anti-MDA5 Antibody-positive Dermatomyositis Research Articles

Efficacy of plasma exchange in anti-Ro52 and anti-MDA5 antibody-positive dermatomyositis with progressive interstitial lung disease: a case report

Efficacy of plasma exchange in anti-Ro52 and anti-MDA5 antibody-positive dermatomyositis with progressive interstitial lung disease: a case report

Serum interleukin-34 levels in dermatomyositis: a potential biomarker for anti-MDA5-antibody-associated interstitial lung disease.

Interleukin (IL)-34 is a hematopoietic cytokine that promotes macrophage activation. Macrophage activation in interstitial lung disease (ILD) in patients with dermatomyositis (DM), especially in those with anti-melanoma differentiation-associated gene 5 (MDA5) antibody suggests the involvement of IL-34 in the disease. However, the association between IL-34 and DM is unknown. In this study, we aimed to determine serum IL-34 levels in DM patients and evaluate their association with DM-ILD. We measured serum IL-34 levels in 56 DM patients and 14 age- and sex- matched healthy controls by enzyme-linked immunosorbent assay, and examined their correlation with clinical parameters. In addition, pre- and post-treatment serum IL-34 levels were examined using serum samples from 7 anti-MDA5 antibody-positive DM patients. Serum IL-34 levels were significantly elevated in DM patients, especially in those with anti-MDA5 antibody, compared with healthy controls. In anti-MDA5-antibody-positive DM patients, serum IL-34 levels positively correlated with serum levels of ferritin and anti-MDA5 antibody, which are known biomarkers for rapidly progressive (RP)-ILD. Following combined immunosuppressive therapy, serum IL-34 levels decreased along with ferritin and anti-MDA5 antibody. These data suggest that IL-34 may be involved in the development of RP-ILD in anti-MDA5 antibody-positive DM. Serum IL-34 levels can serve as a potential biomarker for RP-ILD in this clinical entity.

From machine learning to clinical practice: phenotypic clusters of anti-MDA5 antibody-positive dermatomyositis.

From machine learning to clinical practice: phenotypic clusters of anti-MDA5 antibody-positive dermatomyositis.

Human umbilical cord mesenchymal stem cells treated anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease: a case report.

Human umbilical cord mesenchymal stem cells treated anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease: a case report.

Assessing Time of Onset for Interstitial Lung Disease in Anti-MDA5 Antibody-Positive Dermatomyositis

This cohort study seeks to describe the time interval between interstitial lung disease and anti–melanoma differentiation-associated gene 5 antibody-positive dermatomyositis diagnoses.

A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.

Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10months later, both values were significantly higher than normal. This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.

Global trends in research of melanoma differentiation-associated gene 5: a bibliometric analysis from 2002 to 2022.

Melanoma differentiation-associated gene 5 (MDA5), as a cytoplasmic sensor for viral double-stranded RNAs, has received increasing attention in recent years. Although considerable headway has been made on the functional role of MDA5 in antiviral immunity and autoimmune disease, the available literature is insufficient to assess the vast field. This study performed a bibliometric analysis to investigate current hotspots in the global scientific output of MDA5 over the past two decades. Related publications and recorded information from 2002 to 2022 in the Web of Science Core Collection (WoSCC) database were retrieved. VOSviewer and CiteSpace were used for quantitative evaluation and visualization. A total of 2267 original articles and reviews were obtained, and the annual number of publications related to MDA5 was increasing rapidly. China has published the most papers, while the USA was the most influential country with the most citations and the highest H-index. The Chinese Academy of Sciences, the United States Department of Health and Human Services, and the Journal of Virology were the most prolific research affiliation, funding source, and journal, respectively. Fujita T (Kyoto University) was the most productive author with the highest H-index and had close cooperation with Kato H and Yoneyama M. The keywords "RIG-I," "MDA5," "innate immunity," "double-stranded-RNA," and "recognition" had the highest frequency, while "dermatomyositis" as well as "autoantibody" seemed to be the emerging hotspots. This study comprehensively demonstrated the research frontiers of MDA5 and will provide a useful resource for scholars to conduct future decisions. We conducted the first in-depth survey of the research frontiers on melanoma differentiation-associated gene 5 (MDA5) over the past two decades via bibliometric analysis. We found that many early breakthroughs have been made in the mechanism of MDA5-mediated antiviral immune responses, and the role of MDA5 in autoimmune and autoinflammatory diseases has raised the recent concern. We identified that the virus infection-associated pathogenesis and effective therapeutic strategy of anti-MDA5 antibody-positive dermatomyositis will remain the hotspots in the future.

Spontaneous pneumomediastinum in anti-MDA5-positive dermatomyositis: Prevalence, risk factors, and prognosis

ObjectiveTo depict the clinical panorama of spontaneous pneumomediastinum (SPM) in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5+ DM). MethodsA total of 1352 patients with idiopathic inflammatory myopathy (IIM), including 384 anti-MDA5+ DM patients were retrospectively enrolled. The clinical profiles of anti-MDA5+ DM-associated SPM were analyzed. ResultsWe identified that 9.4 % (36/384) of anti-MDA5+ DM patients were complicated with SPM, which was significantly higher than that of non-anti-MDA5+ DM and other IIM subtypes (P all <0.001). SPM developed at a median of 5.5 (3.0, 12.0) months after anti-MDA5+ DM onset. Anti-MDA5+ DM patients complicated with SPM showed a significantly higher frequency of fever, dyspnea, and pulmonary infection including viral and fungal infections compared to those without SPM (P all < 0.05). Cytomegalovirus (CMV) and fungal infections were identified to be independent risk factors for SPM development in the anti-MDA5+ DM. SPM and non-SPM patients in our anti-MDA5+ DM cohort showed comparable short-term and long-term survival (P = 0.236). Furthermore, in the SPM group, we found that the non-survivors had a lower peripheral lymphocyte count, higher LDH level, and higher frequency of intensification of immunosuppressive treatment (IST) than survivors. The elevated LDH level and intensification of IST were independent risk factors for increased mortality in anti-MDA5+ DM-associated SPM patients. ConclusionsNearly one-tenth of patients with anti-MDA5+ DM develop SPM. Both CMV and fungal infections are risk factors for SPM occurrence. The development of SPM does not worsen the prognosis of anti-MDA5+ DM patients, and the intensification of IST does harm to the SPM prognosis.

Diagnosis of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis led by sarcoplasmic myxovirus resistance protein A expression on muscle pathology

A 44-year-old woman with autism spectrum disorder developed bulbar symptoms and generalized muscle weakness 7 months before referral. Six months before, she was administered glucocorticoid for liver involvement. During the course, while she presented alopecia, skin ulcers, and poikiloderma, hyperCKemia was observed only twice. Due to complications including cardiac involvement and hearing loss as well, we suspected mitochondrial disease and performed a muscle biopsy. The muscle pathology showed sarcoplasmic myxovirus resistance A (MxA) expression with scattered pattern. Since anti-melanoma differentiation-associated gene 5 (MDA5) antibody was detected, we diagnosed the patient with anti-MDA5 antibody-positive dermatomyositis (DM). We reinforced immunosuppressive therapy, and her clinical symptoms and liver involvement were improved. When we diagnose a case of anti-MDA5 antibody-positive DM who is difficult to make clinical diagnosis, it may be valuable to evaluate sarcoplasmic MxA expression on muscle pathology.

Melanoma Differentiation-associated Gene 5-Positive Rapidly Progressive Interstitial Lung Disease Successfully Treated with Tofacitinib.

Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis is associated with rapidly progressive interstitial lung disease (RP-ILD). We encountered a man in his 40s who presented with a history of a fever and dry cough. Based on laboratory tests and computed tomography scans of his chest, he was diagnosed with anti-MDA5 antibody-positive dermatomyositis with RP-ILD refractory to antimicrobial agents. Although the patient was treated with glucocorticoids, calcineurin inhibitors, intravenous cyclophosphamide, and plasma exchange, ventilatory management was still required. The patient survived additional therapy with tofacitinib; however, he developed a catheter-related pulmonary embolism as a complication.

Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress.

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and pathology remain unclear, increasing evidence suggests that viral infection is a potential trigger of MDA5-DM. Multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5-DM. Distinctive skin rashes, rapidly progressive interstitial lung disease, peripheral lymphopenia and elevated serum ferritin levels are the most prominent clinical and laboratory features of MDA5-DM. Concomitant infection is a common complication of MDA5-DM. The proper evaluation of patients with MDA5-DM requires knowledge of the disease heterogeneity and clinical course variability. Several biomarkers, including serum levels of anti-MDA5 antibodies and biomarkers related to macrophage activation, have been identified as useful tools for monitoring disease activity and prognosis. MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis. Therefore, there is an urgent need to explore the key pathogenic mechanisms of MDA5-DM and develop novel therapeutic options for patients. This Review discusses recent clinical progress and pathogenic findings of MDA5-DM.

Correlation between B-cell epitope profile and clinical features of anti-MDA5 antibody-positive dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis. Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Spearman's rank correlation coefficients. Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0-74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n = 11), vascular dysfunction (n = 9) and interstitial lung disease (ILD) (n = 16). Female patients exhibited higher titres of antibodies recognizing fragment H (aa 905-1026) compared with male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646-801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130-284) and E (aa 517-671) antibody titres than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1-155) antibody titres than the other 20 patients. Differences in the ratio of anti-fragment to anti-full-length MDA5 antibody titres were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5). Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course.

Clinical features of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with macrophage activation syndrome.

This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) who had macrophage activation syndrome (MAS). We retrospectively examined 44 patients with anti-MDA5-positive DM and compared the clinical features between patients with MAS (n = 11) and those without (n=33). Patients without MAS were selected randomly in the same year as those with MAS at a ratio of 3:1. Among patients with MAS, we compared the features between non-survivors and survivors. We used Fisher's exact test, Student's t test, the Mann-Whitney U test and the log-rank test for statistical analysis. Patients complicated with MAS had a significantly higher incidence of infection, heliotrope sign, Gottron's papule, V-neck sign, and higher serum levels of ferritin, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) than those without MAS (p<0.05). Among the 11 patients with MAS, 4 (36.4%) died after intensive treatment. Deceased patients were older, given more combination therapy with tofacitinib (TOF) and had a higher incidence of rapid progressive interstitial lung disease, infection, heart failure and renal impairment than those who survived (p<0.05). Among anti-MDA5-positive DM, Infection, DM typical rashes, and higher serum levels of ferritin, AST, LDH, and CK were more common in patients complicated with MAS. The mortality of patients with MAS was high, particularly among patients who were older, given more combination therapy with TOF, and had RP-ILD, infection, heart failure and renal impairment.

Intramuscular lesions in musculoskeletal MRI as a favourable prognostic sign in patients with anti-MDA5 antibody-positive dermatomyositis

ObjectivesAnti-differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis, which has been described as clinically amyopathic dermatomyositis, complicates rapidly progressive interstitial lung disease (ILD). Owing to the absence of significant muscle symptoms, musculoskeletal...

Efficacy and Safety of Tofacitinib in Anti-Melanoma Differentiation-Associated 5 Gene Antibody-Positive Dermatomyositis.

This study aimed to evaluate the efficacy and safety of tofacitinib for the treatment of anti-melanoma differentiation-associated 5 gene (anti-MDA5) antibody-positive dermatomyositis (DM). This study included 52 patients with anti-MDA5 antibody-positive DM (MDA5+DM) who were treated with tofacitinib and followed up. Clinical and laboratory data of these patients were recorded between January 2019 and June 2022. SPSS was used for all statistical analyses. The mean age of patients with MDA5+DM was 45 ± 12.4 years, and the median disease duration was 6.5 months (range, 3-13 months). The mean dosage of glucocorticoids was 34.7 ± 20.9 mg/d at the initiation of tofacitinib therapy. Overall, 47 patients were followed up for a mean duration of 7.8 ± 6.2 months. We found that the clinical symptoms of 28 patients (59.6%) were improved, but 1 patient (2.1%) died because of severe infection. Moreover, complications occurred in 25 patients (53.2%), among whom 19 patients had infections. Older age and C-reactive protein levels close to the upper value in reference range at the initial treatment were found to be the potential risk factors of infection. Furthermore, patients with cutaneous ulcers were found to have a lower risk of infection. Tofacitinib can be used as a potential therapeutic option for MDA5+DM. The occurrence of infection requires special attention during treatment, particularly in patients with older age and C-reactive protein levels close to the upper value in reference range.

A nomogram based on clinical factors and CT radiomics for predicting anti-MDA5+ DM complicated by RP-ILD.

Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) DM complicated by rapidly progressive interstitial lung disease (RP-ILD) has a high incidence and poor prognosis. The objective of this study was to establish a model for the prediction and early diagnosis of anti-MDA5+ DM-associated RP-ILD based on clinical manifestations and imaging features. A total of 103 patients with anti-MDA5+ DM were included. The patients were randomly split into training and testing sets of 72 and 31 patients, respectively. After image analysis, we collected clinical, imaging and radiomics features from each patient. Feature selection was performed first with the minimum redundancy and maximum relevance algorithm and then with the best subset selection method. The final remaining features comprised the radscore. A clinical model and imaging model were then constructed with the selected independent risk factors for the prediction of non-RP-ILD and RP-ILD. We also combined these models in different ways and compared their predictive abilities. A nomogram was also established. The predictive performances of the models were assessed based on receiver operating characteristics curves, calibration curves, discriminability and clinical utility. The analyses showed that two clinical factors, dyspnoea (P = 0.000) and duration of illness in months (P = 0.001), and three radiomics features (P = 0.001, 0.044 and 0.008, separately) were independent predictors of non-RP-ILD and RP-ILD. However, no imaging features were significantly different between the two groups. The radiomics model built with the three radiomics features performed worse than the clinical model and showed areas under the curve (AUCs) of 0.805 and 0.754 in the training and test sets, respectively. The clinical model demonstrated a good predictive ability for RP-ILD in MDA5+ DM patients, with an AUC, sensitivity, specificity and accuracy of 0.954, 0.931, 0.837 and 0.847 in the training set and 0.890, 0.875, 0.800 and 0.774 in the testing set, respectively. The combination model built with clinical and radiomics features performed slightly better than the clinical model, with an AUC, sensitivity, specificity and accuracy of 0.994, 0.966, 0.977 and 0.931 in the training set and 0.890, 0.812, 1.000 and 0.839 in the testing set, respectively. The calibration curve and decision curve analyses showed satisfactory consistency and clinical utility of the nomogram. Our results suggest that the combination model built with clinical and radiomics features could reliably predict the occurrence of RP-ILD in MDA5+ DM patients.

Soluble CD206 levels correlate with disease deterioration and predict prognosis of anti-MDA5 antibody-positive dermatomyositis related interstitial lung disease.

The prognosis of anti-MDA5 antibody-positive dermatomyositis/clinically amyopathic dermatomyositis-associated interstitial lung disease (MDA5-DM/CADM-ILD) is poor. This study was to evaluate the effect of serum soluble CD206 (sCD206), a biomarker of macrophage activation, on predicting the interstitial lung disease (ILD) deterioration and prognosis for MDA5-DM/CADM-ILD. Forty-one patients diagnosed with MDA5-DM/CADM-ILD were retrospectively included. The clinical data were analyzed. Serum sCD206 levels were measured in 41 patients and 30 healthy controls. The relation between sCD206 levels and ILD deterioration was assessed. Receiver operating characteristic (ROC) curve was generated to determine the optimal cut-off value of sCD206 for predicting outcome. The association between sCD206 and survival was examined. The median serum sCD206 level in patients was significantly higher than healthy controls (464.1 ng/mL vs. 349.1 ng/mL, P= 0.002). In DM/CADM patients, the sCD206 level was significantly higher in patients with acute/subacute interstitial lung disease (AILD/SILD) than those with chronic interstitial lung disease (CILD) (539.2ng/mL vs. 309.4ng/mL, P= 0.005). The AUC of sCD206 was 0.885 for predicting mortality (95% CI 0.779-0.990). Patients were divided into two groups: sCD206 high level group (≥400 ng/mL) and sCD206 low level group (<400 ng/mL). Patients with sCD206 high level had significantly decreased survival rate than those with low level (25% vs. 88%, P< 0.001). The adjusted hazard ratio of sCD206 for mortality was 1.003 (adjusted for age and gender, P< 0.001), with sCD206 high level associated with higher death risk (HR 4.857, P= 0.006). Serum sCD206 might be a potential predictor of ILD deterioration and prognosis for Chinese patients with MDA5-DM/CADM-ILD.

Type I interferon score is associated with the severity and poor prognosis in anti-MDA5 antibody-positive dermatomyositis patients.

To investigate the clinical significance of the interferon (IFN) score, especially the IFN-I score, in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (anti-MDA5+ DM). We enrolled 262 patients with different autoimmune diseases, including idiopathic inflammatory myopathy, systemic lupus erythematosus, rheumatoid arthritis, adult-onset Still's disease, and Sjögren's syndrome, as well as 58 healthy controls. Multiplex quantitative real-time polymerase chain reaction (RT-qPCR) using four TaqMan probes was used to evaluate type I IFN-stimulated genes (IFI44 and MX1), one type II IFN-stimulated gene (IRF1), and one internal control gene (HRPT1), which were used to determine the IFN-I score. The clinical features and disease activity index were compared between the high and low IFN-I score groups in 61 patients with anti-MDA5+ DM. The associations between laboratory findings and the predictive value of the baseline IFN-I score for mortality were analyzed. The IFN score was significantly higher in patients with anti-MDA5+ DM than in healthy controls. The IFN-I score was positively correlated with the serum IFN-α concentration, ferritin concentration, and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score. Compared with patients with a low IFN-I score, patients with a high IFN-I score showed a higher MYOACT score, C-reactive protein concentration, aspartate transaminase concentration, ferritin concentration, plasma cell percentage, and CD3+ T-cell percentage, as well as lower lymphocyte, natural killer cell, and monocyte counts. The 3-month survival rate was significantly lower in patients with an IFN-I score of >4.9 than in those with an IFN-I score of ≤4.9 (72.9% vs. 100%, respectively; P = 0.044). The IFN score, especially the IFN-I score, measured by multiplex RT-qPCR is a valuable tool to monitor disease activity and predict mortality in patients with anti-MDA5+ DM.

Risk Factors of Rapidly Progressive Interstitial Lung Disease in Patients With Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis

To investigate the conditions of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis combined with rapidly progressive interstitial lung disease (RPILD), and to analyze the risk factors. A total of 145 patients diagnosed with anti-MDA5 antibody-positive dermatomyositis at West China Hospital, Sichuan University between January 2018 and September 2021 were selected, and their general and clinical data were collected. The patients were divided into two groups, a RPILD group of patients with comorbid RPILD and a non-RPILD group of those who did not have comorbid RPILD. Factors that might affect whether patients with anti-MDA5 antibody-positive dermatomyositis also had comorbid RPILD were screened out and binary logistic regression analysis was performed. Among the 145 patients with anti-MDA5 antibody-positive dermatomyositis, 32 (22.07%) patients had comorbid RPILD, while the remaining 113 (77.93%) did not have comorbid RPILD. Binary logistic regression analysis showed that lactate dehydrogenase≥370 IU/L (compared with <370 IU/L, OR=4.066, 95% CI: 1.616-10.230) and carcinoembryo antigen≥5 ng/mL (compared with <5 ng/mL, OR=6.070, 95% CI: 2.013-18.303) were risk factors for comorbid RPILD in patients with anti-MDA5 antibody-positive dermatomyositis ( β>0, OR>1, P<0.05). It is recommended that close attention be given to changes in high-resolution chest CT and pulmonary functions in patients with lactate dehydrogenase≥370 IU/L and carcinoembryo antigen≥5 ng/mL. If rapid progression of lung disease is detected, it is necessary to strengthen the treatment of the lung disease, thereby improving the prognosis of patients.

High prevalence and mortality of Pneumocystis jirovecii pneumonia in anti-MDA5 antibody-positive dermatomyositis.

To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS). Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods. 91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P < 0.001). PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected.