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 rituximab treatment for severe rapidly progressive interstitial lung disease with anti-MDA5 antibody-positive juvenile dermatomyositis: a case report and literature review.

Rapidly progressive (RP) interstitial lung disease (ILD) is a life-threatening complication of juvenile dermatomyositis (JDM); however, it is generally refractory to treatment; to the best of our knowledge, no evidence-based treatment has been established for RP-ILD yet. We present the case of a 2-year-old girl with RP-ILD who showed resistance to treatment with methylprednisolone, cyclosporine A, cyclophosphamide, immunoglobulin, and plasma exchange (PE) and was finally treated with extracorporeal membrane oxygenation. We further present a literature review of 18 cases of JDM with RP-ILD. A 2-year-old girl presented with malar rash, mild muscle weakness, and weight loss for a few months before admission. She had a history of dry cough and dyspnea for a few days, followed by rapid respiratory failure. The patient was diagnosed with JDM with RP-ILD through physical examination (malar rashes and Gottron's sign) and based on the finding of myositis on femoral magnetic resonance imaging, elevated levels of serum muscle enzymes, positive anti-melanoma differentiation-association gene 5 (MDA5) antibody (> 7,500 index), elevated level of Krebs von den Lungen-6 glycoprotein (KL-6; 3,420 U/mL), and extensive ground-glass opacities with consolidation in the bilateral lungs on chest high-resolution computed tomography. She received combination therapy, including methylprednisolone pulse therapy, followed by oral prednisolone and intravenous cyclosporine A, cyclophosphamide, and immunoglobulin. On day 11 of hospitalization, she was placed on ventilation support and PE was initiated. However, her respiratory condition continued to deteriorate and veno-venous extracorporeal membrane oxygenation was started on day 24 of hospitalization. Rituximab was administered on day 28. After 2 weeks of rituximab therapy initiation, her respiratory condition showed gradual improvements. Eventually, on day 52 of hospitalization, the patient could be weaned off extracorporeal membrane oxygenation. Finally, she was discharged with minimal ventilation support and no neurological complications 11 months after admission. Our literature review suggest that JDM with RP-ILD has a high mortality rate. In JDM, rituximab may be a promising treatment option for RP-ILD. In the future, the efficacy of rituximab in the early phases of ILD should be investigated.

Nishi K ，Ogura M ，Tamai N ，Gima M ，Ide K ，Koinuma G ，Kamei K ，Ito S ... -  《Pediatric Rheumatology》

Adolescent-onset anti-MDA5 antibody-positive juvenile dermatomyositis with rapidly progressive interstitial lung disease and spontaneous pneumomediastinum: a case report and literature review.

Yeung TW ，Cheong KN ，Lau YL ，Tse KN ... -  《Pediatric Rheumatology》

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 ... -  《-》

[Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury].

Zhang PL ，Yang HX ，Zhang LN ，Ge YP ，Peng QL ，Wang GC ，Lu X ... -  《-》