Validating a diagnostic GCA ultrasonography service against temporal artery biopsy and long-term clinical outcomes.

Currently, there is no mechanism for service validation of diagnostic ultrasonography (US) for giant cell arteritis (GCA). Temporal artery biopsy (TAB) and classification criteria are poor benchmarks. We validated our service against physician-verified diagnosis at 100 weeks (100wD). Twenty-five patients underwent US within 7 days, and TAB within 28 days, of commencing prednisolone. US, TAB and baseline diagnosis (bD) were all compared with 100wD using Cohen's kappa. Fourteen US and 8 TABs were positive. Twenty at baseline and 14 at 100 weeks had diagnosis of GCA. The kappa (95% CI) were 0.4 (0.1, 0.7) for US vs. TAB; 0.5 (0.2, 0.8) for US vs. bD and 0.2 (0.0, 0.4) for TAB vs. bD. Versus 100wD, the kappa (95% CI) were 0.8 (0.6, 1.0) for US; 0.4 (0.1, 0.7) for TAB and 0.6 (0.3, 0.9) for bD. Seven cases were US+/TAB-. Four had alternate confirmation: 18FDG-PET (n = 1), CT Aorta (n = 1) and US at relapse (n = 2). At 100 weeks, 4 cases (all US-/TAB-) with bD of GCA had alternative diagnoses including cancer (n = 2). This is the first study validating US service provision for GCA. Twenty-five US with a robust kappa on comparison with long-term diagnosis validates our service. A diagnosis of GCA should be made with extreme caution for US-/TAB- cases.Key Points• This is the first study offering a way to validate a new diagnostic US service by validation against TAB and long-term physician-verified diagnosis.• US has substantial to near-perfect agreement with long-term physician-verified diagnosis and is more reliable than TAB in our hands.• Alternative diagnoses should be sought in patients with dual negativity for US and TAB.

Vasculitis and inflammatory arthritis.

Vasculitis has been described in most types of inflammatory arthritis. The best described and most widely recognised form is rheumatoid vasculitis. The incidence of systemic rheumatoid vasculitis has declined significantly following the general early use of methotrexate in the 1990s, and it is now a rare form of vasculitis. Treatment of rheumatoid vasculitis is conventionally with glucocorticoids and cyclophosphamide, but there is an increasing role for rituximab similar to that in other types of vasculitis. Despite these developments the mortality of rheumatoid vasculitis remains high. Vasculitis in other types of inflammatory arthritis is less well described and the treatment remains empirical.

Optimizing Methotrexate Treatment in Rheumatoid Arthritis: The Case for Subcutaneous Methotrexate Prior to Biologics.

Methotrexate is the most common disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA). Current evidence supports its efficacy in the treatment of RA, resulting in improved short-term disease control and long-term outcomes in terms of radiographic progression. Oral methotrexate has traditionally been used first-line due to various reasons, including ease of administration, low cost and easy availability. A methotrexate dose of >15 mg/week is generally required for disease control but oral methotrexate may be only partially effective or poorly tolerated in some patients. The rationale for using subcutaneous (SC) methotrexate is based on its improved bioavailability at higher doses and better tolerability in some patients who have side effects when receiving oral methotrexate. Current guidance advocates 'treating to target', with the aim of inducing remission in RA patients. In some patients, this can be achieved using methotrexate alone or in combination with other traditional DMARDs. Patients who have not responded to two DMARDs, including methotrexate, are eligible for biological therapy as per current National Institute for Health and Care Excellence (NICE) guidance in the UK. Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment.

The outcome and cost-effectiveness of nurse-led care in the community for people with rheumatoid arthritis: a non-randomised pragmatic study.

OBJECTIVE: To determine the outcome and cost-effectiveness of nurse-led care in the community for people with rheumatoid arthritis (RA). DESIGN: Non-randomised pragmatic study. SETTING: Primary (7 primary care practices) and secondary care (single centre) in the UK. METHODS: In a single area, pragmatic non-randomised study, we assessed the outcome, cost-effectiveness of community-based nurse-led care (NLC) compared with rheumatologist-led outpatient care (RLC). Participants were 349 adults (70% female) with stable RA assessed at baseline, 6 and 12 months. In the community NLC arm there were 192 participants. Outcome was assessed using Stanford Health Assessment Questionnaire (HAQ). The economic evaluation (healthcare perspective) estimated cost relative to change in HAQ and quality-adjusted life years (QALY) derived from EQ-5D-3L. We report complete case and multiple imputation results from regression analyses. RESULTS: The demographics and baseline characteristics of patients in the community group were comparable to those under hospital care apart from use of biological disease-modifying antirheumatic drugs (DMARDS), which were adjusted for in the analysis. The mean incremental cost was estimated to be £224 less for RLC compared to the community NLC, with wide CIs (CI -£213 to £701, p=0.296). Levels of functional disability were not clinically significantly higher in the community NLC group: HAQ 0.096 (95% CI -0.026 to 0.206; p=0.169) and QALY 0.023 (95% CI -0.059 to 0.012; p=0.194). CONCLUSIONS: The results suggest that community care may be associated with non-significant higher costs with no significant differences in clinical outcomes, and this suggests a low probability that it is cost-effective.

Systemic rheumatoid vasculitis in the era of modern immunosuppressive therapy.

OBJECTIVES: Systemic rheumatoid vasculitis (SRV) is a rare but potentially serious systemic disease manifestation of rheumatoid arthritis (RA) characterized by the development of necrotizing vasculitis. The incidence of SRV appears to be decreasing possibly reflecting progress in RA treatment. The aims of this study were to review the clinical manifestations of SRV in a stable well-defined population during 2001-10 and to compare with our previous cohort (1988-2000) and also a cohort from 1975 to 1981. METHODS: Using Norfolk Vasculitis Register, a prospective register of patients with systemic vasculitis since 1988, all patients with a diagnosis of SRV from 1 January 2001 until 31 December 2010 were identified. SRV was defined according to the Scott and Bacon criteria (1984). Clinical features were obtained by retrospective case note review. RESULTS: Eighteen patients with SRV were identified (10 male), median age at diagnosis was 72 years and average disease duration 15.6 years. The average annual incidence for 2001-10 was 3.9 per million. One-year mortality was 12% and 5-year mortality 60%. The clinical manifestations were similar apart from systemic and cutaneous features which were more common in the earlier cohorts. CONCLUSION: The incidence of SRV has declined significantly in the last 40 years; but the clinical manifestations remain similar. Systemic symptoms, and cutaneous manifestations such as infarcts and nodules, are slightly less common in the recent cohort. Despite modern immunosuppressive therapy the prognosis remains poor.

Epidemiology and clinical features of systemic vasculitis.

Different vasculitic syndromes present in different age groups. Immunoglobulin (Ig)A vasculitis and Kawasaki disease usually present in children whereas giant cell arteritis (GCA) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually present in the middle aged/elderly. In Northern Europe, granulomatosis with polyangiitis (GPA; Wegener's) is commoner than microscopic polyangiitis (MPA) and MPA is more common than eosinophilic granulomatosis with polyangiitis (EPGA; Churg-Strauss syndrome). In Southern Europe, MPA is commoner than GPA and in Japan MPA is much more common than GPA. Major differences exist worldwide in ANCA specificity which are not entirely related to different phenotypes. GPA, like GCA, has a cyclical pattern of onset suggesting possible infection as an aetiological agent. International studies have given important clues to possible aetiology including silica dust and infection and genetic influences, as shown by the recently published genome-wide association study which revealed that single-nucleotide polymorphisms associate more strongly with ANCA than clinical syndromes. A brief description of the main clinical features of ANCA-associated vasculitis is also given.

Voice symptoms in patients with autoimmune disease: a cross-sectional epidemiological study.

OBJECTIVE: To assess the prevalence and severity of voice symptoms in individuals with a diagnosis of autoimmune disease. STUDY DESIGN: Cross-sectional survey. SETTING: Study participants were recruited from a rheumatology tertiary referral clinic at Norfolk and Norwich University Hospital. SUBJECTS AND METHODS: A cross-sectional questionnaire analyzing 109 patients with autoimmune disease (rheumatoid arthritis, seronegative spondyloarthritis, connective tissue disease) and a control group of 41 patients with non-autoimmune disease (osteoarthritis/osteoporosis). Main outcome measures were the Voice Handicap Index-10 (VHI-10), xerostomia scale, acid reflux inquiry, and anxiety/depression scale. RESULTS: Patients with autoimmune disease were more likely to experience voice symptoms as assessed by the VHI-10 questionnaire (P = .0035). Subgroup analysis showed autoimmune patients were more likely to report voice symptoms regardless of whether they were on a disease-modifying antirheumatic drug (DMARD; P = .0010) or non-DMARD (P = .017), suggesting autoimmune disease may be an independent risk factor from pharmacotherapy. Xerostomia was more common in an autoimmune population compared with the control group (P = .02). A positive correlation between xerostomia and VHI-10 scores was found for the DMARD group (Spearman rank coefficient = 0.49, P < .001). No significant difference in acid reflux inquiry (P = .44) or the anxiety/depression scale (P = .36) was found when comparing the autoimmune and control groups. CONCLUSION: Patients with autoimmune disease have increased likelihood of voice symptoms when compared with a control population with non-autoimmune disease. Further prospective studies to elucidate the cause of voice disorder would be valuable.

An evaluation of rheumatology practitioner outreach clinics: a qualitative study.

BACKGROUND: Services for Rheumatoid Arthritis (RA) have evolved with the development of independently led outreach Rheumatology Practitioner (RP) clinics in Primary Care (PC). Their clinical and cost effectiveness, compared with Secondary Care (SC) services, has not been assessed. The RECIPROCATE study aims to evaluate their clinical and cost effectiveness. This part of the study aimed to explore health professionals' opinions of rheumatology outreach service. METHODS: Using a qualitative design, semi-structured interviews were conducted with GPs, practice nurses, hospital doctors and RPs, from one hospital and seven PC practices in Norfolk, to elicit their opinions of the service. The interviews were analysed using thematic analysis. RESULTS: All participants agreed the service was supportive and valuable providing high quality personalised care, disease management, social, and educational support. Advantages identified included convenience, continuity of care and proximity of services to home. RPs helped bridge the communication gap between PC and SC. Some participants suggested having a doctor alongside RPs. The service was considered to be cost effective for patients but there was uncertainty about cost effectiveness for service providers. Few disadvantages were identified the most recurring being the lack of other onsite services when needed. It was noted that more services could be provided by RPs such as prescribing and joint injections as well as playing a more active role in knowledge transfer to PC. CONCLUSIONS: Professionals involved in the care of RA patients recognised the valuable role of the RP outreach clinics. This service can be further developed in rheumatology and the example can be replicated for other chronic conditions.

The contrasting epidemiology of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis.

OBJECTIVES: Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are uncommon and have unknown aetiology. The aim of the study was to investigate the epidemiology of GPA and MPA in a stable, well-defined population looking for differences in the pattern of occurrence, which might suggest a different aetiology. METHODS: Since 1988, we have maintained a prospective register of all patients with systemic vasculitis attending the Norfolk and Norwich University Hospital. Patients presenting with new-onset GPA and MPA as defined by the European Medicines Agency algorithm and registered with general practitioners in the former Norwich Health Authority area between 1988 and 2010 were identified. The population in 2008 was estimated to be 459 000 (221 000 males). RESULTS: One hundred and eleven GPA and 58 MPA incident cases were identified during 1988-2010. The overall annual incidence of GPA and MPA was 11.3/million and 5.9/million, respectively. There was evidence of a cyclical pattern of occurrence with a periodicity of 7.6 years for GPA with a peak incidence of 28.3/million in 2005 and the lowest in 2002 (2.2/million). Other lesser peaks occurred in 1990 and 1996. While the peak incidence of MPA was in 2008 (15.2/million), there was no convincing evidence of periodicity. The incidence of cANCA/PR3- or pANCA/MPO-positive vasculitis showed a similar pattern to GPA and MPA, respectively. CONCLUSION: This study lends support to the notion that the aetiology of GPA and MPA may be distinct conditions with different aetiologies. The cyclical incidence of GPA is possibly an indication for the influence of infection.

Recommendations for the use of rituximab in anti-neutrophil cytoplasm antibody-associated vasculitis.

OBJECTIVES: To perform a literature review and develop recommendations for the use of rituximab in ANCA-associated vasculitis. METHODS: A committee of experts (five rheumatologists, five nephrologists and one paediatrician) conducted a modified Delphi exercise to identify five topics for a systematic literature search. The evidence was then reviewed, categorized according to international criteria and assimilated to form five recommendations statements and a research agenda. RESULTS: Forty-three studies met the review criteria. These included two randomized controlled trials and a predominance of small, uncontrolled series. In refractory ANCA-associated vasculitis, remission rates of >80% are obtained with rituximab. In newly diagnosed disease, rituximab is at least as effective as conventional therapy. Fifteen recommendations were made. Their strength was restricted by the low quality of the evidence. Six areas for future research were identified. CONCLUSION: On the basis of the available evidence and expert consensus, recommendations have been made for the use of rituximab as a treatment of ANCA-associated vasculitis. Further questions, in particular regarding long-term outcomes, remain to be explored.

Comparison of the epidemiology of anti-neutrophil cytoplasmic antibody-associated vasculitis between Japan and the U.K.

OBJECTIVES: The epidemiological manifestations of ANCA-associated vasculitis (AAV) differ geographically. However, there have been no prospective studies comparing the incidence of AAV between Japan and Europe over the same time period using the same case definitions. METHODS: The incidence of AAV was determined by a population-based method in Miyazaki prefecture, Japan, and Norfolk, U.K., between 2005 and 2009. Patients with AAV were defined and classified according to the European Medicines Agency (EMEA) algorithm. RESULTS: The number of incident cases of AAV in Japan and the U.K. were 86 and 50, respectively, and the average annual incidence over the 5-year period was 22.6/million (95% CI 19.1, 26.2) and 21.8/million (95% CI 12.6, 30.9) in Japan and the U.K., respectively. The average age was higher in patients in Japan than in patients in the U.K. [mean (median), 69.7 (72) vs. 60.5 (61) years]. Microscopic polyangiitis (MPA) was the predominant subtype in Japan (83%), while granulomatosis with polyangiitis (Wegener's) was more frequent in the U.K. (66%). As for the pattern of ANCA positivity, >80% of Japanese patients were pANCA/MPO positive, whereas two-thirds of U.K. patients were cANCA/PR3 positive. Renal involvement in MPA was very common in both countries, but was much less common in granulomatosis with polyangiitis in Japan compared with the U.K. CONCLUSION: There was no major difference in AAV incidence between Japan and the U.K., but this prospective study found MPA and MPO-ANCA to be more common in Japan and granulomatosis with polyangiitis and PR3-ANCA to be more common in the U.K., in line with earlier reports.

In patients with early inflammatory polyarthritis, ACPA positivity, younger age and inefficacy of the first non-biological DMARD are predictors for receiving biological therapy: results from the Norfolk Arthritis Register.

OBJECTIVES: To identify baseline disease-related predictors in patients with early inflammatory polyarthritis (IP) for starting subsequent biological therapy and to determine if patients who failed their first non-biological disease-modifying antirheumatic drug (DMARD) within 6 months were more likely to need biological therapy. METHODS: Patients with early IP recruited between 1990 and 1994 (cohort 1) and between 2000 and 2004 (cohort 2) in the Norfolk Arthritis Register were included in this study. The association between possible predictors with the start of biological therapy was assessed using Cox proportional hazards regression models. RESULTS: 32/407 (7.9%) patients in cohort 1 and 45/416 (10.8%) patients in cohort 2 received biological therapy during follow-up. In both cohorts, anti-citrullinated protein antibody (ACPA) positivity (cohort 1, HR 7.62, 95% CI 2.46 to 23.58; cohort 2, HR 4.68, 95% CI 2.23 to 9.78) was the strongest predictor for starting biological therapy. In cohort 2, younger patients (HR 0.97, 95% CI 0.95 to 0.99) and patients who failed their first non-biological DMARD within 6 months due to inefficacy were also more likely to receive biological therapy (HR 2.35, 95% CI 1.05 to 5.27). CONCLUSION: Patients with early IP who are ACPA positive, are younger or who fail their first non-biological DMARD due to inefficacy within 6 months are more likely to need biological therapy.

Epidemiology of ANCA-associated vasculitis.

The epidemiology of the antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), comprising Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, poses considerable challenges to epidemiologists. These challenges include the difficulty of defining a case with a lack of clear distinction between the different disorders, case capture, and case ascertainment. The AAV are rare and therefore a large population is required to determine the incidence and prevalence, and this poses questions of feasibility. Despite these difficulties a considerable body of data on the epidemiology of the AAV has been built in the past 20 years with an interesting age, geographic, and ethnic tropism gradually being revealed. Most of the data come from White populations of European descent, and the overall annual incidence is estimated at approximately 10-20/million with a peak age of onset in those aged 65 to 74 years.