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OBJECTIVE: Primary Sjogren’s Syndrome (pSS) is a systemic autoimmune disorder characterized by infiltration of the exocrine glands leading to secretory insufficiency. Despite the progress made in understanding the pathogenesis of the SS, many aspects remain to be clarified. Interleukin-33 (IL33) is a recently discovered cytokine, belonging to IL-1 superfamily. IL33 and its soluble receptor ST2 were implied in a number of immune and in autoimmune diseases pathogenesis. In this work, we analyzed expression of IL33 and ST2 in Sjogren’s syndrome. PATIENTS AND METHODS: Serum IL-33 and soluble ST2 were analyzed using commercial ELISA kit in 15 pSS, 9 patients with Systemic Lupus Erythematosus and 9 controls. RESULTS: We found significant hyperexpression of sST2 in sera of SS patients and SLE patients compared to healthy subjects (p = 0.04 and p = 0.07, respectively). In pSS, sST2 levels in pSS positively correlated with activity index SSDAI (r = 0.662, p = 0.007). In SLE, we found positive correlation between ST2 and SLEDAI 2K (r = 0.685, p = 0.04). Circulating levels of IL-33 were detectable in 2 of 15 SS patients, in 2 SLE patients and in 1 of control subjects. CONCLUSIONS: We found an hyperexpression of sST2 in pSS and SLE patients with a possible immune modulatory role, because of a substantial suppression of circulating IL33. In our pSS and SLE cohort, sST2 levels were in correlation with disease activity indices. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Crescent literature data demonstrated a role of adipokines in immune responses, particularly leptin is involved in wide spectrum of pro-inflammatory functions. Several evidences suggested that leptin is able to inhibit T regulatory cells proliferation and function in vitro models. In the present study, we investigate the relationship between leptin and circulating T regulatory cells (Tregs) in patients affected by systemic lupus erythematosus (SLE). PATIENTS AND METHODS: 13 SLE patients and 11 healthy controls were enrolled. Metabolic syndrome and cardiovascular parameters were evaluated. Serum leptin levels were detected by commercial ELISA kit and circulating regulatory T cells were determined by FACS analysis as CD4+CD25highFOP3+ lymphocytes. RESULTS: Metabolic syndrome, defined by ATPIII criteria, was more prevalent in SLE compared to controls (38.4% vs. 0%, p = 0.04), as well as arterial hypertension (38.4% vs. 0%, p = 0.04). We did not find significant differences in mean leptin levels among SLE and controls (13.13±1.51 ng/ml vs. 9.48±8.67 ng/ml, p = 0.6). Mean Tregs percentage of total CD4 were 1.27±0.9 in SLE vs. 2.8±1.2 in healthy controls (p = 0.001). We found a negative correlation between leptin levels and Tregs percentage of total CD4 in SLE patients (r = 0.4, p = 0.01). CONCLUSIONS: Our results suggest a role of leptin in the regulation of circulating T regulatory cells amount in human SLE. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is one of the most common diseases occurring in both hospitalized and community subjects. Urine culture is the gold standard test for the diagnosis of UTI, but approximately 80% are negative. The aim of this study was to evaluate the performance of the automated urinalysis system Atellica® 1500 (Siemens Healthineers, Erlangen, Germany) as screening tool for ruling out UTI. A total of 5,490 urine specimens from outpatients, that had simultaneous requests for urinalysis and urine culture, were evaluated. Of the 5,490 samples, 833 (15.2 %) resulted positive for urine culture. Among UTI-related parameters, bacterial count was considered the most apt to be diagnostic of subjects affected by UTI. Using a cutoff value for bacteria count equal to 180 elements/µL, Atellica® 1500 detected bacteriuria with diagnostic sensitivity (Se) of 88.1 %, diagnostic specificity (Sp) of 82.1 %, and negative predictive value (NPV) of 95.2 %. Comparing our results with the literature's data, we observed that our Se and NPV were lower, while our Sp was higher. Our data showed that the Atellica® 1500 system detected bacteria with satisfactory analytical performance, but the results obtained do not make it a reliable tool for excluding UTI with urinalysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children., (© 2021. The Author(s).)

The B cell activating factor (BAFF), or B lymphocyte stimulator (BLyS), is a B cell survival factor which supports autoreactive B cells and prevents their deletion. BAFF expression is closely linked with autoimmunity and is enhanced by genetic alterations and viral infections. Furthermore, BAFF seems to be involved in adipogenesis, atherosclerosis, neuro-inflammatory processes and ischemia reperfusion (I/R) injury. BAFF is commonly overexpressed in Systemic Lupus Erythematosus (SLE) and strongly involved in the pathogenesis of the disease. The relationship between BAFF levels, disease activity and damage accrual in SLE is controversial, but growing evidence is emerging on its role in renal involvement. Belimumab, a biologic BAFF inhibitor, has been the first biologic agent licensed for SLE therapy so far. As Rituximab (RTX) has been shown to increase BAFF levels following B cell depletion, the combination therapy of RTX plus belimumab (being evaluated in two RCT) seems to be a valuable option for several clinical scenarios. In this review we will highlight the growing body of evidence of immune and non-immune related BAFF expression in experimental and clinical settings., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

Objectives: To systematically evaluate, through a Medline search, the role of omalizumab in eosinophilic granulomatosis with polyangiitis (EGPA)., Methods: A systematic review was performed with the following inclusion criteria: original articles and case reports written in English and reporting an association between omalizumab and EGPA., Results: We found 18 papers on EGPA (14 case reports, 3 retrospective cohort studies, 1 prospective cohort study). Omalizumab showed to be effective as corticosteroid-sparing agent in EGPA patients with severe asthmatic manifestations. On the contrary, conflicting results concerned its use in refractory forms of EGPA. Plausible is the increased risk of EGPA onset among asthmatic patients treated with omalizumab, probably related to steroid reduction, even if it cannot be excluded that omalizumab might be occasionally directly involved in the pathogenesis., Conclusions: Our findings support the use of omalizumab in selected forms of EGPA, but caution in the tapering of corticosteroids is also recommended. Quality of evidence is limited, as the source of information was mainly case reports. Clinical trials are required in order to evaluate the role of omalizumab in EGPA and to ascertain the risk of asthmatic patients given omalizumab to develop EGPA.

Objectives: To identify the distribution of patients with systemic lupus erythematosus (SLE) in clusters according to the levels of health-related quality of life (HRQoL), entity of pain, fatigue and depression., Methods: We performed a hierarchical cluster analysis. The following measures were used as clustering variables, after canonical transformation: the SF36 physical and mental component summary (PCS and MCS), the Beck Depression Inventory II (entity of depression), the Facit-Fatigue, all assessed during the last visit. Consecutive SLE patients were enrolled from two Italian cohorts. Lupus remission was retrospectively assessed over a period of 5 years before the last visit and was defined as a continuative period of no clinical disease activity according to SLEDAI2K and the maximum dose of prednisone allowed of 5 mg/day., Results: We enrolled 130 female SLE patients. We identified three clusters. The first cluster (43 patients) was characterised by the highest levels of MCS and PCS and the lowest entity of pain, fatigue and depression. Cluster 2 (35 patients) was defined by a reduction of MCS and increase of pain, fatigue and depression; conversely, PCS levels were similar to cluster 1. In cluster 3 (52 patients) we found a reduction of MCS and increase of depression and fatigue (similar to cluster 2) but also a decrease in PCS levels and Bodily Pain (meaning increase in pain). In cluster 3 we found a decreased prevalence of remission ≥5 years., Conclusions: Identification of clusters of patients according to HRQoL levels could be useful to improve SLE management, aiming at personalised medicine.

Objective: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age., Methods: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149)., Results: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning., Conclusion: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objectives: To investigate how the different components of sleep dysfunction described in SLE patients combine together in sleep clusters., Methods: We conducted a cross-sectional study on a perspective cohort of 79 SLE patients (mean age 8.2 ± 14.3 years). Sleep was evaluated using Pittsburgh Sleep Quality Index (PSQI). Clusters were defined using the single components of PSQI in a hierarchical clustering model. We used Beck Depression Inventory, Hamilton Anxiety Rating Scale, and Medical Outcomes Study Short Form 36 (SF36) to measure depressive symptoms, anxiety, and quality of life, respectively., Results: Three sleep clusters were identified. The cluster 1 (N = 47) is characterized by the lowest values of PSQI total score. The cluster 2 (N = 21) presents higher values of sleep latency, but sleep duration similar to cluster 1. In cluster 3 (N = 11), we found sleep latency increased as in cluster 2, but the highest values of PSQI total score and reduced sleep duration. Scores of anxiety and sedentary time were higher in clusters 2 and 3 than in cluster 1. Cluster 3 presented the highest scores of depression and reduced mental and physical components of SF36., Conclusions: The combination of different sleep components in SLE patients allowed us to identify three patterns of dysfunction: a first cluster with better sleep latency and duration, a second with increased sleep latency but conserved duration, and a third with impairment of both latency and duration. The stratification of sleep disorders in clusters might be useful for the personalization of therapy in relation to sleep cluster membership.

To assess clinical and psychosocial factors related to alexithymia in systemic sclerosis (SSc). We enrolled 40 consecutive SSc patients in a cross-sectional study evaluating alexithymia with Toronto Alexithymia scale (TAS-20). We measured Beck Depression inventory (BDI), Hamilton Anxiety rating scale (HAM-H), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Visual Analog Scale (VAS) pain, Pittsburgh Sleep Quality Index (PSQI), Satisfaction with Appearance Scale (SWAP), and Mouth Handicap in Systemic Sclerosis (MHISS). The prevalence of alexithymia was 42%. Alexithymic patients presented increased depressive (p = ≤ 0.001) and anxiety symptoms (p = ≤ 0.001), sleep disorders (p = 0.03), pain (p = 0.02), esthetic concerns (p = 0.03), disability in activities (p = 0.03) and reduced scores of SF-36 in mental components summary (MCS) (p = ≤ 0.001) and physical components summary (PCS) (p = 0.01). We found significant correlations with sleep disorders (r = 0.41, p = ≤ 0.001), BID (r = 0.35, p = 0.04), facial image dissatisfaction (r = 0.35, p = 0.04), mouth disability (r = 0.51, p = 0.005), depressive (r = 0.6, p = ≤ 0.001), and anxiety symptoms (r = 0.48, p = ≤ 0.001), fatigue (r = - 0.45 p = 0.005), SF-36 PCS (r = - 0.51, p = ≤ 0.001) and MCS (r = - 0.65, p = ≤ 0.001). In multiple linear regression analysis, SWAP facial was the only variable associated with TAS-20 [0.99 (0.48) p = 0.05]. Alexithymia correlates with several psychosocial factors but seems strongly related to facial image dissatisfaction.

Objectives: The ability of ultrasound (US) to identify subclinical joint inflammation in rheumatoid arthritis (RA) patients in remission has been already reported. Nonetheless, current studies present a lack of homogeneity in patient's characteristics and number of joints assessed by US. The aim of this study was to identify a reduced set of target joints to be scanned in RA patients in clinical remission in order to detect subclinical synovitis., Methods: Forty RA patients in clinical remission (DAS28 ≤2.6) for at least 3 months underwent an US examination of 18 joints: wrist, II-III-IV-V metacarpophalangeal (MCP) and II-III-IV-V metatarsophalangeal joints bilaterally. The presence of synovial hypertrophy (SH) and power-Doppler (PD) signal was registered following the OMERACT definitions and was graded according to a 4-point scale (0-3). Then, by applying a process of data reduction based on the frequency of joint involvement, a reduced assessment was obtained., Results: Twenty (50%) subjects had at least one joint affected by active synovitis; 17.5% presented grade 1 PD and 32.5% grade 2 PD. The joints most frequently affected by active synovitis were the wrists (75%) and the II MCP joints (55%). After data reduction, the evaluation of 3 joints (both wrists and the II MCP of the dominant hand) obtained a sensitivity of 90% for the detection of subclinical synovitis., Conclusions: The US scan of 3 target joints showed a high sensitivity in detecting subclinical active synovitis in RA patients in clinical remission and can be feasible in the routine assessment of these patients.

Objectives: To systematically review fatigue in systemic sclerosis (SSc) in terms of prevalence, features, correlates, predictors and management., Methods: We performed a literature search in PubMed (Medline), EBSCO and COCHRANE databases up to June 2017 selecting articles regarding fatigue in SSc. The articles finally selected fulfilled the following eligibility criteria: written in English, referred to fatigue in SSc, reporting original data, including validated questionnaires measuring fatigue., Results: A total of 43 records were included. Fatigue in SSc has a prevalence similar to that of other rheumatic diseases and is one of the most prevalent and debilitating symptom experienced by SSc patients. Fatigue leads to a significant impairment of quality of life, parenting, household and work ability. Fatigue is associated with psychosocial factors (depression, pain and sleep disorders), sociodemographic factors and clinical manifestations of the disease (pulmonary and gastrointestinal involvement). Indeed, the relationship with scores of disease activity is uncertain. Pharmacological therapeutic approaches were broadly ineffective in reducing fatigue. More encouraging results concern physical activity, complementary and alternative medicine., Conclusions: Adequate management of fatigue could lead to a marked improvement of the patient's quality of life, also contributing to reduction in SSc indirect costs.

The endocannabinoid (eCB) system plays a key role in many physiological and pathological conditions and its dysregulation has been described in several rheumatological and autoimmune diseases. Yet, its possible alteration in systemic lupus erythematosus (SLE) has never been investigated. Here, we aimed filling this gap in plasma and peripheral blood mononuclear cells (PBMCs) of patients with SLE and age- and sex- matched healthy subjects (HS). Liquid chromatography-mass spectrometry quantitation of eCB levels highlighted that plasma levels of 2-arachidonoylglycerol (2-AG) were significantly increased in SLE patients compared to HS (p = 0.0059), and among SLE patients, highest 2-AG levels were associated with a lower disease activity. No differences were found in N-arachidonoylethanolamine (AEA) and its congeners N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA) concentrations between the two groups. Moreover, gene expression analysis of metabolic enzymes and receptor targets of eCBs and investigation of functional activity and protein expression of selected components of eCB system disclosed a deranged 2-AG metabolism in patients with SLE. Indeed, expression and functional activity of 2-AG biosynthetic enzyme DAGL were selectively enhanced in PBMCs of SLE patients compared to HS. In conclusion, our results demonstrate, for the first time, an alteration of eCB system in SLE patients. They represents the first step toward the understanding of the role of eCB system in SLE that likely suggest DAGL and 2-AG as potential biomarkers of SLE in easily accessible blood samples. Our data provides proof-of-concept to the development of cannabis-based medicine as immune-modulating agents., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The treatment of Lupus Nephritis (LN) is an unmet need in the management of patients with Systemic Lupus Erythematosus (SLE). CASE PRESENTATION : We report two cases of women affected by Lupus Nephritis (LN) ISN/RNP Class IV with serological active disease, high disease activity and marked fatigue. In both cases, Mycophenolate mofetil (MMF), as induction therapy, was poorly tolerated because of gastrointestinal toxicity. Belimumab, together with low-doses of MMF, was effective as induction treatment leading to early achievement of complete renal response in these two selected cases of LN., Conclusions: We also report a literature review concerning the efficacy and safety of Belimumab in Lupus Nephritis. Further studies are needed to evaluate the use of Belimumab to manage the renal involvement in patients with Systemic Lupus Erythematosus, waiting for the results of ongoing randomized clinical trials.

Introduction: The aim of this study was to evaluate the proportion of patients with Systemic Lupus Erythematosus (SLE) who did not met the WHO recommendations for physical activity and to evaluate the amount of time spent in sedentary behavior., Methods: SLE patients were consecutively enrolled in a cross sectional study. The type and the time spent in physical activity and sedentary behavior were evaluated using the IPAQ short form questionnaire. The adequate physical activity was defined according to the 2010 WHO recommendations for health and the sedentary behavior according to the 2017 SBRN consensus. We also assessed quality of life using SF-36, mood disorders using BDI and HAM-H, fatigue using Facit-Fatigue and sleep disorders using PSQI scores., Results: Physical activity was not sufficient to meet WHO recommendations in 56 of 93 SLE patients (60%). SLE patients spent a median (95% range) of 180 (0-600) minutes everyday in sedentary activities. The length of daily sedentary time was more than 6 hours in 25% of SLE patients. In multivariable analysis, the factors associated to the probability of not meeting WHO criteria was only the time of exposure to antimalarials (OR 0.88, p 0.03) and the factors related to the probability of being in the upper tertile of sedentary time (more than 270 minutes) were age (OR 1.04, p 0.02), disease activity expressed by SELENA-SLEDAI score (OR 1.2, p 0.01) and Facit-fatigue score (OR 0.94, p 0.04)., Conclusion: A relevant proportion of SLE patients were inadequately physically active. It is essential to improve the awareness of the importance of increase physical activity and reduce sedentary time. A better control of disease activity and fatigue and a prolonged use of antimalarials could help to reach this notable goal.

Introduction: Systemic Lupus Erythematosus (SLE) is associated to an increased prevalence of Metabolic Syndrome (MeS) and to a reduction of Quality of Life (QoL). The aim of this study is to evaluate the association between MeS and QoL in SLE., Methods: SLE patients were consecutively enrolled in a cross sectional study. MeS was defined according to IFD definition. Therapy with glucocorticoids (GC) and antimalarial was analyzed as cumulative years of exposure. We used a cut off of 7.5 mg of prednisone to define high daily dose of GC. QoL was quantified using SF-36. We used BDI and HAM-H to assess symptoms of mood disorders. Fatigue was evaluated using Facit-Fatigue, physical activity using IPAQ, sleep quality using PSQI and alexithymia using TAS-20., Results: We enrolled 100 SLE patients. MeS prevalence was 34%. Patients with MeS presented reduced scores in SF-36 MCS and PCS compared to patients without MeS (p 0.03 and p 0.004). BDI and HAM-H score were significantly higher in patients meeting MeS criteria compared to subjects without MeS (p 0.004, p 0.02). These results were confirmed after adjustment for confounders. Compared to patients without MeS, those with MeS presented higher age, lower education level, higher recent SELENA-SLEDAI, higher number of flares, increased SDI, longer cumulative exposure to high dose GC and shorter duration of antimalarial therapy. In the multiple logistic regression model, the variable associated to the Odds Ratio of having MeS were: the average of recent SELENA-SLEDAI (OR 1.15 p 0.04), the years of exposure to high dose of GC (OR 1.18 p 0.004), the years of exposure to antimalarials (OR 0.82 p 0.03) and the BDI score (OR 1.1 p 0.005)., Conclusion: A modern management of SLE should not miss to take all the possible measures to ensure an adequate QoL to SLE patients, with particular attention to those affected by MeS.

Background/aim: Low levels of vitamin D play a role progression of cardiovascular diseases. Knowledge lacks whether a relationship exists between vitamin D levels and subclinical carotid atherosclerosis in patients with primary Sjögren's syndrome (pSS)., Patients and Methods: We evaluated vitamin D levels and subclinical carotid atherosclerosis in 25 patients with pSS compared to 22 mild ostheoarthritic control patients (OCp)., Results: Intima-media thickness (IMT) and levels of vitamin D were significantly increased and decreased in pSS, respectively. No correlation was observed between low levels of vitamin D and IMT in pSS. Significant positive correlation between disease duration and IMT and negative between vitamin D levels and increased Sjögren syndrome disease activity index (SSDAI) and syndrome disease damage index (SSDDI) were also found in pSS., Conclusion: IMT of pSS with long disease duration is significantly increased with respect to that of OCp. Vitamin D deficiency does not play a role on IMT of pSS, whereas it plays a role in disease damage and activity. A long disease duration is associated with subclinical atherosclerosis in pSS., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)