Abstract
GCA is a chronic, idiopathic, granulomatous vasculitis of medium and large arteries. It comprises overlapping phenotypes including classic cranial arteritis and extra-cranial GCA, otherwise ...termed large-vessel GCA (LV-GCA). Vascular complications associated with LV-GCA may be due, in part, to delayed diagnosis, highlighting the importance of early identification and prompt initiation of effective therapy. Advancements in imaging techniques, including magnetic resonance angiography, CT angiography, PET and colour duplex ultrasonography, have led to improvements in the diagnosis of LV-GCA; however, the role imaging modalities play in the assessment of disease activity and long-term outcomes remains unclear. Glucocorticoids are the mainstay of therapy in LV-GCA, but their prolonged use is associated with multiple, sometimes serious, adverse effects. Recent data suggest that biologic therapies, such as tocilizumab, may be effective and safe steroid-sparing options for patients with GCA. However, data specifically evaluating the management of LV-GCA are limited.
The objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men ...with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.
To evaluate characteristics of relapse, relapse rates, treatment and outcomes among patients with biopsy-proven GCA in a large, single-institution cohort.
We conducted a retrospective review of all ...patients with biopsy-proven GCA from 1998 to 2013. Demographic, clinical, laboratory and treatment data at presentation and during follow-up were collected. Comparisons by relapse rate were performed using chi-square tests. Prednisone discontinuation by initial oral dose ≤40 and >40 mg/day was compared using Cox models.
The cohort included 286 patients 74% female, mean age at diagnosis 75.0 years (s.d. 7.6), median follow-up 5.1 years). During follow-up, 73 patients did not relapse, 80 patients had one relapse and 133 had two or more relapses. The first relapse occurred during the first year in 50% of patients, by 2 years in 68% and by 5 years in 79%. More patients with established hypertension (P = 0.007) and diabetes (P = 0.039) at GCA diagnosis were in the high relapse rate group ( ≥ 0.5 relapses/year) and more females were in the low or high relapse groups than in the no relapse group (P = 0.034). Patients receiving an initial oral prednisone dose >40 mg/day were able to reach a dose of <5 mg/day hazard ratio (HR) 1.46 (95% CI 1.09, 1.96) and discontinue prednisone HR 1.56 (95% CI 1.09, 2.23) sooner than patients receiving ≤40 mg/day without an increase in observed glucocorticoid-associated adverse events.
Females and patients with hypertension or diabetes at GCA diagnosis have more relapses during follow-up. Patients treated with an initial oral prednisone dose >40 mg/day achieved earlier prednisone discontinuation.
This article critically reviews the advances in medical management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) with a focus on recent developments in targeted biologic therapy.
The ...role of biologics in the treatment of large vessel vasculitis (LVV) is expanding. TNFα inhibitors appear to be effective in the treatment of TAK but have little benefit in GCA. Preliminary clinical trial data suggest that abatacept and tocilizumab reduce the risk of relapse in GCA. Increasing observational evidence supports the use of interleukin-6 inhibitors in TAK. Based on a small open-label study, ustekinumab appears safe and potentially effective for refractory GCA. A possible role of B cell dysregulation may contribute to pathogenic mechanisms in LVV, but support for the use of B cell depleting therapy is limited.
Interleukin-6 inhibitors appear efficacious in the treatment of refractory cases of LVV; however, utility in newly diagnosed immunosuppressive-naïve patients is less well established. Abatacept and ustekinumab are promising targets for therapy in LVV but further investigation is needed before routine use is considered.
Abstract Objective To investigate the association between giant cell arteritis (GCA) and risk of coronary artery disease (CAD). Methods We conducted a systematic review and meta-analysis of ...observational studies that reported relative risks, hazard ratios, or standardized incidence ratios with 95% confidence interval comparing CAD risk in patients with GCA versus non-GCA controls. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, generic inverse variance of DerSimonian and Laird. Result Six studies with 10,868 patients with GCA and 245,323 controls were identified and included in our data analysis. The pooled risk ratio of CAD in patients with GCA was 1.51 and did not achieve statistical significance (95% CI: 0.88–2.61). The statistical heterogeneity was high with an I 2 of 97%. Conclusion In contrast to other chronic systemic inflammatory disorders, our meta-analysis did not show any statistically significant increased risk of CAD among patients with GCA.
Giant cell arteritis (GCA) is the most common primary systemic vasculitis in adults 50 years or older. Expanded use of advanced arterial imaging has assisted both in the diagnosis of GCA and ...recognition of disease subsets. Although glucocorticoids have been the mainstay of treatment for almost 7 decades, new therapeutic options have emerged. This review aims to provide the clinician with a pragmatic approach to evaluating and managing patients with GCA while also addressing recent diagnostic and therapeutic developments.
Blood vessels are indispensable for host survival and are protected from inappropriate inflammation by immune privilege. This protection is lost in patients with autoimmune vasculitides, a ...heterogeneous group of diseases causing damage to arteries, arterioles, and capillaries. Vasculitis leads to vascular wall destruction and/or luminal occlusion, resulting in hemorrhage and tissue ischemia. Failure in the quantity and quality of immunosuppressive regulatory T cells (Treg) has been implicated in the breakdown of the vascular immune privilege. Emerging data suggest that Treg deficiencies are disease-specific, affecting distinct pathways in distinct vasculitides. Mechanistic studies have identified faulty CD8
Tregs in Giant Cell Arteritis (GCA), a vasculitis of the aorta and the large aortic branch vessels. Specifically, aberrant signaling through the NOTCH4 receptor expressed on CD8
Treg cells leads to rerouting of intracellular vesicle trafficking and failure in the release of immunosuppressive exosomes, ultimately boosting inflammatory attack to medium and large arteries. In Kawasaki's disease, a medium vessel vasculitis targeting the coronary arteries, aberrant expression of miR-155 and dysregulated STAT5 signaling have been implicated in undermining CD4
Treg function. Explorations of mechanisms leading to insufficient immunosuppression and uncontrolled vascular inflammation hold the promise to discover novel therapeutic interventions that could potentially restore the immune privilege of blood vessels and pave the way for urgently needed innovations in vasculitis management.
Giant cell arteritis (GCA) in patients with systemic sclerosis (SSc) is rare, and optimal treatment strategies for this group of patients have not been defined. We aim to describe the first case ...series of GCA/SSc overlap.
A single-institution retrospective study was performed reviewing all patients that had diagnosis codes for both SSc and GCA between January 1, 1996, and December 31, 2020. Demographic characteristic, clinical presentation, diagnostic modality, treatment, and outcome data were abstracted. Diagnosis of both SSc and GCA by a rheumatologist was required for inclusion.
Eight patients were retrospectively identified, all of which were female. Seven patients fully met both respective ACR/EULAR classification criteria sets. One patient fulfilled GCA criteria and had 8/9 points for SSc criteria plus an oesophagogram which was consistent with clinical diagnosis of SSc. Three patients had a previous history of scleroderma renal crisis (SRC) prior to glucocorticoid initiation for GCA. No episodes of SRC occurred following initiation of glucocorticoids. Three patients were treated with tocilizumab. One patient developed a diverticular perforation while on tocilizumab requiring colonic resection and colostomy, one patient discontinued tocilizumab after a medication-unrelated complication and one patient has remained on treatment and in remission.
Herein we present the largest single-institution series of patients with a history of GCA and SSc, an uncommon combination. Glucocorticoid treatment for GCA did not precipitate SRC, even in those with prior history of SRC. Further investigation regarding the benefit of tocilizumab in patients with SSc and GCA is required.
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