The First Nations experience of accessing rheumatology services in a metropolitan hospital: A qualitative study.

OBJECTIVE: First Nations Australians experience a higher burden and severity of Rheumatic Disease with poorer outcomes than the general population. Despite a widely acknowledged need to improve health outcomes, there has been minimal research assessing existing models of care from a First Nations perspective in Australia. The objective of this study was to describe First Nations experiences and barriers and enablers to accessing a hospital-based adult Rheumatology service in Sydney. METHODS: A qualitative study using semi-structured interviews was undertaken. Patients who self-identified as First Nations attending the Prince of Wales Hospital Rheumatology Clinic in 2021 were invited to participate. Interviews were conducted face-to-face or by telephone using culturally-appropriate Yarning methods with an Aboriginal Health Worker (AHW) at the request of participants. Thematic analysis was done in consultation with an Aboriginal Reference Group (ARG). RESULTS: Four categories, which encapsulated 11 themes were identified. Participants reported barriers to care such as logistics of the referral process, not feeling culturally safe because of uncomfortable clinic environments and health worker behaviours, inadequate cultural support and community perceptions of the specialty. Enabling factors included family member involvement, AHW support and telehealth consultation. CONCLUSION: The current model of care perpetuates access challenges for First Nations Australians within rheumatology. Barriers to care include the delayed referral process, limited cultural responsivity in the clinic environment and poor cross-cultural communication. There is a need for models of care that are co-designed with First Nations Peoples to address these barriers. PATIENT AND PUBLIC CONTRIBUTION: Participants were First Nations Australians with lived experience attending the rheumatology clinic. All interviewees were offered the opportunity to review their transcripts to ensure trustworthiness of the data. Preliminary thematic analysis was conducted in partnership with the AHW who has over 20 years experience. Following preliminary coding, a list of themes were presented to the ARG for iterative discussion and refinement. The ARG provided community representation and ensured that First Nations voices were privileged in the analysis. It's intended that the findings of this study will support the upcoming co-design of a First Nations health service for Rheumatology patients.

The impact of coronavirus-19 vaccination on anti-nuclear cytoplasmic antibody vasculitis hospitalisations in a Sydney health network.

There have been reports of COVID-19 vaccination triggering anti-nuclear cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but no robust studies have examined the link. This retrospective cohort study assessed the impact of COVID vaccination on the rate of denovo and relapsed AAV in a Sydney Local Health District from 2018 to 2022. Despite more than 95% of the population receiving vaccination, the case rate of AAV was stable. These findings do not support a relationship between COVID vaccination and AAV.

VEXAS syndrome: lessons learnt from an early Australian case series.

VEXAS is a newly recognised adult-onset autoinflammatory syndrome resulting from a somatic mutation in the UBA1 gene. Herein, we present three cases of VEXAS syndrome in Sydney, Australia, that capture key clinical features and the refractory nature of the condition. They highlight the importance of multidisciplinary collaboration for early diagnosis and the need for new therapeutic options.

The Clinical Significance of Small Vessel Vasculitis on Temporal Artery Biopsies.

BACKGROUND: Giant cell arteritis (GCA) is the most common type of systemic vasculitis in the elderly. Untreated, it can lead to irreversible blindness. Its diagnosis relies on a temporal artery biopsy (TAB). However, a proportion of patients have small vessel vasculitis (SVV) on biopsy; the prognosis of which remains unclear. The aim of this study is to compare the clinical presentation and long-term outcomes of those with SVV with negative and positive biopsies to determine whether long-term corticosteroid therapy can be avoided in these patients. METHODS: Post hoc analysis of patients with suspected GCA who underwent TAB and fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan as part of a prospective GCA and PET cohort. Patients were divided in to 3 groups based on TAB result: positive (inflammation in the main artery wall), negative (no inflammation), and SVV (isolated vasa vasorum or periadventitial SVV). Clinical, serological, and PET/CT data of patients with SVV were compared with those with positive and those with negative biopsies. RESULTS: For the 58 eligible patients recruited between May 2016 and December 2017, 11 had SVV, 12 had positive, and 35 had negative biopsies. Patients with SVV had similar clinical, serological, and PET/CT findings to those with negative biopsies. Compared with those with positive biopsies, patients with SVV had lower erythrocyte sedimentation rate (25 vs 78 mm/hour; P = 0.02), platelet count (296 vs 385 ×109/L; P = 0.03), and a lower median total vascular score on PET/CT scan (1.0 vs 13.5; P = 0.01). Median prednisone dose was lower (4.8 vs 11.7 mg; P = 0.015) and fewer were on steroid-sparing agents (20% vs 67%; P = 0.043) at 6 months. The percentage of patients with a clinical diagnosis of GCA was similar between those with SVV (3/11, 27.3%) and those with negative biopsies (5/35, 14.3%; P = 0.374). CONCLUSIONS: Patients with SVV on TAB had similar clinical features, PET/CT findings, and 6-month outcomes to those with negative biopsies. Small vessel vasculitis can be treated as equivalent to a negative biopsy when being considered for diagnosis and treatment of GCA.

Post-operative outcomes of inflammatory thoracic aortitis: a study of 41 patients from a cohort of 1119 surgical cases.

Aortitis is found in 2-12% of thoracic aortic aneurysm repair/replacement surgeries. Yet little is known about such patients' post-operative outcomes or the role of post-operative corticosteroids. The study was undertaken across three tertiary referral hospitals in Sydney, Australia. Prospectively collected data for all thoracic aortic repair/replacement patients between 2004 and 2018 was accessed from a national surgical registry and analysed. Histopathology records identified cases of inflammatory aortitis which were subclassified as clinically isolated aortitis (CIA), giant cell arteritis (GCA), Takayasu (TAK) or other aortitis. Between-group outcomes were compared utilising logistic and median regression analyses. Between 2004 and 2018, a total of 1119 thoracic aortic surgeries were performed of which 41 (3.7%) were inflammatory aortitis cases (66% CIA, 27% GCA, 5% TAK, 2% other). Eight out of 41 (20%) aortitis patients received post-operative corticosteroids. Compared to non-aortitis patients, the aortitis group was predominantly female (53.7% vs. 28.1%, p < 0.01), was older (mean 70 vs. 62 years, p < 0.01) and had higher prevalence of hypertension (82.9% vs. 67.1%, p = 0.03) and pre-operative immunosuppression (9.8% vs. 1.4%, p < 0.01). There was no difference (p > 0.05) between aortitis and non-aortitis groups for 30-day mortality (7.3% vs 6.5%), significant morbidity (14.6% vs. 22.4%), or infection (9.8% vs. 6.4%). Outcomes were similar for the non-corticosteroid-treated aortitis subgroup. Histologic evidence of inflammatory thoracic aortitis following surgery did not affect post-operative mortality or morbidity. Withholding corticosteroids did not adversely affect patient outcomes. These findings will assist rheumatologists and surgeons in the post-operative management of aortitis.

Prevalence of Neuropsychiatric Lupus in Psychosis Patients Who Have Tested Positive for Antinuclear Antibodies.

OBJECTIVE: Psychosis is a rare manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE). Current guidelines do not make a recommendation regarding the use of antinuclear antibody (ANA) testing in the assessment of patients with psychosis. The present study was undertaken to determine the prevalence of NPSLE in patients with psychosis who were positive for ANAs. METHODS: A retrospective review of patients who were admitted to the mental health service of 2 metropolitan tertiary referral centers with a diagnosis of psychosis and had been tested for ANAs was conducted. A diagnosis of SLE was made when the 2019 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria were fulfilled. Attribution of psychosis-related events to NPSLE were made according to validated criteria. RESULTS: There were 10,205 mental health admissions with diagnoses of psychosis representing 4,766 individual patients, 911 patients (19%) were tested for ANAs, 135 (15%) of those tests returned a positive result with a titer of ≥1:160. The mean ± SD follow-up time was 47 ± 26 months. At discharge, there were 4 patients who met 2019 ACR/EULAR criteria for SLE, 2 of whom met criteria for NPSLE (2 patients had other manifestations of SLE), yielding an NPSLE prevalence of 1.5% (2 of 135) among patients who were positive for ANAs, and 0.2% (2 of 911) among all patients who underwent testing for ANAs. CONCLUSION: The prevalence of NPSLE in patients with psychosis who were positive for ANAs was low, at 1.5%. The low rate of clinically significant positive results would argue against routine testing for ANAs in patients with psychosis.

Adalimumab in patients with vision-threatening uveitis: real-world clinical experience.

OBJECTIVES: Biologics are rapidly emerging as an effective vision saving addition to systemic uveitis therapy. The aim of this multicentre retrospective study is to review the outcomes of a large group of patients treated with adalimumab. METHODS: A retrospective chart review of patients with refractory non-infectious, active uveitis treated with adalimumab was conducted. The main outcome measures were ability to reduce prednisolone dose, ability to control uveitis, final visual acuity and time to treatment failure. RESULTS: Forty-six patients with uveitis, treated with adalimumab were included in the study. The most common anatomical uveitis phenotype was panuveitis (n=17, 37.0%). The most common diagnosis was idiopathic uveitis (n=19, 41.3%). At their latest review (mean: 4.46 years; median 4.40 years), 35 (76.1%) patients were able to discontinue corticosteroids, 11 (23.9%) patients were able to taper to <7.5 mg/day and only 1 (2.2%) patient required 10 mg of prednisone. The mean visual acuity at the latest follow-up of the worse eye was logarithm of the minimum angle of resolution (logMAR) 0.42 (SD 0.72), while the mean visual acuity of the better eye was logMAR 0.19 (SD 0.34). Of the 89 eyes, 21 (23.6%) eyes improved by at least 2 lines, 5 eyes (5.6%) deteriorated by ≥2 lines while vision was unchanged in the remaining 63 (70.8%) eyes. The time to recurrence was 1 in 12.47 person-years for adalimumab, with a 17.4% (8 patient) relapse rate. There were no serious adverse events. CONCLUSIONS: This study highlights the efficacy of adalimumab in patients with vision-threatening non-infectious uveitis, preserving vision and allowing reduction of corticosteroid dose.

Limited utility of novel serological biomarkers in patients newly suspected of having giant cell arteritis.

AIM: Diagnosing and monitoring vascular activity in giant cell arteritis (GCA) is difficult due to the paucity of specific serological biomarkers. We assessed the utility of 8 novel biomarkers in an inception cohort of newly suspected GCA patients. METHOD: Consecutive patients were enrolled between May 2016 and December 2017. Serum was collected within 72 hours of commencing corticosteroids and at 6 months. It was analyzed for levels of intra-cellular adhesion molecule 1, vascular endothelial growth factor (VEGF), pentraxin 3, von Willebrand factor and procalcitonin (5-plex R&D Systems multiplex assay) and interleukin (IL)6, IL12 and interferon-γ (high-sensitivity 3-plex ProcartaPlex multiplex assay). A GCA specific positron emission tomography / computed tomography (PET/CT) scan was performed at enrolment with uptake in each vascular territory graded and summed to derive a total vascular score (TVS). RESULTS: For the 63 patients enrolled, 12 (19%) had a final diagnosis of biopsy-positive GCA and a further 9 had a clinical diagnosis of biopsy-negative GCA. None of the 8 biomarkers was significantly higher in GCA patients compared with those with alternative diagnoses, or demonstrated a positive correlation with the PET/CT TVS. This was in contrast to the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) which were higher in the biopsy-positive GCA cohort (P < .04) and showed weak positive correlations with the TVS (correlation coefficient 0.34, P < .01). Procalcitonin did not distinguish between GCA and infection. Concentrations of CRP, ESR, VEGF and pentraxin 3 decreased between diagnosis and 6 months in GCA patients. CONCLUSION: This study did not identify new serological biomarkers to assist in diagnosing or assessing the vasculitis burden in GCA.

Cranial and large vessel activity on positron emission tomography scan at diagnosis and 6 months in giant cell arteritis.

AIM: Positron emission tomography/computed tomography (PET/CT) can detect cranial and large vessel inflammation in giant cell arteritis (GCA). We aimed to determine the change and significance of vascular activity at diagnosis and 6 months. METHOD: Newly diagnosed GCA patients underwent time-of-flight fluorine-18-fluoro-2-deoxyglucose PET/CT from vertex to diaphragm within 72 hours of commencing corticosteroids and were followed for 12 months. A 6 months scan was performed in patients with inflammatory features on biopsy or CT aortitis. Vascular uptake was visually graded by 2 blinded readers across 18 artery segments from 0 (no increased uptake) to 3 (very marked uptake). Scores were summed to give a total vascular score (TVS). RESULTS: We enrolled 21 GCA patients and 15 underwent the serial scan. Twelve (57%) patients experienced a relapse and 5 of these had ischemic features of vision disturbance, jaw or limb claudication. The median TVS fell from 14 (interquartile range [IQR] 4-24) at baseline to 5 (IQR 0-10) at 6 months (P < .01) with reduction in both cranial and large artery scores. While the overall relapse rate was similar between patients with a high (≥10) and low baseline TVS, patients with high scores were numerically more likely to experience an ischemic relapse (33% vs 11%, P = .34). Five out of 15 patients had persistent uptake in at least 1 vessel on the serial PET/CT but none experienced a subsequent relapse. CONCLUSION: Vascular activity decreased in cranial and large arteries between diagnosis and 6 months. Persistent activity did not predict subsequent relapse.

Assessment for varicella zoster virus in patients newly suspected of having giant cell arteritis.

OBJECTIVES: There is uncertainty if varicella zoster virus (VZV) triggers GCA. This is based on discordant reports of VZV detection in GCA temporal artery biopsies. We conducted a multimodal evaluation for VZV in the inception Giant Cell Arteritis and PET Scan (GAPS) cohort. METHODS: Consecutive patients who underwent temporal artery biopsy for suspected GCA were clinically reviewed for active and past VZV infection and followed for 6 months. Serum was tested for VZV IgM and IgG. Temporal artery biopsy (TAB) sections were stained for VZV antigen using the VZV Mouse Cocktail Antibody (Cell Marque, Rocklin, CA, USA). A selection of GCA and control tissues were stained with the VZV gE antibody (Santa Cruz Biotechnology, Dallas, TX, USA), which was used in previous studies. RESULTS: A total of 58 patients met inclusion criteria, 12 (21%) had biopsy-positive GCA and 20 had clinically positive GCA. None had herpes zoster at enrolment and only one patient developed a VZV clinical syndrome (zoster ophthalmicus) on follow-up. There was no difference in VZV exposure between GCA and non-GCA patients. None of the 53 patients who had VZV serology collected had positive VZV IgM antibodies. VZV antigen was not convincingly demonstrated in any of the TAB specimens; 57 TABs stained negative and 1 stained equivocally positive. The Santa Cruz Biotechnology VZV antibody exhibited positive staining in a range of negative control tissues, questioning its specificity for VZV antigen. CONCLUSION: The absence of active infection markers argues against VZV reactivation being the trigger for GCA. Non-specific immunohistochemistry staining may account for positive findings in previous studies.

Diagnostic Accuracy of Positron Emission Tomography/Computed Tomography of the Head, Neck, and Chest for Giant Cell Arteritis: A Prospective, Double-Blind, Cross-Sectional Study.

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) has not been well studied as a first-line test for giant cell arteritis (GCA), due, in part, to historical limitations in visualizing the cranial arteries. The Giant Cell Arteritis and PET Scan (GAPS) study was therefore carried out to assess the accuracy of a newer generation PET/CT of the head, neck, and chest for determining a diagnosis of GCA. METHODS: In the GAPS study cohort, 64 patients with newly suspected GCA underwent time-of-flight PET/CT (1-mm slice thickness from the vertex to diaphragm) within 72 hours of starting glucocorticoids and before undergoing temporal artery biopsy (TAB). Two physicians with experience in PET reviewed the patients' scans in a blinded manner and reported the scans as globally positive or negative for GCA. Tracer uptake was graded across 18 artery segments. The clinical diagnosis was confirmed at 6 months' follow-up. RESULTS: In total, 58 of 64 patients underwent TAB, and 12 (21%) of the biopsies were considered positive for GCA. Twenty-one patients had a clinical diagnosis of GCA. Compared to TAB, the sensitivity of PET/CT for a diagnosis of GCA was 92% (95% confidence interval [95% CI] 62-100%) and specificity was 85% (95% CI 71-94%). The negative predictive value (NPV) was 98% (95% CI 87-100%). Compared to clinical diagnosis, PET/CT had a sensitivity of 71% (95% CI 48-89%) and specificity of 91% (95% CI 78-97%). Interobserver reliability was moderate (κ = 0.65). Among the enrolled patients, 20% had a clinically relevant incidental finding, including 7 with an infection and 5 with a malignancy. Furthermore, 5 (42%) of 12 TAB-positive GCA patients had moderate or marked aortitis. CONCLUSION: The high diagnostic accuracy of this PET/CT protocol would support its use as a first-line test for GCA. The NPV of 98% indicates the particular utility of this test in ruling out the condition in patients considered to be at lower risk of GCA. PET/CT had benefit over TAB in detecting vasculitis mimics and aortitis.