Adult-onset Idiopathic Inflammatory Myopathies Research Articles

International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening: an International Myositis Assessment and Clinical StudiesGroup (IMACS)initiative.

Adult-onset idiopathic inflammatory myopathy (IIM) is associated with an increased cancer risk within the 3 years preceding and following IIM onset. Evidence- and consensus-based recommendations for IIM-associated cancer screening can potentially improve outcomes. This International Guideline for IIM-Associated Cancer Screening provides recommendations addressing IIM-associated cancer risk stratification, cancer screening modalities and screening frequency. The international Expert Group formed a total of 18 recommendations via a modified Delphi approach using a series of online surveys. First, the recommendations enable an individual patient's IIM-associated cancer risk to be stratified into standard, moderate or high risk according to the IIM subtype, autoantibody status and clinical features. Second, the recommendations outline a 'basic' screening panel (including chest radiography and preliminary laboratory tests) and an 'enhanced' screening panel (including CT and tumour markers). Third, the recommendations advise on the timing and frequency of screening via basic and enhanced panels, according to risk status. The recommendations also advise consideration of upper or lower gastrointestinal endoscopy, nasoendoscopy and 18F-FDG PET-CT scanning in specific patient populations. These recommendations are aimed at facilitating earlier IIM-associated cancer detection, especially in those who are at a high risk, thus potentially improving outcomes, including survival.

Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care.

The childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.

Perspectives on glucocorticoid usage in patients with adult inflammatory myopathy.

This study aims to describe the patient perspective on glucocorticoid (GC) treatment and adverse effects (AEs) in idiopathic inflammatory myopathy (IIM). An online survey was distributed to patients with adult-onset IIM using the Myositis UK page on Healthunlocked.com, an online social network for health. Respondents were asked to rate the severity of AEs they attributed to GCs on a Likert scale (0-5), and to report concerns and overall experience of GC treatment. The survey was completed by 122 respondents. The median reported current daily dose of prednisolone was 15mg (interquartile range [IQR] 8, 25) and median treatment duration 5.3years (IQR 3.4, 8.0) at the time of survey completion. Only 54% of respondents "agreed" or "strongly agreed" that the information provided to them about GC treatment was adequate. AEs rated most severe by respondents were weight gain, moon face, sleep disturbances and increased hunger. The duration of GC treatment weakly correlated with the mean number of reported AEs (p = 0.004) and mean severity of AEs (p = 0.017). There was an inverse relationship between age and acne, stretch marks, hair loss, facial hair, nausea and heartburn (p < 0.05). In this first study of patient-reported experiences of GCs specifically in IIM, we describe the burden of treatment and highlight the unmet need for safe and well-tolerated treatments. We report that patients with IIM often remain on long-term GC treatment at moderate doses, and that AEs are common. The reported data will be useful in planning discussions with patients regarding adherence to their treatment options. Key Points • Glucocorticoids (GC) are the first-line treatment in patients with idiopathic inflammatory myopathies (IIM), and are associated with a wide range of adverse effects • The adverse effects related to GC are very common, and those reported most severe by patients included weight gain, moon face, increased hunger or sleep disturbance, which may differ from the primary concerns of their treating clinician • Understanding the patient perspective and concerns about treatment is necessary to maintain a good physician-patient relationship and may help with treatment adherence.

Epidemiology of Idiopathic Inflammatory Myopathies in Africa: A Contemporary Systematic Review.

The epidemiology of idiopathic inflammatory myopathies (IIMs) has been extensively studied in America, Europe, and Asia, but remains unclear in Africa. The aim of this review was to summarize available data on the epidemiology of IIMs in Africa. We searched MEDLINE, EMBASE, and African Journals Online for studies published up to December 30, 2020, and reporting epidemiological data on IIMs in Africa. Data were combined through narrative synthesis. The review protocol was registered with PROSPERO, CRD42020186781. We included 39 studies reporting 683 cases (71.7% adults) of IIMs. Incidence rates of ~7.5/1,000,000 person-years and 1.2/1,000,000 person-years were estimated for dermatomyositis (DM), whereas polymyositis (PM) had an incidence rate of 8.8/1,000,000 person-years. Prevalence estimates of 11.49/100,000 and 11/100,000 (95% confidence interval, 0-32) were provided for IIMs and the PM subtype, respectively. Mean age at diagnosis ranged from 7.9 to 57.2 years, and 50% to 100% of the patients were females. Main subtypes of adult-onset IIMs were DM (21%-93%) and PM (12%-79%), whereas the commonest juvenile subtype was juvenile DM (5.8%-9%). Skeletal muscle involvement (56%-100%) was the main disease feature, and esophagus was the most commonly affected internal organ (6%-65.2%). Anti-Jo1/histidyl tRNA synthetase (7%-100%) and anti-Mi2 (17%-45%) antibodies were the most frequent myositis specific antibodies. Early mortality was high (7.8%-45%), and main death causes were infections, cancers and organ damage in respiratory and cardiovascular domains. Apart from a potential younger age at onset of adult IIMs in Africa, current sparse data mostly suggest a similar epidemiology between Africa and other regions. Further high-quality studies are required to validate these findings.

O33 Earlier cancer diagnosis after myositis onset is associated with improved long term survival: results from UK, French and Czech cohorts

Abstract Background The idiopathic inflammatory myopathies (IIMs) are associated with cancer. Cancer screening is advocated in new IIM cases; however no study has investigated if this confers improved long-term survival. This study aimed to investigate if a shorter time between IIM onset and cancer diagnosis is associated with improved survival. Methods Verified adult-onset IIM (dermatomyositis, polymyositis, anti-synthetase syndrome) cases, according to the International Myositis Classification Criteria, were recruited from three separate UK (UKMYONET), France and Czech-based cohort studies. Only cases with cancer diagnosis following IIM onset were included in analysis. The time between IIM onset and cancer diagnosis was calculated for each case. The relationship between survival at the end of follow up and time between IIM onset and cancer diagnosis was quantified via calculation of hazard ratios using a Cox-proportional hazard model, adjusted for age and gender. Results A total of 193 (66% female) IIM cases with a total of 1,395 person-years follow up were included in the analysis (Table 1). Data of 120 UK, 45 Czech and 28 French participants were analysed. Breast was the most common site of cancer (16%), followed by lung (9%) and bowel (6%). Forty six (24%) deaths occurred within the follow up period. The IIM onset to cancer diagnosis time was shorter for those that survived at the end of follow up, compared to those that died: 4.6 years (IQR 1.2, 10.7), vs 5.8 years (IQR 1.6, 13.8), respectively. Cox-proportional hazard modelling, indicated that a longer time between IIM onset and cancer diagnosis was significantly associated with death (HR 1.06 [95% CI 1.02, 1.10]). This significant relationship was only demonstrated in the female cohort when analysed separately: female HR 1.06 (95% CI 1.01, 1.10), male HR 1.08 (95% CI 0.98, 1.18). Conclusion Using data from three international cohorts, this study has, for the first time, identified that earlier cancer diagnosis after IIM onset is associated with improved long term survival. This finding was observed in the female cohort only. This study therefore indicate that cancer screening in newly diagnosed IIM cases without a preceding cancer history should be carried out, especially in female cases. Disclosures A. Oldroyd None. P. New None. J. Lamb None. W. Ollier None. R. Cooper None. K. Mariampillai None. O. Benveniste None. J. Vencovský None. H. Mann None. H. Chinoy None.

Using serum troponins to screen for cardiac involvement and assess disease activity in the idiopathic inflammatory myopathies.

ObjectivesLimitations in the methods available for identifying cardiac involvement and accurately quantifying disease activity in the idiopathic inflammatory myopathies (IIMs) may contribute to poor outcomes. We investigated the utility of different serum muscle damage markers [total creatine kinase (CK), cardiac troponin T (cTnT) and cardiac troponin I (cTnI)] to address these issues. MethodsWe assessed disease activity and cardiac involvement using the International Myositis Assessment and Clinical Studies Group core set measures in 123 participants with confirmed adult-onset IIM from the UK and Denmark. Total CK, cTnT and cTnI were measured. Associations were assessed using logistic regression and Spearman’s ranked correlation.ResultsCardiac involvement (n = 18) was associated with higher cTnI levels, independent of overall disease activity [adjusted odds ratio 1.03 (95% CI 1.01, 1.05); P = 0.002]. An abnormal cTnI had the highest specificity and positive predictive value for cardiac involvement (95% and 62%, respectively). In those with a normal CK but elevated cTnT or cTnI, an association with increased disease activity scores was observed. Serum cTnT correlated with the physician (ρ = 0.39) and patient-assessed (ρ = 0.28) global visual analogue scales and HAQ (ρ = 0.41) more strongly than CK or cTnI levels. cTnT was the only marker to correlate with manual muscle testing scores (ρ = −0.24).ConclusionSerum cTnI testing may have a role in screening for cardiac involvement in IIMs. Abnormal levels of serum cTnT and cTnI are associated with increased disease activity, including in those with a normal CK.

SAT0314 Pregnancy in Adult-Onset Idiopathic Inflammatory Myopathy. Report from A Cohort of Myositis Patients from A Single Center

BackgroundIdiopathic inflammatory myopathies (IIM) are systemic diseases, characterized by the presence of an inflammatory muscle infiltrate. Although more frequent in women, its relationship with pregnancy has not been extensively studied.ObjectivesOur...

“Pregnancy in adult-onset idiopathic inflammatory myopathy”: Report from a cohort of myositis patients from a single center

Background and purposeIdiopathic inflammatory myopathies (IIM) are systemic diseases, characterized by the presence of an inflammatory muscle infiltrate. Although more frequent in women, its relationship with pregnancy has not been extensively studied. Our goal was to analyze the interaction between pregnancy and myositis in a cohort of IIM women from a single center. MethodsA total of 51 patients from a historical cohort of IIM diagnosed between 1983 and 2013 were interviewed with a specific questionnaire. Comparisons between pregnancies occurring before and after the onset of the disease were performed using generalized mixed-effect models with normal and binomial distributions adjusted for confounding factors and clustering. ResultsA total of 102 pregnancies from 51 patients (41 with dermatomyositis and 10 with polymyositis) were analyzed. A total of 14 pregnancies from 8 patients occurred after disease onset; statistically significant (p = 0.02) clinical improvement during gestation was evident in 7 pregnancies (4 patients), 5 of them (from 2 patients) experienced a relapse of IIM symptoms afterwards, while in the rest, there was no influence of pregnancy on the disease. No disease flare associated with pregnancy was observed. Two patients were diagnosed within the first 6 months after delivery and none during pregnancy. No evidence was found to support pregnancy as a trigger for myopathy (p = 0.71). ConclusionsPregnancy does not seem to carry a worse prognosis for the mother nor for the fetus in patients with IIM; on the contrary, nearly half of the patients in our series improved clinically when they became pregnant, a relapse of IIM symptoms being common afterwards. Pregnancy does not appear to be a trigger for IIM.

Longterm Survival and Associated Risk Factors in Patients with Adult-onset Idiopathic Inflammatory Myopathies and Amyopathic Dermatomyositis: Experience in a Single Institute in Japan

To analyze clinical characteristics, survival, causes of death, and risk factors associated with mortality in patients with adult-onset idiopathic inflammatory myopathies (IIM) in Japan. We retrospectively investigated 197 patients diagnosed with adult-onset IIM at our hospital from 1984 to 2009 according to Bohan and Peter criteria for polymyositis (PM)/dermatomyositis (DM) and modified Sontheimer's criteria for clinically amyopathic DM (ADM). Survival in the whole group at 1, 5, and 10 years was 85%, 75%, and 67%, respectively. Mortality in cancer-associated myositis was the worst (25% at 5 yrs), followed by clinically ADM (61% at 5 yrs) and primary DM (77% at 5 yrs). Primary DM had significantly low survival compared to primary PM (91% at 5 yrs; p = 0.0427). Among the 53 patients who died were 6 patients with ADM (11%) and 20 patients with primary DM (38%). Interstitial lung disease (ILD) was the main cause of death in clinically ADM (71%) and primary DM (60%), most of which occurred within the first few months. Fewer patients died in primary PM (9%) and overlap myositis (13%). Independent risk factors for death were older age (HR 1.031; 95% CI 1.009-1.053) and skin ulcers (HR 3.018; 95% CI 1.340-6.796) in the whole group and ILD with mild serum creatine kinase levels (< 500 IU/l; HR 3.537; 95% CI 1.260-9.928) in primary DM. Survival of clinically ADM and primary DM was low, mainly due to fatal ILD, compared to primary PM. Establishing therapeutic strategy for ILD may improve the survival in our patient population.

P34 Long term survival study of adult onset idiopathic inflammatory myopathies; a single centre experience

P34 Long term survival study of adult onset idiopathic inflammatory myopathies; a single centre experience

Seasonal birth patterns in myositis subgroups suggest an etiologic role of early environmental exposures.

To evaluate whether seasonal early environmental exposures might influence later development of autoimmune disease, by assessing distributions of birth dates in groups of patients with idiopathic inflammatory myopathies (IIMs). We assessed birth patterns in groups of patients with juvenile-onset IIM (n = 307) and controls (n = 3,942) who were born between 1970 and 1999, and in groups of patients with adult-onset IIM (n = 668) and controls (n = 6,991) who were born between 1903 and 1982. Birth dates were analyzed as circular data. Seasonal clustering was assessed by the Rayleigh test, and differences between groups by a rank-based uniform scores test. The overall birth distributions among patients with juvenile IIM and among patients with adult IIM did not differ significantly from those among juvenile and adult controls, respectively. Some subgroups of patients with juvenile IIM had seasonal birth distributions. Hispanic patients with juvenile-onset IIM had a seasonal birth pattern (mean birth date October 16) significantly different from that of Hispanic controls (P = 0.002), who had a uniform birth distribution, and from that of non-Hispanic patients with juvenile-onset IIM (P < 0.001), who had a mean birth date of May 2. Juvenile dermatomyositis patients with p155 autoantibody had a birth distribution that differed significantly from that of p155 antibody-negative juvenile dermatomyositis patients (P = 0.003). Juvenile IIM patients with the HLA risk factor allele DRB1*0301 had a birth distribution significantly different from those without the allele (P = 0.021). Similar results were observed for juvenile and adult IIM patients with the linked allele DQA1*0501, versus juvenile and adult IIM patients without DQA1*0501, respectively. No significant patterns in birth season were found in other subgroups. Birth distributions appear to have stronger seasonality in juvenile than in adult IIM subgroups, suggesting greater influence of perinatal exposures on childhood-onset illness. Seasonal early-life exposures may influence the onset of some autoimmune diseases later in life.

Tumour necrosis factor- single nucleotide polymorphisms are not independent of HLA class I in UK Caucasians with adult onset idiopathic inflammatory myopathies

To investigate haplotype tagging single nucleotide polymorphisms (SNPs) in the tumour necrosis factor alpha (TNF-alpha) gene, in UK Caucasian idiopathic inflammatory myopathy (IIM) patients. A cross-sectional, case-control study of four TNF-alpha SNPs was undertaken, comparing cases of polymyositis (PM) (n = 121), dermatomyositis (DM) (n = 109) and myositis overlapping with other connective tissue diseases (CTD-overlap) (n = 73) with normal subjects (n = 177). Subgroup analyses were undertaken after stratifying for myositis specific/associated antibodies. The TNF-308A allele demonstrated a strong association with each myositis disease subgroup vs controls [PM, odds ratio (OR) 2.8, 95% confidence interval 1.9-4.3; DM, OR 2.5, 1.6-3.8; CTD-overlap, OR 3.3, 2.1-5.1]. The TNF-308GA/AA genotype frequency was significantly increased vs controls (PM, OR 3.7, 2.1-6.3; DM, OR 3.2, 1.8-5.5; CTD-overlap, OR 5.0, 2.6-9.6) suggesting a dominant model. The association was strongest in patients possessing anti-aminoacyl transfer RNA synthetase (anti-synthetase) (OR 5.1, 3.3-8.0) or -PM-Scl (OR 5.0, 2.7-8.9) antibodies. The -1031T allele was also a significant risk factor in DM (OR 2.2, 1.4-3.6), anti-synthetase (OR 2.9, 1.6-5.3) and -PM-Scl (OR 5.6, 1.9-6.4) antibody positive patients. The TNF-308A association was lost after adjusting for HLA-B*08, but remained independent of HLA-DQB1*02 (both are alleles forming part of the common ancestral haplotype). The HLA-B*08/TNF-308A/DRB1*03/DQA1*05/DQB1*02 haplotype was a risk factor in all myositis subgroups vs controls (OR 3.0, 1.8-5.3). TNF-308A and -1031T alleles are significant risk factors in the IIMs. In the IIMs, the TNF-308A allele is part of the common ancestral haplotype, but is not independent of HLA-B*08.

Clinical assessment in adult onset idiopathic inflammatory myopathy

Outcome measures have been developed and validated for many rheumatic diseases and used in clinical trials. The clinical assessment and measures of improvement in clinical trials of patients with idiopathic inflammatory myopathy (IIM) has varied to date and over the past few years an attempt has been made to reach a consensus in defining this improvement. The IMACS group (International Myositis Outcome Assessment Collaborative Study) has proposed core set measures for disease activity and damage assessment in adults. Distinguishing between activity and damage can be difficult and measures to ascertain this are discussed. Significant progress has been made in developing international consensus in the assessment of IIM. Further developments are underway to assess the reliability and validity of measures that should capture the multisystem nature of this disease.