The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: β=-1.91; p=0.029; EDV: β=-0.57; p=0.032) and significantly elevated OND (β = 0.79; p=0.003) compared with controls. RI did not significantly differ from controls (β=-0.06, p=0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (p=0.048) and EDV (p=0.040). No association was found with RI (p=0.249), while a positive significant association was noted with OND (p<0.001). This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Vascular adhesion protein-1 (VAP-1) is a type 2 transmembrane sialoglycoprotein with oxidative deamination functionality, encoded by the amine oxidase copper-containing 3 (AOC3) gene. VAP-1 is widely expressed across various tissues, particularly in highly vascularized tissues and organs essential for lymphocyte circulation. In the vascular system, VAP-1 is predominantly found in vascular smooth muscle cells and endothelial cells, with higher expression levels in vascular smooth muscle cells. Under inflammatory conditions, VAP-1 rapidly translocates to the endothelial cell surface, facilitating leukocyte adhesion and migration through interactions with specific ligands, such as sialic acid-binding immunoglobulin-type lectins (Siglec)-9 on neutrophils and monocytes, and Siglec-10 on B cells, monocytes, and eosinophils. This interaction is crucial for leukocyte transmigration into inflamed tissues. Furthermore, VAP-1’s enzymatic activity generates hydrogen peroxide and advanced glycation end-products, contributing to cytotoxic damage and vascular inflammation. In this context, the soluble form of VAP-1 (sVAP-1), produced by matrix metalloproteinase cleavage from its membrane-bound counterpart, also significantly influences leukocyte migration. This review aims to elucidate the multifaceted pathophysiological roles of VAP-1 in vascular inflammation, particularly in giant cell arteritis (GCA) and associated polymyalgia rheumatica (PMR). By exploring its involvement in immune cell adhesion, migration, and its enzymatic contributions to oxidative stress and tissue damage, we investigate the importance of VAP-1 in GCA. Additionally, we discuss recent advancements in imaging techniques targeting VAP-1, such as [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT, which have provided new insights into VAP-1’s role in GCA and PMR. Overall, understanding VAP-1’s comprehensive roles could pave the way for improved strategies in managing these conditions.

Objectives: To longitudinally assess ocular involvement in newly diagnosed giant cell arteritis (GCA) patients by evaluating changes in transorbital ultrasonography (TOS) parameters and their association with systemic vascular inflammation and treatment response. Methods: In this prospective cohort study, newly diagnosed GCA patients underwent serial TOS assessments of the central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)] and optic nerve diameter (OND) at three-monthly intervals for 12 months. Vascular ultrasonography and calculation of OMERACT Giant Cell Arteritis Ultrasonography (OGUS) Score was conducted. Longitudinal changes and associations were analysed using linear mixed-effects models, accounting for repeated measurements within patients. Results: Thirty-six GCA patients were enrolled. At baseline, 17 (47.2%) patients reported visual symptoms. Compared with baseline, PSV significantly decreased at three (β = −0.81 cm/s, P = 0.046) and nine (β = −0.93 cm/s, P = 0.029) months. OND decreased at three (β = −0.30 mm, P = 0.020) and 12 (β = −0.35 mm, P = 0.008) months, with a consistent trend over follow-up (β = −0.07, P = 0.024). Symptomatic eyes displayed significantly higher PSV (β = 0.96, P = 0.017) and EDV (β = 0.34, P = 0.037) over disease course. Baseline pathological vessel count and OGUS Score were negatively associated with PSV (β = −0.43, P = 0.031; β = −3.15, P = 0.055) and EDV (β = −0.15, P = 0.022; β = −1.45, P = 0.007) and positively associated with OND (β = 0.15, P = 0.006; β = 0.94, P = 0.040). During disease course, significant associations with pathological vessel count and OGUS Score were noted for EDV (β = −0.04, P = 0.024; β = −0.77, P = 0.005) and OND (β = 0.05, P < 0.001; β = 0.72, P < 0.001). Conclusions: Utilizing TOS, we demonstrated progressive decrease in retinal artery flow and OND, indicating ongoing impairment in retinal vascular supply and potential optic nerve atrophy despite clinical improvement post-treatment. Our findings suggest that intracranial vascular changes in GCA may respond less effectively to treatment than extracranial vessels and support a shared pathophysiological mechanism in GCA.

Dear Editor, Giant cell arteritis (GCA) can lead to devastating ophthalmic complications, including sudden complete loss of vision due to anterior ischemic optic neuropathy (AION) secondary to inflammation and occlusion of the short posterior ciliary arteries, which supply the optic nerve head [1, 2]. Ischemia results in retinal changes, such as nerve fiber layer thickening, structural loss and optic disc edema [3, 4]. Assessing ophthalmic involvement in GCA remains challenging. Non-invasive optical coherence tomography angiography (OCTA) of the eye enables us to visualize the retinal and choroidal microcirculation [5, 6]. Additionally, we have recently shown that transorbital ultrasound (TOS) reveals changes in the ocular perfusion of symptomatic eyes in GCA patients [7]. Building on this cohort, we present the first study comparing vascular ultrasound, TOS, and OCTA findings in newly diagnosed GCA patients. The study enrolled newly diagnosed and untreated GCA patients from the Rheumatology Department at the University Hospital Bonn, Germany. Diagnoses were made by a board-certified rheumatologist with patients further meeting the ACR-EULAR classification criteria [8] following ethics approval (ethics committee of the University Hospital Bonn, reference number: 097/18, october 2018). Demographic, clinical, and laboratory data were assessed. Each patient underwent a comprehensive ultrasound examination of superficial temporal, facial, axillary, carotid, and vertebral arteries, along with TOS using a Logiq S8 (2018; GE Healthcare; 6-15 MHz/ 8-18 MHz probes). Flow velocities of the central retinal artery (CRA), including peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI), and optic nerve diameter (OND) were assessed as described previously [7]. OCTA imaging was performed in one eye per participant, prioritizing

Objectives: This cross-sectional study aimed to determine the prevalence, manifestation, and risk factors of pulmonary involvement in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to evaluate the efficacy of various diagnostic tools in screening for pulmonary involvement. Methods: Untreated, newly diagnosed patients with RA and PsA underwent an extensive multimodal diagnostic approach including clinical and laboratory assessment, pulmonary function tests, and chest radiography. Results: We recruited 50 arthritis patients (26 RA, 24 PsA) and 26 control subjects. Respiratory symptoms were found in 36.0 % of arthritis patients and 11.5 % of controls (p = 0.031). Pathologically reduced breathing width (< 3.0 cm) was significantly more common in arthritis patients (64.0 %) than in controls (23.1 %) (p < 0.001). Pulmonary function test results did not differ significantly between groups. Chest radiography revealed pulmonary involvement in 37.0 % of arthritis patients, higher in RA (50.0 %) than in PsA (22.7 %). Notably, only 35.3 % of arthritis patients with radiographic pulmonary involvement were symptomatic, with 64.7 % being asymptomatic. Radiographic pulmonary involvement was associated with advanced age (p = 0.002) and increased rheumatoid factor levels (p = 0.024). Conclusion: Our research underscores the significant prevalence of largely asymptomatic pulmonary involvement in newly diagnosed RA and PsA patients. These findings highlight the importance of an early, multidisciplinary screening approach, particularly for high-risk individuals. Further large-scale studies are needed to develop comprehensive screening protocols to improve early detection and treatment of pulmonary involvement in arthritis.

Objectives: This study aimed to evaluate the diagnostic utility of [⁶⁸Ga]Ga-DOTA-Siglec-9 positron emission tomography-computed tomography (PET/CT) in assessing disease activity in a patient experiencing a relapse of giant cell arteritis (GCA).Case presentation: A 90-year-old male patient with GCA, diagnosed in 2018, was enrolled. Demographic data, disease history, and laboratory parameters, including soluble VAP-1 (sVAP-1) levels, were recorded. The patient underwent a [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT scan. Additional imaging assessments included vascular ultrasound of the superficial temporal arteries, their branches, and the facial, axillary, subclavian, carotid, and vertebral arteries, along with magnetic resonance imaging (MRI) of the aorta.The patient’s sVAP-1 level was 284 ng/ml compared to 123 ng/ml in the control group (SD ± 55). The [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT scan revealed increased tracer uptake (SUVmax) in the subclavian artery (2.5), aortic arch (2.9), and heart (2.9). Notably, the increased uptake in the descending aorta (3.5) abruptly diminished to 2.2 when passing the diaphragm, with no changes in vessel caliber observed in CT. The injection of [⁶⁸Ga]Ga-DOTA-Siglec-9 was well tolerated. Aortic MRI revealed no signs of inflammatory involvement.Conclusions: This study introduces the first application of [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT in a patient with GCA experiencing a relapse, revealing enhanced tracer uptake in the subclavian artery and aortic arch with a localized and abrupt reduction, absent in conventional imaging. These findings suggest that [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT has significant potential for precise, inflammation-specific detection of affected vascular tissue in GCA during relapse.