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Objective:To analyze the Risk factors for rapid progression of inpatients with anti-melanoma differentiation associated gene5 (MDA5) antibody-positive dermamyositis (DM) complicated with interstitial lung disease (ILD), and construct a clinical predictive model.Methods:A total of 63 hospitalized patients with anti MDA5 positive DM combined with ILD (MDA5+ DM-ILD) from January 1, 2016 to May 30, 2022 at the Second Affiliated Hospital of the Air Force Military Medical University were included in the study. They were divided into a control group (DM-ILD) and an observation group (DM-RPPILD) based on whether they had rapidly progressing interstitial lung disease (RPILD). Retrospective collection and organization of clinical case data from patients were conducted, and binary logistic regression was used to summarize the risk factors of DM-RPILD. R software was used to construct a clinical prediction model for RPILD occurrence using training set data, and validation set data was used to verify the predictive ability of the model.Results:The proportion of patients with SpO 2<90% at the initial diagnosis of ILD, the titers of anti MDA5 antibodies, immunoglobulin M (IgM), serum ferritin (FER) levels, and positive rates of anti Ro52 antibodies in the observation group were higher than those in the control group, the lymphocyte (LYM) count level was lower than that of the control group (all P<0.05). Binary logistic regression analysis showed SpO 2<90% at the initial diagnosis of ILD, FER level, LYM count, and anti Ro52 antibody were the influencing factors for the occurrence of RPILD (all P<0.05). The area under the curve (AUC) of the training set prediction model for predicting resistance to MDA5+ DM-RPILD was 0.922(95% CI: 0.887-0.957), with a sensitivity of 95.7% and a specificity of 72.5%; In the validation set, the prediction model predicted an AUC of 0.939(95% CI: 0.904-0.974) for resistance to MDA5+ DM-RPILD, with a sensitivity of 90.0% and a specificity of 88.9%; The calibration curves of the training and validation sets indicated that the predictive model had good calibration ability. Conclusions:SpO 2<90% at the initial diagnosis of ILD, FER levels increase, LYM count levels decrease, and anti Ro52 antibody positivity are risk factors for RPILD. The constructed clinical model has good predictive ability and has certain guiding significance for clinical work.
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Juvenile dermatomyositis (JDM) is the most common subtype of juvenile idiopathic inflammatory myopathy (JIIM), characterized by non-suppurative inflammation of skin and muscle.JDM frequently involves important organs such as lungs.JDM with anti-melanoma differentiation-associated gene (MDA) 5 antibody has unique clinical characteristics, mainly including skin mucosal ulcer, palm papule, hair loss and arthritis.Interstitial lung disease (ILD) is its most serious complication.The levels of serum ferritin, Krebs von den Lungen-6 and interleukin-18 can be used as important indicators of disease activity and prognosis.Glucocorticoids combined with immunosuppressants are the basic treatment for the disease.Immunosuppressants include calcineurin inhibitors (Cyclosporine A and Tacrolimus), Cyclophosphamide, Azathioprine, Mycophenolate Mofetil, etc.Refractory patients can also be treated with Rituximab, Janus kinase inhibitor and human immunoglobulin.Early active treatment of JDM with anti-MDA 5 antibody can alleviate the symptoms, reverse organ damage and improve the long-term prognosis.
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Objective:To clarity the clinical features of juvenile dermatomyositis (JDM) with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody.Methods:Retrospective study.Clinical data of 11 anti-MDA5 autoantibody-positive JDM patients in the Department of Rheumatology and Immunology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2016 to January 2019 were retrospectively recruited for analyzing their clinical characteristics, pulmonary imaging and pulmonary function, thus summarizing treatment experiences.Results:A total of 11 children with anti-MDA5 autoantibody-positive JDM were recruited, involving 2 males and 9 females, with the average onset age of 1-13 (5.8±4.2) years.Clinical manifestations included rash in 11 cases (100.0%), arthritis in 5 cases (45.5%), and myasthenia in 4 cases (36.4%). Muscle enzyme elevated in 10 cases (90.9%) and serum ferritin (SF) elevated in 9 patients (81.8%). Ten cases (90.9%) showed interstitial lung disease (ILD), manifesting as ground glass opacity at subpleural area on CT scans, restrictive ventilation and decreased diffusion function on lung function test, while respiratory symptoms were absent.All patients were treated with glucocorticoid combined with immunosuppressor.Case 2 developed into rapid progressive pulmonary interstitial disease (RPILD), and died of respiratory failure 2 months later.The remaining was followed up for 1-2 years, and the ILD was relieved.Conclusions:All recruited children with anti-MDA5 autoantibody-positive JDM presented typical rash, and mild muscle weakness with a greater tendency to arthritis.Chinese pediatric patients are prone to complicate with ILD with no respiratory symptoms, but ground glass opacity at subpleural area on CT, and restrictive ventilation and decreased diffusion function on lung function test can be detected.Elevated SF is associated with the development of ILD.Glucocorticoid combined with immunosuppressive therapy is effective to JDM with ILD, but ineffective for RPILD.The mortality of anti-MDA5 autoantibody-positive JDM is high without an effective treatment.
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Pseudoangioedema, a new type of skin lesions of dermatomyositis, is characterized by localized or diffused, non-pitting, non-pruritic edema on the face, lips, and limbs, with or without erythema. Most dermatomyositis patients with pseudoangioedema are positive for anti-transcriptional intermediary factor 1γ antibodies, and experience severe muscle injuries, increase of serum creatine kinase levels, and refractory dysphagia. A small number of dermatomyositis patients with pseudoangioedema are positive for anti-melanoma differentiation-associated gene 5 antibodies, and have lung involvement. Therefore, high attention should be paid to the occurrence of pseudoangioedema in patients with dermatomyositis, and the screening of specific antibodies can facilitate early diagnosis and differential treatment, as well as improvement in symptoms and survival rates.
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Objective:To explore the independent risk factors and early diagnosis of dermatomyositis (DM) with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody.Methods:A total of 223 DM patients admitted to the Department of Rheumatology and Immunology, Affiliated Hospital of Xuzhou Medical University from January 2012 to June 2021 were retrospectively analyzed, according to whether the anti-MDA5 antibody was positive or not, the patients were divided into anti-MDA5 antibody positive group ( n= 34) and anti-MDA5 antibody negative group ( n=189). The demographic data, clinical manifestations and laboratory test results of the two groups were compared. The risk factors of DM patients with positive anti-MDA5 antibody were analyzed by binary Logistic regression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of various risk factors for anti-MDA5 antibody positive DM patients. Results:The incidence of skin ulcer [20.6%(7/34) vs 9.0%(17/189), χ2=4.03, P=0.045], the positive rate of anti-Ro52 antibody [61.8%(21/34) vs 21.2%(40/189), χ2=23.90, P<0.001], the incidence of interstitial lung disease (ILD) [91.2% (31/34) vs 38.6%(73/189), χ2=31.98, P<0.001] and rapidly progressive interstitial lung disease (RP-ILD) [67.6%(23/34) vs 5.3%(10/189), χ2=88.87, P<0.001], the levels of D-dimer [1.87(1.23, 2.56) μg/ml vs 1.15(0.59, 1.29) μg/ml, χ2=4.68, P<0.001] and serum ferritin (SF) [931.65(579.12, 1 160.43) ng/ml vs 507.40(200.40, 588.55) ng/ml, χ2=5.60, P<0.001] in the anti-MDA5 antibody positive group were higher than those in the anti-MDA5 antibody negative group, wherease the creatine kinase (CK) level in the anti-MDA5 anti-body positive group was significantly lower than that in the anti-MDA5 antibody negative group [85.50(61.25, 1 55.00) U/L vs 263.00(66.50, 1 111.14) U/L, χ2=3.08, P=0.002]. Multivariate Logistic regression analysis showed that positive anti-Ro52 antibody [ OR(95% CI)=5.027(1.632, 15.483), P=0.005], increased D-dimer level [ OR(95% CI)=1.665(1.124, 2.466), P=0.011], occurrence of ILD [ OR(95% CI)=10.071(2.061, 49.207), P=0.004] and RP-ILD[ OR(95% CI)=10.91(3.294, 36.134), P<0.001] were independent risk factors for anti-MDA5 antibody positive DM patients. The ROC curve showed that the areas under the curve (95% CI) of anti-Ro52 antibody, D-dimer, ILD and RP-ILD were 0.703(0.615, 0.791), 0.752(0.661, 0.843)], 0.763(0.703, 0.822), 0.812(0.730, 0.893) respectively. The P value of all these parameters were <0.001 and their value in predicting anti-MDA5 antibody positive DM was high. Conclusion:Positive anti-Ro52-Ab, increased D-dimer level, presence of ILD and RP-ILD are independent risk factors for anti-MDA5 antibody positive DM patients, and they have certain early diagnostic value for DM patients with positive anti-MDA5 antibody.
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Objective:To investigate the role of HIS (hyperinflammatory syndrome) score in predicting the prognosis of anti-melanoma differentiation associated gene 5(MDA5) antibody-positive dermatomyositis (DM) patients with interstitial lung disease (ILD).Methods:A total of 43 patients with anti-MDA5 antibody-positive dermatomyositis and 228 connective tissue disease (CTD) patients with ILD hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2018 to April 2021 were enrolled into this study. All patients were complicated with ILD and their HIS score were assessed. Non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and receiver operating characteristic (ROC) curve were used for data analysis. Results:The HIS score of 43 patients with anti-MDA5 antibody-positive dermat-omyositis were collected. Among 228 CTD-ILD patients in the control groups, the primary disease consisted of 33(14.5%) anti-synthetase antibody syndrome (ASS), 44(19.3%) rheumatoid arthritis (RA), 65(28.5%) Sj?gren's syndromes (SS), 43 (18.9%) systemic sclerosis (SSc) and 43 (18.9%) systemic lupus erythematosus(SLE). The HIS score of anti-MDA5-positive DM-ILD patients [2(1, 3)] was higher than those in ASS patients [1(0, 2), Z=-2.06, P<0.05] and significantly higher than those in RA-ILD [1(0, 2), Z=-2.87, P<0.01], SS-ILD [0(0,1), Z=-5.78, P<0.01], SSC-ILD [1(0, 1), Z=-3.84, P<0.01] and SLE-ILD [1(0, 2), Z=-3.81, P<0.01]. Comparing HIS score of anti-MDA5-positive DM-ILD patients, the 3-months mortality rate in the low, medium and high groups was 0(0/15), 38.1%(8/21) and 85.7%(6/7). The area under ROC curve (95% CI) was 0.857[(0.747, 0.967), P<0.001] for HIS score in predicting 3-months mortality probability of anti-MDA5-positive DM-ILD. Conclusion:HIS score of anti-MDA5-positive DM-ILD is higher than that in CTD-ILD patients and the baseline level is related to the 3-months mortality rate.
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Objective:To investigate the high resolution computed tomography (HRCT) findings, laboratory test results and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis complicated with lung interstitial lesions, and to analyze the correlation between the HRCT findings and clinical course of disease.Methods:Twenty-seven patients with anti-MDA5 antibody positive associated dermatomyositis (DM) were included and divided into two groups: acute/subacute group ( n=15) and chronic group ( n=12). HRCT images of lung were analyzed. Clinical data including gender, age, clinical manifestations and course of disease, anti-Ro52 antibody, creatine kinase (CK), antinuclear antibody (ANA), anti-Jo-1 antibody and erythrocyte sedimentation rate (ESR) were also collected. χ2 test was adopted for statistical analysis. Results:① Interstitial changes were 100%(27/27). The proportion of unilateral localized distribution was the most [48%(13/27)], followed by bilateral localized distribution [30%(8/27)], and bilateral diffuse distribution [22%(6/27)). ② Among the HRCT findings of lung interstitial changes, ground glass shadow was the most common presentations [59%(16/27)], followed by subpleural curve sign [63%(17/27)] and interlobular septal thickening [56%(15/27)], while honeycomb sign [0(0/27)] had the lowest rate of presentation. ③ Compared with the chronic progressive group, the acute/subacute progressive group presented as chest tightness (80% vs 8%, χ2=13.715, P<0.05) and dyspnea (47% vs 0, χ2=7.560, P<0.05). Acute/subacute HRCT showed ground glass opacity (87% vs 25%, χ2=10.501, P<0.05). The prominent HRCT showed interlobular septal thickening in the chronic course group (83% vs 33%, χ2=6.750, P<0.05). ④ The anti-MDA5 antibody (+++) index was significantly different (88% vs 25%, χ2=8.168, P<0.05). There was no significant difference in anti-Ro52 antibody (+), ANA(+), anti-Jo-1 antibody(+), CK elevation and ESR elevation between the two groups ( P>0.05). Conclusion:Most dermatomyositis patients with positive anti-MDA5 antibody are complicated with interstitial lung lesions, the HRCT manifestations of lung are diverse. In order to confirm the diagnosis of this disease, clinical manifestations, laboratory and pathological examinations are required.
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Objective To investigate the association of human leucocyte antigen (HLA-DRB1) with anti-melanoma differentiation-associated gene 5 (MDA5) expression in polymyositis/dermatomyositis (PM/DM).Methods Seventy patients with PM,104 patients with DM and 400 healthy controls were included.Genotyping of HLA-DRB1 was performed using the sequencing-based typing method.Levels of anti-MDA5 were measued by enzyme linked immunosorbent assay using recombinant MDA5 antigen.The frequencies of HLA-DRB1 alleles were compared between the patients and controls using a chi-square test or Fisher's exact test.Results Frequencies of DRB1 * 04∶01 [17.0％ vs 1.3％,corrected P-value (Pc)=3.8×10-8;odds ratio (OR)=16.2;95％ confidence interval (CI) (6.6,39.7)] and DRB1 * 12∶02 [(42.6％ vs 19.3％,Pc=0.008;OR=3.1;95％ CI(1.7,5.7)] were significantly higher in anti-MDA5 positive PM/DM patients compared with the controls.The frequencies of DRB1 * 04∶01 [P=5.2×10-6,OR=17.1,95％CI:(5.3,54.9)\ and * 12∶02 [P=3.8×10-4,OR=3.1,95％CI(1.7,5.7)] in anti-MDA5 positive DM-interstitial lung disease (ILD) patients were higher than those in the controls,whereas the frequencies of DRB1 * 04∶01 and * 12∶02 did not differ between the anti-MDA5 negative DM-ILD patients and the controls.No difference in the frequency of DRB1 alleles,other than * 04∶01,carrying the shared epitope (SE),i.e.* 01∶01,* 01∶02,* 04∶05 and * 10∶01,was observed between the controls and DM patients stratified by the presence of anti-MDA5 and ILD.Conclusion DRB1 * 04∶01 and * 12∶02 confer susceptibility to anti-MDA5 antibody production in DM,which cannot be explained by the SE hypothesis.
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Objective The current meta-analysis was performed to update the evidcnce on anti-melanoma differentiation-associated gene 5 (MDA5) antibody for the diagnosis of rapid progressive interstitial lung disease (RPILD) and chronic ILD in adult or juvenile dermatomyositis (JDM).Methods The electronic search on PubMed,Embase,Cochrane Library,CNKI,WangFang Data,VIP and China Biology Medicine database was conducted from their inception to May,2017.Meta-disc1.4 was used to calculate heterogeneity and obtain the pool sensitivity,specificity,diagnostic odds ratio,positive and negative likelihood ratios and summarized receiver operating characteristic (SROC) curve.Quality assessment and publication bias were determined by QUADAS-2 and STATA 12.0.Results A total of 32 studies with high quality and middle heterogeneity were selected for the final data synthesis.Anti-MDA5 showed a higher diagnostic and prognostic value for RPILD (AUC =0.927,Q * =0.862),compared with chronic ILD (AUC =0.717,Q * =0.667) in adult dermatomyositis patients.For diagnosing RPILD in JDM,the value of MDA5 detection (AUC =0.836,Q * =0.768)was weak.For the prediction of RPILD,the validity of anti-MDA5 detection in clinical amyopathic dermatomyositis (CADM) (AUC =0.942,Q* =0.880) was higher than that in DM (AUC =0.926,Q * =0.860),which was also more applicable to East-Asia populations (AUC =0.960,Q* =0.891),compared with Chinese (AUC =0.925,Q* =0.859) and Western populations (AUC =0.928,Q* =0.863).The methodological assessment for different anti-MDA5 detection implied ELISA (AUC =0.929,Q* =0.864) was superior in performance as immunoprecipitation (AUC =0.927,Q* =0.859),and there was no publication bias according to Deek's plot.Conclusion Anti-MDA5 antibody should be a significant laboratory index for diagnosis and prediction of ILD in adult DM and JDM with high sensitivity and specificity.