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Objectives To describe the 8-year longitudinal study and long-term prognosis of a large inception cohort of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) DM-interstitial lung disease (ILD) patients. Methods In total, 216 patients diagnosed with MDA5+ DM-ILD were enrolled and followed up to analyse long-term survival rate. Demographic and clinical variables were collected at baseline and each temporal end point. Seventy patients who survived the first year were analysed for the long-term serological and respiratory outcomes. Results A total of 85 patients (39.3%) died during the follow-up period up to 96 months, with 89% of the deaths occurring in the first year after diagnosis. Long-term outcome was reported in 70 patients. Serological markers including anti-MDA5 antibody showed significant improvement with time. Radiographic findings and pulmonary function also improved notably in the follow-up period, especially in rapidly progressive ILD group, as measured by high-resolution computed tomography imaging scores, the estimated forced vital capacity, estimated diffusing capacity of lung carbon monoxide and dyspnoea scores. Early application of anti-fibrosis therapy helped to improve long-term pulmonary function. Conclusions MDA5+ DM-ILD patients had a high mortality rate despite aggressive treatment. Patients who survived the first year usually showed a significant improvement in serological markers and pulmonary function during the long-term follow-up. [ABSTRACT FROM AUTHOR]

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is an autoimmune condition associated with rapidly progressive interstitial lung disease and high mortality. The aetiology and pathogenesis of MDA5+ DM are still largely unknown. Here we describe the immune signatures of MDA5+ DM via single-cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in peripheral B and T cells and in affected lung tissue samples from one patient. We find strong peripheral antibody-secreting cell and CD8+ T cell responses as cellular immune hallmarks, and over-stimulated type I interferon signaling and associated metabolic reprogramming as molecular immune signature in MDA5+ DM. High frequency of circulating ISG15+ CD8+ T cells at baseline predicts poor one-year survival in MDA5+ DM patients. In affected lungs, we find profuse immune cells infiltration, which likely contributes to the pro-fibrotic response via type I interferon production. The importance of type I interferons in MDA5+ DM pathology is further emphasized by our observation in a retrospective cohort of MDA5+ DM patients that combined calcineurin and Janus kinase inhibitor therapy show superior efficacy to calcineurin inhibitor monotherapy. In summary, this study reveals key immune-pathogenic features of MDA5+ DM and provides a potential basis for future tailored therapies. Anti-melanoma differentiation-associated gene 5-positive dermatomyositis is a severe autoimmune disease with largely unknown aetiology. Here authors identify the key immune cell types that contribute to the disease phenotype and implicate type I interferons signalling in the patho-mechanism. [ABSTRACT FROM AUTHOR]

Background: The prognosis of amyopathic dermatomyositis (ADM)-associated interstitial lung disease (ILD) is poor. A mortality risk score model is needed to predict survival in patients with ADM-ILD and to guide clinical treatment.Research Question: How to identify patients with ADM-ILD who are at high risk and to predict patient outcome based on a risk stratification model?Study Design and Methods: We evaluated 207 patients with ADM-ILD in this prospective inception study. We used a multivariable Cox proportional hazards model to identify the independent prognostic risk factors and created a risk score model according to patient data from January 2012 to December 2016. We used the index of prediction accuracy that uses the Brier score to reflect both discrimination and calibration of the model. The model was validated in an independent group of patients from January 2017 to June 2018.Results: We developed a combined risk score, the FLAIR score, that included the following values and scores: ferritin (<636 ng/mL, 0; ≥636 ng/mL, 2), lactate dehydrogenase (<355 U/L, 0; ≥355 U/L, 2), antimelanoma differentiation-associated gene 5 antibody (negative, 0; +, 2; ++, 3; +++, 4), high-resolution CT imaging score (<133, 0; ≥133, 3), and rapidly progressive ILD (RPILD) (non-RPILD, 0; RPILD, 2). We divided patients into three risk groups according to the FLAIR score: low, 0 to 4; medium, 5 to 9; and high, 10 to 13. In both discovery and validation cohorts, high-risk patients had significantly higher mortality rates than low- and medium-risk patients (P < .001).Interpretation: The FLAIR risk score model could help to predict survival in patients with ADM-ILD and to guide further clinical research on risk-based treatment. [ABSTRACT FROM AUTHOR]

On examination, we saw puffy fingers, periungual erythema, dilated capillaries and hemorrhages of the proximal nail folds in all fingers except her thumbs. To observe nail fold capillaries more clearly, placing a dermatoscope on the proximal nail fold can show capillaries appearing as small red dots or loops. [2] Nail fold capillary abnormalities, especially hemorrhages and giant capillaries, are sometimes visible to the unaided eye. [Extracted from the article]