A RARE CASE OF INTERSTITIAL LUNG DISEASE IN IDIOPATHIC INFLAMMATORY MYOSITIS ASSOCIATED WITH ANTI-MDA5

Abstract

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Anti-MDA5 (anti-melanoma differentiation-associated gene-5) associated dermatomyositis (DM) is a rare presentation of idiopathic inflammatory myositis, often presenting with treatment refractory rapidly progressing interstitial lung disease (ILD). Diagnosis is difficult as patients can present without symptoms or biochemical evidence of DM. We report a rare adult case of anti-MDA5 ILD with only pulmonary manifestations. CASE PRESENTATION: 74-year-old female with past medical history of atrial fibrillation status post pacemaker, reactive airway disease, and heart failure with preserved ejection fraction, was referred to pulmonary clinic for abnormal CT scan and dyspnea that began 4 months prior while living in India. Initial chest CT was significant for bi-apical consolidations and bronchiectasis. Bronchoscopy with lavage was positive for Aspergillus galactomannan, and she was treated with isavuconazole, prednisone, and Septra (for pneumocystis prophylaxis). Chest CT 4 weeks later showed improvement in consolidations. 3 months later, dyspnea recurred. She was re-started on prednisone 20 mg daily, and dyspnea resolved. She subsequently relocated to the USA. She had serial negative COVID tests. Pulmonary function test showed a restrictive ventilatory defect with decreased diffusion capacity. Follow-up CT chest revealed bi-apical scarring, and multifocal airspace consolidation. ESR 44 (elevated) and CRP 11.2 (elevated). IGE, aldolase, CK, hypersensitivity pneumonitis antibody panel, Aspergillus antibody, nuclear antibody panel, RF, and anti-CCP were negative. Extended myositis panel revealed high positive titer for anti-MDA5 and RNA polymerase 3 antibodies;subsequently confirmed with a different extended myositis assay. She was referred to a rheumatologist who recommended aggressive immune modulating treatment with prednisone, tacrolimus and cyclophosphamide. After discussion, she opted for mycophenolate mofetil and prednisone. DISCUSSION: Anti-MDA5 associated DM can present with rapidly progressive ILD and is associated with poor prognosis. In a small prospective study, a triple therapy regimen consisting of high dose glucocorticoid, Tacrolimus, and intravenous Cyclophosphamide showed 6-month survival benefit compared to a step-up approach (which entailed starting with high dose glucocorticoids and later combining with immunomodulators). Plasmapheresis has been used for patients who have failed combination immunomodulators in multiple small case studies. CONCLUSIONS: Anti-MDA5 associated ILD should be considered in patients with new ILD, since it can present without evidence of DM. Intense multiple drug immune suppression is recommended from the beginning. Plasmapheresis and lung transplant can be considered if patients become refractory to combination immunosuppression. REFERENCE #1: Gupta R, Kumar S, Gow P, Hsien-Cheng Chang L, Yen L. Anti-MDA5-associated dermatomyositis. Intern Med J. 2020 Apr;50(4):484-487. doi: 10.1111/imj.14789. PMID: 32270621. REFERENCE #2: Fiorentino 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 Jul;65(1):25-34. doi: 10.1016/j.jaad.2010.09.016. Epub 2011 Apr 29. PMID: 21531040;PMCID: PMC3167687. REFERENCE #3: Hall JC, Casciola-Rosen L, Samedy LA, Werner J, Owoyemi K, Danoff SK, Christopher-Stine L. Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum. Arthritis Care Res (Hoboken). 2013 Aug;65(8):1307-15. doi: 10.1002/acr.21992. PMID: 23436757;PMCID: PMC3689861. DISCLOSURES: No relevant relationships by Peter Huh, source=Web Response No relevant relationships by Sudhir Rajan, source=Web Response No relevant relationships by Eduardo Solbes, source=Web Response