{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T06:10:57Z","timestamp":1760335857451,"version":"build-2065373602"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Dermatomyositis (DM) is a rare autoimmune disorder, with the anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody positive subtype associated with severe complications such as rapidly progressive interstitial lung disease (RP-ILD) and, more rarely, spontaneous pneumomediastinum (SPM). This case highlights the challenges of managing a patient with such complex condition, particularly in the context of multiple comorbidities, including a history of cancer and recurrent infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case description<\/jats:title><jats:p>A 45-year-old woman with an history of vulvar squamous cell carcinoma (July 2022) presented with classic features of DM, including Gottron\u2019s papules, proximal muscle weakness, dysphagia, severe cutaneous vasculitis and lymphopenia. She was then diagnosed with anti-MDA5-positive DM in October 2023. High-resolution CT (HRCT) of the lung performed in January 2024, in the absence of respiratory symptoms, revealed early interstitial changes with ground-glass opacities. Initial corticosteroid therapy yielded partial improvement. A <jats:italic>Listeria monocytogenes<\/jats:italic> meningitis in July 2024, coupled with her history of cancer, delayed the start of aggressive immunosuppressive therapy, even though the onset of dyspnea and imaging in June 2024 had already revealed worsening interstitial lung disease (ILD). In the meantime she received two cycles of intravenous immunoglobulin (IVIg). By October 2024, clinical decline with cutaneous ulcers and severe lymphopenia prompted cyclosporine (CyA) initiation. Concurrently, imaging revealed progressing ILD with new-onset pneumomediastinum and subcutaneous emphysema, culminating in massive emphysema requiring hospitalization and bilateral thoracic drainage. A multidisciplinary team approved the escalation to rituximab, which, in combination with her existing regimen, led to clinical stabilization and the resolution of her pulmonary and cutaneous symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case emphasizes the complexity of managing anti-MDA5-positive DM with severe pulmonary complications. Early recognition, a multidisciplinary approach, and personalized treatment are crucial to improving outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1646791","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T05:28:12Z","timestamp":1760333292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Spontaneous pneumomediastinum in a patient with MDA5-positive dermatomyositis and severe pulmonary fibrosis"],"prefix":"10.3389","volume":"12","author":[{"given":"M.","family":"Rizzo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Braga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Raschell\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Maranini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Schifino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Carnevale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Govoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Lo Monaco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"903","DOI":"10.24953\/turkjped.2021.05.018","article-title":"A fatal interstitial lung disease in an anti-MDA5 antibody negative patient with juvenile dermatomyositis","volume":"63","author":"Ye\u015filba\u015f","year":"2021","journal-title":"Turk J Pediatr"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.5387\/fms.2018-01","article-title":"Anti-MDA5 antibody-positive hypomyopathic dermatomyositis complicated with pneumomediastinum","volume":"64","author":"Yashiro","year":"2018","journal-title":"Fukushima J Med Sci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"S574","DOI":"10.1097\/RHU.0000000000000984","article-title":"Successful treatment for refractory interstitial lung disease and pneumomediastinum with multidisciplinary therapy including tofacitinib in a patient with anti-MDA5 antibody-positive dermatomyositis","volume":"27","author":"Kato","year":"2021","journal-title":"J Clin Rheumatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12969-021-00595-1","article-title":"Adolescent-onset anti-MDA5 antibody-positive juvenile dermatomyositis with rapidly progressive interstitial lung disease and spontaneous pneumomediastinum: a case report and literature review","volume":"19","author":"Yeung","year":"2021","journal-title":"Pediatr Rheumatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1093\/rheumatology\/ker518","article-title":"The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM","volume":"51","author":"Koga","year":"2012","journal-title":"Rheumatology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s10067-015-3001-3","article-title":"Clinical and serological features of patients with dermatomyositis complicated by spontaneous pneumomediastinum","volume":"35","author":"Ma","year":"2016","journal-title":"Clin Rheumatol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.1007\/s10067-019-04729-5","article-title":"Clinical features of patients with anti-melanoma differentiation-associated gene-5 antibody-positive dermatomyositis complicated by spontaneous pneumomediastinum","volume":"38","author":"Yamaguchi","year":"2019","journal-title":"Clin Rheumatol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/art.24372","article-title":"Pneumomediastinum in interstitial lung disease associated with dermatomyositis and polymyositis","volume":"61","author":"Le Goff","year":"2009","journal-title":"Arthritis Rheum"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"152352","DOI":"10.1016\/j.semarthrit.2023.152352","article-title":"Spontaneous pneumomediastinum in anti-MDA5-positive dermatomyositis: prevalence, risk factors, and prognosis","volume":"65","author":"Jin","year":"2024","journal-title":"Semin Arthritis Rheum"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"262","DOI":"10.55563\/clinexprheumatol\/84kd56","article-title":"The clinical characteristics of subcutaneous and mediastinal emphysema in anti-melanoma differentiation-associated 5 positive dermatomyositis associated with interstitial lung disease","volume":"42","author":"Huang","year":"2024","journal-title":"Clin Exp Rheumatol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1136\/ard.59.5.372","article-title":"Pneumomediastinum in dermatomyositis: association with cutaneous vasculopathy","volume":"59","author":"Kono","year":"2000","journal-title":"Ann Rheum Dis"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12890-018-0622-8","article-title":"MDA-5 associated rapidly progressive interstitial lung disease with recurrent pneumothoraces: a case report","volume":"18","author":"Alqatari","year":"2018","journal-title":"BMC Pulm Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3760\/cma.j.cn112149-20200429-00631","article-title":"Clinical and chest CT manifestations of anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis","volume":"55","author":"Chen","year":"2021","journal-title":"Chin J Radiol China"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"6097183","DOI":"10.1155\/2021\/6097183","article-title":"Spontaneous pneumomediastinum due to anti-melanoma differentiation-associated protein 5 requiring a bilateral lung transplant","volume":"2021","author":"Jhajj","year":"2021","journal-title":"Case Rep Rheumatol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1080\/24725625.2020.1832755","article-title":"Fatal outcome of anti-MDA5 juvenile dermatomyositis in a paediatric COVID-19 patient: a case report","volume":"5","author":"Quintana-Ortega","year":"2021","journal-title":"Mod Rheumatol Case Rep"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"136","DOI":"10.46497\/ArchRheumatol.2022.8719","article-title":"Spontaneous pneumomediastinum and cutaneous ulcers complicated in a patient with dermatomyositis and interstitial lung disease","volume":"37","author":"Kwon","year":"2022","journal-title":"Arch Rheumatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s10067-005-0109-x","article-title":"Spontaneous pneumomediastinum and dermatomyositis may be a not so rare association: report of a case and review of the literature","volume":"26","author":"de S","year":"2007","journal-title":"Clin Rheumatol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/1756-185X.13112","article-title":"Spontaneous pneumomediastinum in a dermatomyositis patient with anti-melanoma differentiation-associated gene-5 antibody and interstitial lung disease despite an initial response to immunosuppressant","volume":"22","author":"Chan","year":"2019","journal-title":"Int J Rheum Dis"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1684\/ejd.2019.3634","article-title":"Clinical features and poor prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapid progressive interstitial lung disease","volume":"29","author":"Motegi","year":"2019","journal-title":"Eur J Dermatol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s12016-020-08822-5","article-title":"Interstitial lung disease in anti-MDA5 positive dermatomyositis","volume":"60","author":"Wu","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e002770","DOI":"10.1136\/rmdopen-2022-002770","article-title":"Prognosis of spontaneous pneumomediastinum occurring in dermatomyositis or polymyositis patients with interstitial lung disease according to antimelanoma differentiation-associated gene 5 antibody status: a retrospective cohort study","volume":"9","author":"Abe","year":"2023","journal-title":"RMD Open"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1111\/joim.13607","article-title":"Peripheral lymphocyte count defines the clinical phenotypes and prognosis in patients with anti-MDA5-positive dermatomyositis","volume":"293","author":"Jin","year":"2023","journal-title":"J Intern Med"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1080\/08916930600623791","article-title":"In patients with antisynthetase syndrome the occurrence of anti-Ro\/SSA antibodies causes a more severe interstitial lung disease","volume":"39","author":"La Corte","year":"2006","journal-title":"Autoimmunity"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3899\/jrheum.220139","article-title":"Coexistence of anti-Ro52 antibodies in anti-MDA5 antibody-positive dermatomyositis is highly associated with rapidly progressive interstitial lung disease and mortality risk","volume":"50","author":"Lv","year":"2023","journal-title":"J Rheumatol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3343","DOI":"10.1093\/rheumatology\/keaa786","article-title":"Prognostic values of anti-Ro52 antibodies in anti-MDA5-positive clinically amyopathic dermatomyositis associated with interstitial lung disease","volume":"60","author":"Xu","year":"2021","journal-title":"Rheumatology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"274","DOI":"10.55563\/clinexprheumatol\/di1083","article-title":"Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies","volume":"40","author":"Cavagna","year":"2022","journal-title":"Clin Exp Rheumatol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"106134","DOI":"10.1016\/j.rmed.2020.106134","article-title":"Anti-Ro52 antibody is an independent risk factor for interstitial lung disease in dermatomyositis","volume":"172","author":"Xing","year":"2020","journal-title":"Respir Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"161","DOI":"10.3899\/jrheum.221067","article-title":"Ro52, myositis, and interstitial lung disease","volume":"50","author":"McHugh","year":"2023","journal-title":"J Rheumatol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1286973","DOI":"10.3389\/fimmu.2024.1286973","article-title":"Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model","volume":"15","author":"Wang","year":"2024","journal-title":"Front Immunol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1093\/rheumatology\/keac115","article-title":"British Society for Rheumatology guideline on management of paediatric, adolescent and adult patients with idiopathic inflammatory myopathy","volume":"61","author":"Oldroyd","year":"2022","journal-title":"Rheumatology"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.rmcr.2019.01.012","article-title":"Anti-MDA5 antibody-positive rapidly progressive interstitial pneumonia without cutaneous manifestations","volume":"26","author":"Aoyama","year":"2019","journal-title":"Respir Med Case Rep"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1056\/NEJMoa2117912","article-title":"Trial of intravenous immune globulin in dermatomyositis","volume":"387","author":"Aggarwal","year":"2022","journal-title":"N Engl J Med"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1002\/art.42861","article-title":"2023 American College of Rheumatology (ACR)\/American College of CHEST Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases","volume":"76","author":"Johnson","year":"2024","journal-title":"Arthritis Rheumatol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1177\/0961203314554849","article-title":"The efficacy of calcineurin inhibitors for the treatment of interstitial lung disease associated with polymyositis\/dermatomyositis","volume":"24","author":"Kurita","year":"2015","journal-title":"Lupus"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1097\/RHU.0000000000000487","article-title":"Effective use of calcineurin inhibitor in combination therapy for interstitial lung disease in patients with dermatomyositis and polymyositis","volume":"23","author":"Shimojima","year":"2017","journal-title":"J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/art.37754","article-title":"Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial","volume":"65","author":"Oddis","year":"2013","journal-title":"Arthritis Rheum"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"151959","DOI":"10.1016\/j.semarthrit.2022.151959","article-title":"Management of MDA-5 antibody positive clinically amyopathic dermatomyositis associated interstitial lung disease: a systematic review","volume":"53","author":"McPherson","year":"2022","journal-title":"Semin Arthritis Rheum"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1183\/09031936.00163911","article-title":"Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy","volume":"40","author":"Keir","year":"2012","journal-title":"Eur Respir J"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"927","DOI":"10.3390\/jcm11040927","article-title":"Efficacy and safety of rituximab in autoimmune disease-associated interstitial lung disease: a prospective cohort study","volume":"11","author":"Mena-V\u00e1zquez","year":"2022","journal-title":"J Clin Med"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s42358-018-0030-z","article-title":"Favorable rituximab response in patients with refractory idiopathic inflammatory myopathies","volume":"58","author":"de Souza","year":"2018","journal-title":"Adv Rheumatol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"3221","DOI":"10.2169\/internalmedicine.3418-23","article-title":"Tension Pneumomediastinum in anti-MDA5 antibody-positive dermatomyositis-associated interstitial lung disease: a case report and literature review","volume":"63","author":"Okabayashi","year":"2024","journal-title":"Intern Med"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e75865","DOI":"10.7759\/cureus.75865","article-title":"Management of Severe Subcutaneous Emphysema with a subcutaneous cannula: a life-saving approach","volume":"16","author":"Lim","year":"2024","journal-title":"Cureus"},{"key":"ref43","first-page":"129","article-title":"The use of subcutaneous drains to manage subcutaneous emphysema","volume":"26","author":"Sherif","year":"1999","journal-title":"Tex Heart Inst J"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1002\/rcr2.9","article-title":"Management of extensive subcutaneous emphysema with a subcutaneous drain","volume":"1","author":"O'Reilly","year":"2013","journal-title":"Respirol Case Rep"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"386","DOI":"10.55563\/clinexprheumatol\/c0i032","article-title":"Nintedanib could potentially lead to improvements in anti-melanoma differentiation-associated 5 dermatomyositis-associated interstitial lung disease","volume":"42","author":"Chen","year":"2024","journal-title":"Clin Exp Rheumatol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1646791\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T05:28:14Z","timestamp":1760333294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1646791\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":45,"alternative-id":["10.3389\/fmed.2025.1646791"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1646791","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2025,10,13]]},"article-number":"1646791"}}