Analysis of risk factors of interstitial lung disease and mortality rates in Chinese patients with idiopathic inflammatory myopathy.

AIM: To investigate the risk factors for interstitial lung disease (ILD) and prognosis in patients with idiopathic inflammatory myopathy (IIM). METHODS: A retrospective longitudinal study was performed in patients diagnosed with IIM between January 2012 and December 2018. RESULTS: The study cohort included 91 men and 195 women who were classified as having dermatomyositis (DM, n = 183), polymyositis (PM, n = 77), or clinical amyopathic DM (CADM, n = 26). ILD was identified in 46.5% (n = 133) of patients with IIM. The independent risk factors for ILD were age at disease onset, presence of anti-Ro-52 antibody, Gottron's papules, elevated serum immunoglobulin M levels and hypoalbuminemia. Older age at disease onset, ILD, malignancy, and increased serum aspartate aminotransferase and neutrophil-to-lymphocyte ratio (NLR) were identified as the independent predictors for mortality, whereas elevated serum albumin level was associated with a better prognosis. A total of 73 deaths (25.5%) occurred after a median follow-up time of 33 months. Infection (49.3%) was the leading cause of death. In the overall cohort, the 1-year, 5-year and cumulative survival rates were 83.2%, 74.2% and 69.4%, respectively. The receiver operating characteristic curve indicated that the optimal cut-off value of NLR for predicting death in IIM was 6.11. CONCLUSION: IIM patients have a poor prognosis with substantial mortality, especially in patients who have older age at onset, ILD, malignancy and higher NLR. Close monitoring and aggressive therapies are required in patients having poor predictive factors.

High early mortality in idiopathic inflammatory myopathies: results from the inception cohort at a tertiary care centre in northern India.

OBJECTIVES: We determined the mortality along with the proportion of disease related adverse events measured individually and by a composite adverse outcome (devised by including deaths, disability, relapses and minimal response) and its predictors in an inception cohort of idiopathic inflammatory myopathies (IIM). METHODS: IIM from the MyoCite cohort (December 2017-19) were reviewed for early outcomes (mortality, IMACS core set). Comparisons were drawn between those meeting the primary and secondary outcomes. RESULTS: Of 70 patients [62 adults, M:F = 1:4.8, age 43 (28.5-51) and eight children, M:F = 1:1, 14.5 (8.8-16)], dermatomyositis (DM) was the most common subset [29 (41.4%) adults; 7 (87.5%) children]. Over 10 (4-15) months, 10 (15.2%) died and four polymyositis were reclassified. One-year survival for anti-melanoma differentiation antigen 5 (MDA5) subtype was 30% and anti-synthetase syndrome (ARS) subtype was 75%. Overall, lower respiratory infections were the most common cause of death [n = 3 (30%)] followed closely by malignancy and rapidly progressive interstitial lung disease (RP-ILD). Amongst survivors, a major IMACS response was recorded in 54.5% adults and 100% children. Thirty per cent suffered from moderate to severe disability and 16.7% experienced relapses. Overall, two-thirds accrued the composite adverse outcome. On multivariate analysis, older age and anti-MDA5 predicted mortality. Arthritis, rash and positive ANA reduced and anti-MDA5 increased the risk for the composite adverse outcome. CONCLUSION: Indian patients with IIM suffer high early mortality attributable to infection, cancer and RP-ILD, calling for high vigilance post diagnosis. Autoantibodies and certain clinical features identify risk for composite adverse outcomes.

Prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease: a retrospective study of 679 adult cases.

OBJECTIVES: Few studies have investigated the prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) across different clinical/serological phenotypes. METHODS: We conducted a retrospective analysis of patients diagnosed with IIM between January 2012 and December 2017. RESULTS: Of the 760 IIM cases registered, 679 adult cases were included in this study. ILD was present in 508 cases, and the presence of ILD in the clinically amyopathic DM, DM and PM groups was 92.7, 73.6 and 55.1%, respectively (P < 0.01). The prevalence of ILD in the anti-synthetase antibody (ASA)+-IIM group was higher than that in ASA--IIM group (95.2 vs 72.4%, P < 0.01); no such difference was found between the anti-histidyl-tRNA synthetase (Jo-1)+-IIM and Jo-1-ASA+-IIM groups (93.0 vs 98.5%, P > 0.05). The prevalence of ILD in the melanoma differentiation-associated protein-5 (MDA-5)+-IIM group was higher than that in MDA-5--IIM group (97.8 vs 72.1%, P < 0.01). Among adults with IIM, men with concurrent ILD, who were older than 50 years, were most likely to die. No significant difference was found in the all-cause mortality rates between DM-ILD and clinically amyopathic DM-ILD groups (33.3 vs 23%, P > 0.05), although both were higher than that in PM group (13.2%, P = 0.01 and P < 0.05, respectively). No difference was found in the all-cause mortality rates between MDA5-ASA--IM-ILD and MDA5-ASA+-IM-ILD groups (17.2 vs 12.8%, P > 0.05), and both were lower than that in MDA5+ASA--IM-ILD group (33.7%, P < 0.05). CONCLUSION: The prevalence of ILD in IIM and the prognosis of IIM-ILD patients may vary depending on the statuses of the ASA and MDA-5 antibodies.

Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors.

OBJECTIVE: To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes. METHODS: We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available. RESULTS: A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection. CONCLUSION: ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined.

Clinical Characteristics, Treatment, and Outcomes in Patients with Idiopathic Inflammatory Myopathy Concomitant with Heart Failure.

This study sought to evaluate clinical features, treatment patterns, and outcomes of patients with idiopathic inflammatory myopathy (IIM) complicated by heart failure (HF). Thirty-two patients with IIM-HF admitted to the Peking Union Medical College Hospital between January 1999 and January 2018 were retrospectively reviewed, including 14 patients with polymyositis, 11 with dermatomyositis, and 7 with overlap syndrome. Survivors and no-survivors were compared on clinical characteristics and treatment. Although systemic symptoms were variable, all patients presented with elevated troponin I. Rapid atrial arrhythmia was the most frequent arrhythmia. Systolic dysfunction and restrictive diastolic dysfunction were typical presentations in echocardiography. Twenty-nine patients were followed up for a median of 2.8 years (0.1 month to 11 years). We recorded 13 deaths of cardiogenic cause, 1 of serious IIM, and 3 of infective complications. The median survival time from diagnosis of IIM-HF to all-cause mortality was 8.4 months (range from 1 month to 5 years). Both all-cause deaths and cardiogenic deaths were more reported in the methotrexate-alone group than in the combination therapy group (6/7 versus 3/10, P = 0.050; 5/6 versus 2/9, P = 0.041). Combination therapy including methotrexate (HR = 0.188, 95%CI 0.040-0.871, P = 0.033) and taking ß-receptor blockers (HR = 0.249, 95%CI 0.086-0.719, P = 0.010) was associated with reduced risk of all-cause deaths. In conclusion, elevated troponin I, atrial arrhythmia, and systolic and restrictive diastolic dysfunction are typical characteristics of IIM-HF. Combined immunosuppression that includes methotrexate and ß-receptor blockers seems to be important to improve survival.

Single Amino Acid Replacements in RocA Disrupt Protein-Protein Interactions To Alter the Molecular Pathogenesis of Group A Streptococcus.

Group A Streptococcus (GAS) is a human-specific pathogen and major cause of disease worldwide. The molecular pathogenesis of GAS, like many pathogens, is dependent on the coordinated expression of genes encoding different virulence factors. The control of virulence regulator/sensor (CovRS) two-component system is a major virulence regulator of GAS that has been extensively studied. More recent investigations have also involved regulator of Cov (RocA), a regulatory accessory protein to CovRS. RocA interacts, in some manner, with CovRS; however, the precise molecular mechanism is unknown. Here, we demonstrate that RocA is a membrane protein containing seven transmembrane helices with an extracytoplasmically located N terminus and cytoplasmically located C terminus. For the first time, we demonstrate that RocA directly interacts with itself (RocA) and CovS, but not CovR, in intact cells. Single amino acid replacements along the entire length of RocA disrupt RocA-RocA and RocA-CovS interactions to significantly alter the GAS virulence phenotype as defined by secreted virulence factor activity in vitro and tissue destruction and mortality in vivo In summary, we show that single amino acid replacements in a regulatory accessory protein can affect protein-protein interactions to significantly alter the virulence of a major human pathogen.

Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities.

BACKGROUND: In addition to restoring anti-tumor immune responses, immune checkpoint inhibitors (ICI) may also induce immune-related adverse events (irAE) that can affect any organ. We aim to determine the spectrum, timing, clinical features, and fatalities of rheumatic and musculoskeletal immune-related adverse events (RMS-irAE) associated with ICI. PATIENTS METHODS: We performed an observational, retrospective, pharmacovigilance study using the World Health Organization international pharmacovigilance database, VigiBase, from inception to January 2019. RMS-irAE reporting rate on ICI versus full database was performed using disproportionality analysis with computation of reporting-odds-ratios (ROR) and a Bayesian disproportional estimate (information component, IC). IC025 (lower end of the IC 95% credibility interval) >0 is deemed significant. RESULTS: We identified 1288 RMS-irAE significantly associated with ICI: polymyalgia rheumatica (n = 76, ROR = 14.6 [11.6-18.4], IC025 = 3.34), sarcoidosis (n = 94; ROR = 9.6 [7.9-11.9]; IC025 = 2.85), Sjogren's syndrome (n = 49; ROR = 6.9 [5.2-9.2]; IC025 = 2.24), myositis (n = 465; ROR = 4.9 [4.5-5.4]; IC025 = 2.12), arthritis (n = 606; ROR = 1.4 [1.3-1.5]; IC025 = 0.34) and scleroderma (n = 17; ROR = 2.0 [1.2-3.2]; IC025 = 0.17). Arthritis, myositis, and Sjogren's syndrome were over-reported in patients treated with ICI combination versus those treated with ICI monotherapy (ROR = 1.6-2.9, p < .05) and more frequently reported on anti-PD1/PDL1 monotherapy vs. anti-CTLA4 monotherapy (2.1-4.4, p < .05). Median time to onset occurred early for myositis (31 days [19.2-57.8]) and was the most delayed for scleroderma (395 days [323.8-457.2], p < .0001). The fatality rate for RMS-irAE ranged from 24% for myositis (n = 106/441) (up to 56.7% with concurrent myocarditis) to [0-6.7%] for other RMS-irAE (p < .0001). CONCLUSIONS: Clinicians should be aware of the spectrum of RMS-irAE. Myositis can be particularly life-threatening, particularly when associated with myocarditis.

Worldwide trends in all-cause mortality of auto-immune systemic diseases between 2001 and 2014.

AIM: To describe changes in the 2001-2014 mortality of 6 autoimmune systemic diseases (AISDs), namely Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), Idiopathic Inflammatory Myopathies (IIM), Sjögren's Syndrome (SS), Mixed Connective Tissue Disease (MCTD) and ANCA-associated vasculitis (AAV) at the country-, continent-, and world-levels. METHODS: Mortality data were retrieved from the World Health Organization (WHO) mortality database for each disease, based on ICD-10 codes. We computed age-standardized mortality rate (ASMR) as the estimated number of deaths per million inhabitants and its 95% confidence interval (95%CI). The association between gender, geographical areas and disease-specific mortality was analyzed using multivariate Poisson regression. The 2001-2014 temporal trends were analyzed using Jointpoint software. RESULTS: In 2014, the worldwide ASMR for SLE was 2.68 (95%CI: 2.62-2.75) deaths/millions inhabitants, 1.46 (1.42-1.51) for SSc, 0.47 (0.44-0.49) for IIM, 0.17 (0.15-0.18) for SS, 0.11 (0.10-0.13) for MCTD and 0.53 (0.50-0.56) for AAV, with ASMRs generally lower in Europe than in North America, Latin America and Asia. Between 2001 and 2014, the worldwide ASMR decreased significantly for SSc (-0.71%/year), IIM (-1.65%/year) and AAV (-1.01%/year; p < .001 for all) and increased for SS (+1.53%/year, p = .01). The worldwide ASMR of SLE decreased significantly between 2001 and 2003 (-6.37%, p < .05) before increasing slightly between 2004 and 2014 (+0.58%, p < .01). CONCLUSIONS: We observed a strong heterogeneity of standardized mortality rates across all countries analyzed for 6 autoimmune diseases. Those results further highlight the impact of world-wide inequities and major gaps in access to care and strategies for diagnosis and management of rare diseases, a crucial finding for world-wide physicians, patient associations and policy makers.

Clinical characteristics of cancer-associated myositis complicated by interstitial lung disease: a large-scale multicentre cohort study.

OBJECTIVE: To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). METHODS: This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. RESULTS: CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation-associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). CONCLUSION: Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.

Long-term treatment with human immunoglobulin for antisynthetase syndrome-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease-associated antisynthetase syndrome (AS-ILD) carries significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are the mainstay of treatment. Human immunoglobulin (IVIg), an immunomodulator without immunosuppressive properties, is effective in myositis but the evidence supporting its use in ILD is scarce. OBJECTIVE: To describe clinical outcomes of AS-ILD patients receiving IVIg. METHODS: Retrospective analysis of AS-ILD patients. Linear mixed models using restricted maximum likelihood estimation was used to estimate the change in lung function and corticosteroid dose over time. RESULTS: Data from 17 patients was analyzed. Median follow-up was 24.6 months. Fourteen patients had refractory disease. The mean percent-predicted forced vital capacity (FVC%) (p = 0.048) and percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (p = 0.0223) increased over time, while the mean prednisone dose (p < 0.001) decreased over time. Seven patients achieved a >10% increase in FVC%, including two who used IVIg as initial treatment. Five patients showed a >10% increase in DLCO% and TLC%. Nine (53%) patients experienced side effects. CONCLUSIONS: IVIg may be a useful complementary therapy in active progressive AS-ILD but is associated with potential side effects. Fssssurther investigation is required to determine the value of IVIg as an initial treatment in AS-ILD.

The ILD-GAP risk prediction model performs poorly in myositis-associated interstitial lung disease.

PURPOSE: Myositis-associated interstitial lung disease (MA-ILD) is associated with increased mortality, but no prognostic model exists in this population. The ILD-GAP index was developed to predict mortality risk across all subtypes of chronic ILD. The purpose of this study was to validate the ILD-GAP risk prediction model in patients with MA-ILD. PROCEDURES: We completed a retrospective cross-sectional study of patients enrolled in the Johns Hopkins Myositis Center database between 2006 and 2017. Cumulative mortality rates were estimated using the Kaplan-Meier test. Model calibration was determined by using standardized mortality ratios of observed versus expected deaths. MAIN FINDINGS: 179 participants with MA-ILD were included. The mean baseline percent predicted forced vital capacity was 65.2 ±â€¯20.6%, forced expiratory volume in the first second 65.4 ±â€¯20.4%, and carbon monoxide diffusing capacity 61.6 ±â€¯20.0%. Thirty-two participants died (17.9%). The ILD-GAP model had poor discriminative performance and calibration. CONCLUSIONS: The ILD-GAP risk prediction model is a poor predictor of mortality among individuals with MA-ILD. The identification of a better predictive model for MA-ILD is needed to help guide care in this patient population.

Opportunistic infections in patients with idiopathic inflammatory myopathies.

AIM: To describe the prevalence, clinical characteristics and risk factors of opportunistic infection (OI) in a cohort of patients with inflammatory myopathies, and compare mortality rates between those with and without OIs. METHODS: In total, 204 patients from our myositis cohort were reviewed to identify patients who had experienced an OI during the period 1986-2014. The patients' clinical characteristics, treatments received, and outcomes were systematically recorded. Disease activity at the OI diagnosis and the cumulative doses of immunosuppressive drugs were analyzed, as well as the specific pathogens involved and affected organs. RESULTS: The prevalence of OI in the total cohort was 6.4%: viruses, 44.4% (varicella-zoster virus, cytomegalovirus); bacteria, 22.2% (Salmonella sp., Mycobacterium tuberculosis, M. chelonae); fungi, 16.7% (Candida albicans, Pneumocystis jirovecii); and parasites, 16.7% (Toxoplasmosis gondii, Leishmania spp.). Lung and skin/soft tissues were the organs most commonly affected (27.8%). Overall, 55.6% of OIs developed during the first year after the myositis diagnosis and OI was significantly associated with administration of high-dose glucocorticoids (P = 0.0148). Fever at onset of myositis (P = 0.0317), biological therapy (P < 0.001) and sequential administration of four or more immunosuppressive agents during myositis evolution (P = 0.0032) were significantly associated with OI. All-cause mortality in the OI group was 3.69 deaths per 100 patients/year versus 3.40 in the remainder of the cohort (P = 0.996). CONCLUSIONS: The prevalence of OI was 6.4% in our myositis cohort, higher than the rest of the inpatients of our hospital (1.7%; P < 0.01). High-dose glucocorticoids at disease onset and severe immunosuppression are the main factors implicated.

Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study.

Patients with idiopathic inflammatory myopathies (IIMs) suffer an increased burden of comorbidities, but data on mortality in recently diagnosed IIM are conflicting. Also, little is known when, if ever, in relation to IIM diagnosis, mortality is increased. METHODS: A population-based IIM cohort of patients diagnosed between 2002 and 2011 and general population comparators were identified using healthcare registers. They were linked to the cause of death register for follow-up. RESULTS: 224 (31%) of the 716 patients with IIM and 870 (12%) of the 7100 general population died during follow-up. This corresponded to a mortality rate of 60/1000 person-years in IIM and 20/1000 person-years in the general population. The cumulative mortality at 1 year after diagnosis was 9% in IIM and 1% in the general population, and increased in both IIM and the general population with time. The overall hazard ratio (HR) 95%CI of death comparing IIM with the general population was 3.7 (3.2 to 4.4). When we stratified on time since diagnosis, we noted an increase in mortality already within the first year of diagnosis compared with the general population, HR 9.6 (95% CI 6.9 to 13.5). This HR then plateaued around 2 after >10 years with the disease, although the estimates were not statistically significant. Malignancies, diseases of the circulatory and respiratory system were common causes of death. CONCLUSION: Mortality is increased in patients with contemporary IIM. The increased mortality was noted within a year of diagnosis, which calls for extra vigilance during the first year of IIM diagnosis.

Registro de pacientes con miopatía inflamatoria de la Sociedad Madrileña de Reumatología: análisis descriptivo / Multicenter registry on inflammatory myositis from the Rheumatology Society in Madrid, Spain: descriptive analysis

Objetivos. Describir las características clínicas, mortalidad y causas de muerte de una serie de pacientes diagnosticados de miositis inflamatoria idiopática del registro REMICAM de la Sociedad de Reumatología de la Comunidad de Madrid (SORCOM). Métodos. Estudio descriptivo retrospectivo multicéntrico de una cohorte de pacientes con diagnóstico de miositis inflamatoria idiopática en seguimiento en servicios de reumatología de hospitales de la Comunidad de Madrid entre enero de 1980 y diciembre de 2014. Se han recogido hasta un total de 313 variables acerca de aspectos demográficos, clínicos y de morbimortalidad, y se ha realizado una comparación entre subgrupos clínicos. Resultados. Se han reclutado 479 pacientes procedentes de 12 centros, con un 14% de pérdidas durante el periodo de seguimiento. El 74% de los casos eran mujeres, una edad al diagnóstico de 44±23 años, y una media de seguimiento de 10±8 años. Los subgrupos clínicos más frecuentes fueron las formas primarias (PM 29%, DM 22%), seguidas de síndrome de solapamiento (20,5%), miopatías juveniles (18%), miopatías asociadas a cáncer (8%), miopatías necrosantes inmunomediadas (1%) y miositis por cuerpos de inclusión (1%). Durante el periodo de seguimiento se produjeron un total de 114 fallecimientos (28%), siendo las principales causas el cáncer (24%), las infecciones (23%) y los eventos cardiovasculares (21%). Conclusiones. En el registro REMICAM de miopatías inflamatorias de la Comunidad de Madrid se han reclutado 479 casos de miositis inflamatoria idiopática con datos sociodemográficos, clínicos y pronósticos, suponiendo el mayor registro multicéntrico español en el ámbito de la Reumatología hasta la fecha, y constituyendo una fuente importante para la realización de posteriores subestudios (AU)

Objective. To analyze clinical characteristics, survival and causes of death of patients diagnosed with autoimmune inflammatory myositis in the REMICAM registry from the Society of Rheumatology in the Community of Madrid (SORCOM). Methods. Multicenter cohort of patients diagnosed with autoimmune inflammatory myopathy with follow-up between January 1980 and December 2014. A total of 313 variables concerning demographic, clinical and morbidity data were collected, and a comparison was performed between clinical subgroups. Results. A total of 479 patients were recruited from 12 centers, with 14% of patients lost to follow-up. Seventy-four percent of cases were women, age at diagnosis of 44±23 years and a mean follow-up period of 10±8 years. The most frequent clinical subgroups were primary myositis (PM 29%, DM 22%), followed by overlap myositis (20.5%), juvenile myositis (18%), myositis associated with cancer (8%), immune-mediated necrotizing myositis (1%) and inclusion body myositis (1%). During the follow-up period, a total of 114 deaths (28%) were registered, the main causes being cancer (24%), infections (23%) and cardiovascular events (21%). Conclusions. A total of 479 patients were recruited in the REMICAM registry of inflammatory myopathies. Including sociodemographic, clinical and prognostic information, it represents the largest Spanish multicenter registry to date in rheumatology, and constitutes an important source for conducting further substudies (AU)

Mortality and prognostic factors in idiopathic inflammatory myositis: a retrospective analysis of a large multicenter cohort of Spain.

The present study was undertaken to assess mortality, causes of death, and associated prognostic factors in a large cohort of patients diagnosed with idiopathic inflammatory myositis (IIM) from Spain. A retrospective longitudinal study was carried out in 467 consecutive patients with IIM, identified from 12 medical centers. Patients were classified as primary polymyositis, primary dermatomyositis (DM), overlap myositis, cancer-associated myositis (CAM), and juvenile idiopathic inflammatory myopathies. A total of 113 deaths occurred (24%) after a median follow-up time of 9.7 years. In the overall cohort, the 2-, 5-, and 10-year survival probabilities were 91.9, 86.7, and 77%, respectively. Main causes of death were infections and cancer (24% each). Multivariate model revealed that CAM (HR = 24.06), OM (HR = 12.00), DM (HR = 7.26), higher age at diagnosis (HR = 1.02), severe infections (HR = 3.66), interstitial lung disease (HR = 1.61), and baseline elevation of acute phase reactants (HR = 3.03) were associated with a worse prognosis, while edema of the hands (HR = 0.39), female gender (HR = 0.39), and longer disease duration (HR = 0.73) were associated with a better prognosis. The standardized mortality ratio was 1.56 (95% CI 1.28-1.87) compared to the Spanish general population. Our findings indicate that IIM has a high long-term mortality, with an excess of mortality compared to the Spanish population. A more aggressive therapy may be required in IIM patients presenting with poor predictive factors.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.

RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

Clinical Implications and Hospital Outcome of Immune-Mediated Myositis in Horses.

BACKGROUND: Immune-mediated myositis (IMM) is a cause of rhabdomyolysis, stiffness, and muscle atrophy predominantly affecting Quarter horses. Limited information is available with regard to outcome, prognostic indicators, and associations with concurrent diseases. HYPOTHESIS/OBJECTIVES: To report outcomes and associations between outcome and clinical and laboratory parameters, and presence of concurrent illness. ANIMALS: Sixty-eight horses; 52 Quarter horses and related breeds and 16 other breeds. METHODS: Retrospective cohort study (1991-2014). Medical records of horses with histological diagnosis of IMM were reviewed. Data recovery included signalment, laboratory variables, therapy, and outcome. Logistic regression was used to quantify the association between potential prognostic factors and survival to discharge. RESULTS: Quarter horses were younger (mean < 4 years, range 3 months-21 years) than other breeds (mean < 10 years, range 1-23 years). Pathogens causing concurrent or recent infection included S. equi equi, S. equi zooepidemicus, C. pseudotuberculosis, Anaplasma phagocytophilum, herpes virus-1, and influenza. The most common clinical signs consisted of rapidly progressive diffuse symmetrical muscle atrophy (80%), stiff gait (74%), and fever (44%). All horses that received medical therapy immediately upon admission survived to discharge (survival proportion = 87%). Leucocytosis was a common finding (60%). Horses with concurrent fever and other illness had a poor prognosis for hospital discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Horses with IMM can have a favorable outcome. Horses with concurrent fever and another illness had decreased probability of survival to discharge.