Triple Positive for Anti-MDA5, Anti-EJ and Anti-Ro52 Antibodies Dermatomyositis Associated Interstitial Lung Disease：a case report

Triple Positive for Anti-MDA5, Anti-EJ and Anti-Ro52 Antibodies Dermatomyositis Associated Interstitial Lung Disease：a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Triple Positive for Anti-MDA5, Anti-EJ and Anti-Ro52 Antibodies Dermatomyositis Associated Interstitial Lung Disease：a case report Jia Guo, Lingjie Du, Bo Xu, Chunting Tan, Ranran Zhao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4288480/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Clinically amyopathic dermatomyositis (CADM) is a disease with the typical skin manifestations of dermatomyositis (DM) and few or no obvious muscle weakness. The anti-melanoma differentiation associated protein 5（MDA5）antibody positive CADM patients are at a high risk of developing rapidly progressive interstitial lung disease (RP-ILD)，and exhibit immensely poor prognosis and high mortality. The disease course and severity of MDA5+CAMD are highly different, wherein some patients presented marked treatment response and didn’t occur exacerbation. Analysis to these special groups bring us better understanding of MDA5+CADM. Case presentation We presented a patient with anti-MD5 anti-Ro52 anti-EJ-triple positive DM patient. She was initially characteristic with darken skin for 2 years before gradually occurred dry cough, fever and dyspnea. She had a low oxygen saturation and diffusing capacity of the lungs for carbon monoxide. With combination therapy of GCs and two immunosuppressants, the woman obtained a rapid remission and persisted for a long time. Conclusions Patients with anti-MD5 anti-Ro52 anti-EJ-triple positive DM-ILD may present a less aggressive disease course and an individual appropriate therapy may be promising for long-term maintenance. dermatomyositis clinical amyopathic dermatomyositis rapidly progressive interstitial lung disease anti-melanoma differentiation associated protein 5 antibody anti-EJ antibody anti-Ro52 antibody Figures Figure 1 Figure 2 Background Idiopathic inflammatory myopathies (IIM) is a heterogeneous group of diseases characterized by inflammation affecting the skeletal muscles and extramuscular organs, particularly the skin and lungs. Interstitial lung disease (ILD) is among the major extramuscular complications of polymyositis (PM) and dermatomyositis (DM), two common clinical subtypes of IIM. Clinical amyopathic dermatomyositis (CADM) is a subset of DM and presents typical skin manifestations of DM without muscle weakness. ILD accompanied by anti-MDA5 positive dermatomyositis (MDA5 + DM), especially MDA5 + CAMD often progresses rapidly and has poor treatment responses. Although some MDA5 + CADM patients have a chronic course of ILD, these patients may be accompanied some protective factors. Herein, we describe the presentation and management of a patient with triple positive for anti-MDA-5, anti-EJ and anti-Ro52 antibody, who was followed up for 9 months and maintained remission. Analyzing this special subset with less aggressive phenotypes will help us to better understand and give more suitable treatment of MDA5 + CADM. Case presentation A 33-year old woman was admitted to Beijing Friendship Hospital after multiple outpatient presentations at local hospital with dry cough and fever for 10 months. She was received anti-infective therapies with cephalosporin, penicillin and aminoglycosides, but these symptoms repeatedly occurred and progressive dyspnea gradually developed. A detailed medical history revealed that her skin was darken in the last two years from chest to the back and then to the limbs, but she didn’t take it seriously until occurring more discomforts as described above. She has no other significant medical histories. She was a clerk work in office who resided in Zhangjiakou, Hebei Province. She was not married and live alone. She did not have any significant bird or animal contact, also no contact with toxic gas or dust. She had no history of cigarette or recreational drug use. Upon admission, she had a blood pressure of 94/64 mmHg, pulse rate of 98 beats/min, respiratory rate of 24 times/min, oxygen saturation of 90% under room air and temperature of 36.3℃. Physical examination revealed Velcro sounds at bilateral lower lungs. Meanwhile, darkened skin on the chest, back, upper and lower limbs. No other positive signs were detected. Blood investigations revealed leukocytosis and its differential counts in normal range, mildly elevated C-reactive protein (CRP)at 16.7mg/L and obviously elevated erythrocyte sedimentation rate༈ESR༉at 44mm/h. Sputum bacterial and fungi cultures, gram staining, acid-fast bacilli staining and common respiratory virus antibodies were all negative. Myositis autoantibody tests were performed and she was tested positive with anti-MDA5, anti-Ro52 and anti-EJ antibodies. There were no other positive results of autoimmune investigations and no obvious abnormal in tumor makers༈more details see Table 1 ༉. She also underwent pulmonary function tests and was found having decreased diffusing capacity of the lungs for carbon monoxide (DLCO). Additionally, the initial Chest computed tomography (CT) showed bilateral subpleural ground-glass opacities, consolidation and grid shadows, lower lungs predominant (Fig. 2 ). She was finally diagnosed with CADM, moreover, anti-MDA5, anti-Ro52 and anti-EJ-antibody were triple positive, skin and lung were mainly involved. Her condition improved after treatment with glucocorticoids, immunosuppressants and anti-infection agents. Her degree of dyspnea relieved, oxygenation index rose and her skin color lightened distinctly(Figure 1 ). Auxiliary examinations showed disease activity and severity markers, such as CRP、ESR and LDH declined to normal (Table 2 ). Moreover, her DLCO increased from 25.3mmol/min/kPa to 75mmol/min/kPa and a repeat CT chest demonstrated visibly absorption of pulmonary lesions (Fig. 2 ). The patient made good recovery and maintained for an extended period of time. Table 1 Summary of infectious and non-infectious investigations. Investigation(method) result Reference range Infectious aetiology Sputum bacterial smear and culture Negative Negative Fungi smear and culture Negative Negative Acid-fast bacilli staining Negative Negative Chlamydia and mycoplasma antibodies Negative Negative Influenza and parainfluenza virus antibodies Negative Negative Respiratory syncytial virus antibody Negative Negative Adenovirus antibody Negative Negative Legionella pneumophila antibody Negative Negative Rickettsia antibody Negative Negative Epstein-Barr virus and cytomegalovirus antibody Negative Negative Rubella virus antibody Negative Negative Herpes simplex virus antibody Negative Negative Coxsackie B virus antibody Negative Negative T-SPOT Negative Negative 1,3-β-d-Glucan test Negative Negative Anti-tuberculosis antibody Negative Negative Auto-immune aetiology(units) ANA screening 1:80 Fluorescent pattern of ANA cytoplasmic Anti-Ro52 Positive (2+) Negative Anti-double stranded DNA(IU/mL) 67.49 < 300 Anti-neutrophil cytoplasmic antibodies (c-ANCA and p-ANCA) Negative Negative Extractable nuclear antigen antibodies Anti-Ro52 Positive Negative Anti-CCP、anti-MCV、anti-AFP & anti-AKA antibody Negative Negative Myositis-specific antibody MDA-5、EJ、Ro-52 Positive Negative Jo-1、PL-7、PL-12、SRP、Mi-2、TIF1-γ、HMGCR、SAE1/2、NXP-2、OJ、KS、ZO、HA、Scl-70、PM-Sc1100、PM-Scl175、KU、RNA-PIII、Th/To、Fibrillarin、NOR-90 Negative Negative Immunoglobulins IgM (mg/dl) 166 40–230 Immunoglobulins IgA (mg/dl) 331 70–400 Immunoglobulins IgG (mg/dl) 1420 700–1600 C3 Complement (mg/dl) 112 90–180 C4 Complement (mg/dl) 31.3 10–40 Rheumatoid factor (KIU/L) 41.9 0-15.9 Tumor aetiology Tumor markers CA125(U/mL) 52.8 0–35 CA199(U/mL) 52 0–35 CA153(U/mL) 33.1 0-31.3 HE4(pmol/L) 222.6 0-140 NSE、AFP、CEA、CY211、SCC、CA242、CA724、CA50 Normal Table 2 Summary of investigations at presentation and other relevant time-points Investigation (unit, reference range) Baseline 9 − 7 2weeks 9–21 1months 9–27 3months 11–23 6months 3–29 9months 5–16 White cell count (3.5–9.5*10 9 /L) 6.33 14.17 11.22 8.89 5.82 6.93 Haemoglobin (115-150g/L) 133 134 132 151 147 150 Platelet count (125–350*10 9 /L) 271 160 128 165 176 121 C-reactive protein (0-8mg/L) 16.7 < 0.5 < 0.5 2.64 11.26 10.89 Erythrocyte sedimentation rate(mm/h) 44 6 4 Procalcitonin (ng/ml) 0.02 Ferritin(ng/mL) 78.8 LDH 387 166 CK 756 120 Discussion Anti-MDA5-associated DM, which is a rare subtype of DM that presents with unique mucocutaneous features, including Gottron’s sign, Heliotrope rash, V sign, Shawl sign, Periungual erythema, Mechanic’s hand and skin ulcer. It is gaining increasing attention due to its complication of RP-ILD and high mortality. The incidence of anti-MDA5 + DM associated ILD varies in different regions. The prevalence was 11%-75% in Europeans and United States while it was 92%-100% in Asians [ 1 ] . According to previous studies, about 40%-70% of MDA5 associated DM cases developed RP-ILD and died of respiratory failure during half year after admission due to the progressive course and a poor response to the treatment [ 2 ] . However, in our case, the patient with positive of anti-MDA5 had a good treatment effect and maintained remission for more than half year. There are several reflections about why she had a good outcome and why her prognosis modified. Timely diagnosis and multi-combination therapy are important We made a rapid and accurate diagnosis at the early stage. The woman was highly suspected CADM with her outstanding skin manifestations, few myositis evidence, and nonspecific interstitial pneumonia. The diagnosis was finally verified after several myositis-specific antibodies exhibited positive like anti-MDA5, anti-EJ and anti-Ro52. The timely intervention with triple combination therapy of GCs, immunosuppressants in induction phase were extremely important. With consideration of her disease severity and relative chronic disease progression, we applied a moderate-dose GCs and alternate-day intravenous cyclophosphamide further to avoid many common side effects because of high dose. In remission phase, we gradually decreased oral prednisone, meanwhile combining oral cyclophosphamide and tacrolimus to get a long-term maintenance. These triple combination continuous therapies have improved her survival rates and prolonged her recurrence-free survival. Completely learning of clinical conditions is helpful for predicting outcome A current meta-analysis included 29 cohorts with 2645 patients found that old age, male sex, hypoxemia, low FVC, lymphocytopenia, and high levels of ferritin, CRP, creatine kinase, and LDH predicted poor prognosis in patients with MDA5 + DM [ 3 ] . In a large Chinese cohort study of patients with MDA5-DM, patients were classified into three subgroups according to peripheral lymphocyte count. The results proved severe lymphopenia is strongly associated with high mortality, and a normal peripheral lymphocyte number at baseline predicts a better prognosis [ 4 ] . However, a single indicator fails to accurately predict a particular outcome, a prediction model incorporating several relevant risk factors may enhance predictive power. Therefore, several prediction models for monitoring the disease severity or prognosis in MDA5-DM were emerged ( Table 3 ). The CROSS model is one of the prediction models, four variables were included: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. And a point scoring system was used to classify anti-MDA5 + DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high- risk group was about 70–80%, significantly higher than those in the high-risk group (30–40%) and moderate-risk group (6–9%) [ 5 ] . The CRAFT model also included 4 variables, CRP-to-albumin ratio, red blood cell distribution width-coefficient of variation, fever status, and CD3 + T cells [ 6 ] . FLAIR score is a prediction model for mortality risk, which included 5 variables: ferritin, LDH, anti-MDA5 antibody titers, CT imaging score and RP-ILD [ 7 ] . According to these predictors or models, our case was all belonged to a mild or moderate group, indicating a relatively good outcome. Table 3 Several prediction models for RP-ILD risk or mortality in anti-MDA5 + DM patients Variables Subgroups score Prediction risk CROSS model CRP (abnormal,1; normal,0) Ro-52 antibody (positive,1; negative,0) Disease duration (<3 months,2;≥3months,0) Sex (male,1; female,0) Moderate:0–2 High:3–4 Very high:5–6 RP-ILD risk Moderate:6.67% High:41.69% Very high:85.71% CRAFT model CRP-to-albumin ratio, red blood cell distribution width-coefficient of variation, fever status, and CD3 + T cells RP-ILD risk Sensitivity:0.81 Specificity:0.91 FLAIR score Ferritin(<636ng/ml,0;≥636ng/ml,2) LDH(<355U/L,0;≥355U/L,2) anti-MDA5 antibody titers(negative,0;+,2;++,3;+++,4) CT imaging score*(< 133,0;≥133,3) RP-ILD (non-RP-ILD,0;RP-ILD,2) Low:0–4 Medium:5–9 High:10–13 Mortality risk Low:0% Medium:7.7% High:85% * CT imaging score were evaluated based on the method described by Ichikado et al [ 8 ] . Some protective factors may be essential to balance the negative effects. The majority of researchers stated that the coexistence of anti-MDA5 and anti-Ro52 antibodies led to a worse prognosis and lower survival rates [ 9 ][ 10 ] . Besides, a large retrospective case-control study revealed that CAMD was associated with higher rates of mortality, 1-year mortality and RP-ILD than classic DM [ 11 ] . Similarly, some other studies also proved patients with CADM exhibit relatively worse symptoms and prognosis, which doesn’t accord with our case. Some special features for instance onset of black skin maybe one of protective factors. A study identified three different subgroups in MDA5-DM: Patients with RP-ILD show the highest mortality rate, those with skin vasculopathy and clinical myositis exhibit an intermediate prognosis and sole dermato-rheumatologic symptoms were associated with the best outcome [ 12 ] . A report systematically analyses histopathological findings in two MDA-5 + CADM patients with fatal RP-ILD. These two patients both had none or subtle skin changes and no overt muscle symptoms until hospitalization. Noteworthy, the muscle autopsy showed characteristic signs of muscle inflammation, and the lung autopsy showed massive interstitial and alveolaroedema, hyaline membranes and intraluminal fibrinoid deposits [ 13 ] .Thus, the different symptoms in skin may illustrate different pathologies in muscle and lung and then probably affect prognosis. The chronic blacken skin symptom before affected respiratory system may help avoiding disease progression. Moreover, anti-EJ antibody positive may another protective factor. One Chinese retrospective research compared anti-MDA5 and anti-aminoacyl-tRNA synthetase antibody (anti-ARS, including anti-PL-12, anti-PL-7, anti-EJ and anti-Jo1) double-positive dermatomyositis patients (Anti-MDA5+/ARS + group) to single anti-MDA5 positive (Anti-MDA5+/ARS- group) and single anti-ARS positive patients (Anti-MDA5-/ARS + group). The result presented that anti-MDA+/ARS + group had higher ferritin levels than Anti-MDA5-/ARS + group and higher CD4 + T-cell counts than Anti-MDA5+/ARS- group. Individuals with anti-MDA+/ARS + antibodies combined the features of anti-MDA5 + and anti-ARS + individuals and respond well to glucocorticoid therapy [ 14 ] . A latest review summarized the lung manifestations of MDA5 + DM, commonly including organizing pneumonia, which typically presents with subpleural consolidation during the early stage of the disease, non-specific interstitial pneumonia and non-specific interstitial pneumonia–organizing pneumonia overlap [ 2 ] , while grid shadows and pleura thicken seldom appeared as our case. Perhaps the special HRCT images play another important role to change prognosis. High-quality prospective studies are required to confirm our findings. SUMMARY Anti-MDA5 + DM usually has high risk to develop RP-ILD and has poor prognosis. Risk stratification to predict patients who will develop fatal RP-ILD is required for supporting therapy decision-making at early stage. According to our case, female, long disease duration and onset of black skin, coexistence of anti-EJ antibody, timely diagnosis and proper triple combination therapies, slightly damage of muscle perhaps indicate a better prognosis. Insights from our case might be beneficial for better understanding the disease course of anti-MDA + DM. Declarations Authors and Affiliations Department of Respiratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China Jia Guo, Lingjie DU, Bo Xu, Chunting Tan & Ranran Zhao Corresponding author Corresponding to Chunting Tan & Ranran Zhao. Ethics approval and consent to participate This study was approved by the Ethics Committee of Beijing Friendship Hospital. Availability of data and Materials All data used during the current study are available from the corresponding author on reasonable request. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Competing interests The authors declare no competing interests. Authors’ Contribution Jia Guo was involved in literature search and writing the original draft. Lingjie Du & Bo Xu was involved in collecting clinical data and obtaining informed consent from the patient. Ranran Zhao & Chunting Tan was involved in writing-review & editing. All authors read and approved the final manuscript. References DeWane M E, Waldman R, Lu J. Dermatomyositis: Clinical features and pathogenesis.[J]. Journal of the American Academy of Dermatology, United States: 2020, 82(2): 267–281. Lu X, Peng Q, Wang G. Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress.[J]. Nature reviews. Rheumatology, United States: 2024, 20(1): 48–62. Xie H, Zhang D, Wang Y, et al. Risk factors for mortality in patients with anti-MDA5 antibody-positive dermatomyositis: A meta-analysis and systematic review.[J]. Seminars in arthritis and rheumatism, United States: 2023, 62: 152231. Jin Q, Fu L, Yang H, et al. Peripheral lymphocyte count defines the clinical phenotypes and prognosis in patients with anti-MDA5-positive dermatomyositis.[J]. Journal of internal medicine, England: 2023, 293(4): 494–507. Wang L, Lv C, You H, et al. Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.[J]. Frontiers in immunology, Switzerland: 2024, 15: 1286973. Guo J, Mei C, Yu Q, et al. Risk Prediction for Rapidly Progressive Interstitial Lung Disease in Anti-MDA5-Positive Dermatomyositis: The CRAFT Model.[J]. Medical science monitor : international medical journal of experimental and clinical research, United States: 2023, 29: e940251. Lian X, Zou J, Guo Q, et al. Mortality Risk Prediction in Amyopathic Dermatomyositis Associated With Interstitial Lung Disease: The FLAIR Model.[J]. Chest, United States: 2020, 158(4): 1535–1545. Ichikado K, Suga M, Müller N L, et al. Acute interstitial pneumonia: comparison of high-resolution computed tomography findings between survivors and nonsurvivors.[J]. American journal of respiratory and critical care medicine, United States: 2002, 165(11): 1551–1556. Xu A, Ye Y, Fu Q, et al. Prognostic values of anti-Ro52 antibodies in anti-MDA5-positive clinically amyopathic dermatomyositis associated with interstitial lung disease.[J]. Rheumatology (Oxford, England), England: 2021, 60(7): 3343–3351. Cheng L, Xu L, Xu Y, et al. Gender differences in patients with anti-MDA5-positive dermatomyositis: a cohort study of 251 cases.[J]. Clinical rheumatology, Germany: 2024, 43(1): 339–347. Ji Q, Pan W, Zhang D, et al. Comparison of characteristics and anti-MDA5 antibody distribution and effect between clinically amyopathic dermatomyositis and classic dermatomyositis: a retrospective case-control study.[J]. Frontiers in immunology, Switzerland: 2023, 14: 1237209. Allenbach Y, Uzunhan Y, Toquet S, et al. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases.[J]. Neurology, United States: 2020, 95(1): e70–e78. Englert B, Dittmayer C, Goebel H-H, et al. “Amyopathic” MDA5-positive dermatomyositis with severe lung involvement presenting with net myositic morphological features - insights from an autopsy study.[J]. Neuromuscular disorders : NMD, England: 2024, 36: 42–47. Chen X, Zhang L, Jin Q, et al. The clinical features and prognoses of anti-MDA5 and anti-aminoacyl-tRNA synthetase antibody double-positive dermatomyositis patients.[J]. Frontiers in immunology, Switzerland: 2022, 13: 987841. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4288480","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":296624005,"identity":"d8f18efc-8c7c-4944-9278-4654108d41ca","order_by":0,"name":"Jia Guo","email":"","orcid":"","institution":"Beijing Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Guo","suffix":""},{"id":296624006,"identity":"33cc5146-2add-4a5b-a746-73deacaf99a1","order_by":1,"name":"Lingjie Du","email":"","orcid":"","institution":"Beijing Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lingjie","middleName":"","lastName":"Du","suffix":""},{"id":296624007,"identity":"8c8038c0-e233-4c1b-b988-300dcbf7003d","order_by":2,"name":"Bo Xu","email":"","orcid":"","institution":"Beijing Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Xu","suffix":""},{"id":296624014,"identity":"4abaa719-0812-4f4a-994a-544f3269cba7","order_by":3,"name":"Chunting Tan","email":"","orcid":"","institution":"Beijing Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chunting","middleName":"","lastName":"Tan","suffix":""},{"id":296624020,"identity":"80bbe304-cdf4-4574-8c17-54ffaacb64fd","order_by":4,"name":"Ranran Zhao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYNCCAgkgkcDA8AHKl8CnmAdMGkC0MM4gQQsDWAszDzFa7KUPP5P4YGCRJ++e/EzapsYu2uAA88HbPAx2eTht4Uszk5xhIFFseOaZmXTOseTcDQfYkq15GJKLcWrhYTA25jGQSNw4I8FMOrfhAFALj5k0D8OBxAacWtg/G/8Ba0n/Jm0J1sL/jYAWHsPHwBBLnC+RYybNCLGFDb+WMzyFD3uAWjbwvCm27AH6ZeZhNmPLOQbJOLWw97BvOPCjoi5xfnv6xhs/auxy+443P7zxpsIOpxY4MDjAwAKJDmYwl5B6IJBvYGD+QFjZKBgFo2AUjEQAAItjUrgKOE90AAAAAElFTkSuQmCC","orcid":"","institution":"Beijing Friendship Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ranran","middleName":"","lastName":"Zhao","suffix":""}],"badges":[],"createdAt":"2024-04-18 14:39:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4288480/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4288480/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55769503,"identity":"e7ab80c4-88d8-4719-8810-03f833039f41","added_by":"auto","created_at":"2024-05-02 20:42:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3594585,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4288480/v1/6dc69099437e3e03a90d7be8.png"},{"id":55769504,"identity":"272ebeb9-193b-4b4e-8cb1-98cebcbc1c28","added_by":"auto","created_at":"2024-05-02 20:42:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1268431,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4288480/v1/a9a3b7d8c026d91edec13eea.png"},{"id":59472338,"identity":"1ae523ab-175a-43ad-aa47-44ecf7f915c4","added_by":"auto","created_at":"2024-07-02 07:59:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":9076107,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4288480/v1/37430308-d326-4696-8792-31ea9c679323.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eTriple Positive for Anti-MDA5, Anti-EJ and Anti-Ro52 Antibodies Dermatomyositis Associated Interstitial Lung Disease：a case report\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eIdiopathic inflammatory myopathies (IIM) is a heterogeneous group of diseases characterized by inflammation affecting the skeletal muscles and extramuscular organs, particularly the skin and lungs. Interstitial lung disease (ILD) is among the major extramuscular complications of polymyositis (PM) and dermatomyositis (DM), two common clinical subtypes of IIM. Clinical amyopathic dermatomyositis (CADM) is a subset of DM and presents typical skin manifestations of DM without muscle weakness. ILD accompanied by anti-MDA5 positive dermatomyositis (MDA5\u0026thinsp;+\u0026thinsp;DM), especially MDA5\u0026thinsp;+\u0026thinsp;CAMD often progresses rapidly and has poor treatment responses. Although some MDA5\u0026thinsp;+\u0026thinsp;CADM patients have a chronic course of ILD, these patients may be accompanied some protective factors. Herein, we describe the presentation and management of a patient with triple positive for anti-MDA-5, anti-EJ and anti-Ro52 antibody, who was followed up for 9 months and maintained remission. Analyzing this special subset with less aggressive phenotypes will help us to better understand and give more suitable treatment of MDA5\u0026thinsp;+\u0026thinsp;CADM.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 33-year old woman was admitted to Beijing Friendship Hospital after multiple outpatient presentations at local hospital with dry cough and fever for 10 months. She was received anti-infective therapies with cephalosporin, penicillin and aminoglycosides, but these symptoms repeatedly occurred and progressive dyspnea gradually developed. A detailed medical history revealed that her skin was darken in the last two years from chest to the back and then to the limbs, but she didn\u0026rsquo;t take it seriously until occurring more discomforts as described above.\u003c/p\u003e \u003cp\u003eShe has no other significant medical histories. She was a clerk work in office who resided in Zhangjiakou, Hebei Province. She was not married and live alone. She did not have any significant bird or animal contact, also no contact with toxic gas or dust. She had no history of cigarette or recreational drug use.\u003c/p\u003e \u003cp\u003eUpon admission, she had a blood pressure of 94/64 mmHg, pulse rate of 98 beats/min, respiratory rate of 24 times/min, oxygen saturation of 90% under room air and temperature of 36.3℃. Physical examination revealed Velcro sounds at bilateral lower lungs. Meanwhile, darkened skin on the chest, back, upper and lower limbs. No other positive signs were detected.\u003c/p\u003e \u003cp\u003eBlood investigations revealed leukocytosis and its differential counts in normal range, mildly elevated C-reactive protein (CRP)at 16.7mg/L and obviously elevated erythrocyte sedimentation rate༈ESR༉at 44mm/h. Sputum bacterial and fungi cultures, gram staining, acid-fast bacilli staining and common respiratory virus antibodies were all negative. Myositis autoantibody tests were performed and she was tested positive with anti-MDA5, anti-Ro52 and anti-EJ antibodies. There were no other positive results of autoimmune investigations and no obvious abnormal in tumor makers༈more details see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e༉. She also underwent pulmonary function tests and was found having decreased diffusing capacity of the lungs for carbon monoxide (DLCO). Additionally, the initial Chest computed tomography (CT) showed bilateral subpleural ground-glass opacities, consolidation and grid shadows, lower lungs predominant (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eShe was finally diagnosed with CADM, moreover, anti-MDA5, anti-Ro52 and anti-EJ-antibody were triple positive, skin and lung were mainly involved. Her condition improved after treatment with glucocorticoids, immunosuppressants and anti-infection agents. Her degree of dyspnea relieved, oxygenation index rose and her skin color lightened distinctly(Figure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Auxiliary examinations showed disease activity and severity markers, such as CRP、ESR and LDH declined to normal (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Moreover, her DLCO increased from 25.3mmol/min/kPa to 75mmol/min/kPa and a repeat CT chest demonstrated visibly absorption of pulmonary lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The patient made good recovery and maintained for an extended period of time.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of infectious and non-infectious investigations.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvestigation(method)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eresult\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference range\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfectious aetiology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSputum bacterial smear and culture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFungi smear and culture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcid-fast bacilli staining\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChlamydia and mycoplasma antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfluenza and parainfluenza virus antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory syncytial virus antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenovirus antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLegionella pneumophila antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRickettsia antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpstein-Barr virus and cytomegalovirus antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRubella virus antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHerpes simplex virus antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoxsackie B virus antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT-SPOT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1,3-β-d-Glucan test\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-tuberculosis antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAuto-immune aetiology(units)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANA screening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1:80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFluorescent pattern of ANA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecytoplasmic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-Ro52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive (2+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-double stranded DNA(IU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;300\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-neutrophil cytoplasmic antibodies\u003c/p\u003e \u003cp\u003e(c-ANCA and p-ANCA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtractable nuclear antigen antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-Ro52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-CCP、anti-MCV、anti-AFP \u0026amp; anti-AKA antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyositis-specific antibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMDA-5、EJ、Ro-52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJo-1、PL-7、PL-12、SRP、Mi-2、TIF1-γ、HMGCR、SAE1/2、NXP-2、OJ、KS、ZO、HA、Scl-70、PM-Sc1100、PM-Scl175、KU、RNA-PIII、Th/To、Fibrillarin、NOR-90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunoglobulins IgM (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026ndash;230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunoglobulins IgA (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e331\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u0026ndash;400\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunoglobulins IgG (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1420\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e700\u0026ndash;1600\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC3 Complement (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90\u0026ndash;180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC4 Complement (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRheumatoid factor (KIU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-15.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor aetiology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor markers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA125(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA199(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCA153(U/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-31.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHE4(pmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0-140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNSE、AFP、CEA、CY211、SCC、CA242、CA724、CA50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of investigations at presentation and other relevant time-points\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvestigation\u003c/p\u003e \u003cp\u003e(unit, reference range)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003cp\u003e9\u0026thinsp;\u0026minus;\u0026thinsp;7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2weeks\u003c/p\u003e \u003cp\u003e9\u0026ndash;21\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1months\u003c/p\u003e \u003cp\u003e9\u0026ndash;27\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3months\u003c/p\u003e \u003cp\u003e11\u0026ndash;23\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6months\u003c/p\u003e \u003cp\u003e3\u0026ndash;29\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9months\u003c/p\u003e \u003cp\u003e5\u0026ndash;16\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite cell count\u003c/p\u003e \u003cp\u003e(3.5\u0026ndash;9.5*10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin\u003c/p\u003e \u003cp\u003e(115-150g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count\u003c/p\u003e \u003cp\u003e(125\u0026ndash;350*10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003cp\u003e(0-8mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eErythrocyte sedimentation rate(mm/h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcalcitonin (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin(ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e756\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAnti-MDA5-associated DM, which is a rare subtype of DM that presents with unique mucocutaneous features, including Gottron\u0026rsquo;s sign, Heliotrope rash, V sign, Shawl sign, Periungual erythema, Mechanic\u0026rsquo;s hand and skin ulcer. It is gaining increasing attention due to its complication of RP-ILD and high mortality. The incidence of anti-MDA5\u0026thinsp;+\u0026thinsp;DM associated ILD varies in different regions. The prevalence was 11%-75% in Europeans and United States while it was 92%-100% in Asians\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. According to previous studies, about 40%-70% of MDA5 associated DM cases developed RP-ILD and died of respiratory failure during half year after admission due to the progressive course and a poor response to the treatment\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. However, in our case, the patient with positive of anti-MDA5 had a good treatment effect and maintained remission for more than half year. There are several reflections about why she had a good outcome and why her prognosis modified.\u003c/p\u003e\n\u003ch3\u003eTimely diagnosis and multi-combination therapy are important\u003c/h3\u003e\n\u003cp\u003eWe made a rapid and accurate diagnosis at the early stage. The woman was highly suspected CADM with her outstanding skin manifestations, few myositis evidence, and nonspecific interstitial pneumonia. The diagnosis was finally verified after several myositis-specific antibodies exhibited positive like anti-MDA5, anti-EJ and anti-Ro52. The timely intervention with triple combination therapy of GCs, immunosuppressants in induction phase were extremely important. With consideration of her disease severity and relative chronic disease progression, we applied a moderate-dose GCs and alternate-day intravenous cyclophosphamide further to avoid many common side effects because of high dose. In remission phase, we gradually decreased oral prednisone, meanwhile combining oral cyclophosphamide and tacrolimus to get a long-term maintenance. These triple combination continuous therapies have improved her survival rates and prolonged her recurrence-free survival.\u003c/p\u003e\n\u003ch3\u003eCompletely learning of clinical conditions is helpful for predicting outcome\u003c/h3\u003e\n\u003cp\u003eA current meta-analysis included 29 cohorts with 2645 patients found that old age, male sex, hypoxemia, low FVC, lymphocytopenia, and high levels of ferritin, CRP, creatine kinase, and LDH predicted poor prognosis in patients with MDA5\u0026thinsp;+\u0026thinsp;DM\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. In a large Chinese cohort study of patients with MDA5-DM, patients were classified into three subgroups according to peripheral lymphocyte count. The results proved severe lymphopenia is strongly associated with high mortality, and a normal peripheral lymphocyte number at baseline predicts a better prognosis\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. However, a single indicator fails to accurately predict a particular outcome, a prediction model incorporating several relevant risk factors may enhance predictive power. Therefore, several prediction models for monitoring the disease severity or prognosis in MDA5-DM were emerged \u003cem\u003e(\u003c/em\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The CROSS model is one of the prediction models, four variables were included: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. And a point scoring system was used to classify anti-MDA5\u0026thinsp;+\u0026thinsp;DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high- risk group was about 70\u0026ndash;80%, significantly higher than those in the high-risk group (30\u0026ndash;40%) and moderate-risk group (6\u0026ndash;9%)\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. The CRAFT model also included 4 variables, CRP-to-albumin ratio, red blood cell distribution width-coefficient of variation, fever status, and CD3\u0026thinsp;+\u0026thinsp;T cells\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. FLAIR score is a prediction model for mortality risk, which included 5 variables: ferritin, LDH, anti-MDA5 antibody titers, CT imaging score and RP-ILD\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. According to these predictors or models, our case was all belonged to a mild or moderate group, indicating a relatively good outcome.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSeveral prediction models for RP-ILD risk or mortality in anti-MDA5\u0026thinsp;+\u0026thinsp;DM patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSubgroups score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePrediction risk\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCROSS model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRP (abnormal,1; normal,0)\u003c/p\u003e \u003cp\u003eRo-52 antibody (positive,1; negative,0)\u003c/p\u003e \u003cp\u003eDisease duration (\u0026lt;3 months,2;\u0026ge;3months,0)\u003c/p\u003e \u003cp\u003eSex (male,1; female,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate:0\u0026ndash;2\u003c/p\u003e \u003cp\u003eHigh:3\u0026ndash;4\u003c/p\u003e \u003cp\u003eVery high:5\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRP-ILD risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eModerate:6.67%\u003c/p\u003e \u003cp\u003eHigh:41.69%\u003c/p\u003e \u003cp\u003eVery high:85.71%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRAFT model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRP-to-albumin ratio, red blood cell distribution width-coefficient of variation, fever status, and CD3\u0026thinsp;+\u0026thinsp;T cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRP-ILD risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSensitivity:0.81\u003c/p\u003e \u003cp\u003eSpecificity:0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFLAIR score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFerritin(\u0026lt;636ng/ml,0;\u0026ge;636ng/ml,2)\u003c/p\u003e \u003cp\u003eLDH(\u0026lt;355U/L,0;\u0026ge;355U/L,2)\u003c/p\u003e \u003cp\u003eanti-MDA5 antibody titers(negative,0;+,2;++,3;+++,4)\u003c/p\u003e \u003cp\u003eCT imaging score*(\u0026lt;\u0026thinsp;133,0;\u0026ge;133,3)\u003c/p\u003e \u003cp\u003eRP-ILD (non-RP-ILD,0;RP-ILD,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow:0\u0026ndash;4\u003c/p\u003e \u003cp\u003eMedium:5\u0026ndash;9\u003c/p\u003e \u003cp\u003eHigh:10\u0026ndash;13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMortality risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLow:0%\u003c/p\u003e \u003cp\u003eMedium:7.7%\u003c/p\u003e \u003cp\u003eHigh:85%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e*\u003c/b\u003e CT imaging score were evaluated based on the method described by Ichikado et al\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSome protective factors may be essential to balance the negative effects.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe majority of researchers stated that the coexistence of anti-MDA5 and anti-Ro52 antibodies led to a worse prognosis and lower survival rates\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Besides, a large retrospective case-control study revealed that CAMD was associated with higher rates of mortality, 1-year mortality and RP-ILD than classic DM\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Similarly, some other studies also proved patients with CADM exhibit relatively worse symptoms and prognosis, which doesn\u0026rsquo;t accord with our case. Some special features for instance onset of black skin maybe one of protective factors. A study identified three different subgroups in MDA5-DM: Patients with RP-ILD show the highest mortality rate, those with skin vasculopathy and clinical myositis exhibit an intermediate prognosis and sole dermato-rheumatologic symptoms were associated with the best outcome\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. A report systematically analyses histopathological findings in two MDA-5\u0026thinsp;+\u0026thinsp;CADM patients with fatal RP-ILD. These two patients both had none or subtle skin changes and no overt muscle symptoms until hospitalization. Noteworthy, the muscle autopsy showed characteristic signs of muscle inflammation, and the lung autopsy showed massive interstitial and alveolaroedema, hyaline membranes and intraluminal fibrinoid deposits\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.Thus, the different symptoms in skin may illustrate different pathologies in muscle and lung and then probably affect prognosis. The chronic blacken skin symptom before affected respiratory system may help avoiding disease progression. Moreover, anti-EJ antibody positive may another protective factor. One Chinese retrospective research compared anti-MDA5 and anti-aminoacyl-tRNA synthetase antibody (anti-ARS, including anti-PL-12, anti-PL-7, anti-EJ and anti-Jo1) double-positive dermatomyositis patients (Anti-MDA5+/ARS\u0026thinsp;+\u0026thinsp;group) to single anti-MDA5 positive (Anti-MDA5+/ARS- group) and single anti-ARS positive patients (Anti-MDA5-/ARS\u0026thinsp;+\u0026thinsp;group). The result presented that anti-MDA+/ARS\u0026thinsp;+\u0026thinsp;group had higher ferritin levels than Anti-MDA5-/ARS\u0026thinsp;+\u0026thinsp;group and higher CD4\u0026thinsp;+\u0026thinsp;T-cell counts than Anti-MDA5+/ARS- group. Individuals with anti-MDA+/ARS\u0026thinsp;+\u0026thinsp;antibodies combined the features of anti-MDA5\u0026thinsp;+\u0026thinsp;and anti-ARS\u0026thinsp;+\u0026thinsp;individuals and respond well to glucocorticoid therapy\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. A latest review summarized the lung manifestations of MDA5\u0026thinsp;+\u0026thinsp;DM, commonly including organizing pneumonia, which typically presents with subpleural consolidation during the early stage of the disease, non-specific interstitial pneumonia and non-specific interstitial pneumonia\u0026ndash;organizing pneumonia overlap\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, while grid shadows and pleura thicken seldom appeared as our case. Perhaps the special HRCT images play another important role to change prognosis. High-quality prospective studies are required to confirm our findings.\u003c/p\u003e"},{"header":"SUMMARY","content":"\u003cp\u003eAnti-MDA5\u0026thinsp;+\u0026thinsp;DM usually has high risk to develop RP-ILD and has poor prognosis. Risk stratification to predict patients who will develop fatal RP-ILD is required for supporting therapy decision-making at early stage. According to our case, female, long disease duration and onset of black skin, coexistence of anti-EJ antibody, timely diagnosis and proper triple combination therapies, slightly damage of muscle perhaps indicate a better prognosis. Insights from our case might be beneficial for better understanding the disease course of anti-MDA\u0026thinsp;+\u0026thinsp;DM.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Respiratory, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China\u003c/p\u003e\n\u003cp\u003eJia Guo, Lingjie DU, Bo Xu, Chunting Tan \u0026amp; Ranran Zhao\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorresponding to Chunting Tan \u0026amp; Ranran Zhao.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Beijing Friendship Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data used during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJia Guo was involved in literature search and writing the original draft. Lingjie Du \u0026amp; Bo Xu was involved in collecting clinical data and obtaining informed consent from the patient. Ranran Zhao \u0026amp; Chunting Tan was involved in writing-review \u0026amp; editing. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDeWane M E, Waldman R, Lu J. Dermatomyositis: Clinical features and pathogenesis.[J]. Journal of the American Academy of Dermatology, United States: 2020, 82(2): 267\u0026ndash;281.\u003c/li\u003e\n\u003cli\u003eLu X, Peng Q, Wang G. Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress.[J]. Nature reviews. Rheumatology, United States: 2024, 20(1): 48\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eXie H, Zhang D, Wang Y, et al. Risk factors for mortality in patients with anti-MDA5 antibody-positive dermatomyositis: A meta-analysis and systematic review.[J]. Seminars in arthritis and rheumatism, United States: 2023, 62: 152231.\u003c/li\u003e\n\u003cli\u003eJin Q, Fu L, Yang H, et al. Peripheral lymphocyte count defines the clinical phenotypes and prognosis in patients with anti-MDA5-positive dermatomyositis.[J]. Journal of internal medicine, England: 2023, 293(4): 494\u0026ndash;507.\u003c/li\u003e\n\u003cli\u003eWang L, Lv C, You H, et al. Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.[J]. Frontiers in immunology, Switzerland: 2024, 15: 1286973.\u003c/li\u003e\n\u003cli\u003eGuo J, Mei C, Yu Q, et al. Risk Prediction for Rapidly Progressive Interstitial Lung Disease in Anti-MDA5-Positive Dermatomyositis: The CRAFT Model.[J]. Medical science monitor : international medical journal of experimental and clinical research, United States: 2023, 29: e940251.\u003c/li\u003e\n\u003cli\u003eLian X, Zou J, Guo Q, et al. Mortality Risk Prediction in Amyopathic Dermatomyositis Associated With Interstitial Lung Disease: The FLAIR Model.[J]. Chest, United States: 2020, 158(4): 1535\u0026ndash;1545.\u003c/li\u003e\n\u003cli\u003eIchikado K, Suga M, M\u0026uuml;ller N L, et al. Acute interstitial pneumonia: comparison of high-resolution computed tomography findings between survivors and nonsurvivors.[J]. American journal of respiratory and critical care medicine, United States: 2002, 165(11): 1551\u0026ndash;1556.\u003c/li\u003e\n\u003cli\u003eXu A, Ye Y, Fu Q, et al. Prognostic values of anti-Ro52 antibodies in anti-MDA5-positive clinically amyopathic dermatomyositis associated with interstitial lung disease.[J]. Rheumatology (Oxford, England), England: 2021, 60(7): 3343\u0026ndash;3351.\u003c/li\u003e\n\u003cli\u003eCheng L, Xu L, Xu Y, et al. Gender differences in patients with anti-MDA5-positive dermatomyositis: a cohort study of 251 cases.[J]. Clinical rheumatology, Germany: 2024, 43(1): 339\u0026ndash;347.\u003c/li\u003e\n\u003cli\u003eJi Q, Pan W, Zhang D, et al. Comparison of characteristics and anti-MDA5 antibody distribution and effect between clinically amyopathic dermatomyositis and classic dermatomyositis: a retrospective case-control study.[J]. Frontiers in immunology, Switzerland: 2023, 14: 1237209.\u003c/li\u003e\n\u003cli\u003eAllenbach Y, Uzunhan Y, Toquet S, et al. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases.[J]. Neurology, United States: 2020, 95(1): e70\u0026ndash;e78.\u003c/li\u003e\n\u003cli\u003eEnglert B, Dittmayer C, Goebel H-H, et al. \u0026ldquo;Amyopathic\u0026rdquo; MDA5-positive dermatomyositis with severe lung involvement presenting with net myositic morphological features - insights from an autopsy study.[J]. Neuromuscular disorders : NMD, England: 2024, 36: 42\u0026ndash;47.\u003c/li\u003e\n\u003cli\u003eChen X, Zhang L, Jin Q, et al. The clinical features and prognoses of anti-MDA5 and anti-aminoacyl-tRNA synthetase antibody double-positive dermatomyositis patients.[J]. Frontiers in immunology, Switzerland: 2022, 13: 987841.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"dermatomyositis, clinical amyopathic dermatomyositis, rapidly progressive interstitial lung disease, anti-melanoma differentiation associated protein 5 antibody, anti-EJ antibody, anti-Ro52 antibody","lastPublishedDoi":"10.21203/rs.3.rs-4288480/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4288480/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\n\u003cp\u003eClinically amyopathic dermatomyositis (CADM) is a disease with the typical skin manifestations of dermatomyositis (DM) and few or no obvious muscle weakness. The anti-melanoma differentiation associated protein 5（MDA5）antibody positive CADM patients are at a high risk of developing rapidly progressive interstitial lung disease (RP-ILD)，and exhibit immensely poor prognosis and high mortality. The disease course and severity of MDA5+CAMD are highly different, wherein some patients presented marked treatment response and didn’t occur exacerbation. Analysis to these special groups bring us better understanding of MDA5+CADM.\u003c/p\u003e\n\u003cp\u003eCase presentation\u003c/p\u003e\n\u003cp\u003eWe presented a patient with anti-MD5 anti-Ro52 anti-EJ-triple positive DM patient. She was initially characteristic with darken skin for 2 years before gradually occurred dry cough, fever and dyspnea. She had a low oxygen saturation and diffusing capacity of the lungs for carbon monoxide. With combination therapy of GCs and two immunosuppressants, the woman obtained a rapid remission and persisted for a long time.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003ePatients with anti-MD5 anti-Ro52 anti-EJ-triple positive DM-ILD may present a less aggressive disease course and an individual appropriate therapy may be promising for long-term maintenance.\u003c/p\u003e","manuscriptTitle":"Triple Positive for Anti-MDA5, Anti-EJ and Anti-Ro52 Antibodies Dermatomyositis Associated Interstitial Lung Disease：a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-02 20:42:53","doi":"10.21203/rs.3.rs-4288480/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f7433919-34d8-43d9-af9c-c2d275ef6fa3","owner":[],"postedDate":"May 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-02T07:51:33+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-02 20:42:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4288480","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4288480","identity":"rs-4288480","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}