OP0086 GENDER INFLUENCE ON CLINICAL MANIFESTATIONS, DEPRESSIVE SYMPTOMS AND BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) SERUM LEVELS IN PATIENTS AFFECTED BY FIBROMYALGIA

Background:Fibromyalgia (FM) is a common rheumatic disease characterized by chronic widespread pain, sleep and mood disorders. A higher prevalence of FM in women compared with men is well known, although the specific differences in clinical manifestations related to gender are still poorly defined. Brain-Derived Neurotrophic Factor (BDNF) is an endogenous growth factor that gained attention for its potential as biomarker of several diseases, including FM and depression.Objectives:The aims of this study were to investigate gender-related difference among males and females affected by FM in clinical manifestations, depressive features and BDNF serum level, evaluating also the diagnostic potential of the latter.Methods:We consecutively enrolled adult patients affected by FM (ACR 2016) referring to our out-patient clinic. Each subject underwent clinical and answered to questionnaires for the severity of FM symptoms (Revised Fibromyalgia Impact Questionnaire, R-FIQ) and depressive symptoms (Beck Depression Inventory-II, BDI-II). We collected blood samples from a subgroup of patients of both sexes, matched for age, for BDNF serum level dosage through ELISA. BDNF levels were assessed also in a control group, matched for sex and age.Results:The cohort was composed by 201 FM patients (172 F, 29 M), mean age 49.13. Females showed higher values of R-FIQ total score (p=0,0005) as well the specific items of the R-FIQ for pain (p=0,013), fatigue (p=0,014), memory problems (p=0,007), tenderness to touch (p<0,0001), balance problems (p<0,0001) and sensitivity to environmental stimuli (p=0,012) when compared with males (fig. 1). There was no difference in BDI-II between males and females, but notably male patients reported a significantly higher frequency of coexisting depressive disorder (p=0,038) (fig. 2). Serum BDNF levels were evaluated in 40 FM patients and 40 healthy controls (HC) (F:M 1:1). BDNF levels were significantly lower in FM patients compared with HC (p<0,0001). Among FM patients, BDNF levels were lower in males compared with females (p<0,0001) (fig.3). BDNF did not correlate with any clinical and clinimetric parameter. BDNF showed a good diagnostic performance (AUC=0,89, CI95%=0,82-0,9630, p<0,0001) (fig. 4). At a cut-off value <6,47 ng/dl, BDNF showed a specificity of 75% and a sensibility of 92,31%,(CI 95%=79,68-97.35) for FM identification (LR=3,692).Conclusion:FM clinical manifestations are strongly dependant from gender. While females present a more severe disease and a higher burden of symptoms, mood disorders tend to be a major characteristic of males with FM. Reduced BDNF serum levels have been reported as typical of depressive disorders. Our findings of lower BDNF levels in male FM patients compared to females support this hypothesis. BDNF have potential as biomarker of the disease and should be validated in larger cohorts.References:[1]Sarzi-Puttini et al. Nature Reviews 2020[2]Colucci-D'Amato et al. Int J Molecular Sciences 2020[3]Nugraha et al. Rheumatol Int 2012[4]Schmitt et al. Ann Med 2016[5]Melchior et al. Neuroscience 2016[6]Stefani et al. Neuroscience Letters 2012Disclosure of Interests:None declare

Dietary habits and nutrition in rheumatoid arthritis: can diet influence disease development and clinical manifestations?

Rheumatoid arthritis (RA) is a systemic, autoimmune disease characterized by joint involvement, with progressive cartilage and bone destruction. Genetic and environmental factors determine RA susceptibility. In recent years, an increasing number of studies suggested that diet has a central role in disease risk and progression. Several nutrients, such as polyunsaturated fatty acids, present anti-inflammatory and antioxidant properties, featuring a protective role for RA development, while others such as red meat and salt have a harmful effect. Gut microbiota alteration and body composition modifications are indirect mechanisms of how diet influences RA onset and progression. Possible protective effects of some dietary patterns and supplements, such as the Mediterranean Diet (MD), vitamin D and probiotics, could be a possible future adjunctive therapy to standard RA treatment. Therefore, a healthy lifestyle and nutrition have to be encouraged in patients with RA

POS1464-HPR ASSESSMENT OF EMOTIONAL WELL-BEING IN RHEUMATIC PATIENTS DURING COVID-19 LOCKDOWN THROUGH A WEB-BASED SURVEY APPROACH

Background:The severe measures of lockdown imposed in Italy to limit the SARS coronavirus 2 disease (COVID-19) spread caused an increase of reported anxiety, depression and suicidal rate among general population. Patients affected by rheumatic disorders feature an increased risk of mood disorders for the chronic course of the disease itself and for the related disability.Objectives:Aim of this study was to investigate the impact of COVID-19 lockdown on emotional well-being of a large cohort of rheumatic patients through a telemedicine approach.Methods:Patients in follow-up in rheumatologic out-patient clinics of our hospital were invited to participate to an online survey. They were asked also to invite their best friend, matched for age and sex, to participate the survey, as control group. The online survey included demographic questions and validated, psychometric scales for stress vulnerability (Stress Vulnerability Scale-SVS), resilience (Resilience Scale-RS), depression (Zung's depression questionnaire-Zung-D) and anxiety (Zung's anxiety questionnaire-Zung-A) evaluation.Results:The cohort was composed by 484 subjects (84,1% F, 15,9% M). The number of subjects and the frequency of various diagnosis are shown in Table 1. According to the psychometric scales, 55,5% and 43,3% of subject showed respectively an increased stress vulnerability and a reduced resiliency. Moreover, 64% and 40,5% of the enrolled subjects reported respectively anxiety and depressive symptoms worthy of psychiatric attention. There was a significant different distribution of scores for SVS (p<0,0001), Zung-A (p<0,0001) and Zung-D (p<0,0001) among the various diagnosis. In comparison with controls, higher scores of SVS were present in connective tissue diseases (CTD) (p=0,007), Sjogren's Syndrome (SSJ) (p=0,0029) and fibromyalgia (FM) (p<0,0001) patients, higher scores of Zung-A were present in SSJ (p=0,006) and FM (p<0,0001) patients and higher scores of Zung-D were present in FM (p<0,0001) patients (Figure 1). Ordinal regression analysis showed that higher classes of anxiety were independently predicted by the Tension (β=0,32;CI=0,13-0,52;p=0,003) and Demoralization (β=0,22;CI=0,04-0,44;p=0,046) components of SVS and by the Zung-D score (β=0,09;CI=0,05-0,1;p<0,001), while higher classes of depression were independently predicted by SVS total (β=0,17;CI=0,03-0,30;p=0,012), by its subcomponent Demoralization (β=0,22;CI=0,01-0,43;p=0,038), by a lower absolute RS score (β=-0,083;CI=-0,1--0,06;p<0,001) and by the Zung-A score (β=0,11;CI=0,06-0,15;p<0,001). In both cases, a specific diagnosis was not associated to a higher risk of advanced anxiety and depression classes.Conclusion:Rheumatic patients developed a high frequency of anxiety and depressive symptoms following COVID-19 lockdown, of which a large part should be referred for specialist attention according to their severity. There was a large variability of the symptoms reported among the various diagnosis. CTD, SSJ and FM patients were the most susceptible to the development of anxiety, depression and stress vulnerability. The application of psycometric scales through a telemedicine approach represents a useful tool to identify patients with higher levels of anxiety and depression.Table 1.DIAGNOSISFrequencyPercentControls459,3RA8216,9PSA214,3UA40,8SPA71,4CTD7014,5FM7916,3Myositis81,7Behcet's112,3Vasculitis163,3APS61,2Other AID132,7SSJ12225,2Total484100RA: Rheumatoid Arthritis, PSA: Psoriatic Arthritis; UA: Undifferentiated Arthritis; SPA: Spondyloarthritis; CTD: Connective tissues diseases (including Systemic Lupus Erythematosus, Scleroderma, Undifferentiated Connettivitis, Mixed Connettivitis); FM: Fibromyalgia; APS: Anti-phospholipid syndrome; Other AID: Other autoimmune/inflammatory disorders (including Adult-onset Still disease, IgG4 related disease); SSJ: Sjogren SyndromeFigure 1.Disclosure of Interests:None declare

FRI0376 EFFECT OF CARBAMYLATED LOW-DENSITY LIPOPROTEINS ON BONE CELLS HOMEOSTASIS

Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 μg/ml, 100 μg/ml and 200 μg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 μg/ml p=0,0015) and nLDL treated cells (200 μg/ml p= 0,011; 20 μg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 μg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (p<0.05) (Fig 3). nLDL did not affect the ALP expression. Treatment with cLDL stimulated RANKL mRNA expression in osteoblasts increasing the RANKL/OPG ratio (Fig 4).Fig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lill

One year in review. 2019: fibromyalgia

Fibromyalgia is characterised by chronic pain, fatigue and functional symptoms. Its aetiopathogenesis is still a matter of debate, but various pharmacological and non-pharmacological therapies are currently available for its treatment. We review the literature concerning the most recent findings related to the aetiopathogenesis, diagnosis, clinical aspects and treatment of FM published between January 2018 and January 2019

Small-fibre pathology has no impact on somatosensory system function in patients with fibromyalgia

We aimed to investigate whether small-fibre pathology, a common skin biopsy finding in patients with fibromyalgia, implies clinically important abnormalities of somatosensory system function and verify whether it is associated with voltage-gated sodium channel variants. In 57 consecutively enrolled patients with fibromyalgia, we used skin biopsy to distinguish patients with and without small-fibre pathology. In all patients, we assessed somatosensory system function using quantitative sensory testing (QST) and laser-evoked potentials and investigated voltage-gated sodium channel genotyping. We then compared these variables in patients with and without small-fibre pathology. We found that clinical measures, QST, and laser-evoked potential variables did not differ between patients with and without small-fibre pathology. In most patients with small-fibre pathology, QST and laser-evoked potential variables fell within normative ranges commonly used in clinical practice. Of the 57 patients, one patient without small-fibre pathology and 2 patients with small-fibre pathology had rare variants of voltage-gated sodium channels, namely SCN11A, SCN9A, and SCN1A variants. The SCN9A variant, found in a patient with small-fibre pathology, was an already profiled gain-of-function mutation, previously reported in small-fibre neuropathy. Our findings suggest that small-fibre pathology has a negligible impact on somatosensory system function in fibromyalgia. The genetic analysis suggests that patients with rare small-fibre neuropathy due to voltage-gated sodium channel variants may be misdiagnosed as patients with fibromyalgia

THU0549 Fatigue and The Role of Sleep in fibromyalgia: Objective and Subjective Measures

Background: Fibromyalgia (FM) is a chronic widespread pain syndrome asso- ciated with symptoms such as sleep disorders, fatigue, depression, anxiety and cognitive alterations with a severe impairment of the life quality. Objectives: The aim of this study is to examine the relationship between subjective and objective assessment of sleep quality and to analyze the predictors of fatigue in an Italian cohort of FM patients. Methods: Adult outpatients diagnosed with FM, fulfilling both ACR/EULAR 1990 and 2010 criteria were enrolled (1,2). The objective measure of sleep was assessed through an actigraph (AMI MotionloggerWatch), a device which records the parameters of sleep based on electronic measure of the continuous motion detected by an accelerometer. During the study period the patients were invited to wear the actigraph on the non-dominant wrist for one week and concurrently to complete a sleep diary. After seven days the patients returned the actigraph and answered a structured interview conducted by a trained junior psychologist. Sub- jective quality of sleep was assessed by the Sleep Disorder Questionnaire (SDQ) (3) and the patients filled out psychometric scales as the Brief Symptom Inventory (BSI) for anxiety and depression (4) and the Checklist of Individual Strength (CIS20) for perceived fatigue (5). Both pharmacological and not pharmacological treatments were not changed 1 month before and during the study.Results: Twenty-one female patients completed the study, mean age of 46.9 years (range 32–68) and mean disease duration of 7.5 years (range 1–27). The majority of 21 FM patients interviewed (76.2%) described their sleep quality as poor or very poor (mean value 3.10 ±0.89 SD on 4 point Likert scale). All patients (100%) reported insomnia complaints, and 18 (81%) met the DSM V (Diagnostic and Statistical Manual of Mental Disorders) criteria for a diagnosis of Difficulties Initiating and Maintaining Sleep (DIMS). The patients’ perception about the number of slept hours (M=5.7) was significantly lower (t=3.292, p<0.005) than the actigraphic data (M=6.8). Total Sleep Time (TST) measured through actigraphy was directly correlated with the intensity of perceived fatigue (r=.481; p<0.05). A multiple regression analysis considering TST, Total Time in Bed (TTB), depression, and type of fatigue self management, showed TST as the variable that gave a major and unique contribute to the prediction of perceived fatigue. Mean values of TST and TTB both negatively correlated with FM duration (respectively r=-.589, p<0.005; r=-.565, p<0.008). Conclusions: These findings confirm the high prevalence of sleep disturbances in FM and suggest that sleep quality and duration could play an important role in the perceived fatigue severity. Intervention programs for FM should include sleep regulation

THU0082 Lung involvement in acpa positive subjects: a pilot study on the role of laboratory, functional and imaging markers

ackground The ACPA-positive Rheumatoid Arthritis (RA) is a complex disease. Signs of immune activity against citrullinated proteins may be present years before the onset of clinical manifestations. Recent findings suggest that the lung may represent an early site of autoimmune-related injury in ACPA-positive patients without signs of arthritis. Objectives The purpose of the present study was to evaluate the presence of subclinical pulmonary abnormalities in ACPA-positive subjects without arthritis and in RA-patients through laboratory, functional and imaging markers. Methods Eleven ACPA-positive subjects without arthritis, 10 patients naïve to therapy with early ACPA-positive RA (<6 months duration) and 9 with established ACPA-positive RA (<36 months duration) were consecutively enrolled. Subjects underwent baseline pulmonary function tests (PFTs), DLCO measurement and CPET. The evaluation of Surfactant protein D (SP-D) serum levels was performed in all the patients and in 9 healthy controls matched for age and sex with an ELISA test. Twenty-four subjects underwent chest high-resolution computer tomography (HRCT), in order to evaluate parenchymal or airways abnormalities. Results The cohort consisted of 7 men and 23 women, mean age 48,93 (DS+/-12.1). PFTs resulted abnormal only in 2 patients. A DLCO reduction was observed in 54.5% of ACPA-positive subjects without RA, in 60% and in 55.6% of patients with early and established RA, respectively. In RA patients, an inverse correlation between disease duration and DLCO/Va (r=-0.50; p=0.03) was observed. The exercise tolerance at CPET was reduced in 54.5% of ACPA-positive subjects without RA, in 20% of patients with early RA and in 55.6% of those with established RA. Serum SP-D levels were higher in established RA (p=0.079), in ACPA-positive subjects and early RA than in healthy controls. ACPA levels positively correlated (r=0.45;p=0.01) with CPET parameters of ventilation inefficiency, suggesting a ventilation/perfusion mismatch. A negative correlation between ACPA and SP-D levels and CPET metabolic parameters was also observed. The presence of pulmonary nodules was the most common alteration founded at HRCT, equal to 28% in ACPA-positive subjects without arthritis, in 66% and 87% of patients with early and established RA, respectively. In the last group, all patients showed parenchymal abnormalities. There was also a significant (p=0.022) higher frequency of lung abnormalities in patients with established disease compared with the other two groups. Conclusions The early lung involvement in RA is often subclinical and baseline PFT's are scarcely informative. Although preliminary, these findings suggest that DLCO, CPET parameters and SP-D can represent early markers of the subclinical lung injury. Furthermore, lung abnormalities detectable at HRCT seem to develop early in the course of the disease. However, additional studies are needed to clarify lung abnormalities in RA

THU0082 Lung involvement in acpa positive subjects: a pilot study on the role of laboratory, functional and imaging markers

ackground The ACPA-positive Rheumatoid Arthritis (RA) is a complex disease. Signs of immune activity against citrullinated proteins may be present years before the onset of clinical manifestations. Recent findings suggest that the lung may represent an early site of autoimmune-related injury in ACPA-positive patients without signs of arthritis. Objectives The purpose of the present study was to evaluate the presence of subclinical pulmonary abnormalities in ACPA-positive subjects without arthritis and in RA-patients through laboratory, functional and imaging markers. Methods Eleven ACPA-positive subjects without arthritis, 10 patients naïve to therapy with early ACPA-positive RA (<6 months duration) and 9 with established ACPA-positive RA (<36 months duration) were consecutively enrolled. Subjects underwent baseline pulmonary function tests (PFTs), DLCO measurement and CPET. The evaluation of Surfactant protein D (SP-D) serum levels was performed in all the patients and in 9 healthy controls matched for age and sex with an ELISA test. Twenty-four subjects underwent chest high-resolution computer tomography (HRCT), in order to evaluate parenchymal or airways abnormalities. Results The cohort consisted of 7 men and 23 women, mean age 48,93 (DS+/-12.1). PFTs resulted abnormal only in 2 patients. A DLCO reduction was observed in 54.5% of ACPA-positive subjects without RA, in 60% and in 55.6% of patients with early and established RA, respectively. In RA patients, an inverse correlation between disease duration and DLCO/Va (r=-0.50; p=0.03) was observed. The exercise tolerance at CPET was reduced in 54.5% of ACPA-positive subjects without RA, in 20% of patients with early RA and in 55.6% of those with established RA. Serum SP-D levels were higher in established RA (p=0.079), in ACPA-positive subjects and early RA than in healthy controls. ACPA levels positively correlated (r=0.45;p=0.01) with CPET parameters of ventilation inefficiency, suggesting a ventilation/perfusion mismatch. A negative correlation between ACPA and SP-D levels and CPET metabolic parameters was also observed. The presence of pulmonary nodules was the most common alteration founded at HRCT, equal to 28% in ACPA-positive subjects without arthritis, in 66% and 87% of patients with early and established RA, respectively. In the last group, all patients showed parenchymal abnormalities. There was also a significant (p=0.022) higher frequency of lung abnormalities in patients with established disease compared with the other two groups. Conclusions The early lung involvement in RA is often subclinical and baseline PFT's are scarcely informative. Although preliminary, these findings suggest that DLCO, CPET parameters and SP-D can represent early markers of the subclinical lung injury. Furthermore, lung abnormalities detectable at HRCT seem to develop early in the course of the disease. However, additional studies are needed to clarify lung abnormalities in RA