Long-term incidence, risk factors and complications for venous thromboembolism in patients with systemic lupus erythematosus.

AIM: To compare frequency, incidence rates (IR), risk factors and outcomes of a first venous thromboembolic event (VTE) between patients with systemic lupus erythematosus (SLE) and controls. METHODS: Using state-wide longitudinal hospital data from Western Australia (WA), we recorded venous thrombosis (VT) and pulmonary embolism (PE) in patients with SLE (n = 1854, median age 40, 86% female) and matched hospitalised controls (n = 12,107, median age 40 years, females 88.6%) in the period 1985-2015. Results presented are medians, frequency, IR per 1000 person years (PY) and odds, rate, or adjusted hazard ratios (OR/RR/a-HR) with 95% confidence intervals (CI). RESULTS: Patients with SLE had significantly higher odds (12.8 vs 3.3%; OR 4.26, CI 3.60-5.05) and IR for a first VTE (10.09 vs 1.52; RR 6.64; CI 5.56-7.79). Over the three study decades, the IR for PE declined in patients with SLE from 7.74 to 3.75/1000 PY (p < .01) with no changes observed for VT or in controls. VTE recurred more frequently in patients with SLE (24.1% vs 10.2 %) (p < .01). Antiphospholipid antibodies (aPL) (a-HR 4.24, CI 2.50-7.19), serositis (a-HR 2.70, CI 1.86-3.91), lupus nephritis (a-HR 1.75 CI 1.25-2.33) and thrombocytopenia (a-HR 1.65 (1.10-2.49) were the strongest disease risk factors for VTE only in patients with SLE, while arterial hypertension, smoking and obesity were independent VTE risk factors for both groups. VTE was not associated with an increased risk for arterial events, but PE increased the risk for pulmonary hypertension (PH) in both patients with SLE (a-HR 6.47, CI 3.73-11.23) and controls (a-HR 9.09, CI 3.50-23.63). VTE increased the risk of death in both patients with SLE (a-HR 2.02, CI 1.50-2.70) and controls (a-HR 6.63, CI 5.21-8.42) after 10 years of follow-up. CONCLUSIONS: VTE affected 12.8% of patients with SLE at six times the VTE rate in controls with aPL as the strongest, but not the only risk factor in SLE. The risk of PH was increased in both groups following PE, but VTE did not associate with an increased risk of arterial events.

Joint surgery rates in lupus: a long-term cohort study.

AIM: With scarce data on the need and type of joint surgery in SLE, we investigated the long-term rates and underlying causes for arthroplasty, arthrodesis and synovectomy in patients with SLE. METHODS: Procedure dates for arthroplasty, arthrodesis or synovectomy were retrieved from the state-wide Hospital Morbidity Data Collection between 1985 and 2015 for patients with SLE (n=1855) and propensity-matched controls (n=12 840). Patients with SLE with ≥two additional diagnostic codes for rheumatoid arthritis were classified as rhupus. ORs and incidence rates (IRs) per 100 person-years for joint procedures (JPs) were compared among patients with rhupus, patients with other SLE and controls across three study decades by regression analysis. RESULTS: More patients with SLE than controls underwent a JP (11.6% vs 1.3%; OR 10.8, CI 8.86 to 13.24) with a higher IR for JP in patients with SLE (1.9 vs 0.1, rate ratio 19.9, CI 16.83 to 23.55). Among patients with SLE, patients with rhupus (n=120, 60.5%) had the highest odds of arthroplasty (OR 4.49, CI 2.87 to 6.92), arthrodesis (OR 6.64, CI 3.28 to 12.97) and synovectomy (OR 9.02,CI 4.32 to 18.23). Over time, the IR for overall JP in patients with rhupus was unchanged (8.7 to 8.6, R2=0.004, p=0.98), although the IR for avascular necrosis underlying arthroplasty decreased for all patients with SLE (0.52 to 0.10, p=0.02). Patients with other SLE also had significantly higher OR and IR for all three JPs than controls with insignificant decreases in synovectomy and increases in arthroplasty over time in this group. CONCLUSIONS: The overall burden of joint surgery in SLE is high and despite a reduction in avascular necrosis, arthroplasty and arthrodesis rates have not decreased over time. These data indicate a need for increased efforts to prevent joint damage in patients with lupus.

Recommendations for early referral of individuals with suspected polymyalgia rheumatica: an initiative from the international giant cell arteritis and polymyalgia rheumatica study group.

OBJECTIVE: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). METHODS: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated. RESULTS: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. CONCLUSIONS: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.

Cancer development in patients hospitalized with systemic lupus erythematosus: A population-level data linkage study.

AIM: To explore the association between systemic lupus erythematosus (SLE) with the risk of cancer development and subsequent 5-year mortality in Western Australia (WA). METHODS: Population-level, data linkage study of SLE patients (n = 2111) and general population comparators (n = 21 110) hospitalized between 1980 and 2014. SLE patients (identified by ICD-9-CM: 695.4, 710.0, and ICD-10-AM: L93.0, M32.0) were nearest matched (10:1) for age, sex, Aboriginality, and temporality. Follow up was from time zero (index SLE hospitalization) to cancer development, death or 31 December 2014. We assessed the risk of cancer development and subsequent 5-year mortality between SLE patients and comparators with univariate and multivariate-adjusted Cox proportional hazards regression models. RESULTS: SLE patients had similar multivariate-adjusted risk (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.93-1.15; p = .583) of cancer development. Cancer development risk was higher in SLE patients <40 years old (aHR 1.58, 95% CI 1.29-1.94; p < .001), and from 1980 to 1999 (aHR 1.16, 95% CI 1.02-1.31; p < .001). SLE patients had higher risk of developing cancer of the oropharynx (aHR 2.13, 95% CI 1.30-3.50), vulvo-vagina (aHR 3.22, 95% CI 1.34-7.75), skin (aHR 1.20, 95% CI 1.01-1.43), musculoskeletal tissues (aHR 2.26, 95% CI 1.16-4.40), and hematological tissues (aHR 1.78 95% CI 1.25-2.53), all p < .05. After cancer development, SLE patients had increased risk of 5-year mortality (aHR 1.31, 95% CI 1.06-1.61); highest in patients <50 years old (aHR 2.03, 95% CI 1.03-4.00), and in those with reproductive system and skin cancers. CONCLUSIONS: Hospitalized SLE patients had increased risk of multiple cancer sub-types. Following cancer development, SLE patients had increased risk of 5-year mortality. There is scope to improve cancer prevention and surveillance in SLE patients. TRIAL REGISTRATION: Not applicable. This low-risk risk study used de-identified administrative linked health data.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Hospitalisation for systemic lupus erythematosus associates with an increased risk of mortality in Australian patients from 1980 to 2014: a longitudinal, population-level, data linkage, cohort study.

OBJECTIVE: Mortality rates for patients with SLE have not been reported in Australia. This study determined the association between a hospitalisation for SLE with mortality. METHODS: Population-level cohort study of patients with SLE (n=2112; 25 710 person-years) and general population comparators (controls) (n=21, 120; 280 637 person-years) identified from hospital records contained within the WA Rheumatic Disease Epidemiological Registry from 1980 to 2013. SLE was identified by ICD-9-CM: 695.4, 710.0, ICD-10-AM: L93.0, M32.0. Controls were nearest matched (10:1) for age, sex, Aboriginality and temporality. Using longitudinal linked health data, we assessed the association between a hospitalisation for SLE mortality and mortality with univariate and multivariate Cox proportional hazards and competing risks regression models. RESULTS: At timezero, patients with SLE were similar in age (43.96 years), with higher representation of females (85.1% vs 83.4%, p=0.038), Aboriginal Australians (7.8% vs 6.0%) and smokers (20.5% vs 13.2%). Before study entry, patients with SLE (mean lookback 9 years) had higher comorbidity accrual (Charlson Comorbidity Index ≥1 item (42.0% vs 20.5%)), especially cardiovascular disease (CVD) (44.7% vs 21.0%) and nephritis (16.4% vs 0.5%), all p<0.001. During follow-up (mean 12.5 years), 548 (26.0%) patients with SLE and 2450 (11.6%) comparators died. A hospitalisation for SLE increased the unadjusted (HR 2.42, 95% CI 2.20 to 2.65) and multivariate-adjusted risk of mortality (aHR 2.03, 95% CI 1.84 to 2.23), which reduced from 1980 to 1999 (aHR 1.42) to 2000-2014 (aHR 1.27). Females (aHR 2.11), Aboriginal Australians (aHR 3.32), socioeconomically disadvantaged (aHR 2.49), and those <40 years old (aHR 7.46) were most vulnerable. At death, patients with SLE had a higher burden of infection (aHR 4.38), CVD (aHR 2.09) and renal disease (aHR 3.43), all p<0.001. CONCLUSIONS: A hospitalisation for SLE associated with an increased risk of mortality over the 1980-2014 period compared with the general population. The risk was especially high in younger (<40 years old), socioeconomically disadvantaged and Aboriginal Australians.

Muscle shear wave elastography, conventional B mode and power doppler ultrasonography in healthy adults and patients with autoimmune inflammatory myopathies: a pilot cross-sectional study.

BACKGROUND: Before the role of shear wave elastography (SWE) and B mode ultrasound (US) in the diagnosis of different forms of idiopathic inflammatory myopathies (IIM) can be investigated, normative data is required. This study aimed to describe and then compare normative SWE and B mode ultrasound metrics of muscles in healthy controls and patients with IIM. METHODS: Twenty nine healthy adult controls and 10 IIM patients (5 with inclusion body myositis and 5 with necrotising autoimmune myopathy) underwent a full clinical examination, laboratory investigations, SWE and US measurements of selected proximal and distal limb muscles. Shear wave speed (SWS) and multiple US domains [echogenicity, fascial thickness, muscle bulk and power Doppler (PD)] were measured in both groups. RESULTS: In healthy controls (n = 29; mean age 46.60 ± 16.10; 44.8 % female), age was inversely correlated with SWS at the deltoid (stretch) (Rs. -0.40, p = 0.030) and PD score at the deltoid (rest) (Rs. -0.40, P = 0.032). Those ≥ 50 years old had a lower SWS at the deltoid (stretch) compared to the < 50 year group (2.92 m/s vs. 2.40 m/s, P = 0.032). Age correlated with increased echogenicity in the flexor digitorum profundus (Rs. 0.38, P = 0.045). Females had a smaller muscle bulk in the deltoid (P = 0.022). Body mass index (BMI) was inversely associated with SWS in the deltoid (stretch) (Rs - 0.45, P = 0.026), and positively correlated with echogenicity in the deltoid (Rs. 0.69, P = 0.026). In patients ≥50 years of age, patients with IIM (mean age 61.00 ± 8.18; females 20.0 %) had a higher proportion of abnormal echogenicity scores at the flexor digitorum profundus (FDP) (40.00 % vs. 14.30 %, P = 0.022) and tibialis anterior (TA) (80.00 % vs. 28.60 %, P = 0.004). Fascial thickness was lower in the FDP (0.63mm vs. 0.50mm, p = 0.012) and TA (0.58mm vs. 0.45mm, P = 0.001). CONCLUSIONS: Our findings suggest there is scope for US techniques to be useful for diagnostic screening of affected muscles in patients with IIM, especially in those with suspected inclusion body myositis or necrotising autoimmune myopathy. We provide normative data for future studies into SWE and US techniques in skeletal muscle. The differences between IIM patients and controls warrant further study in a broader IIM patient cohort.

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

OBJECTIVE: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard. METHODS: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings. RESULTS: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation. CONCLUSION: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

Mining social media data to investigate patient perceptions regarding DMARD pharmacotherapy for rheumatoid arthritis.

OBJECTIVES: We hypothesise that patients have a positive sentiment regarding biological/targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) and a negative sentiment towards conventional synthetic agents (csDMARDs). We analysed discussions on social media platforms regarding DMARDs to understand the collective sentiment expressed towards these medications. METHODS: Treato analytics were used to download all available posts on social media about DMARDs in the context of rheumatoid arthritis. Strict filters ensured that user generated content was downloaded. The sentiment (positive or negative) expressed in these posts was analysed for each DMARD using sentiment analysis. We also analysed the reason(s) for this sentiment for each DMARD, looking specifically at efficacy and side effects. RESULTS: Computer algorithms analysed millions of social media posts and included 54 742 posts about DMARDs. We found that both classes had an overall positive sentiment. The ratio of positive to negative posts was higher for b/tsDMARDs (1.210) than for csDMARDs (1.048). Efficacy was the most commonly mentioned reason in posts with a positive sentiment and lack of efficacy was the most commonly mentioned reason for a negative sentiment. These were followed by the presence/absence of side effects in negative or positive posts, respectively. CONCLUSIONS: Public opinion on social media is generally positive about DMARDs. Lack of efficacy followed by side effects were the most common themes in posts with a negative sentiment. There are clear reasons why a DMARD generates a positive or negative sentiment, as the sentiment analysis technology becomes more refined, targeted studies could be done to analyse these reasons and allow clinicians to tailor DMARDs to match patient needs.

Imaging in gout: A review of the recent developments.

Gout is a common inflammatory arthritis and is caused by accumulation of monosodium urate crystals in joints and soft tissues. Apart from joint damage, untreated gout is associated with cardiovascular and renal morbidity. Gout, whilst in principle considered to be well understood and simple to treat, often presents diagnostic and management challenges, with evidence to suggest that it is often inadequately treated and poor compliance is a major issue. Imaging tools can aid clinicians in establishing the correct diagnosis, when histological crystal diagnosis is unable to be established, and also assess the burden of inflammatory and structural disease. Imaging can also be used to monitor treatment response. The imaging techniques that currently have a role in the imaging of gout include conventional radiography, ultrasound, computed tomography, dual energy computed tomography, magnetic resonance imaging and nuclear medicine. Despite the lack of major technological advances in imaging of gout in recent years, scientific studies of existing imaging modalities have improved our understanding of the disease, and how to best utilize imaging techniques in the clinical setting.

A systematic review of ultrasonography in gout and asymptomatic hyperuricaemia.

Gout is one of the most common inflammatory arthritides. The literature reveals that management of this condition is often suboptimal. Imaging techniques, such as ultrasound (US), may assist in the diagnosis and management of gout and asymptomatic hyperuricaemia (AH). To undertake a systematic review evaluating US as an outcome tool in gout and asymptomatic hyperuricaemia, articles published in Medline and PubMed (1975-February 2012) were identified. Data was extracted and categorised into four different groups namely tophi, articular cartilage, soft tissue pathologies and bony changes, with a focus on validity, responsiveness, reproducibility and feasibility. Lesions reported in the literature include tophi, cartilage abnormalities, soft tissue lesions and erosions. US is able to detect tophi, using MRI as the gold standard, and is sensitive to change. The double contour sign seen overlying cartilage is specific to gout and sensitive to change. Synovial pathology is identified in gout, with some reporting intrasynovial hyperechogeneicity is suggestive of gout. US was less sensitive than MRI to cortical erosions in gout, but better than conventional radiography. Interobserver reliability when assessed ranged from fair to substantial agreement for soft tissue changes and was very good for assessing tophi, double contour and erosions. US is a promising tool which could be used in the diagnosis and management of gout. More studies are needed to assess responsiveness, reliability and feasibility.