Real-world experience with filgotinib for rheumatoid arthritis in Germany : A retrospective chart review.

BACKGROUND: Real-world data for filgotinib, a Janus kinase (JAK)1 inhibitor, are limited in patients with rheumatoid arthritis (RA). OBJECTIVES: To explore real-world filgotinib use in patients with RA in Germany. MATERIALS AND METHODS: This retrospective chart review included patients aged ≥ 18 years with confirmed moderate to severe RA who initiated filgotinib before December 1, 2021, with ≥ 6 months of medical records available prior to filgotinib initiation or after initial diagnosis. Patient characteristics, prior treatments, reasons for initiating/discontinuing filgotinib, disease activity, dose adjustments and concomitant treatments were recorded. RESULTS: In total, 301 patients from 20 German rheumatology outpatient units were included. One-third were aged ≥ 65 years and almost half had ≥ 1 cardiovascular (CV) risk factor. Most patients initiated filgotinib as monotherapy (83.7%; 12.7% of whom with glucocorticoids) and at the 200 mg dose (84.7%); higher proportions of those initiating the 100 versus 200 mg dose were aged ≥ 65 years and had renal impairment or ≥ 1 CV risk factor. Oral administration (78.4%), fast onset of action (66.8%) and administration as monotherapy (65.4%) were the most common reasons for initiating filgotinib. At 12 months, 41 (18.4%) patients had discontinued filgotinib, most commonly due to lack of effectiveness. After 6­months of follow-up, 36.8% of patients had achieved Clinical Disease Activity Index (CDAI) remission and 45.6% had achieved CDAI low disease activity. CONCLUSIONS: In clinical practice in Germany, reasons for initiating filgotinib in patients with RA were related to dosing flexibility and general JAK inhibitor attributes. Filgotinib was used predominantly as monotherapy and was effective and generally well tolerated; however, longer-term data in larger, prospective cohorts are needed.

[Rheumatoid arthritis: Appraisement of the new security warnings for JAK-inhibitors]. / Rheumatoide Arthritis ­ Einordnung der neuen Sicherheitswarnungen für JAK-Inhibitoren.

Januskinase-Inhibitors (JAKI) are highly effective substances (JAKi) for the treatment of rheumatoid arthritis (RA). In terms of efficiency in reduction of disease activity and induction of remission they are partially prior to biologic (b) DMARDs. Presently the four substances tofacitinib, baricitinib, upadacitinib and filgotinib are approved for the treatment of RA. The prospective controlled ORAL-SURVEILLANCE-trial investigated the safety of tofacitinib in comparison to TNF-inhibitors. Current results now show that treatment with tofacitinib might be associated with an increased risk for cardiovascular events, thromboembolism and certain malignancies. Affected are patients >65y, current or former smoker and, regarding cardiovascular events, patients who already had such an event. On the basis of this trial the Committee for Medical Products for Human Use (CHMP) of the European Medicines Agency (EMA) formulated actual recommendations for prescription of JAKi in order to reduce the risk of severe undesirable effects. These apply not only for tofacitinib but as well for all other JAKI named above, as a class effect was supposed. The data and their consequences are discussed and evaluated in this work.

Hypochromic red cells as a prognostic indicator of survival among patients with systemic sclerosis screened for pulmonary hypertension.

BACKGROUND: Patients with systemic sclerosis (SSc) are frequently affected by iron deficiency, particularly those with pulmonary hypertension (PH). The first data indicate the prognostic importance of hypochromic red cells (% HRC) > 2% among patients with PH. Hence, the objective of our study was to investigate the prognostic value of % HRC in SSc patients screened for PH. METHODS: In this retrospective, single-center cohort study, SSc patients with a screening for PH were enrolled. Clinical characteristics and laboratory and pulmonary functional parameters associated with the prognosis of SSc were analyzed using uni- and multivariable analysis. RESULTS: From 280 SSc patients screened, 171 could be included in the analysis having available data of iron metabolism (81% female, 60 ± 13 years of age, 77% limited cutaneous SSc, 65 manifest PH, and 73 pulmonary fibrosis). The patients were followed for 2.4 ± 1.8 (median 2.4) years. HRC > 2% at baseline was significantly associated with worse survival in the uni- (p = 0.018) and multivariable (p = 0.031) analysis independent from the presence of PH or pulmonary parenchymal manifestations. The combination of HRC > 2% and low diffusion capacity for carbon monoxide (DLCO) ≤ 65% predicted was significantly associated with survival (p < 0.0001). CONCLUSION: This is the first study reporting that HRC > 2% is an independent prognostic predictor of mortality and can possibly be used as a biomarker among SSc patients. The combination of HRC > 2% and DLCO ≤ 65% predicted could serve in the risk stratification of SSc patients. Larger studies are required to confirm these findings.

Real-world treatment persistence in patients with rheumatoid arthritis initiating DMARDs in Germany-a health insurance claims data analysis.

OBJECTIVE: To investigate treatment patterns in patients with rheumatoid arthritis (RA) in Germany who had previously received conventional synthetic (cs) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients with RA who initiated treatment with a csDMARD, bDMARD, or Janus kinase (JAK) inhibitor between 2017 and 2018 and who had previously received csDMARD or bDMARD therapy were retrospectively selected from the Institute for Applied Health Research Berlin GmbH (InGef). Time on treatment and discontinuation risk were assessed using the Kaplan-Meier method. Cox regression identified variables associated with an increased discontinuation risk. RESULTS: A total of 990 patients had received prior csDMARD therapy; 375 had received prior bDMARD therapy. Tumor necrosis factor (TNF)-α inhibitors and JAK inhibitors were the most commonly prescribed DMARD class in those previously treated with a csDMARD or bDMARD, respectively. In both cohorts, more patients received DMARD monotherapy than combination therapy. In the prior csDMARD cohort, median time on treatment was 276, 252, and 148 days with JAK inhibitors, TNF­α inhibitors, and csDMARDs, respectively, and those treated with JAK or TNF­α inhibitors were less likely to discontinue treatment than those on csDMARDs (log-rank test p-value < 0.01 for both comparisons); no significant differences were found within the prior bDMARD cohort. CONCLUSION: This is among the first detailed analyses of RA treatment patterns in a real-world setting in Germany since the introduction of JAK inhibitors. TNF­α inhibitors were the most commonly prescribed DMARD after failure of an initial csDMARD, while JAK inhibitors were the most common among patients previously treated with a bDMARD. In both groups, monotherapy with bDMARD or targeted synthetic DMARD was common. In the prior csDMARD cohort, treatment duration was significantly longer with JAK or TNF­α inhibitors than with csDMARDs.

Fatigue is independently associated with disease activity assessed using the Physician Global Assessment but not the SLEDAI in patients with systemic lupus erythematosus.

OBJECTIVES: To analyse whether reported fatigue, one of the most challenging manifestations of systemic lupus erythematosus (SLE), may bias the assessment of disease activity in SLE according to the Physician Global Assessment (PGA). METHODS: Patients from the Lupus BioBank of the upper Rhein database, a cross-sectional multicentre collection of detailed clinical and biological data from patients with SLE, were included. Patients had to fulfil the 1997 American College of Rheumatology criteria for SLE and the PGA (0-3 scale) at the time of inclusion had to be available. Fatigue was assessed according to the Fatigue Scale for Motor and Cognitive Functions. Univariate and multivariate regression models were built to determine which variables were associated with the PGA. RESULTS: A total of 350 patients (89% female; median age: 42 years, IQR: 34-52) were included. The median Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 4 (IQR: 2-6). Of these 350 patients, 257 (73%) reported significant fatigue. The PGA (p=0.004) but not the SELENA-SLEDAI (p=0.43) was significantly associated with fatigue. Both fatigue and SELENA-SLEDAI were independently associated with the PGA in two different multivariate models. CONCLUSION: Fatigue is independently associated with disease activity assessed using the PGA but not the SLEDAI. These findings highlight the fact that the PGA should capture only objectively active disease manifestations in order to improve its reliability.

[Drug-induced osteopathy in rheumatology]. / Medikamenteninduzierte Osteopathien in der Rheumatologie.

Osteopathy in rheumatology can either be primary a condition as a consequence of inflammatory rheumatic diseases but can also be drug induced. The most severe clinical manifestations are insufficiency fractures and osteonecrosis. The risk of fractures is highest for patients treated with glucocorticoids depending on the daily intake, the cumulative glucocorticoid dosage and the duration of administration. An incidence rate of nearly 13% was reported after administration of glucocorticoids lasting > 1 year. Cases of osteonecrosis under glucocorticoids are, in contrast, less frequent and not associated with glucocorticoid-induced osteoporosis. The antiresorptive substances bisphosphonates and denosumab, as well as romosumab are effective and important in treating osteoporosis; however, they can also cause atypical fractures, particularly of the femur as well as osteonecrosis of the jawbone. According to the most recent guidelines the benefits of bisphosphonate treatment have only been verified for 3-5 years and for denosumab for 3 years. There are clear preventive recommendations to avoid osteonecrosis of the jaw. Ultimately, the disease-modifying antirheumatic drugs (DMARD) methotrexate and leflunomide also affect the metabolism of bones. There is a rare but very characteristic form of osteopathy associated with methotrexate, mainly occurring in cases of long-term treatment. The typical manifestations are insufficiency fractures, particularly of the distal tibia, which persist for many years under continuous methotrexate administration. The treatment is the discontinuation of methotrexate and in most cases the fractures will heal within 3-4 months. Leflunomide has been associated with cases of persisting pseudarthrosis that only disappeared after a wash-out of the active metabolite.

[Treatment of rheumatoid arthritis and spondylarthritis with biologics]. / Biologikatherapie von rheumatoider Arthritis und Spondyloarthritiden.

Biologics are an integral part of modern strategies for treatment of rheumatoid arthritis (RA) and spondylarthritis (SpA), including psoriatic arthritis (PsA). Biologics are biotechnologically produced proteins that have inhibiting effects on humoral and cellular components of rheumatic inflammation. Substance classes used in rheumatology are tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL­6, IL-12, IL-17 and IL-23 inhibitors effective against cytokines as well as the T lymphocyte activation inhibitor abatacept and the B lymphocyte-depleting rituximab. There are clear recommendations for the use of biologics for RA patients inadequately responding to one or more conventional synthetic disease-modifying antirheumatic drugs and for ankylosing spondylitis (AS) and nonradiographical axial SpA patients with an inadequate response to at least two nonsteroidal antirheumatic drugs. For PsA the recommended use depends on the most prominent manifestations in each case. Treatment with biologics should follow the treat to target principle, with a defined and validated treatment target. Treatment in cases of RA and SpA should target remission or at least a low or minimum disease activity. The safety of treatment with biologics has been intensively investigated. There are very specific contraindications for individual substance classes with a focus on an increased risk of infections. The standard procedure before starting treatment with biologics includes the exclusion of latent tuberculosis and hepatitis B. The TNF-alpha inhibitors have a protective effect with respect to myocardial infarction, stroke and venous thromboembolism.

Inflammatory Pseudotumor in the Parapharyngeal Space: Is It Possible to Diagnose by Exclusion?

Inflammatory pseudotumor (IP) is a rare pathologic condition that easily can be confounded with malignancy. The clinical presentation depends on the site of occurrence and the radiological or laboratory findings are not specific. Diagnosis can be established only with histology. We report a case of a 64-year-old woman with IP in an uncommon localization, the parapharyngeal space extending to skull base. Although the diagnosis was not certain after histopathological examination, broad diagnostic workup helped to exclude malignancy or bacterial infection and led to diagnosis of an IP by exclusion. We observed a good clinical and radiological regression of symptoms after administration of oral immunosuppressants, confirming the immunological mechanism of the disease.

[Care atlas rheumatology : Approaches and concepts for improving care in outpatient rheumatology]. / Versorgungsatlas Rheumatologie : Ansätze und Konzepte zur Verbesserung der Versorgung in der ambulanten Rheumatologie.

Inflammatory rheumatic diseases affect 1.5 million adults and an estimated 20,000 children and adolescents throughout Germany. The successful treatment of these patients is largely based on the availability of high-quality medical care. To be able to provide sufficient care and prevent long waiting times even though the number of rheumatologists is below demand, efficient practice structures and approaches that go beyond standard care play an important role. The present study takes a look at the current state of rheumatological outpatient care as well as innovative care initiatives to support the service provision structures and to improve the care situation in rheumatology and points out: to ensure guideline-based care despite scarce resources, selective contracts, integrated outpatient specialist care (ASV), early or emergency consultation hours, disease management programs (DMP) and appropriate delegation of medical services play an important role. New care concepts increasingly focus on interdisciplinary cooperation (DMP and ASV), strengthened self-management through structured patient training (DMP) and targeted patient management through screening tools. To ensure an up to date and high-quality treatment in the long term, an increase in further training in rheumatology is necessary. This should be achieved by attracting more students and, if necessary, adjusting the training system.

[Glucocorticoid-free and low-dose glucocorticoid treatment of rheumatoid arthritis]. / Glukokortikoidfreie und glukokortikoidarme Therapie der rheumatoiden Arthritis.

Systemic glucocorticoids (GC) are a commonly used component in the treatment of rheumatoid arthritis. The aim of this article is to show the evidence for low-dose GC or GC-free RA treatment regimens. Furthermore, concepts for the de-escalation of GC treatment for RA are presented. There is sufficient evidence in the initial phase that GC treatment in addition to methotrexate (MTX) improves the patient's response to the disease activity as well as the subjective perception of impairments. The dosage of GC, however, needs to be weighed critically and the guideline-based gradual reduction leading eventually to discontinuation must consistently be pursued. In the later phases of the treatment algorithm the risks of GC administration outweigh the benefits and long-term GC treatment should therefore be reserved for exceptional cases. The lowest possible dosage always needs to be determined individually. This can be achieved by using a clinically tested scheme of reducing the prednisolone intake by 1 mg every 4 weeks. The scheme should be considered for patients with a low disease activity or remission due to disease-modifying antirheumatic drug (DMARD) treatment, if they receive 5 mg of prednisolone as long-term treatment. On the whole the positive subjective effects of GC treatment must always be weighed up against the risks of such treatment for RA patients. An ongoing process of readjusting treatment following shared-decision rules must both consistently adapt GC doses and constantly check the indications. Even if a GC-free treatment does not seem realistic, a low-dose GC treatment of RA still is and should be pursued to reduce the risks associated with the treatment.

Differential diagnostic value of rheumatic symptoms in patients with Whipple's disease.

Most patients with Whipple's disease have rheumatic symptoms. The aim of our prospective, questionnaire-based, non-interventional clinical study was to assess whether these symptoms are useful in guiding the differential diagnosis to the rheumatic disorders. Forty patients with Whipple's disease, followed by 20 patients for validation and 30 patients with rheumatoid-, 21 with psoriatic-, 15 with palindromic- and 25 with axial spondyloarthritis were recruited for the present investigation. Patients with Whipple's disease and patients with rheumatic disorders were asked to record rheumatic symptoms on pseudonymized questionnaires. The data obtained were subjected to multiple logistic regression analysis. Episodic pain with rapid onset, springing from joint to joint was most common in patients with palindromic arthritis and second most common and somewhat less conspicuous in Whipple's disease. Continuous pain in the same joints predominated in patients with rheumatoid-, psoriatic-, and axial spondyloarthritis. Multiple logistic equations resulted in a predicted probability for the diagnosis of Whipple's disease of 43.4 ± 0.19% (M ± SD) versus a significantly lower probability of 23.8 ± 0.19% (M ± SD) in the aggregate of patients with rheumatic disorders. Mean area under the curve (AUC) ± SD was 0.781 ± 0.044, 95% CI 0.695-0.867, asymptotic significance p < 0.001. The logistic equations predicted probability for the diagnosis of Whipple's disease in the initial series of 40 patients of 43.4 ± 0.19% was not significantly different in the subsequent 20 patients of 38.2 ± 0.28% (M ± SD) (p = 0.376). The data may be useful in a predictive algorithm for diagnosing Whipple's disease. The project is registered as clinical study DRK S0001566.

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.

Patterns of fatigue and association with disease activity and clinical manifestations in systemic lupus erythematosus.

OBJECTIVE: The prevalence of fatigue is high in patients with systemic lupus erythematosus (SLE). In this study, we used latent class analysis to reveal patterns of fatigue, anxiety, depression and organ involvement in a large international cohort of SLE patients. METHODS: We used the Lupus BioBank of the upper Rhein to analyse patterns of fatigue using latent class analysis (LCA). After determining the optimal number of latent classes, patients were assigned according to model generated probabilities, and characteristics of classes were compared. RESULTS: A total of 502 patients were included. Significant fatigue, anxiety and depression were reported by 341 (67.9%), 159 (31.7%) and 52 (10.4%) patients, respectively. LCA revealed a first cluster (67.5% of patients) with low disease activity [median (25th-75th percentile interquartile range) Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI: 2 (0-4)], significant fatigue (55.5%, P < 0.0001), low anxiety (11.8%, P < 0.0001) and depression (0.9%, P < 0.0001). Cluster 2 (25.3%) also comprised patients with low disease activity [SELENA-SLEDAI: 2 (0-6)], but those patients had a very high prevalence of fatigue (100%, P < 0.0001), anxiety (89%, P < 0.0001) and depression (38.6%, P < 0.0001). Cluster 3 (7.2%) comprised patients with high disease activity [SELENA-SLEDAI: 12 (8-17), P < 0.0001] and high fatigue (72.2%, P < 0.0001) with low levels of anxiety (16.7%, P < 0.0001) and no depression (0%, P < 0.0001). CONCLUSION: LCA revealed three patterns of fatigue with important practical implications. Based on these, it is crucial to distinguish patients with active disease (in whom remission will be achieved) from those with no or mild activity but high levels of fatigue, depression and anxiety, for whom psychological counselling should be prioritized.

[Recommendations of the German Society for Rheumatology for management of patients with inflammatory rheumatic diseases in the context of the SARS-CoV-2/COVID-19 pandemic - Update July 2020]. / Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie e. V. für die Betreuung von Patienten mit entzündlich rheumatischen Erkrankungen im Rahmen der SARS-CoV-2/COVID-19-Pandemie ­ Update Juli 2020.

A few days after the SARS-CoV-2 infection was declared a pandemic, the German Society for Rheumatology (DGRh) compiled first recommendations for the care of patients with inflammatory rheumatic diseases (IRD). These first recommendations were based on an expert consensus and were largely non-evidence-based. Now that the first scientific data from registers, cross-sectional studies, case reports and case series are available, the present update is intended to update the previous recommendations and to add new findings. The current recommendations are based on a literature search of publications available up to 15 June 2020 and address preventive measures (such as hygiene measures or vaccinations) and the use of immunomodulatory/immunosuppressive drugs. An important goal of the current recommendations is also to prevent harm to patients with IRD through unjustified restriction of care. The DGRh will continue to update its recommendations in the case of new aspects and will publish them as well as further information on the COVID-19 pandemic on its homepage ( www.dgrh.de ) in an ongoing process.

Systemic lupus erythematosus and neutropaenia: a hallmark of haematological manifestations.

OBJECTIVE: Systemic lupus is a chronic autoimmune disease characterised by its phenotypic heterogeneity. Neutropaenia is a frequent event in SLE occurring in 20%-40% of patients depending on the threshold value of neutrophil count. On a daily basis, the management of neutropaenia in SLE is difficult with several possible causes. Moreover, the infectious consequences of neutropaenia in SLE remain not well defined. METHODS: 998 patients from the Lupus BioBank of the upper Rhein (LBBR), a large German and French cohort of patients with SLE, mostly of Caucasian origin (83%), were included in this study. Neutropaenia was considered when neutrophil count was below 1800×106/L. An additional analysis of detailed medical records was done for 65 LBBR patients with neutropaenia. RESULTS: 208 patients with neutropaenia (21%) were compared with 779 SLE patients without neutropaenia. Neutropaenia in SLE was significantly associated with thrombocytopaenia (OR 4.11 (2.57-10.3)), lymphopaenia (OR 4.41 (2.51-11.5)) and low C3 (OR 1.91 (1.03-4.37)) in multivariate analysis. 65 representative patients with neutropaenia were analysed. Neutropaenia was moderate to severe in 38%, chronic in 31%, and both severe and chronic in 23% of cases. Moderate to severe and chronic neutropaenia were both associated with lymphopaenia and thrombopaenia. Chronic neutropaenia was also associated anti-Ro/SSA antibodies and moderate to severe neutropaenia with oral ulcers. CONCLUSION: This study is to date the largest cohort to describe neutropaenia in SLE. Neutropaenia displays a strong association with other cytopaenias, suggesting a common mechanism. Chronic neutropaenia is associated with anti-Ro/SSA antibodies with or without identified Sjögren's disease.

[German guidelines for the treatment of rheumatoid arthritis with disease modifying anti-rheumatic drugs - What is new?] / S2e-Leitlinie "Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten" ­ Was ist neu?

The new guidelines for the treatment of rheumatoid arthritis with disease modifying antirheumatic drugs are based on a systematic literature research and consensus process. They define the current standard of the treatment of rheumatoid arthritis. Although they are related to the current European guidelines, in some points they are more detailed and place further emphasis.Every patient suffering from active rheumatoid arthritis (RA) is to be treated with a DMARD, but Methotrexate initially remains the first resort therapeutic measure. Treatment shall comply with the "treat-to-target" principle. The therapeutic aim in this is remission, if attainable, or at least a low disease activity. Remission here is defined as a Simplified Disease Activity Score (SDAI) of ≤ 3,3 or as meeting the so called Boolean definition. A first evaluation of response is due after 12 weeks. By that time, there should be a measurable response, defined as an improvement of at least 50 % of the Composite Score, as e. g. of DAS28. If no improvement has been achieved, treatment shall be continued with either a second DMARD strategy with conventionally synthetic DMARD (csDMARD) or an alternative with biological or targeted synthetic (b or ts) DMARD - depending on whether there are risk factors for a severe disease progression. Glucocorticoids are given initially, however they should be tapered and stopped after 3-6 months or at least reduced to a maximal dose of 5 mg/d prednisone. Both a change within b and tsDMARD as well as therapeutic de-escalation are possible measures in the further course of treatment.

[Antisynthetase syndromes]. / Antisynthetasesyndrome.

Antisynthetase syndromes (ASS) are rare autoimmune diseases. Characteristic is the presence of at least one of the three main symptoms myositis, interstitial lung disease (ILD) and arthritis with possible accompanying symptoms, such as mechanic's hands and feet, Raynaud's disease and/or fever in combination with detection of an aminoacyl-tRNA synthetase antibody in peripheral blood. In addition to myositis, ILD is a frequent and often predominant organ involvement and is responsible for morbidity and mortality. Autoantibodies to 11 aminoacyl-tRNA synthetases are known of which 8 have so far been associated with the clinical manifestation of ASS. The Jo-1 antibody is by far the most frequent one. The antibodies differ in the rate and severity of the main and accompanying symptoms. Treatment with selected immunosuppressive medication depends on the extent and severity of organ involvement. With a 5-year survival rate of approximately 90%, the Jo-1 syndrome has the best prognosis.

Reduced Right Ventricular Output Reserve in Patients With Systemic Sclerosis and Mildly Elevated Pulmonary Artery Pressure.

OBJECTIVE: This prospective study was undertaken to evaluate right ventricular function and pulmonary arterial compliance (PAC; ratio of stroke volume to pulse pressure) at rest and during exercise in patients with systemic sclerosis (SSc) with normal mean pulmonary artery pressure (PAP), patients with SSc with mildly elevated mean PAP, and patients with SSc with manifest pulmonary hypertension (PH). METHODS: Patients with SSc (n = 112) underwent clinical assessment and right-sided heart catheterization at rest and during exercise and were divided into 3 groups according to their resting mean PAP values: normal mean PAP (≤20 mm Hg), mildly elevated mean PAP (21-24 mm Hg), and PH (mean PAP ≥25 mm Hg). Results were compared between groups by analysis of variance followed by post hoc Student's t-test. RESULTS: Compared to patients with normal mean PAP, patients with mildly elevated mean PAP had a lower 6-minute walking distance (P = 0.008), lower cardiac index (P = 0.027) and higher pulmonary vascular resistance (P = 0.0002) during exercise, and lower PAC at rest (P = 0.016) and different stages of exercise (P = 0.033 for 25W and P = 0.024 for 75W). CONCLUSION: The results of this study suggest that impaired 6-minute walking distance in SSc patients with mildly elevated mean PAP might be caused by reduced PAC during exercise and reduced right ventricular output reserve, presumably due to impaired coupling between the right ventricle and the pulmonary vasculature. These findings provide further evidence of the clinical relevance of mildly elevated mean PAP in patients with SSc.

Predictors of fatigue and severe fatigue in a large international cohort of patients with systemic lupus erythematosus and a systematic review of the literature.

OBJECTIVE: Fatigue is reported in up to 90% of patients with SLE. This study was conducted to identify the determinants associated with fatigue in a large cohort of patients with SLE, as well as to provide a systematic review of the literature. METHODS: Patients from the Lupus BioBank of the upper Rhein, a large German-French cohort of SLE patients, were included in the FATILUP study if they fulfilled the 1997 ACR criteria for SLE and had Fatigue Scale for Motor and Cognitive Functions scores collected. Multivariate logistic regression analyses were performed to assess the determinants of fatigue and severe fatigue. RESULTS: A total of 570 patients were included (89.1% female). The median age was 42 years (interquartile range 25-75: 34-52). The median value of the SAfety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI was 2 (0-4). Fatigue was reported by 386 patients (67.7%) and severe fatigue by 209 (36.7%). In multivariate analyses, fatigue was associated with depression [odds ratio (OR): 4.72 (95% CI: 1.39-16.05), P = 0.01], anxiety [OR: 4.49 (95% CI: 2.60-7.77), P < 0.0001], glucocorticoid treatment [OR: 1.59 (95% CI 1.05-2.41), P = 0.04], SELENA-SLEDAI scores [OR: 1.05 (95% CI: 1.00-1.12) per 1 point increase, P = 0.043] and age at sampling [OR: 1.01 (95% CI: 1.00-1.03) per 1 year increase, P = 0.03]. Severe fatigue was independently associated with anxiety (P < 0.0001), depression (P < 0.0001), glucocorticoid treatment (P = 0.047) and age at sampling (P = 0.03). CONCLUSION: Both fatigue and severe fatigue are common symptoms in SLE, and are strongly associated with depression and anxiety. Disease activity and the use of glucocorticoids were also independently associated with fatigue, although more weakly.