Slowly progressive interstitial lung disease preceding typical dermatomyositis symptoms in anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

A 73-year-old woman who visited our hospital complaining of dry cough for three months was refractory to antimicrobial therapy. Chest computed tomography revealed subpleural consolidation. Specimens obtained from surgical lung biopsy revealed subpleural perilobular airspace organization and fibrosis. After the biopsy, mechanic's hand and Gottron's papules appeared, and anti-melanoma differentiation-associated gene 5 (MDA5) antibody was found to be positive. Subsequently, anti-MDA5 antibody measured in cryopreserved serum from her first admission proved to be positive. It is difficult to suspect the presence of anti-MDA-5 antibody in patients with interstitial lung disease without typical dermatomyositis symptoms or slow disease progression.

Acute lung injury after plasma exchange in a patient with anti-MDA5 antibody-positive, rapidly progressive, interstitial lung disease：A case report.

The presence of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is closely associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis. Despite intensive immunosuppressive therapies, some of these patients still have a poor prognosis with few treatment options. Although removal of pathogenic autoantibodies and cytokines by plasma exchange (PE) could be a treatment option, its safety and efficacy have never been determined. We report a patient with anti-MDA5 Ab-positive RP-ILD who was refractory to intensive therapies including steroids, cyclosporine, and intravenous cyclophosphamide, and then treated by PE to prevent the progression of RP-ILD. Shortly after the initiation of PE therapy, however, his respiratory condition suddenly deteriorated due to acute pulmonary edema and the patient died on the following day. Transfusion-related acute lung injury (TRALI) would be the most likely cause of the acute pulmonary edema because there was no sign of circulatory overload. To the best of our knowledge, this is the first report showing a critical adverse event associated with PE therapy for these patients. This case supports the idea that the presence of ILD could increase a risk for TRALI and therefore we should carefully evaluate the eligibility for PE therapy of anti-MDA5 Ab-positive RP-ILD patients given the risk of acute lung injury. Further studies collecting more clinical data are necessary to assess the efficacy, safety, and risk factors of PE therapy for these patients.

Anti-MDA5 antibody-positive rapidly progressive interstitial pneumonia without cutaneous manifestations.

A 47-year-old man was referred to our hospital with a 1-month history of fever and dyspnea after inhalation of insecticide in a confined space. We diagnosed rapidly progressive interstitial pneumonia. High-dose methylprednisolone, tacrolimus, and intermittent infusion of cyclophosphamide were administered. His condition rapidly deteriorated; therefore, extracorporeal membrane oxygenation therapy was performed. Unfortunately, he died 69 days after admission. Although typical skin findings suggestive of dermatomyositis were absent, anti-melanoma differentiation-associate gene (anti-MDA5) antibody was positive. Our findings suggest that in patients with hyperferritinemia and rapidly progressive interstitial lung disease (RP-ILD) demonstrating random ground glass shadows and peripheral consolidations by high-resolution computed tomography (HRCT) even if skin manifestations related to dermatomyositis are not complicated, we should assume anti-MDA5 antibody-positive interstitial pneumonia.

Lung histopathological pattern in a survivor with rapidly progressive interstitial lung disease and anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are specific indicators of patients with dermatomyositis, particularly clinically amyopathic dermatomyositis (CADM). CADM is occasionally accompanied by fatal, treatment-resistant, rapidly-progressive interstitial lung disease (RP-ILD). All previous reports showed that histopathological findings in RP-ILD with anti-MDA5 antibody-positive CADM indicated diffuse alveolar damage (DAD). This is the first report describing a non-DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM, which was improved by immunosuppressive therapy. This case may be a milder clinical phenotype than a typical DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM.