Antiplatelet therapy to prevent ischemic events in giant cell arteritis: protocol for a systematic review and meta-analysis.

BACKGROUND: Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. Presenting features include new-onset headaches, constitutional symptoms, jaw claudication, polymyalgia rheumatica, and visual symptoms. Arterial inflammation with subsequent stenosis and occlusion may cause tissue ischemia, leading to blindness, strokes, and myocardial infarction. Oral antiplatelet therapy has been hypothesized to reduce GCA-related ischemic events. However, previous studies have demonstrated conflicting results regarding the efficacy of antiplatelet agents in GCA. The objective of this systematic review is to assess the safety and efficacy of antiplatelet therapy for the prevention of these events in adults with giant cell arteritis. METHODS: In this systematic review, we will include randomized controlled trials (RTCs), quasi-randomized trials, non-randomized intervention studies, cohort studies, and case-control studies on patients with new-onset or relapsing GCA. The intervention of interest will be pre-existing use or initiation of an oral antiplatelet medication (aspirin, clopidogrel, prasugrel, or ticagrelor) at GCA onset or relapse. The comparator of interest will be the absence of antiplatelet therapy. Endpoints will be evaluated after 6 and 12 months of follow-up. The primary outcome will be GCA-related ischemic events, including permanent blindness, stroke, myocardial infarction, and ischemic event-related deaths. Adverse events such as major bleeding and death caused by a bleeding event will be assessed. DISCUSSION: GCA-related ischemic events are catastrophic, sudden, often irreversible, and lead to significant morbidity. Antiplatelet agents are affordable, accessible, and could be effective for the prevention of these events. Nevertheless, the potential benefits of platelet aggregation inhibition must be weighed against their associated risk of bleeding. Assessing the efficacy and safety of antiplatelet therapy in GCA is therefore clinically important. SYSTEMATIC REVIEW REGISTRATION: Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42023441574.

Tocilizumab use in giant cell arteritis: comparing Pharmaceutical Benefits Scheme eligible and ineligible cases in South Australia.

Tocilizumab (TCZ) is increasingly used as a steroid-sparing agent in giant cell arteritis (GCA), but there are strict Pharmaceutical Benefits Scheme (PBS) restrictions for its use in Australia. Patients who do not meet the PBS criteria can obtain TCZ through public hospital individual patient use (IPU) schemes which may not be universally accessible. We compared patients receiving IPU-approved TCZ with patients receiving PBS-subsidised TCZ and found IPU approvals were granted mainly for visual loss, a serious complication of GCA, in patients who otherwise failed to meet PBS criteria. Further studies demonstrating that TCZ is comparatively more effective than prednisolone monotherapy, as well as cost-effective, are needed to substantiate the rationale for expanding PBS approval criteria.

Genetics of vasculitis.

Systemic vasculitis encompasses a wide range of conditions characterized by varying degrees of inflammation in blood vessels. Although the etiology of vasculitis remains unclear, accumulated data suggest that it is triggered in genetically predisposed individuals by the concurrence of certain environmental factors. The importance of the genetic component has been consistently supported by evidence of familial aggregation, differential prevalence by ethnicity, and multiple genetic associations with disease susceptibility and severity reported in recent years. The strongest association signals in most vasculitides correspond to genetic variants within the HLA region, suggesting an important role of the immune system in its pathophysiology. However, each type of vasculitis has distinct defining HLA association markers, likely due to disease-specific differences in antigenic drivers. Furthermore, other genetic polymorphisms located outside the HLA region play an important role in susceptibility to different vasculitides. More recent research has assessed the shared genetic susceptibility evident across different vasculitides. Future studies should focus on the identification of genetic markers that can serve as reliable biomarkers for early diagnosis, prognosis, and treatment response in systemic vasculitis.

Clinical characteristics and courses of Korean patients with giant cell arteritis: a multi-center retrospective study.

Objective: Giant cell arteritis (GCA) is a large-vessel vasculitis that primarily affects elderly individuals. However, data regarding Korean patients with GCA are scarce owing to its extremely low prevalence in East Asia. This study aimed to investigate the clinical characteristics of Korean patients with GCA and their outcomes, focusing on relapse. Methods: The medical records of 27 patients with GCA treated at three tertiary hospitals between 2007 and 2022 were retrospectively reviewed. Results: Seventeen (63.0%) patients were females, and the median age at diagnosis was 75 years. Large vessel involvement (LVI) was detected in 12 (44.4%) patients, and polymyalgia rheumatica (PMR) was present in 14 (51.9%) patients. Twelve (44.4%) patients had fever at onset. The presence of LVI or concurrent PMR at diagnosis was associated with a longer time to normalization of the C-reactive protein level (p=0.039) or erythrocyte sedimentation rate (p=0.034). During follow-up (median 33.8 months), four (14.8%) patients experienced relapse. Kaplan-Meier analyses showed that relapse was associated with visual loss (p=0.008) and the absence of fever (p=0.004) at onset, but not with LVI or concurrent PMR. Conclusion: Concurrent PMR and LVI were observed in approximately half of Korean patients with GCA, and the elapsed time to normalization of inflammatory markers in these patients was longer. The relapse rate in Korean GCA is lower than that in Western countries, and afebrile patients or patients with vision loss at onset have a higher risk of relapse, suggesting that physicians should carefully monitor patients with these characteristics.

Polymyalgia rheumatica is a risk factor for more recalcitrant disease in giant cell arteritis: A retrospective cohort study.

OBJECTIVES: To evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without polymyalgia rheumatica (PMR) symptoms. METHODS: Consecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥12 months at the University Hospitals Leuven (Belgium), were included retrospectively. RESULTS: We included 398 GCA patients, of which 181 (45%) with PMR symptoms. Patients with PMR symptoms had a longer symptom duration (11 vs 6 weeks, p < 0.001). They less frequently reported fever (19% vs 28%, p = 0.030) and fatigue (52% vs 64%, p = 0.015) and tended to have less permanent vision loss (12% vs 19%, p = 0.052). There was no difference in the cumulative oral GC dose at 2 years (4.4 vs 4.3 g methylprednisolone, p = 0.571). However, those with PMR symptoms were treated with higher GC doses during subsequent follow-up (p < 0.05 from 38 months after diagnosis) and had a lower probability of stopping GC (62% vs 71%, HR 0.74 [95%CI 0.58-0.94], p = 0.018) with a longer median duration of GC treatment (29 vs 23 months, p = 0.021). In addition, presence of PMR symptoms was associated with an increased risk of relapse (64% vs 51%, HR 1.38 [95%CI 1.06-1.79], p = 0.017) with a higher number of relapses (1.47 [95%CI 1.30-1.65] vs 1.16 relapses [95%CI 1.02-1.31], p = 0.007). Patients with PMR symptoms less frequently developed thoracic aortic aneurysms during follow-up (3% vs 11%, p = 0.005). CONCLUSION: GCA patients with PMR symptoms had more recalcitrant disease with a higher risk of relapse and longer duration of GC treatment with need for higher GC doses.

Single-cell transcriptomic analysis to identify endomembrane regulation of metalloproteins and motor proteins in autoimmunity.

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.

Taper versus discontinuation of tocilizumab in patients with giant cell arteritis: Real-world experience from a tertiary center.

INTRODUCTION: Following the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation. METHODS: We performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test. RESULTS: We included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events. CONCLUSION: This is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA.

Ultrasonography of the Superficial Temporal and Axillary Arteries in Giant Cell Arteritis diagnosis.

OBJECTIVES: Giant cell arteritis (GCA) is the main systemic vasculitis in individuals aged ≥ 50 years. Color Doppler ultrasound (CDS) has an established role in GCA diagnosis and management. This study aims to assess the clinical characteristics associated with a positive CDS evaluation and the impact of additional axillary artery examination on diagnostic sensitivity. MATERIAL AND METHODS: We conducted a retrospective analysis of patients undergoing CDS of the superficial temporal arteries, with or without axillary artery assessment, at our hospital, between 2009 and 2023. Patients meeting the new 2022 diagnostic criteria for GCA were included and their characteristics were analyzed according to the presence of the halo sign on CDS. RESULTS: Of the 135 included patients (54% female, mean age 75±8 years), the halo sign was observed in 57%, correlating with higher systemic symptom prevalence (61% vs 42%, p=0.035), lower hemoglobin (p<0.001), and higher erythrocyte sedimentation rate (p=0.028). The halo sign inversely related to prior corticosteroid therapy (p=0.033). Patients with axillary halo sign had fewer external carotid symptoms and a higher vertebral halo sign prevalence. Vertebral halo sign was associated with posterior circulation ischemic stroke (65%, p < 0.001). Axillary artery studies improved diagnostic sensitivity by 9%. CONCLUSION: In our study, the halo sign correlated with higher systemic symptoms and analytical abnormalities. Axillary artery examination enhanced CDS sensitivity, linked to severe outcomes like stroke. Prior corticosteroid therapy reduced CDS sensitivity. The correlation of clinical, laboratory, and ultrasound findings provides a more comprehensive understanding of GCA pathogenesis and evolution.

A Case of Large Vessel Giant Cell Arteritis Presenting With Cough and Diagnosed Using an FDG-PET Scan.

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.

Association of clinical, imaging and laboratory parameters with adverse effects of glucocorticoid therapy in patients with giant cell arteritis.

Background: Giant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are effective while potential adverse effects should be considered, especially during long-term use. The aim was to investigate the incidence of glucocorticoids' adverse effects and potential predictors for them. Materials and methods: 138 GCA patients were retrospectively evaluated for newly developed glucocorticoid adverse effects in 2020. Potential predictors, defined as initial glucocorticoid pulse therapy, relapse of GCA and concomitant polymyalgia rheumatica as well as parameters of inflammation and endothelial dysfunction, including pulse-wave velocity and intima-media-thickness, were measured in 2012. Results: Potential new glucocorticoid adverse effects per patient was 1 (25th-75th 0-3) of which chronic kidney disease progression (29%), bone fractures (23.2%), cataracts (18.1%), dementia, and arterial hypertension (each at 12.3%) were most commonly recorded. Significant associations were found between occurrence of any relapse and new diabetes mellitus and between initial glucocorticoid pulse therapy and new dementia (all with p < 0.05). In multivariate regression analysis, any relapse was a predictor for developing diabetes mellitus (OR 9.23 [95% CI 1.33-64.05], p = 0.025). However, no correlations were observed between endothelial dysfunction or inflammatory parameters and development of new glucocorticoid adverse effects. Conclusion: GCA relapses may be associated for development of diabetes mellitus potentially by increasing glucocorticoid doses. Parameters of inflammation and endothelial dysfunction are not suited predictors for glucocorticoid adverse effects.

Updates in the Management of Giant Cell Arteritis.

PURPOSE OF THE REVIEW: To briefly review the latest updates in management in giant cell arteritis, an autoimmune vasculitis affecting the medium to large vessels. RECENT FINDINGS: Here, we review the known and newer trends in management of giant cell arteritis. While high dose glucocorticoids remain the mainstay of therapy, immunosuppressive medications are increasingly utilized to reduce the burden and risk of long-term glucocorticoid use. Published guidelines by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) suggest early use of steroid-sparing immunosuppressive medications in patients with recently diagnosed or relapsing giant cell arteritis. Immunosuppressive medications include oral small molecules such as methotrexate and leflunomide and biologics, including the recently Federal Drug Administration (FDA) approved tocilizumab. Glucocorticoids remain the cornerstone of management for newly diagnosed disease but with the increasing use of medications such as IL-6 inhibitors, patients are decreasing steroid use within weeks, thereby limiting risks associated with long-term steroid use.

Giant Cell Arteritis With Sepsis-Like Symptoms in an Elderly Man: A Case Report.

This case report details the diagnostic challenge and management of an 88-year-old man who presented to a rural Japanese community hospital with sepsis-like symptoms, initially suspected of acute bacterial cholangitis based on his physical and laboratory findings. Despite the antibiotic treatment of tazobactam and piperacillin, the patient's symptoms persisted, leading to further investigations that revealed no signs of infection but notable aortic arch wall thickening on contrast-enhanced computed tomography scans. These findings, combined with the patient's clinical presentation and lack of antibiotic response, redirected the diagnosis toward giant cell arteritis (GCA). The administration of prednisolone of 60 mg daily significantly alleviated symptoms and prevented potential severe complications such as blindness and irreversible neurological damage. This case underscores the importance of considering GCA in elderly patients presenting with systemic inflammatory symptoms and the necessity of timely intervention. It also highlights the challenges in managing high-dose steroid therapy in elderly patients and suggests the potential benefits of integrating immunosuppressants to reduce steroid dependency. This report emphasizes the need for heightened awareness and a comprehensive diagnostic approach in atypical presentations of GCA, particularly in geriatric populations within resource-limited healthcare settings.

The utility of 18F-FDG-PET/CT in detecting extracranial large vessel vasculitis in rheumatic polymyalgia or giant cell arteritis. A systematic review and meta-analysis.

OBJECTIVE: Systematic review of current evidence to analyze the prevalence of extracranial large vessel vasculitis (LVV) using 18F-FDG PET/CT in patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA). MATERIALS AND METHODS: PubMed and EMBASE were searched and the results were screened by two reviewers. Study quality was assessed using a modified version of the Newcastle-Ottawa scale. Heterogeneity between studies was assessed using the I2 statistic and the Q test. Further subgroup analyses were performed by disease type, study quality, and 18F-FDG PET/CT uptake criteria. Publication bias was assessed by funnel plot and Egger's test. RESULTS: 268 publications were identified, of which 17 met the selection criteria and were included in the meta-analysis. The overall pooled prevalence of extracranial LVV by 18F-FDG PET/CT was 54.5% [95% CI: 42.6%-66.1%]. In patients with GCA the prevalence was significantly higher than in patients with PMR (60.1% vs. 41.8%, P = 0.006). Likewise, studies with a lower risk of bias reported a higher prevalence of extracranial LVV (61.1% vs. 46.9%; P = 0.010). No publication bias was observed. CONCLUSIONS: The 18F-FDG PET/CT test may be useful in the detection of extracranial LVV, both in patients with PMR or GCA. Such involvement is more frequent in patients with GCA, and may vary depending on the quality of the studies.

[Unclear cause of unilateral blindness with normal inflammation parameters]. / Unklare Ursache einseitiger Erblindung bei normwertigen Entzündungsparametern.

A 70-year-old female patient presented with unilateral blindness of the right eye. As C­reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were inconspicuous, a nonarteritic embolic occlusion was assumed; however, after detailed anamnesis large vessel vasculitis (LVV) appeared more likely, which was confirmed by the subsequent imaging diagnostics. This rare case of LVV without an increase in one of the inflammatory parameters CRP or ESR highlights the importance of the medical history and targeted diagnostic procedures.

Diagnosing vasculitis with ultrasound: findings and pitfalls.

Rheumatologists are increasingly utilizing ultrasound for suspected giant cell arteritis (GCA) or Takayasu arteritis (TAK). This enables direct confirmation of a suspected diagnosis within the examination room without further referrals. Rheumatologists can ask additional questions and explain findings to their patients while performing ultrasound, preferably in fast-track clinics to prevent vision loss. Vascular ultrasound for suspected vasculitis was recently integrated into rheumatology training in Germany. New European Alliance of Associations for Rheumatology recommendations prioritize ultrasound as the first imaging tool for suspected GCA and recommend it as an imaging option for suspected TAK alongside magnetic resonance imaging, positron emission tomography and computed tomography. Ultrasound is integral to the new classification criteria for GCA and TAK. Diagnosis is based on consistent clinical and ultrasound findings. Inconclusive cases require histology or additional imaging tests. Robust evidence establishes high sensitivities and specificities for ultrasound. Reliability is good among experts. Ultrasound reveals a characteristic non-compressible 'halo sign' indicating intima-media thickening (IMT) and, in acute disease, artery wall oedema. Ultrasound can further identify stenoses, occlusions and aneurysms, and IMT can be measured. In suspected GCA, ultrasound should include at least the temporal and axillary arteries bilaterally. Nearly all other arteries are accessible except the descending thoracic aorta. TAK mostly involves the common carotid and subclavian arteries. Ultrasound detects subclinical GCA in over 20% of polymyalgia rheumatica (PMR) patients without GCA symptoms. Patients with silent GCA should be treated as GCA because they experience more relapses and require higher glucocorticoid doses than PMR patients without GCA. Scores based on intima-thickness (IMT) of temporal and axillary arteries aid follow-up of GCA, particularly in trials. The IMT decreases more rapidly in temporal than in axillary arteries. Ascending aorta ultrasound helps monitor patients with extracranial GCA for the development of aneurysms. Experienced sonologists can easily identify pitfalls, which will be addressed in this article.

Diagnosing vasculitis with ultrasound Rheumatologists use ultrasound to diagnose two types of blood vessel inflammation: giant cell arteritis (GCA) or Takayasu arteritis (TAK). They can do this right in their office during the examination, without sending patients elsewhere. During the ultrasound, rheumatologists can talk with patients about what they see. This is especially helpful in fast-track clinics to prevent vision loss. In Germany, doctors training to become rheumatologists learn how to use ultrasound to check for problems like these. An organization called 'European Alliance of Associations for Rheumatology (EULAR)' recommends using ultrasound as the main way to look for GCA and, if needed, for TAK. Ultrasound is also an important part of the new classification criteria for GCA and TAK. However, doctors do not rely on ultrasound alone. They also look what patients are feeling and do other medical tests. If ultrasound is not clear enough, doctors might need to do more tests like taking a small piece of tissue (biopsy) or using other kinds of imaging like MRI or CT scans. Ultrasound can show some characteristic signs of blood vessel inflammation, like a 'halo sign,' which tells doctors that the blood vessel walls are thicker than normal. It can also spot other problems like blockages or bulges in the blood vessels. When doctors suspect GCA, they should at least examine the arteries at the forehead and at the armpit. Most of the time, these areas are easy to see with ultrasound, but some areas might be harder to reach. Sometimes, people can have blood vessel inflammation without feeling any typical symptoms. Ultrasound can still find this silent inflammation in more than 20% of people with a condition called polymyalgia rheumatica (PMR). Even though these patients do not have typical symptoms of GCA, it is important to treat them the same way as those with GCA. Otherwise, they may have more flare-ups and need higher doses of glucocorticoids. Doctors may measure the thickness of the artery walls over time in research studies. This helps them to see if treatments are working well. The wall thickness decreases faster in arteries of the head than in larger arteries outside the head. Ultrasound of the aorta close to heart helps to find out if a widening of the aorta develops. This can be dangerous because of rupture.

The value of axillary, facial, occipital, subclavian and common carotid arteries ultrasound in the diagnosis of giant cell arteritis.

OBJECTIVE: To assess the diagnostic value for GCA in adding the axillary arteries (AX) to the temporal artery (TA) ultrasound, particularly in patients with a cranial phenotype of the disease; and to investigate the utility of facial (FA), occipital (OC), subclavian (SC), and common carotid (CC) ultrasound in patients with suspected GCA. METHODS: Patients with new-onset GCA and a positive ultrasound of the TA, AX, FA, OC, SC or CC, followed at the rheumatology departments of two academic centres, were retrospectively included. RESULTS: 230 patients were assessed. TA halo sign was identified in 206/230 (89.6%) cases, FA in 40/82 (48.8%), OC in 17/69 (24.6%), AX in 56/230 (24.3%), SC in 31/57 (54.4%), and CC in 14/68 (20.6%). Negative TA ultrasound was found in 24/230 (10.4%) patients: 22 had AX involvement, 1 exclusive OC involvement and 1 exclusive SC involvement. Adding AX evaluation to the TA ultrasound increased the diagnostic yield for GCA in 9.6%, whereas adding OC or SCs to the TA and AX ultrasound increased it in 1.4% and 1.8%, respectively. No value was found in adding the FA or CCs. Notably, 13 patients with cranial symptoms and 4 with exclusively cranial symptoms showed negative TA ultrasound but positive AX ultrasound. CONCLUSION: Adding the evaluation of AXs to the TA ultrasound increased the number of patients diagnosed with GCA, even in cases of predominantly cranial symptoms. In the subset of patients where these arteries were assessed, no substantial benefit was found in adding the FA, OC, SC or CC arteries to the TA and AX ultrasonographic assessment.

Giant Cell Arteritis With Bilateral Central Retinal Artery Occlusion and Tongue Necrosis.

This case report describes a complicated case of giant cell arteritis (GCA) with tongue necrosis and bilateral central retinal artery occlusion (CRAO). An 81-year-old male patient with a history of recent retinal artery occlusion, ischemic stroke, and hypertensive emergency was evaluated. Clinical examination, including a visual acuity assessment, fundus evaluation, and oral examination, was performed. Laboratory investigations, such as erythrocyte sedimentation rate (ESR), were conducted. A temporal artery biopsy was performed to confirm the diagnosis of GCA. The patient presented with sudden vision loss in the left eye following a prior episode of retinal artery occlusion in the right eye. Ophthalmoscopic examination revealed CRAO in the left eye. Additionally, tongue necrosis, a rare manifestation of GCA, was observed. The ESR was significantly elevated. A temporal artery biopsy supported the diagnosis of GCA. The patient was promptly referred for immunologist consultation and initiated on intravenous methylprednisolone therapy. This case highlights the diverse and potentially devastating nature of GCA, involving ocular and systemic manifestations. Bilateral CRAO and tongue necrosis are rare but significant complications of GCA. Prompt diagnosis and early initiation of corticosteroid therapy are crucial to prevent irreversible visual loss and further complications. A multidisciplinary approach involving ophthalmologists and other specialists is essential for the comprehensive management of GCA.

Evaluation of the extracranial "multifocal arcuate sign," a novel MRI finding for the diagnosis of giant cell arteritis, on STIR and contrast-enhanced T1-weighted images.

BACKGROUND: While early diagnosis of giant cell arteritis (GCA) based on clinical criteria and contrast-enhanced MRI findings can lead to early treatment and prevention of blindness and cerebrovascular accidents, previously reported diagnostic methods which utilize contrast-enhanced whole head images are cumbersome. Diagnostic delay is common as patients may not be aware of initial symptoms and their significance. To improve current diagnostic capabilities, new MRI-based diagnostic criteria need to be established. This study aimed to evaluate the "multifocal arcuate sign" on short tau inversion recovery (STIR) and contrast-enhanced T1-weighted (CE-T1W) images as a novel extracranial finding for the diagnosis of GCA. METHODS: A total of 17 consecutive patients (including five with GCA) who underwent CE-T1W and whole-brain axial STIR imaging simultaneously between June 2010 and April 2020 were enrolled. We retrospectively reviewed their MR images. The "multifocal arcuate sign" was defined as "multiple distant arcuate areas with high signal intensity in extracranial soft tissues such as subcutaneous fat, muscles, and tendons." Extracranial abnormal high-signal-intensity areas were classified as "None," when no lesions were detected; "Monofocal," when lesions were detected only in one place; and "Multifocal," when lesions were detected in multiple places. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of "Multifocal" areas were calculated using cross tabulation. Fisher's exact test was used to compare "Multifocal" areas in five patients with GCA and those with other diseases. In addition, mean Cohen's kappa and Fleiss' kappa statistics were used to compare inter-reader agreement. RESULTS: The sensitivity, specificity, PPV, and NPV of the "multifocal arcuate sign" in patients with GCA were 60%, 92-100%, 75-100%, and 85-86%, respectively. Significantly more patients with GCA had "Multifocal" areas compared to those with other diseases (Fisher's exact test, p = 0.008-0.027). Mean Cohen's kappa and Fleiss' kappa for inter-reader agreement with respect to the five GCA patients were 0.52 and 0.49, respectively, for both STIR and CE-T1W sequences. CONCLUSIONS: The new radiologic finding of "multifocal arcuate sign" on STIR and CE-T1W images may be used as a radiologic criterion for the diagnosis of GCA, which can make plain MRI a promising diagnostic modality.

Effectiveness of janus kinase inhibitors in relapsing giant cell arteritis in real-world clinical practice and review of the literature.

BACKGROUND: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature. METHODS: Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted. RESULTS: Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them. CONCLUSIONS: This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).