Epidemiology of the idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases that affect the skeletal muscles and can also involve the skin, joints, lungs and heart. The epidemiology of IIM is obscured by changing classification criteria and the inherent shortcomings of case identification using healthcare record diagnostic coding. The incidence of IIM is estimated to range from 0.2 to 2 per 100,000 person-years, with prevalence from 2 to 25 per 100,000 people. Although the effects of age and gender on incidence are known, there is only sparse understanding of ethnic differences, particularly in indigenous populations. The incidence of IIM has reportedly increased in the twenty-first century, but whether this is a genuine increase is not yet known. Understanding of the genetic risk factors for different IIM subtypes has advanced considerably. Infections, medications, malignancy and geography are also commonly identified risk factors. Potentially, the COVID-19 pandemic has altered IIM incidence, although evidence of this occurrence is limited to case reports and small case series. Consideration of the current understanding of the epidemiology of IIM can highlight important areas of interest for future research into these rare diseases.

Anti-HMGCR immune-mediated necrotising myopathy: Addressing the remaining issues.

The discovery of autoantibodies directed against the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme has defined a sub-set of immune-mediated necrotising myopathy (IMNM) which is strongly associated with exposure to statin medications. Although understanding of anti-HMGCR IMNM has grown considerably with the reporting of multiple cohorts in North America, Europe, Asia and Oceania, there remain many unanswered questions. The true incidence of anti-HMGCR IMNM is not known and heterogeneity of phenotype and treatment response within this autoantibody sub-group is being increasingly recognised. Statin-naïve adults and juvenile patients with anti-HMGCR potentially share characteristics distinct from statin-exposed patients, alluding to unique pathogenesis. Conflicting data exists on whether malignancies are associated with anti-HMGCR and further clarification is required to determine the degree of cancer screening required. Treatment approaches to anti-HMGCR IMNM are heterogeneous but generally highlight the efficacy of intravenous immunoglobulin. Even with multimodal immunosuppression, patients with anti-HMGCR remain prone to relapse, with younger patients generally manifesting more refractory disease. In this Review, we aim to summarise the current literature on anti-HMGCR and discuss the remaining issues.

Defining independence: A scoping review by the OMERACT patient perspective of remission in rheumatoid arthritis group.

AIMS: The Outcome Measures in Rheumatology Trials (OMERACT) Remission in Rheumatoid Arthritis (RA) patient perspective working group has previously found that patients prioritised independence, pain, and fatigue as key domains of remission in RA. However, there is currently no clear definition of independence. Consequently, this scoping review aimed to explore how independence is represented in the RA literature. METHODS: A comprehensive search of the EMBASE, Medline, and PsycInfo databases was performed for publications that used independence or autonomy as a disease activity measure, description of disease in remission or treatment outcome. Papers were included if they involved adult participants and were written in English, with no restrictions on study design or publication year. Two reviewers (TK and AC, AT or BJ) independently screened the abstracts. A thematic approach was applied to derive common definitions and descriptions of independence. RESULTS: 660 articles were identified, of which 58 (25 qualitative, 28 quantitative, one mixed, and four reviews) met the inclusion criteria. 86% of total participants were female. Ten publications referenced remission. Independence took many forms; in addition to physical and functional capability, it was described in relation to work, social activities, autonomy in healthcare, and household activities. Four common themes describing independence were identified: 1. A return to a state before arthritis. 2. Being physically and functionally able. 3. A sense of freedom without needing to rely on others. 4. Having control over the organisation of one's life. CONCLUSION: Although independence is frequently mentioned in the RA literature, it has various meanings, lacks a consistent definition, and is a concept rarely applied to remission. It is multi-factorial, exceeding functional ability alone, and contextualised within sociodemographic and disease factors. This scoping review provides common descriptions of independence to inform future qualitative work towards the development of an outcome measure of independence for the assessment of RA in remission.

Perceptions towards biologic and biosimilar therapy of patients with rheumatic and gastroenterological conditions.

BACKGROUND: Biologic and targeted synthetic disease modifying agents (b/tsDMARDs) have broadened the treatment landscape for autoimmune diseases particularly in patients refractory to conventional DMARDs. More recently, the introduction of biosimilars has reduced the price of bDMARDs, potentially improving accessibility. Though efficacy and safety have been described, patient attitudes to b/tsDMARDs are not well-understood. We aim to investigate patients' beliefs about biologic and biosimilar therapy, and the factors influencing their perceptions. METHODS: Patient consumer groups (Arthritis Australia, Crohn's and Colitis Australia) assisted in advertising an online questionnaire for people with a self-reported diagnosis of inflammatory arthritis (IA) or inflammatory bowel disease (IBD). The questionnaire incorporated the Belief about Medicines Questionnaire (BMQ) and the single-item literacy screener (SILS). Sources and favourability of biologic/biosimilar information were analysed, using the chi-square and a non-parametric trend test for unordered and ordered categorical variables respectively, comparing respondents with IA and IBD. RESULTS: Eight hundred and thirty eight people (686-IA, 144-IBD, 8 both) responded. 658 (79%) used b/tsDMARDs. The BMQ demonstrated high necessity belief (median 4.2) with moderate concerns (median 2.8) about biologics. 95% of respondents obtained medication information from specialists though most used multiple sources (median 4). The most positive resources were specialists and specialist nurses. 73/141 (52%) respondents with IBD obtained information from specialist nurses compared with 202/685 (29%) with IA (p = 0.012). Respondents with limited reading ability on SILS were more likely to discuss information with a general practitioner or pharmacist. Younger respondents and those with higher BMQ concern scores more frequently consulted less reliable sources (e.g. social media). 502 respondents (60%) answered the biosimilar questions. Only 23 (4.6%) reported currently using a biosimilar and 336 (66.9%) were unsure if biosimilars were available in Australia. Specialist recommendation was the most frequent factor that would influence a patient to change from originator to biosimilar (352/495, 71.1%). CONCLUSIONS: There is a high level of trust in specialists' recommendations about b/tsDMARDs, although most people also utilise additional information sources. Contextual factors influencing resource selection include age, reading ability and degree of concern about medicines. People with IA and IBD have similar attitudes though those with IBD more frequently access specialist nurse advice.

Patient Perspectives of Disease Activity, Medications and Substance Use in People with Fibromyalgia.

Objective: To explore patient perspectives on disease activity and experiences, as well as medication use of a group of fibromyalgia patients attending a single-centre rheumatology public hospital outpatient setting. Methods: Patients seen in fibromyalgia clinic within a rheumatology unit from July 2016 to December 2019 were posted a voluntary survey with questionnaires pertaining to patient-reported measures of disease impact (FIQR), fatigue (MFI-20) and psychological distress (K10). A free-text section allowed description of disease impact. Patients were also asked to record medication use and comorbidities, which were then compared to the electronic medical records (EMR) of the overall clinic cohort. Results: Forty-five patients responded to the survey (43/45, 95.6% female; mean age 56.5 years). Respondents had generally severe fibromyalgia (mean FIQR 67.1/100, range 23.7-92.8), moderate psychological distress (mean K10 27.5/50, range 14-45) and high fatigue (mean MFI 74.9/100, range 40-96). Free-text responses generated themes of pervasive disease impact and the necessity of adjusting life around unpredictable symptoms. Almost half reported opioid (21/45, 46.7%) and gabapentinoid (19/45, 42.2%) use. 16/41 (39%) use cannabinoids for their fibromyalgia symptoms. Comparing medication use with survey non-respondents (n=85), there was generally similar representation except for significantly greater NSAID use among survey respondents (33/45, 73.3% vs 22/85, 25.9%, p<0.001). Conclusion: For patients living with fibromyalgia in this study, there were high levels of disease activity, psychological distress and fatigue. Patients described the need to accept disease-imposed limitations and life adjustments. Almost half reported opioid use, despite evidence suggesting poor efficacy and possible harm.

Biologic therapy in the idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases resulting from inflammation of muscle and manifesting as weakness, though a range of extra-muscular manifestations are observed. These are often correlated closely with disease subtype and the presence of myositis-specific/myositis-associated antibodies. IIM are notoriously difficult to treat and often refractory to glucocorticoid therapy and synthetic immunosuppressants. Both the innate and adaptive immune systems are implicated in the pathogenesis of IIM. A growing understanding of the key cytokines as well as the cell-mediated and antibody effectors of disease has identified multiple potential targets for biologic therapy. The most widely used of these is B-cell depletion via rituximab though the tumour necrosis factor inhibitors and other biologic therapies used in diseases such as rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis have also been trialled. This review summarises the literature thus far on biologic therapy in IIM, highlighting both the significant trials that influence current treatment regimens and also the continuing need for further research to inform more effective therapies.

Cardiac involvement in idiopathic inflammatory myopathies detected by cardiac magnetic resonance imaging.

Cardiac involvement in idiopathic inflammatory myopathies (IIM) adversely affects prognosis but is commonly sub-clinical. Cardiac magnetic resonance imaging (CMR) is an effective imaging modality for detecting myocardial inflammation and fibrosis but its use as a screening tool for cardiac disease in IIM has not been fully explored. Nineteen patients with IIM without cardiac symptoms underwent CMR using a specific cardiomyopathy protocol including specific sequences detecting focal and diffuse myocardial fibrosis. 9/19 patients demonstrated late gadolinium enhancement (LGE (3/9 right ventricular insertion, 1/9 sub-endocardial, 7/9 mid-wall/sub-epicardial)). T1 mapping was performed in 15 patients. In total, 7/15 had elevated native T1 values, of which four had detected LGE. Myocardial fibrosis was frequently detected in IIM patients without cardiac history. Detection of LGE and elevated T1 values may have negative prognostic implications. Longitudinal studies determining whether early or augmented treatment has a role in patients with sub-clinical cardiac involvement are needed.Key Points• Cardiac involvement in myositis adversely affects prognosis.• Cardiac magnetic resonance imaging is an effective tool for detecting cardiac involvement.• T1 mapping is a technique which detects diffuse myocardial inflammation and fibrosis.• In our study, focal and diffuse myocardial fibrosis was frequently found in myositis patients without cardiac symptoms.

Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population.

INTRODUCTION: Silicone breast implants (SBI) may induce systemic autoimmune disease as part of autoimmune syndrome induced by adjuvants (ASIA). This syndrome bears similarities to fibromyalgia and chronic fatigue syndrome (CFS). We sought to determine whether there are any associations between SBI and depression, fibromyalgia and CFS in a rheumatology clinic population. METHODS: The electronic files of rheumatology clinic patients at the Royal Adelaide Hospital between 2000 and 2017 were searched for patients who had received SBI prior to rheumatological diagnosis. Demographics, diagnosis, implant history and whether the patient had depression, fibromyalgia or CFS were recorded. Controls were rheumatology clinic patients, half of whom had systemic sclerosis (SSc) and the other half had systemic lupus erythematosus (SLE). They were matched to cases 3:1 for age (within 2 years) and gender. RESULTS: Thirty patients had received SBI (mean age 47.9, 100% female). Twelve had a diagnosis of depression, 6 of fibromyalgia and 3 of CFS. Implant rupture was not associated with any of these (p = 1). There was no difference in the incidence of depression (p = 1), fibromyalgia (p = 0.76) or CFS (p = 0.3) between cases and SLE controls. When compared with SSc controls, there were significantly more patients with fibromyalgia and/or CFS in the case group (20.0% of cases vs 2.2% of SSc controls, p = 0.01) but no difference in depression (p = 0.12). CONCLUSION: Fibromyalgia and CFS are more common in patients with silicone implants than SSc controls but not SLE controls. Prospective study of development of depression, fibromyalgia and CFS in recipients of SBI is required.

Proton pump inhibitors are not associated with inflammatory myopathies: A case control study.

INTRODUCTION: A rare association of proton pump inhibitor (PPI) use with the development of inflammatory myopathies (IM) has been reported, but, unlike with statin medications, there is limited data supporting or refuting this observation. METHODS: A case-control study was conducted on patients with IM. Clinical information, medications, and demographics were recorded. Controls were matched 3:1 for age and gender. RESULTS: Two hundred twenty-one cases of IM were identified. No association of PPI use with IM was observed when compared with controls (odds ratio 1.04 [95% confidence interval 0.68-1.58]) and similar results were observed after adjusting for diabetes, cardiovascular disease, and statin exposure (adjusted odds ratio 1.084 [95% confidence interval 0.69-1.70]). There was no association of any histologic subtype of IM with PPI exposure. DISCUSSION: Our findings do not support an association of PPI exposure with IM. Co-prescription of PPI with other medications was not considered and could be further investigated with larger cohorts. Muscle Nerve 58:855-857, 2018.

Curvilinear bodies are associated with adverse effects on muscle function but not with hydroxychloroquine dosing.

The clinical significance of curvilinear bodies (CB) seen in association with hydroxychloroquine (HCQ) therapy is uncertain. Patients with CB on muscle biopsy performed between 2006 and the present were identified, and their clinical features including body mass index and cumulative HCQ dose were recorded. A control group of 16 patients with idiopathic inflammatory myositis (IIM) on HCQ at time of biopsy but without evidence of CB was identified. Nineteen patients with CB were identified; details were available for 18. Among patients with CB, 7/18 also had IIM. Seven out of ten patients with CB who did not have IIM or MHCI/II expression had proximal weakness; 7/11 had raised serum creatinine kinase (CK) levels. There was no difference in body weight (p = 0.47), body mass index (p = 0.93), cumulative HCQ dose (p = 0.52) or cumulative dose adjusted for body weight (p = 0.39) or body mass index (p = 0.32) between patients with CB and controls. Patients with CB had lower median CK levels than controls (p = 0.034). Weakness was present in 12/17 patients and 12/16 controls (p = 1.0). Concurrent proton-pump inhibitors were co-prescribed in 12/18 (67 %) patients with CB and in 6/16 (38 %) controls (p = 0.17). Development of CB does not appear to be related to cumulative HCQ dose or body weight. Patients with CB frequently have muscle weakness in the absence of MHC1 expression suggesting a role for non-immune mechanisms of muscle injury. A high proportion of patients with CB are co-prescribed proton-pump inhibitors raising the possibility that co-prescription of both agents may disrupt lysosomal function and adversely affect muscle function.