Extracranial Giant Cell Arteritis Research Articles

Comparative analysis of arterial involvement in predominant cranial and isolated extracranial phenotypes of giant cell arteritis using 18F-FDG PET-CT

ObjectiveTo investigate differences in arterial involvement patterns on 18F-FDG PET-CT between predominant cranial and isolated extracranial phenotypes of giant cell arteritis (GCA).MethodsA retrospective review of 18F-FDG PET-CT findings was conducted on 140 patients with confirmed GCA. The patients were divided into two groups: the cranial group, which presented craniofacial ischemic symptoms either at diagnosis or during follow-up, and the isolated extracranial group which never exhibited such manifestations.ResultsOf the 140 patients (90 women), 99 (71%) were considered to have a predominantly cranial phenotype, while 41 (29%) had isolated extracranial GCA. Patients with the extracranial phenotype were younger (p = 0.001), had lower TAB positivity (25%), and experienced longer diagnostic delays (p = 0.004). Polymyalgia rheumatica was more common in the extracranial group (p = 0.029), which also showed fewer constitutional symptoms, milder increases in acute phase reactants, and more frequent limb claudication and aortic complications, although these differences were not statistically significant. When comparing arterial involvement on 18F-FDG PET-CT, we observed statistically significant differences. The extracranial phenotype showed greater involvement across all segments of the thoracic aorta (p = 0.001), as well as in the abdominal aorta (p = 0.005), subclavian (p = 0.021), iliac (p = 0.004), and femoral arteries (p = 0.025). In contrast, the cranial phenotype exhibited a higher frequency of vertebral artery involvement (p < 0.001).ConclusionSignificant differences in arterial involvement patterns on 18F-FDG PET-CT were observed between phenotypes. These findings may explain atypical symptoms such as inflammatory lower back pain or limb claudication and the increased risk of aortic complications in extracranial GCA.

Tocilizumab in cranial and extracranial giant cell arteritis: a national multicenter study of 471 cases.

The spectrum of giant cell arteritis (GCA) includes different vascular phenotypes. Tocilizumab (TCZ) is the only biologic currently approved regardless these phenotypes. We aimed to assess the effectiveness of TCZ in different phenotypes. Multicentre observational study of GCA patients treated with TCZ. They were divided into three phenotypes: a) cranial (cGCA), b) extracranial (ecGCA) and c) mixed (mixGCA). Outcomes included clinical remission, EULAR complete remission, relapses, absence of inflammation in imaging techniques, and safety. We studied 471 patients (342 women; mean age 74.0 ± 9.0 years). The phenotypic distribution was: cGCA (n = 217; 46%), mixGCA (174; 37%) and ecGCA (80; 17%). Patients with ecGCA were younger (66.5 ± 10.1 years) than cGCA (74.8 ± 8.1) and mixGCA (71.4 ± 8.5), and had a longer delayed GCA diagnosis (median [IQR]) (6 [1-14] vs 1 [1-3] vs 2 [1-6] months, respectively). Systemic manifestations were similar in the 3 groups, while ischemic manifestations were more frequent in cGCA. Combined TCZ -besides glucocorticoids- was used more frequently in ecGCA (36%). Clinical remission was observed in 51%/43%/47% in cGCA/ecGCA/mixGCA, respectively, at first month, and in 79%/81%/89% at 24 months. Complete EULAR remission in 35%/27%/28% (1st month) and 72%/73%/67% (24 months).Absence of inflammation in imaging techniques was of 15%/26% (12 months) and of 22%/7% (ecGCA/mixGCA (24 months). Relevant adverse events were observed in 109 (23.1%) patients. TCZ shows a rapid and maintained effectiveness in all GCA phenotypes in clinical and EULAR complete remission. By contrast, absence of inflammation in imaging techniques was much lower in ecGCA and mixGCA.

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

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). 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. 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. 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.

Presence of subclinical giant cell arteritis in patients with morning stiffness of duration less than 45 minutes at the time of diagnosis of polymyalgia rheumatica.

In some patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) is subclinical as underlying inflammation of large vessels (LV) is present without evidence of related clinical manifestations. Different factors have been proposed as predictive of subclinical GCA in PMR patients. To date, the literature reports scant data about the association between subclinical GCA and long-lasting morning stiffness (MS) in patients at the time of diagnosis of PMR. Given this background, the aim of this study was to assess the association between subclinical GCA and MS < 45 min in patients with newly diagnosed PMR. We performed an observational, retrospective, single-centre cohort study of patients consecutively referred to our public out-of-hospital rheumatologic clinic between January 2015 and December 2020, who could be classified as having PMR according to the 2012 EULAR/ACR criteria. Subclinical GCA was investigated through ultrasound examination of a core set of arteries (temporal, axillary, common carotid, and subclavian arteries), in accordance with the EULAR recommendations for the use of imaging in LV vasculitis. Patients who did not have GCA symptoms but showed halo sign in at least one of these arteries were described as having subclinical GCA. We included a total of 143 patients (35 men and 108 women). Their median age was of 71.5 years. Thirty-five had MS duration < 45 min at the time of PMR diagnosis. Subclinical GCA was found in 23 PMR patients (16.1%); 18 had a cranial and 5 an extracranial GCA. A univariate analysis highlighted that MS < 45 min was associated with a lower prevalence of GCA (OR = 0.11, 95% CI: 0.04-0.29; p < 0.0001). This association was retained in a multivariable analysis that accounted for 6 different potential covariates (OR = 0.06, 95% CI: 0.01-0.26; p < 0.0001. In our study MS < 45 min at the time of PMR diagnosis was associated with a significantly lower risk of subclinical GCA, when patients were screened by ultrasound, of approximately 90%. Identification of a more accurate MS cut-off value could improve the accuracy for subclinical GCA in patients with newly diagnosed PMR.

Positron Emission Computed Tomography Spectrum of Large Vessel Vasculitis in a Tertiary Center: Differences in 18F-fluorodeoxyglucose Uptake between Large Vessel Vasculitis with Predominant Cranial and Extracranial Giant Cell Arteritis Phenotypes.

(1) Objective:To assess the spectrum of PET-CT-related large vessel vasculitis (LVV) in a Spanish tertiary center and to determine whether FDG uptake by PET-CT differs between giant cell arteritis (GCA) with predominant cranial or extracranial phenotypes. (2) Methods: The spectrum of patients diagnosed with LVV by PET-CT in a tertiary referral hospital that cares for 450,000 people over a period of two years was reviewed. Moreover, differences in FDG uptake between LVV-GCA with predominantly cranial and extracranial phenotype were analyzed. (3) Results: Eighty patients were diagnosed with LVV by PET-CT. Most were due to systemic vasculitis (n = 64; 80%), especially GCA (n = 54; 67.5%). Other conditions included the presence of rheumatic diseases (n = 4; 3.2%), tumors (n = 9; 7.2%) and infections (n = 3; 2.4%). LVV-GCA patients with predominant extracranial GCA phenotype were younger (mean ± SD: 68.07 ± 9.91 vs. 75.46 ± 7.64 years; p = 0.017) and had a longer delay to the diagnosis (median [interquartile range] 12 [4-18] vs. 4 [3-8]; p = 0.006), but had polymyalgia rheumatica symptoms more frequently than those with predominantly cranial GCA phenotype (46.3% vs. 15.4%, p = 0.057). When FDG uptake was compared according to the two different disease patterns, no statistically significant differences were observed. However, patients with extracranial LVV-GCA showed a non-significantly higher frequency of vasculitic involvement of lower-extremity arteries. (4) Conclusions: Regardless of the predominant phenotype, LVV identified by PET-CT is more commonly due to GCA in the Spanish population. In these GCA patients, younger age, PMR, and a higher frequency of lower-extremity artery vasculitis suggest the presence of LVV.

Imaging of large vessel vasculitis

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the most important primary large vessel vasculitides. A rapid and reliable confirmation of the diagnosis is necessary to prevent ischemic complications. Patients with extracranial GCA and TAK often present with unspecific symptoms. Since 2018 the EULAR has recommended imaging as an alternative to histology for confirming the diagnosis. Ultrasound is particularly recommended as the primary imaging modality for cranial GCA. Alternatively, MRI and PET can be used for the diagnostics of temporal arteritis. Ultrasound is also valuable for extracranial GCA, alternatively MRI, CT or PET-CT can be used. This review discusses the current status of imaging techniques in large vessel vasculitis as well as the advantages and disadvantages. The focus is on ultrasound, which is increasingly being used as the primary diagnostic modality due to its excellent diagnostic quality, wide availability, noninvasiveness, and patient friendliness. Technical aspects, prerequisites, and normal and pathological findings are also presented. Finally, an outlook is given on promising new developments, such as scores for evaluating disease progression and contrast-enhanced ultrasound.

Validation of the 2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis.

The present study validates the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu's arteritis (TAK) compared with 1990 ACR TAK classification criteria. The fulfillment of 2022 ACR/EULAR and 1990 ACR TAK criteria from four referral centers was assessed for TAK compared with extracranial giant cell arteritis (EC-GCA) and other controls. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio of a positive test (LR+) or negative test (LR-), and area under receiver operating characteristics curve (AUC) were calculated. Among 504 TAK (404 females) and 222 controls (151 females, 144 EC-GCA), the 2022 ACR/EULAR criteria had better sensitivity (95.83% vs 82.94%) and NPV but poorer specificity (63.51% vs 90.54%), PPV, LR+, LR-, and AUC at the pre-determined cut-offs than 1990 ACR criteria. The 2022 ACR/EULAR criteria had greater specificity (76.06% vs 57.62%) and AUC (0.845 vs 0.771) with similar sensitivity (93% vs 96.53%) in males than in females. The 2022 ACR/EULAR criteria performed similarly with only EC-GCA as controls (sensitivity 95.83%, specificity 60.42%, AUC 0.781). Sensitivity remained similar, whereas specificity was higher for 40-60 vs < 40 years. Cut-offs ≥6 (sensitivity 91.87%, specificity 82.88%) and ≥7 (sensitivity 86.71%, specificity 86.49%), or removing the point for female sex (sensitivity 92.64%, specificity 81.08%) greatly improved balance between sensitivity and specificity. The poor specificity of the 2022 ACR/EULAR TAK criteria in real-life settings was improved by increasing the cut-off to 6 or 7 or removing the point for female sex.

Response to: 'Biases in Large Vessel Vasculitis' by Mukhtyar.

We thank Mukhtyar for his interest in our report showing the differences of giant cell arteritis (GCA) based on the presence of large vessel involvement (LVI) [1] and for providing some meaningful comments to deepen the discussion [2]. First, Mukhtyar wonders the accuracy of the term of large vessel GCA (LV-GCA). Certainly, it is anatomically correct to use the term ‘cranial or extracranial GCA’ because the Chapel Hill Consensus defines the arteries outside an organ as large vessels, including the superficial temporal artery and the ophthalmic artery distributed in the cranial region [3]. However, ‘LV-GCA’ is also a commonly used term to refer to GCA involving the aorta and/or its branches [4, 5]. Currently, it is still chaotic about the terminology, and the unification is awaited. Second, distinction between GCA and Takayasu arteritis (TAK) is an important and challenging problem. In our cohort, we don’t have any patients that meet the 1990 American College of Rheumatology (ACR) classification for TAK [6], nor the 2022 ACR/EULAR classification criteria for TAK [7]. However, the differentiation of GCA and TAK can be problematic, especially in patients around the age threshold with stenoses of the aortic branches. The 2022 ACR/EULAR classification for TAK and GCA [7, 8] focused on clinical information such as the distribution of affected arteries, and this will help us differentiate GCA and TAK. Also, some recent studies focus on GCA or TAK using genetic or molecular approaches [9]. That kind of research from the perspective of basic medicine can contribute to distinguishing GCA and TAK, and further research is anticipated.

Biases in large-vessel vasculitis.

Dear Sir, I read the paper from Yamaguchi et al. published in the January 2023 edition of Modern Rheumatology with great interest [1]. I thank them for sharing their observations and insights with the world about the differences between those individuals who appear to have extracranial giant cell arteritis (GCA) and those with just cranial arterial disease. I would like to debate the following points with them. The Chapel Hill Consensus Conference effectively defines large vessels as those that are outside an organ [2]. The superficial temporal artery and the maxillary artery are third-generation branches of the aorta and are defined as large vessels with very clear anatomical differentiation of the vessel wall into adventitia, media, and intima. For that reason, it would be inaccurate to name the two groups of their analysis as those involving large vessels and those not involving, since the cranial arteries are also large vessels. I propose the use of anatomically more accurate terms for their groups—cranial verus extracranial OR carotid system versus those with additional aortic and/or subclavian system disease.

Use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography in patients affected by polymyalgia rheumatica and persistent increase of acute phase reactants.

Polymyalgia rheumatica (PMR) is an inflammatory disease affecting older adults characterized by aching pain and morning stiffness of the shoulder and pelvic girdles. Moreover, PMR can be associated with giant cell arteritis (GCA). Generally, PMR is highly responsive to steroids, reaching complete remission in the majority of cases. However, the possibility of occult diseases, including extra-cranial GCA, should be excluded. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is able to detect the presence of peri-/articular or vascular inflammation, which may be both present in PMR, thus representing a useful diagnostic tool, mainly in presence of extra-cranial GCA. We retrospectively evaluated all consecutive patients who received the diagnosis of PMR in our rheumatology clinic, classified according to the 2012 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, in the period between April 2020 and May 2022. Among this case series, we selected the patients who underwent 18F-FDG-positron emission tomography (PET) because of the persistent increase of acute phase reactants (APR) besides the steroid therapy. Eighty patients were diagnosed with PMR. Nine out of them also presented arthritis of the wrists during the follow-up, whereas none showed signs of cranial GCA at the diagnosis. Seventeen out of eighty subjects (mean age 71.5 ± 7.5 years; M/F 2/15) presented persistent increase of erythrocyte sedimentation rate (mean ESR 44.2 ± 20.8 mm/h) and/or C-reactive protein (mean CRP 25.1 ± 17 mg/l), thus they underwent total body 18F-FDG-PET/CT. Large vessel 18F-FDG uptake indicating an occult GCA was found in 5/17 (29.4%) cases. Twelve out of seventeen (70.6%) patients showed persistence of peri-/articular inflammation, suggesting a scarce control of PMR or the presence of chronic arthritis. Finally, in 2 cases, other inflammatory disorders were found, namely an acute thyroiditis and a hip prosthesis occult infection. 18F-FDG-PET/CT in PMR patients with persistent increase of APR is a useful diagnostic technique in order to detect occult GCA, persistence of active PMR or other misdiagnosed inflammatory diseases.

Cranial and extracranial giant cell arteritis do not exhibit differences in the IL6 -174 G/C gene polymorphism.

Since interleukin-6 (IL-6) is a pivotal proinflammatory cytokine implicated in the pathogenesis of giant cell arteritis (GCA), we aimed to determine the potential association of the functional IL6 -174 G/C polymorphism with GCA as well as if the single base change variation at the promoter region in the human IL-6 gene may account for differences in the clinical spectrum of GCA between cranial and extracranial large vessel vasculitis (LVV)-GCA. The IL6 -174 G/C polymorphism (rs1800795) was genotyped in 191 patients with biopsy-proven GCA who had typical cranial manifestations of the disease, 109 patients with extracranial LVV-GCA, without cranial ischaemic manifestations of GCA, and 877 ethnically matched unaffected controls. A comparative study was carried out between patients with cranial and extracranial LVV-GCA and controls. No significant differences in genotype and allele frequencies of IL6 -174 G/C polymorphism were found between the whole cohort of GCA patients and healthy controls. It was also the case when cranial and extracranial LVV-GCA were compared or when each of these subgroups was compared to controls. Moreover, no significant results in genotype and allele frequencies of IL6 -174 G/C polymorphism were disclosed when the whole cohort of GCA patients were stratified according to the presence of polymyalgia rheumatica, severe ischaemic manifestations, including permanent visual loss and peripheral arteriopathy, and HLA-DRB1*04:01 status. Our results show that the IL6 -174 G/C polymorphism does not influence the phenotypic expression of GCA.

The Diagnostic Performance of an Extended Ultrasound Protocol in Patients With Clinically Suspected Giant Cell Arteritis.

ObjectiveTo evaluate the diagnostic performance of an extended ultrasound protocol in patients referred under the suspicion of giant cell arteritis (GCA).MethodsConsecutive patients with suspected GCA were examined with an extended color duplex ultrasound (CDU) protocol during a period of 2 years. The extended CDU protocol included temporal, axillary, subclavian, brachiocephalic, and carotid arteries. The reference was clinically diagnosed GCA, confirmed after ≥6-month follow-up. Hypo- or medium-echogenic, circumferential, homogenous wall thickening, and/or a positive compression sign in temporal arteries, were regarded as typical signs of arteritis.ResultsOf the eligible 201 patients, 83 (41%) received a clinical GCA diagnosis at follow-up ≥6 months post CDU examination. Among these cases, 48 (58%) demonstrated inflammation solely in temporal arteries, 8 (10%) showed abnormalities restricted to extra-cranial vessels, and 23 (28%) patients displayed inflammatory changes in both temporal and extra-cranial arteries. Color duplex ultrasound of temporal arteries yielded a diagnostic sensitivity and specificity [95% confidence intervals (CI)] of 86% (76–92%) and 99% (95–99%), respectively. By adding axillary artery examination, the sensitivity increased to 92% (83–97%) while the specificity remained unchanged. Further, inclusion of subclavian artery marginally increased the sensitivity by 1%. Finally, by also including brachiocephalic and common carotid arteries resulted in a sensitivity of 95% (88–99%) and a specificity of 98% (94–99%).ConclusionsColor duplex ultrasound examination demonstrated a high accuracy in diagnosing patients both with cranial and extra-cranial GCA. Further examination of brachiocephalic and common carotid arteries can increase the sensitivity without affecting the specificity when temporal and axillary findings are indecisive. Finally, the extended CDU protocol allows measurement of the general burden of inflammation, which could be relevant for future monitoring purposes.

The crossbow sign in extracranial giant cell arteritis.

The crossbow sign in extracranial giant cell arteritis.

Vascular endothelial growth factor haplotypes are associated with severe ischaemic complications in giant cell arteritis regardless of the disease phenotype.

To determine whether functional vascular endothelial growth factor (VEGF) polymorphisms influence the expression of the clinical phenotype of giant cell arteritis (GCA). We also evaluated whether VEGF polymorphism is associated with the development of severe ischaemic manifestations in patients with GCA regardless of the clinical phenotype, classic cranial GCA or predominantly extracranial GCA large vessel vasculitis (LVV). VEGF rs833061 T/C, rs2010963 G/C and rs3025039 C/T polymorphisms were genotyped in 185 patients with biopsy-proven cranial GCA, 105 with extracranial LVV-GCA and 490 healthy controls. Allelic combinations (haplotypes) of VEGF were carried out. Comparisons were performed between patients with GCA and healthy controls as well as between patients with GCA stratified according to the clinical phenotype and the presence of severe ischaemic manifestations. No significant differences in genotype, allele, and haplotype frequencies of VEGF were found between patients with GCA and healthy controls as well as between GCA patients with the classic cranial pattern and the extracranial LVV-GCA pattern of the disease. However, the VEGF CGC haplotype (OR= 1.63 [1.05-2.53]) and the CGT haplotype (OR= 2.55 [1.10-5.91]) were significantly more frequent in GCA patients with severe ischaemic complications compared to those patients without these complications. VEGF haplotypes seem to play a role in the development of severe ischaemic manifestations in GCA patients, regardless of the clinical phenotype of expression of the disease.

Characterization of Extracranial Giant Cell Arteritis with Intracranial Involvement and its Rapidly Progressive Subtype.

The objective of this study was to characterize patients with extracranial giant cell arteritis with intracranial involvement. In a multicenter retrospective study, we included 31 patients with systemic giant cell arteritis (GCA) with intracranial involvement. Clinical characteristics, pattern of arterial involvement, and cytokine profiles were assessed. Patients with GCA without intracranial involvement (n=17), and with intracranial atherosclerosis (n=25) served as controls. Erythrocyte sedimentation rate (ESR) was elevated in 18 patients (69.2%) with and in 16 patients (100%) without intracranial involvement (p=0.02). Headache was complained by 15 patients (50.0%) with and 13 patients (76.5%) without intracranial involvement (p=0.03). Posterior circulation arteries were affected in 26 patients (83.9%), anterior circulation arteries in 17 patients (54.8%), and both territories in 12 patients (38.7%). Patients with GCA had vertebral artery stenosis proximal and, in contrast, patients with atherosclerosis distal to the origin of posterior inferior cerebellar artery (PICA). Among patients with GCA with intracranial involvement, 11 patients (37.9%) had a rapid progressive disease course characterized by short-term recurrent ischemic events. The median modified Rankin Scale (mRS) at follow-up in these patients was 4 (interquartile range [IQR] = 2.0-6.0) and 4 patients (36.4%) died. Vessel wall expression of IL-6 and IL-17 was significantly increased in patients with rapid progressive course. Typical characteristics of GCA, headache, and an elevated ESR, are frequently absent in patients with intracranial involvement. However, differentiation of intracranial GCA from atherosclerosis can be facilitated by the typical pattern of vertebral artery stenosis. About one-third of patients with intracranial GCA had a rapid progressive course with poor outcome. IL-17 and IL-6 may represent potential future treatment targets. ANN NEUROL 2021;90:118-129.

P030 Antiphospholipid syndrome and giant cell arteritis: a coincidence or connection?

Abstract Background/Aims Antiphospholipid syndrome (APS) is a multisystem autoimmune disorder, which can be primary or associated with other conditions including systemic lupus erythematosus. Several studies have reported antiphospholipid antibodies, in patients with different vasculitides but little is known about the occurrence of APS and giant cell arteritis (GCA). We report a case of a patient diagnosed with concomitant extracranial GCA and APS. Methods A 74-year-old lady presented to the Emergency department following a fall at home. On further questioning, she reported a rapid history of weight loss (4kg in the previous 4 weeks) but no classical features of giant cell arteritis. Her temporal arteries were pulsatile bilaterally, not tender or thickened. Cranial nerve examination including fundoscopy was normal. Her gait was apraxic, with short stride length and veering to the right with a narrow base. The rest of the examination was unremarkable. Results Laboratory investigations showed an elevated CRP 98mg/L with a normal ESR 23mm/h, ferritin 380 ng/ml, negative ANCA and ANA, with an unremarkable myeloma screen. Microbiology investigations demonstrated negative serial blood cultures, hepatitis screen, and quantiferon. She subsequently underwent intracranial imaging [CT and MRI brain with Gadolinium] which did not demonstrate acute pathology. A PET CT confirmed features in keeping with a large vessel vasculitis without aneurysmal formation. She was treated with pulsed IV methylprednisolone 500mg for 3 consecutive days and started on 60mg oral prednisolone daily. Two days after starting this treatment she developed acute onset double vision: ophthalmologic examination revealed new onset right internuclear ophthalmolplegia (INO). A subsequent CT head angiogram showed non critical stenoses in aorta at origins of great vessels, left vertebral artery, and carotids. Interval MRI brain showed a new infarct in pons corresponding with her INO. Bloods revealed triple positive anti-phospholipid antibodies - [IgG anticardiolipin antibody 102 GPL (0-13), anti-β2 glycoprotein I antibodies 59.8 U/ml (0-18), Lupus anticoagulant detected]. She was commenced on warfarin [target INR 2.5] and aspirin. Due to mental health history and large vessel manifestations, she was started on IV Tocilizumab 8mg/kg and her prednisolone dose was reduced to 40mg when her CRP normalised. Following hospitalisation, she had persistent visual disturbance with ongoing poor spatial co-ordination. Although she remained ataxic, her functional mobility improved. She was transferred to a local stroke unit and was discharged home. Conclusion In summary, this is a case of GCA and APS, treated with prednisolone, aspirin, warfarin and tocilizumab. There is increasing evidence describing the presence of antiphospholipid antibodies in patients with vasculitis. However, the role of these antibodies in GCA and the clinical significance remains unclear. This case reports highlights the need for physicians to consider APS in patients who have a history of GCA and subsequently develop arterial or venous embolic events. Disclosure L. Sammut: None. E. Htut: None.

The presence of both HLA-DRB1*04:01 and HLA-B*15:01 increases the susceptibility to cranial and extracranial giant cell arteritis.

To determine if patients with the predominant extracranial large-vessel-vasculitis (LVV) pattern of giant cell arteritis (GCA) have a distinctive HLA-B association, different from that reported in biopsy-proven cranial GCA patients. In a further step we assessed if the combination of HLA-B and HLA-DRB1 alleles confers an increased risk for GCA susceptibility, either for the cranial and extracranial LVV phenotypes. A total of 184 patients with biopsy-proven cranial GCA, 105 with LVV-GCA and 486 healthy controls were included in our study. We compared HLA-B phenotype frequencies between the three groups. HLA-B*15 phenotype was significantly increased in patients with classic cranial GCA compared to controls (14.7% versus 5.8%, respectively; p<0.01; OR [95% CI] =2.81 [1.54-5.11]). It was mainly due to the HLA-B*15:01 allele (12.5% versus 4.0%, respectively; p<0.01; OR [95% CI] =3.51 [1.77-6.99]) and remained statistically significant after Bonferroni correction. Similar HLA-B*15 association was observed in patients with the LVV-GCA (11.4% versus 5.8%, p=0.04, OR [95% CI] =2.11 [1.04-4.30]). This association was also mainly due to the HLA-B*15:01 allele (10.5% versus 4.0%, respectively; p=0.0054; OR [95% CI] =2.88 [1.19-6.59]). Noteworthy, the presence of HLA-B*15:01 together with HLA-DRB1*04:01 led to an increased risk of developing both cranial and extracranial LVV-GCA. Susceptibility to GCA is strongly related to the HLA region, regardless of the clinical phenotype of expression of the disease.

Extracranial as Silent Giant Cell Arteritis: Case Report

GCA (Giant cell arteritis) is a granulomatous vasculitis of large arteries. Frequently typical cranial symptoms are observed, but sometimes nonspecific extracranial involvements are dominant. Diagnosis of this “occult” or “extracranial” GCA as a medical emergency is crucial to preventing irreversible complications. The current article presents the case of a 52-year-old man with no cranial manifestations who developed acute peritonitis and died. Elevated inflammatory markers without cranial manifestations should cause extracranial GCA to be considered. Delayed diagnosis in GCA, especially the extracranial type, could lead to severe, irreversible complications.

Cranial and extracranial giant cell arteritis share similar HLA-DRB1 association

ObjectiveTo determine whether giant cell arteritis (GCA) patients with the typical pattern of cranial ischemic manifestations and those with the extracranial large-vessel-vasculitis (LVV)-GCA phenotype exhibit different HLA-DRB1 association. Methods178 biopsy-proven GCA patients who had cranial ischemic features but no LVV manifestations, 100 patients with LVV-GCA without cranial ischemic manifestations and 486 ethnically matched healthy controls were recruited. All patients and controls were Spanish of European ancestry. We compared HLA-DRB1 phenotype frequencies between the three groups. ResultsBoth GCA subgroups had well-differentiated clinical features. Patients with LVV-GCA were younger (68.0 ± 10.0 years versus 74.0 ± 10.4 years; p < 0.01) and presented more commonly with polymyalgia rheumatica symptoms (81% versus 39.3%; p < 0.01) than those with the classic cranial GCA phenotype. HLA-DRB1*04 phenotype frequency was significantly increased in patients with classic cranial GCA compared to controls (42.1% versus 23.5%, respectively; p < 0.01; odds ratio-OR [95% confidence interval-CI] = 2.38 [1.62–3.47]). This association was mainly due to the HLA-DRB1*04:01 allele (20.8% versus 5.3%, respectively; p < 0.01; OR [95% CI] = 4.64 [2.63–8.26]). HLA-DRB1*04 association was also observed in LVV-GCA patients when compared to controls (46.0% versus 23.5%, respectively; p < 0.01; OR [95% CI] = 2.78 [1.73–4.44]). Similar to cranial GCA, the association was also mainly due to the HLA-DRB1*04:01 allele (19.0% versus 5.3%, respectively; p < 0.01; OR [95% CI] = 4.15 [2.06–8.19]). Cranial and LVV-GCA patients did not exhibit HLA-DRB1 allele differences. ConclusionCranial and extracranial LVV-GCA share similar HLA-DRB1 association.

Polymyalgia rheumatica mit und ohne Großgefäßvaskulitis

Polymyalgia rheumatica (PMR) is characterized by rapidly evolving shoulder and pelvic girdle pain with fatigue, weight loss, night sweats and elevated CRP and ESR. Giant cell arteritis (GCA) can occur in PMR and vice versa. Headache and scalp tenderness are typical for GCA. GCA may be complicated by visual loss or by strokes.Imaging, particularly ultrasound, is helpful for distinguishing PMR from similar conditions such as shoulder osteoarthritis, rheumatoid arthritis and chondrocalcinosis. Subdeltoid bursitis, biceps tenosynovitis and hip joint effusions are common in PMR. The diagnosis of GCA needs to be either confirmed by imaging or by histology. Ultrasound is the imaging method of choice provided that expertise and adequate equipment are available. Inflamed arteries exhibit a concentric wall thickening. Patients with extracranial GCA are younger, more often female. Vasculitis commonly involves the aorta, subclavian arteries, axillary arteries and other arteries. The diagnosis of extracranial GCA may be confirmed by ultrasound, CT, MRI or PET.Prednisolone with a starting dose of 15-25 mg/d for PMR and of 40-60 mg/d for GCA results in rapid improvement of symptoms. Fast-track clinics provide clinical and ultrasound examinations by experts within 24 hours. Their introduction led to a decrease of visual loss in GCA. The prednisolone dose can be discontinued within 1 year in about 50 % of GCA patients. Additional treatment with tocilizumab allows to reduce flares and decrease glucocorticoid doses. Tocilizumab is particularly useful in patients with relapses and with increased risk of glucocorticoid side effects.