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Several diagnostic criteria have been developed to effectively diagnose systemic lupus erythematosus (SLE). Three criteria are most common, namely the American College of Rheumatology (ACR)-1997, the Systemic Lupus International Collaborating Clinics (SLICC)-2012, and the European League Against Rheumatism (EULAR/ACR)-2019. Whether they also apply to juvenile SLE is unclear. To examine the diagnostic accuracy of ACR-1997, SLICC-2012, and EULAR/ACR-2019 for juvenile SLE. A comprehensive search of PubMed, Cochrane, and Embase was conducted up to 26 March 2022. We included all study designs in which patients had any index tests for ACR-1997, SLICC-2012, or EULAR/ACR-2019; both full-text papers and conference abstracts published in English were used. Exclusion criteria were as follows: (1) case reports; (2) adult subjects; or (3) did not report sufficient information to acquire true positive, false positive, true negative, and false negative values of diagnostic criteria. Two authors independently screened studies, extracted relevant data, and assessed the risk of bias. First, a meta-analysis of the diagnostic accuracy of EULAR/ACR-2019 and a hierarchical summary receiver operating characteristic (HSROC) model was performed to estimate sensitivity and specificity with 95% confidence intervals (CIs). We then carried out a network meta-analysis to compare the performances of these three diagnostic criteria. In total, 17 relevant studies that included 2339 juvenile SLE patients were eligible to analyze pooled accuracy. In the meta-analysis, 10 studies (1613 cases) reported the diagnostic performance of EULAR/ACR-2019, showing a pooled sensitivity of 0.92 (95% CI, 0.89–0.95), pooled specificity of 0.89 (0.77–0.95), and area under HSROC of 0.96 (0.94–0.97). In the network meta-analysis, the SLICC-2012 (0.94, 0.92–0.96) had the highest sensitivity, followed by EULAR/ACR-2019 (0.93, 0.90–0.95), and ACR-1997 (0.78, 0.72–0.82); the ACR-1997 (0.96, 0.92–0.98) demonstrated the highest specificity. EULAR/ACR-2019 (0.92, 0.87–0.96) and SLICC-2012 (0.92, 0.86–0.96) had the similar specificity. We found that the applicability of the new EULAR/ACR-2019 criteria in juvenile SLE is not yet the best diagnostic tool. PROSPERO CRD42022321514. • This study represents the first network meta-analysis of diagnostic test accuracy to compare the performance of ACR-1997, SLICC-2012, and EULAR/ACR-2019 criteria for juvenile systemic lupus erythematosus. • For EULAR/ACR-2019, we determined the performance of the new EULAR/ACR-2019 criteria to have an area under the curve value of 0.96. • Among all of the included studies, we found EULAR/ACR-2019 not to be the best tool for diagnosing juvenile systemic lupus erythematosus; SLICC-2012 has better sensitivity, and ACR-1997 has better specificity. [ABSTRACT FROM AUTHOR]

Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease. To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD). Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor. We limited the search to English language papers with abstracts published over the last 10 years. Abstracts were screened for original data regarding hypogammaglobulinemia following BCTT and the use of IGRT for hypogammaglobulinemia following BCTT. We also searched current recommendations from national/international organisations including British Society for Rheumatology, UK Department of Health, American College of Rheumatology, and American Academy of Asthma, Allergy and Immunology. 222 abstracts were identified. Eight papers had original relevant data that met our search criteria. These studies were largely retrospective cohort studies with small patient numbers receiving IGRT. The literature highlights the induction of a sustained antibody deficiency, risk factors for hypogammaglobulinemia after BCTT including low baseline serum IgG levels, how to monitor patients for the development of hypogammaglobulinemia and the limited evidence available on intervention thresholds for commencing IGRT. The benefit of BCTT needs to be balanced against the risk of inducing a sustained secondary antibody deficiency. Consensus guidelines would be useful to enable appropriate assessment prior to and following BCTT in preventing and diagnosing hypogammaglobulinemia. Definitions for symptomatic hypogammaglobulinemia, intervention thresholds and treatment targets for IGRT, and its cost-effectiveness are required. • Immunoglobulin replacement therapy for secondary hypogammaglobulinemia is increasing in autoimmune rheumatic disease. • We review the currently available literature surrounding hypogammaglobulinemia after B-cell targeted therapy in AIRD. • Consensus guidelines are needed for appropriate assessment to prevent, diagnose and to treat hypogammaglobulinemia in AIRD. [ABSTRACT FROM AUTHOR]

The effectiveness of CD20 targeting in connective tissue diseases (CTD) with lung involvement is controversial. This paper aims to review the current evidence about rituximab (RTX) use in CTD-related interstitial lung disease (ILD). We performed a systematic review of papers published between January 2009 and May 2019. We included clinical trials, case/control studies and cohort studies. We excluded letters, case reports, case series, reviews, and full articles when not in English. The selected studies listed as primary or secondary outcome a variation in pulmonary function tests or in the scores used to radiologically stage lung involvement, in CTD-related ILD patients after RTX. Out of 1206 potentially eligible articles, 24 papers were selected: 3 retrospectively described cohorts of patients with different CTD, 14 dealt with systemic sclerosis (SSc)-related ILD, 5 with idiopathic inflammatory myopathies (IIMs)-related ILD, and 2 with Sjögren's Syndrome-related ILD. A direct comparison of the selected studies was hampered by their heterogeneity for outcomes, follow-up duration, the severity of lung involvement, and clinical features of study populations. However, an overall agreement existed concerning the effectiveness of RTX in the stabilization of lung disease, with some studies reporting an improvement of functional parameters from baseline. IIM-related ILD appeared more responsive than other CTD-related ILD to CD20 targeting. RTX is a promising therapeutic tool in CTD-related ILD. This systematic review remarks the unmet need of multicenter prospective studies aiming to evaluate the effectiveness of RTX with adequate sample size and study design. • Lung involvement is a potentially life-threating complication of CTD. • There is an unmet need of novel therapeutic tool, particularly for resistant cases. • Rituximab is able to stabilize and possibly to improve CTD-related ILD. • There is a need of high-quality studies testing Rituximab in CTD-related ILD. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate whether vitamin D levels are related to the risk of developing autoimmune diseases and whether supplementation with vitamin D can modify the course of the diseases. Methods: We reviewed the most relevant papers published from January 1973 to October 2011, using Medline and EMBASE and the search terms “vitamin D”; “autoimmune disease”; “autoimmunity”; “rheumatoid arthritis”; “systemic lupus erythematosus”; “scleroderma”; “systemic sclerosis”; “type 1 diabetes”; “multiple sclerosis”; and “undifferentiated connective tissue disease”. We selected studies on the environmental, genetic and epidemiologic association of vitamin D with autoimmune diseases. Using the strategy described, we identified 1268 articles. 331 articles were eliminated on the basis of the title and another 703 on the basis of the abstract, since they were considered irrelevant for the purposes of the study. Full-text examination was performed on the remaining 234 studies, and a further 15 studies were excluded from the review, since the results had been confirmed or superseded by more recent research. Finally, a systematic review was conducted on 219 articles concerning cross-sectional data on: vitamin D levels and autoimmune diseases; interventional data on vitamin D supplementation in autoimmune diseases; prospective data linking vitamin D level or intake to autoimmune disease risk. Results: Physiopathology studies confirm that hypovitaminosis D, in genetically predisposed subjects, can impair self tolerance by compromising the regulation of dendritic cells, of regulatory T-lymphocytes and of Th1 cells. Cross-sectional studies show that levels of vitamin D <30ng/mL are present in a significant percentage, not only in patients with autoimmune disease, but also in healthy subjects (30–77%), and link profound deficiency (<10ng/mL) with aggravation of symptomatology, while genetic studies associate polymorphism of vitamin D receptors to various autoimmune diseases. Among experimental studies on humans, only those on type-1 diabetes prove that the risks are significantly reduced in infants treated with vitamin D after the 7th month (OR 0.71, 95% CI, 0.60 to 0.84) and that a dose–response effect exists. Conclusions: Basic, genetic, and epidemiological studies indicate a potential role of vitamin D in the prevention of autoimmune diseases, but randomized and controlled trials are necessary to establish the clinical efficacy of vitamin D supplementation in ill or at-risk subjects. [Copyright &y& Elsevier]

Abstract: Studies of accuracy are often more complex to understand than clinical trials, since there can be more than one outcome and scope (screening, diagnosis, and prognosis) and because results have to be reported in more than one way, than in clinical trials (relative risk or odds ratio). Sensitivity and specificity are common terms for practitioners, but to remember that sensitivity is the “ratio between true positive rate and true positive rate plus false negative rate” may sometime cause some frustration. Moreover, likelihood ratio, predictive values, diagnostic odds ratio, and pre- and post-test probability complicate the framework. To summarize these indexes from multiple studies can be also a little more difficult. However, understanding diagnostic test accuracy from different study results and how to interpret systematic reviews and meta‐analysis can help every practitioner improve critical appraisal of evidence about the best use of diagnostic tests. Avoiding complicated mathematical formulas, this paper attempts to explain the meaning of the most important diagnostic indexes and how to read a Forest plot and a summary Receiver Operative Characteristic curve. [Copyright &y& Elsevier]

To investigate whether nailfold videocapillaroscopy (NVC), an increasingly worldwide used non-invasive tool to reliably evaluate the peripheral microcirculation, may be an outcome measure in future screening algorithms for systemic sclerosis related interstitial lung disease (SSc-ILD). A systematic review to identify original research papers documenting an association between NVC and SSc-ILD was performed in 3 electronic databases according to the PRISMA guidelines. Subsequently, NVC parameters were subdivided according to the consented standardised capillaroscopic definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases / Scleroderma Clinical Trials Consortium on Capillaroscopy, into quantitative (capillary density, capillary dimension, capillary morphology and haemorrhages) and qualitative assessment (NVC pattern). The systematic search identified 310 unique search results, of which 2 cross-sectional and 1 longitudinal study were retained. In both cross-sectional studies, the presence of SSc-ILD was found to be inversely associated with capillary density (p =.008 and p =.005). The presence of a severe (active/late) NVC pattern was evaluated and associated with the presence of SSc-ILD in one of the cross-sectional studies. In the longitudinal study, incident SSc-ILD was associated with progressive capillary loss (p =.03) and the conversion to a worse (active/late) NVC pattern (p =.001/ p =.003). This first systematic literature review investigating the role of NVC in SSc-ILD using standardised capillaroscopic definitions uncovered associations between NVC and (incident) SSc-ILD. If large prospective studies further corroborate and elucidate these findings, NVC might possibly be a candidate outcome measure to be integrated in screening algorithms for incident/progressive SSc-ILD. • This is the first systematic review investigating the role of NVC in SSc-ILD, using consented standardised definitions • Capillary density and (worsening to) a severe NVC pattern are associated with (incident) SSc-ILD • NVC might be integrated as a candidate outcome in future screening algorithms for incident/progressive SSc-ILD [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease; the clinical manifestations are correlated with continuum multiarticular synovitis, cartilage and bone damage, and defeat of joint function, that causes disability. Involvement of internal organs is also frequent. Between the inflammatory cells involved in RA, macrophages play a key role. These cells can polarize in different phenotype and mediate the immune/inflammatory reaction as well as the reparatory phase when possible. The properties of these cells are mediate by the body's environmental factors. In this systematic review, all English-speaking articles concerning the role of M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages in RA were systematically reviewed and categorized according to their polarized-function in RA, especially in the synovial tissue. Analyses of the endogenous molecules and the drugs that could modulate M1 and M2 activity in RA were achieved. A sensitive search was developed in Pubmed, Web of Science, Ovid Med-Line, Embase Database and Science Direct Database (la both from Elsevier) to identify articles to increase the highlighting on the role of macrophages M1 and M2 in RA using the following terms: ((M1 AND M2) AND Rheumatoid Arthritis). All selected papers were read and discussed by two independent reviewers. The selection process was based on title, abstract and full text level. Relevant data were extracted and analyzed using a standardized template designed for this review. In total 39 resulting articles were selected and categorized according to description of M1/M2's role in RA. Data from humans, mice and rats were subcategorized, thus in every section were highlighted the contribute, in peripheral blood and synovial tissue, of both polarized macrophages; section for endogenous molecules and drugs that favor the switch from M1 to M2 macrophages were carried out. The most evinced relevant results, were that in RA blood and in the synovial tissue, there isn't a clear distinction phase with M1 or M2 macrophages (by membrane marker analysis); rather there is M1 and M2 subset disequilibrium and by deeply analyses of mRNA gene and cytokine produced, it emerged that a non-coherent expression inner marker match with membrane molecules, and also the tissue section can define the marker expressed. This systematic review emphasizes that the rigid classical subdivision of M1 and M2 macrophages, as well as the different samples' results comparison, might be questionable. In addition, it is suggested, when taking samples from RA patients, to carefully consider their therapies in order to analyze the M1 and M2 macrophages behavior without drug influence. In line with the advances in M1 and M2 knowledge, and the progression in the single-cell methodologies by identification of individual cell molecular markers, therapeutic approaches seem possible to favor the anti-inflammatory macrophage response in RA (e.g. M2 polarization). • There are no differences in the circulating monocyte populations among RA and HD. • M1/M2 polarization changes through the disease activity phases. • In RA synovial tissue there are both mature macrophages and mixed M1/M2 phenotypes. • Molecular milieu modulates M1/M2 polarization in animal models and humans. • Animal RA models are still unable to reproduce the human disease comparably. [ABSTRACT FROM AUTHOR]

Our purpose was to determine the prevalence of thyroid disorders in myasthenia gravis (MG) or whether MG was associated with an increased risk of thyroid disorders. Pubmed, Embase, Web of Science, Cochrane database, Google Scholar and the Chinese Biomedical Databases were searched about the relationship between thyroid disorders and myasthenia gravis up to November 30, 2018, without language restrictions. The prevalence and relative risk (RR) for thyroid disorders were pooled by the R and STATA software. 39 papers with 24,927 MG patients were ultimately included for analysis in this meta-analysis. The pooled estimate of thyroid autoimmunity prevalence in MG patients was 10.1% (95%CI 6.7%–15.1%). Subgroups in patients with thyroid autoimmunity showed the prevalence of positive TGAb was the highest in MG patients (12.6%, 95%CI 8.1%–19.1%), followed by GD (6.0%, 95%CI 4.2%–8.5%), HT (4.6%, 95%CI 1.9%–10.5%). Moreover, the pooled estimated prevalence of thyroid dysfunction in MG patients was 6.8% (95%CI 4.6%–9.8%). After stratification, the results showed the prevalence of hyperthyroidism and hypothyroidism in MG cases were 5.6% (95%CI 3.9%–8.0%) and 2.6% (95%CI 1.7%–4.1%), respectively. In addition, meta-analysis of 2 studies showed that MG was significantly associated with the increased risk of thyroid autoimmunity (OR = 2.86; 95%CI 1.54–5.28, P =.001). This systemic review and meta-analysis provides reliable evidence that thyroid disorders are prevalent in MG, especially TGAb positivity, GD, hyperthyroidism, and HT, and MG is associated with increased risk for thyroid autoimmunity. [ABSTRACT FROM AUTHOR]