Jane Hollywood

Modification and validation of the Birmingham Vasculitis Activity Score (version 3)

Background: Comprehensive multisystem clinical assessment using the Birmingham Vasculitis Activity score (BVAS) is widely used in therapeutic studies of systemic vasculitis. Extensive use suggested a need to revise the instrument. The previous version of BVAS has been revised, according to usage and reviewed by an expert committee. Objective: To modify and validate version 3 of the BVAS in patients with systemic vasculitis. Methods: The new version of BVAS was tested in a prospective cross-sectional study of patients with vasculitis. Results: The number of items was reduced from 66 to 56. The subscores for new/worse disease and persistent disease were unified. In 313 patients with systemic vasculitis, BVAS(v.3) correlated with treatment decision (Spearman’s rs = 0.66, 95% CI 0.59 to 0.72), BVAS1 of version 2 (rs = 0.94, 95% CI 0.92 to 0.96), BVAS2 of version 2 in patients with persistent disease (rs = 0.60, 95% CI 0.21 to 0.83), C-reactive protein levels (rs = 0.43, 95% CI 0.31 to 0.54), physician’s global assessment (rs = 0.91, 95% CI 0.89 to 0.93) and vasculitis activity index (rs = 0.88, 95% CI 0.86 to 0.91). The intraclass correlation coefficients for reproducibility and repeatability were 0.96 (95% CI 0.95 to 0.97) and 0.96 (95% CI 0.92 to 0.97), respectively. In 39 patients assessed at diagnosis and again at 3 months, the BVAS(v.3) fell by 17 (95% CI 15 to 19) units (p<0.001, paired t test). Conclusion: BVAS(v.3) demonstrates convergence with BVAS(v.2), treatment decision, physician global assessment of disease activity, vasculitis activity index and C-reactive protein. It is repeatable, reproducible and sensitive to change. The new version of BVAS is validated for assessment of systemic vasculitis.

BSR and BHPR guidelines for the management of giant cell arteritis

Scope and purpose GCA is the commonest of all the vasculitides. Visual loss occurs in up to one-fifth of patients, which may be preventable by prompt recognition and treatment [1,2]. The aim of these guidelines is to encourage the prompt diagnosis and management of GCA, with emphasis on the prevention of visual loss. Their scope is to provide evidence-based advice for the assessment and diagnosis of GCA, for initial and further management and for monitoring of disease activity, complications and relapse. This is a summary of the guidelines and the full guideline is available at Rheumatology online.

BSR and BHPR guidelines for the management of polymyalgia rheumatica

PMR is the most common inflammatory rheumaticdisease in the elderly and is one of the biggest indicationsfor long-term steroid therapy. There are difficulties indiagnosis, with heterogeneity in presentation, responseto steroids and disease course.The aim of these guidelines is a safe and specificdiagnostic process for PMR, using continued assessment,and discouragement of hasty initial treatment. Their scopeis to provide advice for the diagnosis of PMR, manage-ment and monitoring of disease activity, complicationsand relapse. The management of GCA is not coveredand is published separately.The full guideline is available at Rheumatology online.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients’ and clinicians’ values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.

2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients’ and clinicians’ values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow‐up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti‐rheumatic drugs (DMARDs), as well as the roles of non‐steroidal anti‐rheumatic drugs and non‐pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.

Investigational Analysis Reveals a Potential Role for Neutrophils in Giant-Cell Arteritis Disease Progression

Rationale: Giant-cell arteritis (GCA) is a large-vessel vasculitis characterized by immune cell infiltration, yet the potential involvement of neutrophils has rarely been studied. Objective: We investigated whether alterations in neutrophil reactivity occurred in the pathogenesis of GCA or during its clinical management with a canonical glucocorticoid dose regimen during a 6-month period. Methods and Results: Blood samples were taken within 48 hours of therapy commencement and at weeks 1, 4, and 24 after glucocorticoid dose. Flow cytometric analysis revealed 3 distinct neutrophil populations and phenotypes. Within 48 hours of steroid treatment, neutrophils displayed an AnxA1hiCD62LloCD11bhi phenotype, whereas week 1 neutrophils were AnxA1hiCD62LloCD11blo and displayed minimal adhesion to endothelial monolayers under flow, and week 24 (ie, lowest glucocorticoid dose) neutrophils were AnxA1hiCD62LhiCD11bhi with increased endothelial adhesion under flow. Week 24 plasma analyses showed high levels of C-X-C motif chemokine ligand 5, interleukin (IL) 8, IL-17, and IL-6. Importantly, comparison of week 1 and week 24 samples revealed a suppressive neutrophil effect on T-cell proliferation at the former time point only. Finally, in vitro incubation of naive neutrophils with concentrations of IL-6 and IL-17 quantified in GCA plasma at weeks 1 and 24 replicated this differential modulation of lymphocyte proliferation. Conclusions: This translational study highlights a novel clinical manifestation of GCA, with evidence for a neutrophil component and an escaped proinflammatory phenotype when glucocorticoid therapy is tapered. These results indicate potential involvement of neutrophils in GCA pathogenesis.

Ischaemic manifestations in giant cell arteritis are associated with area level socio-economic deprivation, but not cardiovascular risk factors

OBJECTIVES To determine whether ischaemic manifestations of GCA are associated with pre-existing hypertension, atherosclerosis or area-level socio-economic deprivation. METHODS We conducted an observational study of rheumatologist/ophthalmologist-diagnosed GCA in eight UK centres. The main outcome measure was ischaemic manifestations observed during active GCA: visual loss/blurring, aura, diplopia, jaw/tongue/limb claudication, cerebral/myocardial ischaemia or scalp necrosis. RESULTS Out of 271 patients, 222 had ischaemic manifestations. Adjusted odds ratios (ORs) for the influence of hypertension and atherosclerosis were 1.6 (95% CI 0.8, 3.1) and 1.5 (0.6, 3.5). The most striking finding was an association of ischaemic manifestations with increasing Index of Deprivation 2007 score: OR 4.2 (95% CI 1.3, 13.6) for the most-deprived quartile compared with the least-deprived quartile. Similar effect sizes were seen within each recruitment centre. Deprivation was associated with smoking and negatively associated with previous polymyalgia. However, neither of these variables, nor hypertension or atherosclerosis, appeared responsible for mediating the effect of deprivation on ischaemic complications. Smoking was not associated with ischaemic manifestations. Median symptom duration before treatment was 30 days; after adjusting for symptom duration, the OR for ischaemic complications was 3.2 (95% CI 1.0, 10.8) for the most-deprived quartile compared with the least-deprived quartile. CONCLUSIONS In GCA, area-level socio-economic deprivation was associated with ischaemic manifestations: this was not mediated by traditional cardiovascular risk factors. These findings are novel and require replication. Delay between first symptoms and treatment may play a role. Public awareness campaigns about GCA should aim especially to engage individuals living in more deprived areas to encourage early presentation and prompt treatment.

Autoantibodies to cyclic citrullinated peptide in a PMR inception cohort from The PMR Outcomes Study

The lack of a laboratory test causes difficulties in distinguishing true polymyalgia rheumatica (PMR) from other inflammatory rheumatic diseases.1 An important differential diagnosis is rheumatoid arthritis (RA), which has been reported to develop in up to a third of patients.2 Antibodies to cyclic citrullinated peptides (CCP) are considered to have 96% specificity for RA.3 A study comparing 57 patients with elderly onset RA with 49 patients with PMR found that 65% in the first group were anti-CCP positive, whereas none of the patients with PMR were positive.4 We have reported on a continuing prospective inception PMR cohort study of clinical outcomes, quality of life and diagnostic uncertainty of patients recruited before the start of …

FRI0366 Gender differences in health-related quality of life in poymyalgia rheumatica

Background The limited evidence on gender differences in outcomes in PMR suggests females experience a more severe and protracted course of disease. Females have longer duration of symptoms, higher relapse rate, higher cumulative steroid dose, and more steroid complications. Objectives To determine gender outcome differences in the first two years of PMR by analysing an existing database. Methods The analyses use data from a UK multi-centre prospective cohort study (2000-2005) of 129 patients (77 females, 52 males). Patients received standard care of, tapering oral prednisolone treatment in-line with current BSR guidelines. Clinical and patient-reported outcomes were assessed prior to starting treatment and at five assessments during two year follow-up. Health-related quality of life was measured using mental and physical component scores of the SF-36. Statistical analysis was done using multivariable linear and logistic regression to examine differences in outcomes by gender. Analyses were adjusted for socio-economic status, age, co-morbidities, and pre-treatment differences in the relevant outcome measure. Results At presentation females had worse mental quality of life (p=0.01.) There was no evidence of a difference in physical quality of life (p=0.54.) During follow-up females had significantly less improvement in physical quality of life (p=0.04 at 12 months, p=0.01 at 24 months). There were no statistically significant differences between females and males in improvement in mental quality of life (p=0.38 at 12 months, p=0.65 at 24 months.) The percentage of females who relapsed in the first two years was higher but non-significant (57% versus 44%). The cumulative steroid dose was higher in females despite their mean 13% lower body weight (3930mg versus 3548mg). Females had twice as many steroid related adverse events as males. Conclusions Females with PMR have worse mental quality of life at initial presentation, a difference that remains during follow-up. Although relapse rates were not significantly different in females and males, there were significant differences in outcome in terms of physical quality of life. Cumulative steroid dose was higher in females despite lower body weight and steroid related adverse events were double those of males. Our findings add to existing evidence of worse outcomes in females and suggest the need to consider alternative approaches to treatment. Disclosure of Interest: None Declared