Background Temporal artery biopsy (TAB) is the recommended index diagnostic method for giant cell arteritis (GCA). Per the British Society for Rheumatology (BSR) guidelines, we assessed our procedural performance. Additionally, we evaluated the occurrence of GCA diagnosis in immunosuppressed patients and other comorbidities. Methods Following the audit registration, a retrospective analysis of prospectively collected data was conducted from 2017 to 2022 at a large university hospital in North Midlands, England. Data on demographics and comorbidities were gathered. The study\'s primary outcome was adherence to BSR guidelines and our service provisions. Secondary outcomes included examining the relationship between biopsy-confirmed GCA and other comorbidities. Statistical analysis was carried out using SPSS version 29 (IBM Corporation, Armonk, New York, United States of America). Two-sample t-test and Chi-square/Fisher exact test were used for continuous and categorical variables, respectively. Holm-Bonferroni method was incorporated to adjust for multiple comparisons. Results A total of 156 patients who underwent temporal artery biopsy (TAB) were included in the study, with a male-to-female ratio of 0.44:1. The median age was 73. Among the patients, 19% were smokers. The procedures were performed by either a vascular surgeon (119, 76%) or by an ophthalmologist (37, 24%). Two-thirds of the patients underwent TAB within seven days of referral. In 73, 47% of cases, the post-fixation biopsy sample size exceeded 10 mm. Positive biopsy results were found in 45 patients (29%). GCA was confirmed in 39% of patients with polymyalgia rheumatica (PMR), 24% with diabetics, 20% with hypothyroidism, 29% with hypertension, 32% with hyperlipidaemia, and 26% with other inflammatory diseases. However, the p-value was below the statistically significant threshold. The biopsy outcome was also not dependent on the speciality, time from referral to biopsy, nor on the length of the post-fixation specimen. Conclusions Temporal artery biopsy remains a valuable and crucial diagnostic tool in challenging equivocal cases of giant cell arteritis (GCA), although it is limited by its sensitivity, but there is also room for improvement. There is still uncertainty regarding the relationship between biopsy positivity, post-fixation sample size, and the interval between referral and procedure. Additionally, the speciality of the clinician performing the biopsy does not appear to significantly influence the likelihood of a positive result. We still do not fully understand why this is, but the association of the GCA with other comorbidities was unpredictably insignificant.

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.

Giant cell arteritis (GCA) is a relatively rare, auto-immune vasculitis, more common in women over age 50. It is important to recognize and treat the disease early to prevent late complications of permanent vision loss. Inflammation-associated weakening of vessel walls involved by GCA may also represent a potential etiology for intracranial aneurysm development. In this report, we describe an atypical presentation of GCA confirmed with temporal artery biopsy with associated manifestations including intracranial right posterior communicating artery aneurysm and extracranial right internal carotid aneurysm. Our patient in a 78-year-old female who presented with progressively worsening headaches that began 10 days prior to admission. These were described as global, non-pulsatile, and located over her occiput. She reported associated jaw soreness while chewing or claudication. Her erythrocyte sedimentation rate (ESR) was elevated at 74 mm/hr. Magnetic resonance angiogram showed a right posterior communicating artery aneurysm measuring 5 mm and a right cervical carotid lengthwise dissecting aneurysm measuring 12 mm. Left temporal artery biopsy confirmed the diagnosis of GCA. High-dose steroid therapy was initiated and was continued for treatment of GCA with resolution of symptoms at her one month follow-up. This case highlights a rare instance of cervical internal carotid aneurysm and intracranial aneurysm associated with GCA, emphasizing the systemic nature of this vasculitis.

UNASSIGNED: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting the medium and large-size arteries, and may present with a range of ophthalmic findings. This review will cover GCA epidemiology, pathophysiology, clinical presentation, diagnostic workup, and treatment.
UNASSIGNED: GCA is commonly found in elderly patients and individuals of Scandinavian descent. Recent publications suggest it may be more common in African Americans and Hispanics than previously thought. It is very rare in Asian and Middle-Eastern populations, and there is little data regarding African populations. Genetic studies have identified increased risk associated with HLA-DRB1*04. Rather than a response to a specific antigen such as varicella zoster virus, current immunology research suggests that GCA results from changes associated with the aging immune system.
UNASSIGNED: Arteritic anterior ischemic optic neuropathy is the most common ophthalmic manifestation of GCA, but central or branch retinal artery occlusion, ophthalmic artery occlusion, cranial neuropathies causing diplopia, and more rarely anterior segment ischemia and anisocoria may also occur. Clinical testing including visual field testing, OCT, OCT-A, ICG and fluorescein angiography can be helpful in suggesting a diagnosis in addition to the clinical exam.
UNASSIGNED: GCA is ultimately a clinical diagnosis, but it is usually supported with lab results, pathology, and/or imaging. Temporal artery biopsy (TAB) remains the gold standard diagnostic test although its sensitivity is debated and practice patterns still vary with respect to sample length and whether unilateral or simultaneous bilateral biopsies are performed. Some studies have reported higher sensitivity of ultrasounds over TAB, with added benefits of time efficiency and cost effectiveness, promoting the diagnostic use of ultrasounds. MRI and even PET CT protocols offer additional options for less invasive diagnostic testing.
UNASSIGNED: Vision-threatening GCA is treated acutely with emergent admission for intravenous methylprednisolone, and long-term high dose oral corticosteroids remain the standard of care, despite common and sometimes serious side effects. The use of steroid-sparing alternatives such as tocilizumab is becoming more common and additional agents are being investigated.

TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue.

Giant-cell arteritis (GCA) is a type of vasculitis characterised by the presence of granulomas. It is the predominant form of systemic vasculitis in adults and primarily affects the larger arteries in individuals aged ≥ 50 years. GCA affects the major arteries, such as the aorta and its branches, particularly the outer branches of the external carotid artery. Signs and symptoms can be categorised into cranial, extracranial, and systemic manifestations. Patients with headaches, jaw claudication, and vision disturbances usually have extracranial branches of the external carotid artery. Aside from being the prevailing manifestation of GCA, our primary concern regarding this variant is the potential for irreversible vision loss if not properly identified and addressed. Conversely, the GCA can also affect other major blood vessels such as the aorta. Here, we present the case of a 70-year-old Caucasian female patient with cranial GCA who had experienced a temporal headache three years prior. The patient was successfully treated with prednisolone, which was gradually reduced to a very low level with the assistance of methotrexate. Recently, the patient presented with a dry cough that lasted for two months and elevated inflammatory markers. After thorough research, it was determined that there was no evidence of infection, including atypical infections, and that no abnormalities were found in the lungs. Ultimately, via an 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan, the patient was diagnosed with large vessel giant cell arteritis (LV-GCA). This impacted the aorta, carotid arteries, and subclavian arteries. The patient experienced notable improvement in her cough and a reduction in inflammatory markers after receiving a high dosage of oral prednisolone. This case exemplifies the unusual manifestation of LV-GCA and verifies that recurring symptoms may differ from the original presentation. While dry cough is not commonly listed as a symptom of LV-GCA, it can be present as a manifestation or the sole presentation in certain patients, particularly when inflammatory markers are consistently high and there is no pulmonary disease.

Giant cell arteritis (GCA) is a form of vasculitis characterized by symptoms that often lead a patient to consult a general dentist. Its rarity in the dental setting and serious life-altering effects make it a formidable diagnosis. We discuss a case of a 60-year-old female with GCA presenting with primary symptoms of excruciating tooth and jaw pain on the left side. We also report secondary symptoms of headache and partial vision loss and engage in a review of the relevant literature. Jaw pain, unexplained toothache, or tissue necrosis in patients aged over 50 years can be misdiagnosed as joint arthritis or temporomandibular disease (TMD), which could lead to severe consequences. Accurately diagnosing this ophthalmic emergency is critical for implementing therapy promptly and preventing ischemic complications. Dentists should maintain a high index of suspicion about its signs and symptoms, which will aid in making an early diagnosis and prompt referral.

UNASSIGNED: A positive PET scan at diagnosis was associated with a greater yearly increase in ascending and descending aortic diameter and thoracic aortic volume in patients with giant cell arteritis (GCA). Radiologic and histopathologic vascular abnormalities persist in a subset of treated patients despite clinical remission. The aim of this study was to evaluate the association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms.
UNASSIGNED: We recently performed a prospective cohort study of 106 GCA patients, who underwent FDG PET and CT imaging at diagnosis and CT imaging yearly for a maximum of 10 years. In this post hoc analysis, GCA patients who also have had FDG PET imaging during follow-up were included. PET scans were visually scored (0-3) at 7 vascular areas. PET scans were considered positive in case of FDG uptake ≥grade 2 in any large vessel.
UNASSIGNED: Eighty-eight repeat PET scans were performed in 52 out of 106 GCA patients, who were included in the original prospective cohort. Fifty-five (63%) PET scans were done at the time of a relapse and 33 (38%) were done while in remission. Nine out of ten patients with an incident thoracic aortic aneurysm had both a positive PET scan at diagnosis and during follow-up.
UNASSIGNED: In addition to the intensity and extent of the initial vascular inflammation, ongoing aortic inflammation may contribute to the development of thoracic aortic aneurysms in GCA. However, this hypothesis should be confirmed in a large prospective trial with repeat PET scans at predefined time points during follow-up.

Acute vision loss is a prevalent clinical manifestation associated with a broad spectrum of differential diagnoses, encompassing demyelinating diseases, neoplastic processes, autoimmune disorders, and infectious conditions. A rare but noteworthy infectious etiology contributing to acute vision loss is neurological Lyme disease (Lyme neuroborreliosis)-induced optic neuritis. Lyme disease, a vector-borne illness caused by the spirochete Borrelia burgdorferi, has the potential to affect multiple physiological systems and unfolds in three distinct stages. Another significant contributor to acute vision loss is giant cell arteritis, an autoimmune vasculitis that commonly affects large- and medium-sized vessels, including the temporal and ophthalmic arteries. This relatively common condition may manifest with symptoms, such as jaw claudication, headaches, and visual disturbances. The precise identification of the underlying cause of acute visual loss is of utmost importance for physicians, as it is instrumental in averting undesirable complications. An 80-year-old female presents to the emergency room with a sudden onset of blurry vision of the left eye, right-sided weakness, dysarthria, jaw pain, headache, and left facial droop. Following consultations with rheumatology and ophthalmology specialists, giant cell arteritis emerged as a primary consideration in the differential diagnosis for the observed vision loss. Subsequently, a temporal artery biopsy was conducted, definitively confirming the diagnosis of giant cell arteritis. Considering the patient\'s residence in an area endemic to Lyme disease, a Lyme immunoglobulin G (IgG) titer was ordered. The results returned positive, suggesting the presence of Lyme neuroborreliosis.

UNASSIGNED: The need to systematically examine patients suspected of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) for malignancy is controversial. The aim of this study was to assess the frequency of malignancy in patients with suspected PMR and/or GCA who have been referred to a 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) as part of the diagnostic investigation.
UNASSIGNED: The records of all patients referred to FDG-PET/CT from Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup with the suspicion of PMR and/or GCA during a two-year period, were retrospectively reviewed. Data was analyzed with descriptive statistics, and a standard incidence ratio was calculated based on background cancer incidences extracted from the NORDCAN database.
UNASSIGNED: 220 patients were included in the study. Findings suspicious of malignancy were found in 19 of the examinations, and in seven cases (3.2%), malignancy was confirmed. In three out of the seven cases the patients were diagnosed with PMR concomitantly with malignancy. The estimated standardized incidence ratio (SIR) for cancer compared to the background incidence of cancer in Denmark was 1.58 (95% CI 0.63-2.97), i.e., not statistically significant. There were no statistically significant differences in characteristics of the patients that were diagnosed with malignancy compared with those that were not.
UNASSIGNED: The frequency of malignancy in this cohort of patients with suspected PMR/GCA who underwent PET/CT was low. Our results, though based on a small cohort, do not suggest that all patients with suspected PMR/GCA should systematically be examined with FDG-PET/CT for excluding malignancy.