Epidemiology of systemic vasculitis.

PURPOSE OF REVIEW: Epidemiology of vasculitides exhibit geographic variation and data from some parts of the world are still scarce. Increased recognition of these rare diseases and improvement in diagnosis and patient care may lead to changes in their epidemiology. In this review, we aimed to highlight the most recent work on the epidemiology of systemic vasculitis. RECENT FINDINGS: New data from countries where information on the epidemiology of giant cell arteritis, Takayasu arteritis and Behçet syndrome were limited have revealed that these conditions are not as rare as previously believed. The incidence rates during the coronavirus disease 2019 pandemic highlight the link between Kawasaki disease and respiratory pathogens. The use of different classification criteria hampers the comparison of true incidence and prevalence rates in antineutophil cytoplasmic antibody (ANCA)-associated vasculitis and its subtypes between geographies and over time. SUMMARY: Recent studies have highlighted the epidemiology of vasculitides in different parts of the world and changing trends. Standardization of study design and disease definitions is needed to improve the reliability and comparability of the results.

Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica.

OBJECTIVE: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach. METHODS: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared. RESULTS: We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate. CONCLUSIONS: Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.

Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways.

OBJECTIVES: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients. METHODS: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed. Synovial tissue specimens from patients with inflammatory arthritis and aorta tissue were used as disease control samples. Senescent cells and their histological origin were identified with specific cellular markers; IL-6 and MMP-9 were investigated as components of the senescent associated secretory phenotype by triple costaining. GCA or PMR artery culture supernatants were applied to fibroblasts, HUVECs and monocytes with or without IL-6R blocking agent to explore the induction of IL-6-associated cellular senescence. RESULTS: Senescent cells were present in GCA arteries at higher proportion compared with PMR (9.50% vs 2.66%, respectively, p<0.0001) and were mainly originated from fibroblasts, macrophages and endothelial cells. IL-6 was expressed by senescent fibroblasts, and macrophages while MMP-9 by senescent fibroblasts only. IL-6(+) senescent cells were associated with the extension of vascular inflammation (transmural inflammation vs adventitia limited disease: 10.02% vs 4.37%, respectively, p<0.0001). GCA but not PMR artery culture supernatant could induce IL-6-associated senescence that was partially inhibited by IL-6R blockade. CONCLUSIONS: Senescent cells with inflammatory phenotype are present in GCA arteries and are associated with the tissue inflammatory bulk, suggesting a potential implication in disease pathogenesis.

Review of phase 2/3 trials in polymyalgia rheumatica and giant cell arteritis.

INTRODUCTION: GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) are two overlapping inflammatory rheumatic conditions that are seen exclusively in older adults, sharing some common features. GCA is a clinical syndrome characterized by inflammation of the medium and large arteries, with both cranial and extracranial symptoms. PMR is a clinical syndrome characterized by stiffness in the neck, shoulder, and pelvic girdle muscles. Both are associated with constitutional symptoms. AREAS COVERED: In this review, we assess the established and upcoming treatments for GCA and PMR. We review the current treatment landscape, completed trials, and upcoming trials in these conditions, to identify new and promising therapies. EXPERT OPINION: Early use of glucocorticoids (GC) remains integral to the immediate management of PMR and GCA but being aware of patient co-morbidities that may influence treatment toxicity is paramount. As such GC sparing agents are required in the treatment of PMR. Currently there are limited treatment options available for PMR and GCA, and significant unmet needs remain. Newer mechanisms of action, and hence therapeutic options being studied include CD4 T cell co-stimulation blockade, IL-17 inhibition, IL-12/23 inhibition, GM-CSF inhibition, IL-1ß inhibition, TNF-α antagonist and Jak inhibition, among others, which will be discussed in this review.

Multimodality imaging to assess diagnosis and evaluate complications of large vesselarteritis.

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 ischemia, 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 the diagnosis and identification of vascular complications in the field of large vessel vasculitis.

Giant cell arteritis in patients with systemic sclerosis: a case series.

OBJECTIVES: Giant cell arteritis (GCA) in patients with systemic sclerosis (SSc) is rare, and optimal treatment strategies for this group of patients have not been defined. We aim to describe the first case series of GCA/SSc overlap. METHODS: A single-institution retrospective study was performed reviewing all patients that had diagnosis codes for both SSc and GCA between January 1, 1996, and December 31, 2020. Demographic characteristic, clinical presentation, diagnostic modality, treatment, and outcome data were abstracted. Diagnosis of both SSc and GCA by a rheumatologist was required for inclusion. RESULTS: Eight patients were retrospectively identified, all of which were female. Seven patients fully met both respective ACR/EULAR classification criteria sets. One patient fulfilled GCA criteria and had 8/9 points for SSc criteria plus an oesophagogram which was consistent with clinical diagnosis of SSc. Three patients had a previous history of scleroderma renal crisis (SRC) prior to glucocorticoid initiation for GCA. No episodes of SRC occurred following initiation of glucocorticoids. Three patients were treated with tocilizumab. One patient developed a diverticular perforation while on tocilizumab requiring colonic resection and colostomy, one patient discontinued tocilizumab after a medication-unrelated complication and one patient has remained on treatment and in remission. CONCLUSIONS: Herein we present the largest single-institution series of patients with a history of GCA and SSc, an uncommon combination. Glucocorticoid treatment for GCA did not precipitate SRC, even in those with prior history of SRC. Further investigation regarding the benefit of tocilizumab in patients with SSc and GCA is required.

Cranial and extracranial manifestations of giant cell arteritis: a single-center observational study.

INTRODUCTION: Giant cell arteritis (GCA) presents two major phenotypes - cranial (cGCA) and extracranial (exGCA). exGCA may be overlooked. The study aimed to compare the clinical characteristics between cGCA and exGCA. METHODS: Electronic medical records of patients treated between January 2015 and July 2023 at the Department of Rheumatology were searched for the diagnosis of GCA. The clinical characteristics of patients with cGCA, exGCA, and overlapping GCA manifestations were compared. RESULTS: Out of 32 patients with GCA, 20 had cGCA, 7 had exGCA, and 5 had overlap manifestations. The groups did not differ significantly in demographics, clinical signs/symptoms, or laboratory test results. Importantly, the combined group of patients with exGCA and overlap GCA had a statistically significant delay in initiating treatment (median 12 weeks) compared to patients with cGCA (median 4 weeks; p = 0.008). CONCLUSION: Our study confirmed the insidious nature of exGCA, which lacks distinctive clinical symptoms and consequently leads to delayed treatment.

Characteristics and Prognosis of Binocular Diplopia in Patients With Giant Cell Arteritis.

BACKGROUND: Giant cell arteritis (GCA) is a large vessel vasculitis associated with a risk of permanent ophthalmologic complications. Data about diplopia prognosis in GCA are scarce. This study was designed to better characterize diplopia in newly diagnosed GCA patients. METHODS: All consecutive patients diagnosed with GCA from January 2015 to April 2021 in a French tertiary ophthalmologic center were retrospectively reviewed. GCA diagnosis relied on a positive temporal artery biopsy or high-definition MRI. RESULTS: Among 111 patients diagnosed with GCA, 30 patients (27%) had diplopia. Characteristics of patients with diplopia were similar to other GCA patients. Diplopia resolved spontaneously in 6 patients (20%). Diplopia was attributed to cranial nerve palsy in 21/24 patients (88%), especially third (46%) and sixth cranial nerve (42%). Ocular ischemic lesions occurred in 11 of the 30 patients with diplopia (37%); 2 patients developed vision loss after initiation of corticosteroids. In the remaining 13 patients, diplopia resolved after treatment onset in 12 patients (92%) with a median delay of 10 days. Patients treated intravenously tended to have a quicker improvement than those treated orally, but with a similar resolution rate of diplopia at 1 month. Two patients had relapse of diplopia at 4 and 6 weeks after an initial treatment course of 24 and 18 months, respectively. CONCLUSIONS: Diplopia is a rare feature at GCA diagnosis, but should raise clinician suspicion for GCA when associated with cephalic symptoms and prompt the initiation of corticosteroids to prevent ocular ischemic complications.

Association Between Vascular 18F-Fluorodeoxyglucose Uptake at Diagnosis and Change in Aortic Dimensions in Giant Cell Arteritis : A Cohort Study.

BACKGROUND: Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular 18F-fluorodeoxyglucose (FDG) uptake at diagnosis are at increased risk for thoracic aortic complications. OBJECTIVE: To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions. DESIGN: Prospective cohort study. SETTING: University Hospitals Leuven. PATIENTS: 106 patients with GCA and FDG positron emission tomography (PET) imaging 3 days or less after initiation of glucocorticoids. MEASUREMENTS: Patients had PET and computed tomography (CT) imaging at diagnosis and CT imaging yearly for a maximum of 10 years. The PET scans were scored 0 to 3 in 7 vascular areas and summed to a total vascular score (TVS). The PET scan results were positive when FDG uptake was grade 2 or greater in any large vessel. The association between vascular FDG uptake and aortic dimensions was estimated by linear mixed-effects models with random intercept and slope. RESULTS: When compared with patients with a negative PET scan result, those with a positive scan result had a greater increase in the diameter of the ascending aorta (difference in 5-year progression, 1.58 mm [95% CI, 0.41 to 2.74 mm]), the diameter of the descending aorta (1.32 mm [CI, 0.38 to 2.26 mm]), and the volume of the thoracic aorta (20.5 cm³ [CI, 4.5 to 36.5 cm³]). These thoracic aortic dimensions were also positively associated with TVS. Patients with a positive PET scan result had a higher risk for thoracic aortic aneurysms (adjusted hazard ratio, 10.21 [CI, 1.25 to 83.3]). LIMITATION: The lengthy inclusion and follow-up period resulted in missing data and the use of different PET machines. CONCLUSION: Higher TVS was associated with greater yearly increase in thoracic aortic dimensions. Performing PET imaging at diagnosis may help to estimate the risk for aortic aneurysm formation. PRIMARY FUNDING SOURCE: None.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis: a prospective study.

OBJECTIVE: To investigate the relation between biomarkers of inflammation and subsequent development of GCA. METHOD: Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30 447), established 1991-96, who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth and year of screening were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics inflammation panel (92 inflammatory proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. Within components selected based on eigenvalues, proteins with a factor loading of >0.50 were investigated. RESULTS: Ninety-four cases with a confirmed incident diagnosis of GCA (median 11.9 years after inclusion) were identified. Among biomarkers with a priori hypotheses, IFN-γ was positively associated with GCA [odds ratio (OR) per s.d. 1.52; 95% CI 1.00, 2.30]. Eight biomarkers in the hypothesis-generating analyses were significantly associated with development of GCA. Among these, higher levels of IFN-γ (OR 2.37; 95% CI 1.14, 4.92) and monocyte chemotactic protein 3 (MCP3) (OR 4.27; 95% CI 1.26, 14.53) were particularly associated with increased risk of GCA in the subset sampled <8.5 years before diagnosis. Several other proteins known to be important for T cell function were also associated with GCA in these analyses, e.g. CXCL9, IL-2, CD40 and CCL25. CONCLUSION: Elevated IFN-γ levels were found years prior to diagnosis of GCA. T cell activation may precede the clinical onset of GCA.

Immune complex-mediated neutrophil activation in patients with polymyalgia rheumatica.

OBJECTIVE: Neutrophils are important in host defence. However, neutrophils are also linked to inflammation and organ damage. The purpose of this study was to assess whether markers of neutrophil activation are increased in PMR. METHODS: Levels of immune complexes (IC), calprotectin and neutrophil extracellular traps (NETs) were measured in plasma of healthy individuals (n = 30) and patients with PMR (n = 60), at flare and upon treatment with glucocorticoids using ELISA. Plasma-mediated neutrophil activation was assessed in presence of an FcγRIIA inhibitory antibody (IV.3). RESULTS: Plasma levels of calprotectin and NETs were elevated in PMR (P < 0.001). Mechanistically, neutrophil activation was driven by ICs, present in plasma, able to up-regulate neutrophil activation markers CD66b and CD11b (P < 0.0001) in an FcγRIIA-dependent manner (P < 0.01). Of note, circulating levels of IC correlated with plasma induced CD66b and CD11b (r = 0.51, P = 0.004, and r = 0.46, P = 0.01, respectively) and decreased after glucocorticoid therapy. In contrast to NETs, calprotectin significantly decreased after glucocorticoid therapy (P < 0.001) and was higher in PMR without overlapping GCA compared with patients with overlapping disease (P = 0.014). Interestingly, musculoskeletal involvement was associated with elevated levels of calprotectin before initiation of glucocorticoid therapy (P = 0.036). CONCLUSIONS: Neutrophil activation, including NET formation, is increased in PMR, through IC-mediated engagement of FcγRIIA. Clinically, neutrophil activation is associated with musculoskeletal involvement, with calprotectin, but not NETs, being a biomarker of treatment response in PMR patients. In all, IC-mediated neutrophil activation is a central process in PMR pathogenesis identifying potential novel therapeutic targets (FcγRIIA), as well as soluble markers for disease monitoring (calprotectin).

Does the halo count on temporal and axillary ultrasound predict time to relapse in giant cell arteritis?

OBJECTIVES: To determine whether the halo count (HC) on temporal and axillary artery US (TAUS) predicts time to relapse in giant cell arteritis (GCA). METHODS: We conducted a single-centre retrospective study of GCA patients. HC, the number of vessels with non-compressible halo on the TAUS at diagnosis, was determined by retrospective review of the US report and images. Relapse was defined as increase in GCA disease activity requiring treatment escalation. Cox proportional hazard regression was used to identify predictors of time to relapse. RESULTS: A total of 72 patients with confirmed GCA were followed up for a median of 20.9 months. Thirty-seven of 72 (51.4%) relapsed during follow-up, at a median prednisolone dose of 9 mg (range 0-40 mg). Large-vessel (axillary artery) involvement did not predict relapse. On univariable analysis, a higher HC was associated with shorter time to relapse (per-halo hazard ratio 1.15, 95% CI 1.02, 1.30; P = 0.028). However, statistical significance was lost when the 10 GCA patients with an HC of zero were excluded from analysis. CONCLUSION: In this real-world setting, relapse occurred at a wide range of glucocorticoid doses and was not predicted by axillary artery involvement. GCA patients with a higher HC at diagnosis were significantly more likely to relapse, but significance was lost on excluding those with HC of zero. HC is feasible in routine care and may be worth incorporating into future prognostic scores. Further research is required to determine whether confirmed GCA patients with negative TAUS represent a qualitatively different subphenotype within the GCA disease spectrum.

Age-related histopathological findings in temporal arteries.

AIMS: Giant cell arteritis (GCA) is a systemic vasculitis affecting medium and large arteries in patients aged over 50 years. Involvement of temporal arteries (TA) can lead to complications such as blindness and stroke. While the diagnostic gold standard is temporal artery biopsy (TAB), comorbidities and age-related changes can make interpretation of such specimens difficult. This study aims to establish a baseline of TA changes in subjects without GCA to facilitate the interpretation of TAB. METHODS AND RESULTS: Bilateral TA specimens were collected from 100 consecutive eligible postmortem examinations. Subjects were divided into four age groups and specimens semiquantitatively evaluated for eccentric intimal fibroplasia, disruption and calcification of the internal elastic lamina (IEL), medial attenuation and degree of lymphocytic inflammation of the peri-adventitia, adventitia, media and intima. The individual scores of intimal fibroplasia, IEL disruption and medial attenuation were added to yield a 'combined score (CS)'. Seventy-eight 78 decedents were included in the final analysis following exclusion of 22 individuals for either lack of clinical information or inability to collect TA tissue. A total of 128 temporal artery specimens (50 bilateral from individual decedents, 28 unilateral) were available for examination. Intimal proliferation, IEL loss, IEL calcification and CS increased with age in a statistically significant fashion. Comparison of the oldest age group with the others showed statistically significant differences, although this was not uniformly preserved in comparison between the three youngest groups. CONCLUSION: Senescent arterial changes and healed GCA exhibit histological similarity and such changes increase proportionally with age. The CS demonstrates significant association with age overall and represents a potential avenue for development to 'normalise' TA biopsies from older individuals.

Intraorbital findings in giant cell arteritis on black blood MRI.

OBJECTIVE: Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls. METHODS: In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms. RESULTS: Eighteen of 56 GCA patients (32%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths (N = 13, 72%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms (p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures. CONCLUSIONS: BB-MRI revealed inflammatory findings in the orbits in up to 32% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms. KEY POINTS: • Up to 32% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI. • Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI. • Features of inflammation of intraorbital structures are independent of clinically reported symptoms.

Orbital magnetic resonance imaging of giant cell arteritis with ocular manifestations: a systematic review and individual participant data meta-analysis.

OBJECTIVES: We conducted a systematic review and individual participant data meta-analysis of publications reporting the ophthalmologic presentation, clinical exam, and orbital MRI findings in patients with giant cell arteritis and ocular manifestations. METHODS: PubMed and Cochrane databases were searched up to January 16, 2022. Publications reporting patient-level data on patients with ophthalmologic symptoms, imaged with orbital MRI, and diagnosed with biopsy-proven giant cell arteritis were included. Demographics, clinical symptoms, exam, lab, imaging, and outcomes data were extracted. The methodological quality and completeness of reporting of case reports were assessed. RESULTS: Thirty-two studies were included comprising 51 patients (females = 24; median age, 76 years). Vision loss (78%) and headache (45%) were commonly reported visual and cranial symptoms. Ophthalmologic presentation was unilateral (41%) or bilateral (59%). Fundus examination most commonly showed disc edema (64%) and pallor (49%). Average visual acuity was very poor (2.28 logMAR ± 2.18). Diagnoses included anterior (61%) and posterior (16%) ischemic optic neuropathy, central retinal artery occlusion (8%), and orbital infarction syndrome (2%). On MRI, enhancement of the optic nerve sheath (53%), intraconal fat (25%), and optic nerve/chiasm (14%) was most prevalent. Among patients with monocular visual symptoms, 38% showed pathologic enhancement in the asymptomatic orbit. Six of seven cases reported imaging resolution after treatment on follow-up MRIs. CONCLUSIONS: Vision loss, pallid disc edema, and optic nerve sheath enhancement are the most common clinical, fundoscopic, and imaging findings reported in patients diagnosed with giant cell arteritis with ocular manifestations, respectively. MRI may detect subclinical inflammation and ischemia in the asymptomatic eye and may be an adjunct diagnostic tool. CLINICAL RELEVANCE STATEMENT: Brain and orbital MRIs may have diagnostic and prognostic roles in patients with suspected giant cell arteritis who present with ophthalmic symptoms.

Listeria rhombencephalitis mimicking stroke in a patient with giant cell arteritis.

Listeria monocytogenes sometimes causes central nervous system infections. However, rhombencephalitis is a rare form of L. monocytogenes infection. Its clinical symptoms and magnetic resonance imaging (MRI) findings are often similar to those of vertebrobasilar stroke. We present the case of a 79-year-old woman with Listeria rhombencephalitis presenting with rhinorrhea and productive cough. She had giant cell arteritis (GCA) treated with prednisolone and methotrexate. She was admitted for loss of appetite, rhinorrhea, and productive cough. These symptoms were alleviated without specific treatment; however, she suddenly developed multiple cranial nerve palsies, and MRI showed hyperintense signals on diffusion-weighted imaging and hypointense signals on apparent diffusion coefficient in the brainstem. Ischemic stroke due to exacerbation of GCA was suspected, and treatment with intravenous methylprednisolone was initiated; however, seizures occurred, and a lumbar puncture was performed. Cerebrospinal fluid and blood cultures revealed L. monocytogenes, and she was diagnosed with Listeria rhombencephalitis. Although antibiotic treatment was continued, the patient died. Thus, when patients with rhinorrhea or productive cough develop sudden cranial nerve palsy, Listeria rhombencephalitis should be considered as a differential diagnosis, and lumbar puncture should be performed.

New-onset giant cell arteritis with lower ESR and CRP level carries a similar ischemic risk to other forms of the disease but has an excellent late prognosis: a case-control study.

INTRODUCTION: Biopsy-proven giant cell arteritis (GCA) occasionally presents without acute-phase reaction. In this setting, GCA may be initially overlooked and glucocorticoid treatment unduly delayed, potentially increasing ischemic risk. PATIENTS AND METHODS: From an inception cohort of patients with newly diagnosed, biopsy-verified GCA, we retrieved all cases without elevation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level before starting glucocorticoid treatment. We compared the baseline features and outcomes of these patients and two additional patients recruited after GCA diagnosis with those of 42 randomly selected patients with high baseline ESR and CRP. RESULTS: Of 396 patients, 14 (3.5%) had lower baseline values of both ESR and CRP. Lower baseline ESR and CRP were associated with fewer American College of Rheumatology criteria met (p < 0.001, 95% CI - 1.1; - 0.9), and less jaw claudication (p = 0.06, 95% CI 0.8; 44.9), but similar rates of permanent blindness (p = 1.0). Patients with lower ESR and CRP also showed obvious differences regarding mean blood cell counts and mean hemoglobin level, but also less anti-cardiolipin antibody positivity (p = 0.04, 95% CI 0.8; ∞) and hepatic cholestasis (p = 0.03, 95% CI 1.0; 422). Patients with lower ESR and CRP had fewer GCA relapses (p = 0.03, 95% CI - 1.1; - 0.1), fewer glucocorticoid-induced complications (p = 0.01, 95% CI - 2.0; - 0.1), and successfully stopped glucocorticoids sooner than the other patients (18.3 months vs 34 months in average, p = 0.02, 95% CI - 27;- 0.9). CONCLUSION: Biopsy-proven GCA presenting with lower ESR and CRP is not an exceptional occurrence. It is clinically less typical but carries similar ischemic risk to other forms of the disease. Conversely, the late GCA prognosis of these patients is excellent.

Sarcoidal Granuloma Annulare-Like Dermatitis and Vasculitis With Granulomatous Features: An Atypical Case of Giant Cell Arteritis.

ABSTRACT: Giant cell arteritis (GCA) is a diagnosis that clinicians should not miss because of the accompanying risk of irreversible vision loss. GCA can present without the classic symptoms of headache and temporal artery tenderness, which may lead to a delay in diagnosis. Cutaneous findings, although rare, have been associated with GCA. Accordingly, it is imperative to be aware of the broad clinical and histological presentations of GCA, including the cutaneous findings, because they may prove to be harbingers of impending disease. We present a unique case of GCA where 2 distinct cutaneous morphologies, sarcoidal granuloma annulare-like dermatitis and leukocytoclastic vasculitis with granulomatous features, presented simultaneously before the classic symptoms of headache and unilateral vision loss.