Mira Merashli

Subclinical atherosclerosis in Behcet's disease: A systematic review and meta-analysis.

OBJECTIVE To evaluate subclinical atherosclerosis in Behcet disease (BD), we performed a systematic review and meta-analysis of studies where atherosclerosis was determined by flow-mediated dilatation (FMD) and endothelial-mediated dilatation (EMD) and by measurement of intima media thickness (IMT) of carotid arteries. METHODS Systematic search of EMBASE and PubMed databases from January 2000 to January 2014 according to PRISMA guidelines. RESULTS Nine studies met the inclusion criteria on FMD/EMD, 11 on IMT and 4 on both. BD had lower FMD than controls (SMD = -0.89, 95% CI: -0.660 to -1.11, p < 0.001), which was confirmed by subgroup analyses on active and inactive patients (SMD = -1.17, 95% CI: -1.45 to -0.89 and SMD = -0.72, 95% CI: -0.97 to -0.46, p = 0.0001 for both). EMD was lower in BD but with a large estimate (SMD = 0.38, 95% CI: -0.79 to -0.03, p = 0.06, I(2) = 82.2%). IMT was greater in BD and the large estimate (SMD = 0.95, 95% CI: 0.63-1.28, p < 0.0001, I(2) = 87.6%) persisted after subgroup analysis on active and inactive patients (I(2) = 88.4% and 86.7%, respectively). Pooling IMT studies by a Newcastle Ottawa Scale of 5 and 6/7 yielded lower estimates (SMD = 0.54, 95% CI: 0.32-0.75, p < 0.0001, I(2) = 58.7% and SMD = 1.72, 95% CI: 1.35-2.09 p < 0.05, I(2) = 48.6%). CONCLUSIONS FMD is impaired in BD even in inactive state and IMT is greater despite a degree of statistical heterogeneity that reflects the clinical heterogeneity of BD. Future prospective studies should account for risk stratification of atherosclerosis in BD.

The problem in differentiation between psoriatic-related polyenthesitis and fibromyalgia

The recognition of the primacy of enthesitis in animal models of spondyloarthritis and the prevalence of clinically occult enthesopathy in psoriatic subjects and of persistent joint pain in PsA subjects who have ostensibly good reduction of joint swelling under biological therapy has highlighted the potential impact of polyenthesitis in psoriatic disease. In daily practice, the formal demonstration of enthesitis is challenging for the following reasons: the relatively avascular nature of enthesis, often leading to the absence of overt clinical inflammatory signs; the frequent lack of elevation of inflammatory markers; and finally, the limitations of current imaging techniques to provide supportive evidence for inflammation in these areas. Consequently, enthesitis may present as widespread pain indistinguishable from FM or may emerge as the dominant feature after successful biological therapy for suppression of synovitis. The unmet needs in the differentiation between FM and enthesitis in psoriatic disease patients are highlighted and critically evaluated in this article.

Clinical relevance of antiphospholipid antibodies in systemic sclerosis: A systematic review and meta-analysis

OBJECTIVE To evaluate the clinical relevance of antiphospholipid antibodies (aPL) in systemic sclerosis (SSc). METHODS A systematic search of EMBASE and PubMed databases from January 1983 to July 2016 was carried out according to PRISMA guidelines whereas Peto׳s odds ratio (OR) for rare events was used for the meta-analysis. RESULTS The pooled prevalence of participants positive for IgG and IgM anticardiolipin (aCL) antibodies was higher in SSc than controls (12.8% vs 1.6% and 7.8% vs 0.6%; p < 0.0001 for both) as was that of IgG and IgM anti-beta-2-glycoprotein-I antibodies (aβ2GPI) (6.1% vs 0.58%, p < 0.0001; 3.5% vs 0.3%, p = 0.001). The pooled prevalence of pulmonary arterial hypertension (PAH) was more common in SSc positive than negative patients for aCL (IgG/IgM combined) (26.5% vs 10.9%, p < 0.0001) whereas the pooled prevalence of renal disease (RD) was more common in IgG aCL positive than negative patients (36.3% vs 10.9%, p = 0.02). The pooled prevalence of thrombosis was higher in IgG aCL, IgM aCL, and IgM aβ2GPI positive than negative SSc patients (12.6% vs 1.4%, p < 0.0001), (15.1% vs 2.7%, p = 0.002) and (15% vs 0.78%, p = 0.009), respectively. The pooled prevalence of digital infarction/ischemia (DI) was higher in IgG aCL and IgM positive than negative SSc (52.8% vs 39.8%, p = 0.002) and (68.1% vs 29%, p = 0.07). CONCLUSIONS A strong relationship exists between aCL and aβ2GPI of IgG/IgM isotype and SSc; patients positive for these antibodies are more likely to suffer from PAH, RD, thrombosis, and DI. However, data expressed as frequency of aPL positive patients rather than average antibody titers preclude further insight into the relevance of these assumptions.

Evidence of response to IL-6 inhibition in some cases of refractory spondyloarthritis-associated peripheral synovitis

Spondyloarthritis (SpA) is a complex polygenic disorder with mixed clinical phenotype. Pro-inflammatory cytokines, including tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23, play key pathogenetic roles in SpA, with their blockade being effective in many, but not all cases. Inhibition of IL-6 effectively suppresses synovitis in rheumatoid arthritis (RA)1 but has failed to show efficacy in ankylosing spondylitis (AS), the prototype SpA, in two controlled clinical trials.2 ,3 This is surprising since genetic and experimental studies indicate a potential role for IL-6 in some SpA subsets.4–6 Here, we report our experience in four men with AS and severe, recurrent peripheral synovitis. Detailed clinical and laboratory characteristics are summarised in table 1 but briefly they all fulfilled the modified New York criteria for AS with two cases (2 and 4) …

Recommendations for the management of rheumatoid arthritis in the Eastern Mediterranean region: an adolopment of the 2015 American College of Rheumatology guidelines

Clinical practice guidelines can assist rheumatologists in the proper prescription of newer treatment for rheumatoid arthritis (RA). The objective of this paper is to report on the recommendations for the management of patients with RA in the Eastern Mediterranean region. We adapted the 2015 American College of Rheumatology guidelines in two separate waves. We used the adolopment methodology, and followed the 18 steps of the “Guidelines 2.0” comprehensive checklist for guideline development. For each question, we updated the original guidelines’ evidence synthesis, and we developed an Evidence Profile (EP) and an Evidence to Decision (EtD) table. In the first wave, we adoloped eight out of the 15 original questions on early RA. The strength changed for five of these recommendations from strong to conditional, due to one or more of the following factors: cost, impact on health equities, the balance of benefits, and harms and acceptability. In the second wave, we adoloped eight out of the original 44 questions on established RA. The strength changed for two of these recommendations from strong to conditional, in both cases due to cost, impact on health equities, balance of benefits and harms, and acceptability. The panel also developed a good practice recommendation. We successfully adoloped 16 recommendations for the management of early and established RA in the Eastern Mediterranean region. The process proved feasible and sensitive to contextual factors.

Survival in primary antiphospholipid syndrome. A single-centre cohort study.

The vascular mortality of antiphospholipid syndrome (APS) ranges from 1.4 % to 5.5 %, but its predictors are poorly known. It was the study objective to evaluate the impact of baseline lupus anticoagulant assays, IgG anticardiolipin (aCL), plasma fibrinogen (FNG) and von Willebrand factor (VWF), platelets (PLT) and of genetic polymorphisms of methylenetetrahydrofolate reductase C677T, of prothrombin G20210A and of paraoxonase-1 Q192R on survival in primary APS (PAPS). Cohort study on 77 thrombotic PAPS and 33 asymptomatic carriers of aPL (PCaPL) seen from 1989 to 2015 and persistently positive for aPL as per annual review. At baseline all participants were tested twice for the ratios of kaolin clotting time (KCTr), activated partial thromboplastin time (aPTTr), dilute Russell viper venom time (DRVVTr), IgG aCL, FNG, VWF and once for PLT. All thrombotic PAPS were on warfarin with regular INR monitoring. During follow-up 11 PAPS deceased (D-PAPS) of recurrent thrombosis mostly arterial, despite adequate anticoagulation yielding an overall vascular mortality of 10 %. D-PAPS had the strongest baseline aPTTr and DRVVTr and the highest mean baseline IgG aCL, FNG, VWF and PLT. Cox proportional hazards model identified baseline DRVVTr and FNG as main predictors of mortality with adjusted hazard ratios of 5.75 (95 % confidence interval [CI]: 1.5, 22.4) and of 1.03 (95 %CI: 1.01, 1.04), respectively. In conclusion, plasma DRVVTr and FNG are strongly associated with the risk of vascular death in PAPS; while FNG lowering agents exist further research should be directed at therapeutic strategies able to dampen aPL production.

ANTIPHOSPHOLIPID ANTIBODIES AND RENAL TRANSPLANT: A SYSTEMATIC REVIEW AND META-ANALYSIS

OBJECTIVE To evaluate the effect of antiphospholipid antibodies (aPL) on renal allograft outcome after kidney transplantation. METHODS A systematic search of EMBASE and PubMed databases from inception to July 2018 was run according to PRISMA guidelines; Petos odds ratio (OR) for rare events was used for the meta-analysis. RESULTS Our inclusion/exclusion criteria were met by 22 cohort studies having different outcomes: allograft thrombosis (n = 9) and thromboprophylaxis (n = 3), allograft loss from any cause (n = 9), allograft malfunction (n = 3), duration (n = 2), glomerular filtration rate at 1 year (n = 3) and allograft rejection (n = 5). The pooled prevalence of allograft thrombosis and of thrombotic microangiopathy was greater in aPL+ve than negative recipients (10.4% vs 1.7%, p < 0.0001 and 10.2% vs 0%, p = 0.005, respectively). The pooled prevalence of allograft thrombosis was 75% in patients not taking anticoagulation whereas none of the anticoagulated recipients developed thrombosis (p < 0.0001). The pooled prevalence of allograft loss was greater in aPL+ve recipients (28% vs 18% respectively, p < 0.0001); the pooled prevalence of aPL was greater in allograft loss recipients compared to those who did not lose it (51% vs 33%, p < 0.0001). The pooled prevalence of allograft malfunction and rejection was similar in aPL-ve and aPL+ve recipients (32.2% vs 40.3% and 14.9% vs 14.4%, respectively) but graft duration was shorter in aPL+ve than aPL-ve recipients (p = 0.001) and glomerular filtration rate at 1 year was lower in aPL + ve than aPL-ve recipients (p < 0.0001). CONCLUSION APL relate strongly to allograft thrombosis, loss and duration but not to allograft malfunction and rejection. Oral antivitamin K anticoagulants effectively prevent allograft thrombosis in aPL recipients. The debate on the role of aPL in renal transplant is limited by the expression of data as percentage of recipients positive for aPL rather than aPL titres in many studies.

Isoprostane in systemic sclerosis: A systematic review and meta-analysis

Abstract Objectives: To further the knowledge of oxidative stress in systemic sclerosis (SSc), we performed a systematic review and meta-analysis on studies measuring isoprostane, a vasoactive agent deriving from arachidonic acid and implicated in the vasculopathy of SSc. Methods: Systematic search following the PRISMA guidelines in PubMed and EMBASE between January-1990/December-2017 using the terms: oxidative stress, isoprostane, systemic sclerosis and scleroderma. Results: After the screening process, 8 studies including 240 SSc patients and 192 controls were included in the systematic review and meta-analysis, 6 investigating urinary and 2 serum isoprostane: random effect meta-analysis revealed isoprostane overgeneration in SSc (p < .001) with wide heterogeneity (I2 = 75%). Subgroup analysis on urinary isoprostane favoured excess excretion in SSc (p = .009) with slightly lower heterogeneity (I2 = 67%); further subgroup analysis according to unit of measurement revealed no increased isoprostane excretion when expressed as pg/mg creatinine but increased when expressed as pmol/mmol creatinine (p = .05) with medium heterogeneity (I2 = 32%). Subgroup analysis on serum isoprostane favoured overproduction in SSc (p < .0001) with no heterogeneity. Conclusion: There is some evidence for isoprostane overgeneration in SSc that confirms the occurrence of oxidative stress in this setting: further prospective studies with specified outcomes are needed to evaluate the prognostic value of this functional biomarker.

Oxidative/nitrative stress in the pathogenesis of systemic sclerosis: are antioxidants beneficial?

Abstract Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future.

Ankylosing Spondylitis among Familial Mediterranean Fever Patients

BACKGROUND Familial Mediterranean Fever (FMF) is one of the most common hereditary auto-inflammatory diseases especially among Arabs, Armenians, Jews, and Turks characterized by recurrent attacks of fever, abdominal pain and arthritis.Whether the prevalence of ankylosing spondylitis (AS) is increased in FMF patients is a matter of debate. This review will summarize all the literature data relevant to this topic. METHODS We searched all the articles through PubMed and Embase databases from 1963 until 2017 addressing the relationship between AS and FMF patients. RESULTS The prevalence of AS among FMF patients is highly variable. However, a significant relationship was found to exist between MEFV gene mutations and AS. Most patients with coexistent MEFV gene mutations and AS were human leucocyte antigen B27 (HLA-B27) negative. The effect of these mutations on AS severity and prognosis was not significant. CONCLUSION Large based population studies are needed to further assess the existence of MEFV gene mutations among AS patients and their effect on the clinical course of the disease in addition to assessment of AS prevalence in patients with FMF.