Cardiovascular involvement in systemic rheumatic diseases: An integrated view for the treating physicians

Systemic autoimmune diseases can affect various kinds of organs including the kidney, the skin, soft tissue and the bone. Among others, cardiovascular involvement in rheumatic diseases has been shown to affect myocardium, pericardium, cardiac vessels, conduction system and valves, eventually leading to increased mortality. In general, underlying chronic inflammation leads to premature atherosclerosis, but also other manifestations such as arrhythmia and heart failure may have a ‘silent’ progress. Traditional cardiovascular risk factors play a secondary role, while disease-specific factors (i.e. disease duration, severity, antibody positivity, persistent disease activity) can directly influence the cardiovascular system. Therefore, early diagnosis is critical to optimize management and to control inflammatory activity and recent data suggest that risk factors (i.e. hypercholesterolemia and hypertension) need intensive treatment as well. With the advent of immunosuppressive agents, most rheumatic diseases are well controlled on treatment, but information related to their cardioprotective efficacy is not well-defined. In this review, we focus on cardiovascular involvement in rheumatic diseases and highlight current evidence which should be of help for the treating physicians. Moreover, cardiotoxicity of immunosuppressive drugs is a rare issue and such potential adverse events will be briefly discussed.     

Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal

Nailfold capillaroscopy is an easy, non-invasive technique to assess microvascular involvement in rheumatic diseases. Multiple studies describe capillaroscopic changes in systemic lupus erythematosus (SLE), including a wide range of non-specific findings. On behalf of the European League Against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases, a systematic review was done to obtain all original research studies (in English) in which SLE patients had capillaroscopy. Forty such studies are identified. This article firstly provides a résumé of the results of these studies according to capillaroscopic parameters (density, dimensions, morphology, haemorrhages), semi-quantitative assessment and qualitative assessment of capillaroscopy in SLE patients. Secondly, the correlations between capillaroscopic parameters in SLE patients and clinical and laboratory parameters (including auto-immune parameters) are outlined. The following capillaroscopic parameters are found to be significantly more prevalent in SLE patients compared to healthy controls: tortuous capillaries, abnormal morphology and haemorrhages. Hairpin-shaped capillaries are significantly less prevalent than in healthy persons. The semi-quantitatively determined nailfold capillaroscopic score (NFC score) in SLE patients is also higher than in healthy controls. Several correlations between clinical and laboratory parameters and capillaroscopic parameters are identified in the review. Disease activity is correlated with NFC score in seven studies, with abnormal morphology (i.e. “meandering”) in one study and with haemorrhages in one study. Frequent attacks of Raynaud's phenomenon (RP) and gangrene are significantly correlated with dilated capillaries. In two studies a possible correlation between anti-SSA antibodies and lower density of capillaries is withheld. About other immune parameters conflicting results are found. In one study a significant negative correlation is found between 24-hour proteinuria and abnormal morphology (i.e. “meandering”). For the first time, an overview of the nailfold capillaroscopic changes that have been described in SLE and their correlations with clinical and laboratory findings is given. Further large-scale research on the identification of capillaroscopic changes in SLE and their correlations with standardised clinical and laboratory parameters, is ongoing at the EULAR study group on microcirculation in rheumatic diseases.     

An emerging role of neutrophils and NETosis in chronic inflammation and fibrosis in systemic lupus erythematosus (SLE) and ANCA-associated vasculitides (AAV): Implications for the pathogenesis and treatment

Neutrophils derive from hematopoietic stem cells (HSCs) with systemic inflammation driving their activation and differentiation to myeloid progenitors to ensure enhanced myelopoiesis. Epigenetic reprograming and re-education of these HSCs produces neutrophils primed towards elimination of pathogens and increased inflammatory response. Neutrophils -an important component of acute inflammation- are not present in chronic inflammatory tissues leading to the false assumption that they may not be as important for the latter. Activated neutrophils may release Neutrophil Extracellular Traps (NETs) during a distinct form of cell death, named NETosis; NETs are rich in bioactive molecules that promote thrombosis (including atherothrombosis), inflammation and fibrosis. Thus, although neutrophils may not be present in chronic inflammatory lesions, their remnants may amplify the inflammatory response beyond their short life-span in the tissues. Herein, we review current evidence supporting a role of neutrophils and NETosis in tissue injury and dysfunction in systemic autoimmunity using as disease paradigms Systemic Lupus Erythematosus (SLE) and the ANCA-associated vasculitides (AAV). We also discuss the mechanisms involved and their potential as targets for novel therapy and drug repositioning.     

Implications of blood indices in systemic lupus erythematosus patients: Two feasible determinants of disease activity and lupus nephritis

Aim of the workTo investigate whether or not neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may by indicators of disease activity in systemic lupus erythematosus (SLE) with and without lupus nephritis (LN).Patients and methodsThis research was carried out on 40 adult SLE patients (20 with LN and 20 without) and 20 controls. The NLR and PLR were calculated. The SLE disease activity index (SLEDAI) was assessed.ResultsThe mean age of the patients was 36.2 ± 7.6 years, 38 females and 2 males (F:M 19:1), with a disease duration of4.3 ± 1.2 years. The mean SLEDAI was 15.1 ± 4.7 being significantly higher in those with LN (17.5 ± 3.5) compared to those without (12.6 ± 4.6) (p = 0.001). The mean NLR (6.1 ± 2.1) and PLR (236.6 ± 86.9) were significantly increased in patients compared to the control (2.7 ± 1.2 and 125.2 ± 38.8 respectively) (p < 0.001). The NLR and PLR were both significantly related to the serum creatinine (r = 0.35, p = 0.03 and r = 0.5, p = 0.001) and SLEDAI (r = 0.36, p = 0.03 and r = 0.34, p = 0.03 respectively). NLR can significantly predict activity of SLE at cut off 5.6 with a sensitivity 80%, specificity 65% (p = 0.007) and PLR at cut off 217 with sensitivity 75%, specificity 65% (p = 0.035). The NLR can significantly predict LN at cut off 3.6 (sensitivity 80%, specificity 40%; p = 0.007) and PLR at cut off 186 (sensitivity 70%, specificity 60%; p = 0.035).ConclusionThere is a remarkable link between PLR and NLR with SLEDAI. Thus, both may serve as promising affordable indicators of inflammation in SLE. The notable relation to LN may signal renal involvement in patients with SLE.     

系统性红斑狼疮成年女性患者月经及相关情况变化

目的 探讨系统性红斑狼疮(SLE)成年女性患者月经及相关情况的变化.方法 选取2015年11月至2016年4月西安交通大学第一附属医院风湿免疫科收住入院的72例SLE成年女性患者,选取同期来自本院体检中心60例健康成年女性作为对照,比较SLE患者与健康对照者月经、绝经、生育史等情况,评估SLE疾病活动指数及糖皮质激素治疗剂量对女性月经情况的影响.结果 在入选的72例SLE成年女性患者中,75.00%(54/72)出现月经异常,SLE患者中绝经年龄较健康对照者提前(t=3.477,P<0.05).已婚的SLE患者中流产或异常产比例高于健康对照者(χ2=6.610,P<0.05).与无月经异常表现的SLE患者相比,有月经异常表现的SLE患者的疾病活动性指数(SLEDAI)评分相对较高(t=2.451,P<0.05)、糖皮质激素服用剂量(mg/d)相对较大(t=2.086,P<0.05),在SLE发病年龄、病程、初潮年龄、体重指数方面无差异(t值分别为0.418、1.692、1.622、0.289,均P>0.05).结论 SLE患者中月经异常、流产或异常产比例较高,绝经年龄提前,有月经异常的SLE患者病情活动度相对高,服用糖皮质激素的平均剂量较大,医护人员需关注SLE患者的月经及相关情况的变化,对SLE患者提供更适宜的治疗方案和护理措施,提高SLE成年女性患者的生活质量.     

复方肾炎片联合来氟米特和泼尼松治疗狼疮性肾炎的临床研究

目的探讨复方肾炎片联合来氟米特和泼尼松治疗狼疮性肾炎(LN)的临床疗效。方法选取2015年1月—2015年6月在海口市人民医院接受治疗的LN患者84例,根据治疗方案的差别分为对照组和治疗组,每组各42例。对照组口服醋酸泼尼松片,1 mg/(kg·d),2个月后逐渐减至10 mg/d;同时口服来氟米特片,20 mg/d。治疗组在对照基础上口服复方肾炎片,3片/次,3次/d。两组患者均连续治疗6个月。观察两组的临床疗效,比较治疗前后两组患者各项血肌酐(Scr)、24 h尿蛋白定量(24 h Upro)、红细胞(RBC)、β2-微球蛋白(β2-MG)、血浆白蛋白(Alb)、红细胞沉降率(ESR)和补体C3情况以及SLEDAI积分变化。结果治疗后,对照组和治疗组的总有效率分别为71.43%、90.48%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者Scr、24 h Upro、RBC计数、β2-MG、ESR水平均较治疗前显著降低,Alb和C3水平显著升高,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者SLEDAI积分均明显降低(P0.05),治疗组患者SLEDAI积分比对照组降低更显著(P0.05)。对照组和治疗组的不良反应发生率分别为26.19%、9.52%,两组比较差异有统计学意义(P0.05)。结论复方肾炎片联合来氟米特、泼尼松治疗LN效果显著,可明显提高临床缓解率,且不良反应发生率低,具有一定的临床推广应用价值。     

Two systemic lupus erythematosus (SLE) global disease activity indexes--the SLE Disease Activity Index and the Systemic Lupus Activity Measure--demonstrate different correlations with activation of peripheral blood CD4+ T cells

Global disease activity measurement in systemic lupus erythematosus (SLE) patients is important for the clinical estimation and adjustment of therapy. By contrast, immune system activation plays a significant role in disease pathogenesis, with CD4+ lymphocytes acting as central cells in the immune response. We investigated which scale better correlates with immunologic changes in the blood of SLE patients, the SLE Disease Activity Index (SLEDAI) or the Systemic Lupus Activity Measure (SLAM) scale. Samples of peripheral blood were obtained from 45 SLE patients with different disease activity as assessed by the SLEDAI and the SLAM scales on the same day. We assessed the percentage of CD4+ T cells with activation-associated receptors: CD69, CD25int, CD95, HLA-DR, and CD4+ T cells with killing properties containing perforin and granzyme B. Our results indicated that the percentage of CD4+CD69+ and CD4+CD25(int) cells did not correlate with either the SLEDAI or the SLAM scale. Significant and positive correlations were observed between percentages of CD4+CD95+ and CD4+HLA-DR+ lymphocytes and SLE activity, but only when activity was measured using the SLAM scale, not with the SLEDAI scale. The percentage of CD4+perforin+ and CD4+granzyme B+ cells also strongly correlated with disease activity measured only with the SLAM scale. We conclude that the SLAM scale better reflects changes of immune system activity in SLE patients compared with the SLEDAI scale.     

Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

OBJECTIVE:

To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features.

METHODS:

We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay.

RESULTS:

We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 first-degree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels.

CONCLUSION:

Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.     

Association between anti-Ro 60 kDa (SS-A) autoantibodies and hypocomplementemia in systemic lupus erythematosus patients from Algiers prefectures

BackgroundSystemic lupus erythematosus (SLE) is characterized by a vicious cycle maintaining systemic inflammation. It starts by autoantibody production, immune complex formation and complement activation that contribute to inflammation, tissue damage and further autoantibody production.Aim of the workTo evaluate the association between the auto-antibodies (abs), circulating immune complexes (CIC), and complement activity in SLE patients.Patients and methodsThis study involved 30 female SLE patients analyzed for autoantibodies, complement profile including complement hemolytic 50 (CH50), alternative pathway 50_, factor B, C1q, C2, C3 and C4 as well as C1q-CIC. SLE disease activity was assessed by the SLE Disease Activity Index (SLEDAI).ResultsThe age of patients was 34 ± 12.8 years, disease duration was 5.2 ± 3.2 years and their mean SLEDAI was 9.96 ± 4.2. Anti-SSA, anti-dsDNA, anti-C1q abs, and CIC were detected in 36.7%, 50%, 50% and 30% of patients, respectively. Anti-SSA were higher in patients with lower compared to normal CH₅₀ activity and C3 level (24.7 vs 88.6 U/ml; p = 0.002 and 118.6 ± 25.18 U/ml vs 15.9 ± 7.3; p < 0.0001 respectively) than the other autoantibodies. Increased CIC were higher in patients with lupus nephritis and were associated with anti-SSA, anti-SSB, anti-C1q, anti-Sm and in patients with low CH50 activity. The CIC significantly correlated with anti-C1q (r = 0.69, p < 0.0001), anti-SSA (r = 0.5, p = 0.005) and negatively with CH₅₀ (r = −0.4, p = 0.046).ConclusionsThe current study confirms that the etiopathogenic anti-SSA autoantibodies are the most associated with hypocomplementemia in SLE. This would stimulate future researches for validation of predictive biomarkers earlier than hypocomplementemia which is still the major unmet need in lupus research and patient care.     

IL22 in Egyptian SLE patients,could it reflect disease activity,skin or renal involvement or is it only an expensive ESR?

Aim of the work

To analyze the level of interleukin 22 (IL-22) in sera of systemic lupus erythematosus (SLE) patients and to associate its level to disease activity, skin involvement and lupus nephritis.