Identifying key health system components associated with improved outcomes to inform the re-configuration of services for adults with rare autoimmune rheumatic diseases: a mixed-methods study.

BACKGROUND: Adults with rare autoimmune rheumatic diseases face unique challenges and struggles to navigate health-care systems designed to manage common conditions. Evidence to inform an optimal service framework for their care is scarce. Using systemic vasculitis as an exemplar, we aimed to identify and explain the key service components underpinning effective care for rare diseases. METHODS: In this mixed-methods study, data were collected as part of a survey of vasculitis service providers across the UK and Ireland, interviews with patients, and from organisational case studies to identify key service components that enable good care. The association between these components and patient outcomes (eg, serious infections, mortality) and provider outcomes (eg, emergency hospital admissions) were examined in a population-based data linkage study using routine health-care data obtained from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis from national health datasets in Scotland. We did univariable and multivariable analyses using Bayesian poisson and negative binomial regression to estimate incident rate ratios (IRRs), and Cox proportional hazards models to estimate hazard ratios (HRs). People with lived experiences were involved in the research and writing process. FINDINGS: Good care was characterised by service components that supported timely access to services, integrated care, and expertise. In 1420 patients with ANCA-associated vasculitis identified from national health datasets, service-reported average waiting times for new patients of less than 1 week were associated with fewer serious infections (IRR 0·70 [95% credibility interval 0·55-0·88]) and fewer emergency hospital admissions (0·78 [0·68-0·92]). Nurse-led advice lines were associated with fewer serious infections (0·76 [0·58-0·93]) and fewer emergency hospital admissions (0·85 [0·74-0·96]). Average waiting times for new patients of less than 1 week were also associated with reduced mortality (HR 0·59 [95% credibility interval 0·37-0·93]). Cohorted clinics, nurse-led clinics, and specialist vasculitis multi-disciplinary team meetings were associated with fewer serious infections (IRR 0·75 [0·59-0·96] for cohorted clinics; 0·65 [0·39-0·84] for nurse-led clinics; 0·72 [0·57-0·90] for specialist vasculitis multi-disciplinary team meetings) and emergency hospital admissions (0·81 [0·71-0·91]; 0·75 [0·65-0·94]; 0·86 [0·75-0·96]). Key components were characterised by their ability to overcome professional tensions between specialties. INTERPRETATION: Key service components associated with important health outcomes and underpinning factors were identified to inform initiatives to improve the design, delivery, and effectiveness of health-care models for rare autoimmune rheumatic diseases. FUNDING: Versus Arthritis.

Novel ultrasonographic Halo Score for giant cell arteritis: assessment of diagnostic accuracy and association with ocular ischaemia.

OBJECTIVES: Ultrasound of temporal and axillary arteries may reveal vessel wall inflammation in patients with giant cell arteritis (GCA). We developed a ultrasound scoring system to quantify the extent of vascular inflammation and investigated its diagnostic accuracy and association with clinical factors in GCA. METHODS: This is a prospective study including 89 patients suspected of having GCA, of whom 58 had a confirmed clinical diagnosis of GCA after 6 months follow-up. All patients underwent bilateral ultrasound examination of the three temporal artery (TA) segments and axillary arteries, prior to TA biopsy. The extent of vascular inflammation was quantified by (1) counting the number of TA segments and axillary arteries with a halo and (2) calculating a composite Halo Score that also incorporated the thickness of each halo. RESULTS: Halo counts and Halo Scores showed moderate diagnostic accuracy for a clinical diagnosis of GCA. They correlated positively with systemic inflammation. When compared with the halo count, the Halo Score correlated better with C-reactive protein (CRP) levels and allowed to firmly establish the diagnosis of GCA in more patients. Higher halo counts and Halo Scores were associated with a higher risk of ocular ischaemia. They allowed to identify subgroups of patients with low risk (≤5%) and high risk of ocular ischaemia (>30%). CONCLUSIONS: Ultrasound halo scoring allows to quantify the extent of vascular inflammation in GCA. Extensive vascular inflammation on ultrasound may provide strong diagnostic confirmation and associates with ocular ischaemia in GCA.

Diagnostic Assessment Strategies and Disease Subsets in Giant Cell Arteritis: Data From an International Observational Cohort.

OBJECTIVE: Diagnostic assessment in giant cell arteritis (GCA) is rapidly changing as vascular imaging becomes more available. This study was undertaken to determine if clinical GCA subsets have distinct profiles or reflect differential diagnostic assessments. METHODS: Patients were recruited from an international cohort and divided into 4 subsets based on a temporal artery (TA) abnormality (positive TA biopsy [TAB] or halo sign on TA ultrasound [TA-US]) and/or evidence of large vessel (LV) involvement on imaging: 1) both TA abnormality and LV involvement (TA+/LV+ GCA); 2) TA abnormality without LV involvement (TA+/LV- GCA); 3) LV involvement without TA abnormality (TA-/LV+ GCA); and 4) clinically diagnosed GCA without LV involvement or TA abnormality (TA-/LV- GCA). RESULTS: Nine hundred forty-one patients with GCA were recruited from 72 international study sites. Most patients received multiple forms of diagnostic assessment, including TAB (n = 705 [75%]), TA-US (n = 328 [35%]), and LV imaging (n = 534 [57%]). Assessment using TAB, TA-US, and LV imaging confirmed the diagnosis of GCA in 66%, 79%, and 40% of cases, respectively. GCA subsets had distinct profiles independent of diagnostic assessment strategies. TA+/LV- were the most common subset (51%), with a high burden of cranial ischemia. Those in the TA-/LV- subset (26%) had a high prevalence of cranial ischemia and musculoskeletal symptoms. Patients in the TA-/LV+ subset (12%) had prevalent upper extremity vascular abnormalities and a low prevalence of vision loss, and those in the TA+/LV+ subset (11%) were older and had a high prevalence of cranial ischemia, constitutional symptoms, and elevated acute-phase reactant levels. CONCLUSION: Vascular imaging is increasingly incorporated into the diagnostic assessment of GCA and identifies clinical subsets of patients based on involvement of temporal and extracranial arteries.

Systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis: focus on giant cell arteritis.

Objectives: To analyse the current evidence for the management of large vessel vasculitis (LVV) to inform the 2018 update of the EULAR recommendations. Methods: Two systematic literature reviews (SLRs) dealing with diagnosis/monitoring and treatment strategies for LVV, respectively, were performed. Medline, Embase and Cochrane databases were searched from inception to 31 December 2017. Evidence on imaging was excluded as recently published in dedicated EULAR recommendations. This paper focuses on the data relevant to giant cell arteritis (GCA). Results: We identified 287 eligible articles (122 studies focused on diagnosis/monitoring, 165 on treatment). The implementation of a fast-track approach to diagnosis significantly lowers the risk of permanent visual loss compared with historical cohorts (level of evidence, LoE 2b). Reliable diagnostic or prognostic biomarkers for GCA are still not available (LoE 3b).The SLR confirms the efficacy of prompt initiation of glucocorticoids (GC). There is no high-quality evidence on the most appropriate starting dose, route of administration, tapering and duration of GC (LoE 4). Patients with GCA are at increased risk of dose-dependent GC-related adverse events (LoE 3b). The addition of methotrexate or tocilizumab reduces relapse rates and GC requirements (LoE 1b). There is no consistent evidence that initiating antiplatelet agents at diagnosis would prevent future ischaemic events (LoE 2a). There is little evidence to guide monitoring of patients with GCA. Conclusions: Results from two SLRs identified novel evidence on the management of GCA to guide the 2018 update of the EULAR recommendations on the management of LVV.

Rheumatoid factor testing in Spanish primary care: A population-based cohort study including 4.8 million subjects and almost half a million measurements.

OBJECTIVE: Rheumatoid factor (RF) testing is used in primary care in the diagnosis of rheumatoid arthritis (RA); however a positive RF may occur without RA. Incorrect use of RF testing may lead to increased costs and delayed diagnoses. The aim was to assess the performance of RF as a test for RA and to estimate the costs associated with its use in a primary care setting. MATERIAL AND METHODS: A retrospective cohort study using the Information System for the Development of Research in Primary Care database (contains primary care records and laboratory results of >80% of the Catalonian population, Spain). Participants were patients ≥18 years with ≥1 RF test performed between 01/01/2006 and 31/12/2011, without a pre-existing diagnosis of RA. Outcome measures were an incident diagnosis of RA within 1 year of testing, and the cost of testing per case of RA. RESULTS: 495,434/4,796,498 (10.3%) patients were tested at least once. 107,362 (21.7%) of those tested were sero-positive of which 2768 (2.6%) were diagnosed with RA within 1 year as were 1141/388,072 (0.3%) sero-negative participants. The sensitivity of RF was 70.8% (95% CI 69.4-72.2), specificity 78.7% (78.6-78.8), and positive and negative predictive values 2.6% (2.5-2.7) and 99.7% (99.6-99.7) respectively. Approximately €3,963,472 was spent, with a cost of €1432 per true positive case. CONCLUSIONS: Although 10% of patients were tested for RF, most did not have RA. Limiting testing to patients with a higher pre-test probability would significantly reduce the cost of testing.

Development of a score for assessment of radiologic damage in large-vessel vasculitis (Combined Arteritis Damage Score, CARDS).

OBJECTIVES: Outcome assessment in large-vessel vasculitis (LVV) remains challenging and this impairs patient management and the conduct of clinical studies. Previous proposals for outcome tools have not included imaging. This study aimed to develop an imaging score to quantify damage in LVV and to assess the difference between Takayasu (TAK) and giant cell arteritis (GCA). METHODS: Ninety-six patients (41 TAK, 55 GCA) were identified from local registries at two University Hospitals in the UK. Radiologic lesions including stenosis, occlusion and aneurysm were evaluated in 25 arterial regions by enhanced computed tomography or magnetic resonance angiography. Lesion correlation with combined damage assessment scores was employed in a multiple regression analysis to define the weight of individual lesions and develop a damage index. RESULTS: A numerical damage index was developed: the "Combined Arteritis Damage Score (CARDS)". The index was derived from a formula: number of regions with mild stenosis × 0.6 + number of regions with moderate to severe stenosis × 1.2 + number with occlusions × 1.6 + number with aneurysms × 0.8 in 25 arterial regions. The median CARDS was higher in TAK than GCA (4.1 and 0.6, interquartile range 1.3-5.7 and 0-3, p<0.001). CONCLUSIONS: We have developed a damage assessment tool, CARDS, based on imaging in LVV of potential value to clinical studies and patient management. TAK and GCA differ in the radiologic severity of disease.

The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study.

BACKGROUND: Giant cell arteritis (GCA) is a relatively common form of primary systemic vasculitis, which, if left untreated, can lead to permanent sight loss. We compared ultrasound as an alternative diagnostic test with temporal artery biopsy, which may be negative in 9-61% of true cases. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of ultrasound with biopsy in diagnosing patients with suspected GCA. DESIGN: Prospective multicentre cohort study. SETTING: Secondary care. PARTICIPANTS: A total of 381 patients referred with newly suspected GCA. MAIN OUTCOME MEASURES: Sensitivity, specificity and cost-effectiveness of ultrasound compared with biopsy or ultrasound combined with biopsy for diagnosing GCA and interobserver reliability in interpreting scan or biopsy findings. RESULTS: We developed and implemented an ultrasound training programme for diagnosing suspected GCA. We recruited 430 patients with suspected GCA. We analysed 381 patients who underwent both ultrasound and biopsy within 10 days of starting treatment for suspected GCA and who attended a follow-up assessment (median age 71.1 years; 72% female). The sensitivity of biopsy was 39% [95% confidence interval (CI) 33% to 46%], which was significantly lower than previously reported and inferior to ultrasound (54%, 95% CI 48% to 60%); the specificity of biopsy (100%, 95% CI 97% to 100%) was superior to ultrasound (81%, 95% CI 73% to 88%). If we scanned all suspected patients and performed biopsies only on negative cases, sensitivity increased to 65% and specificity was maintained at 81%, reducing the need for biopsies by 43%. Strategies combining clinical judgement (clinician's assessment at 2 weeks) with the tests showed sensitivity and specificity of 91% and 81%, respectively, for biopsy and 93% and 77%, respectively, for ultrasound; cost-effectiveness (incremental net monetary benefit) was £485 per patient in favour of ultrasound with both cost savings and a small health gain. Inter-rater analysis revealed moderate agreement among sonographers (intraclass correlation coefficient 0.61, 95% CI 0.48 to 0.75), similar to pathologists (0.62, 95% CI 0.49 to 0.76). LIMITATIONS: There is no independent gold standard diagnosis for GCA. The reference diagnosis used to determine accuracy was based on classification criteria for GCA that include clinical features at presentation and biopsy results. CONCLUSION: We have demonstrated the feasibility of providing training in ultrasound for the diagnosis of GCA. Our results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy. The moderate interobserver agreement for both ultrasound and biopsy indicates scope for improving assessment and reporting of test results and challenges the assumption that a positive biopsy always represents GCA. FUTURE WORK: Further research should address the issue of an independent reference diagnosis, standards for interpreting and reporting test results and the evaluation of ultrasound training, and should also explore the acceptability of these new diagnostic strategies in GCA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Disease assessment in systemic vasculitis.

The anti-neutrophil cytoplasm antibody-associated vasculitides are complex multi-system disorders with many overlapping clinical features. Their outcome has been transformed by effective immunosuppression, preventing death in over 70% of cases. The quality of survival is affected by the disease course, which is characterized by a significant likelihood of relapse in 38%, chronic effects from the disease and its treatment, as well as emerging or worsening comorbidity, all of which contribute to the patient's clinical condition and outcome. Whilst imaging and laboratory testing including histology are important aspects of diagnosis, they are of limited value in assessing response to therapy or subsequent disease course. We have developed standardized validated clinical methods to quantify disease activity and damage; we are developing effective measures of patient experience to complement these procedures. This approach provides a rational basis for clinical management as well as being essential in the conduct of clinical trials and studies in vasculitis, by providing reproducible definitions of relapse, remission and response to therapy for patients with systemic vasculitis. Clinical assessment remains the current gold standard for evaluating disease progress, but requires regular training to ensure standardization. The development of biomarkers in future may produce a more accurate description of disease and identify potential targets for therapy as well as predictors of response to drugs.

Rituximab in combination with corticosteroids for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis: a NICE single technology appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of rituximab (Roche Products) to submit evidence of the clinical and cost effectiveness of rituximab in combination with corticosteroids for treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the manufacturer's submission to NICE. The evidence was derived mainly from a double-blind, phase III, placebo-controlled trial of rituximab in patients with new or relapsed 'severe' AAV, which compared a rituximab treatment regimen with an oral cyclophosphamide treatment regimen. Intravenous cyclophosphamide is also commonly used but was not included in the pivotal trial. The evidence showed that rituximab is noninferior to oral cyclophosphamide in terms of induction of remission in adults with AAV and de novo disease, and is superior to oral cyclophosphamide in terms of remission in adults who have relapsed once on cyclophosphamide. The ERG concluded that the results of the manufacturer's economic evaluation could not be considered robust, because of errors and because the full range of relevant treatment sequences were not modelled. The ERG amended the manufacturer's model and demonstrated that rituximab was likely to represent a cost-effective addition to the treatment sequence if given after cyclophosphamide treatment.

Is rheumatoid factor useful in primary care? A retrospective cross-sectional study.

Rheumatoid factor (RF) is frequently tested in general practice where its utility as a diagnostic test for rheumatoid arthritis (RA) is not known. We undertook a retrospective cross-sectioal study to determine the utility and cost of RF in a primary care population. We compared RF with recorded clinical features based on the American College of Rheumatology (ACR) criteria as a diagnostic test for RA in 235 patients in general practice using receiver operating characteristic curves and calculated the cost of testing per case of RA. We analysed 36,191 RF requests made to one laboratory from 2003-2009 at a mean annual cost of £58,164 and the variation and annual cost of RF testing between 77 practices. The sensitivity and specificity of RF at the optimal cut-off value of 20 U/ml were 0.6 and 0.96 and that of two documented clinical ACR criteria were 0.9 and 0.92, respectively. No ACR criteria were documented in 150 (63.8%) patients who had RF tested. The overall cost of RF testing per case of seropositive RA was £708.75. Of all RF requests, 66.6% was made by GPs, 7.0% by rheumatologists and 26.4% by other hospital departments. The proportion of positive tests was 5.8% in primary care and 17.7% in rheumatology. The mean number of tests performed annually in primary care was 4.65 (SD 2.7) per 1,000 patients. RF is less sensitive for RA than clinical features in primary care and is frequently requested in cases without clinical evidence of the disease, adding to the overall cost.

Disease activity assessment in childhood vasculitis: development and preliminary validation of the Paediatric Vasculitis Activity Score (PVAS).

BACKGROUND: Rare chronic childhood vasculitides lack a reliable disease activity assessment tool. With emerging new treatment modalities such a tool has become increasingly essential for both clinical practice and therapeutic trials to reproducibly quantify change in disease state. OBJECTIVE: To develop and validate a paediatric vasculitis activity assessment tool based on modification of the Birmingham Vasculitis Activity Score (BVASv.3). METHODS: A paediatric vasculitis registry was reviewed to identify clinical features missing in the BVASv.3. A modified nominal group technique was used to develop a working version of the Paediatric Vasculitis Activity Score (PVAS). Prospective validation provided tool reliability, reproducibility and responsiveness to change. Training of assessors was done according to the BVAS principles. RESULTS: BVAS items were redefined (n=22) and eight paediatric items added in Cutaneous (n=4), Cardiovascular (n=3) and Abdominal (n=1) sections. The final PVAS has 64 active items in nine categories. The principles of new/worse and persistently active disease were retained as were the overall score and weighting of categories. The median PVAS in 63 children with systemic vasculitis was 4/63 (0-38/63). There was a high interobserver agreement for the overall as well as for subsystem scores (linear-weighted-κ ≥0.87). PVAS correlated with physician's global assessment (p<0.01); treatment decision (p=<0.01) and erythrocyte sedimentation rate (ESR) (p=0.01). In response to treatment, 15/19 patients assessed demonstrated a significant fall in PVAS (p=0.002), with good agreement among assessors for this change. CONCLUSIONS: The PVAS validity in children with systemic vasculitis was demonstrated. Like the BVAS, we anticipate that the PVAS will provide a robust tool to objectively define disease activity for clinical trials and future research.

Damage assessment in ANCA-associated vasculitis.

Antineutrophil cytoplasm antibody associated vasculitis has been transformed from life-threatening conditions to chronic relapsing long-term diseases as a result of significant advances in immunosuppressive therapy. Although mortality still occurs, it is much less frequent, with an average 5-year survival of over 70 %. In the setting of chronic conditions, it becomes increasingly important to monitor the burden of disease in terms of both active inflammation requiring immunosuppression and chronic damage (scarring) from vasculitis and its treatment and associated comorbidity. The damage that accumulates in patients with vasculitis does not respond to immunosuppressive treatment. It is important to distinguish disease activity from disease damage to prevent unnecessary immunosuppression, but it is equally important to recognize damage for what it is, so that it can be addressed appropriately. Damage is an inevitable consequence of long-term vasculitis for over 80 % of patients, which should not surprise us given the severity of the original illness. There is potential value in measuring damage as a means of providing prognostic information. Using a quantified score such as the Vasculitis Damage Index (VDI) allows us to predict mortality. Patients with at least five items of damage on the VDI score have substantially worse mortality (7- to 11-fold worse risk), as compared with those with lesser amounts of damage. These findings should be taken into context when planning the management of patients with vasculitis, as well as in clinical trials of vasculitis. Disease damage is an important surrogate for long-term outcome in vasculitis, and studies should be designed to limit the amount of damage accumulating as a result of therapeutic intervention, rather than simply controlling disease activity, as is currently the aim in recent randomized controlled trials in vasculitis. Furthermore, careful cataloguing of damage, as well as disease activity items, provides much greater detail in describing and observing the long-term natural history of primary systemic vasculitis in patients treated with immunosuppressive agents who survive their initial disease process.

Performance of Birmingham Vasculitis Activity Score and disease extent index in childhood vasculitides.

OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS: The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS: This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.

Time to focus on outcome assessment tools for childhood vasculitis.

Childhood systemic vasculitides are a group of rare diseases with multi-organ involvement and potentially devastating consequences. After establishment of new classification criteria (Ankara consensus conference in 2008), it is now time to establish measures for proper definition of activity and damage in childhood primary vasculitis. By comparison to adult vasculitis, there is no consensus for indices of activity and damage assessment in childhood vasculitis. Assessment of disease activity is likely to become a major area of interest in pediatric rheumatology in the near future. After defining the classification criteria for primary systemic childhood vasculitis, the next step was to perform a validation study using the original Birmingham vasculitis activity score as well as the disease extent index to measure disease activity in childhood vasculitis. Presently, there are efforts in place to develop a pediatric vasculitis activity score. This paper reviews the current understanding about the assessment tools (i.e., clinical features, laboratory tests, radiologic assessments, etc.) widely used for evaluation of the disease activity and damage status of the children with vasculitis.

Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index.

OBJECTIVES: To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis. METHODS: A total of 283 patients with vasculitis from 11 European centres were evaluated in a cross-sectional study using the VDI and CDA. RESULTS: Wegener's granulomatosis (58.4%) and microscopic polyangiitis (11.0%) were the most common diagnoses. Agreement between VDI and CDA scores (Spearman's correlation) was 0.90 (95% CI 0.87 to 0.92). There was good correlation between individual comparably evaluated organ systems (Spearman's correlation 0.70-0.94). Interobserver reliability (assessed by intraclass correlation coefficient (ICC)) was 0.94 (95% CI 0.89 to 0.98) for VDI and 0.78 (95% CI 0.63 to 0.93) for CDA. Intraobserver reliability was 0.92 (95% CI 0.83 to 1.00) for VDI and 0.87 (95% CI 0.75 to 1.00) for CDA. A total of 13 items were not used in the VDI compared to 23 in the CDA. Observers agreed that the CDA covered the full spectrum of damage attributable to vasculitis but was more time consuming and thus possibly less feasible for clinical and research purposes. CONCLUSIONS: The VDI and CDA capture reliable data on damage among patients with vasculitis. The CDA captures more detail but is more complex and less practical than the VDI. Further evolution of damage assessment in vasculitis is likely to include key elements from both instruments.

Assessment of damage in vasculitis: expert ratings of damage.

OBJECTIVES: Current measures of damage in vasculitis do not account for the possibility that some forms of damage may exert greater impact than others. As part of an international effort to revise how damage is quantified in vasculitis clinical research, an exercise was performed to measure expert ratings of damage items. METHODS: Members of the Vasculitis Clinical Research Consortium and European Vasculitis Study Group were given a list of 129 items of damage related to WG and microscopic polyangiitis (MPA). Participants were asked to rate each item of damage on an integer scale from 0 to 10, where 10 represented the most severe form of damage and 0 indicated 'no impact'. RESULTS: A multidisciplinary panel of 50 investigators from North America, Europe and Australia-New Zealand participated. The highest median ratings (8-10) were assigned to items of damage associated with malignancy, tissue ischaemia, the central nervous system and cardiopulmonary manifestations. The mean scores ranged from 1.3 to 9.5. The highest s.d.s (>or=2.5) were associated with forms of damage that may benefit from surgical intervention or may not be causally associated with WG or MPA. Lower scores were assigned by nephrologists in comparison with rheumatologists and by Americans in comparison to Europeans, although the difference in median ranks used by these groups was not statistically significant (P > 0.05 for the comparisons). CONCLUSIONS: This exercise represents an important step in the development of a weighting system that may increase the utility of damage index scores for the assessment of patients with vasculitis.

Assessment of systemic vasculitis.

The systemic vasculitides are an uncommon group of autoimmune diseases capable of causing multi organ failure and death. Current immunosuppressive strategies have substantially improved the outcome, but the natural history of treated disease is unstable, typically characterised by frequent relapses, drug toxicity and an increasing burden of damage. Early diagnosis, accurate staging and regular evaluation of disease status are important in the management of the vasculitides. Clinical evaluation tools have been developed and provide a comprehensive assessment of patients. Serological markers, especially anti-neutrophil cytoplasm antibody (ANCA), pathology and imaging investigations are a useful addition, but are more valuable in diagnosis rather than monitoring of disease activity. Advances in magnetic resonance imaging in large vessel vasculitis have improved our ability to characterise disease and may lead to earlier diagnosis and better control in future. Development of new biomarkers is required in vasculitis, and this is likely to advance our understanding as well as the management of these complex conditions.