Focus on systemic lupus erythematosus in indigenous Australians: towards a better understanding of autoimmune diseases.

The incidence and prevalence of autoimmune diseases such as rheumatoid arthritis, primary Sjögren syndrome, scleroderma and systemic lupus erythematosus (SLE) varies with geography and ethnicity. For example, SLE is reported to be more common in populations such as African-Caribbeans and Indigenous Australians (IA). As well as socio-economic status, variation in severity of disease may also show ethnic variability. The initial presentation of SLE in IA, in the context of a unique genetic background and distinctive environmental influences, is often florid with a recurring spectrum of clinical phenotypes. These clinical observations suggest a unique pathway for autoimmunity pathogenesis in this population. For instance, the high prevalence of bacterial infections in IA, particularly group A streptococcus, may be a potential explanation not only for increased incidence and prevalence of SLE but also the commonly florid acute disease presentation and propensity for rapidly progressive end organ threatening disease. This article will review the state of research in autoimmune disease of IA, consider key findings related to autoimmune disease in this population and propose a model potentially to explain the involvement of innate immunity and chronic infection in autoimmune disease pathogenesis. Ultimately, understanding of SLE at this level could affect management and result in personalised and targeted therapies to improve the health status of IA as well as better understanding of SLE pathogenesis per se.

The clinical characterisation of systemic lupus erythematosus in a Far North Queensland Indigenous kindred.

The aetiology of systemic lupus erythematosus (SLE) is thought to involve both genetic and environmental factors. In other complex diseases, analysis of large multi-case families has resulted in insights into biological mechanisms. We have sought to characterise the members of an extended Indigenous family, five of whom have been diagnosed with SLE. Pedigree members were evaluated using the Lupus Screening Questionnaire, clinical interviews and medical records. Participants contributed blood and urine samples for laboratory analysis. A Mendelian pattern of inheritance was not observed. The five affected members (all female) shared two American College of Rheumatology criteria (positive ANA and arthritis) but showed a wide variety of other SLE manifestations. Disease onset, severity and progression were discordant. Including the five individuals with SLE, 15 blood relatives and two non-consanguineous spouses had autoimmune manifestations. Autoimmune haemolytic anaemia (one case), idiopathic thrombocytopenic purpura (ITP) (one case) and hypothyroidism (two cases) were observed in non-SLE affected individuals. Anti-nuclear antibodies were present in 12 blood relatives and one non-consanguineous spouse. Infections (especially of the skin) were observed to be common in the kindred. The lack of clear Mendelian inheritance or phenotypic concordance makes a rare monogenic explanation for SLE unlikely in this family. The finding of familial autoimmunity associated with SLE further supports the hypothesis that a common genetic pathway can precipitate autoimmunity, with further genes and possible environmental factors interacting to produce the eventual phenotype. Future genetic linkage studies may reveal a rare 'autoimmune gene' variant in this kindred.

Death of the first white resident of North Queensland.

The first white resident of North Queensland's death certificate gives the final illness as 'arthritis'. This examination of contemporary records and more recent reports, together with the results of discussion with colleagues interested in medicine and history, attempts to suggest the reasons for his various symptoms and his final demise. This life story is reminiscent of a 'Boy's own' adventure with shipwrecks, survival at sea, coexistence with Aboriginal tribesmen before returning to 'white society', marriage and the start of a family. Are there lessons here for the twenty-first century physician and rheumatologist? Would the commonplace illnesses of mid nineteenth-century Queensland be very different to the problems seen in our outpatient clinics today?

Systemic lupus erythematosus in the far north of Queensland.

An assessment of prevalence for systemic lupus erythematosus (SLE) has been attempted for the population of far north Queensland in Australia. This huge area has a majority Caucasian population living in a tropical environment. Roughly 10% of the population comprises people of Australian Aboriginal or Torres Strait Islander descent. The prevalence of disease was high (45.3 per 100000) overall and particularly so in the indigenous population (92.8 per 100000) where the disease appears to be more severe. The pattern of organ involvement and laboratory anomalies did not vary between the populations examined. Disease duration however was different, being longer by comparison in the Caucasian population due to many premature deaths in the indigenous groups. The reasons for such high prevalence figures and some problems encountered in practice are discussed.

Intra-articular distension and steroids in the management of capsulitis of the shoulder.

OBJECTIVE: To determine whether there is any synergistic effect in the administration of intraarticular steroids with distension in the management of early capsulitis of the shoulder. DESIGN: Prospective randomised trial of three treatments--namely distension only, steroid only, and steroid with distension. SETTING: Academic department of orthopaedic and accident surgery at Queen's Medical Centre, Nottingham. SUBJECTS: 47 patients (30 women) with capsulitis affecting 50 shoulders. INTERVENTIONS: Three intra-articular injections into the shoulder given at six week intervals by the same technique. MAIN OUTCOME MEASURES: Passive range of abduction, forward flexion, and external rotation; results of shoulder dynamometry measuring work done and torque produced; pain levels at rest and with resisted movement. RESULTS: All patients reported improvement during the study. Analysis of the mean improvements in abduction and forward flexion showed these to be significantly greater in the steroid with distension and steroid only groups than in the distension only group (mean improvements in abduction (degrees/week (95% confidence interval)) 4.3 (3.4 to 5.2), 3.4 (2.4 to 4.5), and 1.0 (-0.8 to 2.8) in the three groups respectively; mean improvements in flexion (degrees/week (95% confidence interval)) 3.6 (3.2 to 4.0), 3.3 (2.3 to 4.3), and 1.5 (0.5 to 2.5) respectively). Shoulder dynamometry failed to show a significant difference among the treatment groups. No severe complications occurred as a result of the injections, but two patients reported facial flushing related to the use of steroids. CONCLUSION: Intra-articular steroid injections have a useful role in the outpatient management of early capsulitis.

A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of osteoarthritis.

The efficacy and side-effect profiles of two formulations of indomethacin were compared in a multi-centre, double-blind, crossover study in 77 patients with osteoarthritis. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times daily for a period of 4 weeks, after which patients were crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by the investigator and patient indicate that controlled-release indomethacin tablets, 75 mg given at night, were as efficacious as immediate-release indomethacin capsules, 25 mg given 3-times daily, in the treatment of osteoarthritis. The side-effect profiles of the two formulations were similar.

Class specific rheumatoid factors in rheumatoid arthritis: response to chrysotherapy and relationship to disease activity.

IgG rheumatoid factors (RF) may play an important role in the pathogenesis of rheumatoid arthritis (RA). Our study investigates the relationship between class specific RF levels measured by radioimmunoassay and disease activity in patients with RA undergoing chrysotherapy. Nineteen patients were treated with 20 mg disodium aurothiomalate weekly for 6 months. Rheumatoid disease activity was assessed before and after 6 months' treatment and the level of IgG, IgA and IgM RF measured. There were significant falls in disease activity (p less than 0.005), IgA RF (p less than 0.005) IgG RF (p less than 0.005) and SCAT (p less than 0.025), but not IgM RF, over the 6 month treatment period. No correlation was found between absolute levels of IgA, IgG or IgM RF and disease activity before or after 6 months' therapy but there was a highly significant linear correlation between reduction in IgG RF levels and fall in disease activity (r = 0.642, p less than 0.005) with treatment.

An improved assay for IgG rheumatoid factor: its value in the diagnosis of rheumatoid arthritis.

A simple radioimmunoassay suitable for the routine estimation of IgG rheumatoid factors (IgG RF) has been developed. This involves determination of the amount of IgG RF binding to highly purified human IgG Fc on microtiter plates using a radiolabelled F(ab')2 preparation of an antihuman IgG Fd antiserum. A correction for nonspecific binding is made by subtracting sample reactivity with bovine serum albumin. Significantly elevated IgG RF levels were found only in patients with symmetrical peripheral erosive polyarthritis and in some patients with "mixed connective tissue disease."