ECMO as a Bridge to Lung Transplant for Refractory Rapidly Progressive Interstitial Lung Disease

Abstract Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is most frequently associated with dermatomyositis with various degrees of clinical manifestations including rapidly progressive interstitial lung disease (RP-ILD), inflammatory arthritis, vasculopathy, and other cutaneous findings. Clinically amyopathic dermatomyositis (CADM) is frequently associated with RP-ILD and has high mortality rates. Here we present a case of anti-MDA5 associated RP-ILD but without other features of dermatomyositis that did not respond to standard immunosuppressive therapy. A 41-year-old woman with recently diagnosed interstitial lung disease and polyarthritis previously on methotrexate presented with progressive dyspnea and worsening hypoxemic respiratory failure. She was previously admitted for respiratory failure two months prior where high resolution CT revealed moderate to advanced fibrotic lung disease and mediastinal lymphadenopathy and was discharged on a prolonged prednisone taper. Previous studies revealed a positive MDA5 antibody. She was treated initially with intravenous methylprednisolone 1,000 mg for three days then transitioned to oral prednisone. Lung biopsy revealed fibrotic and cellular non-specific interstitial pneumonia (NSIP). She received one cycle of plasmapheresis, followed by a Rituximab infusion in addition to Tacrolimus. She was then transferred to a transplant center where she was placed on veno-arterial-venous extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant. Unfortunately, her respiratory failure worsened, requiring ECMO reconfiguration. She was unable to recover enough for transplant candidacy and transitioned to comfort-focused care, passing away shortly afterwards. RP-ILD is a known complication of anti-MDA5 associated diseases, with mortality approaching 84%. A combination of high-dose glucocorticoids and other immunosuppression agents give the highest probability of survival, though they must be administered early in the disease course. Our patient had a delay in additional immunosuppressive therapy, despite positive antibody titers two months prior, which may have resulted in a more advanced respiratory failure and hypoxemia on presentation, ultimately requiring mechanical ventilation and subsequent ECMO cannulation. A systematic review published in Annals of Rheumatology found that ECMO used a bridge to transplant had an 87.5% survival rate with MDA5 disease-free remission for up to 12 years using standard induction transplant immunosuppressants, which a more recent case report in CHEST exemplified. Our case emphasizes the importance of early antibody screening and prompt initiation of appropriate immunosuppressive therapy to avoid transformation to RP-ILD. Early referral to a transplant center should be pursued in these patients as ECMO has shown promise as a bridge to transplant in this condition.