A previously healthy 2-year-old girl developed malar rash, mild muscle weakness, and weight loss for a few months before admission. Her medication history and family history were unremarkable. She was previously admitted to another hospital due to dry cough and dyspnea, which developed a few days ago. She was diagnosed with JDM based on the elevation of serum muscle enzymes and the finding of myositis on femoral magnetic resonance imaging. Her percutaneous oxygen saturation was 96% on oxygen via nasal canula at 2 L/min. Six days after diagnosis, her respiratory state rapidly deteriorated and she was transferred to our intensive care unit with a diagnosis of JDM-associated RP-ILD.
Upon admission at our institution, she had low-grade fever (37.4℃), tachycardia (158 beats per min), tachypnea (56 breaths per min), with an oxygen saturation of 86–96% on oxygen mask at 8 L/min. Her height and body weight were 92 cm and 11.2 kg with 1.8 kg loss in 5 months, respectively. Malar rashes and Gottron’s sign (i.e., papules on knuckles and elbows) were noted. The laboratory results were as follows: creatinine kinase: 22 U/I, alanine transaminase: 69 U/I, aspartate transaminase: 49 U/I, lactate dehydrogenase: 576 U/L, aldolase: 13.5 U/L (normal: <6.1 U/L), Krebs von den Lungen-6: 3,420 U/mL (normal: <500 U/mL), anti-MDA5 antibody: >7,500 index (normal: <500 index), Interleukin-6: 5.2 pg/mL (normal: <6 pg/mL), and Interleukin-18: 1102.6 pg/mL (normal: <500 pg/mL). Other autoantibodies and infection-related tests were all negative. The results of the arterial blood gas analysis were as follows: pH: 7.43, PaCO2: 34.1 mmHg, PaO2: 68.7 mmHg, and HCO3−: 22.4 mmol/L on oxygen mask at 8 L/min. Chest high-resolution computed tomography (CT) revealed extensive ground-glass opacities with consolidation in the bilateral lungs, greater at the left; these findings are consistent with a diffuse alveolar damage pattern (Fig. I a, b).
Due to the rapid progression of her respiratory failure, the patient was given combination therapy including 4 courses of MPT (30 mg/kg/day for 3 days per course) followed by oral prednisolone (PSL; 1 mg/kg/day), intravenous CyA (starting with 3 mg/kg/day and adjusted to maintain trough levels at 150–200 ng/mL), 2 courses of IVCY (500 mg/m2/dose at a 1-month interval), and IVIG (2 g/kg/dose) (Fig. 2, online). She also received trimethoprim-sulfadiazine as prophylaxis for opportunistic infections. Her respiratory condition deteriorated further, and she was placed on a ventilator support at the 11th hospital day, with the following settings: mean airway pressure (MAP): 12 cmH2O, peak inspiratory pressure (PIP): 20 cmH2O, positive end-expiratory pressure (PEEP): 6 cmH2O, and FiO2: 0.8 (oxygen index: 8.0, PaO2/FiO2: 150).
However, her respiratory condition worsened further, and her anti-MDA-5 antibodies did not decrease. Thus, we attempted PE on the 11th hospital day (Fig. 2, online), and 23 sessions of PE were performed in total. Serum anti-MDA5 antibody titer then decreased temporarily, but soon rebounded markedly. Furthermore, her respiratory status, including oxygen demand, did not improve at all.
On the 24th hospital day, she could no longer maintain an SpO2 of 90% at the following ventilator settings: MAP: 18 cmH2O, PIP: 31 cmH2O, PEEP: 10 cmH2O, FiO2: 1.0 (oxygen index: 20, PaO2/FiO2: 50), and nitric oxide: 5.0 ppm.
We decided to introduce VV-ECMO to her for life support. As her respiratory condition was serious, we could not take a follow-up chest CT after her admission. Plain chest radiography at that time showed diffuse ground-glass opacities (Fig. 1C).
After receiving institutional ethical approval, 375 mg/m2 of RTX was given on the 28th hospital day. Mycophenolate mofetil (MMF) was added on the 40th hospital day. Respiratory physical therapy, including being placed in the prone position, was continued under VV-ECMO. Two weeks after starting RTX therapy, her respiratory status gradually started to improve. She was eventually able to wean off ECMO on the 52nd hospital day. Chest CT taken on the 78th hospital day showed improvement of aeration and decreased the consolidation. However, the ground-glass opacities enlarged and traction bronchiectasis was also marked (Fig. 1D-E). Anti-MDA-5 antibody levels also decreased steadily after the first course of RTX, and thus additional RTX was administered at 2 and 6 months due to the recovery of B cells in peripheral blood.
No severe respiratory complications, such as pneumonia, pneumothorax, pulmonary hemorrhage, or thrombosis occurred in the acute phase. We avoided high ventilation pressures above PIP 30 cmH2O as much as possible to avoid pneumothorax.
Three months after admission, her general condition improved without neurological complications. Her activities of daily living have improved after continuous rehabilitation. She regained the ability to speak, eat, walk, and bathe at 3, 4, 6, and 10 months after admission, respectively. Finally, she was discharged with minimum ventilator support at 11 months after admission. At discharge, she could be weaned from the ventilator for short periods of time. The ventilator settings were as follows: MAP: 8 cmH2O, PIP: 14 cmH2O, PEEP: 7 cmH2O, and FiO2: 0.24. Her chest CT showed remarkable improvement in both lungs at this time as well (Fig. 1F-G).Her anti-MDA5 antibody level was 450 index, and her KL-6 was 1,150 U/m. She is now maintained with PSL 4 mg/day, tacrolimus adjusted with trough levels around 5.0 ng/mL, and MMF 500 mg/day.