In rheumatology, sufficient disease control is a central part of the treatment concept. However, modern treatment strategies are associated with a substantial economic burden for health care systems. Ecological studies offer the unique opportunity to analyse differences between groups as well as group level effects. In the present analytical multi-site ecological study, we investigated whether more powerful national economies as measured by the gross domestic product per capita (GDPpc) are associated with better disease control in RA patients as measured by the disease activity score 28 (DAS28). We used aggregated data on RA patients from the recently published COMORA study as well as the World Health Organization database. There was a strong negative correlation between DAS28 and GDPpc (r = -0.815; p = 0.0002). Adjustment for sex, smoking status, disease duration or current employment status did not significantly change this association. There was a strong, negative correlation between DAS28 and age (r = -0.870; p < 0.001) and a strong, positive correlation between GDPpc and age (r = 0.737; p = 0.002). Adjustment for age reduced the regression coefficient (DAS28/GDPpc) to -0.000018 (p = 0.054). There was a negative correlation between DAS28 and current employment status (r = -0.642; p = 0.008) and a positive correlation between GDPpc and employment status (r = 0.722; p = 0.002). In conclusion, there is evidence of an association between disease control and GDPpc. This association is alleviated after adjustment for age. Of note, in countries with higher GDPpc, a higher proportion of RA patients are currently employed. This is true despite the fact that RA patients in countries with higher GDPpc are also older.

Biological Therapies: Effects of Proinflammatory Pathways and their Inhibition on the Myocardium of Rheumatoid Athritis Patients.

BACKGROUND: The elevated risk of heart failure (HF) in rheumatoid arthritis (RA) is considered to be partly caused by the chronic low-grade systemic inflammation. As potent suppressors of inflammation, biologics were expected to influence HF development in RA. Unfortunately, case reports of HF in RA patients and non-RA HF studies have suggested that these drugs may even increase HF rates in RA. AIM: With this review we want to provide insight into the molecular mechanisms by which elevated cytokines, immune cell alterations and biologics influence myocardial function in RA patients. Beside preclinical data, clinical studies that assess the influence of biologics on HF development are reviewed. RESULTS: Preclinical studies suggest a bidirectional role of the investigated cytokines (TNF-alpha, IL- 1, IL-6) on myocardial function. Common mechanisms of immune cell alterations in HF and RA have been observed in preclinical studies. High doses of infliximab in non-RA patients with HF were found to be harmful. The vast majority of retrospective studies suggest that TNF-alpha inhibitors do not increase the risk of HF development in RA patients. Nevertheless randomized controlled trials are missing and TNF-alpha inhibitors are contraindicated in RA patients with HF NYHA III/IV and should be used with caution in RA patients with HF NYHA I/II based on non-RA HF studies. Due to rare adverse events of HF, rituximab is contraindicated in RA patients with HF NYHA IV. CONCLUSION: Cytokines seem to have a bidirectional influence on HF development in RA. According to the published evidence it is unlikely that TNFalpha inhibitors substantially increase the risk of HF development in an RA population. Nevertheless they are contraindicated in RA patients with HF NYHA III/IV and should be used with caution in RA patients with HF NYHA I/II. The influence of anakinra, tocilizumab, rituximab and abatacept needs to be investigated in future studies.

IgG4- related disease: an orphan disease with many faces.

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD.