Current evidence on the role of fibroblasts in large-vessel vasculitides: From pathogenesis to therapeutics.

Large-vessel vasculitides (LVV) comprise a group of chronic inflammatory diseases of the aorta and its major branches. The most common forms of LVV are giant cell arteritis (GCA) and Takayasu arteritis (TAK). Both GCA and TAK are characterized by granulomatous inflammation of the vessel wall accompanied by a maladaptive immune and vascular response that promotes vascular damage and remodeling. The inflammatory process in LVV starts in the adventitia where fibroblasts constitute the dominant cell population. Fibroblasts are traditionally recognized for synthesizing and renewing the extracellular matrix thereby being major players in maintenance of normal tissue architecture and in tissue repair. More recently, fibroblasts have emerged as a highly plastic cell population exerting various functions, including the regulation of local immune processes and organization of immune cells at the site of inflammation through production of cytokines, chemokines and growth factors as well as cell-cell interaction. In this review, we summarize and discuss the current knowledge on fibroblasts in LVV. Furthermore, we identify key questions that need to be addressed to fully understand the role of fibroblasts in the pathogenesis of LVV.

A direct comparison in diagnostic performance of CDUS, FDG-PET/CT and MRI in patients suspected of giant cell arteritis.

OBJECTIVES: This study directly compares diagnostic performance of Colour Duplex Ultrasound (CDUS), Fluor-18-deoxyglucose Positron Emission Tomography Computed Tomography (FDG-PET/CT) and Magnetic Resonance Imaging (MRI) in patients suspected of giant cell arteritis (GCA). METHODS: Patients with suspected GCA were included in a nested-case control pilot study. CDUS, whole body FDG-PET/CT and cranial MRI were performed within 5 working days after initial clinical evaluation. Clinical diagnosis after six months follow-up by experienced rheumatologists in the field of GCA, blinded for imaging, was used as reference standard. Diagnostic performance of the imaging modalities was determined. Stratification for GCA subtype was performed and imaging results were evaluated in different risk stratification groups. RESULTS: In total, 23 patients with GCA and 19 patients suspected of but not diagnosed with GCA were included. Sensitivity was 69.6% (95%CI 50.4%-88.8%) for CDUS, 52.2% (95%CI 31.4%-73.0%) for FDG-PET/CT and 56.5% (95%CI 35.8%-77.2%) for MRI. Specificity was 100% for CDUS, FDG-PET/CT and MRI. FDG-PET/CT was negative for GCA in all isolated cranial GCA patients (n = 8), while MRI was negative in all isolated extracranial GCA patients (n = 4). In 4 GCA patients with false-negative (n = 2; intermediate and high risk) or inconclusive (n = 2; low and intermediate risk) CDUS results, further imaging confirmed diagnosis. CONCLUSIONS: Sensitivity of CDUS was highest, while specificity was excellent in all imaging modalities. Nevertheless, confidence intervals of all imaging modalities were overlapping. Following EULAR recommendations, CDUS can be used as a first test to diagnose GCA. With insufficient evidence for GCA, further testing considering GCA subtype is warranted.

Multimodality imaging to assess diagnosis and evaluate complications of large vessel arteritis.

Different types of vasculitis can be distinguished according to the blood vessel's size that is preferentially affected: large-vessel, medium-vessel, and small-vessel vasculitides. Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the main forms of large-vessel vasculitis, and may lead to lumen narrowing. Clinical manifestations of arterial narrowing on the short- and long term include vision loss, stroke, limb ischaemia and heart failure. Imaging tools are well established diagnostic tests for large-vessel vasculitis and may aid therapy monitoring in selected cases, while providing important information regarding the occurrence of vascular damage, tissue and organ complications. This review aims to provide the current status of multimodality imaging for diagnosis and identification of vascular complications in the field of large vessel vasculitis.

Large vessel giant cell arteritis.

Giant cell arteritis is the principal form of systemic vasculitis affecting people over 50. Large-vessel involvement, termed large vessel giant cell arteritis, mainly affects the aorta and its branches, often occurring alongside cranial giant cell arteritis, but large vessel giant cell arteritis without cranial giant cell arteritis can also occur. Patients mostly present with constitutional symptoms, with localising large vessel giant cell arteritis symptoms present in a minority of patients only. Large vessel giant cell arteritis is usually overlooked until clinicians seek to exclude it with imaging by ultrasonography, magnetic resonance angiography (MRA), computed tomography angiography (CTA), or [18F]fluorodeoxyglucose-PET-CT. Although the role of imaging in treatment monitoring remains uncertain, imaging by MRA or CTA is crucial for identifying aortic aneurysm formation during patient follow up. In this Series paper, we define the large vessel subset of giant cell arteritis and summarise its clinical challenges. Furthermore, we identify areas for future research regarding the management of large vessel giant cell arteritis.

Altered plasma levels and tissue expression of fibroblast activation protein alpha in giant cell arteritis.

OBJECTIVE: 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 which promotes both inflammation and fibrosis. Here we investigated the plasma levels and vascular expression of FAP in GCA. METHODS: Plasma FAP levels were measured with ELISA in treatment-naive GCA (n=60) and polymyalgia rheumatica (PMR, n=63) patients (compared to age- and sex-matched healthy controls (HC), n=42) and during follow-up, including treatment free remission (TFR). Inflamed temporal artery biopsies (TAB) of GCA patients (n=9), non-inflamed TAB (n=14), aorta samples from GCA- (n=9) and atherosclerosis-related aneurysm (n=11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts(CD90), macrophages(CD68/CD206/FRß), vascular smooth muscle cells(desmin), myofibroblasts(αSMA), interleukin(IL)-6 and matrix metalloproteinase(MMP)-9. RESULTS: Baseline plasma FAP levels were significantly lower in GCA compared to PMR patients and HC, and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months upon remission in GCA, and gradually increased to the level of HC in TFR. FAP expression was increased in inflamed TAB and aorta of GCA patients compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Part of the FAP+ fibroblasts expressed IL-6 and MMP-9. CONCLUSION: 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 target for imaging and therapeutic intervention.

Advances in PET Imaging of Large Vessel Vasculitis: An Update and Future Trends.

Systemic vasculitides are autoimmune diseases characterized by inflammation of blood vessels. They are categorized based on the size of the preferentially affected blood vessels: large-, medium-, and small-vessel vasculitides. The main forms of large-vessel vasculitis include giant cell arteritis (GCA) and Takayasu arteritis (TAK). Depending on the location of the affected vessels, various imaging modalities can be employed for diagnosis of large vessel vasculitis: ultrasonography (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). These imaging tools offer complementary information about vascular changes occurring in vasculitis. Recent advances in PET imaging in large vessel vasculitis include the introduction of digital long axial field-of-view PET/CT, dedicated acquisition, quantitative methodologies, and the availability of novel radiopharmaceuticals. This review aims to provide an update on the current status of PET imaging in large vessel vasculitis and to share the latest developments on imaging vasculitides.

Development of a diagnostic prediction model for giant cell arteritis by sequential application of Southend Giant Cell Arteritis Probability Score and ultrasonography: a prospective multicentre study.

BACKGROUND: Giant cell arteritis is a critically ischaemic disease with protean manifestations that require urgent diagnosis and treatment. European Alliance of Associations for Rheumatology (EULAR) recommendations advocate ultrasonography as the first investigation for suspected giant cell arteritis. We developed a prediction tool that sequentially combines clinical assessment, as determined by the Southend Giant Cell Arteritis Probability Score (SGCAPS), with results of quantitative ultrasonography. METHODS: This prospective, multicentre, inception cohort study included consecutive patients with suspected new onset giant cell arteritis referred to fast-track clinics (seven centres in Italy, the Netherlands, Spain, and UK). Final clinical diagnosis was established at 6 months. SGCAPS and quantitative ultrasonography of temporal and axillary arteries with three scores (ie, halo count, halo score, and OMERACT GCA Score [OGUS]) were performed at diagnosis. We developed prediction models for diagnosis of giant cell arteritis by multivariable logistic regression analysis with SGCAPS and each of the three ultrasonographic scores as predicting variables. We obtained intraclass correlation coefficient for inter-rater and intra-rater reliability in a separate patient-based reliability exercise with five patients and five observers. FINDINGS: Between Oct 1, 2019, and June 30, 2022, we recruited and followed up 229 patients (150 [66%] women and 79 [34%] men; mean age 71 years [SD 10]), of whom 84 were diagnosed with giant cell arteritis and 145 with giant cell arteritis mimics (controls) at 6 months. SGCAPS and all three ultrasonographic scores discriminated well between patients with and without giant cell arteritis. A reliability exercise showed that the inter-rater and intra-rater reliability was high for all three ultrasonographic scores. The prediction model combining SGCAPS with the halo count, which was termed HAS-GCA score, was the most accurate model, with an optimism-adjusted C statistic of 0·969 (95% CI 0·952 to 0·990). The HAS-GCA score could classify 169 (74%) of 229 patients into either the low or high probability groups, with misclassification observed in two (2%) of 105 patients in the low probability group and two (3%) of 64 of patients in the high probability group. A nomogram for easy application of the score in daily practice was created. INTERPRETATION: A prediction tool for giant cell arteritis (the HAS-GCA score), combining SGCAPS and the halo count, reliably confirms and excludes giant cell arteritis from giant cell arteritis mimics in fast-track clinics. These findings require confirmation in an independent, multicentre study. FUNDING: Royal College of Physicians of Ireland, FOREUM.

Immune checkpoint inhibitor-mediated polymyalgia rheumatica versus primary polymyalgia rheumatica: comparison of disease characteristics and treatment requirement.

OBJECTIVES: To compare clinical characteristics, imaging findings and treatment requirements of patients with immune checkpoint inhibitor-mediated polymyalgia rheumatica (ICI-PMR) and primary PMR. METHODS: This single centre, retrospective cohort study compared ICI-PMR in patients with cancer (n = 15) to patients with primary PMR (n = 37). A comparison was made between clinical symptoms, laboratory markers, ultrasonography,18F-FDG-PET/CT findings and treatment requirements related to PMR. RESULTS: Patients with ICI-PMR less frequently fulfilled the EULAR/ACR classification criteria for PMR (66.7%) than patients with primary PMR (97.3%). Morning stiffness, weight loss and elevation of the ESR were less frequently seen in patients with ICI-PMR. No differences were observed regarding the presence of inflammatory lesions on ultrasound of the shoulders and hips between the two groups. The Leuven and the Leuven/Groningen 18F-FDG-PET/CT scores were significantly lower in the ICI-PMR group. Finally, the ICI-PMR group could be managed with less glucocorticoids than the primary PMR group. CONCLUSION: Our findings indicate that ICI-PMR may have a milder course with less inflammation than primary PMR on 18F-FDG-PET/CT. ICI-mediated PMR patients can be managed with a relatively low glucocorticoid dose. Our study underscores that ICI-PMR should be regarded as PMR-like syndrome.

Humoral SARS-CoV-2 Vaccine Responses in Patients With Giant Cell Arteritis and Polymyalgia Rheumatica: Decay After Primary Vaccination and Effects of the Booster.

OBJECTIVE: Vaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10 mg/day of prednisolone and methotrexate was associated with reduced antibody concentrations after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). This follow-up study was undertaken to measure the decay of antibody concentrations and the immunogenicity of SARS-CoV-2 booster vaccination. METHODS: Patients with GCA/PMR included in the primary vaccination (BNT162b2 [Pfizer-BioNTech] or ChAdOx1 [Oxford/AstraZeneca]) study were asked again to donate blood samples 6 months after primary vaccination (n = 24) and 1 month after booster vaccination (n = 46, BNT162b2 or mRNA1273). Data were compared to those of age-, sex-, and vaccine-matched controls (n = 58 and n = 42, respectively). Multiple linear regression was performed with post-booster antibody concentrations as dependent variable and post-primary vaccination antibodies, prednisolone >10mg/day, and methotrexate use as predicting variables. RESULTS: Antibody concentrations decreased faster over time in GCA/PMR patients than in controls, which was associated with prednisolone treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post primary vaccination, but not treatment during booster vaccination, were predictive for antibody concentrations post booster vaccination. CONCLUSION: These results indicate that the decay of humoral immunity after primary vaccination is associated with prednisolone treatment, whereas the subsequent increase after booster vaccination, was not. Patients with low antibody concentrations following primary vaccination remained at an immunogenic disadvantage after a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeated booster vaccination for patients with poor responses to primary vaccination.

Cytokine producing B-cells and their capability to polarize macrophages in giant cell arteritis.

OBJECTIVE: The lack of disease-specific autoantibodies in giant cell arteritis (GCA) suggests an alternative role for B-cells readily detected in the inflamed arteries. Here we study the cytokine profile of tissue infiltrated and peripheral blood B-cells of patients with GCA. Moreover, we investigate the macrophage skewing capability of B-cell-derived cytokines. METHODS: The presence of various cytokines in B-cell areas in temporal artery (n = 11) and aorta (n = 10) was identified by immunohistochemistry. PBMCs of patients with GCA (n = 11) and polymyalgia rheumatica (n = 10), and 14 age- and sex-matched healthy controls (HC) were stimulated, followed by flow cytometry for cytokine expression in B-cells. The skewing potential of B-cell-derived cytokines (n = 6 for GCA and HC) on macrophages was studied in vitro. RESULTS: The presence of IL-6, GM-CSF, TNFα, IFNγ, LTß and IL-10 was documented in B-cells and B-cell rich areas of GCA arteries. In vitro, B-cell-derived cytokines (from both GCA and HC) skewed macrophages towards a pro-inflammatory phenotype with enhanced expression of IL-6, IL-1ß, TNFα, IL-23, YKL-40 and MMP-9. In vitro stimulated peripheral blood B-cells from treatment-naïve GCA patients showed an enhanced frequency of IL-6+ and TNFα+IL-6+ B-cells compared to HCs. This difference was no longer detected in treatment-induced remission. Erythrocyte sedimentation rate positively correlated with IL-6+TNFα+ B-cells. CONCLUSION: B-cells are capable of producing cytokines and steering macrophages towards a pro-inflammatory phenotype. Although the capacity of B-cells in skewing macrophages is not GCA specific, these data support a cytokine-mediated role for B-cells in GCA and provide grounds for B-cell targeted therapy in GCA.

Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica.

Background: Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis. Methods: APCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). We identified three monocyte subsets, and three DC subsets: plasmacytoid DCs (pDCs), CD141+ conventional DCs (cDC1) and CD1c+ conventional DCs (cDC2). Each of these subsets was analyzed for expression of pattern recognition receptors (TLR2, TLR4), immune checkpoints (CD86, PDL1, CD40) and activation markers (HLA-DR, CD11c). Results: t-SNE plots revealed a differential clustering of APCs between GCA/PMR and HCs. Further analyses showed shifts in monocyte subsets and a lower proportion of the small population of cDC1 cells in GCA/PMR, whereas cDC2 proportions correlated negatively with CRP (r=-0.52). Classical monocytes of GCA/PMR patients show reduced expression of TLR2, HLA-DR, CD11c, which was in contrast to non-classical monocytes that showed higher marker expression. Additionally, single cell RNA sequencing in GCA patients identified a number of differentially expressed genes related to inflammation and metabolism in APCs. Conclusion: Circulating non-classical monocytes display an activated phenotype in GCA/PMR patients at diagnosis, whereas classical monocytes show reduced expression of activation markers. Whether these findings reflect APC migration patterns or the effects of long-term inflammation remains to be investigated.

Effect of DMARDs on the immunogenicity of vaccines.

Vaccines are important for protecting individuals at increased risk of severe infections, including patients undergoing DMARD therapy. However, DMARD therapy can also compromise the immune system, leading to impaired responses to vaccination. This Review focuses on the impact of DMARDs on influenza and SARS-CoV-2 vaccinations, as such vaccines have been investigated most thoroughly. Various data suggest that B cell depletion therapy, mycophenolate mofetil, cyclophosphamide, azathioprine and abatacept substantially reduce the immunogenicity of these vaccines. However, the effects of glucocorticoids, methotrexate, TNF inhibitors and JAK inhibitors on vaccine responses remain unclear and could depend on the dosage and type of vaccination. Vaccination is aimed at initiating robust humoral and cellular vaccine responses, which requires efficient interactions between antigen-presenting cells, T cells and B cells. DMARDs impair these cells in different ways and to different degrees, such as the prevention of antigen-presenting cell maturation, alteration of T cell differentiation and selective inhibition of B cell subsets, thus inhibiting processes that are necessary for an effective vaccine response. Innovative modified vaccination strategies are needed to improve vaccination responses in patients undergoing DMARD therapy and to protect these patients from the severe outcomes of infectious diseases.

Disease stratification in GCA and PMR: state of the art and future perspectives.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related conditions characterized by systemic inflammation, a predominant IL-6 signature, an excellent response to glucocorticoids, a tendency to a chronic and relapsing course, and older age of the affected population. This Review highlights the emerging view that these diseases should be approached as linked conditions, unified under the term GCA-PMR spectrum disease (GPSD). In addition, GCA and PMR should be seen as non-monolithic conditions, with different risks of developing acute ischaemic complications and chronic vascular and tissue damage, different responses to available therapies and disparate relapse rates. A comprehensive stratification strategy for GPSD, guided by clinical findings, imaging and laboratory data, facilitates appropriate therapy and cost-effective use of health-economic resources. Patients presenting with predominant cranial symptoms and vascular involvement, who usually have a borderline elevation of inflammatory markers, are at an increased risk of sight loss in early disease but have fewer relapses in the long term, whereas the opposite is observed in patients with predominant large-vessel vasculitis. How the involvement of peripheral joint structures affects disease outcomes remains uncertain and understudied. In the future, all cases of new-onset GPSD should undergo early disease stratification, with their management adapted accordingly.

Role of 18F-FDG PET/CT in Large Vessel Vasculitis and Polymyalgia Rheumatica.

Systemic vasculitides comprise a group of autoimmune diseases affecting blood vessels, including large vessel vasculitis (LVV) and medium-sized vessel vasculitis such as giant cell arteritis (GCA) and Takayasu arteritis (TAK). GCA frequently overlaps with polymyalgia rheumatica (PMR), a rheumatic inflammatory condition affecting bursae, tendons or tendon sheaths, and joints. 18F-FDG PET/CT plays an important role in the diagnostic work-up of GCA, PMR, and TAK and is increasingly used to monitor treatment response. This continuing education article provides up-to-date guidance on the role of 18F-FDG PET/CT in patients with LVV, medium-sized vessel vasculitis, and PMR. It provides a general introduction on the clinical presentation and challenges in the diagnostic work-up of LVV and medium-sized vessel vasculitis, with a focus on the 2 major LVV subtypes: GCA, including PMR, and TAK. Next, practice points to perform and interpret the results of 18F-FDG PET/CT are described in line with the published procedure recommendations. Furthermore, the diagnostic performance and its role for treatment monitoring are discussed, taking into account recent international recommendations for the use of imaging in LVV and medium-sized vessel vasculitis in clinical practice. This is illustrated by several clinically representative PET/CT scan examples. Lastly, knowledge of limitations and pitfalls is essential to understand the role of 18F-FDG PET/CT in LVV, medium-sized vessel vasculitis, and PMR. Challenges and opportunities, as well as future research and conclusions, are highlighted. Learning objectives provide up-to-date guidance for the role of 18F-FDG PET/CT in patients with suspected LVV, medium-sized vessel vasculitis, and PMR.

Positron Emission Tomography Imaging in Vasculitis.

Systemic vasculitides comprise a group of autoimmune diseases affecting blood vessels. [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) plays an important role in the diagnosis and therapeutic monitoring of vasculitides affecting large-sized and medium-sized vessels. FDG-PET/CT also provides complementary information to other vascular imaging tools. The resolution and sensitivity of newer generation scanners continues to increase, hereby improving the ability of FDG-PET/CT to accurately assess the full disease extent in patients with vasculitis. Novel tracers targeting specific immune cells will allow for more detailed detection of vascular infiltrates.

An Automated Method for Artifical Intelligence Assisted Diagnosis of Active Aortitis Using Radiomic Analysis of FDG PET-CT Images.

The aim of this study was to develop and validate an automated pipeline that could assist the diagnosis of active aortitis using radiomic imaging biomarkers derived from [18F]-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET-CT) images. The aorta was automatically segmented by convolutional neural network (CNN) on FDG PET-CT of aortitis and control patients. The FDG PET-CT dataset was split into training (43 aortitis:21 control), test (12 aortitis:5 control) and validation (24 aortitis:14 control) cohorts. Radiomic features (RF), including SUV metrics, were extracted from the segmented data and harmonized. Three radiomic fingerprints were constructed: A-RFs with high diagnostic utility removing highly correlated RFs; B used principal component analysis (PCA); C-Random Forest intrinsic feature selection. The diagnostic utility was evaluated with accuracy and area under the receiver operating characteristic curve (AUC). Several RFs and Fingerprints had high AUC values (AUC > 0.8), confirmed by balanced accuracy, across training, test and external validation datasets. Good diagnostic performance achieved across several multi-centre datasets suggests that a radiomic pipeline can be generalizable. These findings could be used to build an automated clinical decision tool to facilitate objective and standardized assessment regardless of observer experience.

An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

Update on Imaging of Inflammatory Arthritis and Related Disorders.

Arthritis and other rheumatic disorders are very frequent in the general population and responsible for a huge physical and disability burden to affected patients as well as a major cost to the society. Precise evaluation often relies on clinical data only but additional imaging may be required i) for a more objective assessment of the disease status, such as in rheumatoid arthritis (RA) or ankylosing spondyloarthritis (AS), ii) for providing prognostic information and evaluating response to treatment or iii) for establishing diagnosis, in patients with unclear clinical picture, such as polymyalgia rheumatica (PMR) and large-vessel vasculitis (LVV). Besides radiological techniques (x-rays, ultrasound, and MRI), functional and molecular imaging has emerged as a valid tool for this purpose in several disorders. Bone scanning has long been a method of choice but is now more used as a triage tool in patients with unclear complaints, including degenerative disorders (eg osteoarthritis). 18F-FDG-PET/CT (FDG) proved efficient in assessing the extent of the disease and response to treatment in RA and related disorders, and to provide accurate diagnosis in some systemic disorders, including PMR and LVV. Based on glucose metabolism, FDG-PET/CT is able to show increased metabolism in peripheral cells involved in inflammation (eg neutrophils, lymphocytes or monocytes/macrophages) but also in fibroblasts that proliferate in the pannus. The lack of specificity of FDG is a limitation and many alternative tracers were developed at the preclinical stage or applied in the clinics, especially within clinical trials. They include imaging of macrophages using translocator protein (TSPO), folate-receptors or other targets on activated cells. These new tools will undoubtedly become more and more available in the everyday clinical workup of patients with rheumatisms. Finally, it should be kept in mind that a very simple tracer, 18F-fluoride is widely more performant in AS than FDG.

Comparing Diagnostic Performance of Short and Long [18F]FDG-PET Acquisition Times in Giant Cell Arteritis.

(1) Background: In giant cell arteritis (GCA), the assessment of cranial arteries using [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) combined with low-dose computed tomography (CT) may be challenging due to low image quality. This study aimed to investigate the effect of prolonged acquisition time on the diagnostic performance of [18F]FDG PET/CT in GCA. (2) Methods: Patients with suspected GCA underwent [18F]FDG-PET imaging with a short acquisition time (SAT) and long acquisition time (LAT). Two nuclear medicine physicians (NMPs) reported the presence or absence of GCA according to the overall image impression (gestalt) and total vascular score (TVS) of the cranial arteries. Inter-observer agreement and intra-observer agreement were assessed. (3) Results: In total, 38 patients were included, of whom 20 were diagnosed with GCA and 18 were without it. Sensitivity and specificity for GCA on SAT scans were 80% and 72%, respectively, for the first NMP, and 55% and 89% for the second NMP. On the LAT scans, these values were 65% and 83%, and 75% and 83%, respectively. When using the TVS, LAT scans showed especially increased specificity (94% for both NMPs). Observer agreement was higher on the LAT scans compared with that on the SAT scan. (4) Conclusions: LAT combined with the use of the TVS may decrease the number of false-positive assessments of [18F]FDG PET/CT. Additionally, LAT and TVS may increase both inter and intra-observer agreement.