Peter C. Grayson

Hyperuricemia and incident hypertension: A systematic review and meta‐analysis

A novel rodent model and a recent randomized trial of hyperuricemic adolescents with hypertension suggest a pathogenetic role of uric acid in hypertension, but it remains unknown whether these findings would be applicable to adult populations where the larger disease burden exists. We conducted a systematic review and meta‐analysis to determine if hyperuricemia was associated with incident hypertension, particularly in various demographic subgroups.

Distribution of arterial lesions in Takayasu's arteritis and giant cell arteritis

Objectives To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasus arteritis (TAK) and giant cell arteritis (GCA). Methods Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries. Cluster analysis was used to derive patterns of arterial disease in TAK versus GCA and in patients categorised by age at disease onset. Using latent class analysis, computer derived classification models based upon patterns of arterial disease were compared with traditional classification. Results Arteriographic lesions were identified in 145 patients with TAK and 62 patients with GCA. Cluster analysis demonstrated that arterial involvement was contiguous in the aorta and usually symmetric in paired branch vessels for TAK and GCA. There was significantly more left carotid (p=0.03) and mesenteric (p=0.02) artery disease in TAK and more left and right axillary (p<0.01) artery disease in GCA. Subclavian disease clustered asymmetrically in TAK and in patients ≤55 years at disease onset and clustered symmetrically in GCA and patients >55 years at disease onset. Computer derived classification models distinguished TAK from GCA in two subgroups, defining 26% and 18% of the study sample; however, 56% of patients were classified into a subgroup that did not strongly differentiate between TAK and GCA. Conclusions Strong similarities and subtle differences in the distribution of arterial disease were observed between TAK and GCA. These findings suggest that TAK and GCA may exist on a spectrum within the same disease.

ACR/EULAR-endorsed study to develop Diagnostic and Classification Criteria for Vasculitis (DCVAS).

The systemic vasculitides are a group of uncommon diseases characterized by blood vessel inflammation. There are currently no diagnostic criteria for the primary systemic vasculitides and physicians must rely on experience and disease definitions. The absence of validated criteria can result in delays in making the correct diagnosis and starting appropriate therapy. With the increased understanding of the pathophysiology of vasculitis and newer diagnostic tests in widespread clinical use, it is an appropriate time for classification criteria for primary vasculitis to be revised. The Diagnostic and Classification Criteria for Vasculitis (DCVAS) study is a multinational observational study designed to develop and validate diagnostic criteria and to improve and validate classification criteria for primary systemic vasculitis. The analytic approach will be based on the traditional approach of vessel size for classification of vasculitis but will also incorporate detailed clinical data, evaluation of anti-neutrophil cytoplasm antibody diagnostic testing, biopsy and imaging data. The study is following the guidelines for the development of classification criteria established by the American College of Rheumatology and the European League against Rheumatism. The study will incorporate the use of pre-defined cases of each condition to reduce the inherent circularity when developing new classification criteria and will explore alternative approaches to deriving reference standards by creating data-driven classification algorithms. We anticipate recruiting >2,000 patients with primary systemic vasculitis and 1,500 patients with autoimmune diseases and other conditions that mimic vasculitis. As of June 2013, >100 medical centers across 31 countries in Asia, Australasia, Europe, North America, and South America were contributing data to the study. The DCVAS study provides a unique opportunity to increase generalizability and collate a large dataset on the occurrence, presentation, and outcome of vasculitis in different populations.

At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases.

The putative role of neutrophils in host defense against pathogens is a well‐recognized aspect of neutrophil function. The discovery of neutrophil extracellular traps has expanded the known range of neutrophil defense mechanisms and catalyzed a discipline of research focused upon ways in which neutrophils can shape the immunologic landscape of certain autoimmune diseases, including systemic lupus erythematosus. Enhanced neutrophil extracellular trap formation and impaired neutrophil extracellular trap clearance may contribute to immunogenicity in systemic lupus erythematosus and other autoimmune diseases by promoting the externalization of modified autoantigens, inducing synthesis of type I IFNs, stimulating the inflammasome, and activating both the classic and alternative pathways of the complement system. Vasculopathy is a central feature of many autoimmune diseases, and neutrophil extracellular traps may contribute directly to endothelial cell dysfunction, atherosclerotic plaque burden, and thrombosis. The elucidation of the subcellular events of neutrophil extracellular trap formation may generate novel, therapeutic strategies that target the innate immune system in autoimmune and vascular diseases.

Nomenclature and classification of vasculitis - update on the ACR/EULAR diagnosis and classification of vasculitis study (DCVAS).

Classification of vasculitis remains unsatisfactory. This is largely because the pathogenetic mechanisms of this family of related disorders have not been fully understood. Existing classification criteria are useful but limited. This has become more apparent with the advent of more effective and more specific therapies. A rational basis for classification could significantly improve our approach to treatment. The development of diagnostic criteria in vasculitis is an even greater challenge but may ultimately provide more useful for the non‐specialist clinician. International efforts are underway to provide more effective classification and diagnostic criteria.

Neutrophil-Related Gene Expression and Low-Density Granulocytes Associated With Disease Activity and Response to Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

To discover biomarkers involved in the pathophysiology of antineutrophil cytoplasmic antibody–associated vasculitis (AAV) and to determine whether low‐density granulocytes (LDGs) contribute to gene expression signatures in AAV.

New Features of Disease After Diagnosis in 6 Forms of Systemic Vasculitis

Objective. To quantify the occurrence of features of vasculitis that initially present after diagnosis in 6 types of primary vasculitis. Methods. Standardized collection of data on 95 disease manifestations in 6 vasculitides, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA), polyarteritis nodosa (PAN), giant cell arteritis (GCA), and Takayasu arteritis (TAK), was obtained within a set of multicenter longitudinal, observational cohorts. For each form of vasculitis, the frequency of disease-specific manifestations at diagnosis was compared to the cumulative frequency of each manifestation. The percentage of patients who initially developed severe manifestations after diagnosis, defined as organ- or life-threatening in the small and medium vessel vasculitides (GPA, MPA, EGPA, PAN) and as ischemic/vascular in the large vessel vasculitides (GCA, TAK), was reported. Results. Out of 838 patients with vasculitis, 490 (59%) experienced ≥ 1 new disease manifestation after diagnosis. On average, patients with vasculitis experienced 1.3 new manifestations after diagnosis (GPA = 1.9, MPA = 1.2, EGPA = 1.5, PAN = 1.2, GCA = 0.7, and TAK = 1.0). New severe manifestations occurred after diagnosis in 224 (27%) out of 838 patients (GPA = 26%, MPA = 19%, EGPA = 21%, PAN = 23%, GCA = 24%, and TAK = 44%). Timing of onset of new manifestations was not significantly associated with disease duration. Conclusion. A majority of patients with vasculitis develop new disease features after diagnosis, including a substantial number of new, severe manifestations. Ongoing assessment of patients with established vasculitis should remain broad in scope.

Association of Vascular Physical Examination Findings and Arteriographic Lesions in Large Vessel Vasculitis

Objective. To assess the utility of the vascular physical examination to detect arteriographic lesions in patients with established large vessel vasculitis (LVV), including Takayasu’s arteritis (TAK) and giant cell arteritis (GCA). Methods. In total, 100 patients (TAK = 68, GCA = 32) underwent standardized physical examination and angiography of the carotid, subclavian, and axillary arteries. Sensitivity and specificity were calculated for the association between findings on physical examination focusing on the vascular system (absent pulse, bruit, and blood pressure difference) and arteriographic lesions defined as stenosis, occlusion, or aneurysm. Results. We found 67% of patients had at least 1 abnormality on physical examination (74% TAK, 53% GCA). Arteriographic lesions were seen in 76% of patients (82% TAK, 63% GCA). Individual physical examination findings had poor sensitivity (range 14%–50%) and good-excellent specificity (range 71%–98%) to detect arteriographic lesions. Even when considering physical examination findings in combination, at least 30% of arteriographic lesions were missed. Specificity improved (range 88%–100%) if individual physical examination findings were compared to a broader region of vessels rather than specific anatomically correlated vessels and if ≥ 1 physical examination findings were combined. Conclusion. In patients with established LVV, physical examination alone is worthwhile to detect arterial disease but does not always localize or reveal the full extent of arteriographic lesions. Abnormal vascular system findings on physical examination are highly associated with the presence of arterial lesions, but normal findings on physical examination do not exclude the possibility of arterial disease. Serial angiographic assessment is advisable to monitor arterial disease in patients with established LVV.

Illness Perceptions and Fatigue in Systemic Vasculitis

To compare illness perceptions among patients with different forms of vasculitis, identify risk factors for negative illness perceptions, and determine the association between illness perceptions and fatigue.

Value of commonly measured laboratory tests as biomarkers of disease activity and predictors of relapse in eosinophilic granulomatosis with polyangiitis

OBJECTIVE The aim of this study was to assess the clinical value of absolute eosinophil count, serum IgE, ESR and CRP as longitudinal biomarkers of disease activity and predictors of relapse in eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA). METHODS Patients were selected from an observational EGPA cohort. Absolute eosinophil count, IgE, ESR and CRP were measured quarterly. Disease activity was defined by validated assessment tools. The association of tests with disease activity was assessed via regression models, adjusting for repeated measures and treatment status. Survival analysis was used to determine if laboratory tests were predictive of the 3 month future flare risk. RESULTS Seventy-four per cent of 892 study visits in 141 patients occurred while patients were on treatment, mostly during remission or mild disease activity, defined as a BVAS for Wegeners granulomatosis (BVAS/WG) of 1 or 2. Correlations between absolute eosinophil count, IgE, ESR and CRP were mostly low or non-significant (r = -0.08 to 0.44). There were few weak associations with disease activity [absolute eosinophil count: OR) 1.01/100 U (95% CI 1.01, 1.02); ESR: OR 1.15/10 mg/l increase (95% CI 1.04, 1.27)]. When BVAS/WG ≥1 defined active disease, the absolute eosinophil count [hazard ratio (HR) 1.01/100 U (95% CI 1.01, 1.02)] was weakly predictive of flare. When BVAS/WG ≥3 defined active disease, ESR was weakly predictive of flare [HR 1.52/10 mm/h increase (95% CI 1.17, 1.67)]. CONCLUSION The absolute eosinophil count, IgE, ESR and CRP have limitations as longitudinal biomarkers of disease activity or predictors of flare in EGPA. These findings suggest that novel biomarkers of disease activity for EGPA are needed.