Abstract
Objectives
Temporal artery biopsy (TAB) is a reference test for the diagnosis of GCA but reveals inflammatory changes only in a subset of patients. The lack of knowledge of TAB sensitivity ...hampers comparisons with non-invasive techniques such as temporal artery ultrasonography. We performed a systematic literature review and meta-analysis to estimate the sensitivity of TAB in GCA and to identify factors that may influence the estimate.
Methods
A systematic literature review involved searching electronic databases and cross-references. Eligibility criteria included publications reporting at least 30 GCA cases fulfilling the original or modified 1990 ACR classification criteria. The pooled proportion of TAB-positive GCA cases was calculated by using aggregated-data meta-analysis with a random-effects model and assessment of heterogeneity with the I2 statistic. Subgroup analyses and meta-regression were used to examine the effect of patient and study characteristics on TAB positivity.
Results
Among 3820 publications screened, 32 studies (3092 patients) published during 1993–2017 were analysed. The pooled proportion of TAB-positive GCA cases was 77.3% (95% CI: 71.8, 81.9%), with high between-study heterogeneity (I2 = 90%). The proportion of TAB-positive cases was slightly higher in publications before than in 2012 and after (P = 0.001).
Conclusion
The estimated sensitivity of 77% provides indirect evidence that TAB is not less sensitive than temporal artery imaging. The unexplained high between-study heterogeneity could result from differences in TAB sampling, processing or interpretation. The decrease in TAB-positive GCA cases over time could reflect an increasing propensity for clinicians to accept a GCA diagnosis without proof by TAB.
The spondyloarthropathies comprise ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis (PsA) and arthritis associated with inflammatory bowel disease. In this Perspectives article, ...we describe how Behçet disease and several clinically distinct spondyloarthropathies-all associated with MHC class I (MHC-I) alleles such as HLA-B(*)51, HLA-C(*)0602 and HLA-B(*)27 and epistatic ERAP-1 interactions-have a shared immunopathogenetic basis. As a unifying concept, we propose that barrier dysfunction in environmentally exposed organs such as the skin, and aberrant innate immune reactions at sites of mechanical stress, can often trigger secondary adaptive immune CD8(+) T-cell responses with prominent neutrophilic inflammation that culminate in exacerbation and recurrence of these diseases. Of note, these 'MHC-I-opathies' show a differential immunopathology, probably reflecting antigenic differences within target tissues: HLA-B(*)51 is linked to ocular and mucocutaneous disease but not gut involvement, and HLA-C(*)0602 is linked to type I psoriasis but not scalp or nail disease.
Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and ...cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.
Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.
Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.
We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the ...light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.
Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been ...published that have the potential to change clinical care and support the need for an update.
Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations.
Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV.
In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
Objective. The value of repeated ANCA measurements among patients with an established diagnosis of ANCA-associated vasculitis (AAV) remains controversial. The aim of this study was to explore whether ...either of the two distinct patterns of ANCA values during remission, a rise in ANCA or persistently positive ANCA, predicted future relapse.
Methods. MEDLINE and EMBASE searches were performed. Studies with at least 10 subjects with AAV from which both sensitivity and specificity of a rise in ANCA and/or persistent ANCA for future disease relapse could be calculated were included. Likelihood ratios were calculated for each study and pooled to arrive at summary estimates. I
2-values were calculated as a measure of heterogeneity and meta-regression was used to explore sources of heterogeneity.
Results. Nine articles on a rise in ANCA and nine articles on persistent ANCA were included. The summary estimates for positive likelihood ratio (LR+) and negative likelihood ratio (LR−) of a rise in ANCA during remission on subsequent relapse of disease were 2.84 (95% CI 1.65, 4.90) and 0.49 (95% CI 0.27, 0.87), respectively. The summary estimates for LR+ and LR− of persistent ANCA during remission for subsequent disease relapse were 1.97 (95% CI 1.43, 2.70) and 0.73 (95% CI 0.50, 1.06), respectively. There was substantial between-study heterogeneity, which was partially explained by the frequency of ANCA measurements.
Conclusion. Among patients with AAV, a rise in or persistence of ANCA during remission is only modestly predictive of future disease relapse. There is limited use to serial ANCA measurements during disease remission to guide treatment decisions for individual patients with AAV.
Abstract
Background
Surveys of Behçet's disease (BD) have shown substantial geographic variations in prevalence, but some of these differences may result from methodological inconsistencies. This ...meta-analysis explored the effect of geographic location and study methodology on the prevalence of BD.
Methods
We systematically searched the literature in electronic databases and by handsearching to identify population-based prevalence surveys of BD. Studies were eligible if they provided an original population-based prevalence estimate for BD with the number of prevalent cases identified in the study area. Pooled prevalence proportions across all studies were computed by using random effects models based on a Poisson normal distribution. Pre-defined subgroup analyses and meta-regression were used to investigate the effect of covariates on the prevalence proportions.
Results
We included 45 reports published from 1974 to 2015 and covering worldwide areas. The pooled estimates of prevalence proportions (expressed as cases/100 000 inhabitants) were 10.3 (95% CI 6.1, 17.7) for all studies and 119.8 (59.8, 239.9) for Turkey, 31.8 (12.9, 78.4) for the Middle East, 4.5 (2.2, 9.4) for Asia and 3.3 (2.1, 5.2) for Europe. Subgroup analyses showed a strikingly greater prevalence for studies with a sample survey design than a census design 82.5 (95% CI 47.3, 143.9) vs 3.6 (2.6, 5.1). Metaregression identified study design as an independent covariate significantly affecting BD prevalence proportions.
Conclusions
Differences in BD prevalence proportions likely reflect a combination of true geographic variation and methodological artefacts. In particular, use of a sample or census study design may strongly affect the estimated prevalence.
The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitides. However, even when patients receive ...maintenance treatment with azathioprine or methotrexate, the relapse rate remains high. Rituximab may help to maintain remission.
Patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were randomly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6, 12, and 18 after study entry or daily azathioprine until month 22. The primary end point at month 28 was the rate of major relapse (the reappearance of disease activity or worsening, with a Birmingham Vasculitis Activity Score >0, and involvement of one or more major organs, disease-related life-threatening events, or both).
The 115 enrolled patients (87 with granulomatosis with polyangiitis, 23 with microscopic polyangiitis, and 5 with renal-limited ANCA-associated vasculitis) received azathioprine (58 patients) or rituximab (57 patients). At month 28, major relapse had occurred in 17 patients in the azathioprine group (29%) and in 3 patients in the rituximab group (5%) (hazard ratio for relapse, 6.61; 95% confidence interval, 1.56 to 27.96; P=0.002). The frequencies of severe adverse events were similar in the two groups. Twenty-five patients in each group (P=0.92) had severe adverse events; there were 44 events in the azathioprine group and 45 in the rituximab group. Eight patients in the azathioprine group and 11 in the rituximab group had severe infections, and cancer developed in 2 patients in the azathioprine group and 1 in the rituximab group. Two patients in the azathioprine group died (1 from sepsis and 1 from pancreatic cancer).
More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine. (Funded by the French Ministry of Health; MAINRITSAN ClinicalTrials.gov number, NCT00748644; EudraCT number, 2008-002846-51.).
Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of ...patients with ANCA associated vasculitis treated with current regimens is uncertain.
To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease.
Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models.
The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age- and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate <15 ml/min, advancing age, higher Birmingham Vasculitis Activity Score, lower haemoglobin and higher white cell count were significant negative prognostic factors for patient survival.
Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
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