Performance of a novel high-resolution infrared thermography marker in detecting and assessing joint inflammation: a comparison with joint ultrasound.

OBJECTIVES: To examine the value of a novel high-resolution thermographic marker in the detection of joint inflammation compared to joint ultrasound (US) and to suggest thermographic cut-off values of joint inflammatory activity. METHODS: Infrared thermographies were performed in patients with inflammatory arthritides and healthy controls. Patients were moreover examined clinically and by joint-US [Power-Doppler-(PDUS), Greyscale-US (GSUS)]. Regions of interest (ROIs) were defined for every joint and absolute temperature values within the ROIs were documented. The hottest areas ("hotspots") were identified by a clustering algorithm and the Hotspot/ROI-Ratio (HRR)-values were calculated. Subsequently, the HRR of patient-joints with different grades of hypervascularity (PDUS I°-III°) were compared among each other and with PDUS 0° control-joints. Diagnostic HRR-performance was tested by receiver-operating-characteristics. RESULTS: 360 joints of 75 arthritis-patients and 1,808 joints of 70 controls were thermographically examined. HRR-values were statistically different between PDUS I-III vs. PDUS 0 and vs. healthy subjects for all four joint groups as well as in the majority of cases between patient-joints with different grades of hypervascularity (PDUS I°-III°; p<0.05). Taking joint-US as a reference, the best performance of HRR was found at the level of the wrist-joints by an area under the curve (AUC) of 0.91 (95%CI 0.84-0.98) with a sensitivity of 0.83 and specificity of 0.88. CONCLUSIONS: HRR showed an excellent performance in the differentiation of joints with US inflammatory activity from non-inflamed joints. Moreover, HRR was able to differentiate between joints with different grades of hypervascularity, making HRR a promising tool to assist disease activity monitoring.

[Current patient care of systematic lupus erythematosus in Rhineland-Palatinate and Saarland]. / Versorgungssituation des Systemischen Lupus Erythematodes in Rheinland-Pfalz und dem Saarland.

BACKGROUND: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease that is associated with great suffering for those affected, as well as high socioeconomic costs. Early diagnosis and adequate medical care are essential for a mild course of the disease. However, there is a lack of current figures and data on the care situation of patients in the area. METHODOLOGY: A total of 1546 general practitioners, rheumatologists, neurologists, nephrologists and dermatologists in Rhineland-Palatinate and Saarland were interviewed by fax or mail using a questionnaire regarding epidemiology, symptoms, therapy and therapy success. In addition, there was the possibility of making suggestions for improvement. RESULTS: Five out of six of the 635 reported SLE patients were female. The most common main symptoms were arthralgia, fatigue, myalgia, and skin changes. Of the patients, 68% received antimalarials (AMs), whereas 46% were treated with glucocorticoids (GCs) and 50% with an immunosuppressant (IS), mainly methotrexate. In terms of comorbidities, patients suffered mainly from cardiovascular disease, fibromyalgia syndrome and depression. Rheumatologists also frequently described anaemia, diabetes mellitus and osteoporosis. DISCUSSION: Compared with guideline recommendations, the low rate of AMs in therapy was particularly striking in patients not treated by rheumatologists (35% on average compared with 81% for rheumatologists). Additionally, (sustained) high doses of GCs are not in line with literature recommendations. In the free text field, the main requests were for more rheumatologists in private practice and faster appointment scheduling, as well as better communication and networking. In addition, the desire for more training and education was frequently expressed..

Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Rheuma-VOR study: optimising healthcare of rheumatic diseases by multiprofessional coordinating centres.

OBJECTIVES: Early diagnosis of inflammatory arthritis is critical to prevent joint damage and functional incapacities. However, the discrepancy between recommendations of early diagnosis and reality is remarkable. The Rheuma-VOR study aimed to improve the time to diagnosis of patients with early arthritis by coordinating cooperation between primary care physicians, specialists and patients in Germany. METHODS: This prospective non-randomised multicentre study involved 2340 primary care physicians, 72 rheumatologists, 4 university hospitals and 4 rheumatology centres in 4 German Federal States. The two coprimary endpoints (time to diagnosis and screening performance of primary care physicians) were evaluated for early versus late implementation phase. Additionally, time to diagnosis and secondary endpoints (decrease of disease activity, increase in quality of life and overall well-being, improvement of fatigue, depression, functional ability, and work ability, reduction in drug and medical costs and hospitalisation) were compared with a reference cohort of the German Rheumatism Research Centre (DRFZ) reflecting standard care. RESULTS: A total of 7049 patients were enrolled in the coordination centres and 1537 patients were diagnosed with a rheumatic disease and consented to further participation. A follow-up consultation after 1 year was realised in 592 patients. The time to diagnosis endpoint and the secondary endpoints were met. In addition, the calculation of cost-effectiveness shows that Rheuma-VOR has a dominant cost-benefit ratio compared with standard care. DISCUSSION: Rheuma-VOR has shown an improvement in rheumatological care, patient-reported outcome parameters and cost savings by coordinating the cooperation of primary care physicians, rheumatologists and patients, in a nationwide approach.

Arterial Stiffness as a Surrogate Marker of Cardiovascular Disease and Atherosclerosis in Patients with Vasculitides: A Literature Review.

Vasculitis, a group of systemic inflammatory diseases that affect the cardiovascular (CV) system, presents with a variety of clinical manifestations that depend on the size of the affected blood vessels. While some types of vasculitis reveal distinct symptoms, others are characterized by more diffuse and nonspecific presentations that can result in delayed diagnosis and treatment initiation. Interestingly, patients with vasculitides share a significant comorbidity: an elevated CV risk, contributing to increased rates of CV events and mortality. This heightened risk is caused by cumulative inflammatory burden, traditional CV risk factors, medication effects, and reduced physical fitness. Traditional risk assessment tools, commonly used in the general population, frequently underestimate the CV risk in patients with inflammatory rheumatic conditions. Consequently, novel approaches are necessary to stratify the precise CV risk in vasculitis patients. A number of surrogate parameters for CV risk have been investigated, with arterial stiffness emerging as a promising marker. Pulse wave velocity (PWV) is a well-established method for assessing arterial stiffness and predicting CV risk across different populations. Among numerous PWV variants, carotid-femoral PWV (cfPWV) stands out as the most extensively studied and accepted reference standard. It has demonstrated its utility as a surrogate CV parameter both in the general population and in patients with systemic inflammatory rheumatic diseases. In recent years, research has expanded to assess arterial stiffness in systemic rheumatic diseases, such as arthritis, connective tissue diseases, rheumatologic overlap syndromes, and chronic pain disorders, using measurements of PWV and other markers of arterial compliance and elasticity. Despite burgeoning research in rheumatologic diseases, data on CV risk markers in vasculitides remain limited and fragmented. This narrative review aims to provide a comprehensive overview of arterial stiffness as a potential screening marker for CV diseases, atheromatosis, and ultimately CV risk among patients with vasculitides.

Diagnostic Value of Labial Minor Salivary Gland Biopsy: Histological Findings of a Large Sicca Cohort and Clinical Associations.

(1) Background: The aim of this study was to analyze labial minor salivary gland biopsy (MSGB) findings of a large sicca cohort and to examine their associations with Sjogren's syndrome (SS)-associated laboratory markers, phenotypic characteristics and systemic manifestations. Moreover, we sought to explore the ability of MSGB to identify SS patients among subjects with pre-diagnosed fibromyalgia (FM). (2) Methods: Included were all patients of three rheumatology departments having undergone a diagnostic MSGB within 9 years. Next to the examination of histological and immunohistochemical findings, we focused on activity and chronicity parameters of the underlying disease, autoantibodies, presence of systemic and hematologic involvement, as well as chronic pain and SS comorbidities. (3) Results: Among the 678 included patients, 306 (45.1%) had a positive focus score (FS). The remaining patients (n = 372) served as control subjects. There were significant correlations between FS and hypergammaglobulinemia (p < 0.001), ANA and rheumatoid factor positivity (both; p < 0.001), a weak significant correlation with erythrocyte sedimentation rate (rho = 0.235; p < 0.001) and a negative correlation with nicotine use (p = 0.002). Within the primary SS subgroup, FS was associated significantly with glandular enlargement (p = 0.007) and systemic hematologic manifestations (p = 0.002). Next to FS, CD20 cell staining showed an excellent diagnostic performance in the diagnosis of SS by an area under the curve of 0.822 (95%CI 0.780-0.864; p < 0.001). Interestingly, 42.1% of all patients with fibromyalgia (FM) having received an MSGB could be diagnosed with SS. (4) Conclusion: By examining one of the largest cohorts in the literature, we could show that MSGB histological and immunohistochemical findings not only play a key role in the classification and diagnosis of SS but could also provide important information regarding SS phenotype and systemic manifestations. Furthermore, MSGB may help differentiate patients with FM from patients with subclinical SS who suffer primarily from chronic pain.

Arterial Stiffness as a Surrogate Marker of Cardiovascular Disease and Atherosclerosis in Patients with Arthritides and Connective Tissue Diseases: A Literature Review.

The increased cardiovascular (CV) risk among patients with autoimmune rheumatic diseases, such as arthritides and connective tissue diseases, has been extensively documented. From a pathophysiological standpoint, systemic inflammation in the context of the disease can lead to endothelial dysfunction, accelerated atherosclerosis, and structural changes in vessel walls, which, in turn, are associated with exaggerated CV morbidity and mortality. In addition to these abnormalities, the increased prevalence of traditional CV risk factors, such as obesity, dyslipidemia, arterial hypertension, and impaired glucose metabolism, can further worsen the status of and overall prognosis for CV in rheumatic patients. However, data on appropriate CV screening methods for patients with systemic autoimmune diseases are scarce, and traditional algorithms may lead to an underestimation of the true CV risk. The reason for this is that these calculations were developed for the general population and thus do not take into account the effect of the inflammatory burden, as well as other chronic-disease-associated CV risk factors. In recent years, different research groups, including ours, have examined the value of different CV surrogate markers, including carotid sonography, carotid-femoral pulse wave velocity, and flow-mediated arterial dilation, in the assessment of CV risk in healthy and rheumatic populations. In particular, arterial stiffness has been thoroughly examined in a number of studies, showing high diagnostic and predictive value for the occurrence of CV events. To this end, the present narrative review showcases a series of studies examining aortic and peripheral arterial stiffness as surrogates of all-cause CV disease and atherosclerosis in patients with rheumatoid and psoriatic arthritis, as well as in systemic lupus erythematosus and systemic sclerosis. Moreover, we discuss the associations of arterial stiffness with clinical, laboratory, and disease-specific parameters.

Optical spectral transmission to assess glucocorticoid therapy response in patients with arthritis: a longitudinal follow-up comparison with joint ultrasound.

BACKGROUND: Optical spectral transmission (OST) is a modern diagnostic modality, able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with arthritis. To date, there are no adequate data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes, during arthritis follow-up. Objectives of this study were therefore to examine the performance of OST in assessing response to anti-inflammatory therapy in patients with active arthritis and to explore OST associations with clinical, laboratory, and ultrasonographic (US) activity markers. METHODS: 1173 joints of 54 patients with arthritides of the wrist and finger joints were examined by OST before and after oral administration of glucocorticoids (GC), during a disease flare. For the same time-points patients underwent clinical, laboratory, and joint US [grayscale (GSUS), power-Doppler (PDUS)] examinations. The distribution of ΔOST-values between the two time-points was compared with the respective distributions of ΔPDUS and ΔGSUS by Bayesian statistical analyses. Moreover, the diagnostic performance of OST compared to a control group (2508 joints of 114 subjects) was examined by receiver operating characteristics and associations of OST values with clinical, laboratory, and arthrosonographic parameters were evaluated by correlation analyses. RESULTS: OST and US performed similarly in the assessment of inflammatory changes caused by GC (same value-change tendency in 83.2% of the cases). Bayesian statistics revealed no significant differences between ΔOST and ΔPDUS for all 3 examined joint categories (accuracy: metacarpophalangeal (MCP): 68.1%; proximal interphalangeal (PIP): 60.4%; wrists: 50.4%) and between ΔOST and ΔGSUS for MCP and PIP joints (accuracy: 51.1% and 78.7%, respectively). OST diagnostic performance (patients vs. controls) was excellent in both time-points [area under the curve (AUC) before GC=0.883(95%CI=0.83-0.94) and after GC=0.811(95%CI=0.74-0.881); p<0.001]. Furthermore, OST correlated significantly with all examined sonographic activity scores (all; p<0.001) and with swollen joint counts (p<0.01). CONCLUSIONS: OST was able to assess response to therapy in a similar way to joint US and correlated significantly with arthritis activity markers. Therefore, OST has proved to be a valuable tool to assist disease activity monitoring in the examined cohort. TRIAL REGISTRATION: German Registry of Clinical Trials, DRKS00016752.

NMDA Receptors in Health and Diseases: New Roles and Signaling Pathways-Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Autoantibodies as Potential Biomarkers of Fatigue in Patients with Rheumatic Diseases.

Fatigue is a widespread and complex symptom with motor and cognitive components; it is diagnosed predominantly by questionnaire. We recently published a correlation between anti-N-methyl-D-aspartate receptor (NMDAR) antibodies and fatigue in patients with SLE (systemic lupus erythematosus). In the present study, we examined whether this association also applies to patients with other rheumatic diseases. Serum samples of 88 patients with different rheumatic diseases were analyzed for the presence of anti-NR2 antibodies and Neurofilament light chain (NfL) protein. The severity of fatigue was determined according to the FSMC questionnaire (Fatigue Scale for Motor and Cognitive Functions) and correlated with the circulating antibody titer and NfL level accordingly. Positive titers of anti-NR2 antibodies were detected in patients with both autoimmune and non-autoimmune rheumatic diseases. These patients suffer predominantly from severe fatigue. The circulating NfL level did not correlate with the anti-NR2 titer and the fatigue severity in all patient groups. The association of severe fatigue with circulating anti-NR2 antibodies in patients with rheumatic diseases, independently from the main disease, suggests an individual role of these autoantibodies in fatigue pathophysiology. Thus, the detection of these autoantibodies might be a helpful diagnostic tool in rheumatic patients with fatigue.

Novel Surrogate Markers of Cardiovascular Risk in the Setting of Autoimmune Rheumatic Diseases: Current Data and Implications for the Future.

Patients suffering from rheumatologic diseases are known to have an increased risk for cardiovascular disease (CVD). Although the pathological mechanisms behind this excess risk have been increasingly better understood, there still seems to be a general lack of consensus in early detection and treatment of endothelial dysfunction and CVD risk in patients suffering from rheumatologic diseases and in particular in those who haven't yet shown symptoms of CVD. Traditional CVD prediction scores, such as Systematic Coronary Risk Evaluation (SCORE), Framingham, or PROCAM Score have been proposed as valid assessment tools of CVD risk in the general population. However, these risk calculators developed for the general population do not factor in the effect of the inflammatory burden, as well as other factors that can increase CVD risk in patients with rheumatic diseases, such as glucocorticoid therapy, abnormal lipoprotein function, endothelial dysfunction or accelerated atherosclerosis. Thus, their sole use could lead to underestimation of CVD risk in patients with rheumatic diseases. Therefore, there is a need for new biomarkers which will allow a valid and early assessment of CVD risk. In recent years, different research groups, including ours, have examined the value of different CVD risk factors such as carotid sonography, carotid-femoral pulse wave velocity, flow-mediated arterial dilation and others in the assessment of CVD risk. Moreover, various novel CVD laboratory markers have been examined in the setting of autoimmune diseases, such as Paraoxonase activity, Endocan and Osteoprotegerin. Dyslipidemia in rheumatoid arthritis (RA) is for instance better quantified by lipoproteins and apolipoproteins than by cholesterol levels; screening as well as pre-emptive carotid sonography hold promise to identify patients earlier, when prophylaxis is more likely to be effective. The early detection of subtle changes indicating CVD in asymptomatic patients has been facilitated through improved imaging methods; the inclusion of artificial intelligence (AI) shows promising results in more recent studies. Even though the pathophysiology of coronary artery disease in patients with autoimmune rheumatic diseases has been examined in multiple studies, as we continuously gain an increased understanding of this comorbidity, particularly in subclinical cases we still seem to fail in the stratification of who really is at risk-and who is not. A the time being, a multipronged and personalized approach of screening patients for traditional CVD risk factors, integrating modern imaging and further CV diagnostic tools and optimizing treatment seems to be a solid approach. There is promising research on novel biomarkers, likewise, methods using artificial intelligence in imaging provide encouraging data indicating possibilities of risk stratification that might become gold standard in the near future. The present review concentrates on showcasing the newest findings concerning CVD risk in patients with rheumatologic diseases and aims to evaluate screening methods in order to optimize CVD risk evaluation and thus avoiding underdiagnosis and undertreatment, as well as highlighting which patient groups are most at risk.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Development and Validation of Rheumatoid Arthritis Disease Activity Indices Including HandScan (Optical Spectral Transmission) Scores.

OBJECTIVE: To develop and validate a composite rheumatoid arthritis (RA) disease activity index using optical spectral transmission (OST) scores obtained with the HandScan, replacing tender and swollen joint counts. METHODS: RA patients from a single center routinely undergoing HandScan measurements with at least 1 concurrent OST score and Disease Activity Score in 28 joints (DAS28) were included. Data were extracted from medical records. Linear regression analyses with the DAS28 as the outcome were performed to create a disease activity index (DAS-OST). OST score, erythrocyte sedimentation rate (ESR), and patient global assessment (PtGA) visual analog scale (VAS), sex, age, disease duration, and rheumatoid factor status were evaluated as independent variables. Final models were derived based on the statistical significance of coefficients and model fit. Of the data, two-thirds were used for development and one-third for validation; external validation was performed in a cohort from another center. Agreement between DAS-OST and DAS28 was assessed using the Bland-Altman plot method and intraclass correlation coefficient (ICC). Diagnostic value of the DAS-OST was determined for established definitions of remission, low disease activity (LDA), and high disease activity (HDA). RESULTS: Data of 3,358 observations from 1,505 unique RA patients were extracted. DAS-OST was defined as: -0.44 + OST × 0.03 + male × -0.11 + LN(ESR) × 0.77 + PtGA VAS × 0.03. The ICCs between DAS-OST and DAS28 were 0.88 (95% confidence interval [95% CI] 0.87-0.90) and 0.82 (95% CI 0.75-0.86) and measurement errors were 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA, and HDA was 79%, 91%, and 43%, respectively, and specificity was 92%, 80%, and 96% in external validation. CONCLUSION: Using the HandScan, RA disease activity can be accurately estimated if combined with ESR, PtGA VAS, and sex into a disease activity index (DAS-OST).

The clinical phenotype of systemic sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort.

OBJECTIVE: To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD). METHODS: (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl-, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case-control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl- SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset. RESULTS: Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl-, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. CONCLUSION: The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.

Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A.

OBJECTIVES: To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. METHODS: SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media thickness (cIMT), plaques and Doppler sonographic cerebrovascular surrogates [resistance (RI) and pulsatility (PI) indices]. RESULTS: We recruited 66 ASyS patients and 88 controls. According to mSCORE, 10% of the patients had high CV risk. However, cfPWV and carotid sonography revealed an increased CV risk in 21.2% and subclinical carotid atherosclerosis (SCA) in 85.7% of the patients, respectively. cfPWV and cIMT were higher in patients compared with controls (Padj=0.021 and Padj=0.003, respectively). In the ASyS group, cfPWV and cIMT correlated significantly with age (r = 0.679; P<0.001 and r = 0.664; P<0.001, respectively). Moreover, cfPWV correlated with BMI (Padj=0.001) and diabetes (Padj=0.043). CCA-RI and CCA-PI showed significant associations with creatine phosphokinase (r = 0.629; P=0.012 and r = 0.574; P=0.032, respectively) and ICA-RI and ICA-PI were higher in patients with lung involvement (both; P=0.039). CONCLUSION: ASyS patients had higher aortic stiffness and SCA compared with controls, even after adjustment for confounders. SCORE/mSCORE performed poorly in identifying high-risk patients compared with cfPWV and carotid sonography. Thus, cfPWV and carotid sonography may improve CV and cerebrovascular screening in ASyS.

Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New.

Despite recent improvements in the treatment of systemic lupus erythematosus (SLE), disease activity, comorbidities and drug toxicity significantly contribute to the risk of progressive irreversible damage accrual and increased mortality in patients with this chronic disease. Moreover, even lupus patients in remission often report residual symptoms, such as fatigue, which have a considerable impact on their health-related quality of life. In recent decades, SLE treatment has moved from the use of hydroxychloroquine, systemic glucocorticosteroids and conventional immunosuppressive drugs to biologic agents, of which belimumab is the first and only biologic agent approved for the treatment for SLE to date. Novel therapies targeting interferons, cytokines and their receptors, intracellular signals, plasma cells, T lymphocytes and co-stimulatory molecules are being evaluated. In the context of a holistic approach, growing evidence is emerging of the importance of correct lifestyle habits in the management of lupus manifestations and comorbidities. The aim of this paper is to provide an overview of current pharmacological and non-pharmacological treatment options and emerging therapies in SLE.

Diagnostic Value of Optical Spectral Transmission in Rheumatoid Arthritis: Associations with Clinical Characteristics and Comparison with Joint Ultrasonography.

OBJECTIVE: To examine the value of optical spectral transmission (OST) in detecting joint inflammation in patients with rheumatoid arthritis (RA) and to evaluate whether OST correlates with certain patient characteristics. METHODS: OST measurements were performed in the metacarpophalangeal, proximal intraphalangeal, and wrist joints of 168 patients with RA and 114 controls. OST difference between the 2 groups was statistically examined and subsequently controlled for the effect of possible confounding factors. Diagnostic OST performance was tested by receiver-operating characteristics. Moreover, associations of OST with clinical and serological activity markers (patient group), joint ultrasound (US; patient subgroup) and various anthropometric and epidemiologic parameters (patient and control group) were evaluated by Spearman correlation coefficient and a generalized linear statistical adjustment model. RESULTS: OST was significantly higher in the RA group than in the control group, even after adjustment for confounding factors (1.89; 95% CI 0.709-3.070, padj = 0.002). Taking US as a reference, area under the curve for all 1251 joints simultaneously was 0.67 (95% CI 0.631-0.709). In the patient group, correlation and adjustment analyses showed associations of OST with various disease activity markers [28-joint count Disease Activity Score (rho 0.313), swollen joint counts (rho 0.361), C-reactive protein (rho 0.389); all, padj = 0.001], age (rho 0.276, p < 0.001), and osteoarthritis (p = 0.022). Moreover, OST associated with a power Doppler US score (rho 0.442; p = 0.001) and a greyscale US score (rho 0.591; p < 0.001). In both groups males had significantly higher OST values than females and OST associated moderately weakly with body mass index (rho patients 0.316, rho controls 0.24; all, p < 0.001). CONCLUSION: Patients with RA showed higher OST values in comparison to controls. Moreover, OST associated with clinical, US, and laboratory disease activity markers.

Vascular stiffness: influencing factors on carotid-femoral pulse wave velocity in systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are under increased risk for cardiovascular events (CVE) and mortality. Aortic stiffness, as measured by carotid-femoral pulse wave velocity (cfPWV), has been shown to predict CVE and mortality in the general population. The aim of the present study was to examine the factors associated with cfPWV in patients with SLE and to determine differences of SLE patients in comparison to healthy controls. METHODS: 125 patients with SLE and 104 controls were included. Demographic, medication and cardiovascular risk factor data were collected from all participants. Furthermore, clinical and laboratory SLE associated parameters were documented in the patients' group. All subjects underwent measurements of blood pressure and cfPWV. RESULTS: Interestingly, only age (ß=0.55; p<0.001), mean arterial pressure (MAP) (ß=0.29; p<0.001) and estimated glomerular filtration rate (eGFR) (ß=-0.20; p=0.033) were associated independently with cfPWV in patients with SLE. Moreover, there was no difference of cfPWV between patients with SLE and controls before (p=0.301) and after adjustment for disparities between the groups (p=0.671). CONCLUSIONS: Vascular stiffness in patients with SLE seems to be independent from SLE-related factors and from most traditional CVRF and is mainly associated with age, MAP and renal function defined as eGFR. There is an independent correlation between eGFR and cfPWV in a SLE population with a widely normally ranged eGFR. There is no difference of cfPWV between patients with SLE and controls.

Fatigue in SLE: diagnostic and pathogenic impact of anti-N-methyl-D-aspartate receptor (NMDAR) autoantibodies.

OBJECTIVES: We explored the impact of circulating anti-N-methyl-D-aspartate receptor (NMDAR) antibodies on the severity of fatigue in patients with systemic lupus erythematosus (SLE). METHODS: Serum samples of 426 patients with SLE were analysed for the presence of antibodies to the NR2 subunit of the NMDAR. In parallel, the severity of fatigue was determined according to the Fatigue Scale for Motor and Cognitive functions questionnaire. In a subgroup of patients with SLE, the hippocampal volume was correlated with the levels of anti-NR2 antibodies. Isolated immunoglobulin G from patients with anti-NR2 antibodies were used for murine immunohistochemical experiments and functional assays on neuronal cell lines. Treatment effects were studied in 86 patients with lupus under belimumab therapy. RESULTS: We found a close correlation between the titre of anti-NR2 antibodies, the severity of fatigue, the clinical disease activity index (Systemic Lupus Erythematosus Disease Activity Index 2000) and anti-double stranded DNA antibodies-independently of the presence of neuropsychiatric lupus manifestations. Pathogenic effects could be demonstrated by (1) detection of anti-NR2 antibodies in the cerebrospinal fluid, (2) in situ binding of anti-NR2 antibodies to NMDAR of the hippocampus area and (3) distinct functional effects in vitro: downregulating the energy metabolism of neuronal cells without enhanced cytotoxicity. Treatment with belimumab for at least 6 months affected both the severity of fatigue and the levels of anti-NR2 antibodies. CONCLUSION: The presence of anti-NR2 antibodies in patients with SLE with fatigue is a helpful diagnostic tool and may offer a major approach in the therapeutic management of this important disabling symptom in patients with SLE.