Adult Idiopathic Inflammatory Myopathies Research Articles

Cancer and idiopathic inflammatory myopathies –association of autoantibodies with carcinogenesis

The relationship between cancer development in the course of idiopathic inflammatorymyopathies (IIM) has already been noticed at the beginning of the 20th century. However, theunderlying mechanisms remain not fully understood. Risk factors for carcinogenesis in patientswith IIM include male sex, older age, and the presence of specific subtypes of inflammatorymyopathies and clinical manifestations, including dermatomyositis, dysphagia, severe skinchanges, leukocytoclastic vasculitis, acute disease onset and immunosuppressive therapyresistance. The presence of certain autoantibodies in the serum of patients with IIM is a factorof considerable importance in the stratification of cancer risk. Anti-TIF1γ autoantibodies, which might be present in even 38-80% of cancer cases in adult IIM patients, are antibodies with a wellstudiedrelationship with carcinogenesis. The relationship of other antibodies found in IIM withthe risk of carcinogenesis is still discussed. This group includes anti-NXP2, anti-HMGCR, anti-SAE1 and anti-Mi2 antibodies. Due to the contrary reports on the role of these antibodies incancer development and their relatively low prevalence in IIM, the unambiguous classificationas risk factors requires further research in larger study groups. The potential autoantibodiesutility in cancer screening in IIM patients could help detect cancer early, improving prognosisand long-term survival.

Double Negative B cells are decreased in patients with Idiopathic Inflammatory Myopathies.

Abstract Background: Idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases characterized by skeletal muscle inflammation, frequently accompanied by extra muscular features associated with specific autoantibodies. The detailed pathogenesis of IIM remains unclear, but evidence suggests autoreactive B cells may play an essential role in this process. However, little is known about changes in peripheral blood B cell subsets in adult IIM patients. Objective: This study aims to determine the frequency of B cell subsets among patients with IIM and their clinical correlation with disease activity. Methods: Using a multiparametric flow cytometric approach, we determined the frequencies of B cell subsets in a cohort of 36 patients with IIM and correlated their values with clinical and laboratory data. Results: DN B cells (CD27 −IgD −), which represent an atypical B cell subset associated with various autoimmune diseases, showed a significant decrease in frequencies and a correlation with the MMT8 score. Within the DN subset, the DN1 subpopulation (CD21 +CD11c −) showed a significant decrease compared to the control group. There was also a significant decrease in the memory B cell subpopulation (CD27 +CD38 −) and the non-classic memory B cell subpopulation (CD27 −CD38 −CD24 +). A significant increase in naive B cells (CD27 −IgD +) was observed. However, none of the previously described subpopulations correlated with clinical features. Conclusion: This study demonstrated a decrease in frequencies in the double negative B cell subset in adult IIM patients and showed a correlation with clinical features, which suggests that these B cells could be related to disease activity. UNAM-DGAPA-PAPIIT IN212122

Retinal changes in patients with idiopathic inflammatory myopathies: A case-control study in the MyoCite cohort.

Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with Idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Adult and Juvenile IIM patients (2017 ACR/EULAR criteria), visiting a tertiary care center in 2021 were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6 vs. 4.3%, p < 0.001), AV nicking (14 vs. 2.2%, p = 0.053), and vascular tortuosity (18.6 vs. 2.2%, p = 0.012), besides decreased visual acuity (53.5 vs. 10.9%, p<0.001) and immature cataracts (34.9 vs. 2.2%, p < 0.001). Attenuation of vessels [OR 10.9 (1.7-71), p = 0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p = 0.068], especially attenuation of vessels [14(38%) vs. 0(0), p = 0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Retinal microvasculopathy and diminution of vision occur in nearly one-thirds to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Reliability and validity of PROMIS physical function, pain interference, and fatigue as patient reported outcome measures in adult idiopathic inflammatory myopathies: International study from the OMERACT myositis working group

ObjectivePain interference, fatigue, and impaired physical function are common features of idiopathic inflammatory myopathies (IIM). The objective of this study was to evaluate the construct validity and test-retest reliability of the Patient Reported Outcome Information System (PROMIS) Pain Interference 6av1.0, Fatigue 7av1.0, and Physical Function 8bv2.0 instruments. MethodsPatient-Reported Outcome Measures (PROMs) were deployed to adult IIM patients from OMERACT Myositis Working Group (MWG) international clinic sites via two online surveys (2019, 2021). Internal consistency of each PROM was analyzed by Cronbach's α. Construct validity was determined by a priori hypotheses generated by the MWG with >75% agreement for each hypothesis and calculated with Pearson correlations. Test-retest reliability was assessed using intraclass correlation coefficient with PROMIS instruments administered at time zero and 7 days. ResultsSurveys were sent to 368 participants in total; participants who completed each questionnaire varied (n=65 to 263). For construct validity, 10 out of 13 a priori hypotheses were met supporting construct validity of PROMIS instruments (Pain Interference 3/4, fatigue 4/4, and Physical Function 3/5). Test-retest reliability was strong for all PROMIS instruments. All PROMIS instruments demonstrated excellent internal consistency. None of the measures demonstrated any ceiling or floor effects except for a ceiling effect in the Pain Interference instrument. ConclusionsThis study presents test-retest reliability and construct validity evidence supporting PROMIS Pain Interference (6a v1.0), Fatigue (7a v1.0), and Physical Function (8b v2.0) using a large international cohort of patients with IIM. Internal consistency of these instruments was excellent. A ceiling effect was noted in the Pain Interference instrument.

Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features.

Four-and-a-half LIM domains 1 (FHL1) is a muscle-specific protein. Autoantibodies against FHL1 were recently discovered in adults with idiopathic inflammatory myopathies (IIMs) and were found to be associated with clinical features and outcomes indicative of increased disease severity. Anti-FHL1 autoantibodies have not been described in children. Here, the prevalence and clinical features associated with anti-FHL1 autoantibodies were examined in a large North American cohort of juvenile patients with IIM. Sera from 338 juvenile IIM patients and 91 juvenile healthy controls were screened for anti-FHL1 autoantibodies by ELISA. Clinical characteristics and HLA alleles of those with and without anti-FHL1 autoantibodies were compared among those with juvenile IIM. Anti-FHL1 autoantibodies were present in 10.9% of juvenile IIM patients and 1.1% of controls. The frequency of anti-FHL1 autoantibodies among clinical and serologic subgroups did not differ. A higher percentage of Asian patients had anti-FHL1 autoantibodies (11% vs 0.7%; P = 0.002). Myositis-associated autoantibodies (MAAs) [odds ratio (OR) 2.09 (CI 1.03, 4.32)], anti-Ro52 autoantibodies specifically [OR 4.17 (CI 1.83, 9.37)] and V-sign rash [OR 2.59 (CI 1.22, 5.40)] were associated with anti-FHL1 autoantibodies. There were no differences in other features or markers of disease severity. No HLA associations with anti-FHL1 autoantibodies in Caucasian myositis patients were identified. Anti-FHL1 autoantibodies are present in ∼11% of juvenile IIM patients and commonly co-occur with MAAs, including anti-Ro52 autoantibodies. In contrast to adult IIM, anti-FHL1 autoantibodies in juvenile myositis are associated with V-sign rash but not with other distinctive clinical features or worse outcomes.

Alterations of peripheral blood B cell subsets in Chinese patients with adult idiopathic inflammatory myopathies.

Abnormalities and hyperactivation of B cells have been described in idiopathic inflammatory myopathies (IIM). However, little is known about changes in the homeostasis of peripheral blood B cells in adult IIM patients. The aim of this study was to identify phenotypic alterations of B cell subsets and their relation to the overall clinical profile. Blood samples were collected from 25 adult IIM patients and 15 healthy controls. Peripheral B cell subsets were classified into non-switched memory B cells (CD19+CD27+lgD+), switched memory B cells (CD19+CD27+lgD-), double-negative (DN) memory B cells (CD19+CD27-lgD-) and naïve B cells (CD19+CD27-lgD+) based on their surface phenotype as measured by flow cytometry. The clinical profile of IIM and its correlation with B cell subsets was further evaluated. Frequencies of CD19+ B cells and naïve B cells were increased in adult IIM patients compared with healthy controls (p=0.005 and p<0.001, respectively) and the frequency of memory B cells was decreased (p<0.001). Moreover, patients with a rash had lower non-switched memory B cells proportion (p=0.032). Patients with anti-MDA5+ antibodies had higher CD19+ B cells proportion than anti-ARS+ patients (p=0.046). Patients who were not receiving treatment had elevated levels of CD19+ B cells and naïve B cells along with reduced non-switched memory B cells compared with patients who were receiving treatment (p=0.021, p=0.036 and p=0.032, respectively). Our findings demonstrate abnormalities in the homeostasis of the B cell subsets present in adult IIM patients, characterised by expanded CD19+ B cells and naïve B cells but reduced memory B cells. Phenotypic abnormalities of B cell subsets are associated with the presence of a rash, with anti-MDA5 positivity and with treatment.

Distribution and trajectory of direct and indirect costs of idiopathic inflammatory myopathies

ObjectivesTo estimate the annual direct and indirect costs associated with Idiopathic Inflammatory Myopathies (IIM) over time, including the pre-diagnostic period. MethodsA cohort of incident adult IIM patients (n = 673) was identified from the Swedish National Patient Register from 2010 to 2016 and matched with general population comparators (n = 3343). Follow-up started at IIM diagnosis and corresponding date in the general population. International Classification of Diseases codes (ICD-10) were used for IIM case definition. Costs were calculated using national register data. ResultsThe costs related to IIM started to increase 2 years before diagnosis. In the year following diagnosis, the mean annual IIM cost was €21 639 compared to €4816 in the general population. Five years after diagnosis, the mean annual cost in the IIM cohort was €12 796. Outpatient visits, hospitalizations and productivity loss were the components driving the increment in overall annual disease-related expenditures. Indirect costs accounted for a significant portion of IIM long-term societal costs. The highest costs were found in individuals of working age with cancer-associated IIM. ConclusionsThe mean annual costs in IIM were 3 to 5 times higher than in the general population in the 5-year period following diagnosis. These costs started to increase long before diagnosis, were at their peak in the year post-diagnosis and remained elevated thereafter. Indirect costs contributed to a substantial portion of this increment. Early in the IIM disease course, clinicians and allied health professionals should aim to improve function, reduce damage and address barriers to return-to-work to mitigate these costs.

P156 Myositis flares are associated with reduced work productivity and fewer hours worked: illustration of the future potential of digital healthcare solutions in rheumatic diseases

Background/Aims The digital healthcare revolution provides the opportunity for clinicians and researchers to collect useful data on a frequent and remote basis. Work ability is impacted by many rheumatic diseases, including the idiopathic inflammatory myopathies (IIMs), however, methods to assess the real-time impacts are limited. This study aims to explore the impact of IIM flares and symptoms upon employment using frequently collected data via a smartphone-based app. Methods The Myositis Physical Activity Device Study recruited a UK-based adult IIM cohort who completed weekly employment and flare questions via a specially designed smartphone-based app throughout a 91 day period in 2019/20. Employment-related questions were assessed every week (see Table 1 for details). Flares were reported via a weekly question. Employment variables were compared between flare and non-flare weeks using descriptive statistics. The relationship between flares and work productivity was assessed using multi-level mixed effects logistic regression modelling, adjusted for age and sex. Results Data on 13 (69% female) employed participants was analysed. A median of 5 flares were reported per patient during the three month period (IQR 3, 9). Summary employment results are displayed in Table 1. Participants reported greater impact of IIM upon employment, lower productivity and fewer hours worked during a flare week, compared to a non-flare week. There was a significant association between flares and detrimental impact upon work productivity (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.03, 1.12, p < 0.01). Flares were also significantly associated with an increased number of work hours missed due to IIM (OR 1.04, 95% CI 1.01, 1.08, p = 0.02) P156 Table 1:- Summary employment parameters compared between flare and non-flare weeksEmployment parameterAnswer formatWhole study period (159 weeks)Flare weeks (60 weeks)Non-flare weeks (99 weeks)p-value*Number of weeks’ work productivity affected by IIM (%)Dichotomous - “yes”, “no”54 (34.0)33 (55.0)21 (21.2)<0.01Mean effect of IIM upon work productivity (SD)Visual analogue scale - “Myositis had no effect on work" (0);“Myositis completely prevented me from working” (100)29.8 (28.8)46.2 (33.3)19.9 (20.0)<0.01Mean number of scheduled work hours per week per participant (SD)Numerical33.2 (15.8)36.9 (19.33)31.0 (13.0)<0.01Mean number of hours worked per week per participant (SD)Numerical23.5 (15.1)18.86 (17.1)26.23 (13.2)<0.01Proportion of hours worked per week per participant / % (SD)Calculated by research team73.7 (38.7)55.9 (43.2)84.7 (31.1)<0.01Mean number of hours of weekly work missed due to IIM per participant (SD)Numerical6.6 (16.6)14.9 (23.4)1.5 (6.6)<0.01Proportion of hours of weekly work missed due to IIM per participant / % (SD)Calculated by research team12.7% (29.5)29.2 (41.1)2.6 (10.0)<0.01SD = standard deviation *Categorical variables were compared using the Chi-squared test and continuous variables compared using the student t-test. Conclusion Our study has demonstrated that IIM flares are significantly associated with detrimental impact upon employment ability. On average, patients lost 15 hours of work a week during a flare compared to less than 2 hours outside a flare. The economic and personal impact of flares highlights the need for research in this area, with the aim of allowing early identification and instigation of treatment and possible need for supported work. Smartphone based remote monitoring of flares and other pertinent variables could enhance digital consultations, which may become more common in the post COVID-19 setting. Disclosure J.C. Williams: None. A.G.S. Oldroyd: None. W.G. Dixon: None. H. Chinoy: None.

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.

Teleconsultation experience with the idiopathic inflammatory myopathies: a prospective observational cohort study during the COVID-19 pandemic.

Teleconsultation has assumed a central role in the management of chronic and disabling rheumatic diseases, such as the idiopathic inflammatory myopathies (IIM), during COVID-19. However, the feasibility, challenges encountered, and outcomes remain largely unexplored. Here, we describe our teleconsultation experience in a prospectively followed cohort of adult and juvenile IIM. 250 IIM enrolled into the MyoCite cohort (2017-ongoing) were offered the option of audio/visual teleconsultation using WhatsApp during the nationwide lockdown. Clinical outcomes (major/minor relapse) and prescription changes were compared between IIM subsets. Socio-demographic and clinico-serological characteristics of those who sought teleconsultation were compared with those who did not. 151 teleconsultations were sought over a 93 day period by 71 (52.2%) of 136 IIM (median age 38 years, F:M 4.5:1). Nearly one-third (38%) consulted on an emergency basis, with voice consultations being the primary medium of communication. Over a quarter (26.8%) reported relapse (15.5% minor, 11.3% major), these being more common in JDM [71.4%, OR 8.9 (1.5–51)] as compared with adult IIM, but similar across various antibody-based IIM subtypes. Patients who relapsed required more consultations [2(2–3) vs 1(1–2), p 0.009]. The demographic and socioeconomic profile of the patients seeking consultation (n = 71) was not different from those who did not (n = 65). Voice-based teleconsultations may be useful to diagnose and manage relapses in IIM during the pandemic. Patient education for meticulous and timely reporting may be improve care, and larger multicentre studies may identify subsets of IIM that require greater care and early tele-triage for effective management of the condition.

Cardiac involvement in inflammatory myopathies and inherited muscle diseases.

To examine recent developments relating to cardiac involvement in the adult idiopathic inflammatory myopathies (IIM) and those inherited muscle diseases which may present in adulthood and mimic IIM. Cardiac involvement is a common feature of IIM and inherited muscle diseases. Frequency according to disease subtype varies, with serotype having particular influence in IIM, and genotype in the inherited muscle diseases. Innovative techniques for examining cardiac function have been investigated further, including speckle-tracking echocardiography and cardiac magnetic resonance tomography. The present work has highlighted a likely underestimate of the burden of cardiac disease to date. The complex relationship between IIM, atherosclerosis, and traditional cardiovascular risk factors has been further elucidated. Consensus recommendations for managing patients with inherited muscle diseases and prominent cardiac involvement have been recently published. In addition to supportive care, disease modifying treatments are increasingly becoming available for inherited muscle diseases which may also improve cardiac outcomes. Cardiac involvement is associated with significant morbidity and mortality. We suggest having a low threshold for considering the possibility of cardiac involvement in all patients with muscle disease.

Patient-Reported Outcomes in Adult Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIM) have considerable impact on patient symptoms and quality of life. We have reviewed the evolution of patient-centered care and use of patient-reported outcome measures (PROMs) for adults with IIM. Use of PROMs in myositis care and research is limited, although the importance of incorporation into routine practice and trials has become increasingly recognized. Several key domains/measures have been identified including the patient global assessment of disease activity, physical function as measured by the health assessment questionnaire-disability index (HAQ-DI), Short Form Health Survey-36 (SF-36), or the Patient-Reported Outcome Measurement Information System ® (PROMIS®) in adult IIM. Data are limited for these instruments concerning their reliability, content and construct validity, and responsiveness. Incorporation of the patient perspective into clinical care and research may be used to address the unmet/unaddressed needs of the patient living with myositis. Several ongoing projects aim to bring validated PROMs to the IIM community.

Hemophagocytic Lymphohistiocytosis: Prevalence, Risk Factors, Outcome, and Outcome-related Factors in Adult Idiopathic Inflammatory Myopathies.

To clarify the prevalence, risk factors, outcome, and outcome-related factors of hemophagocytic lymphohistiocytosis (HLH) in patients with dermatomyositis (DM), polymyositis (PM), or clinically amyopathic dermatomyositis (CADM). Data of patients with DM, PM, or CADM who were admitted to the First Affiliated Hospital of Zhejiang University from February 2011 to February 2019 were retrospectively collected. Patients diagnosed with HLH constituted the case group. A 1:4 case-control study was performed to identify risk factors for HLH in patients with DM, PM, or CADM through comparison, univariate, and multivariate logistic regression analysis. Intragroup comparison was made among patients with HLH to identify factors influencing unfavorable short-term outcome. HLH was a rare (4.2%) but fatal (77.8%) complication in patients with DM, PM, or CADM. The retrospective case-control study revealed that higher on-admission disease activity (p = 0.008), acute exacerbation of interstitial lung disease (AE-ILD, p = 0.002), and infection (p = 0.002) were risk factors for complication of HLH in patients with DM, PM, or CADM. The following intragroup comparison showed that higher on-admission disease activity (p = 0.035) and diagnosis of CADM (p = 0.039) might influence the short-term outcome of patients with HLH. However, no risk factor was identified after false discovery rate correction. In this study, secondary HLH was a fatal complication, with higher on-admission disease activity, AE-ILD, and infection working as risk factors. The underlying role of infection and autoimmune abnormality in HLH in connective tissue disease was subsequently noted. Clinical factors influencing the short-term outcome of patients with secondary HLH require further study.

The diagnosis and classification of amyopathic dermatomyositis: a historical review and assessment ofexisting criteria.

Diagnostic criteria are used to identify a patient having a disease in a clinical setting, whereas classification criteria create a well-defined population for research purposes. The diagnosis and classification of amyopathic dermatomyositis (ADM) have not been recognized by most existing criteria for idiopathic inflammatory myopathies (IIMs). To address this, several criteria were proposed to define ADM either as a distinct disease entity or as a subset of the spectrum of IIMs. To discuss the diagnosis and classification of ADM and to assesses the available criteria in identifying cases of ADM and/or distinguishing it from dermatological mimickers such as lupus erythematosus. We conducted an extensive literature search using the PubMed database from June 2016 to August 2018, using the search terms 'amyopathic dermatomyositis', 'diagnosis' and 'classification'. The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, which are the only validated classification criteria for adult and juvenile IIM and their major subgroups, include three cutaneous items (Göttron sign, Göttron papules, heliotrope rash) to be able to classify ADM. This international and multispecialty effort is a huge step forward in the classification of skin-predominant disease in dermatomyositis. However, about 25% of the population with ADM do not meet two out of the three skin features and are misdiagnosed or classified as having a different disease entity, most commonly lupus erythematosus. These gaps rationalize the continuous assessment and improvement of existing criteria and/or the development of validated, separate and skin-focused criteria for DM.

OMERACT 2018 Modified Patient-reported Outcome Domain Core Set in the Life Impact Area for Adult Idiopathic Inflammatory Myopathies.

To present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018. Based on results from international focus groups and Delphi surveys, a draft core set was developed. Domains muscle symptoms, fatigue, level of physical activity, and pain reached ≥ 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018. We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections.

Increasing incidence of adult idiopathic inflammatory myopathies in the City of Salford, UK: a 10-year epidemiological study.

ObjectivesThe aim was to identify and characterize all incident adult cases of idiopathic inflammatory myopathies (IIM) between 1 January 2007 and 31 December 2016 in the City of Salford, UK.MethodsAdults first diagnosed with IIM within the study period were identified by: a Salford Royal NHS Foundation Trust (SRFT) inpatient episode IIM-specific ICD-10 coding search; all new patient appointments to SRFT neuromuscular outpatient clinics; and all Salford residents enrolled within the UKMYONET study. All patients with definite IIM by the 2017 EULAR/ACR classification criteria were included, as were probable cases if consensus expert opinion agreed. Cases were excluded if <18 years of age at disease onset, if they did not meet probable criteria or when probable but expert opinion concluded a non-IIM diagnosis.ResultsThe multimodal case ascertainment identified 1156 cases which, after review and application of exclusion criteria, resulted in 32 incident cases during the study period. Twenty-three of 32 were female, with a mean age of 58.1 years. The mean incidence of adult IIM was 17.6/1 000 000 person years, and higher for females than for males (25.2 vs 10.0/1 000 000 person years, respectively). A significant incidence increase over time was apparent (13.6 vs 21.4/1 000 000 person years; P = 0.032). Using EULAR/ACR classification criteria, the largest IIM subtype (21/32) was PM, followed by DM (8/32), IBM (2/32) and amyopathic DM (1/32). Expert opinion subtype differed from EULAR/ACR classification criteria in 19/32 cases.ConclusionThe incidence of adult IIM in Salford is 17.6/1 000 000 person years, higher in females, and is increasing over time. Disagreement exists between EULAR/ACR-derived and expert opinion-derived IIM subtype assignments.

Cardiopulmonary factors affecting 6-min walk distance in patients with idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies involve skeletal muscles and can be associated with interstitial lung disease and/or heart dysfunction, which may reduce exercise capacity. We aimed to clarify cardiopulmonary factors affecting the 6-min walk distance in patients who were able to walk without leg pain or fatigue. Twenty-three patients with inactive adult idiopathic inflammatory myopathies, and 18 age- and gender-matched healthy controls were evaluated for hemodynamic responses using noninvasive impedance cardiography during the 6-min walk test. The patients were also examined by the pulmonary function test for forced vital capacity and diffusing capacity for carbon monoxide (DLCO), and by echocardiography for left ventricular ejection fraction and right ventricular systolic pressure. Interstitial lung disease was diagnosed in 19 patients using high-resolution computed tomography. There was no difference in 6-min walk distance or cardiac output after walking between the patients and healthy controls. However, stroke volume during the 6-min walk test was significantly lower in the patients than in healthy controls, suggesting malfunction in the heart. Moreover, the increased heart rate matched the cardiac output. Spearman’s correlation analysis demonstrated a correlation between 6-min walk distance and stroke volume, cardiac output after walking and DLCO, but not left ventricular ejection fraction or right ventricular systolic pressure, as this study lacked the patients with pulmonary hypertension. In conclusion, impaired DLCO due to interstitial lung disease was suggested to be a fundamental parameter affecting exercise capacity, in addition to heart involvement, in patients with idiopathic inflammatory myopathies.

Treatment of adult idiopathic inflammatory myopathies with conventional immunosuppressive drugs : Results of aretrospective study.

To gain information about the efficacy of immunosuppressive drugs as first-, second-, and third-line treatment of idiopathic inflammatory myopathies (IIM). 112 treatment cycles of 63patients with dermatomyositis (n = 23), polymyositis (n = 33), overlap syndromes (n = 4), and undifferentiated connective tissue diseases (n = 3) were analyzed by retrospective chart analysis. Data regarding muscle strength, muscle enzymes, treatment duration, and treatment discontinuation were collected. Azathioprine (38cycles) and methotrexate (MTX; 24cycles) were applied significantly longer than glucocorticoid monotherapy (9cycles; 25 ± 21, 26 ± 29 and 7 ± 4months, respectively; p < 0.05). MTX and azathioprine achieved asignificant reduction of serum creatine kinase (CK), with MTX showing more marked effects. Treatment cycles with immunosuppressants other than MTX or azathioprine (n = 22) or with combinations of immunosuppressive drugs (n = 19) were mostly applied as third-line therapy, indicating their application in more refractory cases. Significant improvement of muscle strength was confined to MTX and azathioprine and to the first-line treatment. 8% of MTX patients withdrew due to the lack of efficacy, compared with 29% of patients taking azathioprine and 6 of 9patients taking glucocorticoid monotherapy. In the 12patients with Jo-1 syndrome, MTX treatment was effective for alonger time than azathioprine (44 ± 21months vs. 27 ± 24months, p < 0.05). Our data confirm the effectiveness of MTX and azathioprine in the treatment of inflammatory myopathies and stress the importance of apotent first-line therapy.

O23 The incidence of adult idiopathic inflammatory myopathies at a UK specialist neuromuscular centre: a ten-year epidemiology study

O23 The incidence of adult idiopathic inflammatory myopathies at a UK specialist neuromuscular centre: a ten-year epidemiology study

Revisiting Pathological Classification Criteria for Adult Idiopathic Inflammatory Myopathies: In-Depth Analysis of Muscle Biopsies and Correlation Between Pathological Diagnosis and Clinical Manifestations.

The European Neuromuscular Centre (ENMC) pathological classification criteria of idiopathic inflammatory myopathies (IIMs) are debatable. The aim of this study was to explore their practicability and reproducibility. We conducted a retrospective analysis of 57 cases of IIMs excluding dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) by in-depth analysis of muscle biopsies and comparisons of the clinical characteristics among polymyositis (PM), non-specific myositis (NSM) and necrotizing autoimmune myopathy (NAM). In 57 non-DM/sIBM-IIM cases, 25 were classified as PM, 15 as NSM, and 17 as NAM. Among them, 51 underwent multilevel sectioning examination of biopsies, with pathological changes at different levels warranting diagnostic rectification in 11 patients (21.57%): 4 PM were reclassified as NSM, and 7 NSM as NAM. Applying atypical CD8+ T cells surrounding non-necrotic muscle fibers resulted in diagnostic rectification from NSM to PM in 2 patients; using 20 T cells (instead of 10) as the threshold for the perivascular infiltration led to diagnostic rectification from NSM to NAM in 9 patients. There were no differences in disease duration or treatment outcomes among the subgroups. The strict pathological criteria to distinguish non-DM/sIBM-IIMs are of limited practicability and reproducibility, and may be of limited clinical significance.