B Griffiths

Fcγ receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups

OBJECTIVE To investigate a possible association between a functional polymorphism in the intermediate-affinity receptor for IgG called Fc-gamma receptor type IIIA (FcgammaRIIIA [CD16]) and rheumatoid arthritis (RA). METHODS This was an allelic association study in which a single nucleotide polymorphism in FcgammaRIIIA was examined as a susceptibility and/or severity factor for RA. The FcgammaRIIIA-158V/F polymorphism was genotyped by direct sequencing in 2 well-characterized ethnic groups, UK Caucasians (141 RA patients and 124 controls) and North Indians and Pakistanis (108 RA patients and 113 controls). RESULTS The FcgammaRIIIA-158V/F polymorphism was associated with RA in both ethnic groups (P = 0.028 for UK Caucasians, P = 0.050 for North Indians and Pakistanis, and P = 0.003 for both groups combined). FcgammaRIIIA-158VF and -158W individuals had an increased risk of developing RA in both populations (UK Caucasians odds ratio [OR] 1.6, P = 0.050; North Indians and Pakistanis OR 1.9, P = 0.023; and combined groups OR 1.7, P = 0.003). In the UK Caucasian group, the highest risk was for nodular RA, a more severe disease subset, associated with homozygosity for the FcgammaRIIIA-158V allele (OR 4.4, P = 0.004). There was also evidence for an interaction between the RA-associated HLA-DRB1 allele and the presence of at least 1 FcgammaRIIIA-158V allele in predicting susceptibility to RA (OR 5.5, P = 0.000). CONCLUSION We have demonstrated that the FcgammaRIIIA-158V/F polymorphism is a susceptibility and/or severity marker for RA in 2 distinct ethnic groups. This finding may ultimately provide additional insights into the pathogenesis of RA and other autoantibody/immune complex-driven autoimmune diseases.

The development of the L-QoL: a quality-of-life instrument specific to systemic lupus erythematosus

OBJECTIVES Complex diseases, such as systemic lupus erythematosus (SLE), present dilemmas over choice of outcome measures. Using a battery of instruments to capture the impact of different impairments or activity limitations experienced does not provide assessment of the wider impact on quality of life (QoL). This paper describes the development and testing of a new instrument to measure QoL in systemic lupus erythematosus (L-QoL). METHODS The development combines theoretical strengths of the needs-based QoL model with statistical and diagnostic powers of the Rasch model. Content was derived from in-depth interviews with relevant patients. Cognitive debriefing interviews assessed face and content validity. Rasch analysis was applied to data from an initial postal survey to remove misfitting items. A second postal survey assessed scaling properties, reliability, internal consistency and validity. RESULTS A 55-item questionnaire was derived from interview transcripts. Cognitive debriefing confirmed acceptability. Rasch analysis of postal survey data (n = 95) removed misfitting items. A second postal survey (n = 93), produced a 25-item version with good item fit and stability, excellent test-retest reliability (0.92), internal consistency (0.92) and strict unidimensionality. CONCLUSIONS It is concluded that the L-QoL should prove a valuable instrument for assessing patient-based outcome in clinical trials and practice.

The treatment of lupus with cyclosporin A

Cyclosporin is a potent immunosuppressive drug and is frequently used in the therapy of auto-immune diseases, including systemic lupus erythematosus (SLE). Few large studies have been performed using this drug in SLE patients. However, small uncontrolled studies of patients with SLE have shown favourable results with a significant improvement in disease activity, a fall in anti ds DNA titres and proteinuria and an improvement in complement levels,leucopaenia and thrombocytopaenia. Interestingly, a consistent reduction in corticosteroid dosage often by as much as 50% is seen. Toxicity, especially with hypertension and renal impairment, occurs but usually reverses on dose reduction or the addition of an anti-hypertensive agent and isminimised by adherence to the strict monitoring guidelines.Large multi-centre randomised-controlled trials of the use of cyclosporin in SLE patients are underway and the results are eagerly awaited.

The BILAG multi-centre open randomized controlled trial comparing ciclosporin vs azathioprine in patients with severe SLE

OBJECTIVE To determine whether low-dose ciclosporin was a more effective corticosteroid-sparing agent than AZA in patients with SLE. METHODS Patients with SLE requiring a change or initiation of a corticosteroid-sparing agent and who were taking > or =15 mg of prednisolone/day were randomized to receive either ciclosporin or AZA during this 12-month open-label multi-centre trial. There were strict guidelines for the reduction of prednisolone. The primary outcome was the absolute mean change in prednisolone. RESULTS Eighty-nine patients were randomized. Using an intention-to-treat analysis, the absolute mean change in prednisolone dose between baseline and 12 months, adjusted for baseline prednisolone dose, was 9.0 mg for ciclosporin (95% CI 7.2, 10.8) and 10.7 mg for AZA (95% CI 8.8, 12.7). The difference in the change between treatment groups was -1.7 mg (95% CI -4.4, 0.9; P = 0.2). No significant differences were detected for the secondary outcomes: change in disease activity [classic British Isles Lupus Assessment Group (BILAG) index], number of flares, development of new damage or change in quality of life. A similar number of patients in each arm stopped the study drugs due to adverse events and ineffectiveness. No patient developed severe hypertension or a persistent rise in creatinine. One patient in the ciclosporin arm developed a significant increase in proteinuria due to disease activity. CONCLUSIONS Both drugs were effective corticosteroid-sparing agents. Ciclosporin was not a more effective corticosteroid-sparing agent. Ciclosporin may be considered in patients who are unable to tolerate AZA. Patients on ciclosporin require close monitoring of blood pressure and creatinine. TRIAL REGISTRATION Current Controlled Trials, http://www.controlled-trials.com/, ISRCTN35919612.

Is minocycline therapy in acne associated with antineutrophil cytoplasmic antibody positivity? A cross-sectional study.

Background Minocycline (MN), one of the commonly prescribed therapies for acne, is known to be associated with autoimmune disorders including drug‐induced lupus. However, data are sparse regarding the prevalence of autoimmune disease in acne or in patients with acne treated with MN.

Identification of Whole Blood Gene Expression Signature in Primary Sjogren's Syndrome Associated Lymphoma

This free journal suppl. entitled: Special Issue: 2014 ACR/ARHP Annual Meeting Abstract Supplement

THU0323 Predictors of Disease Severity, Lymphoma and Death: Prevalence in Patients Registered on The United Kingdom Primary Sjögren's Syndrome Registry

Background There has been much research aimed at elucidating key biological and clinical features which predict severity of disease and development of lymphoma in patients with primary Sjögrens syndrome (pSS). Key biological predictors identified include the presence of leukopenia or lymphopenia, hypocomplementaemia, cryoglobulinaemia, monoclonal gammopathy; key clinical predictors include younger age at time of symptom onset or diagnosis, peripheral neuropathy, salivary gland enlargement and skin involvement (particularly palpable purpura) [1–4]. The UK Primary Sjögrens Syndrome Registry (UKPSSR) is a MRC funded patient cohort, devised to facilitate research into pSS to improve understanding of the condition. Objectives Ascertain the prevalence of putative clinical predictors amongst UKPSSR patients. Explore the relationship between demographics, clinical parameters, disease severity and lymphoma development. Methods Patients were identified on the UKPSSR (n=868), those with insufficient data were excluded from analysis (n=36). Frequency of the predictors was calculated for remaining 832 patients. Patients were assigned a value for each predictor: 1 for present, 0 for absent. These values were then added to provide the prevalence of each predictor within the cohort, and a cumulative score for each patient. Each patient had 2 cumulative scores: one for disease severity and risk of death, the other for risk of lymphoma. Patients with a recorded age of pSS symptom onset (n=739) were analysed to investigate the relationship between age of onset and development of lymphoma. SPSS used for statistical analysis. Results Pearson Chi-squared analysis found a statistically significant (p=0.004) increased incidence of lymphoma in patients presenting with symptoms of pSS before the age of 35. Predictors of lymphoma development were more common in patients whose symptoms started between age 20–34 (p=0.05). Patients with diagnosed lymphoma had a higher cumulative lymphoma risk score than patients who did not have lymphoma (p=0.05). Predictors of severe disease were found to be more common in patients whose symptoms began before age 35 (p=0.05). Conclusions This analysis corroborates the findings of previous research showing an increased lymphoma prevalence in patients presenting with pSS at a younger age [4]. It also finds a statistically significant link between poor prognostic features and development of lymphoma as described in the literature [2,3]. Further statistical analysis will aim to establish the link between each predictor and the development of systemic manifestations of pSS, baseline and cumulative ESSDAI scores and lymphoma. References Brito-Zeron, P., et al., Systemic activity and mortality in primary Sjögren syndrome. Ann Rheum Dis. Luciano, N., et al., One year in review 2015: Sjögrens syndrome. Clin Exp Rheumatol. Nocturne, G. and X. Mariette, Sjögren syndrome-associated lymphomas. BJH. Ramos-Casals, M., et al., Systemic involvement in primary Sjögrens syndrome evaluated by the EULAR-SS disease activity index. Rheumatology. Disclosure of Interest None declared

Serum Free Light Chains are Associated with Clinical Disease Activity of Primary Sjögren's Syndrome in the Cutaneous, Biological and Renal Domains

Background: Cognitive impairment in primary Sjogren’s syndrome (PSS) has been identified in several small studies using self-reported measures. Objectives: To quantify cognitive impairment symptoms in a large cohort of 150 PSS patients compared with controls and to explore the relationship between cognitive impairment with fatigue, pain and mood symptoms. Methods: PSS patients fulfilling the American European Consensus Criteria were recruited from 12 sites in England. They completed the Cognitive Failures Questionnaire (CFQ) as well as measures of mood (Hospital Anxiety and Depression Scale), fatigue (visual analogue scale (VAS)), dryness (VAS) and pain (VAS). CFQ scores were compared with data from controls. Completion of the CFQ yields a possible score between 0 and 100. The higher the score the greater the impairment. Results: One hundred and fifty PSS patients and 198 controls completed the CFQ. Cognitive symptoms were worse in the PSS group (43.7 ± 17.8 vs 35.9 ± 12.9; P < 0.001). This difference persisted (P < 0.001) following analysis of covariance adjusting for age and gender. There were significant correlations with pain, fatigue, anxiety, depression and subjective dryness scores with CFQ scores. In order to partition the variability in CFQ scores into its component parts, we performed a multiple regression analysis. This confirmed that anxiety was the most important predictor of CFQ scores (P = 0.004). Conclusion: Cognitive symptoms are common in PSS and independently associate with anxiety. Clinicians should give consideration to cognitive failure and anxiety in the management of PSS patients.

Assignable Causes for Fatigue in Primary Sjögren’s Syndrome: Data from the UK Primary Sjögren’s Syndrome Registry

Are Ankylosing Spondylitis, Psoriatic Arthritis and Undifferentiated Spondylarthritis Associated with an Increased Risk of Cardiovascular Disease?For a searchable version of these abstracts, please visit www.acrabstracts.org. Please Note: It may take several minutes for this file to download.Background/Purpose: Person-centred care (PCC) is a holistic approach with respectful and individualized care allowing negotiation of care where persons with health problems are empowered to be involved in health decisions. Patients’ illness narratives constitute a starting point for building a collaboration with health care professionals and to empower them to play an active role in their health care. Little is known of the impact of PCC vs. regular care on patients’ skills as health care consumers. The aim was to study the impact on effective consumers’ skills over 6 and 12 months as measured by the Effective Consumer Scale (EC17) in patients undergoing biological therapy and randomly assigned to either a nurse-led rheumatology clinic (NLC) based on PCC or to a rheumatologist-led clinic (RLC) based on regular care.Methods: A 12 month RCT in 107 patients with chronic inflammatory arthritis1. Inclusion criteria were ongoing biological therapy and a DAS28 ≤3.2. All patients met a rheumatologist at inclusion and after 12 months, while the 6 month follow-up was randomized to either at an NLC (PCC) or at an RLC (regular care). Outcome measure was the EC17, developed and endorsed by the OMERACT, including five subscales; 1. Use of health information, 2. Clarifying personal priorities, 3. Communicating with others, 4. Negotiating roles and 5. Deciding and taking action. EC17 total score ranges from 0-100, worse to best. Differences between and within NLC and RLC were analyzed with Friedmans’ test or Mann Whitney U-test.Results: After 12 months 97 patients completed the RCT (NLC n=47, RLC n=50), mean (SD) age 55.4 (12.7) years, disease duration 16.7 (11.5) years, DAS28 2.1 (0.7), HAQ 0.54 (0.38), global health 20.4 (17.1), pain 21.1 (18.0) and 56% were women. There were no statistically significant differences within or between the two intervention groups at baseline nor in EC17 total score mean (SD) at baseline (NLC 83.5 (9.4) vs. RLC 83.2 (10.8), 6 months (NLC 85.4 (10.4) vs. RLC 82.9 (10.9) and 12 months (NLC 85.3 (11.1) vs. RLC 82.3 (10.9)). However, in NLC there was a statistically significant improvement in EC17 subscale “1. Use of health information” at both 6 and 12 months (p=0.041 and p=0.004 respectively).Conclusion: Replacing just one of three visits over 12 months to an NLC based on PCC instead of an RLC based on regular care resulted in more effective consumers concerning the use of health information. Larger studies over longer time frames focusing on PCC are needed to better understand its full impact on effective consumer skills measured by EC17.References:1. Larsson I, et al. Randomized controlled trial of a nurse-led rheumatology clinic for monitoring biological therapy. J Adv Nurs 2014;70:164-75.Background/Purpose: Chronic widespread pain (CWP), one of the hallmarks of fibromyalgia, is not uncommon in adolescents and it has previously been shown that adolescents with pain often become young adults with pain. CWP often co-varies with anxiety, depression, and stress symptoms in adults, but the knowledge regarding this is small in youth and young adults.The aim was to study the associations between CWP, anxiety, depression and stress in adolescents attending first year of high school.Methods: A computerized questionnaire to 296 adolescents attending Swedish high school, with validated questions regarding presence and distribution of pain (Epipain mannequin), stress symptoms (ELO question), anxiety and depression (Hospital Anxiety and Depression Scale – HADS), and health related quality of life (HRQL as measured by EQ5D). Pain was considered chronic when persistent for more than three months, and the subgroup CWP was defined according to the 1990 ACR criteria for fibromyalgia. Statistical analyses in SPSS v21 with comparison of means by Student’s t-test and proportions by chi2-test or Fischer’s exact test.Results: 257 (87%) out of 296 eligible students, mean (SD) age 16.1 (0.7) and 65.8% girls, responded to the questionnaire. Prevalence of chronic pain was 20.8% and that of the subgroup CWP was 4.7%, without any gender differences (boys 18.2% vs girls 22.2%; p=0.224, and 3.4% vs 5.4%; p=0.692). High level (4 or 5 on a 5 point scale) of stress symptoms were less common in boys (16.0% vs 28.2%; p=0.015), as was possible or probable anxiety (17.1% vs 44.4%; p<0.001), but not depression (10.3% vs 12.5%; p=0.764). Students with high level of stress reported CWP five times more often than those with less stress (30.4% vs 5.8%; p=0.001). Students with probable anxiety reported CWP ten times more often than students with no anxiety (17.6% vs 1.8%; p=0.001), and CWP was also more common, but not statistically significant, in students with probable depression (20.0% vs 3.1%; p=0.163). Those reporting CWP had significantly lower HRQL (0.58 vs 0.87; p=0.038) than students with no chronic pain.Conclusion: The high prevalence of chronic pain and the strong associations between CWP and reports of stress and anxiety in adolescents highlights that a multifactorial background to chronic pain must be considered early in life. An apparent lower score in EQ5D also indicates that the presence of CWP has an marked impact on HRQL also in adolescents.Background/Purpose: The treatment target for axial spondyloarthritis (SpA) is to maximize health-related quality of life (HRQoL) by controlling disease activity and improving functioning. The treatment cornerstones are a combination of patient education, pharmacological and non-pharmacological treatment. Health professionals are familiar with providing patient education but the knowledge is scarce concerning how this education is experienced by the patients.The aim was to describe patients’ experiences of education in SpA management.Methods: The study had a descriptive design with a qualitative conventional content analysis approach performed in seven steps in accordance with Graneheim & Lundman (1). The analysis aimed to describe and preserve contextual meanings. After coding and subgrouping meaningful parts of the text were merged into categories. Eleven interviews were conducted between 2014-2015 in patients with SpA based on a strategic sampling in order to achieve variation with regard to sex (7 men, 4 women), age (38-66 years), subdiagnoses (5 patients with AS, 6 with USpA), quality of life (EQ5D 0.29-1.0), disease activity (BASDAI 1-6), physical function (BASFI 0-5), and global health (BASG 0-7) .Results: Three categories representing patients’ experiences of patient education in disease management emerged; guiding education, reliable education and available education. Guiding education comprised SpA management including disease knowledge such as symptoms, prognosis, treatment, self-management, climate impact, heredity, and assisting devices. Reliable education meant how and by whom the education was communicated and was considered reliable if it was based on science and communicated by specialists, for example by physician, nurse, PT, dietician and senior patients with experience of rheumatic diseases. The patients experienced difficulties in assessing the large flow of education coming from various sources. Individualized education also increased the reliability. Available education meant that the education can and should be presented in varied formats, and that the amount of information could be chosen. The education could be given orally (through meetings, videos, lectures), in writing (by pamphlets, e-mails, journals, webpages) or obtained through own personal experiences. There were requests to utilize newer media like skype, video and chat forums. Furthermore, individual contacts with healthcare professionals when needed were of importance.Conclusion: This study highlights the importance of obtaining a guiding, reliable and available patient education for management of SpA. Health care professionals need to consider the importance of presenting varied formats of education based on patients’ experiences and expectations.References:1.Graneheim UH, Lundman B. Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. Nurse education today 2004;24(2):105-12.PMN Reactivity Contribute to Acute Onset Joint Inflammation By Increasing CXCL8 Production in Joints of RA Patients with Anti-Collagen II AntibodiesBig Data International Primary Sjogren Syndrome Registry : Baseline Characterization and Diagnostic Approach in 6047 Patients Fulfilling the 2002 AE CriteriaThe Link Between DAS28 and the Short-Term Risk of Acute Coronary Syndrome in RA, and Its Driving FactorsHypomethylation in Enhancer and Promoter Regions of Interferon Regulated Genes in Multiple Tissues Is Associated with Primary Sjogrens SyndromeReceptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Sclerostin Are Related to Joint Destruction in Early Rheumatoid Arthritis Unrelated to Polymorphisms of the Genes

Patient Sub-Phenotyping in Primary Sjogren's Syndrome

Background: Cognitive impairment in primary Sjogren’s syndrome (PSS) has been identified in several small studies using self-reported measures. Objectives: To quantify cognitive impairment symptoms in a large cohort of 150 PSS patients compared with controls and to explore the relationship between cognitive impairment with fatigue, pain and mood symptoms. Methods: PSS patients fulfilling the American European Consensus Criteria were recruited from 12 sites in England. They completed the Cognitive Failures Questionnaire (CFQ) as well as measures of mood (Hospital Anxiety and Depression Scale), fatigue (visual analogue scale (VAS)), dryness (VAS) and pain (VAS). CFQ scores were compared with data from controls. Completion of the CFQ yields a possible score between 0 and 100. The higher the score the greater the impairment. Results: One hundred and fifty PSS patients and 198 controls completed the CFQ. Cognitive symptoms were worse in the PSS group (43.7 ± 17.8 vs 35.9 ± 12.9; P < 0.001). This difference persisted (P < 0.001) following analysis of covariance adjusting for age and gender. There were significant correlations with pain, fatigue, anxiety, depression and subjective dryness scores with CFQ scores. In order to partition the variability in CFQ scores into its component parts, we performed a multiple regression analysis. This confirmed that anxiety was the most important predictor of CFQ scores (P = 0.004). Conclusion: Cognitive symptoms are common in PSS and independently associate with anxiety. Clinicians should give consideration to cognitive failure and anxiety in the management of PSS patients.