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.

Relationship between cutaneous polyarteritis nodosa (cPAN) and macular lymphocytic arteritis (MLA): Blinded histologic assessment of 35 cPAN cases.

BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a skin medium vessel neutrophilic arteritis with livedo, nodules, and ulcerations. Macular lymphocytic arteritis (MLA) is a small arteritis with erythematous or pigmented macules and typical histologic features (a lymphocytic infiltrate, concentric fibrin ring, no disruption of the internal elastic lamina). OBJECTIVE: We sought to assess the frequency of clinical and histologic features of MLA in patients with cPAN. METHODS: This was a monocentric retrospective analysis of patients given the diagnosis of cPAN with blinded assessment of skin biopsy specimens. RESULTS: All 35 patients included had an infiltrated livedo, nodules, or both. Ulceration was rare. Erythematous or pigmented lesions were present in 54% of patients. Predominantly lymphocytic arteritis, a paucity of neutrophils, concentric fibrin ring, and absence of internal lamina elastic disruption were present in 60%, 20%, 18%, and 23% of patients, respectively. Median follow-up was 11 years. None of the patients had systemic involvement, and 57% had a complete remission. The incidence of complete remission was not different between patients having a predominant lymphocyte infiltrate or few neutrophils. LIMITATIONS: This was a retrospective, monocentric study without a control group of patients with MLA. CONCLUSIONS: Our data do not favor the classification of cPAN and MLA as distinct entities.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etiopathogenesis, assessment and management.

PURPOSE OF REVIEW: Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome) is a peculiar hybrid condition of a systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and a hypereosinophilic disorder with frequent lung involvement that occurs in people with asthma. This review focuses on areas of evidence or persistent uncertainty in the classification, epidemiology, clinical presentation, diagnosis, prognosis and management of EGPA and attempts to identify clues to the mechanisms in the development or course of the disease. RECENT FINDINGS: The 2013 revision of the EGPA definition formally placed the disease in the subset of ANCA-associated vasculitides. Recently published large case series underlined that the presence of ANCAs, found in 30-40% of EGPA, determines distinct but partly overlapping disease expression and the major detrimental effect of heart involvement on survival. There is some evidence that asthma in EGPA resembles a nonallergic eosinophilic asthma phenotype. Encouraging results have been reported for the treatment of EGPA with rituximab or with the eosinophil-targeted antiinterleukin-5 agent mepolizumab. SUMMARY: The understanding of EGPA continues to advance, but many gaps in knowledge remain. The nomenclature remains a source of conceptual variance in terms of demonstrated presence or not of vessel inflammation or ANCAs in the diagnosis of EGPA. Distinguishing EGPA from hypereosinophilic syndromes can be problematic, and an understanding of the mechanistic relation between the vasculitis and the eosinophilic proliferation is profoundly lacking. Some evidence suggests distinct disease phenotypes, but this concept has not yet been translated to phenotype-adapted therapy.

The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort.

The 1996 Five-Factor Score (FFS) for systemic necrotizing vasculitides (polyarteritis nodosa [PAN], microscopic polyangiitis [MPA], and Churg-Strauss syndrome [CSS]) is used to evaluate prognosis at diagnosis. In the current study we revisited the FFS, this time including Wegener granulomatosis (WG).We analyzed clinical, laboratory, and immunologic manifestations present at diagnosis of systemic necrotizing vasculitides for 1108 consecutive patients registered in the French Vasculitis Study Group database. All patients met the American College of Rheumatology and Chapel Hill nomenclature criteria. Univariable and multivariable analyses yielded the 2009 FFS for the 4 systemic necrotizing vasculitides.Overall mortality was 19.8% (219/1108); mortality for each of the SNV is listed in descending order: MPA (60/218, 27.5%), PAN (86/349, 24.6%), CSS (32/230, 13.9%), and WG (41/311, 13.2%) (p < 0.001). The following factors were significantly associated with higher 5-year mortality: age >65 years, cardiac symptoms, gastrointestinal involvement, and renal insufficiency (stabilized peak creatinine ≥150 µmol/L). All were disease-specific (p < 0.001); the presence of each was accorded +1 point. Ear, nose, and throat (ENT) symptoms, affecting patients with WG and CSS, were associated with a lower relative risk of death, and their absence was scored +1 point (p < 0.001). Only renal insufficiency was retained (not proteinuria or microscopic hematuria) as impinging on outcome. According to the 2009 FFS, 5-year mortality rates for scores of 0, 1, and ≥2 were 9%, 21% (p < 0.005), and 40% (p < 0.0001), respectively.The revised FFS for the 4 systemic necrotizing vasculitides now comprises 4 factors associated with poorer prognosis and 1 with better outcome. The retained items demonstrate that visceral involvement weighs heavily on outcome. The better WG prognosis for patients with ENT manifestations, even for patients with other visceral involvement, compared with the prognosis for those without ENT manifestations, probably reflects WG phenotype heterogeneity.

Assessment of the item selection and weighting in the Birmingham vasculitis activity score for Wegener's granulomatosis.

OBJECTIVE: To assess the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) with respect to its selection and weighting of items. METHODS: This study used the BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial. The scoring frequencies of the 34 predefined items and any "other" items added by clinicians were calculated. Using linear regression with generalized estimating equations in which the physician global assessment (PGA) of disease activity was the dependent variable, we computed weights for all predefined items. We also created variables for clinical manifestations frequently added as other items, and computed weights for these as well. We searched for the model that included the items and their generated weights yielding an activity score with the highest R(2) to predict the PGA. RESULTS: We analyzed 2,044 BVAS/WG assessments from 180 patients; 734 assessments were scored during active disease. The highest R(2) with the PGA was obtained by scoring WG activity based on the following items: the 25 predefined items rated on >or=5 visits, the 2 newly created fatigue and weight loss variables, the remaining minor other and major other items, and a variable that signified whether new or worse items were present at a specific visit. The weights assigned to the items ranged from 1 to 21. Compared with the original BVAS/WG, this modified score correlated significantly more strongly with the PGA. CONCLUSION: This study suggests possibilities to enhance the item selection and weighting of the BVAS/WG. These changes may increase this instrument's ability to capture the continuum of disease activity in WG.

The future of damage assessment in vasculitis.

Damage denotes the aspects of chronic disease that do not reverse with therapy. This concept is particularly important for the primary systemic vasculitides, since the careful differentiation between activity and damage may help avoid unnecessary exposure to cytotoxic medications. Damage significantly influences both longterm prognosis and quality of life. Because the primary systemic vasculitides have diverse manifestations, the use of a damage assessment instrument is crucial to ensure reproducibility. The Vasculitis Damage Index (VDI) is the only validated measure for damage assessment in vasculitis. Use of the VDI in recent clinical trials has shown that it may not adequately determine the full spectrum of damage experienced by patients with vasculitis of small- and medium-size vessels. We propose reexamining the way in which damage is assessed, focusing on vasculitides of small- and medium-size vessels, and outline an initiative to create a substantially revised and improved damage assessment instrument using data-driven approaches. This initiative is part of a larger international effort to create a unified approach to disease assessment for the primary systemic vasculitides.