Simon Bowman

Accurate detection of changes in disease activity in primary Sjögren's syndrome by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index

To assess and compare the sensitivity to change of the European League Against Rheumatism Sjögrens Syndrome Disease Activity Index (ESSDAI) with that of other primary Sjögrens syndrome (SS) disease activity indexes.

The assessment of fatigue in primary Sjögren's syndrome.

Objective. Disabling fatigue is a prominent feature of primary Sjögrens syndrome (PSS). We evaluated a number of questionnaires for their ability to discriminate fatigue in PSS from that in other rheumatic disorders and healthy controls. Methods. 33 female caucasian patients with PSS, 45 with rheumatoid arthritis (RA), 16 with systemic lupus erythematosus (SLE) and 30 controls completed self‐administered questionnaires including; Visual Analogue Scales (VAS), the Chalder Fatigue Scale (CFS), the Nottingham Health Profile (NHP) and the Medical Outcomes Short Form 36 Questionnaire (SF‐36). Results. All patient groups scored significantly worse than controls on the ‘Energy’ dimension of the NHP, the fatigue VAS and the ‘Vitality’ domain of the SF‐36. No significant differences were observed between PSS patients and controls using the CFS. Conclusions. The NHP, VAS and SF‐36 are useful in identifying fatigue in these rheumatic disorders. Further work is required to identify the characteristic features of fatigue in these conditions.

Daytime patterning of fatigue and its associations with the previous night’s discomfort and poor sleep among women with primary Sjögren’s syndrome or rheumatoid arthritis

OBJECTIVESnFatigue is a prominent symptom in many rheumatic diseases and has a substantial impact on many outcomes. In previous research, fatigue has been linked with poor sleep and discomfort, including joint pain and sicca symptoms. The aim of the present study was to investigate prospectively the daily variations in fatigue and the roles of discomfort and adequacy of sleep the previous night in that fatigue for people with primary Sjögrens syndrome (pSS) or rheumatoid arthritis (RA).nnnMETHODSnThirty-nine women with pSS or RA reported their discomfort and fatigue for 35 days using the Profile of Fatigue and Discomfort. Sleep was monitored with wrist actigraphy, and the quantity and quality of the nights sleep was reported in a diary each morning.nnnRESULTSnThe pattern of fatigue did not differ significantly between women with pSS and women with RA. For participants with either condition, both somatic and mental fatigue increased steadily throughout the day. Multi-level regressions indicated that evenings of worse discomfort were followed by poorer reported quantity/quality of sleep and worse sleep efficiency (percentage of time asleep when in bed). In addition, a night of worse discomfort and poor sleep was followed by more severe fatigue compared with the individuals average.nnnCONCLUSIONSnFatigue management for people with rheumatic disease could include strategies for coping with discomfort at night and difficulties in sleeping. Further research into ameliorating fatigue should include assessments of persistent discomfort or periods of insomnia and identify disease-specific needs that require targeted intervention.

Rheumatoid Arthritis is Associated with IgG Antibodies to Human Endogenous Retrovirus Gag Matrix: A Potential Pathogenic Mechanism of Disease?

Objective. Human endogenous retrovirus (HERV)-K10 has been implicated in the etiology and pathogenesis of rheumatoid arthritis (RA). A secondary immune response to this virus might suggest an antigen-driven response in patients. The Gag region of HERV-K10 could provide a key epitope important for immunological reactivity. We investigated the presence of IgG antibodies to this region and assessed its significance in RA. Methods. We determined an antigenic peptide on the matrix segment of HERV-K10 and developed an ELISA system to detect IgG antibodies in patients with RA and controls. The presence of antibodies to the matrix peptide (denoted as MAG1: RIGKELKQAGRKGNI) was correlated with patient details. Results. On screening patients’ serum, we found a significantly higher mean IgG antibody response to MAG1 in 30 patients with RA as compared to 23 patients with inflammatory bowel disease (p = 0.003), 29 patients with osteoarthritis (p = 0.001), and 43 healthy individuals (p = 0.002). Reactivity was not observed to a control peptide possessing a nonhomologous amino acid sequence. On evaluating clinical details with serological activity, no correlation with disease duration (p = 0.128), sex (p = 0.768), or rheumatoid factor status (p = 0.576) was found. Conclusion. A significantly elevated IgG antibody response to an HERV-K10 Gag matrix peptide was observed in patients with RA, suggesting that the exposure of HERV-K10 may cause a secondary, antigenic driven immune response in RA.

Endogenous retrovirus Erv-3 is not implicated in rheumatoid arthritis but may provide a biomarker for osteoarthritis

Rheumatoid arthritis (RA) is an autoimmune disease with chronic inflammation of the synovial membrane culminating in the destruction of cartilage and bone. The etiology is unknown, although possible causes include viral triggers1. The latter may include human endogenous retroviral (HERV) families: HERV-K, HERV-L, ERV-9, and ERV-32,3. We have reported a novel reverse transcriptase polymerase chain reaction (RT-PCR) system to identify HERV-K10 and identified significantly high levels of messenger RNA in the peripheral blood (and synovial fluid) of patients with RA compared to osteoarthritis (OA) and healthy controls4. In our study, we modified the RT-PCR system to analyze ERV-3 expression in these patients.nnPeripheral blood mononuclear cells (PBMC) from 20 RA patients who fulfilled American Rheumatism Association criteria were used to extract … nnAddress correspondence to Dr. P. Nelson; E-mail: p.n.nelson{at}wlv.ac.uk

Sjögren Syndrome and Work Disability

Primary Sjogren syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lachrymal glands associated with oral and ocular dryness. It is 9 to 13 times more common in women than men and typically affects women between the ages of 40 and 60 years1. Fatigue and pain are common symptoms, reported by > 60% of patients. They are closely linked with low mood and reduced health-related quality of life in patients with this condition and can be disabling in severity2.nnAs a result, pSS has potential health economic consequences. This is of particular importance as we move into an era of clinical trials for (expensive) biologic agents for pSS manifestations. There are a limited number of published papers about the effect of developing pSS on patients’ employment and ability to work and what aspects of the disease may predict work disability3,4,5. In this issue of The Journal , Mandl, et al report the results of their study of work disability in newly diagnosed patients with pSS in Skane County in Sweden6. This study prospectively collected clinical data of 51 patients with pSS from the Malmo Sjogren’s Syndrome Register and linked these data to employment data from 1 year before to 2 years after the diagnosis of pSS. The employment data came from the Swedish Social Insurance Agency. This was compared to employment data from age-, sex-, and residence-matched controls from the Swedish population register in a 1:4 ratio. At the time of diagnosis, 16% of patients with pSS were already receiving a disability pension and 10% were on sick leave. After the diagnosis, the authors showed a steady increase in work disability, initially including … nnAddress correspondence to Prof. S.J. Bowman, Rheumatology Dept., Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. E-mail: simon.bowman{at}uhb.nhs.uk

FRI0421 Development of Clinessdai Score (Clinical Eular Sjögren's Syndrome Disease Activity Index) Without Biological Domain: A Tool For Biological Studies

Background ESSDAI is a validated activity index in primary Sjögrens syndrome more and more used in clinical trials but also for finding biomarkers associated with activity of the disease. In this context, the presence of the biological domain in the ESSDAI score may induce circular reasoning and colinearity of data. Objectives To develop the ClinESSDAI, derived from the ESSDAI score after deleting biological domain, and to validate if by comparison with the original ESSDAI. Methods The 702 fictive vignettes created using data from 96 real cases of pSS for the study of development ESSDAI were used. As for the development of the original score, the assessment by the 39 experts who participated to the development study of disease activity using a scale ranging from 0-10 was used as the “gold standard” for weighting domains in the robust regression model. The explanatory variables included all domain of ESSDAI except the biological domain. The ClinESSDAI was compared to original ESSDAI to assess if it could be a surrogate of the original score by assessing its reproducibility using ESSDAI as gold standard. The validity of ClinESSDAI (including construct validity, reliability and sensitivity to change) was then assessed and compared to that of ESSDAI. Validation populations included the 96 real cases and the 395 patients of the EULAR cohort. Results In the multivariate model, each of the 11 areas was significantly associated with disease activity. The weight of the domains was slightly different from the fields of ESSDAI (table). The ClinESSDAI was an excellent surrogate of the original ESSDAI, since the ICC between ESSDAI and ClinESSDAI were0.98 [0.97; 0.98] for fictive vignettes, 0.99 [0.98; 0.99] for the real case and0.90 [0.87; 0.92] in the EULAR cohort. Psychometric properties of the ClinESSDAI (construct validity, reliability and sensitivity to change) were very close to that of ESSDAI. Conclusions Declination of the ESSDAI score without biological domain appears valid and very close to the original score. In this score, weights of some domains changed. This score will allow an evaluation of disease activity that is independent ofB-cell biomarkers, which will be useful in biological studies to avoid circular reasoning and colinearity of data. In addition, it may be helpful in clinical practice to assess disease activity when immunological tests have not been carried out. Disclosure of Interest None declared

Looking into the Future—The EULAR Disease Activity Scores: Toward a Consensual Evaluation of Primary Sjogren’s Syndrome

In primary Sjogren’s syndrome (SS), clinical features can be divided into two facets: the benign subjective but disabling manifestations such as dryness, articular and muscular pain, and fatigue, and the systemic manifestations such as synovitis, vasculitis, skin, lung, renal and neurological involvement, or lymphoma. Great efforts have been made to develop valid activity indexes needed to assess the effectiveness of new therapies. First, for evaluation of patients’ symptoms: the Profile of Fatigue and Discomfort (PROFAD) and Sicca Symptoms Inventory (SSI) then for systemic features: the SS Disease Activity Index (SSDAI) and Sjogren’s Systemic Clinical Activity Index (SCAI). The development of these indexes served as bases of an international collaborative project promoted by European League Against Rheumatism (EULAR). Thirty-nine primary SS experts were involved in the development of these two consensus disease activity indexes: the EULAR Sjogren’s Syndrome Patients Reported Index (ESSPRI), a patient-administered questionnaire to assess subjective features, and the EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI), a systemic activity index to assess systemic complications. Both indexes have good correlations with existing scores and also global evaluation of disease activity by physician for ESSDAI and by patient for ESSPRI. In addition, ESSDAI had a good sensitivity to change and detects changes more accurately, when compared to other scores. These both indexes are simple and aimed to be used for both clinical trials and clinical practice. They are currently being validated for that purpose.