A Novel Tool for Predicting Malignant Disease in Adult Patients With Dermatomyositis

Some autoantibodies have been identified to be closely associated with the clinical phenotypes and prognosis of dermatomyositis, such as anti-melanoma differentiation-associated gene 5 (MDA5) antibody, anti-transcriptional intermediary factor 1-γ (TIF-1γ) antibody, anti-nuclear matrix protein-2 (NXP-2) antibody, anti-glycyl-tRNA synthetase (anti-EJ) antibody, anti-nucleosome remodelling and histone deacetylase complex (anti-Mi-2) antibody, anti-histidyl-tRNA synthetase (anti-Jo-1) antibody, and so on. Anti-MDA5, anti-EJ and anti-Jo-1 antibodies are all related to dermatomyositis complicated by interstitial lung disease, especially anti-MDA5 antibody, which is significantly associated with the occurrence, disease activity and high mortality of dermatomyositis complicated by interstitial lung disease. Usually, anti-MDA5 antibody-positive patients have poor response to conventional immunosuppressive treatments. Anti-TIF-1γ and anti-NXP-2 antibodies are related to cancer-associated dermatomyositis. Moreover, anti-TIF-1γ and anti-NXP-2 antibodies are linked to some other distinctive clinical phenotypes of dermatomyositis. For example, obviously increased occurrence of psoriasis-like lesions and hyperkeratotic papules of palms is observed in anti-TIF-1γ antibody-positive patients, while muscle weakness in the forearms, lower legs and neck occurs more commonly in anti-NXP-2 antibody-positive patients. However, anti-Mi-2 antibody-positive patients have significantly decreased risk of interstitial lung disease and prolonged duration of treatment. Thus, wide application of the detection of these autoantibodies will be helpful to guide the diagnosis and treatment of dermatomyositis. Key words: Dermatomyositis; Autoantibodies; Antibodies, anti-MDA5; Antibodies, anti-TIF-lγ; Antibodies, anti- NXP-2; Antibodies, anti-EJ; Antibodies, anti- Mi-2; Antibodies, anti- Jo-1

Number, characteristics, and classification of patients with dermatomyositis seen by dermatology and rheumatology departments at a large tertiary medical center

Dermatomyositis (DM) is an idiopathic inflammatory myopathy. Because of clinical heterogeneity, the metabolite profile of DM patients with different myositis-specific autoantibodies (MSAs) remains elusive. This study aimed to explore the metabolomics characteristics of the serum in DM with different MSAs, low or high disease activity, and interstitial lung disease. Untargeted metabolomics profiling was performed in the serum of a discovery cohort (n=96) and a validation cohort (n=40), consisting of DM patients with MSAs, low or high disease activity, and/or interstitial lung disease (DM-ILD) compared to age- and gender-matched healthy controls (HCs). The lipid profile in DM was found to be abnormal, especially dysregulated glycerophospholipid metabolism and fatty acid oxidation, which might affect the pathogenesis of DM by disrupting the balance of Th17 and Treg. We identified potential biomarkers of DM that can distinguish between low or high disease activity and reflect lung involvement. Two metabolite combinations including pro-leu, FA 14:0;O can distinguish high disease activity DM from low disease activity DM and HCs, and five including indole-3-lactic acid, dihydrosphingosine, SM 32:1;O2, NAE 17:1, and cholic acid can distinguish DM-ILD from DM without ILD (DM-nonILD). DM with different MSAs had unique metabolic characteristics, which can distinguish between MDA5+DM, Jo-1+DM, and TIF1-γ+DM, and from the antibody-negative groups. The sphingosine metabolism has been found to play an important role in MDA5+DM, which was associated with the occurrence of ILD. Altered metabolic profiles of dermatomyositis were associated with different myositisspecific autoantibodies, disease activity, and interstitial lung disease, which can help in the early diagnosis, prognosis, or selection of new therapeutic targets for DM.

Background Dermatomyositis (DM) is a heterogeneous disease with a wide range of clinical manifestations. Bohan and Peter suggested four subtypes of DM: idiopathic DM, juvenile DM, DM associated with cancer, and DM associated with other connective tissue diseases. Different DM subtypes have distinct clinical manifestations, responses to therapy and prognoses. Objectives The aim of the present study was to identify the clinical subtypes of DM by applying cluster analysis. Methods We retrospectively reviewed the medical records of 720 DM patients and selected 21 variables for analysis, including clinical characteristics, laboratory findings, and comorbidities. Principal component analysis (PCA) was first conducted to transform the 21 variables into independent principal components. Patient classification was then performed using cluster analysis based on the PCA-transformed data. The relationships among the clinical variables were also assessed. Results We transformed the 21 clinical variables into 9 independent principal components by PCA and identified 6 distinct subgroups. Cluster A was composed of two sub-clusters of patients with classical or moderate DM. Cluster-B patients were older and had malignancies. Cluster C was characterized by interstitial lung disease (ILD), skin ulcer, and minimal muscle involvement. Cluster D included patients with prominent lung, muscle, and skin involvement. Cluster E contained DM patients with other connective tissue diseases. Cluster F included all patients with myocarditis and prominent myositis and ILD. We found significant differences in treatment across the six clusters, with clusters C, D, and E being more likely to receive aggressive immunosuppressive therapy. Conclusion We applied cluster analysis to a large group of DM patients and identified six clinical subgroups, underscoring the need for better phenotypic characterization to help develop individualized treatments and improve prognosis.

Objective To investigate the clinical characteristics of patients with polymyositis (PM) and dermatomyositis (DM) to provide a basis for clinical diagnosis and treatment of these conditions. Methods Three hundred and eight patients with PM and DM admitted to the Department of Rheumatology and Immunology of the Third Hospital Affiliated to Soochow University were collected from January 1998 to March 2018, and the clinical manifestations, muscle enzymes, electromyogram (EMG), muscle biopsy and treatment outcome were retrospectively analyzed. Results The most common initial symptom of PM was muscle weakness, accounting for 92.8% of all cases, while rash was the most common initial presentation in DM cases, accounting for 66.7%. The incidence of interstitial lung disease (ILD) (69.8% vs 37.5%, χ2=20.790, P=0.000) and concomitant tumors (95.6% vs 4.3%, χ2=6.956891, P=0.008350) was significantly higher in DM patients than in PM patients. The percentages of PM patients with elevated CK (t=-6.684, P=0.000) and CK-MB (t=-6.964, P=0.000) were significantly higher than those of DM patients. The pathological changes in PM patients mainly consisted of myofiber degeneration and connective tissue hyperplasia, while those in DM patients were mainly characterized by peripapillary atrophy, vacuolar degeneration and inflammatory cell infiltration between the intermuscular and perivascular tissues. Follow-up was performed in 243 patients. The mortality of DM was higher than that of PM (18.7% vs 7.1%, χ2=4.392, P=0.036). The main causes of death were pulmonary infections and tumors. Conclusions PM and DM patients are different in clinical manifestations, muscle enzymes, pathology and mortality. Infection secondary to ILD and tumor are more common in DM, with a higher mortality rate, than in PM. Key words: Polymyositis; Dermatomyositis; Clinical characteristics

Dermatomyositis (DM) is a rare condition which causes inflammation in the skin and muscles. There are different subtypes of DM, which are defined by genetic differences. One subtype of DM, characterised by a gene called anti‐melanoma differentiation‐associated gene 5 (anti‐MDA5 DM), is linked to an extremely high risk of interstitial lung disease (ILD). In Asia, 10‐48% of DM patients have this type of DM. This study, from China, aimed to explore the role of certain proteins, together known as the type 1 interferon system, in development of this type of DM. Patients with anti‐MDA5 DM were studied and compared with patients who suffered from other variations of DM. The levels of specific proteins in the blood (inflammatory cytokines, B cell activating factor or ‘BAFF’, Krebs von den Lungen‐6) and in skin lesions (STAT1, ISG15 and MxA) were tested. The levels of the protein plasma IFN‐α was much higher in anti‐MDA5 DM patients than those of other DM subtypes. Skin biopsies from anti‐MDA5 DM patients were characterized by the strong expressions of (presence of) STAT1, ISG15, and MxA proteins. In the anti‐MDA5 DM/ILD patients with high IFN‐α production, there was a relationship between IFN‐α and BAFF levels. In addition, the higher levels of BAFF paralleled to the higher concentrations of KL‐6. This study confirms the abnormal activation of type I IFN protein system in anti‐MDA5 DM. Overproduction of IFN‐α linked with BAFF may be implicated in the development of ILD.

Melanoma differentiation-associated protein 5 (MDA-5) is a novel autoantibody frequently characterized by interstitial lung disease and a distinct cutaneous phenotype with palmar papules, ulceration, and rash. Virtually all patients have underlying dermatomyositis, but many lack the characteristic clinical myopathy associated with it. In the setting of amyopathic disease, the absence of clinically available biomarkers or clear pathologic diagnosis can complicate effective prognostic and therapeutic intervention. Until recently the presence of MDA-5 antibody associated dermato-pulmonary syndrome was described only in Asian populations. We present 2 cases of MDA-5-associated dermato-pulmonary syndrome and provide a comprehensive review of available literature.

Amyopathic dermatomyositis (ADM) is characterized by the presence of dermatomyositis (DM) for 6 months or more in individuals who have normal muscle enzymes and no clinically significant muscle weakness. The aim of the study was to investigate the initial laboratory data, clinical manifestations, complications, and clinical outcomes of patients with the diagnosis of ADM. We reported 16 cases with the cutaneous findings of dermatomyositis without clinical or laboratory evidence of muscle disease for at least 2 years after onset of the skin manifestations in the Department of Dermatology and Rheumatology at Shanghai Ruijin Hospital between 1998 and 2004. All patients had Gottron's papules, periungual erythema/telangiectasia, and violaceous discoloration of the face, neck, upper chest, and back at some time during the course of their disease. Follow-up of 1 to 10 years after diagnosis found muscle weakness in three patients (18.75%) within 5 years of diagnosis. One patient (6.15%) was rediagnosed as chronic cutaneous lupus erythematosus (CCLE). Four patients (25%) had associated malignancies. Twelve patients (75%) had radiographic evidence indicative of interstitial fibrosis irrespective of respiratory symptoms. Patients with ADM appear to be at risk for developing the same potentially fatal disease complications as those patients with DM (e.g., interstitial lung disease and internal malignancy). These cases further emphasize that the cutaneous manifestations of dermatomyositis are pathognomonic for DM and we propose the term dermatomyositis-like skin disease as a better designation than amyopathic dermatomyositis to describe this distinctive subset of cutaneous symptoms. Dermatomyositis-like skin disease is a complex syndrome, which includes the characteristic cutaneous eruption of dermatomyositis without clinical evidence of muscle disease. Our findings suggest that patients diagnosed with this syndrome are at risk for fatal interstitial lung disease, malignancy, and/or delayed onset of DM or CCLE. Cautious systematic clinical trials should be considered for this group of patients.

Dermatomyositis (DM) is associated with increased rates of hospitalization and mortality. However, characteristics present at the time of admission that are associated with in-hospital mortality remain poorly defined in the US. To evaluate whether features of DM present at admission, including active rash and muscle disease, interstitial lung disease (ILD), elevated neutrophil to lymphocyte ratio (NLR), myositis-specific autoantibody status, and baseline treatment regimens, are associated with in-hospital mortality among patients admitted with DM. This cohort study included adults with pre-existing DM (confirmed by documentation by a dermatologist or rheumatologist) who were admitted for any cause at a single tertiary referral center from January 2013 to May 2024. Data were analyzed from August 2024 to August 2025. Clinical, serologic, and laboratory features of DM at the time of admission as well as baseline treatment prior to hospitalization. The primary outcome was in-hospital mortality. Statistical analyses included descriptive statistics and multivariable logistic regression with the Firth correction, adjusting for demographics and DM subtype. Bonferroni correction was applied to control for multiple comparisons. Among 153 patients with DM (113 females [73.9%]; mean [SD] age, 56.5 [14.3] years), 16 (10.5%) died during hospitalization. Deceased patients were more likely than survivors to have active rash (13 of 16 [81.3%] vs 47 of 137 [34.3%]), ILD (14 of 16 [87.5%] vs 57 of 137 [41.6%]), and elevated NLR (mean [SD], 12.5 [7.43] vs 4.90 [3.82]). Myositis prevalence did not differ significantly between deceased patients and survivors. In multivariable analysis, active rash (odds ratio [OR], 12.13; 95% CI, 3.18-46.28; P = .003), ILD (OR, 6.43; 95% CI, 1.78-23.13; P = .04), and NLR (OR per 1-unit increase, 1.29 [95% CI, 1.16-1.44]; P < .001) were independently associated with mortality. No association with baseline intravenous immunoglobulin use was observed among patients who died after Bonferroni correction. In this study, active rash, ILD, and elevated NLR were independently associated with in-hospital mortality in patients with DM, regardless of disease subtype or myositis-specific autoantibody status. Recognizing these high-risk features may guide inpatient management and support future risk stratification strategies.

To explore the clinical features and prognosis of dermatomyositis patients with interstitial lung disease (ILD) as an initial manifestation. Medical records of 184 dermatomyositis inpatients complicated with ILD, admitted into Peking Union Medical College Hospital from January 1999 to January 2013, were retrospectively analyzed. The clinical features, biochemical parameters, positive rates of autoantibodies, radiology, pulmonary function tests, pathology, treatments and prognosis were compared between two subgroups of ILD-initial and non-ILD-initial dermatomyositis. The incidence of ILD of dermatomyositis inpatients was 17%. The average age was 48 ± 12 years and the gender ratio of male-to-female was 63: 121. Eighty eight (47.8%) dermatomyositis patients had ILD as an initial manifestation, including (n = 42, 22.8%) of ILD concomitant dermatomyositis (within 1 month) and (n = 46, 25.0%) of ILD before dermatomyositis with an average ahead time of (11 ± 3) months. Patients of ILD-initial dermatomyositis had a higher incidence of dyspnea on exertion, cough and lung crackles, but there were lower incidences of heliotrope rash, chest V area rash, shawl sign and joint involvement than non-ILD-initial dermatomyositis (P < 0.05). The positive rate of anti-Jo-1 antibodies of ILD-initial dermatomyositis group was 13.6%. The main performances of ILD-initial dermatomyositis on pulmonary function tests were diffusing and restrictive ventilation impairment. And there was a lower diffusing rate of carbon monoxide than non-ILD-initial dermatomyositis group (P < 0.01). Organic and non-specific interstitial pneumonias were the major clinical pathology types of ILD-initial dermatomyositis. The mortality rate of ILD-initial dermatomyositis patients was 19.3% and there was no significant difference from non-ILD-initial dermatomyositis (P > 0.05). The main course of ILD-initial dermatomyositis was respiratory failure due to progressive ILD (n = 13, 76.5%). ILD as an initial manifestation is a common complication and a major mortality cause of dermatomyositis inpatients. And the frequent clinical pathology types are organic and non-specific interstitial pneumonias. Symptoms of skin and muscle, creatine kinase and anti-synthetase antibodies should be closely monitored.

Objective: To investigate the clinical and immunological features of cardiac involvement in patients with dermatomyositis (DM). Methods: Data of 271 adult patients with DM diagnosed in the Department of Rheumatology and Immunology, Peking University People's Hospital from 2003 to 2018 were collected retrospectively and analyzed statistically. Results: The occurrence of cardiac involvement in DM was 15.9% (43/271). Main feature of cardiac involvement in DM was elevated cardiac troponin I (cTnI). The most common abnormalities of ECG were T wave abnormality (27.9%, 12/43), sinus tachycardia (16.3%,7/43), ST-T change (14%, 6/43) and right bundle branch block (7%, 3/43). The common manifestations of echocardiography were left ventricular diastolic dysfunction (23.3%, 10/43) and pericardial effusion (23.3%, 10/43). As compared with DM patients without cardiac involvement, DM patients with cardiac damage were more likely to have rapidly progressive interstitial lung disease (ILD), skin damage, anemia, elevated creatine kinase, decreased C3 and serum albumin (P<0.05). Positive anti-Ro-52 antibody and Jo-1 antibody were detected more common in DM with cardiac involvement(P<0.05). Conclusions: Cardiac damage is common complication of DM. Manifestations of cardiac damaging are varied. Rapid progressive ILD and positive Jo-1 and Ro-52 antibodies are more common in this group. Clinicians should improve the awareness of cardiac involvement in DM patients.

BackgroundWe aimed to develop a risk score to predict hepatic complications including hepatic decompensation and hepatocellular carcinoma in patients with non-alcoholic fatty liver disease (NAFLD).MethodsThe training cohort included adult NAFLD...

Anti-Ro52 antibody is an independent risk factor for interstitial lung disease in dermatomyositis

Objective To investigate the clinical and immunological features of rapid progressive interstitial lung disease(ILD) in patients with idiopathic inflammatory myopathy(IIM). Methods The medical records of 146 adult IIM patients associated with ILD in Peking University People's Hospital from February 1996 to February 2015 were retrospectively analyzed. They were divided into three subgroups: the classic DM, PM and the clinical amyopathic dermatomyositis(CADM), and were further stratified based on with or without rapid progressive ILD(RP-ILD). Chi-squared test was used for group comparisons of categorical data and independent-sample t test for numerical data. Results ① Among 146 patients, 62(42.5%) developed RP-ILD. The prevalence of RP-ILD in CADM was signifcantly higher than dermatomyositis(DM) and polymyositis(PM). ② ILD occurred after or at the same time with IIM in more than 90% of patients. ILD arising before or simultaneously with DM(named ILD) tended to progress rapidly. ③ For the DM group, mechanic's hands, fever, lymphopenia, hypoxemia, hypoalbuminemia, and the elevation of globulin α1 were associated with RP-ILD. CADM-ILD with weakness of swallow muscles, increasing C-reactive protein(CRP) and globulin α2, decreased vital capacity and the relatively high level of segmented granulocytes in bron-choalveolar lavage fluid tended to undergo a rapid progressive clinical course. Additionally, the decreased free triiodothyronine(FT3) and the elevation of tumor markers including carcino-embryonic antigen(CEA), neuron specific enolase(NSE), cytokerantin-19-fragment(CYFRA211) and ferritin were significantly more frequent both in DM and CADM with RP-ILD(P<0.05) patients. ④ According to multivariate analysis, mechanic's hands [HR=31.747, 95%CI(2.367, 425.817),P=0.009] and the elevation of CEA [HR=57.047, 95%CI(1.140, 2 854.885),P=0.043] and CRP [HR=31.568, 95%CI(1.818, 548.093),P=0.018] were potential predictive factors for RP-ILD in DM and CADM patients, respectively. Conclusion The prevalence of RP-ILD in CADM is higher than DM and PM. ILD usually occurs after or simultaneously with IIM, early-onset ILD in DM patients tends to progressive rapidly. Increased tumor markers and decreased FT3 indicate the deterioration of disease. Mechanic's hands and the elevation of CEA and CRP are potential predictive factors for RP-ILD in DM and CADM patients, respectively. Key words: Myositis; Lung disease, interstitial; Allergy and Immunology

Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibody (Ab) is significantly associated with internal malignancies in adult patients with dermatomyositis (DM). Although pathogenesis of cancer-associated DM is unknown, TIF1γ overexpression in tumors has been considered to be critical for the development of DM. The objective of this study was to investigate clinical characteristics of patients with anti-TIF1γ Ab-positive DM and elucidate risk factors that are potentially associated with internal malignancy. In addition, we compared the expression of TIF1γ in tumor tissues of patients with anti-TIF1γ Ab-positive DM, anti-TIF1γ Ab-negative DM and without DM in order to investigate the pathogenesis of cancer-associated DM. We analyzed 77 Japanese patients with DM, and found 19 patients to be positive for anti-TIF1γ Ab. Patients with anti-TIF1γ Ab-positive DM were older and presented heliotrope rash and flagellate erythema more frequently than patients without anti-TIF1γ Ab (P<0.05). Interstitial lung disease (ILD) and rapidly progressive ILD, as well as palmar violaceous erythema, were less frequent in patients with anti-TIF1γ Ab than in patients without. Furthermore, internal malignancy and dysphagia were significantly more frequent in the anti-TIF1γ Ab-positive group (P<0.01). Male sex and dysphagia were significantly associated with internal malignancy in patients with anti-TIF1γ Ab-positive DM (P<0.01 and <0.05, respectively). Using immunohistochemistry, we examined the TIF1γ expression in tumors of 11 patients with cancer-associated DM (anti-TIF1γ Ab-positive, nine; anti-TIF1γ Ab-negative, two) and 25 patients without DM. TIF1γ was highly expressed in all tumors, and there was no significant difference in TIF1γ expression between patients with and without DM. Furthermore, TIF1γ expressions in tumors were similar irrespective of the presence of anti-TIF1γ Ab. These results suggest that anti-TIF1γ antibody may not be simply induced by overexpression of TIF1γ in tumors in patients with DM, but that other mechanisms may exist.