Onset Of Idiopathic Inflammatory Myopathies Research Articles

Novel B cell subsets as potential biomarkers in Idiopathic Inflammatory Myopathies: insights into disease pathogenesis and disease activity.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double negative subsets, as well as an expansion of the naïve compartment relative to healthy controls, that contribute to defining disease-associated B cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathies onset or development.

Genetic Influences in Cancer-Associated Myositis.

Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.

Prevalence of avascular necrosis in idiopathic inflammatory myopathies: a single-centre experience.

To assess the prevalence of avascular necrosis (AVN) in a large cohort of patients with idiopathic inflammatory myopathies (IIM) and define the major associated risk factors. We retrospectively reviewed the electronic medical records of all patients with a definitive diagnosis of IIM enrolled in our registry between 2003 and 2017, and followed until 2020. Pertinent demographic, clinical, serologic and imaging data were collected. A matched group of patients without AVN was then selected for comparison. A total of 1680 patients were diagnosed with IIM. Fifty-one patients developed AVN, with an overall prevalence of 3%. Musculoskeletal MRI was available for 1085 patients and AVN was present in 46 patients (43 lower extremities and 3 upper extremities MRI studies), with a relative prevalence of 4.2%. Most patients with AVN were Caucasian females (57%) with a mean (s.d.) age at diagnosis of 44.5 (12.4) years. Sixty-one percent had DM and 29% had PM. The median time from onset of IIM to diagnosis of AVN was 46 months. The hip joint was most commonly involved in 76% of cases, followed by the knee joint in 15% and shoulder joint in 9%. Some 81% of patients were asymptomatic. Established risk factors for AVN were not found to be associated with the development of AVN in IIM patients. Although mostly asymptomatic and incidental, the overall prevalence of AVN in IIM was 3% and the prevalence by MRI was 4.2%. None of the established risk factors was found to be associated with AVN development.

AB0610 SEASONAL VARIATION IN IDIOPATHIC INFLAMMATORY MYOPATHIES INCIDENCE AND PRESENTATION: A RETROSPECTIVE STUDY IN BEIJING AND HONG KONG

Background:Seasonal patterns of disease onset and severity in idiopathic inflammatory myopathies (IIMs) as a whole are conflicting [1-3]. In recent years, over 10 myositis-specific antibodies (MSAs) have been identified. They are able to divide patients into homogenous subgroups and inform on prognosis [4].Objectives:The objective of the study was to investigate the seasonal variation of onset of IIMs characterised serologically.Methods:This was a multi-centred retrospective observational study. Consecutive Chinese patients with IIMs admitted to the rheumatology wards of the participating major regional hospitals in Beijing and Hong Kong from July 2013 to June 2018 were recruited. The diagnosis of IIMs was based on the Bohan and Peter’s criteria with definite or probable cases being included [5]. Patients with clinically amyopathic disease must have the typical Gottron’s papules or heliotrope rash as determined by rheumatologists or dermatologists, and with no symptoms or signs of muscle involvement according to Sontheimer [6]. Patients with juvenile myositis, inclusion body myositis, cancer-associated myositis and myositis associated with other connective tissue disease were excluded. A commercial line blot immunoassay kit (EUROLINE) was used to detect the MSAs.Results:All together 495 patients were studied. The mean age of the patients at disease onset was 48.1 years (S.D. 13.3). There was a female predominance (68.3%). The subgroups of IIMs were: dermatomyositis (61.0%), polymyositis (21.8%), clinically amyopathic dermatomyositis (12.9%), immune mediated necrotising myopathy (3.8%) and nonspecific myositis (0.4%). No particular seasonal pattern in disease onset was observed in IIM patients as a whole (Figure 1) or in any classical subgroups. However, significantly more patients with any one MSA had their disease started in the first half of the year (p=0.007) as shown in Figure 2. Patients with either anti-synthetase or anti-MDA5 antibodies, which are associated with interstitial lung disease, had more frequent disease onset from November to February, which might coincide with the local flu season. It was also found that MSA positivity was associated with infection of the patient (p=0.005). Further analyses showed that patients with MSAs which are typically associated with severe skin disease (MDA5, TIF1g, NXP2, SAE) had more hospitalisation from April to September where excessive sun exposure is expected. There were no major differences between the Beijing and Hong Kong subgroups.Conclusion:Apparent seasonal patterns were noticed in our ethno-serologically defined IIM patients. Certain environmental factors, particularly infection or UV exposure, could be potential triggers. Our findings could shed light on the identification of etiologic factors and enhance our understanding of disease pathogenesis.

Temporal relationship between idiopathic inflammatory myopathies and malignancies and its mortality: a nationwide population-based study.

To examine the temporal relationship between malignancies and idiopathic inflammatory myopathies (IIMs) and its impact on mortality. A retrospective cohort for IIM patients was conducted using the Korean National Health Insurance Service databases. We observed more than 5years before and after the diagnosis of IIM (2002~2016) to identify IIM patients who developed any malignancy and classified these patients into two groups: the cancer-associated myositis (CAM) group, who developed malignancy within 3years before or after the diagnosis of IIM and the cancer-not-associated myositis (CNAM) group, who developed malignancy beyond 3years of IIM onset. The survival rates of the two groups were compared. We identified 1072 incident cases of IIM between 2007 and 2011. A total 225 patients of these patients were diagnosed with malignancy. The development of malignancy was frequent within 1year before and after the time of IIM diagnosis. The common sites of malignancies in the CAM group differed from those in the CNAM group: the lung, hematologic malignancy, and the liver were common in both groups, but thyroid and oropharynx followed them in CAM while prostate, stomach, breast, and thyroid followed them in CNAM. CAM patient mortality was worse compared with CNAM patients (log-rank test, p < 0.01). Among IIM patients with malignancy, common sites of malignancy were different between the CAM and CNAM groups, and patients with CAM had poor prognosis compared with CNAM patients. Key Points • The malignancies commonly occurred in incident idiopathic inflammatory myopathy (IIM) patients, especially within 1year before and after the initial IIM diagnosis. • Patients with malignancy had poor survival compared with patients without malignancy. • Among the IIM patients with malignancy, patients who developed malignancy within 3years of IIM diagnosis (cancer-associated myositis, or CAM, group) showed higher mortality than cancer-not-associated myositis, CNAM group. • We also found that the common types of malignancy were different between the CAM and CNAM groups.

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.

Inflammatory lung disease a potential risk factor for onset of idiopathic inflammatory myopathies: results from a pilot study

ObjectivesTo assess the association between inflammatory lung disease and the risk of developing idiopathic inflammatory myopathies.MethodsA population-based case–control study was conducted. Adult myositis cases, identified from the Swedish inpatient registry...

Pulmonary arterial hypertension in idiopathic inflammatory myopathies

Occurrence of pulmonary arterial hypertension (PAH) in idiopathic inflammatory myopathies (IIMs) without extensive interstitial lung disease (ILD) has rarely been described in the medical literature. This study aimed to report all cases with association of PAH and IIM in the French Pulmonary Hypertension (PH) Registry, to identify IIM features associated with the presence of PAH, and to describe treatment modalities of these patients.All cases of IIM-PAH were retrieved from the French PH Registry, which gathers PH patients prospectively enrolled by 27 referral hospital centers across France. Patients were excluded if they had an extensive ILD or overlap syndrome. Characteristics of IIM-PAH patients were compared with a control group of IIM patients without PH.Among the 5223 PH patients in the Registry, 34 had a diagnosis of IIM. Among them, 3 IIM-PAH patients (2 females and 1 male) had no evidence of extensive ILD or overlap syndrome, and were included in this study. In these 3 patients, dermatomyositis (DM) was the only identified IIM. One patient had autoantibodies classically associated with IIM (anti-Ku). PAH had always developed after IIM onset, was severe in all cases, and led to a marked functional impairment.By pooling our cases with 6 patients previously reported in the literature, and comparing them with a control cohort of 35 IIM patients without PH, we identify several IIM characteristics possibly associated with PAH occurrence, including DM subtype (78% vs 46%; P = 0.02), skin involvement (P = 0.04), anti-SSA antibodies (P = 0.05), and peripheral microangiopathy (P = 0.06).Overall, IIM-PAH patients were managed by corticosteroids and/or immunosuppressants, either alone or combined with PAH therapy. Patients did not seem to respond to IIM treatment alone.Our study reports for the first time the rare but possible association of PAH and IIM in a large prospective PH Registry. In that setting, PAH seems associated with DM, skin involvement, peripheral microangiopathy, and anti-SSA positivity. The best therapeutic strategy for IIM-PAH remains to be defined.

Dermatomyositis and Polymyositis in the Intensive Care Unit: A Single-Center Retrospective Cohort Study of 102 Patients.

IntroductionPatients with idiopathic inflammatory myopathies (IIMs) are sometimes complicated with life-threatening conditions requiring intensive care unit (ICU) admission. In the past, owing to the low incidence of IIM, little was known about such patients. Our aim was to investigate the clinical features and outcomes of these patients and identify their risk factors for mortality.MethodsA retrospective study was performed of IIM patients admitted over an 8-year period to the medical ICU of a tertiary referral center in China. We collected data regarding demographic features, IIM-related clinical characteristics, reasons for admission, organ dysfunction, and outcomes. Independent predictors of ICU mortality were identified through multivariate logistic regression analysis.ResultsOf the 102 patients in our cohort, polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM) accounted for 23.5%, 64.7%, and 11.7% respectively. The median duration from the onset of IIM to ICU admission was 4.3 months (interquartile range [IQR], 2.6–9.4 months). Reasons for ICU admission were infection alone (39.2%), acute exacerbation of IIM alone (27.5%), the coexistence of both (27.5%), or other reasons (5.8%). Pneumonia accounted for 97% of the infections; 63.2% of infections with documented pathogens were caused by opportunistic agents. Rapid progressive interstitial lung disease (RP-ILD) was responsible for 87.5% of acute exacerbation of IIM. The median Acute Physiology and Chronic Health Evaluation II (APACHE II) score on ICU day 1 was 17 (IQR 14–20). On ICU admission, acute respiratory failure (ARF) was the most common type (80.4%) of organ failure. The mortality rate in the ICU was 79.4%. Factors associated with increased ICU mortality included a diagnosis of DM (including CADM), a high APACHE II score, the presence of ARF, a decreased PaO2/FiO2 ratio, and a low lymphocyte count at the time of ICU admission.ConclusionsThe outcome of IIM patients admitted to the ICU was extremely poor. A diagnosis of DM/CADM, the presence and severity of ARF, and the lymphocyte counts at ICU admission were shown to be valuable for predicting outcome. Opportunistic infections and rapidly progressive interstitial lung disease warrant concern in treating these patients.

High Frequencies and co-existing of myositis-specific autoantibodies in patients with idiopathic inflammatory myopathies overlapped to rheumatoid arthritis

A small proportion of patients with rheumatoid arthritis (RA) develop idiopathic inflammatory myopathies (IIM); however, the clinical and immunological characteristics of these patients have not been elucidated. In the present study, we evaluate the frequency of autoantibodies and the accompanying clinical features in patients with IIM overlapped to RA (IIM-RA) and in patients with IIM without RA. Twelve patients with IIM-RA were selected from 142 patients with IIM who were admitted to our hospital. Clinical and laboratory data, including autoantibody test results, were collected from patient medical records. Myositis-specific antibodies (MSAs) were analyzed by immunoprecipitation. Clinically, patients with IIM-RA were more likely to be male, to have polymyositis, and to be older at the time of IIM onset than patients with IIM without RA. Patients with IIM-RA had been treated for 2-25 years prior to the onset of IIM with more than two disease-modifying antirheumatic drugs (DMARDs). Patients with IIM-RA had a high frequency (75.0%) of positivity for MSAs, including anti-Jo-1, anti-PL-7, anti-PL-12, or anti-signal recognition particle (SRP) antibodies; anti-Jo-1 antibody was detected in 4 patients (33.3%). In addition, 2 out of 12 patients with IIM-RA were concurrently positive for two different MSAs, anti-Jo-1, and anti-PL-7 antibodies. In 3 other patients with IIM-RA, anti-Jo-1 antibody, or anti-PL-7 antibody was detected in serum samples collected 6-18 months prior to development of myositis. High frequency and coexistence of MSAs were detected in patients with IIM-RA. MSAs detected in patients with RA even without symptoms of myositis may indicate possible future development of myositis.

Aspectos da saúde reprodutiva em homens com miopatia inflamatória idiopática: um estudo multicêntrico

OBJETIVO: Avaliar a saude reprodutiva de homens com miopatia inflamatoria idiopatica (MII) e compara-la com controles saudaveis. METODOS: Vinte e cinco pacientes com MII (dermatomiosite ou polimiosite) foram avaliados com relacao aos dados demograficos, exame urologico (incluindo parâmetros pubertarios e funcao sexual/eretil), ultrassonografia testicular, perfil hormonal, analise seminal, caracteristicas clinicas e tratamento. O grupo controle incluiu 25 homens saudaveis. RESULTADOS: A mediana da idade atual foi similar nos pacientes com MII e controles (24 versus 27 anos, P = 0,566). As frequencias de atividade sexual, numero de parceiras com gestacoes espontâneas apos inicio da doenca e uso de preservativo masculino foram significativamente menores nos pacientes com MII versus controles (60% versus 96%, P = 0,004; 16% versus 60%, P = 0,0031; 40% versus 76%, P = 0,021; respectivamente). Alem disso, as frequencias de atrofia testicular (28% versus 4%, P = 0,049), niveis elevados de FSH e/ou LH (25% versus 0%, P = 0,05) e alteracoes dos espermatozoides (40% versus 0%, P = 0,0006) foram estatisticamente maiores nos pacientes com MII quando comparados aos controles. As medianas das idades de inicio da doenca e atual foram estatisticamente maiores nos pacientes com MII que apresentaram disfuncao sexual/eretil versus sem disfuncao (41 versus 12,5 anos, P = 0,014; 46 versus 21 anos, P = 0,027; respectivamente). Entretanto, comparando-se, pacientes com disfuncao sexual/eretil e sem disfuncao, nenhuma diferenca foi evidenciada em relacao a idade da espermarca, parâmetros de funcao gonadal, atividade da doenca, enzimas musculares e tratamento. CONCLUSAO: Este foi o primeiro estudo que identificou alteracoes da saude reprodutiva e disfuncao gonadal em homens com MII. Reumatologistas devem discutir problemas sexuais e orientar contracepcao aos seus pacientes.

Seasonal influence on the onset of idiopathic inflammatory myopathies in serologically defined groups

To assess possible seasonal patterns in the onset of polymyositis (PM) and dermatomyositis (DM). The study group comprised 503 patients who met the criteria for probable or definite PM or DM and for whom detailed data on the time of myositis onset were available. Statistical analyses were performed using a Poisson model that assessed associations of ethnicity, sex, autoantibody presence, and month of onset of muscle weakness. There were no significant seasonal patterns of disease onset in myositis patients as a whole or in the total PM or DM populations. Significant seasonal associations were present, however, in the serologically defined groups. In the 131 patients with antisynthetase autoantibodies who were categorized as non-black, myositis onset peaked in March-April (P = 0.03). Among the antisynthetase-positive patients, the association was predominantly in those with PM (n = 85; P = 0.05) and in men (n = 51; P = 0.042). Patients with anti-signal recognition particle autoantibodies, however, did not have a significant seasonal onset, which is in contrast to previous findings. Patients without myositis-specific autoantibodies showed a significant peak in summer, with myositis onset in June-July (n = 252; P = 0.03); this seasonal association was significant in women (n = 182; P = 0.005), whereas there was no seasonal pattern in men (P = 0.9). These findings, in conjunction with other data, suggest that diverse environmental agents, acting upon different immunogenetic backgrounds, result in distinct immune responses and clinical syndromes in the idiopathic inflammatory myopathies. Our results emphasize the importance of considering more homogeneous disease groups, based on clinicopathologic features, immune responses, ethnicity, and sex, when attempting to decipher the pathogeneses of autoimmune disorders.