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Objective Diagnosing septic arthritis can be challenging and frequently involves clinical assessment, laboratory investigations and synovial fluid analysis. We sought to determine the utility of synovial aspiration and intra-operative synovial fluid and tissue culture for the accurate diagnosis of septic arthritis. Methods We carried out a retrospective review of the records of patients referred to a tertiary orthopaedic unit with possible septic arthritis between 2015 and 2019 inclusive, including clinical and laboratory data for this cohort study. Performance characteristics were determined for synovial aspiration, intra-operative synovial fluid and tissue culture in diagnosing expert review-determined true septic arthritis. Concordance between discharge diagnosis, antibiotic prescribing and true septic arthritis was determined. Results Of 268 patients identified with suspected septic arthritis, 143 underwent both synovial fluid aspiration and intra-operative synovial fluid and tissue biopsy culture. True septic arthritis was not differentiated significantly by laboratory parameters including serum white cell count (WCC), CRP or synovial WCC. Considering only patients with negative pre-operative synovial aspirate cultures, intra-operative samples led to diagnosis of true septic arthritis in 6 of 63 patients [number needed to treat (NNT) 10.5]. For all patients sampled in theatre, positive synovial tissue biopsy was the only evidence of true septic arthritis in six (NNT 23.9). Despite insufficient microbiological evidence, 27 of the 59 patients who did not have septic arthritis received a discharge diagnosis of septic arthritis, 26 of whom were discharged with antibiotics. Conclusion Intra-operative sample collection, particularly tissue biopsy, increases the likelihood of a true septic arthritis diagnosis. Such measures might help to reduce diagnostic ambiguity in clinical practice and might therefore reduce overtreatment.

Contains fulltext : 249973.pdf (Publisher’s version ) (Closed access) Over the last decade, evidence has demonstrated that long-term, low-dose colchicine (0.5 mg daily) is effective for preventing gout flare and cardiovascular (CV) events in a wide range of patients. Given the potentially expanding use of colchicine in CV disease, we here review and update the biologic effects and safety of colchicine based on recent data gathered from bench and pharmacodynamic studies, clinical reports, controlled clinical trials, and meta-analyses, integrated with important studies over the last 50 years, to offer a consensus perspective by experts from multiple specialties familiar with colchicine's long-term use. We conclude that the clinical benefits of colchicine in gout and CV disease achieved at low dose do not sustain serum levels above the upper limit of safety when used in patients without advanced renal or liver disease or when used concomitantly with most medications. Further, data accrued over the last 50 years strongly suggest that the biologic effects of long-term colchicine do not increase the risk of cancer, sepsis, cytopenia, or myotoxicity.

Deep learning has emerged as the leading method in machine learning, spawning a rapidly growing field of academic research and commercial applications across medicine. Deep learning could have particular relevance to rheumatology if correctly utilized. The greatest benefits of deep learning methods are seen with unstructured data frequently found in rheumatology, such as images and text, where traditional machine learning methods have struggled to unlock the trove of information held within these data formats. The basis for this success comes from the ability of deep learning to learn the structure of the underlying data. It is no surprise that the first areas of medicine that have started to experience impact from deep learning heavily rely on interpreting visual data, such as triaging radiology workflows and computer-assisted colonoscopy. Applications in rheumatology are beginning to emerge, with recent successes in areas as diverse as detecting joint erosions on plain radiography, predicting future rheumatoid arthritis disease activity, and identifying halo sign on temporal artery ultrasound. Given the important role deep learning methods are likely to play in the future of rheumatology, it is imperative that rheumatologists understand the methods and assumptions that underlie the deep learning algorithms in widespread use today, their limitations and the landscape of deep learning research that will inform algorithm development, and clinical decision support tools of the future. The best applications of deep learning in rheumatology must be informed by the clinical experience of rheumatologists, so that algorithms can be developed to tackle the most relevant clinical problems.

Coronavirus disease 2019 (COVID-19) currently has few effective treatments. Given the uncertainty surrounding the effectiveness and uptake of a vaccine, it is important that the search for treatments continue. An exaggerated inflammatory state is likely responsible for much of the morbidity and mortality in COVID-19. Elevated levels of tumor necrosis factor (TNF), a key pro-inflammatory cytokine, have been shown to be associated with increased COVID-19 mortality. In patients with rheumatoid arthritis, TNF blockade reduces not only biologically active TNF but other pro-inflammatory cytokines important in COVID-19 hyperinflammation. Observational data from patients already on anti-TNF therapy show a reduced rate of COVID-19 poor outcomes and death compared with other immune-suppressing therapies. Anti-TNF has a long history of safe use, including in special at-risk populations, and is widely available. The case to adequately assess anti-TNF as a treatment for COVID-19 is compelling., Robinson et al. discuss the potential of TNF blockade in the management of COVID-19. The rationale for the therapeutic benefit of anti-TNF is outlined, including the pathogenic role of TNF in COVID-19, the mechanism of action of anti-TNF, animal data, and supportive observational data from those on anti-TNF who develop COVID-19.

The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably the greatest medical emergency of the last century. COVID-19 has highlighted health disparities both within and between countries and will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades has facilitated a rapid scientific response with innovations in viral characterization, testing, and sequencing. Perhaps most remarkably, this permitted the development of highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for the established disease have delivered limited benefits so far. Innovative and rapid approaches in the design and execution of large-scale clinical trials and repurposing of existing drugs have saved many lives; however, many more remain at risk. In this review we describe challenges and unmet needs, discuss existing therapeutics, and address future opportunities. Consideration is given to factors that have hindered drug development in order to support planning for the next pandemic challenge and to allow rapid and cost-effective development of new therapeutics with equitable delivery.

Objectives To determine COVID-19 vaccine hesitancy rates in inflammatory arthritis patients and identify factors associated with changing vaccine hesitancy over time. Methods This investigation was a prospective cohort study of inflammatory arthritis patients from community and public hospital outpatient rheumatology clinics enrolled in the Australian Rheumatology Association Database (ARAD). Two surveys were conducted, one immediately prior to (pre-pandemic) and another approximately 1 year after the start of the pandemic (follow-up). Coronavirus disease 2019 (COVID-19) vaccine hesitancy was measured at follow-up, and general vaccine hesitancy was inferred pre-pandemic; these were used to identify factors associated with fixed and changing vaccine beliefs, including sources of information and broader beliefs about medication. Results Of the 594 participants who completed both surveys, 74 (12%) were COVID-19 vaccine hesitant. This was associated with pre-pandemic beliefs about medications being harmful (P Conclusion In this study of vaccine beliefs before and during the COVID-19 pandemic, factors associated with COVID-19 vaccine hesitancy in inflammatory arthritis patients varied, depending on vaccine attitudes immediately prior to the start of the pandemic. Fixed beliefs reflected broader views about medications, while fluid beliefs were highly influenced by whether they sought out information from health-care professionals, including rheumatologists.

Aim Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) correlate with disease activity in several rheumatic diseases; however, their utility in polymyalgia rheumatica (PMR) remains unclear. This study evaluated their relationship with disease activity and glucocorticoid resistance in PMR. Method Data for disease activity (PMR-AS) and full blood examination was obtained from a prospective observational cohort comprising newly diagnosed, steroid-naive PMR patients treated with low-dose glucocorticoid therapy. Glucocorticoid resistance was defined as non-response to prednisolone 15 mg/d or initial response followed by flare (PMR-AS ≥ 9.35 or ∆ ≥6.6) upon weaning to 5 mg/d. Univariable Bayesian linear regression analysis of the relationship between PMR-AS (baseline and mean) and NLR and PLR was performed. Predictors of glucocorticoid resistance were identified using a multivariable outcome model, with variables derived from Bayesian model selection. Results Of the 32 included patients, 16 (50%) fulfilled the primary outcome measure of glucocorticoid resistance. These participants were older, typically female, and had higher baseline C-reactive protein than their glucocorticoid-responsive counterparts. A statistically significant relationship was identified between PMR-AS and both NLR (odds ratio [OR] 28.1; 95% CI 1.6-54.7) and PLR (OR 40.6; 95% CI 10.1-71.4) at baseline, with PLR also found to correlate with disease activity during follow-up (OR 15.6; 95% CI 2.7-28.2). Baseline NLR proved a statistically significant predictor of glucocorticoid-resistant PMR (OR 14.01; 95% CI 1.49-278.06). Conclusion Baseline NLR can predict glucocorticoid resistance in newly diagnosed PMR patients. Both NLR and PLR may be reliable biomarkers of disease activity in PMR.

SUMMARY Misuse of opioid analgesics and other psychoactive medicines is a serious and increasing problem in Australia. Measures are being taken to try and prevent this progressing to a public health crisis like the opioid overdose epidemic seen in the USA One measure is real-time prescription monitoring. This provides real-time information about the patient’s supply of psychoactive medicines which have a high risk of being misused Having identified a patient at risk, many factors may delay appropriate management or result in the patient being discharged from care. These factors include subconscious negative stereotyping, a focus on preventing ‘doctor shoppers’ diverting psychoactive medicines, and a fear of sanction by regulators The Medical Board of Australia provides guidance about good practice. Patients should be treated with respect, free from bias and discrimination, and without prejudicing care because of the belief that their behaviour has contributed to their problems

Malignant pleural mesothelioma (MPM) remains a deadly disease with limited therapeutic options beyond platinum/pemetrexed chemotherapy. Immune checkpoint inhibitors have demonstrated modest benefit in the second to later-line settings. An MPM patient from our institute developed myocarditis and myositis after 2 cycles of second-line nivolumab. Despite immunosuppression with corticosteroids and mycophenolate mofetil, there was ongoing rise in troponin levels which remained elevated for months. The patient developed an impressive but brief response following cessation of nivolumab. Myocarditis and myositis are rare complications of immune checkpoint inhibitors. Clinicians should be aware of these possible complications as myocarditis can result in mortality.

To evaluate the sensitivity and specificity of PET/CT findings in PMR and generate a diagnostic algorithm utilizing a minimum number of musculoskeletal sites. Steroid-naive patients with newly diagnosed PMR (2012 EULAR/ACR classification criteria) were prospectively recruited to undergo whole-body 18F−FDG PET/CT. Each PMR case was age- and sex-matched to four PET/CT controls. Control scan indication, diagnosis and medical history were extracted from the clinical record. Qualitative and semi-quantitative scoring (maximum standardized uptake value [SUVmax]) of abnormal 18F-FDG uptake at 21 musculoskeletal sites was undertaken for cases and controls. Results informed the development of a novel PET/CT diagnostic algorithm using a classification and regression trees (CART) method. Thirty-three cases met the inclusion criteria and were matched to 132 controls. Mean age was 68.6 ± 7.4 years for cases compared with 68.2 ± 7.3 for controls, and 54.5% were male. Median CRP was 49 mg/L (32–65) and ESR 41.5 mm/h (24.6–64.4) in the PMR group. The predominant control indication for PET/CT was malignancy (63.6%). Individual musculoskeletal sites proved insufficient for diagnostic purposes. A novel algorithm comprising 18F-FDG uptake ≥ 2 adjacent to the ischial tuberosities in combination with either abnormalities at the peri-articular shoulder or interspinous bursa achieved a sensitivity of 90.9% and specificity of 92.4% for diagnosing PMR. The presence of abnormal 18F-FDG uptake adjacent to the ischial tuberosities together with findings at the peri-articular shoulder or interspinous bursa on whole-body PET/CT is highly sensitive and specific for a diagnosis of PMR. Clinical Trial Registration: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au , ACTRN1261400696695

Summary Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behcet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. Funding American College of Rheumatology and the European Alliance of Associations for Rheumatology.

BackgroundWe describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.MethodsFrom 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.ResultsWe analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%.ConclusionAmong adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

Introduction The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of inflammatory bowel disease (IBD) events compared to placebo. Methods MEDLINE, EMBASE, and The Cochrane Library were searched for double-blind, randomized placebo-controlled anti-TNF and anti-IL-17 trials of included diseases. Inflammatory bowel disease events from the RCT period were pooled and meta-analyzed using statistical methods suitable for low-event-rate meta-analysis (Peto’s, Mantel–Haenszel, hypergeometric-normal model, and Shuster-Guo-Skyler). When observed data were insufficient, we performed an exploratory sensitivity analysis to compare methods. Results We identified 9551 original papers, and included 96 publications: 65 anti-TNF and 31 anti-IL-17 trials, containing 21 new and 12 flare IBD events in 28,209 participants. New IBD on anti-IL-17 occurred 0.23/100 patient-years (PY) in psoriasis, 0.61/100 PY in PsA and 1.63/100 PY in spondyloarthritis, rates similar to observational cohorts, and less commonly on anti-TNF (0/100 PY, 0/100 PY, 0.32/100 PY, respectively). No evidence of difference between groups was found, with wide CI from many pooled counts of zero, especially in placebo arms. Conclusions IBD events were rare, occurring at rates similar to biologic-naive groups. We could not find statistically significant differences in risk of new or recurrent IBD between treatment and control groups using selected meta-analytical methods for low event rate scenarios. Meta-analyses of this topic require more IBD events, ideally without pooling heterogeneous groups. Larger, thoroughly reported trials with systematic and detailed safety reporting are required to improve risk estimation and to make accurate inferences. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00360-6.

Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjogren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. Funding: American College of Rheumatology.

This review examines axial spondyloarthritis (axSpA) and the wider field of rheumatology through a value-based healthcare (VBHC) lens. VBHC is focused on ensuring patients receive high quality care to improve outcomes and reduce unnecessary costs. There are many opportunities to apply the principles of VBHC in axSpA. These include the appropriate utilization of diagnostic investigations, such as HLA-B27 and magnetic resonance imaging, assessing outcomes meaningful to patients, and optimizing care pathways. Multidisciplinary care may improve value, and reduced specialist review and medication tapering may be appropriate. Increasing the value of the care we provide to patients can occur across domains and directly and indirectly improves patient outcomes. Taking the time to integrate principles of VBHC into our practice will allow us to justifiably gain and maintain access to diagnostic and therapeutic advances for the benefit of all our patients.

COVID-19 brings with it unprecedented challenges in clinical management. An important component of care is the provision of safe and effective symptom control. Given the emerging literature reporting on the risk of QT prolongation and arrhythmias associated with COVID-19 disease and experimental therapies, we highlight some considerations for the prescribing of palliative care medications in this context. Based on the experience gained from palliative care referrals at our institution prior to and during the COVID-19 pandemic, and in collaboration with our clinical pharmacology colleagues, we outline some general prescribing principles which may assist with weighing the risks and benefits of prescribing symptomatic medications in and beyond the current pandemic.

Aim To investigate whether any patient or treatment characteristics are associated with the development of rheumatic immune-related adverse events (irAEs) following programmed cell death protein 1 (PD-1) inhibitor therapy for cancer. Method This was a retrospective chart review of all patients who were dispensed nivolumab or pembrolizumab at a single center before 1 January, 2017, with follow-up until 1 July, 2017. Patients with any diagnosis of a non-cutaneous irAE were identified, regardless of severity, and rheumatic irAEs were characterized. Results Of 244 episodes of therapy, a non-cutaneous irAE occurred in 72 (29.5%). Rheumatic irAEs were diagnosed in 19 episodes of therapy (7.8%), with 12 de novo diagnoses (5.1% of episodes without a pre-existing autoimmune rheumatic disease) and 7 exacerbations of existing disease. Review by a rheumatologist occurred in only 11 of these. Rheumatic irAEs were more common in patients with a good oncological response to therapy (relative risk [RR] 11.16), those being treated for melanoma (RR 2.94) and those who developed another non-cutaneous irAE (RR 2.64). Conclusion Rheumatic irAEs are relatively common with PD-1 inhibitor therapy, and appear to be associated with a good oncological response to therapy. Many rheumatic irAEs were not referred to rheumatological services. Prospective systematic investigation would be of benefit to explore these characteristics.

Despite being the most common inflammatory rheumatic disease of the elderly, and despite significant scientific breakthroughs in the related condition giant cell arteritis (GCA), the paradigm of polymyalgia rheumatica (PMR) has failed to progress beyond its earliest descriptions as a glucocorticoid-responsive syndrome of shoulder and pelvic girdle pain and stiffness. In the absence of a gold standard test, diagnosis is based on laboratory evidence of systemic inflammation and the exclusion of other relevant differentials. Ultrasound findings including subacromial bursitis, biceps tenosynovitis, and glenohumeral synovitis at the shoulders, and synovitis and trochanteric bursitis at the hips, improve the specificity of clinical classification criteria1. However, the precise pathology underpinning PMR remains unclear2. A mild synovitis with CD4+ T cell and macrophage infiltration characterizes arthroscopic biopsies taken from the glenohumeral joints of patients with PMR, while histopathologic studies of muscle have consistently revealed only minor immunologic abnormalities3,4. Such uncertainty surrounding disease pathophysiology has undoubtedly hindered therapeutic advances in PMR, with the majority of patients still condemned to longterm prednisolone treatment and its attendant glucocorticoid-related complications. Modern advances in our understanding of PMR as a distinct disease entity have come largely courtesy of imaging. McGonagle, et al first reported an anatomical difference in the distribution of inflammation in their magnetic resonance imaging (MRI) study contrasting the shoulders of PMR and rheumatoid arthritis (RA) patients5. Extracapsular soft tissue edema differentiated the PMR group from its RA counterpart, whereas bursitis, tenosynovitis, and joint effusion did not. A subsequent study by the same authors investigating MRI findings at the metacarpophalangeal joints in PMR and RA similarly documented comparable rates of synovitis, tenosynovitis, and even bone erosions, with a much greater degree of gadolinium-enhancement noted in the extracapsular soft tissues of patients with PMR6. More recently, … Address correspondence to Dr. C.E. Owen, Rheumatology Department, Austin Health, Repatriation Campus, Level 1, North Wing, 300 Waterdale Road, Heidelberg West, Victoria, Australia 3081. E-mail: claire.owen{at}austin.org.au

Polymyalgia rheumatica is a common inflammatory condition but can be difficult to diagnose. Treatment is warranted in all cases to manage disabling symptoms. Low–moderate doses of oral corticosteroids are highly effective. Once symptoms improve they can often be gradually reduced over months, but most patients require either prolonged or continuous treatment. Despite their effectiveness, corticosteroids cause disproportionate damage in polymyalgia rheumatica compared to other rheumatic diseases. The therapeutic aim is to prescribe the minimum possible dose required for symptom control. There is a lack of definitive evidence for steroid-sparing drugs in polymyalgia rheumatica. Methotrexate is typically used for relapsing disease. Leflunomide and tocilizumab are being investigated, but further research is needed.

Objectives To characterize 18F-fluorodeoxyglucose (18F-FDG) uptake on whole-body PET/CT in PMR, and identify its precise anatomic correlate using MRI. Methods Patients with newly diagnosed PMR according to the 2012 EULAR/ACR classification criteria were prospectively recruited. Participants with GCA were excluded. A whole-body 18F-FDG PET/CT scan was performed in all untreated patients. Qualitative and semiquantitative [standardized uptake value maximum (SUVmax)] scoring of abnormal 18F-FDG uptake was undertaken. MRI of the pelvis, knee and wrist and hand was performed in three representative patients with anatomical correlation of FDG-avid sites carried out using Medview fusion software. Results Twenty-two patients with PMR were recruited. Their mean age was 68.3 years (s.d. 6.3) and 13/22 were male. On whole-body PET/CT, 18F-FDG uptake adjacent to the ischial tuberosities was observed in 21 participants (95.4%) and recorded the highest mean SUVmax value [3.6 (s.d. 1.7)]. A high frequency of posteromedial knee (61.9%) and wrist and/or hand involvement (66.7%) was also appreciated. MRI of the pelvis revealed high T2 signal surrounding the proximal hamstring tendon origins of both semimembranosus and the conjoint tendon of the semitendinosus and biceps femoris. At the knee, peritendonitis at the distal insertion of the semimembranosus was observed. PET/MRI fusion at the pelvis and knee confirmed semimembranosus peritendonitis as the anatomical correlate of 18F-FDG uptake adjacent to the ischial tuberosities and of posteromedial knee structures. Conclusion Hamstring peritendonitis is a common and distinctive manifestation of PMR on whole-body PET/CT. Trial registration Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au, ACTRN1261400696695.

Background: RA patients are known to be at increased risk of serious infection(1), particularly for respiratory infections such as influenza which are known to be associated with increased morbidity and mortality(2). Currently RA patients do not have enhanced access to high-dose influenza vaccination in our jurisdiction, despite the reported benefit in RA(3) and enhanced access for patients older than 65 years old. The magnitude of the risk from RA compared to smoking or age greater than 65 years old remains incompletely understood. Objectives: To examine the association of RA, smoking, and age greater than 65 years old with hospital inpatient admissions for influenza. Methods: We examined general medical inpatient admissions in a large tertiary hospital between January 2012 and December 2018. Major confounders (smoking status, age and gender) were selected based on causal inference analysis using a directed acyclic graph. Natural language processing and ICD-10 codes were used to determine the diagnosis of rheumatoid arthritis, smoking status and influenza diagnosis. These variables were used in a multivariable logistic regression analysis. The strength of association was assessed using adjusted odds ratios and associated 95% confidence intervals. Results: We assessed 19,010 patients with at least one general medical inpatient admission during the study period, of which 495 had at least one admission primarily for influenza (Table 1). Within this cohort, there were 3791 patients identified as active smokers and 731 with a history of RA. In the multivariable model, patients with a history of RA were more likely to have at least one admission for influenza (OR 1.65 [1.12 - 2.36]). This risk was comparable to that experienced by patients older than 65 years old in an unadjusted analysis (OR 1.62 [1.29 – 2.04]) and stronger than that experienced by smokers in an unadjusted analysis (OR 1.38 [1.12 - 1.69]). Conclusion: RA patients are at independent risk of influenza leading to a hospital inpatient admission, with a magnitude comparable to that of patients aged over 65 years old and greater than that of smokers. Funding authorities should consider making influenza vaccination available for RA patients in a comparable way to that available to patients aged over 65 years old. References: [1] Listing, J., K. Gerhold, and A. Zink, The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford), 2013. 52(1): p. 53-61. [2] Blumentals, W.A., et al., Rheumatoid arthritis and the incidence of influenza and influenza-related complications: a retrospective cohort study. BMC Musculoskelet Disord, 2012. 13: p. 158. [3] Colmegna I, Useche M, Rodriguez K, Hudson M, Bernatsky S, Nedjar H, Rahme E, Ward B. Efficacy of High-Dose Versus Standard-Dose Influenza Vaccine in Seropositive Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). Disclosure of Interests: None declared

Background The ImmunoCancer International Registry (ICIR) is a Big Data-Sharing multidisciplinary network composed by 39 specialists in Rheumatology, Internal Medicine, Immunology and Oncology from 18 countries focused on immune-related adverse events (irAEs) related to cancer immunotherapies (CIs). Objectives To analyse the worldwide scenario of irAEs associated with the use of CIs in this Century. Methods The first objective of the ICIR has been the development of a systematic literature review crossing CIs terms with immune diseases defined according to MedDRAVR 15.0. Results The cumulated number of cases per year of irAEs has increased exponentially, with 12,648 patients who developed 13,051 irAEs reported until Dec 31, 2018: Combined CIs were used in 1962 (16%) patients, checkpoint inhibitors in 7099 (66%, overwhelmingly CTLA4 and PD1 inhibitors) and Tyrosine Kinase inhibitors in 3327 (31%); ipilimumab, nivolumab and pembrolizumab were associated with nearly 60% of reported cases. Organ-specific classification of irAEs is summarized in the figure: The Top10 irAEs included enterocolitis (18%), pneumonitis (12%), thyroiditis (11%), myocarditis (6%), myositis (5%), hypophysitis (5%), hepatitis (5%), neuropathy (4%), adrenal (3%) and joint involvement (3%). Most irAEs are organ-specific symptoms not fulfilled criteria of systemic/rheumatic diseases. Conclusion More than 13,000 cases of irAEs triggered by CIs have been reported, with the organ-specific autoimmune damage of the endocrine, digestive and pulmonary systems accounting for 70% of the total reported irAEs. Disclosure of Interests Manuel Ramos-Casals: None declared, Oliver Lambotte: None declared, Marie Kostine: None declared, Leonard Calabrese Consultant for: Bristol-Myers-Squibb, Genentech and Astra-Zeneca., Maria Suarez-Almazor : None declared, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Timothy R. Radstake: None declared, Chiara Baldini: None declared, Thierry Schaeverbeke: None declared, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Hendrik Schulze-Koops Grant/research support from: Novartis, Pfizer, Roche, Consultant for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Paid instructor for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Speakers bureau: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Jan Leipe Grant/research support from: Novartis, Pfizer; Scientific Support: Novartis, Pfizer, Consultant for: AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene, Hospira, Janssen-Cilag, LEO Pharma, Lilly, Novartis, Roche, Sanofi, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Lilly, Novartis, MSD, Pfizer, Roche, Sanofi, UCB, cassandra calabrese Speakers bureau: Regeneron/Sanofi, Pilar Brito-Zeron: None declared, Alejandra Flores-Chavez: None declared, Belchin Kostov: None declared, Soledad Retamozo: None declared, Gustavo Citera: None declared, Eva Aguilar: None declared, Michael Richter: None declared, Merav Lidar: None declared, Benjamin Fisher Consultant for: Novartis, Roche, MedImmune, Bristol-Myers Squibb, Jean-Marie Michot: None declared, David Liew: None declared, Russell Buchanan: None declared, Marte Schrumpf-Heiberg: None declared, Philippe Guilpain: None declared, Debashish Danda: None declared, Peter Olsson: None declared, Yasunori Suzuki: None declared, Saadettin Kilickap: None declared, Gabriela Hernandez-Molina: None declared, Virginia Fernandes Moca Trevisani: None declared, Sonja Praprotnik: None declared, Ildiko Fanny Horvath: None declared, Naoto Azuma: None declared, Berkan Armagan: None declared, Munther Khamashta: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma

Background The ImmunoCancer International Registry is a Big Data-Sharing multidisciplinary network focused on the research of the immune-related adverse events (irAEs) related to cancer immunotherapies (CIs). Objectives To analyse the worldwide scenario of rheumatic/systemic autoimmune diseases (RSirAEs) associated with the use of CIs during the last 20 years. Methods The first objective was to develop a systematic literature review crossing the CIs terms with rheumatic and systemic autoimmune diseases using MedDRAVR 15.0 terms. Results RSirAEs were identified in 11% of 12648 patients with irAEs, including 1435 cases (30% fulfilled criteria for a systemic disease) that were classified in 5 phenotypic clusters: Non-characterized cases included myositis (25%), arthritis (12%), arthralgias (8%), sicca syndrome (7%) and vasculitis (6%); sarcoidosis (6%), myasthenia gravis (5%), polymyalgia rheumatica (4%), leukocytoclastic vasculitis (3%) and giant cell arteritis (2%) were the most frequent systemic diseases identified: In comparison with patients with organ-specific irAEs, RSirAEs were more frequently associated with combined therapies (OR 2.46, CI 2.16-2.81), checkpoint inhibitors -ICis- (OR 4.01 vs TKis, CI 3.26-4.92), and PD-1is (OR 2.46 vs CTLA4is, CI95% 2.16-2.81) Conclusion Rheumatic/systemic irAEs can be divided into 5 phenotypic clusters: articular, muscular, granulomatous, vasculitic and systemic. These findings must be confirmed in real-life patients, and an international data-sharing ICIR registry is planned to be launched. References: Disclosure of Interests: Manuel Ramos-Casals: None declared, Oliver Lambotte: None declared, Marie Kostine: None declared, Leonard Calabrese Consultant for: Bristol-Myers-Squibb, Genentech and Astra-Zeneca., Maria Suarez-Almazor : None declared, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Timothy R. Radstake: None declared, Chiara Baldini: None declared, Thierry Schaeverbeke: None declared, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Hendrik Schulze-Koops Grant/research support from: Novartis, Pfizer, Roche, Consultant for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Paid instructor for: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Speakers bureau: Abbvie, Actelion, Amgen, AstraZeneca, Biogen International, BMS, Celgene, Chugai, GSK, Hospira, Janssen-Cilag, Leo Pharmaceuticals, Lilly, MSD, Medac, Merck, Novartis, Pfizer, Hexal Sandoz, Sanofi, Roche, UCB, Jan Leipe Grant/research support from: Novartis, Pfizer; Scientific Support: Novartis, Pfizer, Consultant for: AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene, Hospira, Janssen-Cilag, LEO Pharma, Lilly, Novartis, Roche, Sanofi, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Lilly, Novartis, MSD, Pfizer, Roche, Sanofi, UCB, cassandra calabrese Speakers bureau: Regeneron/Sanofi, Pilar Brito-Zeron: None declared, Alejandra Flores-Chavez: None declared, Belchin Kostov: None declared, Soledad Retamozo: None declared, Gustavo Citera: None declared, Eva Aguilar: None declared, Michael Richter: None declared, Merav Lidar: None declared, Benjamin Fisher Consultant for: Novartis, Roche, MedImmune, Bristol-Myers Squibb, Jean-Marie Michot: None declared, David Liew: None declared, Russell Buchanan: None declared, Marte Schrumpf-Heiberg: None declared, Philippe Guilpain: None declared, Debashish Danda: None declared, Peter Olsson: None declared, Yasunori Suzuki: None declared, Saadettin Kilickap: None declared, Gabriela Hernandez-Molina: None declared, Virginia Fernandes Moca Trevisani: None declared, Sonja Praprotnik: None declared, Ildiko Fanny Horvath: None declared, Naoto Azuma: None declared, Berkan Armagan: None declared, Munther Khamashta: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma

Background Rheumatic immune-related adverse events (irAEs) following immune checkpoint inhibitor (ICI) therapy for cancer are an increasing burden on rheumatological services but have also been associated with subsequent good oncological outcomes(1). A clinical need for biomarkers to predict rheumatic irAEs exists. High serum albumin and low lactate dehydrogenase (LDH)(2) prior to ICI therapy has been associated with subsequent good oncological outcomes, and may therefore predict rheumatic irAEs, but to the best of our knowledge this has not previously been examined. Objectives To determine the relationship between serum albumin and LDH of immune-related adverse events (irAEs) and oncological outcomes following treatment with the main classes of ICI therapy for cancer, programmed cell death protein 1 (PD-1) inhibitors and programmed death-ligand 1 (PD-L1) inhibitors. Methods We retrospectively examined all patients at a single centre who had a serum albumin performed in the institutional laboratory before treatment with a PD-1 or PD-L1 inhibitor before January 1, 2018, with follow-up until October 1, 2018. Patients with any diagnosis of a rheumatic irAE were identified. Treatment response was determined based on assessment by the treating oncologist, with favourable oncological response defined as complete or partial response. Statistical tests were performed using two-tail t-tests. Missing laboratory values were imputed using median imputation. Results There were 401 episodes of therapy which met criteria, of which 324 had a serum albumin level and 244 had serum LDH prior to the commencement of therapy. A rheumatic irAE was diagnosed in 26 of the 401 patients (6.5%) and a good oncological response was noted in 140 patients (34.9%). There was a statistically significant relationship between higher baseline serum albumin and favourable oncological response (p Conclusion High serum albumin was associated with good oncological outcomes following ICI therapy with a PD-1 or PD-L1, but not with rheumatic irAEs. The reason for this dissonance is not clear. Not all markers of good oncological response predict rheumatic irAEs and further study should focus on consequent implications for rheumatic irAE pathophysiology. References [1] Kostine M, Rouxel L, Barnetche T, Veillon R, Martin F, Dutriaux C, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis. 2017. [2] Bigot F, Castanon E, Baldini C, Hollebecque A, Carmona A, Postel-Vinay S, et al. Prospective validation of a prognostic score for patients in immunotherapy phase I trials: The Gustave Roussy Immune Score (GRIm-Score). European Journal of Cancer. 2017;84:212-8. Disclosure of Interests None declared

Adverse drug reaction (ADR) detection in hospitals is heavily reliant on spontaneous reporting by clinical staff, with studies in the literature pointing to high rates of underreporting [1]. International Classification of Diseases, 10th Revision (ICD-10) codes have been used in epidemiological studies of ADRs and offer the potential for automated ADR detection systems. The aim of this study was to develop an automated ADR detection system based on ICD-10 codes, using machine-learning algorithms to improve accuracy and efficiency. For a 12-month period from December 2016 to November 2017, every inpatient episode receiving an ICD-10 code in the range Y40.0–Y59.9 (ADR code) was flagged for review as a potential ADR. Each flagged admission was assessed by an expert pharmacist and, if needed, reviewed at regular ADR committee meetings. For each report, a determination was made about ADR probability and severity. The dataset was randomly split into training and test sets. A machine-learning model using the random forest algorithm was developed on the training set to discriminate between true and false ADR reports. The model was then applied to the test set to assess accuracy using the area under the receiver operating characteristic (AUC). In the study period, 2917 Y40.0–Y59.9 codes were applied to admissions, resulting in 245 ADR reports after review. These 245 reports accounted for 44.5% of all ADR reporting in our hospital in the study period. A random forest model built on the training set was able to discriminate between true and false reports on the test set with an AUC of 0.803. Automated ADR detection using ICD-10 coding significantly improved ADR detection in the study period, with improved discrimination between true and false reports by applying a machine-learning model.

Background:The pathogenesis of rheumatic immune-related adverse events (irAEs) from checkpoint inhibitor cancer immunotherapy directed against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) remains unknown, even though they are a consequence of pharmacologic inhibition of a specific immune mechanism. Given that some irAEs resemble polymyalgia rheumatica (PMR) or giant cell arteritis (GCA), a disease whose pathogenesis is poorly understood, observations regarding the pathogenesis of PMR-like or GCA-like irAEs are of significant interest. One proposed pathogenic mechanism involves generalized immune activation leading to a spectrum of subclinical disease. Interrogation of this hypothesis may be aided by PET/CT, which is frequently utilized for oncological staging purposes but is also useful in classical PMR or GCA diagnosis. If PMR or GCA irAEs merely represent a spectrum of generalized immune activation, low-grade subclinical PMR or GCA-related changes on PET/CT might be expected to be seen in patients who receive immunotherapy, irrespective of whether they develop clinically evident rheumatic irAEs.Objectives:This study investigated whether such changes occurred in patients receiving immunotherapy who did not develop clinically evident rheumatic irAEs.Methods:Consecutive patients exposed to PD-1 or PD-L1 inhibitor immunotherapy at a single center had scintigraphic uptake calculated by a nuclear medicine physician experienced in assessment of vasculitis. Patients were included if they had had 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging both within the two weeks prior to immunotherapy initiation and after at least eleven weeks of immunotherapy. Patients who went on to develop a rheumatic irAE were excluded, as were patients with scintigraphic evidence of liver metastases owing to their potential influence on scoring of uptake. Quantification of 18F-FDG uptake by maximum standardized uptake values (maximum standard unit value, SUVmax) was performed at sites relevant to PMR or GCA (17 sites relevant to PMR, 17 sites relevant to GCA) in paired scans, and the difference calculated.Results:Twenty-four patients receiving nivolumab, pembrolizumab or avelumab met the inclusion criteria, primarily for melanoma, non-small cell lung cancer, or lymphoma. The mean age was 67 at the time of the first scan, 71% were male, and 66% had a complete or partial oncological response at best response. No statistically or clinically significant difference in SUVmax was noted at any PMR or GCA-relevant anatomical site interrogated. Latent class analysis did not reveal clusters identifiable by cancer type, best response, or presence of combination therapy.Conclusion:Patients treated with PD-1/PD-L1 inhibitors without clinically evident rheumatic irAEs do not develop subclinical PMR or GCA-like changes on PET/CT. This supports the proposition that PMR-like and GCA-like irAEs are a distinct entity with stochastic onset, and do not simply represent generalized immune activation induced by immunotherapy.Acknowledgements:David Liew is the recipient of the Ronald John Gleghorn Bursary from the University of Melbourne.Disclosure of Interests:David Liew: None declared, Aurora Poon: None declared, Christopher McMaster: None declared, Claire Owen Speakers bureau: Roche, Jessica Leung Speakers bureau: GIlead, Novartis, Albert Frauman: None declared, Jonathan Cebon: None declared, Andrew Scott: None declared, Russell Buchanan: None declared

Background:Giant cell arteritis (GCA), if left untreated, confers the threat of serious cranial ischaemic complications including permanent visual loss. Although achieving a prompt and accurate diagnosis remains challenging, early diagnosis is viewed as being paramount in preventing significant morbidity.1 This raises the question of whether GCA patients are at greater risk of developing visual sequelae if there is a longer window between symptom onset and presentation.Objectives:To compare the frequency of lasting visual loss in patients diagnosed with GCA undergoing temporal artery biopsy (TAB) within three months and after three months of symptom onset.Methods:Patients who underwent TAB from January 2011 to November 2020 were identified from the pathology database of an Australian rheumatology referral centre. The diagnosis of GCA was established for each patient based on either positive TAB or, in the setting of negative TAB, clinical diagnosis by a rheumatologist. Baseline demographics, symptoms and major confounders – including age, sex, history of polymyalgia rheumatica or inflammatory arthritis, headache, jaw pain, fatigue, temporal artery tenderness or diminished pulse, and number of 1990 American College of Rheumatology (ACR) classification criteria for GCA2 fulfilled – were manually extracted from electronic medical records, as was the duration between onset of GCA symptoms and TAB, and the presence of visual loss before and after TAB. Logistic regression log-likelihood tests were used to examine the two cohorts presenting before and after three months.Results:There were 167 patients who underwent TAB during the study period with accessible clinical information. Of these, 31 (19%) had a delayed presentation of greater than three months from symptom onset. There were no statistical differences in patient demographics between the two groups (Table 1). No patients with delayed presentation experienced lasting, objective visual loss. In contrast, there were three cases in the cohort of patients who presented more promptly; these included two patients who developed permanent unilateral blindness, and one who experienced unilateral vision loss with some improvement at three months of follow-up.Table 1.Patient characteristics by time from symptom onset to TAB.Presentation Presentation ≥3 monthsp-valueAge (years)73.45±10.0669.84±10.750.080Female92 (67.65%)20 (64.52%)0.738History of polymyalgia rheumatica23 (16.91%)4 (12.90%)0.586History of inflammatory arthritis6 (4.41%)2 (6.45%)0.633Headache110 (80.88%)23 (74.19%)0.406Jaw pain37 (27.21%)5 (16.13%)0.206Fatigue28 (20.59%)6 (19.35%)0.878Temporal artery tenderness or diminished pulse46 (33.82%)11 (35.48%)0.860ACR classification criteria2.83±0.992.58±0.890.199Conclusion:GCA patients with a lengthier course of symptoms before diagnosis did not experience any enduring visual loss. This may reflect a pattern of more aggressive disease leading to earlier presentation, but further study should explore whether longer symptom duration before diagnosis necessitates a higher degree of clinical concern.References:[1]Font C, Cid MC, Coll-Vinent B, López-Soto A, Grau JM. Clinical features in patients with permanent visual loss due to biopsy-proven giant cell arteritis. Br J Rheumatol. 1997 Feb;36(2):251-4. doi: 10.1093/rheumatology/36.2.251. PMID: 9133940.[2]Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990 Aug;33(8):1122-8. doi: 10.1002/art.1780330810. PMID: 2202311.Disclosure of Interests:None declared

Background:Temporal artery biopsy (TAB) is widely recognised as the diagnostic gold standard for GCA despite having a poor sensitivity due to the presence of ‘skip’ lesions. There is, however, a lack of consensus guiding TAB practice, particularly in relation to optimal length, need for bilateral specimens, and number of segments examined.Objectives:To investigate the impact of factors such as total biopsied length, laterality, segment number, and referral centre on histopathological outcomes in an Australian setting.Methods:Reports for all available biopsy specimens labelled “temporal artery” were extracted from the pathology service records of two rheumatology referral centres with adjacent geographic catchments. Each histopathology report was manually reviewed to establish length of biopsied artery, laterality, and number of segments, along with patient demographics such as age, sex, and referral centre. Key histopathological findings including intimal hyperplasia, disruption of the internal elastic lamina, presence of giant cells, and adventitial inflammation were recorded. Multivariable logistic regression with site-varying intercept was performed.Results:TAB reports from a total of 577 patients were captured, with results available from the two centres from 1999-2019 and 2010-2019 respectively. The mean age in this group was 73, and 69% were female (Table 1). A bilateral TAB was performed in 29%, and the mean total biopsy length was 2.5cm. Of these patients, 122 had positive biopsies (21%), with intimal hyperplasia reported in 100 (17%), giant cells in 83 (14%), and adventitial findings in 68 (12%). Positive biopsy weakly correlated with increased total length of biopsy in centimetres (OR 1.25 [1.06-1.47]) (Figure 1) and increased age in years (OR 1.02 [1.00-1.05]) but not laterality or sex (Table 2). There was a substantial difference between the two centres, which was incompletely accounted for once corrected for total biopsy length and calendar year of biopsy, suggesting either unmeasured differences in patient demographics or a difference in clinical practice. This change was preserved across analysis of different histopathological subtypes.Table 1.Patient characteristics by biopsy result.Negative(n = 455)Positive(n = 122)Total(n = 577)Age (years) Mean (SD)72 (± 11)75 (± 8.9)73 (± 10)Sex Female310 (68%)88 (72%)398 (69%) Male145 (32%)34 (28%)179 (31%)Maximum biopsy length (cm) Mean (SD)1.8 (± 0.86)2.0 (± 1.10)1.9 (± 0.92)Total biopsy length (cm) Mean (SD)2.4 (± 1.6)2.8 (± 2.1)2.5 (± 1.7)Mean biopsy length (cm) Mean (SD)1.7 (± 0.78)1.9 (± 0.97)1.7 (± 0.83)Laterality Bilateral130 (29%)39 (32%)169 (29%) Unilateral325 (71%)83 (68%)408 (71%)Table 2.Associations with positive TAB on multivariable logistic regression.Overall positive findingIntimal hyperplasiaGiant cellsAdventitial inflammationTotal biopsy length (cm)1.25(1.06-1.47)1.18(0.98-1.40)1.21(1.00-1.46)1.07(0.87-1.31)Unilateral (vs. bilateral)1.56(0.82-3.07)1.12(0.56-2.30)1.28(0.61-2.77)0.82(0.38-1.82)Age (years)1.02(1.00-1.05)1.02(1.00-1.04)1.03(1.00-1.05)1.00(0.98-1.03)Male (vs. female)0.83(0.52-1.29)0.63(0.37-1.05)0.59(0.32-0.92)0.75(0.41-1.31)Centre 2 (vs. centre 1)0.54(0.34-0.84)0.41(0.24-0.68)0.55(0.32-0.92)0.46(0.25-0.82)Figure 1.The effect of total biopsy length on result, stratified by laterality.Conclusion:Total biopsy length was weakly associated with a positive TAB result, but differences in results between referral centres independent of biopsy length suggest other selection factors may be important in determining TAB yield. Examination of differences in results between a greater number of referral centres would assist in determining the extent of this variability.Disclosure of Interests:None declared

Background Septic arthritis is a rheumatologic emergency associated with significant morbidity and mortality1. Timely and accurate diagnosis in the emergency department is essential for early medical and surgical involvement. Objectives To examine the predictive value of investigations used to diagnose septic arthritis in the acute setting. Methods A retrospective chart review was conducted on all patients referred from the emergency department to the orthopaedic surgery service with a potential diagnosis of septic arthritis between June 2010 and December 2015 at the Austin Hospital in Melbourne, Australia. Data was collected regarding demographic details, risk factors, pathology results, antibiotic prescribing, joint aspirate and theatre samples. Results The study included 126 patients with 132 emergency department presentations involving 141 joints. The median age of patients was 70 (IQR 52.3–79.8); 86 (68.3%) were male. The most common joints involved were the knee (49.6%) and hip (17.7%). In 88 of the 132 presentations (67%), culture of the synovial fluid was positive. 19 of these 88 (22%) culture positive presentations had no classical risk factors for septic arthritis (joint prosthesis, previous septic arthritis, immunosuppressed, previous joint disease, intravenous drug use). 12 of the 88 (13%) culture positive patients had symptoms for longer than 4 weeks on presentation in contrast to 2 of the 44 (5%) in culture negative group. There were 8 presentations with multiple joints involved. None of these presentations were in the culture positive group. There was no evidence of a relationship between WCC and culture status (p=0.56) or CRP and culture status (p=0.64), either singly or when combined. There were 94 joint aspirations performed in 132 presentations. 30 (32%) joint aspirations required ultrasound guidance. 42 (45%) joint aspirations had antibiotics administered prior to sample collection. In the culture positive presentations 25 (28.4%) did not have a joint aspirate performed prior to surgical washout. Crystals were seen in 19 (30.2%) culture positive patients. 26 (29.5%) culture positive presentations had no growth on aspirate culture but had positive theatre cultures. Conclusions While septic arthritis is a common emergency presentation, there are few useful non-invasive diagnostic tests. Although risk factors aid in stratifying risk, duration of symptoms and inflammatory markers are poor differentiators. Neither the presence of crystals nor the absence of growth on aspirate culture exclude septic arthritis. Reference [1] Gupta M, Sturrock R, Field M. A prospective 2-year study of 75 patients with adult-onset septic arthritis. Rheumatology2001(40):24–30. Disclosure of Interest None declared

Background Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome describes a clinical entity characterised by distal synovitis with pitting oedema, the absence of rheumatoid factor (RhF) and an excellent response to glucocorticoid therapy.[1 Most frequently associated with polymyalgia rheumatica (PMR), tenosynovial sheath inflammation represents the magnetic resonance imaging (MRI) hallmark of this condition, with concomitant joint synovitis also present in some cases.[1 More recently, diffusely increased 18F-fluorodeoxyglucose (18F-FDG) uptake in the soft tissues around the ankles and feet has been described as the correlate of RS3PE on whole body positron emission tomography/computed tomography (PET/CT).[2 Objectives To document the clinical and radiologic appearance of RS3PE syndrome affecting the hands on MRI and whole body PET/CT in PMR patients. Methods Patients with newly diagnosed PMR were prospectively recruited as part of the Melbourne Predictors of Relapse in PMR (MPR-PMR) study. A standard physical examination was carried out with specific focus upon the presence of peripheral synovitis and pitting oedema. In patients with findings suggestive of RS3PE, clinical photography was undertaken. All study participants underwent a whole body PET/CT scan including dedicated views of the hands using the Phillips T/F machine prior to prednisolone commencement. To precisely identify anatomic correlates of abnormal 18F-FDG uptake in patients with RS3PE, MRI of the wrist and hand was performed using a 1.5 Tesla magnet. Results 3/35 patients (0.86%) were noted to have distal synovitis and pitting oedema of the hands at enrolment. Mean age was 70.9±10.1 years, two patients were male, and all were Caucasian. RhF and anti-citrullinated peptide autoantibodies were negative in all cases. On whole body PET/CT, intense 18F-FDG uptake was visualised at the wrist joint and hand in a distinctive volar distribution. MRI of the wrist and hand in two participants (contraindicated in the third) confirmed flexor tenosynovitis (white arrows) and intercarpal synovitis (yellow arrow) in keeping with RS3PE syndrome. Conclusions On whole body PET/CT, RS3PE syndrome is associated with a distinctive volar pattern of abnormal 18F-FDG uptake at the wrist and hand, which correlates with flexor tenosynovitis and intercarpal synovitis as previously described on MRI. References [1] Cantini F, Salvarani C, Olivieri I, et al. Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study. Annals of the Rheumatic Diseases. 1999;58(4):230–6. [2] Wang J, Pu C, Wang Z, Yang J. Remitting Seronegative Symmetrical Synovitis With Pitting Edema: Appearance on FDG PET/CT. Clin Nucl Med. 2017;42(6):492–5. Disclosure of Interest None declared

Background Programmed cell death protein (PD-1) inhibitor immunotherapy is being increasingly used in oncology, but may cause immune-related adverse events (irAEs) resembling classical rheumatic and non-rheumatic autoimmune diseases. While oncological response to therapy has been associated with the development of rheumatic irAEs, no biomarker to predict the development of rheumatic irAEs has yet been identified. Thyroid stimulating hormone (TSH) is readily available in clinical practice and is frequently tested prior to the administration of PD-1 inhibitors to screen for existing thyroid disease. Objectives To investigate whether thyroid stimulating hormone, or changes to it, are associated with the development of immune-related adverse events (irAEs) following PD-1 inhibitor therapy for cancer. Methods This was a retrospective chart review of all patients at a single centre who had a TSH level performed in the institutional laboratory prior to the patient being dispensed nivolumab or pembrolizumab before January 1, 2017, with follow-up until July 1, 2017. TSH levels before and during PD-1 inhibitor therapy were recorded. Patients with any diagnosis of a rheumatic irAE or any non-cutaneous irAE were identified. Linear regression was performed to determine the relationship between TSH and the development of irAEs. Youden’s index was used to derive the optimal cut-off point. Recursive partitioning methods with imbalanced prior probabilities were used to create a decision tree model. Results There were 213 episodes of therapy which met criteria, of which a non-cutaneous irAE occurred in 62 episodes (29.1%), thyroid irAEs occurred in 22 episodes (10.3%) and rheumatic irAEs were diagnosed in 16 episodes (7.5%). Even when corrected for duration of exposure to PD-1 inhibitor therapy, elevated TSH levels (>4.2 mU/L) were statistically significantly associated with the development of rheumatic irAEs (adjusted OR 6.08, 1.53–24.22), and this was not weakened by excluding patients who went on to develop thyroid irAEs. There was no significant association between elevated TSH levels and the development of any non-cutaneous irAE. Change in TSH levels with PD-1 inhibitor therapy was also not associated with the development of non-cutaneous irAEs or rheumatic irAEs specifically. Using a TSH level >2.4 to predict rheumatic irAEs led to a positive predictive value of 25% and a negative predictive value of 93% in our cohort. A decision tree model to predict rheumatic irAEs combining a pre-PD-1 inhibitor TSH level >2.4 and an oncological response to therapy led to a positive predictive value of 50% and a negative predictive value of 94% in our cohort. Conclusions Elevated TSH levels may be a potential biomarker for the development of rheumatic irAEs. In particular, a pre-PD-1 inhibitor TSH level of >2.4 mU/L, in combination with oncological response to therapy, may identify patients at risk of rheumatic irAEs. Associations observed in this cohort should be examined in larger cohorts to determine the clinical utility of TSH in predicting rheumatic irAEs. Disclosure of Interest None declared

Background Despite abnormal C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) being required in the 2012 EULAR/ACR classification criteria, 7%–20% of polymyalgia rheumatica (PMR) patients possess normal inflammatory markers at diagnosis.1 A characteristic pattern of 18F-fluorodeoxyglucose (18F-FDG) uptake is seen on whole body positron emission tomography/computed tomography (PET/CT) in PMR, hence this imaging modality may be a useful diagnostic test in this clinical scenario. Objectives To report the utility of whole body PET/CT for diagnosing PMR in patients with normal inflammatory markers and compare the clinical and radiologic characteristics of this subgroup with patients from the Melbourne Predictors of Relapse in PMR (MPR-PMR) study. Methods Patients presenting with clinical features of PMR according to the 2012 EULAR/ACR classification criteria but normal CRP and ESR underwent 18F-FDG PET/CT as part of their diagnostic work-up. A whole body scan from skull vertex to feet (including dedicated hand views) was performed using the Phillips T/F machine prior to prednisolone commencement. Qualitative and semi-quantitative (standardised uptake value maximum [SUVmax]) scoring of abnormal 18F-FDG uptake was undertaken. Newly diagnosed and untreated PMR patients who underwent the same 18F-FDG PET/CT protocol as part of the MPR-PMR study were used as the comparator group. Statistical analysis was conducted using Stata 13.1 (StataCorp, College Station, TX, USA). Results Three patients with normal inflammatory markers (Median CRP 1 [0.9–2], median ESR 61 – 7) underwent 18F-FDG PET/CT. Mean age was 60.15±7.55 years, two patients (66.67%) were male and all were Caucasian. Shoulder and hip pain was present in all cases, but only one patient reported peripheral joint involvement. Median early morning stiffness (EMS) was 30 min.15 – 60 On whole body PET/CT, characteristic 18F-FDG uptake was visualised in each patient at the shoulder capsule, trochanteric bursae and adjacent to the ischial tuberosities, with hip capsule involvement similarly present in 2/3. When compared with 35 patients from the MPR-PMR study, there were no statistically significant differences in the clinical characteristics nor the distribution or intensity of abnormal 18F-FDG uptake between the two populations. Conclusions In patients with suggestive clinical features but normal inflammatory markers, whole body PET/CT may be utilised to confirm a diagnosis of PMR. Reference [1] Cantini F, Salvarani C, Olivieri I, et al. Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study. Seminars in Arthritis & Rheumatism. 2000;30(1):17–24. Disclosure of Interest None declared

Background Gout is a common inflammatory arthropathy with a reported prevalence ranging from 1.7% to 4% within Australia – one of the highest in the world, second only to New Zealand.1 Epidemiological studies have established that its prevalence has increased steadily over recent years, with the impact of the disease on the rise.2 Gout has painful and debilitating effects on patients leading to impact on their quality of life. Even though usually managed in the primary care setting, many patients are ultimately admitted as inpatients to hospital with the associated increased resource utilisation and cost. There is a growing recognition of the economic burden of gout.3 A Canadian study estimated 5-year total health costs of patients with gout at $10,332 more than comparable gout free patients.4 Objectives To identify factors potentially contributing to increased length of inpatient hospital stay for acute exacerbations of gout in a teaching hospital in Melbourne, Australia. Methods Patients admitted to The Northern Hospital, Melbourne, Australia with a discharge diagnosis of gout as their only acute medical problem between 1st July 2014 and 30th June 2016 were identified using ICD-10 disease coding from institutional compensation reports. Retrospective chart review was performed identifying length of stay and for variables which may potentially affect it. Results 121 patients were discharged with an acute gout flare over the 2 years with a mean age of 66±15 years. The vast majority of patients in this cohort were male (86%). The mean length of stay was 2.3 days (95% CI 1.83–2.78 days), with a median of 1 day. The median length of hospital stay was increased by 2 days if patients lived alone (p=0.042) and 1 extra day if the C-Reactive Protein (CRP) measured at admission was >100 mg/L (p=0.001). Hospital stay was similarly prolonged by a single day if more than one joint was involved in the flare (p=0.003). Conclusions Gout without antecedent acute medical comorbidity is a common acute medical presentation to hospital with a large corresponding economic burden. Factors affecting length of inpatient stay include social status, marked elevation of CRP and polyarticular involvement. This study identifies factors which warrant further investigation as to how they may be ameliorated in order to improve health resource utilisation. References Smit E, Hoy D, Cross M et al. Burden of disability due to musculoskeletal (MSK) disorders. Ann Rheum Dis 2014; 73: 1470–1476. Becker MA. Recent developments in the management of gout. Rheumatology 2012;51:i1. Shields GE, Beard SM. A systematic review of the economic and humanistic burden of gout. PharmacoEconomics 2015;33: 1029–1047. Fischer A, Cloutier M, Goodfield J, Borrelli R, Marvin D, Dziarmaga A. The direct economic burden of gout in an elderly Canadian population. J Rheumatol 2017;44(1):95–101. Disclosure of Interest None declared

CK: Principal Investigator. CM and CK were responsible for the study design and conception; all authors were responsible for acquisition and validation of the data; CM was responsible for analysis and interpretation of the data; and all authors contributed to reviewing drafts of the manuscript and approved the final version for publication.

Melbourne: Therapeutic Guidelines Limited; 2017.331 pagesAlso available at www.tg.org.auThe complex world of...

A 59-year-old female underwent a renal transplant in early 2015. Her initial immunosuppression regimen was mycophenolate mofetil, prednisolone and tacrolimus.

Background Propofol, sevoflurane, and desflurane may cause hemodynamic compromise during anesthesia and critical care management. The aim of the study was to compare these anesthetics during increased dose and recovery to maintenance level. Methods Anesthetized, open-chest New Zealand White rabbits were used to acquire dose-response curves with sevoflurane, desflurane, and propofol, followed by reduction to baseline infusion. Simultaneous high-fidelity left ventricular pressure and volume data were acquired during caval occlusion with a dual-field conductance catheter inserted via an apical stab. The preload recruitable stroke work and the end-diastolic pressure-volume relationship were used as the primary measures of contractility and diastolic function. Results The time-matched controls were stable over time. Propofol and desflurane but not sevoflurane caused dose-dependent reductions in myocardial contractility, although sevoflurane reduced contractility more at 1 minimal alveolar concentration. All anesthetics reduced mean arterial pressure, and significant recovery occurred for sevoflurane and desflurane but not for propofol. The end-diastolic pressure-volume relationship was increased by sevoflurane. Ejection fraction decreased with sevoflurane only. All anesthetics caused dose-dependent vasodilation, with recovery for desflurane and sevoflurane but not propofol. Heart rate was decreased with propofol without significant recovery. Propofol plasma concentrations remained elevated after dose return to baseline infusion rate, suggestive of distribution compartment saturation. Conclusion All three anesthetics caused dose-dependent decreases in cardiovascular function. Recovery of cardiovascular function occurred rapidly with sevoflurane and desflurane, but persistent depression of contractility, vasodilation, mean arterial pressure, and heart rate occurred with propofol during a 30-min recovery period.