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Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present investigation. Serum levels of sST2 were measured in 49 patients with SSc, recruited prospectively between November 2017 and March 2019. Patients were divided into those with progressive and those with stable disease. Receiver operating characteristics (ROC) curve analysis was applied to study sST2 as a marker for identifying patients with progressive disease. We used multivariate logistic regression analysis to evaluate the predictive value of sST2 for progressive disease after adjustment for potential confounding factors. Serum sST2 levels in patients with progressive disease were significantly elevated compared with patients with stable disease (mean ± sem: 50.4 ± 4.7 ng/mL vs 29.2 ± 2.97 ng/mL, p < 0.001). ROC curve analysis identified an sST2 cut-off value of 37.8 ng/mL as optimal for discriminating patients with progressive disease from those with stable disease (sensitivity 80.0%, specificity 79.3%, area under the curve 0.80). After controlling for potential confounding factors (age, gender, C-reactive protein, pro-brain natriuretic peptide, and sum of internal medicine comorbidities), sST2 remained predictive of progressive disease (odds ratio 1.070, 95% confidence interval 1.017–1.126, p < 0.009). In the present study, sST2 serum levels were predictive of disease progression in patients with SSc. [ABSTRACT FROM AUTHOR]

Objectives: The diagnosis of Whipple's disease (WD) is commonly confirmed by histology demonstrating Periodic Acid Schiff (PAS)-positive macrophages in the duodenal mucosa. Analysis of intestinal tissue or other specimens using polymerase chain reaction (PCR) is a more sensitive method. However, the relevance of positive PCR findings is still controversial. Therefore, we evaluated the relevance of histology and PCR findings to establishing the diagnosis of WD in a series of WD patients initially presenting with suspected rheumatic diseases.Method: Between 2006 and 2014, 20 patients with seronegative rheumatic diseases tested positive for Tropheryma whipplei (Tw) by PCR and/or histology and were enrolled in a retrospective analysis of the diagnostic value of both procedures.Results: Seven of the 20 cases (35%) were diagnosed with 'classic' WD as indicated by PAS-positive macrophages. In the remaining 13 patients, the presence of Tw was detected by intestinal (n = 10) or synovial PCR analysis (n = 3). Two of the 20 patients (10%) with evidence of Tw did not respond to antibiotic therapy. They were not considered to suffer from WD. Therefore, relying only on histological findings of intestinal biopsies would have missed 11 (61%) of the 18 patients with WD in our cohort. In comparison, PCR of intestinal biopsies detected Tw-DNA in 14 (93%) of the 15 WD patients evaluated. Patients with a positive histology did not differ from PCR-positive patients with regard to sex, age, or duration of disease, but more often presented with gastrointestinal symptoms.Conclusions: A substantial number of WD patients present without typical intestinal histology findings. Additional PCR analysis of intestinal tissue or synovial fluid increased the sensitivity of the diagnostic evaluation and should be considered particularly in patients presenting with atypical seronegative rheumatic diseases and a high-risk profile for WD. [ABSTRACT FROM AUTHOR]

Objective Patients with acute sarcoidosis frequently present with bilateral painful swelling of the ankles, establishing ankle arthritis as a hallmark of Lofgren's syndrome. Standardized high-resolution musculoskeletal ultrasound (MSUS), including power Doppler, has been utilized to further characterize the nature of ankle swelling in patients presenting with Lofgren's syndrome. Methods The ankle joints of 36 consecutive patients with Lofgren's syndrome were investigated by high-resolution MSUS using B-mode and power Doppler mode. The presence of effusion/synovitis and tenosynovitis was determined, and hyperperfusion was scored in a semiquantitative fashion (grade 0-3). Results The majority of patients (26 [72.2%] of 36) did not present characteristic arthrosonographic findings of an acute arthritis (distension of the capsule and hyperperfusion). Ankle joint effusion was only observed in 9 (25%) of the 36 patients, with a generally mild character (grade I ankle joint effusion: n = 8 [88.8%], grade II ankle joint effusion: n = 1 [11.2%]). In contrast, an extensive subcutaneous edema indicating periarthritis was detected in 23 (92%) of 25 patients. In addition, tenosynovitis could be visualized in 14 patients (38.8%) using MSUS. Conclusion Utilizing MSUS, including power Doppler, the present results clearly demonstrate that ankle swelling in patients with Lofgren's syndrome is predominantly due to periarticular soft tissue swelling and tenosynovitis. In contrast, distinct articular synovitis is rare and if present, only to a mild degree, without relevant power Doppler activity. [ABSTRACT FROM AUTHOR]

One hundred and three patients who had previously tested positive for community-acquired methicillin-resistant Staphylococcus aureus (cMRSA) were followed up for a mean time of 32.6 months. Eighty patients had a history of skin or soft tissue infection, and the remainder were mostly asymptomatic carriers. Of 103 patients, only two reported ongoing symptoms with abscess formation. Of 81 nasal swabs available, 30.9% were positive for S. aureus but only four yielded Panton-Valentine leukocidin- positive methicillin-resistant S. aureus. In summary, we were unable to find persistent health issues or nasal colonization with cMRSA in a cohort of previously cMRSA-infected/colonized patients. [ABSTRACT FROM AUTHOR]

Abstract Background Cryptococcus neoformans is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, C. neoformans causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis. Case Presentation An 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with Cryptococcus neoformans, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed. Conclusions Opportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.

Abstract Background Pfeifer-Weber-Christian disease (PWCD) is a rare inflammatory disorder of the subcutaneous fatty tissue. The diagnosis and therapy of this rare type of panniculitis is still controversial and will be discussed in this article. Case presentation We here report the rare case of a 64-year old male patient, with PWCD. The patient suffered from rheumatoid arthritis for several years, but then developed relapsing fever and recently occurring painful subcutaneous nodules predominantly at the inner part of his left upper limb with no signs of synovitis. Finally, a biopsy from one of the nodules revealed lobular panniculitis with mixed cell infiltrate, which was conformable only with PWCD, after excluding several differential diagnoses. In our patient PWCD developed despite immunosuppressive therapy with steroids and different disease modifying drugs, which the patient received to treat his underlying rheumatoid arthritis. However, when DMARD therapy was switched to Ciclosporin A the patient's symptoms resolved. Conclusion Our observation supports the hypothesis that T cells are involved in the pathogenesis of PWCD. Thus, T cell modifying drugs should be primarily used to treat patients with this rare disorder.

Abstract Background Timely identification of pathogens is crucial to minimize mortality in patients with severe infections. Detection of bacterial and fungal pathogens in blood by nucleic acid amplification promises to yield results faster than blood cultures (BC). We analyzed the clinical impact of a commercially available multiplex PCR system in patients with suspected sepsis. Methods Blood samples from patients with presumed sepsis were cultured with the Bactec 9240™ system (Becton Dickinson, Heidelberg, Germany) and aliquots subjected to analysis with the LightCycler® SeptiFast® (SF) Test (Roche Diagnostics, Mannheim, Germany) at a tertiary care centre. For samples with PCR-detected pathogens, the actual impact on clinical management was determined by chart review. Furthermore a comparison between the time to a positive blood culture result and the SF result, based on a fictive assumption that it was done either on a once or twice daily basis, was made. Results Of 101 blood samples from 77 patients, 63 (62%) yielded concordant negative results, 14 (13%) concordant positive and 9 (9%) were BC positive only. In 14 (13%) samples pathogens were detected by SF only, resulting in adjustment of antibiotic therapy in 5 patients (7,7% of patients). In 3 samples a treatment adjustment would have been made earlier resulting in a total of 8 adjustments in all 101 samples (8%). Conclusion The addition of multiplex PCR to conventional blood cultures had a relevant impact on clinical management for a subset of patients with presumed sepsis.

Abstract Background The identification of clinical factors associated with negative blood cultures could help to avoid unnecessary blood cultures. C-reactive protein (CRP) is a well-established inflammation marker commonly used in the management of medical inpatients. Methods We studied the association of clinical factors, CRP levels and changes of CRP documented prior to blood culture draws with the absence of bacteremia for hospitalized medical patients. Results In the retrospective analysis of 710 blood cultures obtained from 310 medical inpatients of non-intensive-care wards during one year (admission blood cultures obtained in the emergency room were excluded), the following retrospectively available factors were the only independent predictors of blood cultures negative for obligate pathogens: a good clinical condition represented by the lowest of three general nursing categories (OR 4.2, 95% CI 1.8 – 9.5), a CRP rise > 50 mg/L documented before the blood culture draw (OR 2.0 95% CI 1.8–9.5) and any antibiotic treatment in the previous seven days (OR 2.0, 95% CI 1.1–3.5). Conclusion Including the general clinical condition, antibiotic pre-treatment and a substantial rise of CRP into the decision, whether or not to obtain blood cultures from medical inpatients with a suspected infection, could improve the diagnostic yield.

Abstract Background Conflicts between professional duties and fear of influenza transmission to family members may arise among health care professionals (HCP). Methods We surveyed employees at our university hospital regarding ethical issues arising during the management of an influenza pandemic. Results Of 644 respondents, 182 (28%) agreed that it would be professionally acceptable for HCP to abandon their workplace during a pandemic in order to protect themselves and their families, 337 (52%) disagreed with this statement and 125 (19%) had no opinion, with a higher rate of disagreement among physicians (65%) and nurses (54%) compared with administrators (32%). Of all respondents, 375 (58%) did not believe that the decision to report to work during a pandemic should be left to the individual HCP and 496 (77%) disagreed with the statement that HCP should be permanently dismissed for not reporting to work during a pandemic. Only 136 (21%) respondents agreed that HCW without children should primarily care for the influenza patients. Conclusion Our results suggest that a modest majority of HCP, but only a minority of hospital administrators, recognises the obligation to treat patients despite the potential risks. Professional ethical guidelines allowing for balancing the needs of society with personal risks are needed to help HCP fulfil their duties in the case of a pandemic influenza.

Objective: Soluble transferrin receptor (sTfR) is considered to be a useful biomarker for the diagnosis of iron deficiency, especially in the setting of inflammation, as it is thought to not be affected by inflammation. We analyzed the relationship between sTfR levels and inflammatory markers in patients with known or suspected inflammatory rheumatic disease (IRD)., Methods: Blood samples of 1001 patients with known or suspected IRD referred to a tertiary rheumatology center were analyzed. Study participants were classified as patients with active IRD and patients with inactive IRD or without IRD. Correlation analyses were used to explore the relationship between sTfR levels and inflammatory markers (ie, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). We applied multiple linear regression analysis to evaluate the predictive value of CRP levels for sTfR concentrations after adjustment for potential confounding factors., Results: There were positive correlations between inflammatory markers (CRP, ESR) and serum sTfR levels (ρ 0.44, ρ 0.43, respectively; P < 0.001), exceeding the strength of correlation between inflammatory markers and the acute phase reactant ferritin (ρ 0.30, ρ 0.23, respectively; P < 0.001). Patients with active IRD demonstrated higher serum sTfR levels compared to patients with inactive or without IRD (mean 3.99 [SD 1.69] mg/L vs 3.31 [SD 1.57] mg/L; P < 0.001). After adjustment for potential confounding factors, CRP levels are predictive for serum sTfR concentrations ( P < 0.001)., Conclusion: The study provides evidence against the concept that sTfR is a biomarker not affected by inflammation., (Copyright © 2024 by the Journal of Rheumatology.)

Aim: We analyzed the added value of sTfR measurement in routine clinical practice to standard parameters (SP) of iron deficiency in the detection of iron deficiency anemia (IDA) in patients with rheumatoid arthritis (RA)., Methods: Blood samples from 116 patients with RA were analyzed in a prospective study. Based on biochemical parameters, patients were classified as having IDA, anemia of chronic disease (ACD), IDA with concomitant ACD (ACD/IDA), or "other anemia." Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of sTfR and SP of iron status alone and in combination were calculated for the diagnosis of IDA in general, i.e., IDA or ACD/IDA., Results: In the whole sample, with regard to the diagnosis of iron deficiency (IDA or ACD/IDA), sTfR had a higher sensitivity compared both to the combined use of SP and to the combination of SP with sTfR (80.9% versus 66.7/54.8%). Specificity, PPV and NPV did not differ substantially. When patients were stratified in groups with high (CRP levels above the median, i.e., 24.1 mg/l) and low (CRP levels less or equal to the median) inflammation, the diagnostic superiority of sTfR was restricted to patients with high inflammation. In this group, the diagnostic performance of sTfR was superior both to the combined use of SP and the combination of SP with sTfR with higher sensitivity (100% versus 52.4%) and NPV (100% versus 77.7/76.7%) and comparable specificity and PPV., Conclusion: For the detection of iron depletion (IDA or ACD/IDA) in anemic RA patients, sTfR is superior to SP of iron deficiency only in highly inflammatory states., Competing Interests: There is no potential conflict of interest., (Copyright © 2022 Florian Günther et al.)

Purpose: SARS-CoV-2 is a recently emerged ß-coronavirus. Here we present the current knowledge on its epidemiologic features., Methods: Non-systematic review., Results: SARS-CoV-2 replicates in the upper and lower respiratory tract. It is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The consensus estimate for the basis reproduction number (R 0 ) is between 2 and 3, and the median incubation period is 5.7 (range 2-14) days. Similar to SARS and MERS, superspreading events have been reported, the dispersion parameter (kappa) is estimated at 0.1. Most infections are uncomplicated, and 5-10% of patients are hospitalized, mainly due to pneumonia with severe inflammation. Complications are respiratory and multiorgan failure; risk factors for complicated disease are higher age, hypertension, diabetes, chronic cardiovascular, chronic pulmonary disease and immunodeficiency. Nosocomial and infections in medical personnel have been reported. Drastic reductions of social contacts have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions. Most interventions have used bundles, but which of the measures have been more or less effective is still unknown. The current estimate for the infection's fatality rate is 0.5-1%. Using current models of age-dependent infection fatality rates, upper and lower limits for the attack rate in Germany can be estimated between 0.4 and 1.6%, lower than in most European countries., Conclusions: Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures.

Objectives: It is still controversial whether autoantibody (AAb) serum levels have a value for response monitoring in rheumatoid arthritis (RA). Therefore, we retrospectively investigated a real-life outpatient RA cohort to determine which factors are associated with change in serum AAb levels and RA disease activity. The primary goal of the study was to determine predictors for changes in DAS28 and autoantibodies over time and identify traits of non-rituximab treated patients, which would define strong association of disease activity with changes in AAb-levels., Methods: Seventy-eight patients with seropositive RA were monitored for DAS28, CRP, ESR, anti-cyclic citrullinated peptides (CCP), anti-mutated citrullinated vimentin (MCV), and rheumatoid factor (RF). Using linear mixed regression modelling, factors influencing DAS28 and serum AAb were determined. Patients showing above (good correlators) and below (bad correlators) average correlation of serum AAb with DAS28 were further characterised., Results: In non-rituximab treated patients (88.5%), associations of changes in AAb and DAS28 were strengthened with more morning stiffness (p=0.002), DMARD use (p=0.02), tender joints (p=0.01), swollen joints (p<0.01), higher ESR (p<0.01) and VAS (p<0.001) at baseline. Decrease of anti-CCP was also predicted by longer disease duration (-4.4 U/ml per year disease duration, p=0.048) and/or no erosions (-2.0 U/ml/month, p<0.01) at baseline, whereas erosive disease predicted an increase (+1.4 U/ml/month, p=0.015) in anti-CCP. Conversely, patients with erosive disease showed a trend to decrease RF (-1.9 U/ml/month, p=0.06)., Conclusions: In non-rituximab treated RA patients, the association between disease activity and change in autoantibody levels is not static, but strengthens with increase in signs of inflammation (ESR, VAS, swollen joints, tender joints, morning stiffness) at baseline. Therefore, studies of changes in AAb need to consider baseline inflammation as confounder.

Objective: Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis (AS). The present multicenter study, the International Spondyloarthritis Autoantibody (InterSpA) trial, was undertaken to compare the sensitivity and specificity of anti-CD74 and HLA-B27 in identifying patients with nonradiographic axial spondyloarthritis (axSpA)., Methods: Patients ages 18-45 years with inflammatory back pain of ≤2 years' duration and a clinical suspicion of axSpA were recruited. HLA-B27 genotyping and magnetic resonance imaging of sacroiliac joints were performed in all patients. One hundred forty-nine patients with chronic inflammatory back pain (IBP) not caused by axSpA served as controls, and additional controls included 50 AS patients and 100 blood donors whose specimens were analyzed., Results: One hundred patients with inflammatory back pain received a diagnosis of nonradiographic axSpA from the investigators and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria. The mean age was 29 years, and the mean symptom duration was 12.5 months. The sensitivity of IgA anti-CD74 and IgG anti-CD74 for identifying the 100 axSpA patients was 47% and 17%, respectively. The specificity of both IgA anti-CD74 and IgG anti-CD74 was 95.3%. The sensitivity of HLA-B27 was 81%. The positive likelihood ratios were 10.0 (IgA anti-CD74), 3.6 (IgG anti-CD74), and 8.1 (HLA-B27). Assuming a 5% pretest probability of axSpA in chronic back pain patients, the posttest probability, after consideration of the respective positive test results, was 33.3% for IgA anti-CD74, 15.3% for IgG anti-CD74, and 28.8% for HLA-B27. A combination of IgA anti-CD74 and HLA-B27 results in a posttest probability of 80.2%., Conclusion: IgA anti-CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test in daily practice requires further confirmation., (© 2018, American College of Rheumatology.)

Background: Aggregatibacter actinomycetemcomitans ( Aa ) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis (RA) pathogenesis. Although mechanistic and clinical association studies implicate Aa infection in the initiation of autoimmunity in RA, direct evidence in humans is lacking. Case: We describe a 59-year-old man with anti-citrullinated protein antibody (ACPA)-positive RA who presented for evaluation of refractory disease. He was found to have Aa endocarditis. Following antibiotic treatment, joint symptoms resolved and ACPAs normalized. Given the implications for RA immunopathogenesis, we further investigated the bacterial, genetic and immune factors that may have contributed to the patient's clinical and autoimmune phenotypes. Methods: DNA was extracted from serum and used to amplify the Aa leukotoxin ( ltx) promoter region by PCR, which was further analyzed by Sanger sequencing. High-resolution identification of HLA alleles was performed by sequenced based typing (SBT). TNF-α, IFN-γ, GM-CSF, IL-1β, IL-6, IL-8, IL-17A, IL-18, IL-21, and IL-22 were quantified in serum by a multiplex immunoassay. IgG and IgA antibodies to Aa LtxA were assayed by ELISA. Results: Aa genotyping confirmed infection with a highly leukotoxic strain carrying a 530-bp ltx promoter deletion, shown to result in 10- to 20-fold higher bacterial expression of LtxA. Immuno-phenotyping showed high anti-LtxA antibodies, elevated cytokines implicated in RA pathogenesis (Th1/Th17), and specific host susceptibility conferred by three HLA alleles strongly linked to ACPAs and RA (DRB1 * 04:04, DRB1 * 15:01, and DPB1 * 04:01). One year after eradication of Aa , the patient remained free of arthritis and anti-CCP antibodies. Conclusion: In the context of genetic risk for RA, systemic subacute infection with a leukotoxic strain of Aa can drive ACPA production and a clinical phenotype similar to RA.

Objectives: We aimed to study the ability of board-certified rheumatologists, blinded to all prior diagnostic test results, to establish the presence/absence of an inflammatory rheumatic disease (IRD) or RA among polyarthralgia or arthritis patients, solely relying on clinical assessment., Methods: We performed a prospective, examiner-blinded, cross-sectional study documenting the diagnostic work in four sequential steps (medical history, physical examination, musculoskeletal ultrasonography and laboratory tests) of board-certified rheumatologists in a convenience cohort of 100 patients referred for inpatient diagnostic workup to a tertiary care rheumatology centre., Results: The ability to correctly identify patients with or without an IRD (diagnostic accuracy) increased from 27% after the clinical assessment to 53% after the ultrasonography and to 70% after taking laboratory test results into account. The corresponding values for correctly identifying patients with or without RA were 19, 42 and 60%, respectively. Therefore the diagnostic accuracy of solely clinical assessment for determining the diagnosis of IRD or RA compared with the diagnosis established by a consecutive thorough in-patient workup was only 27 and 19% in our cohort, respectively. Pretreatment with corticosteroids (in the prior 7 days) vs none did not alter these results substantially (20 vs 29% for IRD, 15% vs 20% for RA)., Conclusion: Experienced rheumatologists, if deprived of information on prior external imaging and laboratory workup by blinding, were not able to correctly classify the majority of patients presenting with polyarthralgia or arthritis symptoms for inpatient workup, relying only on a brief symptom-focused medical history and physical examination.

The 'necessity-concerns framework' postulates that patients' adherence behaviour is influenced by beliefs about the necessity and the concerns patients have regarding their prescribed medicines. We hypothesized that depression moderates the associations between beliefs about medicines and medication adherence among people with rheumatoid arthritis. Using multivariate logistic regression, we observed that people experiencing more depressive symptoms showed stronger associations between necessity beliefs and adherence as well as attenuated associations between concerns and adherence, respectively, in a cross-sectional sample ( N = 361). Thus, depression moderates the associations postulated in the 'necessity-concerns framework' in a differential way in people with rheumatoid arthritis.

This study aimed to compare the diagnostic value of ultrasonography to conventional radiography in detecting osteophytes and erosions in the midfoot joints in patients suffering from inflammatory and non-inflammatory joint disease. Patients with current foot radiographs were included and stratified in two cohorts: inflammatory and non-inflammatory joint disease. The ten midfoot joints of each foot were evaluated by conventional radiography assessing the presence of osteophytes and erosions and by ultrasonography determining the presence of osteophytes, erosions, and joint effusion. Power Doppler activity was scored semi-quantitatively from 0 to 3. A total of 2445 joints in 124 patients (90 with inflammatory joint disease, 34 with non-inflammatory joint disease) were assessed. Ultrasonography detected significantly more osteophytes than conventional radiography (344; 14.1% vs. 13; 0.5%), as well as more erosions (60; 2.5% vs. 3; 0.1%). There was weak agreement between the two modalities (κ-statistic 0.029-0.035). Power Doppler ultrasonography demonstrated no significant difference in hyperperfusion comparing patients with inflammatory joint disease and non-inflammatory joint disease. Ultrasonography of the midfoot is more sensitive than conventional radiography in the detection of osteophytes and erosions in patients suffering from inflammatory and non-inflammatory joint disease. Thus, midfoot ultrasonography may be a useful tool in the diagnosis of joint diseases as rheumatoid arthritis and osteoarthritis.

This study investigated as to how social support influences health among people with rheumatoid arthritis (RA). We refer to the stress-buffering hypothesis of social support which suggests that the negative consequences of stressors on health outcomes can be buffered by social support. In this study, pain represents a stressor and depressive symptoms represent negative health outcomes. It was hypothesized that higher levels of social support should attenuate the association between pain and depression in RA. A cross-sectional study was conducted in 361 patients with RA. They completed questionnaires on social support, depression and perceived pain. Linear regression analysis was applied, with pain as the main explanatory variable, depression as a dependent variable, and an interaction term "social support × pain". Both pain and social support showed significant associations with depression, with more severe pain and lower social support going along with a higher depression score. However, the interaction term "social support × pain" was not significant, indicating that social support did not attenuate the association between pain and depression. Social support was inversely associated with the experience of depressive symptoms among people suffering from RA. However, it had no buffering effect in attenuating the postulated association between the stressor "pain" and the negative health outcomes assessed as depressive symptoms. The stress-buffering hypothesis of social support was not supported by data from this study among people suffering from RA.

The aim of the study is to investigate water compartments in patients with rheumatoid arthritis (RA). Acute inflammatory episodes such as infection stimulate water retention, chiefly implemented by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism due to expected water loss (sweating etc.). Since SNS and HPA axis are activated in RA, inflammation might be accompanied by water retention. Using bioimpedance analysis, body composition was investigated in 429 controls and 156 treatment-naïve RA patients between January 2008 and December 2014. A group of 34 RA patients was tested before and after 10 days of intensified therapy. Levels of pro-atrial natriuretic peptide (proANP) and expression of atrial natriuretic peptide in synovial tissue were investigated in 15 controls and 14 RA patients. Extracellular water was higher in RA patients than controls (mean ± SEM: 49.5 ± 0.3 vs. 36.7 ± 0.1, % of total body water, p < 0.0001). Plasma levels of proANP were higher in RA than controls. RA patients expressed ANP in synovial tissue, but synovial fluid levels and synovial tissue superfusate levels were much lower than plasma levels indicating systemic origin. Systolic/diastolic blood pressure was higher in RA patients than controls. Extracellular water levels did not change in RA patients despite 10 days of intensified treatment. This study demonstrates signs of intravascular overload in RA patients. Short-term intensification of anti-inflammatory therapy induced no change of a longer-lasting imprinting of water retention indicating the requirement of additional treatment. The study can direct attention to the area of volume overload.

Objectives: Epidemiological studies have linked arthritis to depression. However, it remains unclear to what degree the association between arthritis and depression extends to low income countries and whether it can be replicated for inflammatory arthritis (IA). We aimed to address these knowledge gaps based on a large multi-national sample., Methods: Cross-sectional data was drawn from the 2002 World Health Survey. IA was defined as reports of either a diagnosis or treatment of arthritis and morning stiffness for >30min. Self-reported depression was defined as positive if participants reported its prior diagnosis or treatment or if they were classified as suffering from a major depressive episode by a seven-item screening instrument. Multivariable logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the entire sample and stratified by sex and continent., Results: The odds of IA was 2.6-fold increased in those with depression compared to those without (OR=2.64, 95% CI 2.18-3.21) in the entire sample. This association was observed in both men (OR=3.06, 95% CI 2.19-4.27) and women (OR=2.50, 95% CI 1.95-3.21). Similar associations were found on the continent level, but were generally stronger for the Americas and Asia compared to Africa and Europe., Conclusions: Although our definition of IA was limited by the use of self-reported morning stiffness, this study suggests that there is a positive association between inflammatory arthritis and depression in Western and Non-Western countries, suggesting that this relationship represents a universal phenomenon., (Copyright © 2016. Published by Elsevier Inc.)

The human complement factor H-related protein-3 (FHR-3) is a soluble regulator of the complement system. Homozygous cfhr3/1 deletion is a genetic risk factor for the autoimmune form of atypical hemolytic-uremic syndrome (aHUS), while also found to be protective in age-related macular degeneration (AMD). The precise function of FHR-3 remains to be fully characterized. We generated four mouse monoclonal antibodies (mAbs) for FHR-3 (RETC) without cross-reactivity to the complement factor H (FH)-family. These antibodies detected FHR-3 from human serum with a mean concentration of 1 μg/mL. FHR-3 levels in patients were significantly increased in sera from systemic lupus erythematosus, rheumatoid arthritis, and polymyalgia rheumatica but remained almost unchanged in samples from AMD or aHUS patients. Moreover, by immunostaining of an aged human donor retina, we discovered a local FHR-3 production by microglia/macrophages. The mAb RETC-2 modulated FHR-3 binding to C3b but not the binding of FHR-3 to heparin. Interestingly, FHR-3 competed with FH for binding C3b and the mAb RETC-2 reduced the interaction of FHR-3 and C3b, resulting in increased FH binding. Our results unveil a previously unknown systemic involvement of FHR-3 in rheumatoid diseases and a putative local role of FHR-3 mediated by microglia/macrophages in the damaged retina. We conclude that the local FHR-3/FH equilibrium in AMD is a potential therapeutic target, which can be modulated by our specific mAb RETC-2.

Objectives: Many rheumatic diseases as well as their medications may cause gastrointestinal (GI) pathologies; in addition, some primary GI diseases may contribute or lead to rheumatic disease manifestations. The aim of this study is to analyze the clinical relevance of esophagogastroduodenoscopy (EGD) and ileocolonoscopy (IC) in patients suffering from inflammatory rheumatic diseases., Methods: A retrospective chart review was performed for all rheumatological inpatients who underwent EGD and/or IC within 2 years., Results: Within 2 years, 456 patients (261 female, 195 male) underwent 752 endoscopic investigations of the GI tract (419 EGDs and 333 ICs). Of all patients, 152 (33.3%) did not report any GI complaints. However, 28 of these asymptomatic patients (18.4%) suffered from esophagitis, a gastric ulcer could be identified in 20 patients (13%), whereas unspecific colitis was diagnosed in 19 patients (12.5%). In addition, 14 patients (9.2%) suffered from clinically unapparent Crohn's disease and two patients from Whipple's disease. In one patient with polymyalgia rheumatica, colon cancer was diagnosed. Altogether 304 patients reported GI complaints. Of these, 292 (39%) endoscopic investigations had impact on the final diagnosis or therapeutic strategy. The antirheumatic medication or the concomitant medication was changed in 18% of the patients due to the endoscopic findings; in 29 patients (6.5%) the initially clinically presumed diagnosis had to be corrected. In 70 patients (15%) with an undefined rheumatic diagnosis prior to endoscopy, endoscopic findings were decisive to establish the final diagnosis., Conclusion: EGD and IC have a high diagnostic impact on patients with rheumatic diseases presenting with or without concomitant GI symptoms.

Objective: This study aimed to explore medication adherence among adherent and non-adherent persons suffering from rheumatoid arthritis (RA). A special focus was put on the reasons accounting for successful medication adherence and on potential barriers or facilitating factors., Design: A qualitative study with semi-structured interviews was conducted. Eighteen participants were recruited through stratified purposive sampling according to their medication adherence level. Interviews were analysed by interpretative phenomenological analysis., Results: Medication adherence behaviour was described on a continuum ranging from non-adherent to adherent. Participants' current adherence level was represented as a result of inner negotiations between a variety of influential factors and the successful application of a range of strategies. The influential factors were: experiences with medication, outcome expectations, knowledge of therapeutic options, the traits 'openness' and 'conscientiousness', belief in medical progress, characteristics of the medication, level of trust in one's physician, and perceived autonomy. Facilitating strategies were: establishing routines, using social support and the deliberate suppression of information about potential adverse events., Conclusion: The experience of and the reasons for medication (non-)adherence from the perspective of people with RA were explored comprehensively. Participants' ongoing negotiations between adherence and non-adherence emerged as a key finding with implications for health service providers.

Objective: Ankle joints are frequently neglected in activity scoring systems, including the Disease Activity Score in 28 joints (DAS28). Only a few studies have assessed pathologies detected by ultrasonography of the ankles in symptomatic rheumatoid arthritis (RA) patients. We evaluated ankle joints in RA patients regardless of symptomatology, using musculoskeletal ultrasound (MSUS) as well as power Doppler ultrasound (PDUS)., Methods: A total of 160 ankle joints of 80 RA patients were examined using MSUS and PDUS, according to the European League Against Rheumatism MSUS guidelines. Additionally, the talonavicular joints (TNJs) and the medial and the lateral tendon compartments were examined. The visual analog scale (VAS) score was recorded for each patient., Results: A total of 80 RA patients with a median age of 60 years and disease duration of 5 years were enrolled in our study. The median DAS28 score was 5. A total of 97 ankles were painful (VAS 1-10), whereas 63 ankles were asymptomatic (VAS 0). Overall, the predominant pathology was arthritis of the tibiotalar joint (TTJ) and/or TNJ in 124 ankles (77%), followed by tenosynovitis of the medial compartment tendons in 44 ankles (28%). Arthritis of the TTJ was present in 59% and synovitis of the TNJ in 35% of the symptomatic ankles. In asymptomatic ankles, TTJ synovitis was detected in 35%, whereas TNJ arthritis was observed in 18%. PDUS activity was higher in the subgroup of symptomatic ankles., Conclusion: The most frequent pathologies detected by MSUS were arthritis of the TTJ and TNJ, followed by tenosynovitis of the medial compartment tendons. Pathologic findings were more frequent in symptomatic but also common in asymptomatic patients, whereas PDUS activity was generally low and mainly observed in symptomatic patients., (© 2016, American College of Rheumatology.)

Automated interpretation (AI) systems for antinuclear antibody (ANA) analysis have been introduced based on assessment of indirect immunofluorescence (IIF) patterns. The diagnostic performance of a novel automated IIF reading system was compared with visual interpretation (VI) of IIF in daily clinical practice to evaluate the reduction of workload. ANA-IIF tests of consecutive serum samples from patients with suspected connective tissue disease were carried out using HEp-2 cells according to routine clinical care. AI was performed using a visual analyser (Zenit G-Sight, Menarini, Germany). Agreement rates between ANA results by AI and VI were calculated. Of the 336 samples investigated, VI yielded 205 (61%) negative, 42 (13%) ambiguous, and 89 (26%) positive results, whereas 82 (24%) were determined to be negative, 176 (52%) ambiguous, and 78 (24%) positive by AI. AI displayed a diagnostic accuracy of 175/336 samples (52%) with a kappa coefficient of 0.34 compared to VI being the gold standard. Solely relying on AI, with VI only performed for all ambiguous samples by AI, would have missed 1 of 89 (1%) positive results by VI and misclassified 2 of 205 (1%) negative results by VI as positive. The use of AI in daily clinical practice resulted only in a moderate reduction of the VI workload (82 of 336 samples: 24%).

Objective: To assess the outcomes in a large cohort of patients suffering from rheumatic diseases admitted to the ICU of a tertiary university medical center., Methods: A retrospective chart analysis was performed in 108 patients suffering from various rheumatic diseases and the outcomes, including morbidity and mortality, were assessed in relation to the underlying diseases, treatments and complications., Results: Overall, 48 patients with rheumatoid arthritis, five patients with spondyloarthritis, 14 patients with vasculitis, 30 patients with connective tissue diseases and 11 patients suffering from other rheumatologic conditions were admitted to the intensive care unit (ICU). The reasons for ICU admission included infection (30%), cardiovascular complications (22%), gastrointestinal problems (18%), endocrinological disorders (7%), neurological complications (2%) and others (3%). A total of 4% of the admitted patients required close monitoring and 14% suffered from acute exacerbation of the underlying rheumatic disease. The ICU mortality rate was 16%, whereas the overall hospital mortality rate was 20%. Fatal outcomes were related to exacerbation of the rheumatic disease in 14% of the patients, infectious complications in 46% of the patients and other reasons in 41% of the patients. An increased Apache II score, the need for mechanical ventilation, renal replacement therapy, treatment with vasopressor drugs and plasma exchange therapy were identified as risk factors for mortality., Conclusion: The overall outcomes of critically ill patients with rheumatic diseases are impaired compared to that observed in other patient groups. However, there were no significant differences in outcomes between the different rheumatic disease groups or based on the use of immunosuppressive therapy in this study. An increased Apache II score, the need for mechanical ventilation, renal replacement therapy, treatment with vasopressor drugs and plasma exchange therapy were identified as risk factors for mortality.

The complement system is an essential part of the innate immune system by acting as a first line of defense which is stabilized by properdin, the sole known positive regulator of the alternative complement pathway. Dysregulation of complement can promote a diversity of human inflammatory diseases which are treated by complement inhibitors. Here, we generated a novel blocking monoclonal antibody (mAb) against properdin and devised a new diagnostic assay for this important complement regulator. Mouse mAb 1340 specifically detected native properdin from human samples with high avidity. MAb 1340 inhibited specifically the alternative complement mediated cell lysis within a concentration range of 1-10 µg/mL. Thus, in vitro anti-properdin mAb 1340 was up to fifteen times more efficient in blocking the complement system as compared to anti-C5 or anti-Ba antibodies. Computer-assisted modelling suggested a three-dimensional binding epitope in a properdin-C3(H2O)-clusterin complex to be responsible for the inhibition. Recovery of properdin in a newly established sandwich ELISA using mAb 1340 was determined at 80-125% for blood sample dilutions above 1∶50. Reproducibility assays showed a variation below 25% at dilutions less than 1∶1,000. Systemic properdin concentrations of healthy controls and patients with age-related macular degeneration or rheumatic diseases were all in the range of 13-30 µg/mL and did not reveal significant differences. These initial results encourage further investigation into the functional role of properdin in the development, progression and treatment of diseases related to the alternative complement pathway. Thus, mAb 1340 represents a potent properdin inhibitor suitable for further research to understand the exact mechanisms how properdin activates the complement C3-convertase and to determine quantitative levels of properdin in biological samples.

Objective: To assess joint involvement and the contribution of musculoskeletal ultrasound (MSUS) to the novel European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2012 classification criteria in patients with polymyalgia rheumatic (PMR)., Methods: MSUS was performed in 54 consecutive patients with recent-onset PMR., Results: Biceps tenosynovitis of at least 1 shoulder has been observed in 70.4% of patients, and 64.8% had a bilateral biceps tenosynovitis. Subdeltoid bursitis (27.8% unilateral, 5.6% bilateral), glenohumeral synovitis (22.2% unilateral, 9.3% bilateral), and hip involvement (22.2% unilateral, 16.7% bilateral) were observed less frequently. The sensitivities of the classification criteria were 85.2% for EULAR/ACR without MSUS and 81.5% for EULAR/ACR with MSUS., Conclusion: The most common MSUS pathology was a biceps tenosynovitis. However, US findings had no effect on the sensitivity of the novel EULAR/ACR criteria for PMR.

Background: To evaluate the utility of the recently introduced SOLAR score (sonography of large joints in Rheumatology), which has been validated in RA patients, in a cohort of patients with Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) presenting with involvement of large peripheral joints., Methods: The recently established SOLAR score has been designed to determine the degree of inflammation in the shoulder, the elbow, the hip and the knee joint in patients suffering from RA. Since large joints are frequently involved in PsA and AS, synovitis and synovial vascularity were scored semiquantitatively (grade 0-3) by grey scale (GSUS) and power Doppler ultrasound (PDUS) utilizing the validated scoring system. Each joint was scanned from different angles, the knee joint for example was divided into four areas to score for synovitis: the suprapatellar longitudinal, the medial longitudinal, the lateral longitudinal, and the posterior region. Each area was scored from 0-3, so a maximum score of 12 could be achieved. PsA and AS patients presenting with peripheral joint disease involving large joints were examined at baseline, 3 and 6 months after initiation of local or systemic therapy (DMARDs/Biologics). For evaluation of the inflammatory status, the erythrocyte sedimentation rate (ESR) was determined., Results: A cohort of 126 patients were enclosed, and 83 of these were followed for 6 months. At baseline before modification of the therapy, patients received DMARDs (n = 83), DMARDs plus biologics (n = 30), or biologic monotherapy (n = 29). Following intervention, all US scores demonstrated a marked improvement. The GSUS and the PDUS scores for all joint areas, except the PDUS score of the hip, exhibited a significant improvement (p < 0.05), while the GSUS of the knee showed even a highly significant (p < 0.001) change. The ESR displayed a significant decrease from 27 to 19 mm (p < 0.002) representing good treatment response., Conclusion: The SOLAR score, which has been recently introduced for RA patients, is a very suitable instrument for the qualitative and quantitative evaluation of large joint involvement in PsA and AS patients and allows for treatment monitoring.