Successful Treatment of Anti-MDA5 Antibody-Positive Dermatomyositis-Associated Rapidly Progressive-Interstitial Lung Disease by Plasma Exchange: Two Case Reports.

Patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) are frequently accompanied by rapidly progressive-interstitial lung disease (RP-ILD). They are often refractory to intensive immunosuppressive therapy and have poor prognosis. A 73-year-old woman presented with fever, cold symptoms, and skin eruption for a month. She also exhibited muscle weakness on upper extremities slightly. The titer of anti-MDA5 antibody was extremely high, and computed tomography showed ground glass opacity and reticular shadows in the lungs. She was diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD and treated with intensive immunosuppressive therapy. However, the titer of anti-MDA5 antibody did not decrease satisfactorily, and plasma exchange was alternatively initiated. The titer decreased remarkably, and she obtained disease remission. Similarly, a 63-year-old woman presented with stiffness of the neck and hands, fever and cough. She was also diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD, because she had skin eruptions, slight muscle weakness, an elevation in anti-MDA5 antibody, and RP-ILD. She was unresponsive to intensive immunosuppressive therapy, but plasma exchange successfully improved the titer of anti-MDA5 antibody, the symptoms, and the findings of computed tomography. Although anti-MDA5 antibody-positive DM-associated RP-ILD has a high mortality rate, this report suggests the usefulness of plasma exchange to improve the prognosis.

Takahashi R ，Yoshida T ，Morimoto K ，Kondo Y ，Kikuchi J ，Saito S ，Ishigaki S ，Kaneko Y ，Takeuchi T ，Itoh H ，Oya M ... -  《-》

Successful treatment of plasma exchange for rapidly progressive interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis: A case report.

Endo Y ，Koga T ，Suzuki T ，Hara K ，Ishida M ，Fujita Y ，Tsuji S ，Takatani A ，Shimizu T ，Sumiyoshi R ，Igawa T ，Umeda M ，Fukui S ，Nishino A ，Kawashiri SY ，Iwamoto N ，Ichinose K ，Tamai M ，Nakamura H ，Origuchi T ，Kuwana M ，Kawakami A ... -  《-》

Successful treatment of anti-MDA5 antibody-positive refractory interstitial lung disease with plasma exchange therapy.

We examined the effectiveness of plasma exchange (PE) therapy to reduce the mortality of rapidly progressive interstitial lung disease (RP-ILD) in patients positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies. Among 142 patients newly diagnosed with PM/DM or clinically amyopathic DM from 2008 to 2019 at our hospital, 10 were diagnosed with refractory RP-ILD and were positive for anti-MDA5 antibodies. PE was used as an adjunct to standard therapy and consisted of fresh frozen plasma as replacement solution. The primary outcome was non-disease-specific mortality. Anti-MDA5 antibodies were detected in 28 patients, of whom 21 were diagnosed with RP-ILD and 10 were refractory to intensive immunosuppressive therapy. Six patients received PE (PE group) and four did not (non-PE group). The 1-year survival rate of the PE group was higher than that of the non-PE group (100% and 25%, respectively, P = 0.033). Regarding adverse events associated with PE, two patients had anaphylactic shock, one had high fever due to fresh frozen plasma allergy and one had a catheter infection. All adverse events resolved with appropriate treatment. We evaluated the association between 1-year survival rate and PE for refractory RP-ILD in patients positive for anti-MDA5 antibodies. Intensive immunosuppressive therapy improved the survival rate in RP-ILD patients with anti-MDA5 antibodies, but 20-30% of cases were still fatal. PE could be administered to patients with active infectious disease who were immunocompromised by intensive immunosuppressive therapy. PE may be considered in refractory RP-ILD patients positive for anti-MDA5 antibodies.

Abe Y ，Kusaoi M ，Tada K ，Yamaji K ，Tamura N ... -  《-》

Asymptomatic and slowly progressive anti-MDA5 ILD: A report of three cases deviating from a notoriously rapidly progressive ILD.

Anti-melanoma differentiation-associated gene 5-positive (anti-MDA5) dermatomyositis (DM) is a rare autoimmune disease associated with rapidly-progressive interstitial lung disease (RP-ILD.) The reported morbidity and 6-month mortality remains high from 33 to 66 % with RP-ILD most often developing within three months of diagnosis. Most cases require aggressive immunosuppression with combination therapy. Asymptomatic or slowly progressive cases of anti-MDA5 ILD are not well described in the literature. We report three cases of Latino patients with asymptomatic or slowly progressive anti-MDA5 ILD.Case descriptions. A 54-year-old woman from Honduras with known diagnosis of anti-MDA5 dermatomyositis presented for ILD. She denied respiratory symptoms. Computed tomography (CT) chest showed multifocal patchy areas of scattered groundglass opacities throughout all lobes of the lungs, predominately in a subpleural distribution within the lower lobes. Pulmonary function testing (PFTs) showed mild-to-moderate restriction. She was treated with mycophenolate mofetil monotherapy for her skin manifestations. At 18 months follow-up, she denied respiratory symptoms, and PFTs were normal. An 80-year-old man from Cuba was seen in pulmonary clinic to establish care. He was diagnosed with pulmonary fibrosis 11 years earlier with positive anti-MDA5. He denied respiratory symptoms. PFTs showed moderate obstruction and mild to moderate restriction. CT chest showed reduced lung volumes and findings compatible with usual interstitial pneumonia. He was started on nintedanib. Fifteen months following the initial visit, his PFTs remained stable. Follow-up CT chest showed stable pulmonary fibrosis. At all subsequent visits, he reported mild to moderate, slowly progressive dyspnea on exertion and was maintained on nintedanib. Thirteen years after his initial ILD diagnosis, he was diagnosed with pancreatic adenocarcinoma. A 70-year-old woman from Peru presented to pulmonary clinic with cough for two months. She also reported pain in several metacarpophalangeal joints. She denied dyspnea. Rheumatologic serologies revealed positive anti-MDA5. PFTs were normal. Her cough was treated with cough suppressants and resolved. At a subsequent visit 8 months after presentation, she denied respiratory symptoms, and her joint pain remained mild. Given her lack of respiratory symptoms and normal PFTs, she was not initiated on ILD-specific treatment. While anti-MDA5 ILD is certainly associated with RP-ILD, clinicians should maintain awareness that there may be cases of asymptomatic or slowly progressive ILD as well.

Puthumana RM ，Koch AL ，Schettino C ，Vehar SJ ... -  《Respiratory Medicine Case Reports》

Successful treatment of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapidly progressive interstitial lung disease complicated by bilateral breast cancer following the additional tofacitinib: A case report.

Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis (MDA5-DM) often causes rapidly progressive interstitial lung disease (RP-ILD). Although cancer complications in MDA5-DM are less frequently reported compared to other forms of DM, they do occur. For MDA5-DM patients with cancer, particularly in paraneoplastic settings, the primary treatment strategy often targets the malignancy first. However, surgery, chemotherapy, and radiotherapy carry significant risks of exacerbating ILD, especially in patients with respiratory failure. Despite improved prognosis with initial immunosuppressive combination therapy, some cases of MDA5-DM with RP-ILD remain refractory to treatment. Recent studies have shown the potential benefit of Janus kinase (JAK) inhibitors for refractory cases, though their impact on cancer progression remains a concern. We report a 48-year-old woman with MDA5-DM, RP-ILD, and bilateral breast cancer. Due to her respiratory condition, radical surgery and chemotherapy were initially not possible. Endocrine therapy and immunosuppressive therapy were administered, but the disease remained refractory. Tofacitinib, combined with plasma exchange, improved her ILD, allowing for bilateral mastectomy. One year later, MDA5 antibody titers became negative, and glucocorticoids were discontinued after two years. Three years later, neither MDA5-DM nor breast cancer has recurred. This is the first report of MDA5-DM complicated by breast cancer, and the first use of JAK inhibitors in such a case. Effective treatment requires close collaboration with oncologists to balance the risks and benefits of therapy in cases of MDA5-DM with RP-ILD and cancer.

Yamane T ，Kitayama M 《-》