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.
There are few data on clinical profiles of ANCA-associated vasculitis (AAV) in different ethnic populations. The aim of this study was to examine the differences in the ANCA type and clinical ...features of AAV between populations using the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) dataset.
The DCVAS is an international, multicentre, observational study recruiting in 133 sites. Eight ethnic categories were analysed: Northern European, Caucasian American, Southern European, Middle Eastern/Turkish, Chinese, Japanese, Indian subcontinent and other. ANCA type was categorized as myeloperoxidase (MPO), PR3 and ANCA negative. Organ system involvement was recorded using a standard dataset. Differences were analysed by chi-squared tests using a Bonferroni correction and logistic regression (adjusting for age and sex). Northern European was the reference population.
Data from 1217 patients with AAV were available and the 967 (79.5%) patients recruited by rheumatology departments were analysed to reduce confounding by recruitment specialty. There were differences in ANCA type between ethnic categories (P < 0.001): MPO-ANCA was more common than PR3-ANCA in Japanese, Chinese and Southern Europeans; PR3-ANCA was more common in the other groups. Compared with Northern Europeans, Japanese had a nearly 60-fold increased chance of having MPO-ANCA (vs PR3-ANCA) odds ratio (OR) 59.2 (95% CI 8.0, 440.7), P < 0.001 and Chinese had a nearly 7-times increased chance OR 6.8 (95% CI 2.6, 17.8), P < 0.001. Ophthalmologic and otorhinolaryngologic involvement were less common in Japanese and Chinese populations than Northern Europeans; otherwise, there were few differences in organ involvement between ethnic groups.
This study confirms the previously observed differential occurrence of MPO-AAV and PR3-AAV between different ethnic groups.
Objective
Cutaneous manifestations of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and ...eosinophilic granulomatosis with polyangiitis (EGPA), are poorly characterized. This report describes the dermatologic features of AAV and their association with systemic manifestations of vasculitis.
Methods
A cross‐sectional study identifying and comparing the cutaneous manifestations of AAV was performed using data from a large, international, collaborative effort in order to collect comprehensive clinical data on patients with vasculitis.
Results
Data from 1,184 patients with AAV from 130 centers worldwide were available. Cutaneous manifestations were common in all AAV subtypes: GPA (223 of 656, or 34%), MPA (85 of 302, or 28%), and EGPA (106 of 226, or 47%). The most frequent cutaneous manifestation in AAV (all types) was petechiae/purpura, which was observed in 181 patients (15%). Allergic and nonspecific manifestations, such as pruritus, urticaria, and maculopapular rash, were more common in EGPA than in other disease subtypes (all P < 0.01). Skin biopsy, while underutilized (performed in 22–44% of patients), was frequently found to be an effective test suitable for diagnosis of AAV (diagnostic in 68–94% of patients). Compared to patients without cutaneous manifestations, those with skin lesions more frequently had severe systemic manifestations of vasculitis (such as alveolar hemorrhage and glomerulonephritis), specifically patients with GPA or EGPA and cytoplasmic/anti–proteinase 3 (anti‐PR3) ANCA–positive or ANCA‐negative patients (hazard ratio >1.9 for all), but not those with MPA or perinuclear/antimyeloperoxidase ANCAs.
Conclusion
Cutaneous manifestations are common and varied in AAV and are associated with disease severity in patients with GPA, EGPA, cytoplasmic/anti‐PR3 ANCA, or ANCA‐negative disease. These findings underscore the potential diagnostic and prognostic importance of the cutaneous examination in the evaluation and management of AAV.
Advances in diagnostic techniques have led to better distinction between types of vasculitis, potentially affecting the utility of the 1990 ACR classification criteria for vasculitis. This study ...tested the performance of these criteria in a contemporary vasculitis cohort.
The Diagnosis and Classification in Vasculitis Study provided detailed clinical, serological, pathological and radiological data from patients with primary systemic vasculitis and clinical context-specific comparator conditions. Fulfilment of six ACR criteria sets and their diagnostic performance was evaluated in patients with a given type of vasculitis and its comparator conditions.
Data from 1095 patients with primary systemic vasculitis and 415 with comparator conditions were available. For classification, sensitivities and specificities for ACR classification criteria were, respectively, 81.1% and 94.9% for GCA; 73.6% and 98.3% for Takayasu's arteritis; 65.6% and 88.7% for granulomatosis with polyangiitis; 57.0% and 99.8% for eosinophilic granulomatosis with polyangiitis; 40.6% and 87.8% for polyarteritis nodosa; 28.9% and 88.5% for microscopic polyangiitis; and 72.7% and 96.3% for IgA-vasculitis. Overall sensitivity was 67.1%. Of cases identified by their respective criteria, 16.9% also met criteria for other vasculitides. Diagnostic specificity ranged from 64.2 to 98.9%; overall, 113/415 comparators (27.2%) fulfilled at least one of the ACR classification criteria sets.
Since publication of the ACR criteria for vasculitis, the sensitivity for each type of vasculitis, except GCA, has diminished, although the specificities have remained high, highlighting the need for updated classification criteria.
To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls.
A UK General Practice Research Database (GPRD) parallel ...cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors.
Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm.
Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated.
To assess self-reported symptoms of neuropathy, disability, pain, health-related quality of life (HR-QOL), and autonomic dysfunction in patients with vasculitis.
Patients with vasculitis (with or ...without neuropathy) were invited by Vasculitis UK to complete an anonymous online survey.
312 patients (71% female) responded. Median age was 61-70 years. Median duration of vasculitis was 4 years (<2 months to > 15 years). Vasculitic types included granulomatosis with polyangiitis (34%), unspecified ANCA-associated vasculitis (13%), microscopic polyangiitis (11%), eosinophilic granulomatosis with polyangiitis (11%), giant cell arteritis (10%), non-systemic vasculitic neuropathy (2%), and other (19%). Many patients reported foot/hand symptoms suggestive of neuropathy, including numbness (64%), pain (54%), or weakness (40%). 242 patients (78%) met our definition of probable vasculitic neuropathy: diagnosis of neuropathy by vasculitis team OR numbness OR weakness in feet/hands. Only 52% had been formally diagnosed with neuropathy. Compared with 70 patients without neuropathy, neuropathy patients had greater disability measured by the inflammatory Rasch-built Overall Disability Scale (centile mean 63.1 (SD 17.3) vs 75.2 (16.7); p< 0.0001), Inflammatory Neuropathy Cause and Treatment scale (median 2 (IQR 1-4) vs 0.5 (0-2); p< 0.0001), and modified Rankin scale (median 2 (IQR 1-3) vs 2 (1-2); p= 0.0002); greater pain on an 11-point rating scale (mean 4.6 (SD 2.6) vs 3.5 (2.8); p= 0.0009); and poorer HR-QOL on the EQ5D-3L (summary index mean 0.58 (SD 0.29) vs 0.69 (0.28); p<0.0001). Two-thirds reported autonomic symptoms (not associated with neuropathy).
Neuropathy is common and associated with significant disability, pain, and impaired HR-QOL in patients with systemic vasculitis.
Abstract
Objective
To develop and explore a protocol for using colour duplex sonography (CDS) in the routine care of GCA.
Methods
We tested CDS of temporal arteries and axillary arteries (AXs) on ...consecutive patients with suspected or established GCA, between July 2014 and September 2016.
Results
We assessed 293 patients age 72 (10), female/male 196/97, of whom 118 had clinically confirmed GCA. Seventy-three percent of patients had already received high-dose glucocorticoids (GCs) for 17 (33) days. Among new referrals with <7 days of GC treatment (n = 55), the sensitivity of CDS was 63.3% (95% CI: 44%, 80%), specificity 100% (95% CI: 83%, 100%), positive predictive value 100% and negative predictive value 64.5% (95% CI: 53%, 74%). Sensitivity rose to 81.8% in patients with jaw claudication and high inflammatory markers. During the observation period, the rate of temporal artery biopsies decreased from 72 (42%) to 36 (25%) (P = 0.002). CDS was positive in 21% of 89 follow-up scans in asymptomatic individuals, compared with 37% in patients experiencing clinical flares. Over time, the number of halos reduced; only new or flaring patients showed a halo in four or more sites. The diameter of axillary halos reduced from referral 1.6 (0.4) mm to follow-up 1.4 (0.2) mm, P = 0.01 or flares 1.4 (0.2) mm, P = 0.02.
Conclusion
CDS provides high positive predictive value for diagnosing GCA and allows for a significant reduction in temporal artery biopsies. We explored the role of CDS in detecting flares and demonstrated a relationship to the extent of the distribution of halos, but not to their size.
There has been a marked increase in the past 15 years in the number and quality of clinical trials in the idiopathic inflammatory vasculitides, especially the small-vessel vasculitides known as ...antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis AAV; granulomatosis, with polyangiitis (Wegener's). These trials have been conducted by multicenter, international groups in Europe and the United States with financial support provided by government agencies and biopharmaceutical companies. This increased clinical trial activity in vasculitis has been accompanied by the development and validation of new outcome measures--a challenging process for these complex, multiorgan system diseases. The international OMERACT Vasculitis Working Group has developed and implemented an iterative research agenda that has utilized accumulated experience and datasets from several multicenter clinical trials and large cohort studies. This work has led to the development, evaluation, validation, and endorsement, through the OMERACT consensus and validation processes, of a "core set" of outcome measurements for use in clinical trials of AAV. The core set includes domains of disease activity, damage assessment, patient-reported outcomes, and mortality; there is at least one validated outcome measurement instrument available for each domain. This report reviews the domains of illness in AAV included in the OMERACT core set, describes the instruments validated to measure these domains, and presents the approved core set.
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