T.A. Gheita

Subclinical reduced G6PD activity in rheumatoid arthritis and Sjögren's Syndrome patients: Relation to clinical characteristics, disease activity and metabolic syndrome

Abstract Objective. Glucose-6-phosphate dehydrogenase (G6PD) is an important site of metabolic control in the pentose phosphate pathway. The purpose of this study was to investigate the enzyme activity of G6PD in Rheumatoid Arthritis (RA) and Sjögrens Syndrome (SS) patients not known to be deficient in this enzyme. It was also within the scope of the aim to find the relation of G6PD to the presence of metabolic syndrome (MetS) in these patients. Methods. Erythrocyte G6PD activity was evaluated in 40 RA patients, 30 SS patients and in 30 age- and sex-matched control. The clinical characteristics, disease activity score (DAS28), SS disease activity (SSDAI) and damage (SSDDI) indices and presence of MetS of the included patients were analyzed in relation to the enzyme level. Results. The G6PD activity in RA patients (7.72 ± 3.57 U/g Hb) was significantly reduced compared to that in the SS patients (11.55 ± 3.14 U/g Hb) and control (13.23 ± 3.34 U/g Hb) especially those with MetS (4.61 ± 1.84 U/g Hb) (p < 0.001). There was a significant negative correlation of the G6PD activity with the disease duration and DAS28 (p < 0.001). Conclusion. The results of this study, suggest that G6PD not only does not protect against MetS in RA, but may even be considered a risk factor for the development of this disorder. The identification of regulatory tools for G6PD activity may prove promising for treating the associated metabolic disorders and chronic inflammation in RA.

The Effectiveness of Intraocular Methotrexate in the Treatment of Posterior Uveitis in Behçet’s Disease Patients Compared to Retrobulbar Steroids Injection

Aim of Work. To evaluate the efficacy of intravitreal methotrexate (MTX) compared to retrobulbar triamcinolone acetonide (TAA), in controlling posterior segment involvement and inducing remissions among Behçets disease (BD) patients. Study Design. This is a cross-sectional nonrandomized comparative study. Patients and Methods. 31 adult BD male patients with a mean disease duration of 5.45 years who presented with bilateral posterior segment involvement were included. Each patient received intravitreal injection of 400u2009μg/0.1u2009mL (MTX) for the right eye (Group A) and 1u2009mL of retrobulbar 40u2009mg/mL TAA for the left eye (Group B). Results. 90% of eyes showed complete improvement of anterior chamber reaction, whereas an improvement in vitreous activity in 77% with no significant differences between both groups (p ≤ 0.1). BCVA improved in 77.4% eyes (Group A) compared to 87.1% (Group B) (p ≤ 0.4). Relapses were noted in 11 eyes (35.5%), in group A, with the mean duration of remission being 19.1 weeks ± 2.13 compared to 7.35 ± 2.8 in 20 eyes (64.5%) in group B (p ≤ 0.1). Conclusion. No statistical differences were found between both treatment modalities; however, based on clinical observations, intravitreal MTX may ensure better control of inflammatory reaction and may encourage longer remission as compared to retrobulbar TAA in BD patients.

Vascular endothelial growth factor G1612A (rs10434) gene polymorphism and neuropsychiatric manifestations in systemic lupus erythematosus patients

AIMnTo investigate the relation between vascular endothelial growth factor (VEGF) gene polymorphism in systemic lupus erythematosus (SLE) patients and lupus related neuropsychiatric manifestations.nnnPATIENTS AND METHODSnSixty adult SLE patients recruited from the Rheumatology and Neurology departments of Cairo University hospitals were classified into two groups; Group A: 30 patients with neuropsychiatric manifestations (NPSLE) and Group B: 30 patients without. For both groups the SNP G1612A (rs10434) of the VEGF gene was genotyped by real time polymerase chain reaction (RT-PCR).nnnRESULTSnStatistically significant difference was found in genotype and allele frequencies between both groups (AA [70% vs 13.3%, p<0.001] and GG [10% vs 66.7%, p<0.001]).nnnCONCLUSIONnPolymorphism in the gene coding for VEGF may be associated with increased incidence of neuropsychiatric lupus in SLE patients.

AB0706 Ocular presentation in granulomatosis with polyangiitis (GPA) patients: relation to autoantibodies and disease activity

Objectives To study the disease characteristics, autoantibodies and activity in granulomatosis with polyangiitis (GPA) patients with ocular manifestations. Methods 46u2009GPA patients visiting the ophthalmology clinic were included. Ocular manifestations, clinical and slit lamp examination were performed. The Birmingham Vasculitis Activity Score (BVAS) was recorded. Laboratory investigations were recorded and the antineutrophil cytoplasmic antibody (ANCA) performed. Results The median age of the patients was 44.5 (32–63) years, 22 males:24 females and disease duration 6.5 (1–16) years. Ocular manifestations were present in all patients; 12 (26.1%) had proptosis, 40 (87%) scleritis/episcleritis with perforation in 3 (6.5%), keratoconjunctivitis in 33 (71.7%) – acute infiltrative stromal keratitis in 11, peripheral ulcerative keratitis in 15 and sclerosing keratitis in 11 patients. Uveitis was present in 11 (23.9%) and retinal changes included vasculitis, exudates and haemorrhage was present in 7 (15.2%). 43 (93.5% of the patients had blurring of vision and vision loss was present in 2 (4.3%). Glaucoma was present in 4 (8.7%) and hypotony in 2 (4.3%). Involvement was bilateral in 32 (69.6%) patients. Rheumatoid factor was positive in 56.5% and significantly associated with uveitis (p=0.04) while ANA was positive in 45.7% and significantly associated with keratoconjuctivitis (p=0.04). BVAS tended to be higher in those with uveitis (p=0.05). Conclusions Ocular involvement must be considered in all GPA patients and referral to an experienced ophthalmologist is mandatory for proper management and improved outcome of such a rare systemic disease. ANA and RF positivity may raise suspicion for KC or uveitis respectively. There was a remarkable association between uveitis and disease activity. Disclosure of Interest None declared

THU0352 Worldwide Heterogeneous Diagnostic Approach To Primary Sjögren Syndrome in 8315 Patients (EULAR-SS Task Force Big Data Sjögren Project)

Objectives To analyse the diagnostic approach used in the largest international cohort of patients with primary Sjögren syndrome (pSS) Methods The Big Data Sjögren Project is a multicentre registry formed in 2014 by experts participating in the EULAR-SS Task Force. By January 2016, the database included 8315 consecutive patients fulfilling the 2002 criteria. The main features at diagnosis/recruitment (time of criteria fulfilment) were collected and analysed Results The cohort included 7753 (93%) women (mean age at diagnosis 53 years). Sicca symptoms were reported in more than 90% of patients at diagnosis (92% for dry eye and 92.5% for dry mouth). The diagnostic tests used included the determination of anti-Ro/La antibodies in 8250 (99%) patients, Schirmer test in 6205 (75%), salivary gland biopsy in 5988 (72%), salivary flows in 4941 (59%), corneal stainings in 3304 (40%), scintigraphy in 2578 (31%) and sialography in 873 (10%) patients. The mean number of diagnostic tests included in the 2002 AE criteria was 4.85 ± 1.44 (of a maximum of 8 different tests), and was higher in patients with negative ANA (5.18 vs 4.80 in ANA+, p<0.001) or negative RF (5.06 vs 4.81 in RF+, p<0.001), and was also higher in American patients vs European or Asian patients (5.28 vs 4.83 and 4.63, respectively). A correlation was found between the number of tests carried out and the number of 2002 criteria finally fulfilled (R=0.48) Conclusions We found a heterogeneous diagnostic approach of pSS with respect to the number of 2002AE diagnostic tests carried out; the approach varied significantly according to geographic origin and baseline immunological profile Disclosure of Interest None declared

AB0644 Subclinical Hearing Loss in Systemic Sclerosis Patients: Relation To Disease Severity

Background Systemic sclerosis (SSc) is one of the most complex systemic autoimmune diseases1. Ear involvement is not uncommon and should be taken into consideration during diagnostic and therapeutic procedures of SSc2 Objectives The aim of the present study was to assess hearing in asymptomatic SSc patients and correlate the findings with clinical characteristics and disease severity. Methods The study included 35 female SSc patients and 35 matched controls. Skin thickness was assessed using modified Rodnan skin score (mRSS) and disease activity by Medsger severity score (MSS). Audiological tests including pure tone audiometry, speech audiometry, impedance audiometry and auditory brainstem response (ABR) were performed Results The mean age of patients was 40.3±6.2 years, and disease duration 7.3±4.6 years. Mild bilateral symmetrical sensorineural hearing loss (SNHL) was present in 27/35 (77.1%) mostly at high frequencies. Hearing thresholds, pure tone average and speech reception threshold were significantly higher (p=0.001) in SSc patients than in control. In those with hearing loss, word discrimination score (WDS) was lower and ABR-I delayed compared to those without (p=0.001,p<0.0001 respectively) with consequently shorter inter-peak interval (IPI) I-III (p=0.01) and IPI I-V (p=0.004). In patients with hearing loss there was an increased frequency of acro-osteolysis (51.9%), telangiectasia (59.3%), arthralgia (70.4%) and peripheral neuritis (44.4%) compared to those with normal hearing. The MSS and mRSS significantly correlated with the high frequency hearing threshold and negatively with WDS. Audiometric parameters were comparable between patients with diffuse (n=14) and limited (n=21) cutaneous SSc. Conclusions Audiometric tests may detect subclinical SNHL mostly cochlear in SSc patients. The significant association between SNHL with telangiectasia and neuritis raises the likelihood that the SNHL may be due to an underlying vasculopathy or neuritis. References Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of Systemic Sclerosis. Front Immunol. 2015;6:272. Maciaszczyk K, Waszczykowska E, Pajor A, Bartkowiak-Dziankowska B, Durko T. Hearing organ disorders in patients with systemic sclerosis. Rheumatol Int. 2011;31(11):1423–8. Disclosure of Interest None declared

SAT0019 Tumor Necrosis Factor-α -308 A/G Gene Polymorphism in Children with Juvenile Idiopathic Arthritis: Relation To Disease Activity, Damage and Disability

Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and an important cause of disability1. Its cause remains unknown, but likely includes complex interactions between genes and environmental exposures resulting in dysregulation of the immune system2. TNF-α is a cytokine with an important role in inflammation and immune function3. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only very small minority have proven functional consequences and were associated with JIA susceptibility4 Objectives To evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNFα) and -308 A/G promoter polymorphism in JIA patients and find any association to the subsets, clinical and laboratory features, disease activity and damage as well as functional disability Methods Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) assessed and Childhood Health Assessment Questionnaire (CHAQ) to measure the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism determined by polymerase chain reaction. Results The 48 JIA children (mean age: 11.5±2.8 years) were 13 systemic, 17 oligoarticular and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4±6.3 ng/ml) compared to control (3.5±2.6 ng/ml) (p<0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r=0.32, p=0.03) and CHAQ (r=0.37, p=0.01) and negatively with the presence of GG alleles (r=-0.48, p=0.001). The GG alleles were significantly negatively associated with C-reactive protein (r=-0.32, p=0.03) with a tendency to negatively correlate with JADAS-27, CHAQ and JADI-extrarticular (r=-0.28, p=0.06; r=-0.25, p=0.09 and r=-0.25, p=0.09 respectively). Conclusions There is evidence of a possible influence of the −308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment. References Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369(9563):767–78. Moncrieffe H, Prahalad S, Thompson SD. Genetics of juvenile idiopathic arthritis: new tools bring new approaches. Curr Opin Rheumatol. 2014;26(5):579–84. van den Ham HJ, de Jager W, Bijlsma JW, Prakken BJ, de Boer RJ. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis. Rheumatology. 2009;48:899–905 Scardapane A, Breda L, Lucantoni M, Chiarelli F. TNF-α polymorphisms in juvenile idiopathic arthritis: which potential clinical implications? Int J Rheumatol. 2012;2012:756291. Disclosure of Interest None declared

AB0394 The Body Mass Index Predicts the Serum and Synovial Cartilage Oligomeric Matrix Protein Level in Early and Established Rheumatoid Arthritis Patients

Background Cartilage oligomeric matrix protein (COMP) is a major non-collagenous component of cartilage that accounts for approximately 1% of the wet weight of articular tissue. Objectives To assess the COMP levels in serum and synovial fluid in early and established rheumatoid arthritis (RA) patients and correlate the levels with clinical, laboratory and radiological characteristics. Methods Twenty-four female RA patients were included. Full history taking, thorough clinical examination and laboratory investigations were performed and the body mass index (BMI) recorded. Radiological damage was assessed according to the modified Larsen score. Disease activity score-28 (DAS-28) was calculated. Thirty age and sex matched subjects constituted the control. The serum COMP level was determined by ELISA. Results The patients age was 44.04±10.5 years. Twelve had early RA and another 12 had established disease with joint destruction; 5 of each group had knee effusion. The serum COMP was significantly higher in the patients (19.54±5.47μg/ml) compared with the control (5.93±1.95μg/ml) (p<0.001). It was significantly higher in the patients with established disease (23.9±3.1μg/ml) compared to early ones (15.1±3.2μg/ml) (p<0.001). Synovial COMPA was also significantly increased in established cases compared to early (31.2±9.8μg/ml vs 51.6±10.4μg/ml, p=0.013). The serum and synovial COMP significantly correlated with the age, disease duration, BMI, DAS28 and modified Larsen score. On performing the regression analysis in the RA patients, only the BMI could predict the serum level of COMP (p=0.02). Conclusions In conclusion, COMP is a promising biomarker of disease activity in RA making it a potential therapeutic target. The obvious correlation with the body mass index throws light on the importance of weight control not only in OA but in RA. Disclosure of Interest None declared

AB0362 B-Cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) in Postmenopausal Rheumatoid Arthritis Patients with Low Bone Mass: A Possible Protective Role of Hydroxychloroquine

Background The increasing role of B-cells in the pathogenesis and management of RA, the common occurrence of postmenopausal osteoporosis with RA and the suggested responsibility of BAFF in autoantibodies production with affection of bone density were main motives to research in this area Objectives The aim of the present work was to study the serum concentration of BAFF in relation to postmenopausal low bone mass (LBM) associated with RA compared to those without RA and to study its relation to the bone turnover markers and bone mineral density. Comparing the results with an RA group with normal BMD was considered with the healthy control subjects. Relation of the findings to intake of hydroxychloroquine (HCQ) was considered. Methods The study included 68 postmenopausal LBM patients 34 with RA and another 34 without. Thirty age-matched postmenopausal healthy subjects were included as control. The laboratory investigations performed for the patients and control, included markers of bone formation; Osteocalcin (OC) and bone-specific alkaline phosphatase (b-ALP) and a marker of bone resorption; N- terminal cross linked telopeptides of type I collagen. Serum BAFF level was assessed in patients and control. Bone mineral density was quantified by dual energy x-ray absorptiometry (DXA). Results The bone turnover markers and DXA t scores were significantly different in the patients compared to control. The level of BAFF was significantly higher in RA patient with LBM (1.58±1.17 ng/ml) compared to patients with LBM only (1.03±1.04 ng/ml) (p=0.045) but was insignificantly different from the level in RA patients with normal BMD (1.29±0.87 ng/ml). BAFF significantly correlated with the DXA t score over distal radius and negatively correlated with the b-ALP. In the present study, the t score of the hip was significantly improved and the BAFF level significantly lower in those RA patients receiving hydroxychloroquine (HCQ). Conclusions the responsibility of B-cells and BAFF in the pathogenesis of postmenopausal LBM (osteopenia/osteoporosis) is shown in addition to their established role in RA. Hydroxychloroquine has a potential effect in reducing bone loss and should be considered among the first line armamentarium regimens in the management of RA cases. Introduction of new therapeutic options that selectively inhibit B-cells and target BAFF in osteoporosis should be considered especially when associated with RA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1444