OBJECTIVE: To assess the maintenance of efficacy of one year of tocilizumab (TCZ) monotherapy after its discontinuation in large vessel-GCA (LV-GCA).
METHODS: 17 patients with active LV-GCA were previously treated with 3 boluses of intravenous methylprednisone and weekly subcutaneous TCZ in monotherapy for 52 weeks. Patients in relapse-free clinical remission at week 52 discontinued TCZ and entered part two, which was a 26-week observational follow-up period. PET/CT was performed in all patients at the end of the 26-week observational period (week 78). End points were the variation in PET vascular activity score (PETVAS) at week 78 compared with baseline and with week 52, and the proportion of patients with relapse-free clinical remission at week 78 and at the end of the follow-up.
RESULTS: Compared with baseline, a significant reduction in PETVAS was observed at week 78, mean (95% CI) change -6.6 (-9.5 to -3.7). However, compared with week 52, PETVAS significantly increase 6 months after TCZ discontinuation (week 78), mean (95% CI) change 4.6 (0.7-8.5). The proportion of patients with relapse-free clinical remission at weeks 78 and at the end of the follow-up (median time from TCZ discontinuation 148 weeks) was 11/17 (65%, 95% CI 38-86) and 8/17 (47%, 95% CI 23-72), respectively. Age and sex-adjusted HR (95% CI) for each unit increase of PETVAS indicating subsequent relapse was 1.36 (0.92-2.00).
CONCLUSIONS: One year of TCZ monotherapy was effective in maintaining drug-free clinical remission in LV-GCA. Changes in PETVAS early after TCZ discontinuation may predict subsequent relapses.
BACKGROUND: ClinicalTrials.gov, NCT05394909.

UNASSIGNED: To evaluate relapses in giant cell arteritis (GCA), investigate the utility of vascular ultrasound to detect relapses, and develop and assess a composite score for GCA disease activity (GCAS) based on clinical symptoms, ultrasound imaging activity, and C-reactive protein (CRP).
UNASSIGNED: Patients with GCA were prospectively followed with scheduled visits, including assessment for clinical relapse, protocol ultrasound examination, and CRP. At each visit, patients were defined as having ultrasound remission or relapse. GCAS was calculated at every visit.
UNASSIGNED: The study included 132 patients, with a median follow-up time of 25 months [interquartile range (IR) 21]. The clinical relapse rate was 60.6%. There were no differences in relapse rates between GCA subtypes (cranial-GCA, large vessel (LV)-GCA, and mixed-GCA) (p = 0.83). Ultrasound yielded a sensitivity of 61.2% and a specificity of 72.3% for diagnosing GCA- relapse in our cohort. In 7.7% of follow-up visits with clinical relapses, neither high CRP nor findings of ultrasound relapse were registered. In comparison, in 10.3% of follow-up visits without symptoms of clinical relapse, there were both a high CRP and findings of ultrasound relapse.
UNASSIGNED: We found moderate sensitivity and specificity for ultrasound as a monitoring tool for relapse in this prospective cohort of GCA patients. The extent or subtype of vasculitis at the diagnosis did not influence the number of relapses. Based on a combination of clinical symptoms, elevated CRP, and ultrasound findings, a composite score for GCA activity is proposed.

UNASSIGNED: Primary Sjögren\'s syndrome (PSS) is a systemic autoimmune disease that mainly affects exocrine glands. Little is known about PSS associated cervical and intracranial cerebral large-vessel vasculitis outside of individual case reports.
UNASSIGNED: We present 5 cases of ischemic stroke or transient ischemic stroke (TIA) caused by PSS associated cervical and intracranial large-vessel vasculitis. Literature review was performed to summarize and identify the demographic, clinical features, treatment, and prognosis of this condition.
UNASSIGNED: The review resulted in 8 included articles with 8 patients, plus our 5 new patients, leading to a total of 13 subjects included in the analysis. The median age was 43 (range, 17-69) years old, among which 69.2 % (9/13) were female, and 92.3 % (12/13) came from Asia. Among them, 84.6 % (11/13) presented with cerebral infarction and 70.0 % (7/10) with watershed infarction. Middle cerebral artery (MCA) (6/13, 46.2 %) and internal carotid artery (ICA) (6/13, 46.2 %) were the most frequently involved arteries. Remarkable vessel wall concentric thickening and enhancement was observed in 57.1 % (4/7) patients and intravascular thrombi was identified in 28.6 % (2/7) patients. Glucocorticoid combined with non-glucocorticoid immunosuppressants (8/12, 66.7 %) were the most often chosen medication therapy and 4 patients received surgical intervention.
UNASSIGNED: Asian females are the most vulnerable population to ischemic stroke or TIA due to PSS associated cervical and intracranial large-vessel vasculitis. Cerebral infarctions were characterized by recurrence and watershed pattern. Magnetic resonance vessel wall imaging (MR-VWI) helps to identify the inflammatory pathology of large vessel lesion in PSS.

UNASSIGNED: The objective of this study was 2-fold: first, to evaluate whether superb microvascular imaging (SMI) could be used to visualize neovascularization in temporal arteries, and, second, to evaluate the diagnostic performance of high frequency ultrasound with SMI using an extended protocol in patients with suspected giant cell arteritis (GCA).
UNASSIGNED: This retrospective study comprised 120 patients consecutively examined with an extended CDU protocol (temporal, facial, axillary, subclavian, brachiocephalic, and carotid arteries) between 2020 and 2022. Of all patients, 107 had no previous GCA diagnosis and 13 had a previous GCA diagnosis. SMI was used to evaluate neovascularization in the temporal arteries. Arteritis were characterized as low- or medium-echogenic, homogeneous wall thickening, with or without a positive compression sign in the temporal arteries. The Halo count, i.e., the number of temporal and axillary artery segments with signs of arteritis, was evaluated. The reference was clinically diagnosed GCA confirmed after ≥6-month follow-up.
UNASSIGNED: Of the eligible 107 patients with new suspected GCA, 33 (31%) received a clinical GCA diagnosis. Neovascularization was detected in 14 patients (43%). Patients with neovascularization displayed a higher halo count [median 6 (25th-75th percentile 4.75-7) vs. 3 (2-4-4), p = 0.005]. CDU of only the temporal arteries showed sensitivity and specificity (95% confidence intervals) of 94% (80-100%) and 100% (95-100%), respectively. The addition of extra-cranial arteries increased the sensitivity to 100%. Of the 13 patients investigated for suspected relapse, three had a clinically confirmed relapse. One of them displayed neovascularization together with other signs of inflammation.
UNASSIGNED: We show for the first time that inflammatory neovascularization of the temporal arteries can be detected by SMI. Neovascularization is associated with a more-widespread cranial disease. The value of neovascularization should be further investigated, especially for the detection of GCA relapse.

Pulmonary vasculitis identifies a heterogeneous group of diseases characterized by inflammation, damage and necrosis of the wall of pulmonary vessels. The most common approach to classify vasculitis is according to etiology, therefore dividing them into primary and secondary, with a further sub-classification of primary vasculitis based on the size of the affected vessels (large, medium, and small). Pulmonary involvement is frequently observed in patients with systemic vasculitis and radiological presentation is not pathognomonic, but may vary between diseases. The main findings using high-resolution computed tomography (HRCT) include small vessel wall thickening, nodular lesions, cavitary lesions, reticular opacities, ground-glass opacities (GGO), consolidations, interlobular septal thickening, tracheobronchial stenosis, and aneurysmal dilatation of pulmonary arteries, with or without pleural effusion. Radiological diagnosis alone is difficult since signs and symptoms of lung vessel involvement are often non-specific and might overlap with other conditions such as infections, connective tissue diseases and neoplasms. Therefore, the aim of this review is to describe the most common radiological features of lung involvement in pulmonary vasculitis so that, alongside detailed clinical history and laboratory tests, a prompt diagnosis can be performed.

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).
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.

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).

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.

UNASSIGNED: The aim of this study is to evaluate the baseline F18-FDG PET/CT findings of individuals diagnosed with giant cell arteritis (GCA) and to explore its association with clinical findings and classification criteria.
UNASSIGNED: We analysed data from patients who underwent F18-FDG PET/CT scans to investigate large vessel (LV) involvement between 2010 and 2019. Only patients with a clinical diagnosis of GCA and at least 6 months of follow-up were included. We compared initial clinical features and laboratory findings based on the presence of LV vasculitis on PET/CT and the maximum standard uptake value (SUVmax) of vascular territories.
UNASSIGNED: Twenty-nine patients (median age at diagnosis: 70, F/M: 24/5) were included in the study. Among them, 21 patients (72.4%) presented with cranial symptoms, while 8 patients (27.5%) had isolated LV-GCA. Twenty-two patients (75.9%) met the ACR/EULAR 2022 GCA classification criteria. LV vasculitis was detected on PET/CT in 23 patients (79.3%). A positive correlation was observed between SUVmax in the thoracic aorta and both CRP and ESR levels (r = 0.50, p = 0.026 and r = 0.63, p = 0.002, respectively). PET/CT positive patients were found to be younger (p = 0.016) and more frequently female (p = 0.017). They also exhibited fewer headaches (56.5% vs. 100%, p = 0.04), experienced fewer flares during follow-up (p = 0.03), and had a lower cumulative glucocorticoid dose at the 6th month (p = 0.036). Comparison of PET/CT-positive patients (n = 23) based on the fulfilment of the ACR/EULAR 2022 classification criteria revealed that patients who met these criteria were older (p = 0.02) and had significantly lower CRP levels at diagnosis (p = 0.02).
UNASSIGNED: The performance of F18-FDG PET/CT in diagnosing LV involvement in GCA is favourable, and the severity of FDG uptake in the vessel wall correlates with the acute phase response. Patients with extracranial involvement on PET/CT exhibit distinct features, including a younger age and female predominance. Additionally, these patients appear to experience fewer relapses and require lower doses of glucocorticoids. However, the clinical significance of PET/CT in patients who met ACR/EULAR classification criteria, predominantly consisting of patients with ischemic cranial symptoms, could not be determined in our study.

OBJECTIVE: To assess the prognosis and outcome of patients with isolated carotid vasculitis.
METHODS: We performed a retrospective multicenter study of 36 patients (median age at diagnosis was 37 [IQR 27-45] years and 11 [31 %] patients were men) with initial presentation as isolated carotid vasculitis. Study endpoints included vascular complications, relapses, and progression to large vessel vasculitis (i.e. Giant cell arteritis or Takayasu).
RESULTS: The most frequent involvement was the left internal carotid artery (39 %), and 81 % had stenosis. After a median follow-up of 32 months [IQR 12-96], 21 (58 %) patients had a vascular event, including 31 % of new onset vascular lesions and 25 % of stroke/transient ischemic attack. Patients with stroke had less carotidynia at diagnosis (33 % vs 74 %, p = 0.046), higher significant carotid stenosis (i.e. > 50 %) (89 % vs. 30 %, p = 0.026) and higher severe carotid stenosis (i.e. >70 %) (67 % vs 19 %, p = 0.012), compared to those without stroke. Twenty (52 %) patients experienced relapses. High CRP at diagnosis was associated with relapses (p = 0.022). At the end of follow-up, 21 (58 %) patients were classified as having Takayasu arteritis, 13 (36 %) as isolated carotid vasculitis, and two (6 %) as giant cell arteritis.
CONCLUSIONS: Carotid vasculitis may occur as a topographically limited lesion and is associated with significant rate of vascular complications.