Seasonality of birth patterns in an Australian cohort of patients with biopsy-confirmed idiopathic inflammatory myopathy.

Environmental exposures in the foetal period may predispose to autoimmunity. Aim of this study is to investigate whether seasonality in birth patterns exists in idiopathic inflammatory myopathies (IIM). We used Stata (StataCorp USA, version 13.0) and the user-written routine command 'circsummarise' to assess birth seasonality among South Australian patients with histologically confirmed IIM subsequent to 1980 using their date of birth. There was no evidence for a seasonal birth pattern among IIM patients overall (n = 568), however there were some ethnic variances in birth patterns among non-Caucasian patients. There was evidence for birth seasonality among both Aboriginal (mean = 7 July, Rayleigh P = 0.04) and Asian patients (mean = 12 August, Rayleigh P-value = 0.038). Non-Caucasians born in the third quarter of the calendar year may have an increased risk of developing IIM. Large international studies of IIM patients of diverse ethnicity are required to clarify the role of perinatal exposures in disease susceptibility.

Serious statin-associated myotoxicity and rhabdomyolysis in Aboriginal and Torres Strait Islanders: a case series.

BACKGROUND: Statins are associated with skeletal muscle adverse effects. These are generally considered mild and reversible, with more severe toxicity occurring rarely. There is little known regarding statin myotoxicity in Aboriginal and Torres Strait Islander Australians who are at high cardiovascular risk and likely to receive statins. AIMS: To describe features of serious statin-associated myotoxicity (SSAM) occurring in Indigenous Australians and increase awareness of this condition. METHODS: Observational case series of SSAM in Aboriginal or Torres Strait Islanders. Cases were identified from personal clinical experience, referrals, reports to the Therapeutic Goods Administration, medical literature, an Internet search and reports from a histopathology laboratory. Information was collected onto a standardised data collection form. RESULTS: Fifteen cases of serious myotoxicity in Aboriginal or Torres Strait Islanders exposed to statins were identified from 2006 to 2012. The mean age was 55 (range 35-69). Painless weakness was the most common presentation. Interacting drugs were involved in seven cases. Biopsies were done in eight cases, three showed inflammatory polymyositis and five necrotising myositis. Three patients died and two had permanent severe disability. Resolution of symptoms after statin cessation was variable. CONCLUSIONS: SSAM has occurred in the Indigenous Australian population with some fatalities. Awareness of the potential for SSAM is essential for early recognition and effective management to reduce probability of avoidable catastrophic harm. Safe, as well as effective use of medication, is essential for optimum health outcomes. Effective pharmacovigilance and therapeutic risk management are important for Aboriginal and Torres Strait Islander Australians.

Efficacy of rituximab in refractory antisynthetase syndrome.

We report the successful use of repeated administration of rituximab in a patient with antisynthetase syndrome refractory to conventional immunosuppressive medications. A literature review revealed that previous experience with rituximab in this condition has been sparse. The rationale for the use of B-cell depleting therapies in antisynthetase syndrome has been explored in light of the current understanding of the pathogenesis of this condition.

Mortality and its predominant causes in a large cohort of patients with biopsy-determined inflammatory myositis.

BACKGROUND: There is a paucity of literature on the patterns and predictors of mortality in idiopathic inflammatory myopathies (IIM). AIMS: To determine the patterns and predictors of mortality in a South Australian cohort of patients with biopsy-proven IIM. METHODS: The living/deceased status (and for deceased patients the causes of death) of patients with histologically determined IIM was determined from the Births, Deaths and Marriages Registry. Standardised mortality ratios (SMR) were generated compared with the age/gender matched South Australian population. The effect of presence/absence of the components of the Bohan and Peter criteria on risk ratios (RR) for mortality was determined. The effect of comorbidities and autoantibodies on mortality was investigated. RESULTS: The SMR for mortality in IIM was 1.75 and was significantly increased in all disease subgroups, being highest in patients with dermatomyositis (2.40). Dominant causes of death were cardiovascular disease (31%), infections (22%) and malignancy (11%). Risk factors for death were age at time of biopsy (hazard ratio 1.05), ischaemic heart disease (RR 2.97, P < 0.0001), proximal weakness at diagnosis (RR 1.8, P= 0.03), definite diagnosis of IIM per the Bohan and Peter criteria (RR 2.14, P < 0.0001), and the absence of autoantibodies (RR 1.9, P < 0.001). CONCLUSIONS: Patients with IIM are at 75% increased risk for mortality, and cardiovascular diseases account for the commonest causes of death. This study suggests a thorough cardiovascular evaluation of these patients is indicated, and raises the possibility that targeted interventions such as the use of aspirin or statins may improve outcomes in IIM.

Clinical heterogeneity and prognostic features of South Australian patients with anti-synthetase autoantibodies.

AIM: To determine the clinical, serological and prognostic features of patients with autoantibodies against three aminoacyl-transfer RNA synthetases (ARS), namely Jo-1 (histidyl-tRNA synthetase), PL-7 (threonyl-tRNA synthetase) and PL-12 (alanyl-tRNA synthetase) in South Australia. METHODS: Patients with autoantibodies against ARS detected by line immunoassay (anti-Jo1, anti-PL7, anti-PL12) or enzyme-linked immunosorbent assay (anti-Jo1) were identified from existing laboratory databases for the period 1994-2009. Demographic, clinical and serological data were obtained by retrospective review of patients' medical records and laboratory databases. RESULTS: Forty-two patients with autoantibodies were identified (anti-Jo1 = 37, anti-PL7 = 4, anti-PL12 = 1). Females were more commonly affected than males (M : F = 12:30). Twenty-one patients had polymyositis (anti-Jo1 = 17, anti-PL7 = 4), seven dermatomyositis (anti-Jo1 = 6, anti-PL12 = 1), 10 overlap syndrome (anti-Jo1 = 10; lupus = 4, scleroderma = 3, Sjögren's syndrome = 2 and rheumatoid arthritis = 2) and four had interstitial lung disease (ILD) only (anti-Jo1 = 4). ILD was present in 69%, polyarthritis in 59% and positive anti-nuclear antibody (ANA) in 43% of patients. Concurrence of autoantibodies against Ro-52 with Jo-1 was seen in 12 patients. The mean follow-up period was 8.3 years (95% CI 5.8-10.8) with 12 deaths. Poor prognostic indicators were age of onset >60 years (P= 0.001), cancer (P= 0.002), negative ANA (P= 0.006) and negative autoantibodies to extractable nuclear antigens (P= 0.02). CONCLUSION: Patients with autoantibodies against ARS present with varied clinical features and occasionally with isolated lung involvement (amyopathic ILD). Older age of onset, malignancy and negative immunologic tests are predictors of poor prognosis. Concurrence of autoantibodies against Jo-1 and Ro-52 may reflect a coupling effect during generation of autoimmunity.

Idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies are a group of systemic autoimmune syndromes characterized by striated muscle inflammation. Here, we discuss the clinical features of this group of conditions and review the recent developments in the understanding of the pathogenesis and immunogenetics of the idiopathic inflammatory myopathies. The role of myositis-specific autoantibodies and their clinical significance and an overview of management are also provided.

Evaluation of hand function in patients undergoing long term haemodialysis.

OBJECTIVE: Haemodialysis is associated with the deposition of beta(2) microglobulin in musculoskeletal structures, leading to the syndrome of dialysis related amyloidosis and impairment of hand function. This study aimed at assessing hand function using the Sollerman test in a cross section of patients undergoing haemodialysis. METHODS: Recipients of haemodialysis underwent the Sollerman test of hand grip function, which assesses 20 activities of daily living using eight grip types, and the JAMAR grip strength test, visual analogue scales (VAS) for pain (VAS-P) and function (VAS-F), and Health Assessment Questionnaire (HAQ) were determined. Results-Thirty five subjects (26 male), with mean age 53.2 years, participated. The average duration of haemodialysis was 6.2 years (range one month to 25 years). The median Sollerman score was 77, with 19/35 (54%) patients receiving haemodialysis having a score below the lower normal value of 78-80. The log Sollerman score correlated poorly with age (rs=0.16, p=0.35), and significantly with the HAQ score (r(s)=-0.66, p<0.00005), duration of haemodialysis (rs=-0.39, p<0.05), VAS-F (rs=-0.41, p<0.05), VAS-P (rs=-0.34, p<0.05), and JAMAR score (rs=0.57, p<0.05). Sollerman scores were highly correlated between dominant and non-dominant hands (rs=0.69, p<000005). CONCLUSIONS: Hand dysfunction is a common finding among patients undergoing long term haemodialysis. The Sollerman test accurately reflects patient function as measured by HAQ, VAS-F, and grip strength, but less so pain. Its use for the early detection of dialysis related amyloidosis and in the serial monitoring of the effects of hand treatment programmes is encouraged.

The clinical associations of mitotic spindle autoantibodies in a South Australian cohort.

BACKGROUND: The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins involved in the segregation and reorganisation of chromosomes during cell division. Autoantibodies to the MSA (anti-MSA) are reported to occur rarely, but are easily identified during the immunofluorescent detection of anti-nuclear antibodies (ANA), and are generally reported as part of that investigation. AIMS: As the clinical significance of these antibodies is unknown, our aim was to identify the clinical features of subjects identified with anti-MSA, and in a subset investigate the co-association with organ specific anti-thyroid antibodies. METHODS: All ANA results from the three major immunology laboratories serving South Australia between January 1993 and June 1998 were retrospectively reviewed to identify anti-MSA subjects. Clinical details were extracted from hospital or general practice records using a standard proforma. Thyroid autoantibodies were measured using standard technique. A control group of consecutive ANA positive, anti-MSA negative individuals had anti-thyroid antibodies measured. Statistical comparison used chi2 test. RESULTS: Fifty-five subjects (43F) were identified with mean age 59.8 (range 17-91); 39 had specific diagnoses, with 16 identified as part of non-specific investigations. 'Arthritis' broadly accounted for the largest group, transient inflammatory arthritis n=7, degenerative joint disease n=6, rheumatoid arthritis n=5. Adenocarcinoma and mesothelioma accounted for one case each. Thirty-two subjects had anti-thyroid antibodies tested, with ten of 21 and two of 11 positive among the groups with anti-MSA titre >1:80 and <1:40 respectively, chi2=2.7, p=0.1. Anti-thyroid antibodies were detected more frequently among the high titre anti-MSA group (ten of 21) compared with high titre positive ANA, negative anti-MSA group (two of 11), RRisk 4.4, chi2=5.34, p=0.02. CONCLUSION: This study confirmed the relative rarity of anti-MSA and that its association is primarily with rheumatic diseases. The coincidence of mesothelioma is novel with only two previous reports of malignancy and anti-MSA. The co-association of high titre anti-MSA and thyroid autoantibodies suggest that the latter should be a follow up investigation if the former is identified as part of an investigative screen.

Evaluation of antibodies to beta2-glycoprotein 1 in the causation of coronary atherosclerosis as part of the antiphospholipid syndrome.

BACKGROUND: Anticardiolipin antibodies (aCL) are associated with accelerated coronary atherosclerosis. Beta2-glycoprotein 1 is a cofactor necessary for the binding of aCL. AIM: The aim of this study was to determine whether antibodies to beta2-glycoprotein 1 (anti-beta2GP1) predispose to coronary artery disease (CAD), and whether the measurement of anti-beta2GP1 will be more useful than aCL alone in the evaluation of coronary risk. METHODS: Persons who had undergone coronary angiography were invited to participate, and risk factors for coronary atherosclerosis recorded. IgG aCL and anti-beta2GP1 were measured and fasting triglyceride (TG) and total cholesterol (TC) levels were determined. Angiographic score (AS) was defined as the number of diseased vessels (0, 1, 2, 3), (>50% stenosis). Ethics Committee approval was obtained. Statistical comparison used the Student's t test and Chi-squared test. RESULTS: Ninety-seven subjects (63 male) with age range 38-81 years (mean 66.0) participated. There were 31 subjects with AS=0, 27 with AS=1, 22 with AS=2, and 17 with AS=3. The three subjects with positive aCL all had CAD, as did three of the four subjects with positive anti-beta2GP1. Among patients with CAD, there was an equal incidence (4.5%, three/66) of aCL and anti-beta2GP1, and an incidence of either aCL or anti-beta2GP1 of 7.6% (five/66). Compared to the group with AS=0, those with AS=1, 2 or 3 comprised a higher mean age (p=0.001) however, there was no significant difference in the prevalence of other coronary risk factors between the two groups. There was no difference in the proportions of patients with either aCL or anti-beta2GP1 in the group with AS=1, 2, or 3, compared to the group with AS=0 (5/66 c.f. 1/31, chi2=0.146, p>0.5). CONCLUSIONS: Our study has not supported an association between anti-beta2GP1 and CAD. The measurement of anti-beta2GP1 (or aCL) in the investigation of premature CAD is not justified on the basis of our results.