Giant Cell Arteritis Research Articles

Mönckeberg calcification in a temporal artery

Mönckeberg’s calcification is a disease of low prevalence and unknown etiology that causes calcification of the middle layer of medium and small arteries. It usually presents with a clinical picture similar to giant cell arteritis, so a differential diagnosis with similar entities should be made. The diagnosis is anatomopathological, and there is no treatment that has shown significant results. Herein, we present the case of a 74-year-old male patient with recurrent syncope and chest pain, in whom giant cell arteritis was suspected and a temporal artery biopsy was taken with the incidental finding of calcification of Mönckeberg’s media. Key words: Calcification, Arteritis, Giant cell, Mönckeberg

Rheumatic diseases in the elderly: Challenges and management

Abstract The elderly demographic is seeing a gradual rise as a proportion of the overall global population, whilst also experiencing high rates of musculoskeletal issues, requiring specialized care. The management of rheumatic diseases in the elderly presents unique challenges due to the complex interplay among physiological changes, cognitive decline, and altered immune responses. Such conditions can be categorized into those progressing from earlier life stages (such as rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis, and gout) and those predominantly emerging in old age (such as polymyalgia rheumatica, giant cell arteritis, osteoarthritis, crystal arthropathies, and osteoporosis), each with distinct characteristics and management needs. These diseases often present atypically with nonspecific symptoms and altered serological markers, complicating diagnosis and management due to increased toxicity risks and comorbidities. Comprehensive, multidisciplinary care that includes cardiovascular health monitoring, bone density maintenance, gastrointestinal tolerance management, infection prevention, and mental health support are essential to improve outcomes and quality of life for elderly patients with rheumatic diseases.

Ultrasonography of the superficial temporal and axillary arteries in giant cell arteritis diagnosis

ObjectivesGiant 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 methodsWe 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. ResultsOf 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 %. ConclusionIn 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.

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

ObjectivesTo evaluate differences in presentation and outcome of giant cell arteritis (GCA) patients with and without polymyalgia rheumatica (PMR) symptoms. MethodsConsecutive patients diagnosed with GCA between 2000 and 2020 and followed for ≥12 months at the University Hospitals Leuven (Belgium), were included retrospectively. ResultsWe 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). ConclusionGCA 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.

BG03 A case of nasal tip necrosis secondary to giant cell arteritis and a review of the cutaneous manifestations reported in large-vessel vasculitis

BG03 A case of nasal tip necrosis secondary to giant cell arteritis and a review of the cutaneous manifestations reported in large-vessel vasculitis

Current management of giant cell arteritis and its complications.

This review provides an update on current management strategies for giant cell arteritis (GCA), emphasizing the need for alternative therapies to reduce disease relapses and mitigate glucocorticoid (GC)-related morbidity. The standard of care for GCA has traditionally involved prolonged use of GC, and recent studies are exploring faster GC tapering regimens in an effort to reduce adverse effects while maintaining disease control. Randomized clinical trials have highlighted the efficacy of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in reducing disease flares and sparing GCs. However, the optimal treatment duration with TCZ is unknown and patients remain at risk of relapse after treatment discontinuation. An unmet therapeutic need persists for patients who are not candidates for TCZ, and for those who have inadequate response to this biologic. Therefore, investigations into alternative therapies such as targeting interleukin-17A, blocking T-cell activation or inhibiting the Janus kinase-signal transducer and activator of transcription pathway, showcase potential avenues for tailored treatments. While GCs remain the cornerstone of therapy, TCZ emerges as a promising GC-sparing agent. Ongoing research targeting different pathways implicated in GCA pathogenesis have led to encouraging results. However, the preliminary nature of these findings necessitates larger randomized controlled trials to establish their efficacy conclusively.

Updates in the Management of Giant Cell Arteritis.

To briefly review the latest updates in management in giant cell arteritis, an autoimmune vasculitis affecting the medium to large vessels. 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.

GMCSF: More an Inflammatory Immune ‘Cytokine’ Than a Growth Factor

GMCSF, discovered in 1977, was one of the first growth factors for myelopoiesis. However, over time, it has been found to be redundant for basal myelopoiesis. Rather, its important function seems to be its effect on mature myeloid cells and the immune system. It is produced by a variety of cells, including macrophages, endothelial cells, T-cells etc. and works on the GMCSF receptor, which is mainly expressed by mature myeloid cells such as neutrophils, monocytes and macrophages. It has been found to be an important mediator of at least two autoimmune diseases: rheumatoid arthritis and multiple sclerosis. Animal models prove that GMCSF produced from T-cells play a crucial role in their pathogenesis of both these autoimmune diseases. This has led to the development of therapeutics which target GMCSF or its receptor. Clinical trials have been carried out in rheumatoid arthritis, which have shown modest efficacy. In addition, anti-GMCSF therapy has shown promise in giant cell arteritis.

Utilidad del 18F-FDG-PET/TC en la detección de vasculitis de gran vaso extracraneal en pacientes con polimialgia reumática o arteritis de células gigantes: revisión sistemática y metaanálisis

ObjectiveSystematic 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 methodsPubMed 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. Results268 publications were identified, of which 17 met the selection criteria and were included in the meta-analysis. The overall pooled prevalence of extracranial VGV by 18F-FDG PET/CT was 54.5% [95% CI: 42.6% to 66.1%]. In patients with GCA the prevalence was significantly higher than in patients with PMR (60.1% vs. 41.8%, P= .006). Likewise, studies with a lower risk of bias reported a higher prevalence of extracranial VGV (61.1% vs. 46.9%; P= .010). No publication bias was observed. ConclusionsThe 18F-FDGPET/CT test may be useful in the detection of extracranial VGV, 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.

Imaging findings in Giant Cell Arteritis: Don't Turn A Blind Eye To The Obvious!

Giant cell arteritis (GCA) is the most common primary large vessel systemic vasculitis in the western world. Even though the involvement of scalp and intracranial vessels has received much attention in the neuroradiology literature, GCA, being a systemic vasculitis can involve multiple other larger vessels including aorta and its major head and neck branches. Herein, the authors present a pictorial review of the various cranial, extracranial and orbital manifestations of GCA. An increased awareness of this entity may help with timely and accurate diagnosis, helping expedite therapy and preventing serious complications.ABBREVIATIONS: ACR= American College of Rheumatology, AION= Anterior Ischemic Optic Neuropathy, EULAR= European League Against Rheumatism, GCA= Giant Cell Arteritis, LV-GCA= Large vessel GCA, PMR= Polymyalgia Rheumatica, US= Ultrasound, VWI= Vessel Wall Imaging.

Histopathology reporting of temporal artery biopsy specimens for giant cell arteritis: results of a modified Delphi study

The temporal artery biopsy (TAB) is regarded as the gold-standard test in the diagnosis of giant cell arteritis (GCA). There is a lack of agreement among experienced pathologists regarding the...

Altered Plasma Levels and Tissue Expression of Fibroblast Activation Protein Alpha in Giant Cell Arteritis.

Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the medium- and large-sized arteries accompanied by remodeling of the vessel wall. Fibroblast activation protein alpha (FAP) is a serine protease that promotes both inflammation and fibrosis. Here, we investigated the plasma levels and vascular expression of FAP in GCA. Plasma FAP levels were measured with enzyme-linked immunosorbent assay in treatment-naive patients with GCA (n = 60) and polymyalgia rheumatica (PMR) (n = 63) compared with age- and sex-matched healthy controls (HCs) (n = 42) and during follow-up, including treatment-free remission (TFR). Inflamed temporal artery biopsies (TABs) of patients with GCA (n = 9), noninflamed TABs (n = 14), and aorta samples from GCA-related (n = 9) and atherosclerosis-related aneurysm (n = 11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts (CD90), macrophages (CD68/CD206/folate receptor beta), vascular smooth muscle cells (desmin), myofibroblasts (α-smooth muscle actin), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). Baseline plasma FAP levels were significantly lower in patients with GCA compared with patients with PMR and HCs and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months on remission in patients with GCA and gradually increased to the level of HCs in TFR. FAP expression was increased in inflamed TABs and aorta of patients with GCA compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Some of the FAP+ fibroblasts expressed IL-6 and MMP-9. FAP expression in GCA is clearly modulated both in plasma and in vessels. FAP may be involved in the inflammatory and remodeling processes in GCA and have utility as a target for imaging and therapeutic intervention.

Identification of two autoantigens recognised by circulating autoantibodies as potential biomarkers for diagnosing giant cell arteritis.

Giant cell arteritis (GCA) is a common vasculitis affecting patients aged 50 and older. GCA leads to chronic inflammation of large/medium-sized vessel walls with complications such as permanent vision loss and risk of stroke and aortic aneurysms. Early diagnosis is crucial and relies on temporal artery biopsy (TAB) and ultrasound imaging of temporal and axillary arteries. However, these methods have limitations. Serum biomarkers as autoantibodies have been reported but with inconclusive data for their use in the clinical setting. Additionally, C-reactive protein and erythrocyte sedimentation rate are non-specific and limited in reflecting disease activity, particularly in patients treated with IL-6 inhibitors. This study aimed to identify serum autoantibodies as new diagnostic biomarkers for GCA using a human protein array. One commercial and one proprietary human protein array were used for antibody profiling of sera from patients with GCA (n=55), Takayasu (TAK n=7), and Healthy Controls (HC n=28). The identified candidate autoantigens were purified and tested for specific autoantibodies by ELISA. Antibodies against two proteins, VSIG10L (V-Set and Immunoglobulin Domain Containing 10 Like) and DCBLD1 (discoidin), were identified and found to be associated with GCA, with an overall prevalence of 43-57%, respectively, and high specificity as individual antibodies. A control series of TAK sera tested negative. Detecting GCA-specific autoantibodies may offer a new, non-invasive tool for improving our diagnostic power in GCA. Even though cell-mediated immune responses are crucial for GCA pathogenesis, this finding opens the way for investigating the additional role of humoral immune responses in the disease.

SA40 A Targeted Literature Review of Economic Evaluations, Health-Related Quality of Life, Healthcare Resource Use, and Economic Outcomes Associated With Giant Cell Arteritis

SA40 A Targeted Literature Review of Economic Evaluations, Health-Related Quality of Life, Healthcare Resource Use, and Economic Outcomes Associated With Giant Cell Arteritis

Ultrasound Examination of Common Carotid Adventitial Thickness Can Differentiate Takayasu Arteritis and Large Vessel Giant Cell Arteritis.

Pathological studies have demonstrated that the adventitial layer is markedly thickened in Takayasu (TAK) as compared to large vessel giant cell arteritis (LV-GCA). An ultrasound (US) examination of the arterial vessels allows the determination of intima media thickness (IMT) and of adventitial layer thickness (extra media thickness (EMT)). No previous study has evaluated if there are differences in EMT thickness between TAK and LV-GCA. In this cross-sectional retrospective study of stored ultrasound (US) imaging, we have compared common carotid artery (CCA) EMT and IMT in a series of consecutive TAK and LV-GCA patients. US examination CCA IMT and EMT were significantly higher in TAK as compared to LV-GCA. With ROC curve analysis, we have found that an EMT > 0.76 mm has high sensitivity and specificity for TAK CCA examination. The percentage of CCA at EMT > 0.76 mm and the total arterial wall thickening were significantly higher in TAK group examinations. EMT thickness correlated with disease duration and IMT in the TAK group, as well as with the IMT and ESR values in the LV-GCA group. Upon multivariate logistic regression analysis, factors independently associated with TAK CCA were EMT > 0.76 mm and age. No significant variation in IMT and EMT could be demonstrated in subsequent US CCA examinations.

Scleritis as the Presenting Sign of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in the Setting of Temporal Arteritis.

Scleritis as the Presenting Sign of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in the Setting of Temporal Arteritis.

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

Abstract 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 Two hundred and thirty 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, one exclusive OC involvement and one exclusive SC involvement. Adding AX evaluation to the TA ultrasound increased the diagnostic yield for GCA by 9.6%, whereas adding OC or SCs to the TA and AX ultrasound increased it by 1.4% and 1.8%, respectively. No value was found in adding the FA or CCs. Notably, 13 patients with cranial symptoms and four 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.

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

ObjectiveSystematic 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 methodsPubMed 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. Results268 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. ConclusionsThe 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.

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

BackgroundA 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.MethodsRetrospective 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.ResultsThirty-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.ConclusionsThis 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).

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

BackgroundWhile 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.MethodsA 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.ResultsThe 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.ConclusionsThe 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.