<p>Giant Cell Arteritis: The Experience of Two Collaborative Referral Centers and an Overview of Disease Pathogenesis and Therapeutic Advancements</p>

Abstract

Giant cell arteritis (GCA), a chronic vasculitis of the large and medium-sized arteries, affects people >50 years of age. This study assessed the prevalence of visual manifestations and other clinical features at presentation in an Italian cohort of GCA patients. Recent advances in the pathophysiology, diagnosis, and therapy of GCA are also reviewed. Methods: This retrospective, single-center study conducted by the ophthalmology and internal medicine clinics of one university recruited 56 patients from 2005 to 2016 and followed them for 11-54 months. Results: Ocular involvement was diagnosed in 19 patients (33.9%), with permanent vision loss in 19.6% (7.1% of the cohort with bilateral vision loss). Arteritic anterior and posterior ischemic optic neuropathy were diagnosed in 11 patients (57.9%) and 1 patient (5.3%), respectively, cotton wool spots in 3 patients (15.8%), central retinal artery occlusion in 2 patients (10.5%), and anterior segment ischemia and multifocal choroidal ischemia in 1 patient each (5.3%). Polymyalgia rheumatica was associated with GCA in 44.6% of the patients. The most common extra-ocular manifestation was constitutional symptoms (82.1% of the patients). Large-vessel involvement, including of the ascending aorta, aortic arch, and left axillary artery, was diagnosed by magnetic resonance or computed tomography (CT) angiography and 18 FDG positron emission/CT. Glucocorticoids (GCs) remain the standard-of -care worldwide, but methotrexate, provided as a steroid-sparing drug in 41% of the patients, resulted in earlier tapering, a lower cumulative dose of GCs, and a lower rate of relapse. Among the combinations of GCs and immunosuppressive drugs proposed to treat GCA, only tocilizumab has effectively induced and maintained disease remission. Conclusion: According to our data and literature reports: a) GCA is a systemic disease; b) its diagnosis is expedited by the adjunct use of imaging techniques; c) insights into the pathogenesis of GCA may allow an improved, differentiated therapeutic approach.

Advances in the Treatment of Giant Cell Arteritis

“…In fact, a strong association of GCA with HLA class I and II molecules, particularly with HLA-DRB1*04 alleles, has been described [ 18 , 19 ]. The current hypothesis on the pathogenesis of GCA invokes collaboration between the innate and adaptive immune systems and different compartments of the vessel wall, including endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) [ 14 , 17 , 20 ] ( Figure 1 ). Histologically, GCA is characterized by a pathological granulomatous inflammatory infiltrate within the vessel wall [ 21 , 22 ].…”

“…In addition, CCL19 and CCL21 magnify the inflammatory reaction at the adventitia by recruiting and retaining more and more dendritic cells. DCs also release other cytokines, such as interleukin (IL)-1β, IL-6, IL-23 and IL-21 or IL-12 and IL-18, which respectively divide into two distinct immune cell networks [ 14 , 20 , 23 , 24 ] ( Figure 1 ). The first one drives the differentiation of activated T cells into Th17 cells; the second one drives Th1 cell formation.…”

“…The first one drives the differentiation of activated T cells into Th17 cells; the second one drives Th1 cell formation. Th-17 lymphocytes produce mainly IL-17, IL-21, IL-22, IL-23, and colony-stimulating factor (CSF)-2, which subsequently result in the recruitment of innate immune cells (monocytes, fibroblasts and natural killers), the proliferation of local mesenchymal cells, and the secretion of acute phase reactants (APR) by hepatocytes [ 20 , 23 ]. Th-1 lymphocytes produce mainly interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) that favor the production of adhesion molecules, other chemokines (CCL2, CXCL9, CXCL10 and CXCL11) and growth factors (GF), such as platelet-derived growth factors (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF2).…”

Cervical duplex ultrasound for the diagnosis of giant cell arteritis with vertebral artery involvement

“…In a series of 56 patients, vision loss occurred in 19 patients (33.9%) and was attributed to arteritic anterior and posterior ischemic optic neuropathy, cotton wool spots, central retinal artery occlusion, anterior segment ischemia, and multifocal choroidal ischemia. 6 Other ischemic cerebrovascular events are less frequent in GCA.…”

“…Its incidence is largely related to the timing of diagnosis and treatment initiation. In a series of 56 patients, vision loss occurred in 19 patients (33.9%) and was attributed to arteritic anterior and posterior ischemic optic neuropathy, cotton wool spots, central retinal artery occlusion, anterior segment ischemia, and multifocal choroidal ischemia 6 …”