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Objective.We evaluated potential circulating biomarkers of disease activity in giant cell arteritis (GCA), Takayasu arteritis (TA), polyarteritis nodosa (PAN), and eosinophilic granulomatosis with polyangiitis (EGPA).Methods.A panel of 22 serum proteins was tested in patients enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies of GCA, TA, PAN, or EGPA. Mixed models were used for most analyses. A J48 classification tree method was used to find the most relevant markers to differentiate between active and inactive GCA.Results.Tests were done on 418 samples from 152 patients (60 GCA, 29 TA, 26 PAN, 37 EGPA), during both active vasculitis and remission. In GCA, these showed significant (p < 0.05) differences between disease states: B cell–attracting chemokine 1 (BCA)-1/CXC motif ligand 13 (CXCL13), erythrocyte sedimentation rate (ESR), interferon-γ—induced protein 10/CXC motif chemokine 10, soluble interleukin 2 receptor α (sIL-2Rα), and tissue inhibitor of metalloproteinase-1 (TIMP-1). In EGPA, these showed significant increases during active disease: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage—CSF, interleukin (IL)-6, IL-15, and sIL-2Rα. BCA-1/CXCL13 also showed such increases, but only after adjustment for treatment. In PAN, ESR and matrix metalloprotease (MMP)-3 showed significant differences between disease states. Differences in biomarker levels between diseases were significant for 11 markers and were more striking (all p < 0.01) than differences related to disease activity. A combination of lower values of TIMP-1, IL-6, interferon-γ, and MMP-3 correctly classified 87% of samples with inactive GCA.Conclusion.We identified novel biomarkers of disease activity in GCA and EGPA. Differences of biomarker levels between diseases, independent of disease activity, were more apparent than differences related to disease activity. Further studies are needed to determine whether these serum proteins have potential for clinical use in distinguishing active disease from remission or in predicting longer-term outcomes.

Objective.To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) in the assessment of disease activity in giant cell arteritis (GCA).Methods.Patients with GCA enrolled in a prospective, multicenter, longitudinal study with symptoms of active vasculitis during any visit were included. Spearman’s rank correlation was used to explore the association of the BVAS with other measures of disease activity.Results.During a mean (SD) followup of 2.3 (1.6) years, symptoms of active GCA were present in 236 visits in 136 subjects (100 female, 74%). Median (range) BVAS1 (new/worse symptoms) was 1 (0–10) and median (range) BVAS2 (persistent symptoms) was 0 (0–5). Median (range) physician’s global assessment (PGA) was 4 (0–9) for disease activity in the past 28 days and 2 (0–9) for activity on the day of the visit. Important ischemic manifestations of active vasculitis not recorded by the BVAS included tongue/jaw claudication (27%), upper extremity claudication (15%), lower extremity claudication (5%), carotidynia (7%), and ischemic retinopathy (5%). During 25 visits (11%) with active disease, all symptoms of active vasculitis were placed in the “Other” category yet still resulted in a BVAS1 and BVAS2 of 0. BVAS1 moderately correlated with PGA for the past 28 days (Spearman’s correlation 0.50) and physician-rated disease activity for the past 28 days (Spearman’s correlation 0.46).Conclusion.The BVAS has limited utility in GCA. Patients with active GCA can have a BVAS of 0. Many important ischemic symptoms attributable to active vasculitis are not included in the composite score.

Objective.To evaluate the frequency, timing, and clinical features of relapses in giant cell arteritis (GCA).Methods.Patients with GCA enrolled in a prospective, multicenter, longitudinal study were included in the analysis. Relapse was defined as either new disease activity after a period of remission or worsening disease activity.Results.The study included 128 subjects: 102 women (80%) and 26 men (20%). Mean ± SD age at diagnosis of GCA was 69.9 ± 8.6 years. Mean followup for the cohort was 21.4 ± 13.9 months. Median (interquartile range) duration of disease at study enrollment was 4.6 months (1.2, 16.8). During followup, 59 relapses were observed in 44 patients (34%). Ten patients (8%) experienced 2 or more relapses. The most common symptoms at relapse were headache (42%) and polymyalgia rheumatica (51%), but ischemic (some transient) manifestations (visual symptoms, tongue or jaw claudication, and/or limb claudication) occurred in 29% of relapses (12% cohort). Forty-three relapses (73%) occurred while patients were taking glucocorticoid therapy at a median (range) prednisone dose of 7.5 (0–35) mg. In 21% of relapses, both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal. Among 69 patients enrolled in the cohort with newly diagnosed disease, 24% experienced a first relapse within 12 months after diagnosis.Conclusion.Among patients with GCA, relapses are common, often occurring during treatment. ESR and CRP are frequently normal at times of clinical relapse, highlighting the need for better biomarkers to assess disease activity in GCA. There remains a need for effective therapeutic alternatives to glucocorticoids in GCA.

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.

It is well established that active antineutrophil cytoplasmic antibody-associated vasculitis (AAV) — granulomatosis with polyangiitis (Wegener’s; GPA) or microscopic polyangiitis — is associated with a very high risk of venous thromboembolic events (VTE): about 7 per 100 person-years1,2,3,4, compared to 0.15–0.31 in the general population5,6,7. Risk probably remains elevated, although to a much lower degree, during remission. Such risk has been calculated (1.0 per 100 person-years) in only 1 study4 and was not formally compared to the published data on healthy persons available at the time5; but dissection of data from the other studies of VTE in AAV1,2,3 and addition of data from new and very large cohorts of healthy persons support the statement that the relative risk of VTE during quiescent AAV is elevated, probably to about the same degree as in rheumatoid arthritis or inflammatory bowel disease6,7,8. The increased risk of VTE in AAV, regardless of disease activity, cannot be attributed to the known risk factors for VTE2,4,9. It is on this background that Hilhorst, et al looked for evidence of hypercoagulability in patients with quiescent AAV10. At first glance, it might appear that investigating active AAV would be more fruitful, but since abnormalities related to … Address correspondence to Dr. Monach. E-mail: pmonach{at}bu.edu