Fernando Augusto Peres

Neurologic Involvement in Scleroderma en Coup de Sabre

Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. In scleroderma en coup de sabre (LScs) the atrophic lesion in frontoparietal area is the disease hallmark. Skin and subcutaneous are the mainly affected tissues, but case reports of muscle, cartilage, and bone involvement are frequent. These cases pose a difficult differential diagnosis with Parry-Romberg syndrome. Once considered an exclusive cutaneous disorder, the neurologic involvement present in LScs has been described in several case reports. Seizures are most frequently observed, but focal neurologic deficits, movement disorders, trigeminal neuralgia, and mimics of hemiplegic migraines have been reported. Computed tomography and magnetic resonance imaging have aided the characterization of central nervous system lesions, and cerebral angiograms have pointed to vasculitis as a part of disease pathogenesis. In this paper we describe the clinical and radiologic aspects of neurologic involvement in LScs.

Obesity and Cytokines in Childhood-Onset Systemic Lupus Erythematosus

Background. In systemic lupus erythematosus (SLE), atherosclerosis is attributed to traditional and lupus related risk factors, including metabolic syndrome (MetS), obesity, and inflammation. Objective. To evaluate the association between obesity, measures of body fat content, serum tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 and -10 levels in childhood-onset SLE (cSLE). Methods. We screened consecutive cSLE patients followed up in the Pediatric Rheumatology Outpatient Clinic of the State University of Campinas. cSLE patients were assessed for disease and damage. Obesity was definite as body mass index (BMI) ≥30 kg/m2. Serum TNF-α, IL-6, and IL-10 levels were measured by ELISA. Dual-energy X-ray absorptiometry was used to determine total fat mass, lean mass, and percent of body fat. Results. We included 52 cSLE patients and 52 controls. cSLE patients had higher serum TNF-α  (P = 0.004), IL-6 (P = 0.002), and IL-10 (P < 0.001) levels compared to controls. We observed higher serum TNF-α  (P = 0.036) levels in cSLE patients with obesity. An association between serum TNF-α levels and body fat percent (P = 0.046) and total fat mass on trunk region (P = 0.035) was observed. Conclusion. Serum TNF-α levels were associated with obesity and body fat content in cSLE. Our finding suggests that obesity may contribute to the increase of serum TNF-α levels in cSLE.

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus.

Cognitive Dysfunction and Antiphospholipid Antibodies

Antiphospholipid syndrome (APS) is a multisystem prothrombotic condition, however, in recent years, its inflammatory nature has been studied extensively. Cerebral involvement is commonly observed in APS and results in different clinical manifestations. However, most of the studies include secondary APS. In this article, we review the prevalence, clinical characteristics, and physiopathology of cognitive impairment in patients with primary APS.

Comparison of estimates of body fat content in childhood-onset systemic lupus erythematosus.

Objective We aimed to compare estimates of body fat content with respect to their ability to predict the percentage of body fat, confirmed by dual-energy X-ray absorptiometry scans in childhood-onset systemic lupus erythematosus. Methods We included 64 consecutive childhood-onset systemic lupus erythematosus patients and 64 healthy age and sex-matched controls in a cross-sectional study. Anthropometric data, body mass index and body adiposity index were calculated for all subjects. Childhood-onset systemic lupus erythematosus patients were further assessed for clinical and laboratory childhood-onset systemic lupus erythematosus manifestations and fat mass, lean mass and percentage of body fat evaluated by dual-energy X-ray absorptiometry. Results Elevated waist/hip ratio was observed in childhood-onset systemic lupus erythematosus patients when compared to controls (p < 0.001). We did not find differences between body mass index and body adiposity index classification in childhood-onset systemic lupus erythematosus patients and controls. Using dual-energy X-ray absorptiometry as gold standard we observed that all indirect estimates of body fat were correlated with whole body fat mass. We observed a correlation between height and cumulative corticosteroid dose adjusted by weight (r = 0.429, p = 0.005) in childhood-onset systemic lupus erythematosus. On whole body analysis we observed a correlation between lean mass and ACR Damage Index scores (r = −0.395; p = 0.019); percentage of body fat and adjusted Systemic Lupus Erythematosus Disease Activity Index (r = 0.402; p = 0.008), disease duration (r = −0.370; p = 0.012). On trunk analysis we observed a correlation between lean mass and ACR Damage Index (r = −0.319; p = 0.042); percentage of body fat with adjusted Systemic Lupus Erythematosus Disease Activity Index (r = 0.402; p = 0.005), disease duration (r = −0.408; p = 0.005). Conclusions This is the first study analyzing body adiposity index in childhood-onset systemic lupus erythematosus patients. We observed that all indirect estimates of body fat were correlated with whole body fat mass. This study shows that we should not replace body mass index by body adiposity index to evaluating fat levels in childhood-onset systemic lupus erythematosus. In consideration of the importance of overweight classification in cardiovascular diseases, any direct estimates of body fat can be used in an attempt to improve the prognosis of patients. Note We believe that we have presented evidence of body adiposity index accuracy in childhood-onset systemic lupus erythematosus patients but further research on the generalizability of body adiposity index to other patient groups needs to be done.

Biomarcadores no envolvimento do sistema nervoso central no Lupus eritematoso sistemico

Introdução O Lúpus é uma doença autoimune, inflamatória crônica sistêmica de origem desconhecida, caracterizada por atingir pele, rins e o sistema nervoso central (SNC). Estudos indicam que a doença está associada a fatores genéticos ambientais e hormonais, estudos afirmam que a cada 10 pacientes diagnosticados com o LES, 9 são mulheres assim afetando nos exames clínicos o que aumenta a necessidade de detecção de biomarcadores séricos que possam auxiliar no diagnóstico precoce e em uma rápida conduta terapêutica.

Low-Density Lipoprotein Cholesterol Is Associated With Asymptomatic Sensorineural Hearing Loss in Patients With Systemic Lupus Erythematosus.

ObjectiveThe aims of this study were to determine the frequency of asymptomatic sensorineural hearing loss (SNHL) in systemic lupus erythematosus (SLE) and to determine the association between SNHL and demographic, clinical, and laboratory features and cardiovascular risk factors. MethodsWe conducted a cross-sectional study including consecutive female SLE patients. We performed audiometry and clinical and laboratory evaluation and determined cardiovascular risk factors in all patients. Statistical analysis included principal component analysis and logistic regression. ResultsEighty-nine women were included with mean age of 38.98 (SD, 7.77) years and mean disease duration of 10.29 (SD, 9.19) years. Asymptomatic SNHL was observed in 14 patients (16%). In logistic regression model, only low-density lipoprotein levels (z = 2.64; P = 0.008) were associated with SNHL. ConclusionsWe observed asymptomatic SNHL in 16% of SLE and an association with low-density lipoprotein levels suggesting atherosclerosis as a mechanism. Follow-up is needed to determine clinical implications.

SAT0476 Cognitive Impairment and Mood Disorders are Associated with Hippocampal and Amigdala Volumes in Systemic Sclerosis

Objectives To determine hippocampal and amigdala abnormalities in systemic sclerosis (SSc) and to determine the possible relationship with clinical, laboratory and treatment features of the disease. Methods A total of 41 SSc patients and sixty-six health age and sex matched volunteers. A complete clinical, laboratory and neurological evaluation was performed in all subjects. Cognitive evaluation was performed in all participants using the Montreal Cognitive Assessment (MoCA). Mood disorders were determined through Becks Depression and Becks Anxiety Inventories. SSc patients were further assessed for disease activity (Valentini Activity Index), severity activity (Medsger Severity Index) and current drug exposure. MRI scans were performed in a 3T Phillips® scanner. Coronal T1 weighted were used for manual volumetric measurements. Results We included 27 (65.9%) limited SSc (lSSc) and 14 (34.1%) diffuse SSc (dSSc) with mean disease duration of 10.4 (SD 6.9) years. Active disease was identified in 12 (29.3%) SSc patients. Abnormal neurological examination was observed in 27 (65.8%) and cognitive impairment in 36 (87.8%) SSc patients. Mood disorders were identified in 25 (60.9%) SSc patients. In dSSc, hippocampal (mean volume =2.95 cm3;; SD=0.13) and amigdala (mean volume =1.81 cm3;; SD=0.09) were significantly smaller when compared to hippocampal (mean volume =3.19 cm3;; SD=0.08; p=0.03) and amigdala (mean volume =2.12 cm3;; SD=0.09 p=0.02) volumes of lSSc and to hippocampal (mean volume =3.26 cm3;; SD=0.09; p=0.03) and amigdala (mean volume =2.15 cm3;; SD=0.10; p=0.02) volumes of healthy volunteers. No difference between hippocampal (p=0.08) and amigdala (p=0.12) volumes of lSSC and healthy controls were observed. Depression correlated with left hippocampal volume in dSSc (r=-0.51, p=0.003). No correlation between depression and amigdala volumes was observed. Anxiety correlated with hippocampal volume in dSSc (r=-0.38; p=0.03) and with amigdala volume in both dSSc (r=-0.29, p=0.04) and lSSc (r=-0.28, p=0.04).MoCA scores correlated with hippocampal volume in dSSc (r=0.44; p=0.03) and lSSc (r=0.32; p=0.04) and with amigdala volume in dSSc (r=0.36; p=0.04) and lSSc (r=0.35; p=0.03). No correlation was found between disease activity and hippocampal volume (r=-0.06; p=0.16) or amigdala volume (r=-0.09; p=0.19). No association was found between organic impairment and hippocampal volume (r=-0.05; p=0.11) or amigdala volume (r=-0.04; p=0.12). Conclusions This is the first study to analyze hippocampal and amigdala volume in SSc. We observed significant reduced hippocampal and amigdala volumes in dSSc when compared to lSSc and healthy volunteers. Hippocampal and amigdala volumes correlated with cognitive impairment and mood disorders in SSc. Disclosure of Interest None declared

FRI0488 Prevalence and Clinical Significance of Cognitive Impairment in Systemic Sclerosis

Background There is an increased appreciation of the burden of cognitive impairment in people with autoimmune diseases. Autoantibodies, cytokines and cardiovascular disease (CVD) risk factors have been shown to contribute in different levels. Furthermore, recent studies have demonstrated diffuse white matter involvement and cerebral hypoperfusion in Systemic Sclerosis (SSc) patients. Objectives To evaluate the prevalence of cognitive impairment in SSc and to determine the role of disease related features and CVD risk factors in its occurrence. Methods Consecutive SSc patients [42 (68.85%) limited SSc (lSSc) and 19 (31.15%) with diffuse SSc (dSSc)] from the State University of Campinas were enrolled. Controls were age and sex matched and had the same educational level and sociodemographic background as SSc patients. Montreal Cognitive Assessment (MoCA) was used to assess cognitive dysfunction and scores ≤26 were considered abnormal. Mood disorders were determined through Becks Depression and Anxiety Inventory in all participants. CVD risk factors (hypertension, diabetes mellitus, insulin resistance, obesity, dyslipidemia) were screened in all individuals according to 2009 Joint Interim Statement on Metabolic Syndrome. SSc patients were further clinically and laboratory assessed to determine organ involvement, autoantibody profile (anti-topoisomerase I, anticentromere, and anti-RNA polymerase III), disease activity (Valentine Activity Index) and disease severity (Medsger Severity Index). Data were compared by non-parametric tests. Results A total of 61 SSc (55 female; mean age =50.9; SD ±11.6) and 40 health subjects (38 female; mean age=53.1; SD ±13.1) (p=0.7) were included in the study. Active disease was observed in 15 (24.59%) SSc patients. Cognitive impairment was identified in 53 (86.89%) SSc patients (38 lSSc and 15 dSSc) and in 5 (12.5%) health controls (p<0.001). Cognitive impaired SSc patients were significantly younger than controls (p=0.01). Cognitive impaired SSc patients were significantly older [mean age of 52.30 (SD=11.58); vs 41.95 (SD=9.17); p=0.016] and had higher insulin resistance evaluated by homeostatic model assessment (HOMA) (p=0.01) when compared to SSc without cognitive impairment. No association with other metabolic or disease related variables, diseases activity or severity was identified. Conclusions An increased prevalence of cognitive impairment was observed in SSc and associated with age and insulin resistance. Nonetheless, cognitive impairment seems to be an early age-related process in SSc when compared to healthy controls. Disclosure of Interest None declared

AB0616 Biomarkers for Neuropsychiatric Manifestations in Systemic Lupus Erythematosus

Background Neuropsychiatric manifestations areconsidered to be a serious complication in systemic lupus erythematosus (SLE).The pathogenesis of neuropsychiatric manifestations has been attributed to autoantibody-mediated neural dysfunction. Objectives To investigate the prevalence and associations of neuropsychiatric manifestations and serum biomarkers in SLE. Methods We included consecutive SLE followed at the rheumatology unit of the State University of Campinas. Neurological manifestations were analyzed according to the ACR classification criteria. Mood disorders were determined through Becks Depression and Anxiety Inventory in all participants. SLE patients were further assessed for clinical and laboratory SLE manifestations, disease activity [SLE Disease Activity Index (SLEDAI)], damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] and current drug exposures. Total dose of corticosteroids and other immunosuppressant medications used since the onset of disease were calculated by data obtained by careful review of the medical charts.Serum biomarkers (S100β, NF-H and antiribossomal P (Anti-P) and anticardiolipin antibodies levels were measured by enzyme-linked immunosorbent assay using commercial kits from BioVendor, Inc (Czech Republic). Anti-double stranded DNA (dsDNA) antibodies were determined by indirect immunofluorescence using Crithidia as substrate and considered positive if ≥1:20.Precipitating antibodies to extractable nuclear antigens (ENAs),including Ro (SSA), La (SSB), and Sm were detected by a standardizedELISA method, and considered positive if higher than 1:40. Data were compared by non-parametric tests. Results We included 146 SLE patients (138 women; mean age of 26.60±13.42 years; range 9-67). The mean disease duration was 8.13±7.05 years (range 0-39 years). At time of study entry, 50 (34.24%) SLE patients had active disease (mean SLEDAI scores3.68±3.97; range 0-14). Forty (27.39%) cSLE had cumulative damage (mean SDI scores 0.68±1.04; range0-4). We observed neuropsychiatric manifestations in 59 (40.41%) SLE. The most frequent manifestations observed in our cohort were anxiety (43.83%), headache (39.04%), depression (34.24%) and seizure (11.64%). We observed an association between neuropsychiatric manifestations and antiribosomal P protein (p=0.001), aCL (p=0.012) and LA (p<0.001). In the analyses of each individual manifestation, anxiety was associated with antiribosomal P protein (p=0.003) and anti-Smith (p=0.010), headache with antiribosomal P protein (p<0.001) and LA (p=0.006) and depression was associated with antiribosomal P protein (p=0.031). Conclusions Autoantibodies such as antiribosomal P protein antibodies, aCL and LA, anti-Ro, anti-dsDNA and anti-Smith are associated with neuropsychiatric manifestations in SLE, suggesting the autoantibodies pathway in neural dysfunction in SLE. Acknowledgements Grants: Research Support Foundation of São Paulo –FAPESP (Simone 2008/02917-0, Mariana 2011/03788-2, Aline 2013/09480-5) CNPQ (300447/2009-4 and 471343/2011-0; 302205/2012-8; 473328/2013-5) Disclosure of Interest None declared