Cancer Risk and Mortality in Hospitalized Patients With Idiopathic Inflammatory Myopathies in Western Australia.

OBJECTIVE: To compare cancer incidence, type, and survival between patients with idiopathic inflammatory myopathies (IIMs) in Western Australia (WA) and the general population. METHODS: Administrative health data for hospitalized patients with incident IIM (n = 803, 56.5% female, median age 62.0 yrs), classified by a validated algorithm as polymyositis (PM; 36.2%), dermatomyositis (DM; 27.4%), inclusion body myositis (IBM; 17.1%), overlap myositis (OM; 10.7%), and other IIM (8.6%), were linked to WA cancer and death registries for the period of 1980 to 2014. Cancer incidence rates (CIRs) before and after IIM diagnosis as well as cancer mortality were compared with age-, sex-, and calendar year-matched controls (n = 3225, 54.9% female, median age 64 yrs) by rate ratios (RRs) and Kaplan-Meier survival estimates. RESULTS: The prediagnosis CIR was similar for patients with IIM and controls (6.57 vs 5.95; RR 1.11, 95% CI 0.88-1.39) and for patients evolving to DM (n = 220) or other IIM subtypes (6.59 vs 6.56; RR 1.01, 95% CI 0.38-3.69). During follow-up, CIR was higher for all DM (4.05, 95% CI 3.04-5.29), with increased CIR for lung cancer vs controls (1.05 vs 0.33; RR 3.18, 95% CI 1.71-5.47). Cancer post diagnosis shortened life span by 59 months for patients with IIM (103 vs 162 months, P < 0.01), but reduced survival rates were observed only in patients with DM and IBM. CONCLUSION: Cancer risk was not increased prior to IIM, but CIR for lung cancer was increased following DM diagnosis. As cancer reduced survival only in patients with DM and IBM, these data support a strategy of limited cancer screening in IIM.

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.

Comparison of pregnancy outcomes between indigenous and non-indigenous lupus patients.

AIM: To compare pregnancy outcomes between IA and non IA lupus patients. BACKGROUND: Pregnancy in lupus patients confers an increased risk of maternal and fetal morbidity. There are no data on pregnancy outcomes for indigenous Australian (IA) patients with lupus. METHODS: Using state-wide longitudinal hospital morbidity data, we studied 702 pregnancies in IA (n = 31) and non-indigenous (NI) patients with lupus (n = 357) in Western Australia and compared rates for live birth (LB), preterm birth (PB) and gestational complications in the period 1985-2015. Results are presented as medians or frequency. RESULTS: IA patients had proportionally more pre-existing renal disease (35 vs 13%, P < 0.01) and lower socio-economic status (P = 0.02). Age at first pregnancy was lower in IA patients (27 vs 30 years, P < 0.001), recorded gravidity was similar (2 vs 2, P > 0.6) and elective termination (n = 138) was more frequent in NI than IA pregnancies (21.1 vs 4.8%, P < 0.01). For continued pregnancies (59 in IA and 505 in NI), respective outcomes were as follows: LB 84.7% versus 91.5% (P = 0.15), spontaneous abortion 13.5% versus 6.9% (P = 0.13), (pre-)eclampsia 8% versus 9.9% (P = 0.89), PB 12% versus 13.4% (P = 0.98) and caesarean delivery 30% versus 47.2% (P = 0.02). Gestational diabetes (26% vs 6.1%), renal flares (20% vs 5.6%) and infections (22% vs 6.3%) were all more frequent in IA lupus pregnancies (all P < 0.001). CONCLUSIONS: The burden of comorbidities was higher in IA patients with lupus due to renal flares, gestational DM and infections. Although PB rates were overall high, they were, however, similar for IA and NI lupus pregnancies, as were LB rates.

The spectrum of idiopathic inflammatory myopathies in Western Australia: epidemiological characteristics and mortality over time.

To determine long term overall and subgroup specific incidence rates and associated mortality for idiopathic inflammatory myopathies (IIM) in a population wide study. We included patients hospitalised between 1980 and 2015 with incident IIM as defined by relevant diagnostic codes for dermatomyositis (DM) polymyositis (PM), inclusion body myositis (IBM), other IIM and overlap myositis (OM) in the Western Australia Health Hospital Morbidity Data Collection (n = 846). Trends over time for annual incidence rate per million population (AIR) were analysed by least square regression and Kaplan-Meier survival and mortality rates (MR)/100 person years compared with a matched control group (n = 3681). The averaged AIR for all IIM was 19 (CI 10.4-27.5) and stable over time with point prevalence reaching 205.3 (CI 185.6-226.6) per million in 2015. Over time, the AIR for DM 5.0 (CI 0.6-9.4) and IBM 3.3 (CI 0.7-9.6) was stable, while AIR decreased for PM (p < 0.01) and increased for other IIM (p < 0.01) and OM (p < 0.01). IBM patients were eldest at diagnosis (68 years, CI 59-77) with male preponderance in IBM (53.4%) and other IIM (55.8%) groups. Crude mortality (54.5 vs 41.3%), MR ratio (6.65 vs 5.91) and 5 (65.8% vs 71.6%) and 10-year (52.5% vs 58.7%) survival were all worse for IIM patients (all p < 0.05). IBM patients had highest MR (10.1; CI 8.38-12.14) and lowest 10-year survival (39.2%). While cardiovascular disease and cancer were predominant causes of death, they were proportionally lower in IIM patients, where respiratory and rheumatic disease were more frequent causes of death. While the overall incidence of IIM in WA was stable over 35 years, the spectrum of IIM has changed significantly with increases especially in other IIM and OM. The overall prognosis with IIM remains guarded with 10-year survival just over 50%.

The temporal association between adverse drug reactions and antirheumatic drugs utilisation in Western Australia: a retrospective study from real-world data (1995-2015).

BACKGROUND/OBJECTIVES: Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with antirheumatic medications, this study aims to analyse and compare ADR reporting for these drugs in the pharmacovigilance datasets of Western Australia (WA) and the United States (US). METHODS: Therapeutic Goods Administration provided WA pharmacovigilance data of selected antirheumatic drugs to from 1995 to 2015. The proportional reporting ratio (PRR) for WA case reports was compared to corresponding USA pharmacovigilance data by assessing the disproportionality of each ADR. clinically significant or true ADRs were determined using the Evans 2001 criteria (n > 2, chi-square > 4, PRR > 2). RESULTS: A total of 232 reports were found in WA, mostly on sixty-nine women aged 45 to 69. Methotrexate, leflunomide, azathioprine, sulfasalazine, and infliximab had the highest reported ADRs, related to gastrointestinal disorders. Patients who used biological agents in WA had 2.7 times the likelihood of reporting true ADRs compared to conventional antirheumatic drugs. The ADR rates in the two datasets were comparable over the study period. CONCLUSIONS: The PRR values of ADRs were consistent between WA and US databases. Methotrexate and infliximab use were commonly associated with ADR reports in WA females, with incidence rates comparable to the US; while patients using biological agents were more likely to report true ADRs than those on conventional antirheumatic drugs in WA.

Systemic juvenile idiopathic arthritis: frequency and long-term outcome in Western Australia.

Systemic juvenile idiopathic arthritis (S-JIA) is a rare but potentially life threatening autoinflammatory condition of childhood. Given the limited data on S-JIA from the Australasian region, we investigated the epidemiological characteristics and long-term disease outcome in S-JIA. All hospitalised patients under the age of 16 years registered with ICD-10-AM code M08.2 in in the period 1999-2014 were identified in longitudinally linked administrative health data across all Western Australian (WA) hospitals. Incidence and point prevalence estimate were per 100,000 population with Poisson regression to analyse the incidence trend. Readmissions with S-JIA as primary diagnosis were considered flares with rates for flare and other complication reported per 100 person years with 95% confidence intervals (CI). Annual S-JIA incidence was 0.61/100,000 (CI 0.28-1.25) (46 incident cases, 71.7% girls, median age 6.5 years) and stable over time as S-JIA point prevalence reached 7.15/100,000 (CI 5.29-7.45) at the end of study. Most incident cases were diagnosed in winter and spring, but documented preceding infections were rare. During a median follow-up of 8 years, disease flares occurred in 24% of patients with higher flares rate in boys (58.3; CI 44.5-74.9) than girls (14.7; CI 9.9-20.9). No deaths occurred and arthroplasty was the main, but uncommon S-JIA complication (4%). However, readmission (86.3; CI 76.4-97.2) and ED visit (73.3; CI 64.2-83.4) rates for illnesses other than S-JIA were substantial. S-JIA is as rare in WA as in other regions and while s-JIA incurred no deaths in the era of biologics, it associated with a significant long-term burden of (co-) morbidity.

Mortality and cause of death in patients with ANCA-associated vasculitis and polyarteritis nodosa in Australia-a population-based study.

OBJECTIVES: We compared survival and causes of death in Western Australian (WA) ANCA-associated vasculitis (AAV) and PAN patients with controls and the WA population. METHODS: In this data linkage study, we identified patients with incident AAV/PAN and age, sex and temporally matched controls 1980-2014 from the WA Rheumatic Disease Epidemiological Registry. Survival analyses and time-varying analyses were performed. RESULTS: Six hundred and fourteen patients with incident AAV/PAN were compared with 6672 controls; 229 AAV/PAN patients died over 5277 person-years of follow-up and 1009 controls died over 73835 person-years. Survival was reduced in patients with AAV/PAN compared with matched controls [hazard ratio (HR) 3.5 (95% CI: 3.1, 4.1)], and matched WA population rates [standardized mortality ratio 3.3 (95% CI: 2.9, 3.8)]. Greatest excess mortality in AAV/PAN patients was observed in the first year after diagnosis and remained higher than controls throughout follow-up. Greater excess mortality was observed in patients >60 years at diagnosis. In cause-specific analyses, mortality HR for vasculitis, infection and non-infective respiratory disease were greatest early after diagnosis and remained persistently elevated. The HRs for malignancy and cerebrovascular disease related deaths increased during follow-up, and were constant for ischaemic heart disease related deaths. CONCLUSION: Mortality was increased in AAV/PAN patients compared with controls, with patients older at diagnosis at greater risk. These findings provide mortality risk for AAV/PAN in an Australian population, highlighting key contributors to mortality at different time periods over follow-up and potential areas of focus for reducing mortality.

Temporal trends in hospitalisation for opportunistic infections in lupus patients in Western Australia.

BACKGROUND: Lupus patients often require aggressive immunosuppressive therapy, which increases the risk for infections. We studied the temporal rates for opportunistic infections (OI) and associated mortality in lupus patients hospitalised in Western Australia. METHODS: All patients hospitalized in the period 1985-2015 with ≥2 ICD based diagnostic codes for SLE were included. OI was defined as a microbiologically confirmed mycobacterial, fungal, or viral infection. Descriptive data are given as median (IQR) and frequency (%) with incidence rates (IR) calculated per 1000 person years and IR trend rates analysed across 10-year periods by least square regression (R2). RESULTS: The study cohort (n = 1408) contained 85.3% females with age at entry 35 years (IQR 22-51). During median follow-up of 21.1 years (IQR 17.5-29.6) hospitalisation for OI occurred in 121 (8.6%) patients with recurrent or multiple OI observed in 42 (34.7%) patients. During 29.771 thousand person years, a total of 295 OI were diagnosed for an overall IR rate of 9.91 (CI 8.82-11.09)/1000 person years which did not decrease significantly over time (R2 0.14). Significant decreases were however seen in the IR for tuberculosis (R2 0.88), cryptococcal (R2 0.98) and pneumocystis (R2 0.98) infections, with increasing IR observed for other mycobacteria (R2 0.99) and aspergillosis (R2 0.55) and little change seen for H Zoster (R2 0.18) and Varicella (R2 0.10) infections. In-hospital death during OI admission occurred in 9/121 patients (7.4%). There was no significant gender difference in IR or outcome of OI. CONCLUSIONS: Hospitalization rates for OI in lupus patients have not changed significantly over time, but there has been a clear shift in the underlying OI. The decrease in mycobacterial and pneumocystis infections suggest successful prophylaxis but the increase in viral and mycotic infections indicate a sustained need to improve prevention of these OI in lupus patients.

Septic arthritis due to Neisseria gonorrhoea in Western Australia.

BACKGROUND: A high prevalence of gonococcal infections has been reported from remote parts of Western Australia, but the occurrence of disseminated infection leading to arthritis has not been studied. AIMS: To investigate the frequency, risk factors and long-term outcome of gonococcal arthritis (GA) in Western Australia (WA). METHODS: A population-based data linkage study of patients with a hospital-based diagnosis of GA in WA between 1990 and 2014. Demographics, standardised incidence rates per million and comorbidity accrued before (lookback 186 months, interquartile range (IQR) 86-267) and after the index hospital contact for GA (follow up 100 months, IQR 60-209) are presented as frequency (%), median (IQR) or rates /1000 months. RESULTS: In total, 98 patients were diagnosed with GA. The annual incidence of GA increased from 1.35 to 2.10 per million between 1990 and 2014, but the rate of GA complicating all gonococcal infections was stable around 0.25%. Female patients with GA (54%; n = 53/98) were younger (24 vs 38 years) and more frequently identified as indigenous (88% vs 49%) than male patients (46%; n = 45/98; P = 0.002). Female patients had higher rates of prior infections (15.5 vs 8.1 per 1000 months; P = 0.002) and diabetes mellitus (15.9% vs 2.5%; P = 0.03) and a longer hospital stay (10 vs 8 days; P = 0.02). GA recurrence rate during follow up was low (2%), but a broad range of comorbidities developed contributing to a 14% crude death rate. CONCLUSIONS: GA stably complicates 0.25% of gonococcal infections in WA with young indigenous females and middle-aged non-indigenous males most affected. Prior infectious disease and diabetes mellitus are potential risk factors for GA in females. GA recurs rarely, but its development reflects a high risk of morbidity and mortality over the following 10 years.

The temporal association between hospital admissions, biological therapy usage and direct health care costs in rheumatoid arthritis patients.

The Australian Pharmaceutical Benefits Scheme (PBS) has subsidised biological therapy since 2003. We investigated the association between biological therapy for RA hospitalisation rates and health-care costs.Hospital admissions for RA patients between 1995 and 2014 were identified in the Western Australia (WA) Hospital Morbidity Data Collection (ICD codes 714 and M05.00-M06.99). State-specific dispensing data for conventional and biological therapies for RA was obtained from Statistics Australia and expressed as defined daily doses/1000 population/day (DDD) using WA population census. Principal component analysis (PCA) was applied to determine the relationship between DMARDs use and hospital admission rates.A total of 17,125 patients had 50,353 admissions with a diagnostic code for RA. Between 1995 and 2002, the number of RA admissions fell from 7.9 to 2.6/1000 admissions, while conventional therapy use rose from 1.45 to 1.84 DDD. Between 2003 and 2014, RA admissions decreased further to 1.9/1000 hospital admissions, while conventional therapy use increased to 2.19 DDD and biological therapy from 0.01 to 1.0 DDD. In PCA, conventional and biological therapies use had an inverse relationship with hospital admission rates. Annual costs of biological therapy utilisation was 22.5 million in 2003-2014, while the annual cost saving of RA hospital admissions was 9.2 million.The increased use of conventional therapy use for RA has coincided with a significant decline in hospital admissions for RA patients in WA, while a more modest further decline followed biological therapy introduction. Biological therapy was not as cost-effective as conventional in relation to RA hospital admissions costs.

Morbidity and mortality in adult-onset IgA vasculitis: a long-term population-based cohort study.

OBJECTIVES: With sparse data available, we investigated mortality and risk factors in adults with IgA vasculitis (IgAV). METHODS: This was an observational population-based cohort study using state-wide linked longitudinal health data for hospitalized adults with IgAV (n = 267) and matched comparators (n = 1080) between 1980 and 2015. Charlson comorbidity index (CCI) and serious infections (SIs) were recorded over an extensive lookback period prior to diagnosis. Date and causes of death were extracted from the Western Australia Death Registry. Mortality rate (deaths/1000 person-years) ratios (MRRs) and hazard ratio (HR) for survival were assessed. RESULTS: During 9.9 (9.8) years lookback patients with IgAV accrued higher CCI scores (2.60 vs 1.50, P < 0.001) and had higher risk of SI (OR = 8.4, P < 0.001), not fully explained by CCI scores. During 19 years' follow-up, the rate of death in patients with IgAV (n = 137) was higher than in comparators (n = 397) (MRR = 2.06, 95% CI: 1.70-2.50; P < 0.01) and the general population (standardized mortality rate ratio = 5.64, 95% CI: 4.25, 7.53; P < 0.001). Survival in IgAV was reduced at 5 (72.7 vs 89.7%) and 20 years (45.2% vs 65.6%) (both P < 0.05). CCI (HR = 1.88, 95% CI: 1.25, 2.73; P = 0.001), renal failure (HR = 1.48, 95% CI: 1.04, 2.22; P = 0.03) and prior SI (HR = 1.48, 95% CI: 1.01, 2.16; P = 0.04) were independent risk factors. Death from infections (5.8 vs 1.8%, P = 0.02) was significantly more frequent in patients with IgAV. CONCLUSION: Premorbid comorbidity accrual appears increased in hospitalized patients with IgAV and predicts premature death. As comorbidity does not fully explain the increased risk of premorbid infections or the increased mortality due to infections in IgAV, prospective studies are needed.

The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review.

The objective is to determine the global population prevalence of rheumatoid arthritis (RA) based on population-based studies and assess factors that influence RA prevalence estimates. Four electronic databases were searched (ProQuest Central, MEDLINE, Web of Science, and EMBASE) for peer-reviewed English publications that report prevalence estimates of RA from 1980 and 2019. We included case-control studies, cross-sectional studies, and prospective or retrospective cohort studies in our search strategy. A random-effect meta-analysis model was used to produce the pooled prevalence estimates. The potential between-study heterogeneity was identified using sensitivity analysis, sub-group and meta-regression analyses. A total of 67 studies were included in the meta-analysis, containing 742,246 RA patients and 211,592,925 healthy controls in the study period. The global RA prevalence estimate was 0.46% (95% confidence interval [CI] 0.39-0.54; I2 = 99.9%) with a 95% prediction interval (0.06-1.27). The RA point-prevalence was 0.45% (95% CI 0.38-0.53%) between 1986 and 2014, while the pooled period-prevalence was 0.46% (95% CI 0.36% and 0.57%) from 1955 to 2015. The highest RA pooled prevalence (0.69%; 95% CI 0.47-0.95) was derived from linked data source studies. Based on meta-regression, the factors that explain the studies' heterogeneity of RA prevalence, including geographical location, the risk bias assessment of studies and sample size. The global prevalence of RA between 1980 and 2019 was 460 per 100,000 population, with variations due to geographical location and study methodology. Linked data are the preferred method to estimate RA population prevalence as they provide the best case ascertainment.

The accuracy of administrative health data for identifying patients with rheumatoid arthritis: a retrospective validation study using medical records in Western Australia.

The use of administrative health datasets is increasingly important for research on disease trends and outcome. The Western Australian (WA) Rheumatic Disease Epidemiological Registry contains longitudinal health data for over 10,000 patients with rheumatoid arthritis (RA). Accurate coding for RA is essential to the validity of this dataset. Investigate the diagnostic accuracy of International Classification of Diseases (ICD)-based discharge codes for RA at WA's largest tertiary hospital. Medical records for a sample of randomly selected patients with ICD-10 codes (M05.00-M06.99) in the hospital discharge database between 2008 and 2020 were retrospectively reviewed. Rheumatologist-reported diagnoses and ACR/EULAR classification criteria were used as reference standards to determine accuracy measures. Medical chart review was completed for 87 patients (mean (± SD) age 64.7 ± 17.2 years), 67.8% female). A total of 80 (91.9%) patients had specialist confirmed RA diagnosis, while seven patients (8%) had alternate clinical diagnoses. Among 87 patients, 69 patients (79.3%) were fulfilled ACR/EULAR classification criteria. The agreement between the reference standards was moderate (Kappa 0.41). Based on rheumatologist-reported diagnoses and ACR/EULAR classification criteria, primary diagnostic codes for RA alone had a sensitivity of (90% vs 89.8%), and PPV (90.9% vs 63.6%), respectively. A combination of a diagnostic RA code with biologic infusion codes in two or more codes increased the PPV to 97.9%. Hospital discharge diagnostic codes in WA identify RA patients with a high degree of accuracy. Combining a primary diagnostic code for RA with biological infusion codes can further increase the PPV.

Pregnancy outcomes in women with a history of immunoglobulin A vasculitis.

OBJECTIVES: Case series suggest an increased risk of pregnancy complications in women with a history of IgA vasculitis (IgAV); however, no large quantitative studies have examined this possible association to date. We compared pregnancy rates and outcomes between female IgAV patients and controls and assessed flare risk of IgAV during pregnancy. METHODS: Using state-wide hospital morbidity data we compared rates for live birth, preterm birth, abortive outcome and gestational complications between female IgAV patients (International Classification of Diseases-9-Clinical Modification 287.0; International Classification of Diseases-10-Australian Modification D69.0) (n = 121) and non-exposed age-matched controls (n = 284) in Western Australia. Results presented are means compared by Kruskal-Wallis test and proportions with odds ratios (ORs) (95% CI) compared by χ2 testing. RESULTS: There were 247 pregnancies in IgAV patients during which no disease flares were recorded and 556 pregnancies in controls. IgAV patients were younger at first pregnancy (24.7 vs 27.0 years, P < 0.01) and had 43 unsuccessful pregnancies (17.4%) and 204 live births with 17 preterm deliveries (8.3%). Women with IgAV had increased odds of spontaneous abortion (OR 1.9, 95% CI 1.1, 3.1, P = 0.04), preterm delivery (OR 2.0, 95% CI 1.1, 3.9, P = 0.02) and gestational hypertension (OR 4.7, 95% CI 2.3, 9.8). While gravidity did not differ (mean pregnancy number 2.4 vs 2.3, P = 0.36), IgAV patients had over a two-fold greater number of obstetric visits than controls (5.1 vs 2.5, P < 0.01). CONCLUSIONS: Hospitalization for IgAV has little impact on fertility and IgAV rarely flares during pregnancy. However, a history of IgAV associates with increased odds of spontaneous abortions, gestational hypertension and preterm delivery.

Principal component analysis reveals disconnect between regulatory cytokines and disease activity in Systemic Lupus Erythematosus.

OBJECTIVE: Cytokine dysregulation contributes to inflammation and organ damage in Systemic Lupus Erythematosus (SLE). Principle Component Analysis (PCA) can determine which groups of cytokines have the most influence across disease activity states. MATERIAL AND METHOD: A cross-sectional study of age- and gender-matched SLE patients (n = 100) and controls (n = 31). SLE patients had a median Systemic Lupus Erythematosus Disease Activity Index - 2000 (SLEDAI-2K) score of 6 (IQR 2, 11). IFN-γ, interleukin (IL)-1ß, IL-4, IL-6, IL-10, IL-12, IL-17, BAFF, TNF-α, TGF-ß1, MIP-1α, MIP-1ß and MCP-1 levels were quantified by sandwich ELISA, and compared non-parametrically between groups. PCA was used to determine the principal components across controls, SLE patients in states of remission (SLEDAI-2K = 0), low disease activity (LDA = SLEDAI-2K from 1 ≤ x ≤ 4) or high disease activity (HDA = SLEDAI-2K > 4). RESULTS: TGF-ß1 (Rs -0.266, p = 0.005) and IL-1ß (Rs -0.199, p = 0.004) inversely correlated, whereas BAFF correlated with increasing disease activity (Rs 0.465, p < 0.001). IL-1ß, IL-4, IL-10, IL-12, IL-17, IFN-γ, MCP-1, and TNF-α were featured consistently in the PC1 of all study groups. PC1 changes from controls to SLE-HDA patients, included: the increased impact of IL-1ß (from 0.58 to >0.95); increased impact of IL-6 in HDA (0.76); increased influence of MIP-1α (0.60) and MIP-1ß (0.85); and the uncoupling of TGF-ß1 (0.14). PC2 changes from healthy controls to the HDA state, included: the increased influence of BAFF (from -0.18 to 0.88); the oppositional effect of TGF-ß1 (-0.36); and, the inclusion of MCP-1 (0.65). Levels of cytokine profiles were equivalent between controls and SLE patients (p > 0.18). BAFF was not associated with the cytokine profiles. TGF-ß1 associated with Th1 (Rs 0.36), Th1 + Th17 (Rs 0.22), and inversely with Th17/Th2 (Rs -0.23) profiles. IL-1ß associated with the proinflammatory (Rs 0.47), Th1 (Rs 0.55), Th2 (Rs 0.55), Th17 (Rs 0.51), Th1 + Th17 (Rs 0.56), Th2 + Treg (Rs 0.45), and inversely with the (Th1 + Th17 / Th2 + Treg) (Rs -0.22) and Th17/Th2 (Rs -0.27) profiles (all, p < 0.05). CONCLUSION: Principal component analysis helped to describe the influence of complex cytokine interactions in SLE in a manner congruent with the wider literature. The typical univariate changes in BAFF and TGF-ß1 levels with increasing levels of disease activity, were not the dominant factors (in PC1) in the PCA. The PCA demonstrated that IL-1ß did not seem to change its regulatory function in SLE.

Hospitalisation rates and characteristics for adult and childhood immunoglobulin A vasculitis in Western Australia.

BACKGROUND: Immunoglobulin A vasculitis (IgAV) is a systemic small-vessel vasculitis of unknown aetiology. Although commonest in children, onset in adulthood is not unusual. AIM: As Australian data are lacking, we investigated longitudinal hospitalisation rates and characteristics for both adult and paediatric IgAV patients in Western Australia (WA). METHODS: Data were extracted from a state-wide register for all first hospital contacts in WA between 1980 and 2015 for patients with a primary diagnosis of IgAV. Paediatric cases were defined as those <20 years and compared with adult cases for admission rates per 100 000, demographics, complications, length of stay (LOS) and readmission rates. RESULTS: The study cohort included 476 children (median age 5 years; interquartile range (IQR) 3-7) and 144 adults (median age 50 years; IQR 36-77). Childhood admission rates declined from 3.85 to 0.31 over time (P < 0.001) but age at admission and LOS remained unchanged. For adults, admission rates declined from 0.40 to 0.17 (P = 0.02) while age at admission (43 vs 63 years, P = 0.01) and LOS (5 vs 9 days, P = 0.02) increased. More adults had renal (11.8 vs 1.3%, P < 0.01), intestinal (3.5 vs 0.8%, P = 0.04) and infectious (14.6% vs 5.3%, P < 0.01) complications. Readmission was more frequent in childhood cases (23.1% vs 7.6%, P < 0.05) occurring mostly within 30 days of discharge. CONCLUSION: Hospitalisation rates for adults with IgAV now nearly equal those in children as adult IgAV leads to more complications. The sharp decline in childhood IgAV admissions suggests that confidence to manage children with IgAV outside the hospital setting has increased.

Rheumatoid factors do not predict cardiovascular disease and mortality in the general population in the Busselton Health Survey.

BACKGROUND: Rheumatoid Factors (RF) are antibodies directed against the Fc portion of IgG and are involved in clearance of immune complexes. While RF can develop in a wide range of conditions, higher RF levels indicate a greater risk for a severe disease course in Rheumatoid Arthritis (RA) patients including cardiovascular complications and premature death. We investigated whether RF also constitute a risk factor for these outcomes in the general population. METHODS: We included 2,323 participants (46% male, mean age 50 years) free of CVD at baseline in 1972. RF positivity was defined as a score of ≥2 by latex agglutination (scale 0-5). All outcomes during 42-year follow-up were obtained from state-wide registries. The predictive value of RF for coronary heart disease, all cardiovascular disease and all-cause mortality was estimated by adjusted hazard ratios (HR) from Cox regression models. RESULTS: After adjustment for standard risk factors, RF positivity was not predictive of future CHD (HR 1.05, p = 0.61), CVD (HR 1,04, p = 0.63) or mortality (HR 1.03, p = 0.70) in the full CVD-free cohort. In an interaction model, RF in 41 out of 355 participants with an RA history was not predictive of CHD (HR 0.92, p = 0.77) or CVD events (HR 1.15, p = 0.51), but there was a borderline significant association with overall mortality (HR 1.41, CI 0.97-2.04, p = 0.07). CONCLUSIONS: RF detected by Latex agglutination do not independently predict future CHD, CVD or death in the general population. However, the presence of RF in the context of a history of RA is associated with a moderate, borderline significant increase in the long term adjusted risk for all-cause mortality.

Frequency, presentation, and outcome of Takayasu arteritis in Western Australia.

OBJECTIVES: Takayasu arteritis (TAK) is large-vessel vasculitis that predominantly affects young women. There is worldwide variation in the frequency of TAK depending on genetic and/or environmental factors. With Australian data lacking, we describe the epidemiology, clinical features and outcomes of TAK in Western Australia (WA). METHODS: Retrospective case cohort study of incident TAK cases between 1 January 2000 and 30 June 2015 in WA identified from multiple sources. Data on disease presentation and outcome were extracted from medical records. RESULTS: Eighteen patients received a clinical diagnosis with thirteen cases meeting 1990 ACR criteria for TAK (all female, 77% Caucasian, age at diagnosis 39 years) included in this analysis. Per million inhabitants the annual incidence and prevalence (2015) was 0.3 and 3.2 for Caucasians and 1.1 and 15 for Asians. Limb claudication and bruit were commonest symptoms; ESR or CRP was raised in 61% at diagnosis while aortic involvement Hata type IIb most prevalent (30%). Despite general combination therapy with corticosteroids and immunosuppressant drugs, four patients suffered a stroke, two patients developed myocardial infarction, and five patients required vascular intervention. Three Caucasian patients died during the study period. CONCLUSION: TAK is much more prevalent in the Asian than Caucasian population of WA and associates with significant long-term morbidity and mortality despite standard therapy.

Asymptomatic hyperuricemia is not an independent risk factor for cardiovascular events or overall mortality in the general population of the Busselton Health Study.

BACKGROUND: To investigate the impact of uric acid (UA) levels on cardiovascular disease and mortality at a population level. METHODS: Prospective analysis of baseline serum UA measurement and 15 year follow-up data from the Busselton Health Survey (n = 4,173), stratified by existence or absence of baseline cardiovascular disease. Outcomes were ascertained from state-wide hospital discharge and mortality registries. Cox regression produced adjusted hazard ratios (HR) for UA level as continuous and categorical (low, medium, high) predictor for cardiovascular events (CVE) and mortality. Gout was defined as a patient's self-reported history of gout. RESULTS: After age and gender adjustment each 0.1 mmol/L rise in UA level was associated with increased mortality (HR 1.19, CI 1.04-1.36), cardiovascular mortality (HR 1.27, CI 1.03-1.57) and first CVE (HR 1.28, CI 1.13-1.44) in participants with no history of CVE. Adjustment for behavioural and biomedical risk factors of cardiovascular disease attenuated these associations. Results for participants with a history of CVE and for a subset of 1,632 participants using UA levels (2-6 measurements) averaged over time were similar. The overall prevalence of hyperuricemia was 10.7%. When stratified by history of gout, UA level was significantly associated with increased risk of cardiovascular mortality only in participants with a history of CVE (HR 2.13, CI 1.03-4.43). CONCLUSIONS: Despite the considerable prevalence of hyperuricemia in 10.7% of the population, single or time averaged measures of UA were not independently predictive of incident cardiovascular disease or mortality. Hyperuricemia did associate with an increased risk of cardiovascular death only in participants with gout and existing cardiovascular disease.

Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with rituximab in patients with granulomatosis with polyangiitis.

OBJECTIVE: Rituximab (RTX) is a B cell depleting agent used to induce and maintain remission in patients with granulomatosis with polyangiitis (GPA). As the development of hypogammaglobulinaemia in GPA patients on long-term RTX has not been addressed, the aim of this study was to investigate changes in immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term RTX maintenance therapy in GPA. METHODS: We used a single-centre cohort study of 29 GPA patients who received a median total cumulative dose of CYC of 17 g and were treated with 2 g RTX followed by re-treatment with either 2 g once annually, 1 g biannually or a combination of both. Ig levels were measured before each RTX re-treatment and hypogammaglobulinaemia was defined as levels of total immunoglobulin <6 g/l. RESULTS: During a median follow-up of 4 years, patients received a cumulative dose of 9 g RTX. While serum Ig levels decreased during RTX maintenance, the largest decrease occurred after the first infusion. Baseline Ig levels and the CYC cumulative dose predicted Ig levels, whereas the RTX cumulative dose did not. Eight patients (28%) discontinued RTX due to hypogammaglobulinaemia. Male gender [hazard ratio (HR) = 8.7, P = 0.044], kidney involvement (HR = 6.5, P = 0.083) and the 1 g biannual regimen (HR = 8.0, P = 0.024) increased the risk to discontinue RTX due to hypogammaglobulinaemia, whereas orbital-subglottic involvement (HR = 0.23, P = 0.080) decreased it. CONCLUSION: Hypogammaglobulinaemia occurred in one-quarter of GPA patients during RTX maintenance, independent of the RTX cumulative dose. Male gender, kidney involvement and the 1 g biannual RTX regimen constitute risk factors for severe hypogammaglobulinaemia necessitating withdrawal of RTX.