Fundus fluorescein angiography and optical coherence tomography findings in ocular and non-ocular Behҫet’s disease

Aim of the workThis study aimed at early detection of fundus fluorescein angiography (FFA) findings and optical coherence tomography (OCT) changes denoting active posterior uveitis in Behçet’s Disease (BD) patients before they are clinically evident.Patients and methodsThis study included 50 BD patients subgrouped according to ocular involvement into ocular and non-ocular Behçet patients. All patients underwent thorough ophthalmological examination. Fundus examination was done to detect signs of intermediate and/or posterior uveitis. OCT conventional and enhanced depth techniques were used for assessment of the macular area and choroidal thickness respectively. FFA was done for assessment of retinal vasculature.ResultsThe mean age of the BD patients was 33.26 ± 7.3 years, the disease duration was 8.34 ± 6.6 years and they were 38 males and 12 females. In non-ocular Behçet (n = 25; 49 eyes), 26.5% of eyes showed FFA changes. The mean age at diagnosis in patients showing FFA changes was significantly lower than in those showing no changes (21.08 ± 2.8 years versus 26.53 ± 6.8 years, p = 0.007). There was no significant difference in choroidal thickness between ocular and non-ocular patients (341.4 ± 84.2µ vs 334.24 ± 56.42µ; p = 0.12). In ocular BD (n = 25; 45 eyes: 23 inactive and 22 active) the mean choroidal thickness in patients with uveitic activity was significantly higher than in those with inactivity (377.1 ± 102.9µ versus 307.2 ± 39.9µ, p < 0.0001).ConclusionFFA and OCT are essential and complementary tools for early detection of ocular involvement even before it is clinically evident and for evaluation of the pattern of retinal and choroidal involvement and complications in BD patients.     

Ocular manifestations and complications in a cohort of Behçet’s disease patients in a tertiary hospital

Aim of the workTo determine the frequency of initial ocular findings and subsequent ocular complications among a cohort of Behçets disease (BD) patients attending the outpatient clinic of a tertiary hospital.Patients and methodsThe medical records of 94 BD patients attending the Rhuematology and Ophthalmology outpatient clinics of Ain Shams University Hospitals were retrospectively reviewed. The frequency of ocular findings and subsequent complications were recorded.ResultsThe mean age of patients at diagnosis was 37 ± 12 years; 65 were males and 29 females (M:F 2.24:1); 93.6% resided in urban and 6.38% in rural areas. Current management regimen included oral steroids in 60 patients, with pulse steroids given in case of disease activity. 32 patients received azathioprine and 48 patients received colchicine. Ocular manifestations were the presenting complaint in 7 (7.4%) patients; 5 complaining of redness, and 2 photophobia and excessive lacrimation, and 95.7% (n = 90) had ocular findings later on. The mean intraocular pressure was 13.8 ± 2.5 mmHg in the right eye and 15.5 ± 2.6 mmHg in the left. Anterior uveitis was present in 41.5%, posterior in 26.6% amd pan uveitis in 28.7%. 3 had a lost eye, 10 cataract, 6 glucoma and others (n = 5) had macular oedema and phthisis bulbi. Visual acuity was 6/12 in 64 (68.1%).ConclusionOcular manifestations were the presenting complaint in fewer than 10% of patients, and subsequent frequency of ocular complications reported in our study is among the highest recorded. Further multicenter studies are needed to identify ocular complications in BD.     

Depression in Behçet’s disease patients: Relationship with disease pattern,activity and quality of life

Aim of the workTo determine the frequency of depression in Behçet’s disease (BD) patients and to clarify its burden on patients’ clinical manifestations, disease activity status and quality of life (QoL).Patients and methods35 BD patients with 35 matched control were included in this study. Disease activity was assessed by Behçet Syndrome Activity Score (BSAS). All participants were requested to complete the Hamilton depression rating scale (HDRS), Multidimensional assessment of fatigue (MAF) questionnaire and the short form-36 (SF-36) QoL Scale.ResultsThe mean age of the patients was 40.3 ± 13.5 years (17–72 years) and they were 27 males and 8 females. The frequency of depression in BD patients was 74.3% with increased male frequency (p = 0.007) and major organ involvement (p = 0.04) among depressed patients. Significant differences (p < 0.001, p = 0.04, p = 0.001 respectively) between depressed and non depressed BD patients with respect to BSAS, MAF and SF-36. Highly significant positive correlations between HDRS and number of major organ, BSAS, MAF, (p < 0.001) and significant correlation with number of non major organs (r = 0.3, p = 0.04). Significant negative associations were observed between HDRS and SF-36 (r = ?0.6, p < 0.001). On regression number of major organ involvement (p < 0.001), BSAS (p = 0.01), MAF (p = 0.002), and SF-36 QoL (p < 0.001) significantly correlated with HDRS.ConclusionDepression is a significant comorbidity in patients with BD and is closely related to fatigue, number of major organ involvement and overall disease activity with a negative impact on QoL. Therefore, early interference and depression management in routine clinical practice is important to reduce patients’ symptoms, and improve QoL.     

Optical coherence tomography angiography (OCTA) findings in juvenile idiopathic arthritis

Aim of the workTo report optical coherence tomography angiography (OCTA) findings in juvenile idiopathic arthritis (JIA) patients and to study the relation to disease activity.Patients and methodsThe study included 20 JIA patients (38 eyes) who underwent ophthalmologic and rheumatologic examination plus OCT/OCTA. Juvenile arthritis disease activity score (JADAS27) was assessed, and patients were divided into those with no/low activity (group 1; n = 13) and moderate/severe activity (group 2; n = 7). OCTA findings were compared with 11 control (11 eyes).ResultsThe study included 20 JIA-U patients (38 eyes) with a mean age of 10.7 ± 2.6 years and disease duration of 72.5 ± 34.7 months and they were 9/20 (45 %) females. 13(65 %) patients had no/mild activity (group 1, 25 eyes) while 7(35 %) had moderate to severe activity (group 2, 13 eyes). The mean foveal superficial and deep capillary plexuses (SCP/DCP) vascular density (VD) were significantly lower in patients with moderate/severe activity (3x3 scan: p = 0.001 and p < 0.001; 6x6 scan p = 0.008 and p = 0.001 respectively). The foveal avascular zone (FAZ) 3x3 and 6x6 scans were significantly increased and the central macular thickness (CMT) decreased in patients with moderate/severe disease activity (p < 0.001, p = 0.001, and p = 0.001). Fovea SCP VD in 6x6 and 3x3 scans were significantly different between JIA subtypes (p = 0.01 and p = 0.03, respectively), with less VD in oligoarticular type. FAZ, CMT and DCP-VD significantly correlated with visual analogue scale (r = 0.58, p < 0.001; r = ?0.5, p = 0.01; r = ?0.58, p < 0.001, respectively).ConclusionsNon-invasive OCTA-derived vascular parameters of the macula could be potential biomarkers for evaluating the severity of the systemic disease activity in JIA patients.     

Effect of vitamin D receptor gene polymorphism on lipid profile in Egyptian children with juvenile idiopathic arthritis

Aim of the workTo assess the effect of vitamin D receptor (VDR) polymorphism on lipid profile in patients with juvenile idiopathic arthritis (JIA) and study its relation to disease characteristics.Patients and methodsThe study included 55 JIA children and 55 matched controls. The lipid profile including cholesterol, high and low-density lipoprotein (HDL and LDL), and triglycerides was assessed. The single nucleotide polymorphism (SNP) VDR gene (rs2228570) polymorphism was assayed by real-time polymerase chain reaction (PCR) in patients and control. Results:55 JIA patients were 36 girls and 19 boys (F:M 1.9:1) and with a mean of age 8.4 ± 3.1 years (3–13 years) and disease duration 1.8 ± 1.4 years (2 months ?8 years). Cholesterol, LDL, and triglycerides were significantly higher (175.4 ± 12.9 mg/dl vs 140.4 ± 7.3 mg/dl, 95.9 ± 9.3 mg/dl vs 71.4 ± 8.1 mg/dl, 95.4 ± 8.3 mg/dl vs 89.3 ± 9.1 mg/dl respectively) while the HDL was significantly lower (52.6 ± 4.5 mg/dl vs 54.9 ± 2.2 mg/dl)(p < 0.001) among JIA children as compared to control. The FF genotype was significantly more frequent in JIA (n = 35; 63.6%) than control(n = 19; 34.5%)(p < 0.001)(Odds ratio 3.3; CI 95% 1.5–7.2) while the Ff genotype was more in the control (n = 29; 52.7% vs n = 5; 9.1%)(p < 0.001). There were no significant variations in the lipid profile across VDR genotypes (p greater than 0.05).There was a significant association of FF genotype (n = 35; 100%) with the oligoarticular subtype of JIA and Ff (n = 3; 60%), ff (n = 9; 60%) with the polyarticular subtype of JIA (p < 0.001).ConclusionVDR FF genotype is associated with three folds risk for JIA and VDR polymorphism is not associated with dyslipidemia in JIA.     

Serum,synovial and mRNA expression of interleukin-33 in juvenile idiopathic arthritis patients: Potential role as a marker of disease activity and relation to musculoskeletal ultrasound

Aim of the workTo measure interleukin-33 (IL-33) serum and synovial fluid (SF) levels as well as its relative expression in peripheral blood mononuclear cells (PBMC) of juvenile idiopathic arthritis (JIA) patients and to study their relation to clinical, laboratory and musculoskeletal ultrasound characteristics, disease activity and functional status.Patients and methodsThe study included 60 JIA patients and 60 healthy controls and SF levels were measured in 20. Juvenile arthritis disease activity score (JADAS27) and Juvenile Arthritis Multidimensional Assessment Report (JAMAR) were assessed; Ten-joint grey scale (GS) and power Doppler (PD) MSUS score was performed. Rheumatoid factor (RF) titer and C-reactive protein (CRP) levels were measured.ResultsIn JIA patients, serum IL-33 levels (median 12.6; 7.4–23.8 ng/l) and its relative mRNA expression (median 3.3; 2.5–3.7) were significantly higher than their levels in the controls (median 1.7; 0.8–2.4 ng/l and median 1 ng/ml; p < 0.001). Polyarticular subtype (n = 20) had higher IL-33 serum levels compared to oligoarticular (n = 28, p < 0.001) and systemic-onset (n = 12, p = 0.006) subtypes. In JIA patients, the serum and SF levels of IL-33 significantly correlated with JADAS27 (p < 0.001 and 0.002 respectively), CRP (p < 0.001 and 0.007 respectively), GS (p < 0.001 and 0.001 respectively) and PD (p < 0.001 and 0.005 respectively). Serum IL-33 correlated with RF (p = 0.039) while, SF IL-33 correlated with physical function (p = 0.02).ConclusionsJIA patients have significantly elevated IL-33 serum concentrations and mRNA expression that considerably correlated with different inflammatory parameters, RF and physical function suggesting that it could be a valuable marker of JIA disease activity and implies a possible prognostic role.     

Patient-reported outcome measure of the quality of life in Ugandans living with autoimmune rheumatic diseases

Aim of the workTo assess the patient reported outcome measure (PROM) of the quality of life (QoL) of patients with autoimmune rheumatic diseases (RDs) attending two tertiary care rheumatology clinics in Uganda.Patients and methodsPatients with a confirmed diagnosis of RD and receiving disease modifying anti-rheumatic drugs (DMARDs) were studied. Health index and overall self-rated health status were assessed using the EuroQol 5-dimension (ED-5D-5L) questionnaire tool.Results74 patients were studied: 48 (64.9%) had rheumatoid arthritis (RA), 14(18.9%) systemic lupus erythematosus (SLE), and 12(16.2%) had other RDs; spondyloarthritis (n = 5), systemic sclerosis (n = 3), juvenile idiopathic arthritis (n = 2), and idiopathic inflammatory myositis (n = 2). Their mean age was 45 ± 17 years and 69 (93.2%) were female. 14(18.9%) were on concomitant herbal medication and 26(35.1%) self-reported at least 1 adverse drug reaction. Any level of problem was reported by 54(72.5%) participants for mobility, 47(63.5%) for self-care, 56(75.6%) for usual activity, 66(89.1%) for pain and discomfort, and 56(75.6%) for anxiety/depression. The mean health index of the patients was 0.64 ± 0.16 and the overall self-rated health status was 58.1 ± 16.7. Patients with SLE (0.74 ± 0.12) had higher health index compared to those with RA (0.60 ± 0.17) or other RDs (0.70 ± 0.1) (p < 0.007). Overall self-rated health status was comparable across clinical diagnoses (p = 0.23). Both the index and self-reported status were better for patients who received private hospital care compared to public hospital (p < 0.0001 and p = 0.01).ConclusionThere is a substantial negative impact of autoimmune rheumatic diseases on quality of life of patients, especially those receiving care from a public facility in Uganda.     

Assessment of long non-coding RNA (THRIL and TMEVPG1) among Behçets' disease patients

BackgroundBehçet’s disease (BD) is a chronic inflammatory disorder with multifactorial cause. Long non-coding RNAs (lncRNAs) perform an essential role in gene regulation, and there is ongoing research in their contribution to autoimmune diseases.Aim of the workTo determine expression levels and diagnostic value of Theiler's Murine Encephalitis Virus Possible Gene1 (TMEVPG1) and TNFα and hnRNPL related immunoregulatory long non-coding RNA (THRIL) in BD, and to assess their role in the clinical characteristics of BD and disease activity.Patients and methodsStudy included 30 BD patients (12 females and 18 males) and 30 matched controls. Expression levels of TMEVPG1 and THRIL were detected by real-time polymerase chain reaction.ResultsThe mean age of patients was 37.5 ± 11.3 years and disease duration was 7.7 ± 6 years. Expression levels of TMEVPG1 and THRIL were upregulated significantly in serum of patients compared with controls (set as 1). TMEVPG1 fold change = 3.0 with interquartile range (0.2–546.9) (p < 0.0001), while THRIL fold change = 3.6 with interquartile range (0.1–112.3) (p < 0.0001). There was significant correlation between TMEVPG1 and THRIL (r = 0.48, p = 0.007). TMEVPG1 did not correlate with the clinical characteristics of patients, while THRIL correlated only with central nervous system manifestations. At a cut-off point of 1.3 the sensitivity of TMEVPG1 was 76.7%, while THRIL at 1.08 was 73.3% and specificity was 100% for both.ConclusionTMEVPG1 and THRIL were differentially expressed in the serum of BD patients and both had potential diagnostic value. Furthermore, an association between the expression level of THRIL and CNS symptoms was observed.     

Protein Z (rs3024735; G79A and rs3024719; G-103A) gene polymorphisms in Behçet’s disease patients

Aim of the workTo investigate protein Z (PZ) gene polymorphic variations; PZ G79A (rs3024735) and PZ G-103A (rs3024719) in Behçet's disease (BD) patients and their possible relation with disease manifestations, activity and damage.Patients and methodsThis study included 100 BD patients and 100 controls. BD current activity form (BDCAF) and the BD damage index (BDI) were assessed. Genomic DNA analysis of PZ G79A (rs3024735) and PZ G-103A (rs3024719) single nucleotide polymorphisms, was assessed by Real-time PCR-TaqMan SNP genotyping assay.ResultsThe mean age of patients was 33.4 ± 6.8 years and median disease duration was 9 years. AA and GA genotypes of PZ G79A polymorphism were significantly higher in patients than controls (p = 0.003 and p = 0.004 respectively). The frequency of A allele was significantly higher in patients than controls (p < 0.001). There was no difference between patients and controls regarding AA and GA genotypes of PZ G-103A polymorphism (p = 0.5 and p = 0.2 respectively). There was a significant association between AA and GA genotypes of PZ G79A polymorphism with retinal vascular occlusion (RVO) (p < 0.001) and deep vein thrombosis (DVT) (p = 0.003), neutrophil–lymphocyte ratio (p < 0.001) and BDI (p < 0.001). There was no association between PZ G79A genotypes and BDCAF (p = 0.8). A allele of PZ G79A polymorphism was associated with increased BD susceptibility (p < 0.001), RVO (p = 0.001) and DVT (p = 0.01).ConclusionPZ G79A (rs3024735) polymorphism A allele was associated with increased susceptibility to BD with increased risk of developing RVO, DVT and damage, while AA and GA genotypes of PZ G-103A polymorphism were not significantly increased in BD patients.     

Frequency,characteristics and outcome of corona virus disease 2019 (COVID-19) infection in Iranian patients with rheumatic diseases

Aim of the workTo investigate the frequency, clinical characteristics and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in rheumatic diseases patients.Patients and methodsOne thousand patients with rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), systemic sclerosis (SSc), Sjögren’s syndrome (SS), Behçets disease (BD), vasculitis, idiopathic inflammatory myositis (IIM), relapsing polychondritis, sarcoidosis and antiphospholipid syndrome (APS) were studied. The following data were collected: age, sex, disease diagnosis, rheumatic disease medication. Rheumatic diseases patients were divided into two groups of infected and non-infected patients with COVID-19 and collected data were compared.ResultsThe 1000 patients mean age was 43.4 ± 13 years and 84.1% were females. The main diagnosis was RA (37.1%), followed by SLE (23.8%), SpA (13.4%), SSc (12.4%), vasculitis, BD and rhupus in 2.4%, 2.3% and 2.2% respectively, SS and SSc in 0.7% each. Most patients were taking glucocorticoids (78.4%). A large majority of patients were taking at least one of the cDMARDs. 16.1% were taking biologic therapy. 221 rheumatic diseases patients with COVID-19 were identified. Of these, 38 patients (17.2%) were hospitalized and 9 patients (4.1%) died. No significant difference was observed for compared variables in patients with and without COVID-19 except for prednisolone >20 mg/d (0.64% vs 2.26%; p = 0.048).ConclusionMost rheumatic diseases do not seem to be a risk factor for developing COVID-19 infection and despite immunosuppressive therapies, there is no poorer outcome. Only, patients using prednisolone >20 mg/d are at higher risk of developing COVID-19 infection.     

Assessment of nutritional deficiency manifestations in patients with rheumatic diseases

BackgroundInflammatory diseases can interfere with adequate nutrition and even lead to a malnourished state. Nutritional deficiency manifestations may be similar to rheumatologic manifestations.Aim of the workTo assess whether malnutrition is an associated feature of rheumatic diseases (RDs).Patients and methodsA multicenter study included Egyptian patients with different RDs; nutrition measurements and common features of deficiency were assessed; general appearance, skin, hair/nail changes, spooning of nails, night blindness, mouth problems, edema, tetany, dysphagia, diarrhea, thyromegaly, loss of appetite and weight loss.ResultsThe study included 284 patients with various RDs: rheumatoid arthritis (RA) (n = 128), systemic lupus erythematosus (n = 120), Behçet’s disease (n = 17), spondyloarthritis (n = 6), systemic sclerosis (n = 5), dermatomyositis (n = 2), relapsing polychondritis (n = 2), and one patient each with familial Mediterranean fever, Gout, Still's disease and undifferentiated connective tissue disease. Muscle wasting was present in 44(15.5%) patients, spooning of nails in 26(9.2%), night blindness in 38(13.4%), glossitis in 48(16.9%), tetany in 32(11.3%) and loss of appetite in 51(18%). Although there was significant differences among RDs in some nutritional deficiency signs, the type and their durations did not significantly affect symptoms or signs of nutritional deficiency, while age was associated with peripheral edema (p = 0.014) and tetany (p = 0.009); azathioprine was associated with hair/nail changes (p = 0.04); methotrexate with peripheral edema and hair/nail changes (p = 0.002, p = 0.01 respectively); and hydroxychloroquine was negatively associated with skin rash, wasting and hair/nail changes (p = 0.011, p = 0.001 and p < 0.0001 respectively).ConclusionNutritional deficiency is common among RD patients especially elderly and should be monitored frequently regardless type and onset.     

Frequency of fibromyalgia syndrome and anxiety post-corona virus disease-2019 (COVID-19) in patients attending the rheumatology clinic

Aim of the workTo screen for the new development of fibromyalgia syndrome (FMS) and anxiety in rheumatic diseases (RDs) patients and control who recovered from coronavirus disease 2019 (COVID-19).Patients and methodsThe study included 200 RDs patients and 100 matched controls with no previous history of FMS and who recovered from COVID-19. The patients’ RDs included rheumatoid arthritis (RA) (n = 50), systemic lupus erythematosus (SLE) (n = 50), juvenile idiopathic arthritis (JIA) (n = 40) and spondyloarthritis (SpA) (n = 60). The fibromyalgia symptom scale (FS), fibromyalgia impact questionnaire (FIQ) and Hamilton Anxiety rating scale were assessed.ResultsThe mean age of patients was 35.9 ± 8.5 years with female: male 2.6:1. Fibromyalgia and anxiety were significantly higher in cases than control (22.5 % vs 12 % and 27 % vs16 %, p = 0.002, p = 0.03 respectively). Hypertension, obesity, anxiety, severe COVID-19, frequency of SLE and SpA were significantly higher in patients with FMS compared to those without (31.1 % vs 11.6 %, 68.9 % vs 21.9 %, 84.4 % vs 10.3 %, 48.9 % vs 16.8 %, 31.1 % vs 23.2 % and 40 % vs 27.1; p = 0.002, p < 0.001, p < 0.001, p < 0.001, p = 0.014, p = 0.004 respectively).Severity of COVID-19, diabetes and anxiety were significant predictors of FMS(β = 1.1, p = 0.007; β = 3.03, p = 0.001 and β = 4.44, p < 0.001 respectively). Fibromyalgia increases with increase anxiety grade; the percentage of fibromyalgia was 4.7 %, 50 %, 90 % and 100 % among patients with no anxiety, mild, moderate, and severe anxiety respectively (p < 0.001).ConclusionFibromyalgia is common in RDs patients post-COVID-19. Diabetes, COVID-19 infection severity and anxiety predict the risk of developing post-COVID-19 fibromyalgia. Post-COVID-19 fibromyalgia occurred more in hypertensive, obese, anxious and patients with severe COVID infection.     

Systematic review on the use of adalimumab in autoinmune. Efficacy and safety in 54 patients

ObjectiveTo analyze published evidence about adalimumab use in autoimmune diseases.MethodsSystematic review of MEDLINE database of citations included from January 1990 to December 2008 employing the terms “adalimumab” and the different systemic autoimmune diseases.ResultsOur search identified 241 potentially relevant citations. 154 were retrieved for detailed evaluation. Finally, 18 were selected as relevant, including 54 patients. The reported diseases were as follow: Behçet disease in 16 patients, idiopathic uveitis in 13, sarcoidosis in 5, uveitis associated with rheumatologic diseases in 5 (psoriasis in 2, ankylosing spondylitis in 1, juvenile idiopathic arthritis in 1, Crohn disease in 1), Vogt-Koyanagi-Harada disease in 4, Birdshot uveitis in 4, vasculitis in 3 (1 temporal arteritis, 1 Takayasu′s disease, 1 skin vasculitis associated with rheumatoid arthritis), adult onset Still disease in 2, relapsing polychondritis in 1 and systemic sclerosis in 1. The clinical spectrum included uveitis (39 cases), skin and/or mucosae (9), vasculitis (3), arthritis (6), lung (3). These patients were refractory to standard therapy, including corticosteroids (42 cases, 78%), immunosuppressants (42, 78%) and biologics (29, 54%). Fifty (93%) patients responded to adalimumab. The clinical response was similar in those patients who had been treated with other biologic and in those who had not received biologic therapy before adalimumab. The patients were followed for 11.9 months. Twelve (22%) patients relapsed. Five (9%) patients suffer some side effect (3 local skin reaction, 1 angioedema, 1 lung fibrosis). One patient (2%) died due to progression of her disease.ConclusionsAvailable data about the use of adalimumab in autoinmune diseases come from case reports and uncontrolled studies, that include patients with severe disease and refractory to standard therapy. In this setting, it seems to be an effective and safe treatment option, especially in patients with uveitis and Behçet's disease. This initial data must be confirmed by controlled assays before extending adalimumab use.     

Substrate for the Myocardial Inflammation–Heart Failure Hypothesis Identified Using Novel USPIO Methodology

ObjectivesThe purpose of this study was to identify where ultrasmall superparamagnetic particles of iron oxide (USPIO) locate to in myocardium, develop a methodology that differentiates active macrophage uptake of USPIO from passive tissue distribution; and investigate myocardial inflammation in cardiovascular diseases.BackgroundMyocardial inflammation is hypothesized to be a key pathophysiological mechanism of heart failure (HF), but human evidence is limited, partly because evaluation is challenging. USPIO-magnetic resonance imaging (MRI) potentially allows specific identification of myocardial inflammation but it remains unclear what the USPIO-MRI signal represents.MethodsHistological validation was performed using a murine acute myocardial infarction (MI) model. A multiparametric, multi-time-point MRI methodology was developed, which was applied in patients with acute MI (n = 12), chronic ischemic cardiomyopathy (n = 7), myocarditis (n = 6), dilated cardiomyopathy (n = 5), and chronic sarcoidosis (n = 5).ResultsUSPIO were identified in myocardial macrophages and myocardial interstitium. R1 time-course reflected passive interstitial distribution whereas multi-time-point R2* was also sensitive to active macrophage uptake. R2*/R1 ratio provided a quantitative measurement of myocardial macrophage infiltration. R2* behavior and R2*/R1 ratio were higher in infarcted (p = 0.001) and remote (p = 0.033) myocardium in acute MI and in chronic ischemic cardiomyopathy (infarct: p = 0.008; remote p = 0.010), and were borderline higher in DCM (p = 0.096), in comparison to healthy controls, but were no different in myocarditis or sarcoidosis. An R2*/R1 threshold of 25 had a sensitivity and specificity of 90% and 83%, respectively, for detecting active USPIO uptake.ConclusionsUSPIO are phagocytized by cardiac macrophages but are also passively present in myocardial interstitium. A multiparametric multi-time-point MRI methodology specifically identifies active myocardial macrophage infiltration. Persistent active macrophage infiltration is present in infarcted and remote myocardium in chronic ischemic cardiomyopathy, providing a substrate for HF.     

The prognostic nutritional index might predict clinical outcomes in patients with idiopathic dilated cardiomyopathy

Background and aimsThe prognostic nutritional index (PNI) had been associated with adverse outcomes in numerous clinical conditions. However, its influence on idiopathic dilated cardiomyopathy (DCM) was not determined. This aim of this study was to determine the predictive ability of PNI in patients with idiopathic DCM.Methods and resultsA total of 1021 consecutive patients with idiopathic DCM were retrospectively included and divided into three groups based on admission PNI tertiles: <41.7 (n = 339), 41.7–47.3 (n = 342), >47.3 (n = 340). The association of PNI with in-hospital major adverse clinical events (MACEs) and death during follow-up was evaluated. In-hospital mortality (2.9% vs. 1.5% vs. 0.0%, respectively; p = 0.006) and MACEs (13.6% vs. 6.7% vs. 3.5%, respectively; p < 0.001) decreased from the lowest to the highest PNI tertile. The optimal cut-off value of PNI to predict in-hospital MACEs was 44.0 (area under the curve: 0.689; 95% confidence interval [CI]: 0.626–0.753; p < 0.001). Multivariate analysis showed that a PNI≤44.0 was an independent risk factor of in-hospital MACEs (odd ratio: 2.86; 95% CI: 1.64–4.98; p < 0.001) and all-cause mortality at a median follow-up of 27 months (hazard ratio: 1.67; 95% CI: 1.11–2.49; p = 0.013). In addition, patients with a PNI≤44.0 had a lower cumulative survival rate during follow-up (log-rank: 35.62; p < 0.001).ConclusionThe PNI was an independent risk factor for in-hospital MACEs and all-cause mortality at a median follow-up of 27 months in patients with idiopathic DCM; hence, it may be considered a tool for risk assessment.     

Soluble intercellular adhesion molecule-1 (ICAM-1), CD4, CD8 and interleukin-2 receptor in patients with Beh?et's disease and Vogt-Koyanagi-Harada's disease.

OBJECTIVES: In a search for serum markers of disease activity in uveitis, we measured the levels of the soluble form of ICAM-1 (sICAM-1), CD4 (sCD4), CD8 (sCD8) and interleukin-2 receptor (sIL-2R) in the serum of patients with Beh?et's disease (BD) and Vogt-Koyanagi-Harada's disease (VKH). METHODS: The study population consisted of 20 patients with active BD (treated with tacrolimus), 15 patients with inactive BD, 24 patients with VKH [20 of them successfully treated with systemic corticosteroids (cured group) and 4 of them with two or more episodes of uveitis after withdrawal of systemic steroid (recurrence group)], and 20 normal individuals. The levels of serum sICAM-1, sCD4, sCD8 and sIL-2R were measured by sandwich ELISA. RESULTS: Sera from patients with BD in the convalescent stage showed significantly higher levels of sICAM-1 than those in the acute stage. Patients with active BD in both stages or VKH in the acute stage had significantly higher levels of serum sCD4 and sIL-2R than the controls. The levels of sCD8 in patients with both diseases in both stages differed significantly compared to the controls. No difference was noted in the pattern of decline of these soluble markers after treatment in the cured and recurrence groups of VKH patients. A positive correlation was found between the serum levels of sCD4 and sIL-2R in patients with both diseases in the acute stage. CONCLUSIONS: The results suggest that these soluble markers may represent potentially useful parameters to monitor disease activity or chronic inflammation in certain types of autoimmune uveitis.     

Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels

ObjectivesIn this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD).MethodsFrom the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121–140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease.ResultsAmong 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51–9.54), 3.78 (95% CI:2.27–6.28), 2.78 (95% CI:1.55–4.97), and 1.03 (95% CI:1.02–1.05), respectively.ConclusionEven in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.     

Endoscopic sphincterotomy (ES) may not alter the natural history of idiopathic recurrent acute pancreatitis (IRAP)

BackgroundThe role of endoscopic sphincterotomy (ES) in idiopathic recurrent acute pancreatitis (IRAP) is unclear. We hypothesized that ES will alter the natural history of IRAP.MethodsWe retrospectively studied the course of 50 IRAP patients from the NAPS2 study from UPMC based on whether they underwent ES or were managed medically. Data included age at first AP, rate of attacks, and history of severe AP. Primary outcomes were any subsequent AP and rate of attacks; secondary outcome was chronic pancreatitis (CP) diagnosis during follow-up. Similar data was abstracted for alcoholic RAP.ResultsWhen compared with medically managed IRAP patients (n = 24, 48%), those who underwent ES (n = 26, 52%) had similar rate of attacks/year (median 1.54 vs. 1.41, p = 0.63), but significantly more attacks (median 3 vs. 2, p = 0.04) at baseline. During follow-up (median 7 years), rate of attacks/year decreased significantly, and were similar in both groups (median 0.16 vs. 0, p = ns). Predictors for rate of attacks during follow-up were sex (ratio 0.54 in females, p = 0.045) and rate of attacks at baseline (ratio for doubling 1.2, p = 0.025), but not ES. Alcoholic RAP patients had lower rate of attacks at baseline, but higher risk of subsequent AP (80 vs. 46%, p = 0.021) and rate of attacks/year (median 0.25 vs. 0, p = 0.016) during follow-up. Progression to CP occurred in IRAP and ES, medically managed IRAP, and alcoholic RAP in 27%, 8% and 27% respectively (p = ns).ConclusionsES, chosen in patients with higher burden of attacks, does not seem to impact the natural history of IRAP.     

Prevalencia e impacto clínico de las enfermedades reumatológicas autoinmunitarias sistémicas en pacientes con silicosis

BackgroundSilicosis is associated with an increased risk of developing systemic autoimmune rheumatic disease (SARD). The prognostic implications of this association are poorly characterized. The aim of this study was to determine the prevalence of SARD and autoimmune markers in a cohort of patients with exposure to silica and assess their impact on prognosis.MethodWe performed a prospective observational study of all patients attending the dedicated silicosis clinic of our pulmonology unit between 2009 and December 2017. Diagnosis was confirmed by a rheumatologist according to Spanish Rheumatology Society criteria. Autoimmune markers, pulmonary function tests, radiological progression, visits to the emergency department and primary care center, and hospital admissions for respiratory causes, and mortality were analyzed.ResultsOverall, 489 cases of silicosis and 95 cases of exposure were studied. In total, 54 (11.0%) patients with silicosis had SARD: 12 (2.4%) rheumatoid arthritis, 10 (2.0%) systemic lupus erythematosus, 10 (2.0%) systemic sclerosis, 3 (0.6%) Sjögren syndrome, 2 (0.4%) vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA +), 6 (1.2%) psoriatic arthritis, 3 (0.6%) ankylosing spondylitis, and 8 (1.6%) other autoimmune diseases with no special features. The patients with SARD visited the emergency room more often (63.0 vs. 42.5%; p = 0.004), and progressed more rapidly (22.2 vs. 11.7%; p = 0.030).ConclusionsThe presence of systemic rheumatic autoimmune diseases involves radiological progression and a higher clinical impact.     

Coronary Vessel Wall Contrast Enhancement Imaging as a Potential Direct Marker of Coronary Involvement: Integration of Findings From CAD and SLE Patients

ObjectivesThis study investigated the feasibility of visual and quantitative assessment of coronary vessel wall contrast enhancement (CE) for detection of symptomatic atherosclerotic coronary artery disease (CAD) and subclinical coronary vasculitis in autoimmune inflammatory disease (systemic lupus erythematosus [SLE]), as well as the association with aortic stiffness, an established marker of risk.BackgroundCoronary CE by cardiac magnetic resonance (CMR) is a novel noninvasive approach to visualize gadolinium contrast uptake within the coronary artery vessel wall.MethodsA total of 75 subjects (CAD: n = 25; SLE: n = 27; control: n = 23) underwent CMR imaging using a 3-T clinical scanner. Coronary arteries were visualized by a T2-prepared steady state free precession technique. Coronary wall CE was visualized using inversion-recovery T1 weighted gradient echo sequence 40 min after administration of 0.2 mmol/kg gadobutrol. Proximal coronary segments were visually examined for distribution of CE and quantified for contrast-to-noise ratio (CNR) and total CE area.ResultsCoronary CE was prevalent in patients (93%, n = 42) with a diffuse pattern for SLE and a patchy/regional distribution in CAD patients. Compared with control subjects, CNR values and total CE area in patients with CAD and SLE were significantly higher (mean CNR: 3.9 ± 2.5 vs. 6.9 ± 2.5 vs. 6.8 ± 2.0, respectively; p < 0.001; total CE area: median 0.8 [interquartile range (IQR): 0.6 to 1.2] vs. 3.2 [IQR: 2.6 to 4.0] vs. 3.3 [IQR: 1.9 to 4.5], respectively; p < 0.001). Both measures were positively associated with aortic stiffness (CNR: r = 0.61, p < 0.01; total CE area: 0.36, p = 0.03), hypercholesterolemia (r = 0.68, p < 0.001; r = 0.61, p < 0.001) and hypertension (r = 0.40, p < 0.01; r = 0.32, p < 0.05).ConclusionsWe demonstrate that quantification of coronary CE by CNR and total CE area is feasible for detection of subclinical and clinical uptake of gadolinium within the coronary vessel wall. Coronary vessel wall CE may become an instrumental novel direct marker of vessel wall injury and remodeling in subpopulations at risk.