Anti-melanoma differentiation-associated gene 5 (Anti-MDA5) antibody dermatomyositis: Clinical features and outcomes in a racially diverse patient cohort

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Koyoda, Fatema Ezzy, Dawn Wahezi, Anand Kumthekar, Xianhong Xie, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5085511/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Jan, 2025 Read the published version in BMC Rheumatology → Version 1 posted 4 You are reading this latest preprint version Abstract Background: The anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody dermatomyositis is known for its association with rapidly progressive interstitial lung disease (RP-ILD) and ulcerative skin lesions, often presenting with or without muscle involvement. The aim of this study was to identify distinct clinical and laboratory features that could be used to evaluate disease progression in an ethnically diverse cohort of anti-MDA5 dermatomyositis patients at a U.S. academic center. Methods: A retrospective chart review was conducted on dermatomyositis patients hospitalized at our institution between January 2014 and June 2023. The data were analyzed via Fischer’s exact test and a t test. Results Among the 195 dermatomyositis patients reviewed, 22 tested positive for the MDA5 antibody, comprising thirteen adults and nine pediatric patients. Among these individuals, ten adults exhibited ILD, three of whom were classified as having RP-ILD. Notably, all pediatric patients displayed some level of muscle weakness. The five pediatric patients diagnosed with ILD had a higher prevalence of myositis. The incidence of ILD was significantly greater in the adult Black Hispanic and African American populations (10/15 cases, p = 0.035) than in the other ethnicities, with three cases resulting in fatal RP-ILD. The overall mortality rate of 13.6% was more favorable than the previously reported 40–60% rates. Conclusion: In conclusion, while the general disease characteristics were similar between adult and pediatric patients, myositis was more prevalent in the pediatric population. Adults, particularly those from Black and African American backgrounds, experienced a greater incidence of ILD, leading to poorer outcomes. MDA5 autoantibody Dermatomyositis Race & Ethnicity Interstitial Lung Disease Figures Figure 1 Background Anti-melanoma differentiation-associated protein 5 (anti-MDA5) antibody-positive dermatomyositis is an idiopathic inflammatory musculoskeletal disorder that is relatively rare and challenging to diagnose. The key distinguishing features include clinically amyopathic dermatomyositis (CADM) or hypomyopathic disease, characteristic deep skin ulcerations over joints often mirroring typical dermatomyositis lesions (Heliotrope rash, Gottron sign, Gottron papules, and Holster sign), and frequently rapidly progressive interstitial lung disease (RP-ILD) (1). These features help differentiate it from other forms of dermatomyositis, including anti-synthetase syndrome, which is more likely to present with Raynaud's phenomenon, mechanic's hands, and anti-synthetase autoantibodies (14). Patients may also exhibit nonspecific symptoms such as inflammatory arthritis, fever, fatigue, and weight loss, which are common in other idiopathic inflammatory myopathies (11,15). The association of RP-ILD myositis with antibodies against MDA5 (encoded by the gene interferon-induced helicase C domain [(IFIH]-containing protein 1) was first identified in a Japanese cohort, initially labeled anti-CADM 140 (anticlinically amyopathic dermatomyositis 140 kDa peptide), which was later recognized to share specificity with anti-MDA5 (16,17). While initially thought to be more prevalent in Asian populations, recent data indicate rising incidence rates in Europe and the U.S. across all ethnicities (18,19). Notably, there is significant variability in disease presentation among ethnic groups, with a higher ILD risk observed in Asians, even in pediatric patients (20,21). RP-ILD, which is resistant to standard immunosuppressive therapy, is the primary cause of mortality in this population. The presence of anti-MDA5 antibodies has a sensitivity of 77% and specificity of 86% for RP-ILD development, with associated 6-month mortality rates ranging from approximately 40–60% (8, 9). Early aggressive therapy and potential lung transplants have improved survival outcomes (1, 10). Therefore, early clinical diagnosis is essential, particularly because anti-MDA5 autoantibody testing is not available in most centers and must be sent to a reference laboratory, resulting in processing delays that can hinder timely laboratory confirmation. While early studies focused on Asian cohorts, information on disease presentation in diverse U.S. populations remains limited. Our study aimed to identify distinct clinical and laboratory features for assessing disease progression in individuals with anti-MDA5 dermatomyositis on the basis of serologic, histopathological, and radiographic status to aid in early diagnosis and treatment. We analyzed and compared the disease phenotypes of a racially diverse population of both juvenile and adult patients with anti-MDA5 dermatomyositis. Methods Following Institutional Review Board approval, we accessed the electronic health records at Montefiore Medical Center, NY, via Epic Systems Corporation (Verona, WI, USA; 2022). Our search identified 195 dermatomyositis patients, 22 of whom tested positive for MDA5 antibodies between January 2014 and June 2023. A retrospective chart review of both inpatient and outpatient records was conducted to extract clinical data, including demographics, comorbidities, signs and symptoms, serological findings, radiographic details, and treatment used. Interstitial lung disease (ILD) was confirmed through high-resolution computed tomography of the thorax. Adult patients were subjected to anti-MDA5 antibodies (CADM-140) (testing as part of the Myomarker Panel (Laboratory Corporation of America, Burlington, NC, USA), whereas pediatric patients’ myositis-specific antibody testing was performed by the Oklahoma Myositis Testing Laboratory in Oklahoma City, OK, USA. Fischer’s exact test and t test were used to compare disease features between adult and pediatric patients with anti-MDA5 dermatomyositis. Statistical analyses were conducted via Statistical Analysis System Software version 9.4 (Cary, NC, USA), with a significance threshold set at a P value of < 0.05. Results Among the 195 dermatomyositis patients reviewed, 22 were positive for anti-MDA5 antibodies. The group comprised 13 adult patients (8.7% of all adult patients; 13/149) and 9 pediatric patients (19% of pediatric patients; 9/46) (p = 0.060), with a female-to-male ratio of approximately 2:1 in both groups. The median age for adult-onset DM was 40 years (Q1 35 years, Q3 61.5 years), with a mean follow-up duration of 2.40 years (SD 1.95 years). The median age of onset in children was 5 years (Q1 2.5 years, Q3 10 years). Among adults, the majority were African American (53.8%), followed by non-Black Hispanic (30.8%), Black Hispanic (7.7%), and Caucasian (7.7%) (Table 1; Supplementary Table 1). In the pediatric group, three African Americans (33.3%) and six nonblack Hispanics (66.6%) were included (Figure 1). Skin rash was the most common symptom at presentation in adults, followed by dyspnea and inflammatory arthritis (Supplementary Table 1). In pediatric patients, muscle weakness was the predominant presenting symptom (9/9 pediatric patients vs. 4/13 adult patients; p=0.002), although all of them presented with skin manifestations at some stage during the disease course. (Table 1; Supplementary Table 2). Methotrexate was the primary choice of disease-modifying drug in pediatric patients, with rituximab being a common alternative (Table 1; Supplementary Table 4). Ten adults and five pediatric patients presented with interstitial lung disease (ILD). Among adult patients, ILD was significantly more prevalent in the Black Hispanic and African American populations (100% vs. 40% in other ethnic groups; p = 0.035). However, this difference was not detected when the entire cohort of adult and pediatric patients was considered (p = 0.064) (Tables 1, 2). Three African American patients and one Black Hispanic patient, all adults except one child, were responsible for all cases of RP-ILD and had a high mortality rate of 75%. The presence of the anti-Ro52 antibody was noted in all adult RP-ILD patients but did not significantly differ across the entire cohort (Supplementary Tables 1 and 3). Raynaud’s phenomenon tended to be associated with the presence of ILD ( p = 0.06) (Table 3), whereas skin ulcers did not correlate with the occurrence of ILD ( p = 0.38) (Table 3). Although MDA5 dermatomyositis is not strongly linked to malignancy (12), two adult patients had ovarian malignancies. The overall mortality rate of 13.6% in our cohort was lower than the reported rate of 40–60% (13). Mycophenolate was the preferred disease-modifying agent, followed by Rituximab and Intravenous Immunoglobulin therapy (IVIG) (Supplementary Table 3). Methotrexate was the primary choice of disease-modifying drug in pediatric patients, with Rituximab being a common alternative (Table 1; Supplementary Table 4). For ILD, the preferred agents of choice were Rituximab and Mycophenolate mofetil in our cohort (Supplementary Tables 2 and 4). Discussion Anti-MDA5 dermatomyositis has been reported to affect both sexes at a female-to-male ratio of 2:1, which is consistent with our population demographics (22). Overall, the disease characteristics were similar between adult and pediatric patients, except for a higher prevalence of myositis in the pediatric group, as noted in other studies (12). The pediatric cohort generally experienced milder disease than did the adult cohort, with less severe ILD (23). African descent was associated with worse pulmonary outcomes due to a greater association with RP-ILD. This phenomenon has been reported frequently in Japanese and Chinese patients (17, 38–43) as well as in predominantly Caucasian population studies conducted in the U.S. (5,6). These results, however, were not reproduced in the study performed in the Brazilian White population. Deep ulcerative skin lesions were present in 7 adults and 6 pediatric patients in our study; however, these lesions did not correlate with ILD incidence in our combined cohort, unlike associations reported in previous studies (24,25). Raynaud's phenomenon showed a trend toward a greater prevalence in patients with ILD. The coexistence of anti-Ro 52 autoantibodies was noted in all adults with RP-ILD, which has been linked to a poorer prognosis in other studies (26). In 2020, Allenbach et al. (10) categorized the manifestations of MDA-5 DM in 83 French patients in the form of clusters. Cluster 1, the MDA-5 RP-ILD type, represented patients with primarily ILD, usually RP-ILD, leading to worse outcomes. They frequently had mechanic’s hands. Cluster 2, the MDA-5 rheumatic DM type, was more common in women, presented with inflammatory arthralgia and arthritis, and had a favorable prognosis. In Cluster 3, the MDA-5 vasculopathy DM type, which is more common in men, has an intermediate prognosis and is associated with severe vasculopathy findings of Raynaud’s phenomenon, digital necrosis, and calcinosis alongside an increased incidence of myositis. In our cohort, patients with RP-ILD were in cluster one (Patients G and H), with increased mortality, although they did not have mechanic’s hands. Patients A, B, D, E, J, K, and M could be grouped into cluster 3 on the basis of the above criterion given the findings of skin ulcers with a male predominance. Half of the patients had severe vasculopathy and Raynaud’s syndrome. Patient M presented with a mixed picture, having RP-ILD, mechanic’s hands, severe vasculopathy, and skin ulcers with a good prognosis, which, if the above classification was used, would be more suitably placed under cluster 3 instead of cluster 1. Patients C, F, I, and L could be grouped under cluster 2 with milder arthritis symptoms. Except for no findings of mechanics hands in cluster 1 patients, the other observations made by Allenbach et al. held true for our population, although given the small sample size (n = 2) in this group, there remains a large margin of error. In our cohort, two adult female patients over 40 years of age had ovarian cancer; one had a low titer of anti-TIF-1 g and SAE1 antibodies, whereas the other, interestingly, lacked additional autoantibodies, with the exception of anti-MDA-5 antibodies. While the association of the former antibodies with malignancy is well established (27), notably, the anti-MDA5 autoantibody has not been definitively linked to malignancy in previous studies, and the risk is less pronounced, which is consistent with our dataset(28). Early diagnosis and treatment are crucial for improving patient prognosis. Recognizing the amyopathic or hypomyopathic nature of the disease, where weakness may not correlate with myopathy and muscle enzyme elevation, is important. Assessment of inflammatory markers, myositis-specific autoantibodies, electromyography, imaging modalities, and muscle biopsy can assist in establishing a diagnosis. High clinical suspicion is needed, and the anti-MDA5 antibody provides confirmation. There are no standard treatment guidelines for anti-MDA5 dermatomyositis. Interventions include IVIG, calcineurin inhibitors, azathioprine, mycophenolate, biologics such as abatacept and rituximab, and targeted DMARD therapies such as tofacitinib, often with background steroid use. (12,30,31). Adjunctive therapies such as plasma exchange and Polymyxin-B direct hemoperfusion have also been employed. (32). Poor prognostic factors include elevated bronchoalveolar lavage neutrophil counts; early pulmonary involvement with hypoxemia and traction bronchiectasis; and increased serum CX3CL1, CXCR4, and interleukin-18 levels (32,33). Anti-MDA5 antibody titers are correlated with disease severity and clinical response (34). Serum Krebs von den Lungen-6 and ferritin levels have been used to monitor therapeutic response. (32,35). The main limitations of this study are its descriptive, single-center, retrospective nature and small cohort. Additionally, all patients self-identified as White, Black, African American, or Hispanic, with only one category selected except for one patient who identified as Black Hispanic, precluding a definitive assessment of the associations among race, age of onset, disease phenotype, and severity. Larger, more diverse cohorts are needed to corroborate these findings. Conclusion Anti-MDA5 dermatomyositis is rare and difficult to diagnose. The disease characteristics of our cohort were similar between adult and pediatric patients, except for a greater prevalence of myositis in the pediatric group. In contrast, adults, especially African Americans, had a higher incidence of ILD with poorer outcomes. Rapidly escalating therapy, including rituximab, which is often combined with mycophenolate, may improve patient outcomes compared with those of historical controls (36). Early aggressive combination immunosuppression shows promise for improving patient prognosis (37). Clinicians should be alerted to the presence of MDA5 dermatomyositis due to characteristic skin ulcerations, ILD, and possibly Raynaud's phenomenon. Muscle involvement should be considered particularly in pediatric patients. The increased mortality observed in African Americans underscores the importance of prompt diagnosis and intervention to improve prognosis. However, our study's limitations prevent further exploration of factors contributing to poorer outcomes in this population. Controlled studies are essential to assess appropriate treatment strategies for patients with anti-MDA5 dermatomyositis and to prevent adverse outcomes. Abbreviations Anti-MDA5: Anti-melanoma differentiation-associated gene 5 RP-ILD: Rapidly progressive interstitial lung disease ILD: Interstitial lung disease IVIG: Intravenous immunoglobulin CADM: Clinically amyopathic dermatomyositis IFIH: Interferon-induced helicase C domain Anti-TIF-γ: Anti-Transcription intermediary factor 1 gamma Anti-SAE: Anti-small ubiquitin-like modifier activating enzyme CX3CL1: Chemokine (C-X3-C motif) ligand 1 CXCR4: Chemokine receptor type 4 Declarations Ethics approval and consent to participate: We received approval from the Montefiore/Albert Einstein College of Medicine Institutional Review Board for this retrospective chart review study, which did not involve any active intervention; hence, the requirement for consent to participate was waived. Consent for publication: Not applicable Availability of data and materials Patient data were collected from the Epic electronic medical records via a search tool to identify all the myositis patients. The dataset was stored on Epic and deidentified patient information compiled into a spreadsheet and shared as supplementary charts/additional files for review. Competing interests: Not applicable Funding: No funding was received for the study. Authors' contributions SK: Data collection, writing and editing of the tables and manuscript FE: Data review, writing and editing the manuscript DW: Writing and editing the manuscript AK: Writing and editing the manuscript XX: Worked on statistics, data analysis and editing the manuscript CT: Data collection, writing and editing of the tables and manuscript BA: Data collection, writing and editing the manuscript Acknowledgments: Not applicable Clinical trial number: Not applicable References Sakamoto N, Ishimoto H, Nakashima S, Yura H, Miyamura T, Okuno D, et al. Clinical Features of Anti-MDA5 Antibody-positive Rapidly Progressive Interstitial Lung Disease without Signs of Dermatomyositis. Intern Med. 2019;58(6):837-41. 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Study patient characteristics Adult MDA5 Dermatomyositis N = 13 Pediatric MDA5 Dermatomyositis N = 9 P value Mean age at disease onset Years, (SD) 44.6 (13.93) 6.5 (4.9) Sex (Male, Female) 5,8 3,6 ns Race/Ethnicity Caucasian Hispanic African American Black Hispanic 1 4 7 1 0 6 3 0 0.50 ILD Absent Stable ILD RP-ILD 3 7 3 4 4 1 0.61 Skin ulcers 7 6 0.67 Arthritis 9 7 ns Myositis 4 9 0.002 Raynaud’s phenomenon 8 3 0.39 ANA 6 4 ns Ro 52 8 3 0.39 Table 2. Clinical characteristics of patients by Race/Ethnicity Race/Ethnicity P value Study characteristic Hispanic African American Non-Hispanic White Black Hispanic ILD Absent Stable RP-ILD 6 4 1 6 3 1 1 0.06 § 0.04* Myositis 8 5 0 0 0.28 Skin ulcers 6 5 1 1 0.81 Raynaud’s phenomenon 4 5 1 1 0.67 Arthritis 8 7 1 0 ns ANA 4 5 0 0 0.81 Ro 52 5 4 1 1 ns Note: * - Black Hispanic or African American compared to other for RP-ILD; § - Black Hispanic or African American compared to other for ILD Table 3. Relationship of ILD to clinic and laboratory characteristics ILD, N=15 No ILD, N=7 P value RP-ILD, N=4 Stable/No ILD, N=18 P value Skin ulcers 10(66.7%) 3(42.9%) 0.38 1(25%) 12(66.7%) 0.26 Raynaud’s 10(66.7%) 1(14.3%) 0.06 1(25%) 11(61.1%) 0.29 Ro 52 8(53.3%) 3(42.9%) ns 3(75%) 8(44.4%) 0.59 Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables.docx Supplementary Tables Detailed tables of the clinical, serologic, and radiographic characteristics of the adult (Table 1) and pediatric (Table 3) anti-MDA5 patients. The treatment regimens and disease outcomes of the adult and pediatric anti-MDA5 patients are summarized in Tables 2 and 4 respectively. Supplementary Table 1 Clinical, radiographic and serologic characteristics of adult anti-MDA5 patients. Supplementary Table 2 Summary of adult anti-MDA5 patient treatment and outcomes. Supplementary Table 3 Clinical, radiographic and serologic characteristics of pediatric anti-MDA5 patients. Supplementary Table 4 Summary of pediatric anti-MDA5 patient treatment and outcomes. Cite Share Download PDF Status: Published Journal Publication published 09 Jan, 2025 Read the published version in BMC Rheumatology → Version 1 posted Editorial decision: Revision requested 26 Sep, 2024 Editor assigned by journal 23 Sep, 2024 Submission checks completed at journal 23 Sep, 2024 First submitted to journal 13 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Koyoda","email":"","orcid":"","institution":"Montefiore Medical Center, Albert Einstein College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sai","middleName":"K.","lastName":"Koyoda","suffix":""},{"id":359258787,"identity":"122b5fc3-6500-4009-aa5e-cc53bb15482f","order_by":1,"name":"Fatema Ezzy","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIiWNgGAWjYNACGwh14EOFjRyY8YCgljQGCSDJeHDGmTRjsJYEIrUwH+ZtO5zYABLAp4Wf//gzCYYEuzp+scMPgFrS0ueHHX4ItMVOTrcBuxbJhgNpQC3JEpKz0wwOzjlnk7vxdpoBUEuysdkB7FoMDjYck2D8wSxhcDvB4MCbsrTcjbMTQFoOJG7DocX+MGMb0JZ6Cfvb6R8O8LAdTjecDWTg02LAxswG1HJYwkA6x+AgT9vhBHkgA68WiTNszBYJCcclZ9zOKQAFsuEG6ZyCAwkGuP3C33/84Y0PCdX8/LPTN38ARqW8PIRhJ4dLCxCwSCSgOBWs0gCnchBg/oDClW/Aq3oUjIJRMApGIAAA2NNmMDWfmRYAAAAASUVORK5CYII=","orcid":"","institution":"Jacobi Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Fatema","middleName":"","lastName":"Ezzy","suffix":""},{"id":359258788,"identity":"2edc5573-8c14-43aa-a8f8-d58acc47dc04","order_by":2,"name":"Dawn Wahezi","email":"","orcid":"","institution":"Children's Hospital at Montefiore","correspondingAuthor":false,"prefix":"","firstName":"Dawn","middleName":"","lastName":"Wahezi","suffix":""},{"id":359258789,"identity":"d92e5163-cedd-47f6-a542-ae98bbc9d959","order_by":3,"name":"Anand Kumthekar","email":"","orcid":"","institution":"Montefiore Medical Center, Albert Einstein College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Anand","middleName":"","lastName":"Kumthekar","suffix":""},{"id":359258790,"identity":"ec389b88-6d63-42de-8491-4dd514c4b2a2","order_by":4,"name":"Xianhong Xie","email":"","orcid":"","institution":"Albert Einstein College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xianhong","middleName":"","lastName":"Xie","suffix":""},{"id":359258791,"identity":"ace9b561-0521-4695-92a8-02587d77a30d","order_by":5,"name":"Clement E. Tagoe","email":"","orcid":"","institution":"Montefiore Medical Center, Albert Einstein College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Clement","middleName":"E.","lastName":"Tagoe","suffix":""},{"id":359258792,"identity":"7161f933-702b-4cb6-998d-45191dca379e","order_by":6,"name":"Bibi Ayesha","email":"","orcid":"","institution":"Montefiore Medical Center, Albert Einstein College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Bibi","middleName":"","lastName":"Ayesha","suffix":""}],"badges":[],"createdAt":"2024-09-13 17:59:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5085511/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5085511/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s41927-025-00455-5","type":"published","date":"2025-01-09T15:57:43+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":70206050,"identity":"fdd84027-fafa-4c54-9725-c0f3fd05d9b8","added_by":"auto","created_at":"2024-11-29 13:43:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":32920,"visible":true,"origin":"","legend":"\u003cp\u003eFlow Diagram Showing Study Population\u003c/p\u003e\n\u003cp\u003eAnti-MDA5: Anti-melanoma differentiation-associated gene 5; ILD: Interstitial lung disease\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5085511/v1/d31b22d91ae11cf9a2d50c04.png"},{"id":73694020,"identity":"04575604-d03e-41ec-9935-6da92a023ac7","added_by":"auto","created_at":"2025-01-13 16:10:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":506610,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5085511/v1/16345802-d0b6-455d-95b5-bcfad888fd57.pdf"},{"id":70205178,"identity":"386baae6-f8c5-4e10-bd58-4c89306a1c65","added_by":"auto","created_at":"2024-11-29 13:35:02","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":208563,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Tables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDetailed tables of the clinical, serologic, and radiographic characteristics of the adult (Table 1) and pediatric (Table 3) anti-MDA5 patients. The treatment regimens and disease outcomes of the adult and pediatric anti-MDA5 patients are summarized in Tables 2 and 4 respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical, radiographic and serologic characteristics of adult anti-MDA5 patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table 2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSummary of adult anti-MDA5 patient treatment and outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table 3\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical, radiographic and serologic characteristics of pediatric anti-MDA5 patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Table 4\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSummary of pediatric anti-MDA5 patient treatment and outcomes.\u003c/p\u003e","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-5085511/v1/671201563eb7afffd7454f5a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anti-melanoma differentiation-associated gene 5 (Anti-MDA5) antibody dermatomyositis: Clinical features and outcomes in a racially diverse patient cohort","fulltext":[{"header":"Background","content":"\u003cp\u003eAnti-melanoma differentiation-associated protein 5 (anti-MDA5) antibody-positive dermatomyositis is an idiopathic inflammatory musculoskeletal disorder that is relatively rare and challenging to diagnose. The key distinguishing features include clinically amyopathic dermatomyositis (CADM) or hypomyopathic disease, characteristic deep skin ulcerations over joints often mirroring typical dermatomyositis lesions (Heliotrope rash, Gottron sign, Gottron papules, and Holster sign), and frequently rapidly progressive interstitial lung disease (RP-ILD) (1). These features help differentiate it from other forms of dermatomyositis, including anti-synthetase syndrome, which is more likely to present with Raynaud's phenomenon, mechanic's hands, and anti-synthetase autoantibodies (14). Patients may also exhibit nonspecific symptoms such as inflammatory arthritis, fever, fatigue, and weight loss, which are common in other idiopathic inflammatory myopathies (11,15).\u003c/p\u003e \u003cp\u003eThe association of RP-ILD myositis with antibodies against MDA5 (encoded by the gene interferon-induced helicase C domain [(IFIH]-containing protein 1) was first identified in a Japanese cohort, initially labeled anti-CADM 140 (anticlinically amyopathic dermatomyositis 140 kDa peptide), which was later recognized to share specificity with anti-MDA5 (16,17). While initially thought to be more prevalent in Asian populations, recent data indicate rising incidence rates in Europe and the U.S. across all ethnicities (18,19). Notably, there is significant variability in disease presentation among ethnic groups, with a higher ILD risk observed in Asians, even in pediatric patients (20,21). RP-ILD, which is resistant to standard immunosuppressive therapy, is the primary cause of mortality in this population. The presence of anti-MDA5 antibodies has a sensitivity of 77% and specificity of 86% for RP-ILD development, with associated 6-month mortality rates ranging from approximately 40\u0026ndash;60% (8, 9). Early aggressive therapy and potential lung transplants have improved survival outcomes (1, 10). Therefore, early clinical diagnosis is essential, particularly because anti-MDA5 autoantibody testing is not available in most centers and must be sent to a reference laboratory, resulting in processing delays that can hinder timely laboratory confirmation.\u003c/p\u003e \u003cp\u003eWhile early studies focused on Asian cohorts, information on disease presentation in diverse U.S. populations remains limited. Our study aimed to identify distinct clinical and laboratory features for assessing disease progression in individuals with anti-MDA5 dermatomyositis on the basis of serologic, histopathological, and radiographic status to aid in early diagnosis and treatment. We analyzed and compared the disease phenotypes of a racially diverse population of both juvenile and adult patients with anti-MDA5 dermatomyositis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e Following Institutional Review Board approval, we accessed the electronic health records at Montefiore Medical Center, NY, via Epic Systems Corporation (Verona, WI, USA; 2022). Our search identified 195 dermatomyositis patients, 22 of whom tested positive for MDA5 antibodies between January 2014 and June 2023. A retrospective chart review of both inpatient and outpatient records was conducted to extract clinical data, including demographics, comorbidities, signs and symptoms, serological findings, radiographic details, and treatment used. Interstitial lung disease (ILD) was confirmed through high-resolution computed tomography of the thorax. Adult patients were subjected to anti-MDA5 antibodies (CADM-140) (testing as part of the Myomarker Panel (Laboratory Corporation of America, Burlington, NC, USA), whereas pediatric patients\u0026rsquo; myositis-specific antibody testing was performed by the Oklahoma Myositis Testing Laboratory in Oklahoma City, OK, USA.\u003c/p\u003e \u003cp\u003eFischer\u0026rsquo;s exact test and t test were used to compare disease features between adult and pediatric patients with anti-MDA5 dermatomyositis. Statistical analyses were conducted via Statistical Analysis System Software version 9.4 (Cary, NC, USA), with a significance threshold set at a P value of \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAmong the 195 dermatomyositis patients reviewed, 22 were positive for anti-MDA5 antibodies. The group comprised 13 adult patients (8.7% of all adult patients; 13/149) and 9 pediatric patients (19% of pediatric patients; 9/46) (p = 0.060), with a female-to-male ratio of approximately 2:1 in both groups. The median age for adult-onset DM was 40 years (Q1 35 years, Q3 61.5 years), with a mean follow-up duration of 2.40 years (SD 1.95 years). The median age of onset in children was 5 years (Q1 2.5 years, Q3 10 years). Among adults, the majority were African American (53.8%), followed by non-Black Hispanic (30.8%), Black Hispanic (7.7%), and Caucasian (7.7%) (Table 1; Supplementary Table 1). In the pediatric group, three African Americans (33.3%) and six nonblack Hispanics (66.6%) were included (Figure 1).\u003c/p\u003e\n\u003cp\u003eSkin rash was the most common symptom at presentation in adults, followed by dyspnea and inflammatory arthritis (Supplementary Table 1). In pediatric patients, muscle weakness was the predominant presenting symptom (9/9 pediatric patients vs. 4/13 adult patients; p=0.002), although all of them presented with skin manifestations at some stage during the disease course. (Table 1; Supplementary Table 2). Methotrexate was the primary choice of disease-modifying drug in pediatric patients, with rituximab being a common alternative (Table 1; Supplementary Table 4).\u003c/p\u003e\n\u003cp\u003eTen adults and five pediatric patients presented with interstitial lung disease (ILD). Among adult patients, ILD was significantly more prevalent in the Black Hispanic and African American populations (100% vs. 40% in other ethnic groups; p = 0.035). However, this difference was not detected when the entire cohort of adult and pediatric patients was considered (p = 0.064) (Tables 1, 2). Three African American patients and one Black Hispanic patient, all adults except one child, were responsible for all cases of RP-ILD and had a high mortality rate of 75%.\u003c/p\u003e\n\u003cp\u003eThe presence of the anti-Ro52 antibody was noted in all adult RP-ILD patients but did not significantly differ across the entire cohort (Supplementary Tables 1 and 3). Raynaud’s phenomenon tended to be associated with the presence of ILD (\u003cem\u003ep\u003c/em\u003e = 0.06) (Table 3), whereas skin ulcers did not correlate with the occurrence of ILD (\u003cem\u003ep\u003c/em\u003e = 0.38) (Table 3).\u003c/p\u003e\n\u003cp\u003eAlthough MDA5 dermatomyositis is not strongly linked to malignancy (12), two adult patients had ovarian malignancies. The overall mortality rate of 13.6% in our cohort was lower than the reported rate of 40–60% (13).\u003c/p\u003e\n\u003cp\u003eMycophenolate was the preferred disease-modifying agent, followed by Rituximab and Intravenous Immunoglobulin therapy (IVIG) (Supplementary Table 3). Methotrexate was the primary choice of disease-modifying drug in pediatric patients, with Rituximab being a common alternative (Table 1; Supplementary Table 4). For ILD, the preferred agents of choice were Rituximab and Mycophenolate mofetil in our cohort (Supplementary Tables 2 and 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAnti-MDA5 dermatomyositis has been reported to affect both sexes at a female-to-male ratio of 2:1, which is consistent with our population demographics (22). Overall, the disease characteristics were similar between adult and pediatric patients, except for a higher prevalence of myositis in the pediatric group, as noted in other studies (12).\u003c/p\u003e \u003cp\u003eThe pediatric cohort generally experienced milder disease than did the adult cohort, with less severe ILD (23). African descent was associated with worse pulmonary outcomes due to a greater association with RP-ILD. This phenomenon has been reported frequently in Japanese and Chinese patients (17, 38\u0026ndash;43) as well as in predominantly Caucasian population studies conducted in the U.S. (5,6). These results, however, were not reproduced in the study performed in the Brazilian White population.\u003c/p\u003e \u003cp\u003eDeep ulcerative skin lesions were present in 7 adults and 6 pediatric patients in our study; however, these lesions did not correlate with ILD incidence in our combined cohort, unlike associations reported in previous studies (24,25). Raynaud's phenomenon showed a trend toward a greater prevalence in patients with ILD. The coexistence of anti-Ro 52 autoantibodies was noted in all adults with RP-ILD, which has been linked to a poorer prognosis in other studies (26).\u003c/p\u003e \u003cp\u003eIn 2020, Allenbach et al. (10) categorized the manifestations of MDA-5 DM in 83 French patients in the form of clusters. Cluster 1, the MDA-5 RP-ILD type, represented patients with primarily ILD, usually RP-ILD, leading to worse outcomes. They frequently had mechanic\u0026rsquo;s hands. Cluster 2, the MDA-5 rheumatic DM type, was more common in women, presented with inflammatory arthralgia and arthritis, and had a favorable prognosis. In Cluster 3, the MDA-5 vasculopathy DM type, which is more common in men, has an intermediate prognosis and is associated with severe vasculopathy findings of Raynaud\u0026rsquo;s phenomenon, digital necrosis, and calcinosis alongside an increased incidence of myositis.\u003c/p\u003e \u003cp\u003eIn our cohort, patients with RP-ILD were in cluster one (Patients G and H), with increased mortality, although they did not have mechanic\u0026rsquo;s hands. Patients A, B, D, E, J, K, and M could be grouped into cluster 3 on the basis of the above criterion given the findings of skin ulcers with a male predominance. Half of the patients had severe vasculopathy and Raynaud\u0026rsquo;s syndrome. Patient M presented with a mixed picture, having RP-ILD, mechanic\u0026rsquo;s hands, severe vasculopathy, and skin ulcers with a good prognosis, which, if the above classification was used, would be more suitably placed under cluster 3 instead of cluster 1. Patients C, F, I, and L could be grouped under cluster 2 with milder arthritis symptoms. Except for no findings of mechanics hands in cluster 1 patients, the other observations made by Allenbach et al. held true for our population, although given the small sample size (n\u0026thinsp;=\u0026thinsp;2) in this group, there remains a large margin of error.\u003c/p\u003e \u003cp\u003eIn our cohort, two adult female patients over 40 years of age had ovarian cancer; one had a low titer of anti-TIF-1 g and SAE1 antibodies, whereas the other, interestingly, lacked additional autoantibodies, with the exception of anti-MDA-5 antibodies. While the association of the former antibodies with malignancy is well established (27), notably, the anti-MDA5 autoantibody has not been definitively linked to malignancy in previous studies, and the risk is less pronounced, which is consistent with our dataset(28).\u003c/p\u003e \u003cp\u003eEarly diagnosis and treatment are crucial for improving patient prognosis. Recognizing the amyopathic or hypomyopathic nature of the disease, where weakness may not correlate with myopathy and muscle enzyme elevation, is important. Assessment of inflammatory markers, myositis-specific autoantibodies, electromyography, imaging modalities, and muscle biopsy can assist in establishing a diagnosis. High clinical suspicion is needed, and the anti-MDA5 antibody provides confirmation.\u003c/p\u003e \u003cp\u003e There are no standard treatment guidelines for anti-MDA5 dermatomyositis. Interventions include IVIG, calcineurin inhibitors, azathioprine, mycophenolate, biologics such as abatacept and rituximab, and targeted DMARD therapies such as tofacitinib, often with background steroid use. (12,30,31). Adjunctive therapies such as plasma exchange and Polymyxin-B direct hemoperfusion have also been employed. (32). Poor prognostic factors include elevated bronchoalveolar lavage neutrophil counts; early pulmonary involvement with hypoxemia and traction bronchiectasis; and increased serum CX3CL1, CXCR4, and interleukin-18 levels (32,33). Anti-MDA5 antibody titers are correlated with disease severity and clinical response (34). Serum Krebs von den Lungen-6 and ferritin levels have been used to monitor therapeutic response. (32,35).\u003c/p\u003e \u003cp\u003eThe main limitations of this study are its descriptive, single-center, retrospective nature and small cohort. Additionally, all patients self-identified as White, Black, African American, or Hispanic, with only one category selected except for one patient who identified as Black Hispanic, precluding a definitive assessment of the associations among race, age of onset, disease phenotype, and severity. Larger, more diverse cohorts are needed to corroborate these findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAnti-MDA5 dermatomyositis is rare and difficult to diagnose. The disease characteristics of our cohort were similar between adult and pediatric patients, except for a greater prevalence of myositis in the pediatric group. In contrast, adults, especially African Americans, had a higher incidence of ILD with poorer outcomes. Rapidly escalating therapy, including rituximab, which is often combined with mycophenolate, may improve patient outcomes compared with those of historical controls (36). Early aggressive combination immunosuppression shows promise for improving patient prognosis (37). Clinicians should be alerted to the presence of MDA5 dermatomyositis due to characteristic skin ulcerations, ILD, and possibly Raynaud's phenomenon. Muscle involvement should be considered particularly in pediatric patients. The increased mortality observed in African Americans underscores the importance of prompt diagnosis and intervention to improve prognosis. However, our study's limitations prevent further exploration of factors contributing to poorer outcomes in this population. Controlled studies are essential to assess appropriate treatment strategies for patients with anti-MDA5 dermatomyositis and to prevent adverse outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAnti-MDA5: Anti-melanoma differentiation-associated gene 5\u003c/p\u003e\n\u003cp\u003eRP-ILD: Rapidly progressive interstitial lung disease\u003c/p\u003e\n\u003cp\u003eILD: Interstitial lung disease\u003c/p\u003e\n\u003cp\u003eIVIG: Intravenous immunoglobulin\u003c/p\u003e\n\u003cp\u003eCADM: Clinically amyopathic dermatomyositis\u003c/p\u003e\n\u003cp\u003eIFIH: Interferon-induced helicase C domain\u003c/p\u003e\n\u003cp\u003eAnti-TIF-\u0026gamma;: Anti-Transcription intermediary factor 1 gamma\u003c/p\u003e\n\u003cp\u003eAnti-SAE: Anti-small ubiquitin-like modifier activating enzyme\u003c/p\u003e\n\u003cp\u003eCX3CL1: Chemokine (C-X3-C motif) ligand 1\u003c/p\u003e\n\u003cp\u003eCXCR4: Chemokine receptor type 4\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n \u003cli\u003eEthics approval and consent to participate:\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWe received approval from the Montefiore/Albert Einstein College of Medicine Institutional Review Board for this retrospective chart review study, which did not involve any active intervention; hence, the requirement for consent to participate was waived.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eConsent for publication: Not applicable\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003ePatient data were collected from the Epic electronic medical records via a search tool to identify all the myositis patients. The dataset was stored on Epic and deidentified patient information compiled into a spreadsheet and shared as supplementary charts/additional files for review.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eCompeting interests: Not applicable\u003c/li\u003e\n \u003cli\u003eFunding: No funding was received for the study.\u003c/li\u003e\n \u003cli\u003eAuthors\u0026apos; contributions\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eSK: Data collection, writing and editing of the tables and manuscript\u003c/p\u003e\n\u003cp\u003eFE: Data review, writing and editing the manuscript\u003c/p\u003e\n\u003cp\u003eDW: Writing and editing the manuscript\u003c/p\u003e\n\u003cp\u003eAK: Writing and editing the manuscript\u003c/p\u003e\n\u003cp\u003eXX: Worked on statistics, data analysis and editing the manuscript\u003c/p\u003e\n\u003cp\u003eCT: Data collection, writing and editing of the tables and manuscript\u003c/p\u003e\n\u003cp\u003eBA: Data collection, writing and editing the manuscript\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eAcknowledgments: Not applicable\u003c/li\u003e\n \u003cli\u003eClinical trial number: Not applicable\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSakamoto N, Ishimoto H, Nakashima S, Yura H, Miyamura T, Okuno D, et al. Clinical Features of Anti-MDA5 Antibody-positive Rapidly Progressive Interstitial Lung Disease without Signs of Dermatomyositis. Intern Med. 2019;58(6):837-41.\u003c/li\u003e\n\u003cli\u003eFiorentino D, Chung L, Zwerner J, Rosen A, Casciola-Rosen L. The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study. J Am Acad Dermatol. 2011;65(1):25-34.\u003c/li\u003e\n\u003cli\u003eCao H, Xia Q, Pan M, Zhao X, Li X, Shi R, et al. Gottron Papules and Gottron Sign with Ulceration: A Distinctive Cutaneous Feature in a Subset of Patients with Classic Dermatomyositis and Clinically Amyopathic Dermatomyositis. J Rheumatol. 2016;43(9):1735-42.\u003c/li\u003e\n\u003cli\u003eKurtzman DJB, Vleugels RA. Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis: A concise review with an emphasis on distinctive clinical features. J Am Acad Dermatol. 2018;78(4):776-85.\u003c/li\u003e\n\u003cli\u003eMoghadam-Kia S, Oddis CV, Sato S, Kuwana M, Aggarwal R. Antimelanoma Differentiation-associated Gene 5 Antibody: Expanding the Clinical Spectrum in North American Patients with Dermatomyositis. J Rheumatol. 2017;44(3):319-25.\u003c/li\u003e\n\u003cli\u003eMoghadam-Kia S, Oddis CV, Aggarwal R. Anti-MDA5 Antibody Spectrum in Western World. Curr Rheumatol Rep. 2018;20(12):78.\u003c/li\u003e\n\u003cli\u003eGil B, Merav L, Pnina L, Chagai G. Diagnosis and treatment of clinically amyopathic dermatomyositis (CADM): a case series and literature review. Clin Rheumatol. 2016;35(8):2125-30.\u003c/li\u003e\n\u003cli\u003eAbe Y, Matsushita M, Tada K, Yamaji K, Takasaki Y, Tamura N. Clinical characteristics and change in the antibody titers of patients with anti-MDA5 antibody-positive inflammatory myositis. Rheumatology (Oxford). 2017;56(9):1492-7.\u003c/li\u003e\n\u003cli\u003eChen Z, Cao M, Plana MN, Liang J, Cai H, Kuwana M, et al. Utility of anti-melanoma differentiation-associated gene 5 antibody measurement in identifying patients with dermatomyositis and a high risk for developing rapidly progressive interstitial lung disease: a review of the literature and a meta-analysis. Arthritis Care Res (Hoboken). 2013;65(8):1316-24.\u003c/li\u003e\n\u003cli\u003eAllenbach Y, Uzunhan Y, Toquet S, Leroux G, Gallay L, Marquet A, et al. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases. Neurology. 2020;95(1):e70-e8.\u003c/li\u003e\n\u003cli\u003ePerron MM, Vasquez-Canizares N, Tarshish G, Wahezi DM. Myositis autoantibodies in a racially diverse population of children with idiopathic inflammatory myopathies. Pediatr Rheumatol Online J. 2021;19(1):92.\u003c/li\u003e\n\u003cli\u003eNombel A, Fabien N, Coutant F. Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies. Front Immunol. 2021;12:773352.\u003c/li\u003e\n\u003cli\u003eHe S, Zhou Y, Fan C, Ma J, Chen Y, Wu W, et al. Differences in sex- and Age-Associated Mortality in Patients with anti-MDA5 Positive Dermatomyositis. Mod Rheumatol. 2022.\u003c/li\u003e\n\u003cli\u003eCassius C, Amode R, Delord M, Battistella M, Poirot J, How-Kit A, et al. MDA5(+) Dermatomyositis Is Associated with Stronger Skin Type I Interferon Transcriptomic Signature with Upregulation of IFN-kappa Transcript. J Invest Dermatol. 2020;140(6):1276-9 e7.\u003c/li\u003e\n\u003cli\u003eLi D, Tansley SL. Juvenile Dermatomyositis-Clinical Phenotypes. Curr Rheumatol Rep. 2019;21(12):74.\u003c/li\u003e\n\u003cli\u003eNakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H, Nojima T, et al. The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology (Oxford). 2010;49(3):433-40.\u003c/li\u003e\n\u003cli\u003eSato S, Hirakata M, Kuwana M, Suwa A, Inada S, Mimori T, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum. 2005;52(5):1571-6.\u003c/li\u003e\n\u003cli\u003eParronchi P, Radice A, Palterer B, Liotta F, Scaletti C. MDA5-positive dermatomyositis: an uncommon entity in Europe with variable clinical presentations. Clin Mol Allergy. 2015;13:22.\u003c/li\u003e\n\u003cli\u003eCeribelli A, Fredi M, Taraborelli M, Cavazzana I, Tincani A, Selmi C, et al. Prevalence and clinical significance of anti-MDA5 antibodies in European patients with polymyositis/dermatomyositis. Clin Exp Rheumatol. 2014;32(6):891-7.\u003c/li\u003e\n\u003cli\u003eSontheimer RD. MDA5 autoantibody-another indicator of clinical diversity in dermatomyositis. Ann Transl Med. 2017;5(7):160.\u003c/li\u003e\n\u003cli\u003eYeung TW, Cheong KN, Lau YL, Tse KN. Adolescent-onset anti-MDA5 antibody-positive juvenile dermatomyositis with rapidly progressive interstitial lung disease and spontaneous pneumomediastinum: a case report and literature review. Pediatr Rheumatol Online J. 2021;19(1):103.\u003c/li\u003e\n\u003cli\u003eFindlay AR, Goyal NA, Mozaffar T. An overview of polymyositis and dermatomyositis. Muscle Nerve. 2015;51(5):638-56.\u003c/li\u003e\n\u003cli\u003eMamyrova G, Kishi T, Shi M, Targoff IN, Huber AM, Curiel RV, et al. Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America. Rheumatology (Oxford). 2021;60(4):1839-49.\u003c/li\u003e\n\u003cli\u003eNarang NS, Casciola-Rosen L, Li S, Chung L, Fiorentino DF. Cutaneous ulceration in dermatomyositis: association with anti-melanoma differentiation-associated gene 5 antibodies and interstitial lung disease. Arthritis Care Res (Hoboken). 2015;67(5):667-72.\u003c/li\u003e\n\u003cli\u003eMa X, Chen Z, Hu W, Guo Z, Wang Y, Kuwana M, et al. Clinical and serological features of patients with dermatomyositis complicated by spontaneous pneumomediastinum. Clin Rheumatol. 2016;35(2):489-93.\u003c/li\u003e\n\u003cli\u003eLv C, You H, Xu L, Wang L, Yuan F, Li J, et al. Coexistence of Anti-Ro52 Antibodies in Anti-MDA5 Antibody-Positive Dermatomyositis Is Highly Associated With Rapidly Progressive Interstitial Lung Disease and Mortality Risk. J Rheumatol. 2023;50(2):219-26.\u003c/li\u003e\n\u003cli\u003eKoga T, Okamoto M, Satoh M, Fujimoto K, Zaizen Y, Chikasue T, et al. Positive Autoantibody Is Associated with Malignancies in Patients with Idiopathic Interstitial Pneumonias. Biomedicines. 2022;10(10).\u003c/li\u003e\n\u003cli\u003eMecoli CA, Igusa T, Chen M, Wang X, Albayda J, Paik JJ, et al. Subsets of Idiopathic Inflammatory Myositis Enriched for Contemporaneous Cancer Relative to the General Population. Arthritis Rheumatol. 2023;75(4):620-9.\u003c/li\u003e\n\u003cli\u003eLi Y, Wu J, Miao M, Gao X, Cai W, Shao M, et al. Predictors of Poor Outcome of Anti-MDA5-Associated Rapidly Progressive Interstitial Lung Disease in a Chinese Cohort with Dermatomyositis. J Immunol Res. 2020;2020:2024869.\u003c/li\u003e\n\u003cli\u003eSabbagh S, Almeida de Jesus A, Hwang S, Kuehn HS, Kim H, Jung L, et al. Treatment of anti-MDA5 autoantibody-positive juvenile dermatomyositis using tofacitinib. Brain. 2019;142(11):e59.\u003c/li\u003e\n\u003cli\u003eHallowell RW, Paik JJ. Myositis-associated interstitial lung disease: a comprehensive approach to diagnosis and management. Clin Exp Rheumatol. 2022;40(2):373-83.\u003c/li\u003e\n\u003cli\u003eShirakashi M, Nakashima R, Tsuji H, Tanizawa K, Handa T, Hosono Y, et al. Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment. Rheumatology (Oxford). 2020;59(11):3284-92.\u003c/li\u003e\n\u003cli\u003eTakada T, Aoki A, Asakawa K, Sakagami T, Moriyama H, Narita I, et al. Serum cytokine profiles of patients with interstitial lung disease associated with anti-CADM-140/MDA5 antibody positive amyopathic dermatomyositis. Respir Med. 2015;109(9):1174-80.\u003c/li\u003e\n\u003cli\u003eKoga T, Fujikawa K, Horai Y, Okada A, Kawashiri SY, Iwamoto N, et al. The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology (Oxford). 2012;51(7):1278-84.\u003c/li\u003e\n\u003cli\u003eMimori T, Nakashima R, Hosono Y. Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep. 2012;14(3):264-74.\u003c/li\u003e\n\u003cli\u003eSo H, Wong VTL, Lao VWN, Pang HT, Yip RML. Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis. Clin Rheumatol. 2018;37(7):1983-9.\u003c/li\u003e\n\u003cli\u003eTsuji H, Nakashima R, Hosono Y, Imura Y, Yagita M, Yoshifuji H, et al. Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis. Arthritis Rheumatol. 2020;72(3):488-98.\u003c/li\u003e\n\u003cli\u003eBorges, I. B., Silva, M. G., \u0026amp; Shinjo, S. K. (2018). Prevalence and reactivity of anti-melanoma differentiation-associated gene 5 (anti-MDA-5) autoantibody in Brazilian patients with dermatomyositis. \u003cem\u003eAnais Brasileiros de Dermatologia\u003c/em\u003e, \u003cem\u003e93\u003c/em\u003e(4), 517\u0026ndash;523. https://doi.org/10.1590/abd1806-4841.20186803\u003c/li\u003e\n\u003cli\u003eSato S, Kuwana M, Fujita T, Suzuki Y. Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol. 2013;23:496\u0026ndash;502.\u003c/li\u003e\n\u003cli\u003eMukae H, Ishimoto H, Sakamoto N, Hara S, Kakugawa T, Nakayama S. Clinical differences between interstitial lung disease associated with clinically amyopathic dermatomyositis and classic dermatomyositis. Chest. 2009;136:1341\u0026ndash;1347.\u003c/li\u003e\n\u003cli\u003eYe S, Chen XX, Lu XY, Wu MF, Deng Y, Huang WQ. Adult clinically amyopathic dermatomyositis with rapid progressive interstitial lung disease: a retrospective cohort study. Clin Rheumatol. 2007;26:1647\u0026ndash;1654.\u003c/li\u003e\n\u003cli\u003eJi SY, Zeng FQ, Guo Q, Tan GZ, Tang HF, Luo YJ. Predictive factors and unfavorable prognostic factors of interstitial lung disease in patients with polymyositis or dermatomyositis: a retrospective study. Chin Med J (Engl) 2010;123:517\u0026ndash;522.\u003c/li\u003e\n\u003cli\u003eSontheimer RD. clinically amyopathic dermatomyositis: what can we now tell our patients? Arch Dermatol. 2010;146:76\u0026ndash;80.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Study patient characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003eAdult MDA5 Dermatomyositis\u003c/p\u003e\n \u003cp\u003eN = 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003ePediatric MDA5 Dermatomyositis\u003c/p\u003e\n \u003cp\u003eN = 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eMean age at disease onset Years, (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e44.6 (13.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e6.5 (4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eSex (Male, Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e5,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e3,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eRace/Ethnicity\u003c/p\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003cp\u003eHispanic\u003c/p\u003e\n \u003cp\u003eAfrican American\u003c/p\u003e\n \u003cp\u003eBlack Hispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eILD\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003cp\u003eStable ILD\u003c/p\u003e\n \u003cp\u003eRP-ILD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eSkin ulcers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eArthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eMyositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eRaynaud\u0026rsquo;s phenomenon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eANA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.1281%;\"\u003e\n \u003cp\u003eRo 52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4559%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29.2845%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.1314%;\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2. Clinical characteristics of patients by Race/Ethnicity\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 33.6559%;\"\u003e\n \u003cp\u003eRace/Ethnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eStudy characteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eHispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003eAfrican American\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003eNon-Hispanic White\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003eBlack Hispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eILD\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003cp\u003eStable\u003c/p\u003e\n \u003cp\u003eRP-ILD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.06\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0.04*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eMyositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eSkin ulcers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eRaynaud\u0026rsquo;s phenomenon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eArthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eANA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.5269%;\"\u003e\n \u003cp\u003eRo 52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.8817%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.7742%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.3763%;\"\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eNote: * - Black Hispanic or African American compared to other for RP-ILD;\u0026nbsp;\u003c/em\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e - \u003cem\u003eBlack Hispanic or African American compared to other for ILD\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTable 3. Relationship of ILD to clinic and laboratory characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eILD, N=15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eNo ILD, N=7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eRP-ILD, N=4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003eStable/No ILD, N=18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003eSkin ulcers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e10(66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e3(42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1(25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e12(66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003eRaynaud\u0026rsquo;s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e10(66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1(14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e1(25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e11(61.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003eRo 52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e8(53.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e3(42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003ens\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e3(75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e8(44.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"MDA5 autoantibody, Dermatomyositis, Race \u0026 Ethnicity, Interstitial Lung Disease","lastPublishedDoi":"10.21203/rs.3.rs-5085511/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5085511/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eThe anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody dermatomyositis is known for its association with rapidly progressive interstitial lung disease (RP-ILD) and ulcerative skin lesions, often presenting with or without muscle involvement. The aim of this study was to identify distinct clinical and laboratory features that could be used to evaluate disease progression in an ethnically diverse cohort of anti-MDA5 dermatomyositis patients at a U.S. academic center.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective chart review was conducted on dermatomyositis patients hospitalized at our institution between January 2014 and June 2023. The data were analyzed via Fischer\u0026rsquo;s exact test and a t test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 195 dermatomyositis patients reviewed, 22 tested positive for the MDA5 antibody, comprising thirteen adults and nine pediatric patients. Among these individuals, ten adults exhibited ILD, three of whom were classified as having RP-ILD. Notably, all pediatric patients displayed some level of muscle weakness. The five pediatric patients diagnosed with ILD had a higher prevalence of myositis. The incidence of ILD was significantly greater in the adult Black Hispanic and African American populations (10/15 cases, p\u0026thinsp;=\u0026thinsp;0.035) than in the other ethnicities, with three cases resulting in fatal RP-ILD. The overall mortality rate of 13.6% was more favorable than the previously reported 40\u0026ndash;60% rates.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eIn conclusion, while the general disease characteristics were similar between adult and pediatric patients, myositis was more prevalent in the pediatric population. Adults, particularly those from Black and African American backgrounds, experienced a greater incidence of ILD, leading to poorer outcomes.\u003c/p\u003e","manuscriptTitle":"Anti-melanoma differentiation-associated gene 5 (Anti-MDA5) antibody dermatomyositis: Clinical features and outcomes in a racially diverse patient cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-29 13:34:57","doi":"10.21203/rs.3.rs-5085511/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-26T08:25:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-23T12:10:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-23T12:05:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Rheumatology","date":"2024-09-13T17:56:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9c4b9038-bc42-4151-8dd2-e5e8bd64a6af","owner":[],"postedDate":"November 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-01-13T16:03:25+00:00","versionOfRecord":{"articleIdentity":"rs-5085511","link":"https://doi.org/10.1186/s41927-025-00455-5","journal":{"identity":"bmc-rheumatology","isVorOnly":false,"title":"BMC Rheumatology"},"publishedOn":"2025-01-09 15:57:43","publishedOnDateReadable":"January 9th, 2025"},"versionCreatedAt":"2024-11-29 13:34:57","video":"","vorDoi":"10.1186/s41927-025-00455-5","vorDoiUrl":"https://doi.org/10.1186/s41927-025-00455-5","workflowStages":[]},"version":"v1","identity":"rs-5085511","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5085511","identity":"rs-5085511","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}