Successful Treatment of the Pediatric Case with Anti-MDA5 Antibody-Positive Interstitial Lung Disease by Plasma Exchange Therapy

Introduction: Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are a type of myositis-specific autoantibodies. They are strongly related to rapid progressive lethal interstitial lung disease (ILD) with dermatomyositis. We experienced the 2 years old pediatric case with refractory anti-MDA5 antibody positive ILD and successfully treated with plasma exchange (PE). Case Description: Two years old girl with normal development showed acute lower extremity weakness, dysphagia and face erythema three months before admission. She developed non-productive cough and fever. She visited nearby hospital one month before admission and was diagnosed as bilateral pneumonia with high KL-6 titer (2500 U/mL). Antibiotics had no effect and she admitted to another hospital. Additional examination revealed the high titer of anti-MDA5 antibody (1270 index) and normal creatinine kinase (48 IU/L) but high aldolase (10.1 IU/L). She also exhibited Heliotrope rash and Gottron's sign. She diagnosed as anti-MDA5 antibody positive juvenile dermatomyositis with ILD. Methylprednisolone pulse therapy (mPSL) and intravenous cyclophosphamide therapy were started but ILD was sustained. She transferred to our hospital for additional therapies. On the second hospital day, intravenous immunoglobulin was given and intravenous rituximab therapy was added on day 7 and 16. In spite of eradication of CD20-positive cells, her symptom was not improved. Therefore, we carried on PE with albumin-based replacement solution. After three courses of PE, the titer of anit-MDA5 antibody decreased to 83 index from 980 index on admission and her respiratory status was significantly improved. Discussion: The mortality of anti-MDA5 antibody-positive ILD was reported as 20-30% regardless of intensive immunosuppressive therapy. Previous studies reported that anti-MDA5 antibody-positive ILD patients had high level of serum inflammatory cytokines and cytokine levels were related to the disease activity of ILD. Lowering them in addition to the titer of anti-MDA5 antibodies by PE may have a crucial therapeutic effect for anti-MDA5 antibody-positive ILD. Plasmapheresis therapy might be one of options to treat anti-MDA5 antibody positive patients with dermatomyositis complicated ILD.