Epidemiology of biopsy-proven giant cell arteritis in South Australia.

BACKGROUND/AIM: To determine the epidemiology and clinical features of biopsy-proven giant cell arteritis (GCA) in South Australia (SA). METHODS: Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies at SA Pathology laboratories, from 1 January 1992, to 31 July 2011. Epidemiological data were collected through patient questionnaires and standardised case note reviews. Incidence was estimated using Australian Bureau of Statistics population data for SA. Seasonality was analysed by Cosinor analysis, and time-to- event analysis was performed for the duration of steroid use. RESULTS: There were 314 cases of biopsy-proven GCA (72% female). The mean age at diagnosis of GCA was 78 years (interquartile range 72-82). The estimated population incidence for people over 50 was 3.2 per 100,000 person years. The female : male incidence ratio was 2.3 (P < 0.001), and incidence increased with each age decade. There was evidence of seasonal variation (P = 0.015), with higher rates observed in the summer months. Clinical data were available for 163 patients (68% female, median age 78 years). The most common presenting clinical features were temporal headache (74%), visual disturbance (68.4%), jaw claudication (59.3%) and symptoms of polymyalgia rheumatica (56%). The median initial steroid dose was 60 mg, with median duration of steroid use 4.5 years. Corticosteroid side-effects were common, affecting 89%, with 34% reporting five or more. CONCLUSIONS: This is the first epidemiological study of Australian biopsy-proven GCA patients. Age at onset and gender associations were similar to other Western populations. There was a high burden of steroid use in these patients.

Survival in scleroderma: results from the population-based South Australian Register.

AIM: To ascertain the mortality risk and investigate clinical and serological factors influencing survival of patients listed on the South Australian Scleroderma Register (SASR). METHODS: The SASR is a population-based register, which was commenced in 1993 and has actively sought to recruit all scleroderma patients diagnosed in SA over a 15-year period. Clinical and serological details have been accessed from questionnaires or from clinical and laboratory files. Standardized mortality ratio (SMR) was calculated and survival analyses performed on all living and deceased patients listed on this SASR (n = 786). RESULTS: Patients with scleroderma had increased mortality compared with the general SA population (SMR 1.46 (95% confidence interval (CI) 1.28-1.69)). Factors that adversely altered survival included older age at onset, male gender, diffuse skin involvement, presence of scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer and anti-topoisomerase (Scl-70) and anti-U1 RNP antibodies, while a trend was observed with increased nailfold capillary dropout. Mean age of death for patients with limited scleroderma was 74.1 years (95% CI 72.5-75.7), diffuse scleroderma 62.9 years (95% CI 59.4-66.4) and overlap disease 57.8 years (95% CI 48.7-66.9). Survival improved over the 15-year study period. CONCLUSIONS: Scleroderma substantially reduces life expectancy. Survival is influenced by age at onset, gender, diffuse involvement of skin fibrosis, visceral involvement, development of cancer, extent of microvascular capillary damage and by the presence of scleroderma-associated antibodies, Scl-70 and RNP. Scleroderma renal crisis continues to carry high mortality. Survival improved over the 15-year study period.

MRI assessment of changes in liver iron deposition post-venesection.

OBJECTIVE: The aim of this study was to determine if changes in hepatic iron content in patients with hemochromatosis pre- and post-venesection could be detected by changes in liver signal intensity with MRI. MATERIALS AND METHODS: The study was performed with institutional ethics approval and with informed consent. Gradient echo images were performed on 20 patients with hemochromatosis pre- and post-venesection and 10 control subjects: gradient echo T1-weighted in- and out-phases (4.54 (in)/2.27 (out), 167 [TE/TR], Flip 70°) and gradient echo T2* (5/18 [TE/TR], Flip 10°). The liver to muscle signal ratio was compared pre- and post-venesection. RESULTS: All MRI sequences showed significant correlation between the liver to muscle signal intensity ratio and the serum ferritin pre-venesection [r=-0.70, -0.65, -0.74, -0.72, in/out/T2*r/T2*, respectively]. There was a significant increase on all sequences in the liver to muscle signal intensity ratio post-venesection (p<0.001). The control group and patients post-venesection had almost identical liver to muscle signal intensity ratios. CONCLUSION: The reduction in liver signal intensity caused by iron excess in hemochromatosis returns to normal post-venesection. Measurement of liver to muscle signal intensity ratios may be a useful tool in assessing treatment response in iron overload states.

Engaging medical students in occupational and environmental medicine--a new approach.

BACKGROUND: For a number of reasons, engaging the interest of medical students in the discipline of occupational and environmental medicine (OEM) can be challenging. AIMS: To renew a curriculum in OEM within a graduate medical programme with an emphasis on student involvement to maximize their interest in the topic. METHODS: A second year student cohort of a 4 year graduate medical programme was surveyed as to their preferences for the content of a short course of OEM embedded in their medical course. The course was extensively rewritten as a result of the student survey, with a number of topics deleted from the old course and new topics added. In order to validate the content of the new course, local occupational physicians (OPs) were also surveyed as to their opinion of an appropriate curriculum in OEM for medical students. The new course was taught to the subsequent cohort of second year medical students. The students' ratings of the course pre- and post-revision were compared. RESULTS: The student satisfaction rates of the course significantly improved as a result of the changes. The content of the student-led curriculum was strikingly similar to the course proposed by the local OP with a few key exceptions. CONCLUSIONS: Student involvement in curriculum design in OEM is entirely feasible. It can result in a curriculum similar to that designed by expert opinion but has the advantage of strongly engaging student interest.

The role of diet in the management of gout: a comparison of knowledge and attitudes to current evidence.

BACKGROUND: Evidence supports dietary modifications in the management of gout. Despite this, the degree of implementation of this evidence by nutrition professionals and rheumatologists and those affected by gout is unknown. The present study aimed to compare usual dietary practices of patients with gout to evidence for dietary management of gout and to investigate whether the knowledge and attitudes of nutrition professionals and rheumatologists reflects current evidence. METHODS: A food frequency questionnaire was used to determine usual dietary intake of patients with gout, a separate questionnaire examined gout-related dietary modifications (n = 29). Online questionnaires to examine attitudes towards dietary management of gout were completed by nutrition professionals and rheumatologists. RESULTS: Proportions of participants whose reported intakes were inconsistent with current evidence for the dietary management of gout were: alcohol, n = 14 (48%); beer, n = 18 (62%); seafood, n = 29 (100%); meat, n = 7 (24%); beef/pork/lamb, n = 24 (83%); dairy products, n = 12 (41%); vitamin C supplementation, n = 29 (100%). Of the 61 rheumatologists and 231 nutrition professionals who completed the online survey, the majority considered that weight loss and decreased alcohol intake were important or very important outcomes. Proportions were lower for decreased purine intake. Thirty-four (56%) rheumatologists do not refer patients with gout to dietetic services and, of those who do, the majority refer less than half. CONCLUSIONS: Overall, patients with gout in the present study were not implementing evidence for dietary management of their condition and complex dietary issues were evident.

Effect of intra-articular infliximab on synovial membrane pathology in a patient with a seronegative spondyloarthropathy.

OBJECTIVE: To demonstrate the efficacy of intra-articular infliximab in a patient with a persistent monarthritis who had previously had two arthroscopic synovectomies with limited success, and to determine the effect of intra-articular infliximab on synovial membrane pathology METHOD: Arthroscopic synovial biopsy specimens were collected before and after treatment with intra-articular infliximab. The synovial tissue was stained for a range of inflammatory cell subsets, cell adhesion molecules and cytokines using immunohistochemical techniques and quantified using digital image analysis and a semiquantitative scoring method. RESULTS: Clinical improvement in the knee synovitis was seen after the first two intra-articular infliximab treatments, with a sustained clinical remission lasting for more than 12 months after the third treatment. Significant changes in cellular infiltration and expression of cytokines and cell adhesion molecules occurred as a result of treatment with intra-articular infliximab, with a reduction in some but not all cells in the inflammatory infiltrate, as well as a reduction in the expression of cell adhesion molecules (intercellular adhesion molecule-1 and vascular adhesion molecule-1) and production of cytokines (interleukin 1beta and tumour necrosis factor alpha). CONCLUSION: Intra-articular infliximab administration is a viable treatment for a persistent monarthritis resistant to other treatment options and can successfully modulate the inflammatory milieu within the synovial membrane.

Wegener's granulomatosis: epidemiological and clinical features in a South Australian study.

BACKGROUND: The epidemiology of Wegener's granulomatosis (WG) has shown a latitude-dependent predisposition in Northern Hemisphere and in New Zealand. There are no studies describing epidemiology or long-term follow up of WG reported from Australia. The aims of this study were to describe the epidemiological and clinical features of WG in South Australia (SA). METHODS: The 5-year incidence of WG in SA over the period 2001-2005 was determined using the International Classification of Diseases classification (M313) of the discharge diagnosis using the Integrated South Australian Activity Collection. A retrospective case record analysis of 30 patients fulfilling the American College of Rheumatology criteria for WG and managed at two regional hospitals over a 20-year period (1985-2004) was carried out. RESULTS: The 5-year incidence of WG in SA was 56 per 10(6) (95% confidence interval 44.1-68.4 per 10(6)). There were no regional or seasonal variations in disease occurrence. The demographic, clinical and serological features in the clinical study were similar to previously published studies. Significant treatment-related morbidity was noted with 50% of patients having atherosclerotic vascular complications. The median survival was 12 years. There were two important periods with greater risk of dying -- in the first 5 years and after 10 years. CONCLUSION: The 5-year incidence of WG in SA is higher than that in the same latitudinal region in New Zealand ( approximately 34 degrees S). Atherosclerotic vascular disease was a major long-term morbidity. There is increased incidence of early mortality, warranting the need for earlier diagnosis and better therapies. Further studies from Southern Hemisphere are required for better epidemiological description of this disease.

Influence of rheumatoid arthritis on work participation in Australia.

BACKGROUND: The aim of the study was to determine the prevalence of work disability in a cohort of Australians with rheumatoid arthritis. METHODS: A cross-sectional study of a sample of 497 individuals aged 18-65 years with rheumatoid arthritis in Adelaide, South Australia, was carried out. RESULTS: Of those employed, 130 (51%) were in full-time employment (> or= 35 h per week) work and 124 (49%) were in part-time employment (average 20 h per week). Overall, the observed/expected numbers working were 254/316 (relative risk 0.8 (0.69-0.91)). Using a comparator adjusted by removing those on the disability support pension, the relative risk of the working was 0.74. The observed/expected numbers working part time in the study group were 124/89 (relative risk 1.4 (1.25-1.65)). Those who continued to work had lower Health Assessment Questionnaire scores, less morning stiffness, superior scores for patient assessed level of function, lower pain scores, lower joint counts, a lower C-reactive protein, better measures of 'patient global assessment' and higher levels of education compared with the group who had ceased work. Overall, of those working at the time of diagnosis, 20% had ceased work within 5 years and approximately 40% had ceased work by 20 years. Of those who ceased work, the mean duration from time of diagnosis to work cessation was 7 years with half the subjects who ceased work doing so within 4 years of diagnosis. CONCLUSION: Work disability associated with rheumatoid arthritis in Australia is very significant and costly. Work disability occurs relatively early in the disease and is associated with several identifiable variables, many of which may be amenable to intervention strategies.

The effect of rheumatoid arthritis on personal income in Australia.

BACKGROUND: The aim of this study was to estimate the effect of rheumatoid arthritis (RA) on the personal income of a cohort of individuals with RA in Australia. METHODS: A cross-sectional study of a sample of 497 working age people with RA in Adelaide, South Australia was carried out. RESULTS: The average personal income of an individual with RA in our cohort in 2003-2004 was $A22 400 compared with the Australian mean annual income of $A38 000. When standardized, the income of our cohort was 66% that of the average income of the Australian population. Overall one-third of the RA cohort relied principally on the social security system for their income and more than 75% of the cohort estimated they had lost greater than $A10 000 per annum in personal income as a result of their disease. Individuals with RA who were not working had annual incomes on average of more than $A20 000 less than those who continued to work. CONCLUSION: The personal income loss associated with RA in Australia is of enormous significance. It reduces a large population of individuals to relative financial poverty and potentially limits their access to a range of services including private health services.

Down-regulation of leucocyte immunoglobulin-like receptor expression in the synovium of rheumatoid arthritis patients after treatment with disease-modifying anti-rheumatic drugs.

OBJECTIVES: To compare the expression of leucocyte immunoglobulin-like receptors (LILRs) also known as ILTs and LIRs in rheumatoid arthritis (RA) synovial membrane before and after treatment with disease-modifying anti-rheumatic drugs (DMARDs) and investigate regulation of LILR-expression and function in vitro. METHODS: A study was performed on serial synovial biopsies obtained from 10 RA patients before and after treatment with DMARDs. Expression of the activating LILRA2 (ILT1 or LIR-7) and inhibitory LILRB2 (ILT4 or LIR-2) and LILRB3 (ILT5 or LIR-3) was evaluated by immunohistochemical staining, and quantified by a validated scoring system. Peripheral blood mononuclear cells and in vitro derived macrophages were used to determine effects of DMARDs on expression and function of LILRs. RESULTS: Abundant expression of LILRB2, B3 and A2 was found in synovial tissue of all patients before treatment. Number of inflammatory cells expressing both inhibitory and activating LILRs dramatically decreased in patients who responded to treatment, but remained high in those who did not. However, treatment of macrophages with DMARDs in vitro did not down-regulate LILR expression. On the other hand, reduction in LILR expression in RA synovia was associated with decreased inflammatory infiltrates in those who responded to treatment. Cross-linking of LILRA2 on macrophages caused substantial production of tumour necrosis factor (TNF-alpha) in a dose- and time-dependent manner that was strongly inhibited by dexamethasone. CONCLUSIONS: We show that expression of LILRs in RA synovium was significantly reduced only in patients who responded to treatment. However, clinical responses may not be due to direct effects of DMARDs on LILR expression but due to partial inhibition of LIRA2-mediated TNF-alpha production by steroids leading to suppression of inflammation.

Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis.

OBJECTIVES: To characterise the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active rheumatoid arthritis (RA). METHODS: Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies to detect dendritic cell subsets, including activation markers and cytokines relevant to dendritic cell function. Co-localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy. RESULTS: The dendritic cells identified in RA synovial tissue that strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid- and plasmacytoid-type dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL12 as well as interferon alpha and gamma. CONCLUSIONS: The close correlation of these dendritic cells with the presence of serum rheumatoid factor, a prognostic factor for worse disease outcome, and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.

Scleroderma in South Australia: further epidemiological observations supporting a stochastic explanation.

The aim of this study was to determine the incidence, prevalence, survival and selective demographic characteristics of scleroderma occurring in South Australia over the 10-year period 1993-2002. Analysis of the database of the South Australian Scleroderma Register: a population-based register established in 1993. Patients with scleroderma resident in South Australia (n = 353 at 2002) were ascertained from multiple sources and clinical and demographic data were obtained from mailed questionnaire and from review of computerized hospital databases, case notes or referring letters. Time-space cluster analysis was carried out according to the Knox method. Control data were obtained from the Australian Bureau of Statistics census. The mean prevalence was 21.4 per 10(5) (95% confidence interval 20.2-22.6) and the mean cumulative incidence of 1.5 per 10(5) (95% confidence interval 1.32-1.73) with no significant change in incidence over the study period (P = 0.13). Cumulative survival improved over the study period, with patients with diffuse disease having significantly reduced survival (as compared with limited disease, P < 0.001). The proportion with diffuse disease ( approximately 22%) remained steady. There was a small but significant predisposition in patients with a continental European birthplace (P < 0.001). A family history of scleroderma was noted in 1.6% with lambda1 (familial risk) of 14.3 (95% confidence interval 5.9-34.5). However, a family history of systemic autoimmunity (especially rheumatoid arthritis) was more common (6%). No socioeconomic stratification, temporal clustering nor spatio-temporal clustering was observed either at time of initial symptom or at 10 years before disease onset. Scleroderma occurs relatively infrequently in South Australia with no significant change in incidence observed over the 10-year study period. However, cumulative survival has improved. Identified risk factors include family history of scleroderma (risk approximately 14-fold), female sex (risk approximately 5-fold) and European birthplace (risk approximately 2.5-fold); however, the majority of the disease variance appears unexplained. A stochastic explanation based on genetic instability is favoured to explain this paradox.

Changes in synovial tissue Jak-STAT expression in rheumatoid arthritis in response to successful DMARD treatment.

BACKGROUND: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis (IA). OBJECTIVE: To examine the effect of successful disease-modifying antirheumatic drug (DMARD) treatment on the expression of Jak-STAT in a cohort of patients with active rheumatoid arthritis. METHODS: Synovial tissue biopsy specimens from 16 patients with active rheumatoid arthritis, taken before and after initiation of DMARD treatment, were examined for the presence of janus kinase (Jak)3, signal transducer and activator of transcription (STAT)1, STAT4 and STAT6 expression using immunohistochemistry. RESULTS: Successful treatment with DMARDs results in reduction in STAT1 expression in the lining, and STAT1 and STAT6 in the sublining of rheumatoid arthritis synovial tissue. Although the overall expression of STAT4 and Jak3 was not significantly altered by DMARD treatment, there was a significant reduction in the expression of the STAT4 and Jak3 bright cells, thought to be an activated dendritic cell subpopulation. CONCLUSION: Results show that Jak3, STAT1, STAT4 expression and STAT6 sublining expression decrease in response to successful treatment of rheumatoid arthritis with standard DMARDs. Therefore, altering the expression of these pathways may represent an alternative treatment option, either through promoting up-regulation of inhibitory pathways, or suppressing inflammatory paths.

Pharmaceutical Benefits Scheme criteria for the use of tumour necrosis factor-alpha inhibitors in the treatment of ankylosing spondylitis in Australia: are they evidence based?

BACKGROUND: In 2004, the Pharmaceutical Benefits Scheme (PBS) listed infliximab as a subsidised treatment for ankylosing spondylitis (AS). Eligibility to receive this treatment for AS involved fulfilling several criteria. AIM: To examine the medical literature concerning response to tumor necrosis factor (TNF)-alpha inhibitors in AS and compare with the PBS criteria for these agents. METHODS: Review of published studies and analysis of the PBS criteria for the prescription of TNF inhibitors for the treatment of AS to assess whether the published criteria are evidence based. RESULTS: The published findings on the prediction of response to TNF inhibitors in the treatment of AS suggest that age, duration of disease, disease activity, functional status at the time of commencement of TNF inhibitors and, possibly, level of acute phase reactants predict the outcome of treatment with TNF inhibitors in AS. The PBS criteria do not reflect the published findings on predictors of response to TNF inhibitors. CONCLUSION: The current PBS criteria that need to be fulfilled for patients to receive subsidised treatment with TNF inhibitors for AS are not evidence based and will lead to the selection of patients with established disease while excluding patients with early disease.