Targeting Inflammation to Prevent Cardiovascular Disease in Chronic Rheumatic Diseases: Myth or Reality?

Evidence for increased risk of cardiovascular morbidity and mortality in chronic inflammatory rheumatic diseases has accumulated during the last years. Traditional cardiovascular risk factors contribute in part to the excess of cardiovascular risk in these patients and several mechanisms, including precocious acceleration of subclinical atherosclerotic damage, inflammation, and immune system deregulation factors, have been demonstrated to strictly interplay in the induction and progression of atherosclerosis. In this setting, chronic inflammation is a cornerstone of rheumatic disease pathogenesis and exerts also a pivotal role in all stages of atherosclerotic damage. The strict link between inflammation and atherosclerosis suggests that cardiovascular risk may be reduced by rheumatic disease activity control. There are data to suggest that biologic therapies, in particular TNFα antagonists, may improve surrogate markers of cardiovascular disease and reduce CV adverse outcome. Thus, abrogation of inflammation is considered an important outcome for achieving not only control of rheumatic disease, but also reduction of cardiovascular risk. However, the actual effect of anti-rheumatic therapies on atherosclerosis progression and CV outcome in these patients is rather uncertain due to great literature inconsistency. In this paper, we will summarize some of the main mechanisms linking the inflammatory pathogenic background underlying rheumatic diseases and the vascular damage observed in these patients, with a particular emphasis on the pathways targeted by currently available therapies. Moreover, we will analyze current evidence on the potential atheroprotective effects of these treatments on cardiovascular outcome pointing out still unresolved questions

Nailfold capillaroscopy in Sjogren's Syndrome: Systematic literature review and analysis of a monocentric cohort

Background: Nailfold capillaroscopy (NC) is a non-invasive, reproducible imaging method to assess microcirculation in rheumatic diseases. In contrast to well-defined capillaroscopic findings in patients with systemic sclerosis, specific capillaroscopic findings in Sjögren’s Syndrome (SS) have not been documented. Methods: The literature was systematically reviewed in three databases (Pubmed/Embase/Web of Science) to identify the role of NC in SS. The results were gathered for capillaroscopic parameters, and in a second time, an overview of correlations between these with clinical and laboratory values was given. All original studies to date published were revised. A quality assessment was applied to all included studies based on: sample size, well described target population, presence of a control group, capillaroscopic tool specifications and/or standardly applied methodology, clear definitions and descriptions of capillaroscopic parameters, statistic analysis used. Following the systematic review of literature (SRL), a prospective monocentric study was carried out in the Rheumatology Unit (Department of Medicine, University of Perugia) from September to November 2019. The NC was performed on 14 healthy controls (HC) and 20 patients with Sjögren’s Syndrome (SS). Either qualitative and quantitative assessment were applied aimed to identify more frequent capillaroscopic alterations and/or pattern. Statistical analysis was performed using Student’s t-test and Mann–Whitney U-test. Results: The literature search resulted in 826 hits. Based on title and abstract screening 519 original studies were retained and of these, 18 full texts describe an assessment by NC in SS. Finally, seven studies passed the quality assessment and form the object of this review: five case-control studies (only two studies compared SS with HC) and two case-series. The studies included on average of 61 SS patients (range 18-136). Five studies performed a quantitative assessment of the NC images describing presence of dilations and haemorrhages in SS whereas abnormal morphology and tortuosity were equally seen in SS patients as in HC. One study performed a semi-quantitative assessment and any significant difference between SS and HC was shown. Six studies performed a qualitative assessment describing normal, non-specific and scleroderma pattern in SS patients. Only one study suggests an association between Raynaud’s phenomenon (RP), anticentromere autoantibodies (ACA) and capillaroscopic findings, though the results were not confirmed by analysis in external cohorts. In our study the only significant difference between SS and HC was observed for the mean number of enlarged capillaries. No capillaroscopic differences in SS patients with and without RP were found, SS patients with double positivity (anti-SSA/Ro, anti-SSB/La antibodies) more frequently showed haemorrhages than patients with isolated positive anti-SSA/Ro antibodies. Conclusion: Until now, the nailfold capillaroscopic assessment in patients with SS has not been uniformly clarified. Overall, the reviewed studies in literature show that capillaroscopic findings observed in SS are not significantly different from those observed in HC. In our study we tried to overcome some limits of previous investigations. We observed two statistically significant differences between SS and HC. In particular, more enlarged capillaries was seen in SS. In addition an increased number of haemorrhages was observed in double positive SS also compared to subjects with isolated anti-Ro circulating antibodies. Further research in this domain and on a larger sample of patients is needed to attest the reliability of this results

Lymphoma and Lymphomagenesis in Primary Sjögren’s Syndrome

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease mainly affecting exocrine glands and leading to impaired secretory function. The clinical picture is dominated by signs and symptoms of mucosal dryness and the course of the disease is mild and indolent in the majority of cases. However, a subgroup of patients can also experience extraglandular manifestations that worsen the disease prognosis. pSS patients are consistently found to have a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autimmune disorders and to the general population. NHL is the most severe comorbidity that can occur in pSS, therefore recent research has aimed to identify reliable clinical, serological, and histological biomarkers able to predict NHL development in these subjects. This review article encompasses the body of evidence published so far in this field highlighting the challenges and pitfalls of different biomarkers within clinical practice. We also provide an overview of epidemiological data, diagnostic procedures, and evidence-based treatment strategies for NHL in pSS

Immunomodulatory effects of intravenous immunoglobulin - assembling a jigsaw puzzle

Intravenous immunoglobulin (IVIG) is widely used for the treatment of autoimmune and inflammatory disorders because of its immunomodulatory effects. The interaction of IVIG with the immune system has been extensively investigated over the past 30 years but, since IVIG modifies responses of many immune cells, a unifying model is far from reach. Here we survey the in vitro studies on the effects on IVIG on macrophages, B cells, T regulatory cells, dendritic cells and soluble factors, as well as the in vivo studies in murine disease models and the preliminary in vivo findings in humans

One year in review 2018: Sjögren's syndrome

Sjögren's syndrome is a complex and potentially disabling slow progressive, systemic disorder. During the last twelve months several original and important contributions have been published on the pathogenesis, diagnosis and therapy of the disease. This review, following the others of this series is aimed at summarising some of the most significant studies that have been recently published. Regarding the pathogenesis, we will specifically focus on novel insights on miRNA, gut microbiota, adaptive and innate autoimmunity and animal models. Concerning novelties in pSS diagnosis, we will focus on salivary gland ultrasonography and histology. Finally, we will conclude with an update of the clinical manifestations of the disease and with an overview of the future therapies

One year in review 2017: systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominately affects women. It is characterised by a broad spectrum of clinical manifestations, however, its course and organ involvement are unpredictable. Although over the last few decades an improvement in survival for SLE patients has been observed, pathogenic mechanisms underlying this disease are still unclear. Comorbidities, due to both disease and treatment, as well as multiple aspects of SLE, are under intensive investigation. Following the previous annual reviews of this series, we hereby provide a critical digest of the recent papers on SLE focusing on pathogenesis, clinical and laboratory features, as well as current and new therapeutic strategies published over the last year

Nailfold capillaroscopy in Sjogren's syndrome : a systematic literature review and standardised interpretation

Objective. We aimed to identify the role of nailfold capillaroscopy (NC) in Sjogren's syndrome (SS). Methods. The literature was systematically reviewed in three databases. All published original studies which assess patients with SS by NC were revised. A quality assessment was applied to all studies based on population description, presence of a control group, presence of instrumental specifications and/or standardly applied NC methodology, presence of clear descriptions of capil-laroscopic characteristics and based on the used statistical analysis. The capil-laroscopic findings per study were described in a EULAR consented standardised way. Significant associations of capillaroscopic characteristics in SS patients with clinical and laboratory variables were summarised. Results. The search resulted in 869 hits. Based on title and abstract screening 29 original studies were identified and of these, 14 full texts described an assessment by NC in SS. Seven studies were retained after performing a critical quality assessment. One study compared NC in SS with healthy controls and attested a lower capillary density in SS. Concerning clinical associations, capillary density was associated with Raynaud's phenomenon in two studies and with interstitial lung disease or systemic manifestations in one study each. No association between serologic features (anti-nuclear antibodies, anti-SSA, anti-SSB and anti-RF) and NC characteristics were found. Conclusion. A small number of studies have investigated the role of NC in SS. More studies, including prospective follow-up studies with standard NC evaluation in SS are needed