Mortality In Idiopathic Inflammatory Myopathies Research Articles

Pleural effusion as a predictor of rapidly progressive interstitial lung disease and mortality in idiopathic inflammatory myopathies.

This study aimed to evaluate the clinical significance of pleural effusion in adult patients with idiopathic inflammatory myopathies (IIM). We assessed a cohort of 158 consecutive patients with IIM. Clinical features and survival rates were compared between patients with and without pleural effusion. Of those 158 IIM patients, 28 (17.7%) developed pleural effusion. 125 (79.1%) IIM patients had interstitial lung disease (ILD), 26 (20.8%) of which developed pleural effusion. Notably, pleural effusion was associated with a higher incidence of lower lung zone consolidation, rapidly progressive ILD (RP-ILD) and elevated high-resolution computed tomography (HRCT) score, and could robustly predict RP-ILD independently [HR 7.863 (2.160-28.617), p=0.002] in IIM-ILD patients. IIM patients with pleural effusion presented with increased systemic inflammatory response, including more fever, elevated white blood cell count, neutrophil/lymphocyte ratio, C-reactive protein, and erythrocyte sedimentation rate, alongside reduced lymphocyte percentage. Pleural effusion was also associated with more ILD, lower lung zone consolidation, pericardial effusion and RP-ILD, higher HRCT score, and lower HB and albumin levels in IIM. Except for neutrophil/lymphocyte ratio, ILD and pericardial effusion, other correlative variables were potential predictors of higher mortality in IIM. Furthermore, pleural effusion remained an independent predictor of higher mortality in IIM [HR 5.05 (1.633-15.62), p=0.005]. Pleural effusion showed a significant positive association with severe phenotypes of ILD and was the powerful predictor of RP-ILD in IIM-ILD. Furthermore, pleural effusion could reveal adverse disease phenotypes with higher systemic inflammatory level and predict higher mortality independently in IIM.

A systematic review and meta-analysis of mycobacterial infections in patients with idiopathic inflammatory myopathies.

Infections including tuberculosis (TB) are a leading cause of morbidity and mortality in idiopathic inflammatory myopathies (IIM). We systematically reviewed the prevalence of mycobacterial infections in patients with IIM. We screened PUBMED, EMBASE and SCOPUS databases and conference abstracts (2015-20) for original articles using Covidence. Pooled estimates of prevalence were calculated. Of 83 studies (28 cohort studies, two case control and 53 case reports), 19 were analysed. Of 14043 IIM patients, DM (54.41%) was the most common subset among TB. Most studies were from Asia with high prevalence (5.86%, 2.33%-10.60%). Pooled prevalence of mycobacterial infections among IIM was 3.58% (95% CI: 2.17%, 5.85%, P< 0.01). Disseminated and extrapulmonary forms (46.58%; 95% CI: 39.02%, 54.31%, P= 1.00) were as common as pulmonary TB (49.07%; 95% CI: 41.43%, 56.75%, P=0.99) both for I2=0. Muscle involvement, an otherwise rare site, was frequently seen in case reports (24.14%). M. tuberculosis (28.84%) was the most common pathogen followed by Mycobacterium avium complex (3.25%). Non-tuberculous mycobacteria were less common overall (6.25; 95% CI: 3.49%, 10.93%) I2=0, P=0.94. Subgroup analysis and meta-regression based on high vs low TB regions found prevalence 6.61% (2.96%, 11.33%) in high TB regions vs 2.05% (0.90%, 3.56%) in low TB regions. While death due to TB was occasionally reported (P=0.82), successful anti-tubercular treatment was common (13.95%). TB is common in IIM, particularly in endemic regions though current data is largely heterogeneous. Extra-pulmonary forms and atypical sites including the muscle are frequent. Limited data suggests fair outcomes, although larger prospective studies may offer better understanding.

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

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). 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. 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. 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.

Predictors and Mortality of Rapidly Progressive Interstitial Lung Disease in Patients With Idiopathic Inflammatory Myopathy: A Series of 474 Patients.

Objective: This study was conducted to identify the characteristics and prognosis of rapidly progressive interstitial lung disease (RP-ILD) in idiopathic inflammatory myopathy (IIM) and to assess the predictors for poor survival of RP-ILD in IIM.Methods: A total of 474 patients with IIM were enrolled retrospectively according to medical records from Peking University People's Hospital. Clinical and laboratory characteristics recorded at the diagnosis of patients with RP-ILD and chronic ILD (C-ILD) were compared. The Kaplan–Meier estimator and univariate and multivariate analyses were used for data analysis.Results: ILD was identified in 65% (308/474) of patients with IIM. Patients with ILD were classified into two groups based on lung features: RP-ILD (38%, 117/308) and C-ILD (62%, 191/308). RP-ILD resulted in significantly higher mortality in IIM compared with C-ILD (27.4 vs. 7.9%, P < 0.05). In this study, by comparing IIM patients with and without RP-ILD, a list of initial predictors for RP-ILD development were identified, which included older age at onset, decreased peripheral lymphocytes, skin involvement (periungual erythema, skin ulceration, and subcutaneous/mediastinal emphysema), presence of anti-MDA5 antibody, serum tumor markers, etc. Further multivariate Cox proportional hazards model analysis identified that anti-MDA5 positivity was an independent risk factor for mortality due to RP-ILD (P < 0.05), and lymphocytes <30% in BALF might also be associated with poor survival of myositis-associated RP-ILD (P < 0.05).Conclusion: Our study shows that RP-ILD results in increased mortality in IIM. Anti-MDA5 positivity and a lower lymphocyte ratio in BALF might be the predictive factor of mortality due to RP-ILD.

Serological risk factors for concomitant interstitial lung disease in patients with idiopathic inflammatory myopathy

Interstitial lung disease (ILD) is an extramuscular manifestation associated with increased mortality in idiopathic inflammatory myopathy (IIM). To identify risk factors for ILD in patients with IIM, this study retrospectively enrolled 117 eligible patients from a university medical center. After a comprehensive chart review, 56 patients were stratified into ILD (n = 28) and non-ILD (n = 28) groups. Clinical features, laboratory data, concomitant diseases, and serology profiles were compared. Patients with ILD had high prevalence of anti-Jo1 antibodies (p = 0.002), anti-Ro52 antibodies (p < 0.001), both anti-Jo1 and anti-Ro52 antibodies (p = 0.008), anti-Jo1 or anti-Ro52 antibodies (p < 0.001), and lower initial creatine kinase (CK) levels (p = 0.006). Moreover, patients with anti-Ro52 antibodies and either anti-Ro52 or anti-Jo1 antibodies had 9.17-fold (95% confidence interval [CI]: 2.858–33.487, p < 0.001) and 13.44-fold (95% CI: 4.008–52.757, p < 0.001) increased odds of developing ILD, respectively. By contrast, patients with higher CK levels had 0.99-fold (95% CI: 0.999–0.999, p = 0.011) increased odds of developing ILD. Both anti-Ro52 and anti-Jo1 antibodies were independent serological risk factors for IIM-associated ILD. Because these serology tests are commonly available, they can be used to guide pulmonary screening for patients with IIM to increase neurologist proactivity in recognizing and treating extramuscular conditions.

Prognostic factors for steroid-free remission in patients with idiopathic inflammatory myopathies: importance of anthropometric measurements.

Background:Several studies have been conducted on factors associated with mortality in idiopathic inflammatory myopathies (IIMs), but few studies have assessed prognostic factors for steroid-free remission in IIM. We investigated the various clinical factors, including body measurements, that affect IIM treatment outcomes.Methods:Patients who were newly diagnosed with IIM between 2000 and 2018 were included. Steroid-free remission was defined as at least 3 months of normalisation of muscle enzymes and no detectable clinical disease activity. The factors associated with steroid-free remission were evaluated by a Cox regression analysis.Results:Of the 106 IIM patients, 35 displayed steroid-free remission during follow-up periods. In the multivariable Cox regression analyses, immunosuppressants’ early use within 1 month after diagnosis [hazard ratio (HR) 6.21, 95% confidence interval (CI) 2.61–14.74, p < 0.001] and sex-specific height quartiles (second and third quartiles versus first quartile, HR 3.65, 95% CI 1.40–9.51, p = 0.008 and HR 2.88, 95% CI 1.13–7.32, p = 0.027, respectively) were positively associated with steroid-free remission. Polymyositis versus dermatomyositis (HR 0.21, 95% CI 0.09–0.53, p = 0.001), presence of dysphagia (HR 0.15, CI 0.05–0.50, p = 0.002) and highest versus lowest quartile of waist circumference (WC; HR 0.24, 95% CI 0.07–0.85, p = 0.027) were negatively associated with steroid-free remission.Conclusion:The early initiation of immunosuppressant therapy, type of myositis and presence of dysphagia are strong predictors of steroid-free remission in IIM; moreover, height and WC measurements at baseline may provide additional important prognostic value.

Long-term pulmonary outcomes and mortality in idiopathic inflammatory myopathies associated with interstitial lung disease.

To study prognostic factors in different types of idiopathic inflammatory myopathies (IIM) associated with interstitial lung disease (ILD). Multicenter retrospective study of a Spanish cohort of patients diagnosed with IIM. Patients were classified into four categories: polymyositis (PM), dermatomyositis (DM), antisynthetase syndrome (ASS), and overlap myositis (OM). Sociodemographic data, clinical characteristics, antibodies, and treatments were collected. Cox regression models were calculated to identify factors associated with mortality, the necessity for long-term oxygen therapy (LTOT), and deterioration in respiratory function tests (RFT). The number of patients included was 478, of whom 112 (23.4%) suffered from ILD: 17% PM, 16% DM, 45% ASS, and 22% OM. Factors associated with mortality in the multivariate analysis were clinically meaningful progression of ILD after 3months (CMP 3m) (hazard ratio (HR) 9.48, p = 0.005), severe infections (HR 6.41, p = 0.016), heliotrope erythema (HR 31.1, p = 0.002), delay in diagnosis (HR 1.29; p = 0.011), and Raynaud's phenomenon (HR 11.9, p = 0.007). However, being female (HR 0.19, p = 0.044) and positivity solely for ANAs (HR 0.08, p = 0.008) presented a protective effect. CMP 3m (HR 22.7, p = 0.027) was associated with the need for LTOT, while basal aldolase (HR 0.90; p = 0.049) had a protective effect. Likewise, joint manifestations (HR 0.04, p = 0.034) were shown to reduce risk of deterioration in RFT. CMP 3m, severe infections, delay in diagnosis, heliotrope erythema, and Raynaud's phenomenon were identified as factors of poor prognosis in different IIM associated with ILD.

Identification of multiple cancer-associated myositis-specific autoantibodies in idiopathic inflammatory myopathies: a large longitudinal cohort study

BackgroundCancer is a significant complication contributing to increased mortality in idiopathic inflammatory myopathies (IIMs), and the association between IIMs and cancer has been extensively reported. Myositis-specific autoantibodies (MSAs) can help to stratify patients into more homogeneous groups and may be used as a biomarker for cancer-associated myositis. In this study, we aimed to systematically define the cancer-associated MSAs in IIMs.MethodsSerum from 627 patients with IIMs was tested for MSAs. The cancer risk with different MSAs was estimated by standardized incidence ratio (SIR). Paraneoplastic manifestation, such as the close temporal relationship between myositis onset and cancer diagnoses in patients with different MSAs, was also evaluated.ResultsCompared with the general Chinese population, patients with IIMs and anti-transcriptional intermediary factor (TIF1)-γ antibodies (SIR = 17.28, 95% CI 11.94 to 24.14), anti-nuclear matrix protein (NXP2) antibodies (SIR = 8.14, 95% CI 1.63 to 23.86), or anti-SAE1 antibodies (SIR = 12.92, 95% CI 3.23 to 32.94), or who were MSAs-negative (SIR = 3.99, 95% CI 1.96 to 7.14) faced increased risk of cancer. There was no association between specific MSAs subtypes and certain types of cancer. Paraneoplastic manifestations were observed in the patients carrying anti-TIF1-γ, as well as other MSAs. There were no prognostic differences among the patients with cancer-associated myositis (CAM) from different MSAs subgroups. However, in comparison to those with cancer unrelated to myositis, CAM had a worse prognosis, with an age-adjusted and sex-adjusted Cox hazard ratio (HR) of 10.8 (95% CI 1.38-84.5, p = 0.02) for all-cause mortality.ConclusionsOur study demonstrates in what is, to our knowledge, the largest population examined to date, that anti-SAE1, and previously reported anti-TIF1-γ and anti-NXP2 antibodies, are all associated with an increased risk of cancer in patients with IIMs. Moreover, our data suggest that in some cases, anti-HMGCR, anti-Jo-1 and anti-PL-12 antibody production might also be driven by malignancy. This can aid in the etiologic research of paraneoplastic myositis and clinical management.

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...

Mortality and its predominant causes in a large cohort of patients with biopsy‐determined inflammatory myositis

There is a paucity of literature on the patterns and predictors of mortality in idiopathic inflammatory myopathies (IIM). To determine the patterns and predictors of mortality in a South Australian cohort of patients with biopsy-proven IIM. The living/deceased status (and for deceased patients the causes of death) of patients with histologically determined IIM was determined from the Births, Deaths and Marriages Registry. Standardised mortality ratios (SMR) were generated compared with the age/gender matched South Australian population. The effect of presence/absence of the components of the Bohan and Peter criteria on risk ratios (RR) for mortality was determined. The effect of comorbidities and autoantibodies on mortality was investigated. The SMR for mortality in IIM was 1.75 and was significantly increased in all disease subgroups, being highest in patients with dermatomyositis (2.40). Dominant causes of death were cardiovascular disease (31%), infections (22%) and malignancy (11%). Risk factors for death were age at time of biopsy (hazard ratio 1.05), ischaemic heart disease (RR 2.97, P < 0.0001), proximal weakness at diagnosis (RR 1.8, P= 0.03), definite diagnosis of IIM per the Bohan and Peter criteria (RR 2.14, P < 0.0001), and the absence of autoantibodies (RR 1.9, P < 0.001). Patients with IIM are at 75% increased risk for mortality, and cardiovascular diseases account for the commonest causes of death. This study suggests a thorough cardiovascular evaluation of these patients is indicated, and raises the possibility that targeted interventions such as the use of aspirin or statins may improve outcomes in IIM.

Interstitial Lung Disease in Idiopathic Inflammatory Myopathy.

The lung is one of the most common extra-muscular targets in idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD) contributes to nearly 80% of the mortality in IIM with a reported prevalence of 65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical and laboratory findings of myositis, overt signs of muscle disease may be absent in the setting of significant lung disease. Understanding the varied scope of presentation of these diseases is essential to providing optimal patient care. This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention.