Introduction

Juvenile dermatomyositis (JDM) is a multisystemic disease of children that affects primarily muscle and skin. The prevalence of pulmonary involvement is not well known but seems to be rarer than in adult patients with dermatomyositis/polymyositis (DM/PM) [1–3]. A wide spectrum of clinical presentations have been described, ranging from asymptomatic patients with merely abnormal pulmonary function tests [4] to severe, potentially fatal cases refractory to immunosuppressive and supportive therapy [5-9]. Here we present the case of a child with JDM and severe interstitial lung disease (ILD) successfully treated with immunosuppressive drugs and extracorporeal membrane oxygenation (ECMO).

Case report

A 3-year-old girl was admitted to a local hospital with a 1-month history of fatigue, arthralgias, and rash. On physical examination she had proximal muscle weakness, vasculitic rash on arms and trunk, capillary nail bed teleangiectasias, and Gottron papules on both hands. The diagnosis of JDM was supported by laboratory findings of elevated muscle enzymes, EMG suggestive of myopathy, and magnetic resonance imaging of the thigh muscles revealing moderate hyperintensity consistent with edema of the crureus and both the internal and external obturator muscles [10]. She was first treated with metylprednisolone pulse therapy (20 mg/kg per day) for 3 days and then with oral prednisone (1 mg/kg per day) tapered to 0.3 mg/kg daily over 2 months. She regained strength and her muscle enzymes dropt down to normal values. Seven months after the diagnosis she suddenly developed malaise and respiratory failure with cough, dyspnea, cyanosis, and cervical edema. She was then intubated, mechanically ventilated, and 3 days later admitted to our pediatric intensive care unit.

On admission the patient was in extremely critical condition, with fever and severe hypoxemia despite sedation, paralysis, and high mechanical ventilation parameters: peak inspiratory pressure 40, positive end-expiratory pressure 10 mmHg, FIO2 1.0, RATE 30 (oxygenation index 52, PaO2/FIO2 36, alveoloar-arterial oxygen pressure difference 585 mmHg). Laboratory investigations showed: white blood cell count 22.4 × 103/μl, hemoglobin 10.8 g/dl, platelets 352 × 103/μl, C-reactive protein 4 mg/l, aspartate aminotransferase 334 U/l, lactate dehydrogenase 3640 U/l, creatine kinase 403 U/l; blood, urine, and bronchoalveolar lavage fluid cultures and serology for virus, bacteria and fungi were negative. Autoantibodies (anti-nuclear antibody, extractable nuclear antibody including myositis-specific autoantibodies Mi-2, tRNA synthetase, and SRP, anti-dsDNA, anticardiolipin and lupus anticoagulant) were all absent. Arterial blood gas analysis showed pH 7.20, PaCO2 73 mmHg, PaO2 36 mmHg, HCO3 29. On chest radiography a diffuse interstitial pattern, alveolitis, pneumothorax, pneumomediastinum, and subcutaneous emphysema were present (Fig. 1). The patient was shifted to high-frequency oscillatory ventilation with the following ventilator settings: mean airway pressure 30 cmH2O, amplitude 60 cmH2O, 8 Hz, FIO2 1.0 (oxygenation index 64, PaO2/FIO2 45, alveoloar-arterial oxygen pressure difference 616 mmHg), and nitric oxide inhalation therapy was started at 10 ppm, increasing to 40 ppm within a few hours. Despite this maximum respiratory support we were not able to raise her arterial oxygen saturation above 85%; the oxygenation Index was stable over 55, PaO2/FIO2 under 45, and alveoloar-arterial oxygen pressure difference over 600 mmHg during the following 18 h, and for these reasons we decided to support her with venovenous ECMO.

Fig. 1
figure 1

a Chest radiography: Diffuse bilateral alveolar opacities of the lungs with air bronchogram, severe pneumomediastinum, and diffuse subcutaneous emphysema of the neck and thoracic walls. b Axial contrast enhanced computed tomography (T8 level) on admission: extensive bilateral lobar consolidation, mainly of the posterior left and of the right lung; anterior pneumomediastinum

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Blood was drained by a 15-F double-lumen cannula from the right internal jugular with the tip in the right atrium and by a 12-F single-lumen cannula inserted into the cephalic portion of the same vein with the tip at the ear lobe level. After oxygenation blood was pumped into the right atrium with a roller pump at 70 ml/kg per minute. The patient was anticoagulated with heparin with the aim to maintain the activated clotting time between 180 and 200 s; during the course of ECMO this ranged between 156 and 296 s. After a transient improvement in the oxygenation parameters, 48 h later her arterial and mixed venous oxygen saturation dropped progressively, and we shifted from venovenous to venoarterial ECMO. For this a 14-F single-lumen cannula was inserted into the right internal carotid artery, and, to maximize extracorporeal blood flow, venous blood was drawn from the internal jugular vein (cephalic and double lumen atrial) and from an additional 12-F single-lumen catheter placed in the right femoral vein. These procedures allowed a progressive reduction in the ventilator setting: 24 h later FIO2 was 0.6, amplitude 50, mean arterial pressure 15 cmH2O, which reduced to 12 cmH2O 48 h later when a second oxygenator was inserted in parallel into the extracorporeal circuit. Despite the reduction in ventilator parameters the patient's air leak did not improve, and the subcutaneous emphysema on the left thorax wall and neck worsened. Depending almost completely on the ECMO support, we decided to exclude the left main bronchus by positioning a cuffed tube and to ventilate selectively only the right lung. After 24 hours, on ECMO day 8, the patient was shifted to conventional, pressure-controlled ventilation, starting with very low settings (peak inspiratory pressure 15 cmH2O, positive end-expiratory pressure 7 cmH2O, FIO2 0.6, RATE 10) for 6 days. The air leak eventually resolved, and on ECMO day 14 the child was shifted again to high-frequency oscillatory ventilation with the purpose of reexpanding the left lung and minimizing the risk of barotrauma. We also decided to turn the patient prone to improve mobilization of fluid and secretions from the dependent parts of the lungs. On ECMO day 17 we were able progressively to reduce the blood flow, and 4 days later we recorded the first 30 min of successful trial-off. The patient was completely disconnected from the extracorporeal circuit on day 23. During extracorporeal treatment no mechanical complications occurred; the child received low-dose dopamine and large amount of blood products (271 ml/kg packed red blood cells transfusion, 101 ml/kg fresh frozen plasma, 101 ml/kg platelets, 1.4 g/kg human albumin). The surgeon tried unsuccessfully to reconstruct the right internal carotid artery, and the artery was therefore ligated.

In association with ECMO the patient was treated with three metylprednisolone pulses daily (30 mg/kg each) and then intravenous prednisone (2 mg/kg per day; Fig. 2). Mechanical ventilation could be stopped 10 weeks after admission, but the oxygen dependency persisted for a further 4 weeks. Three weeks before discharge from the pediatric intensive care unit we introduced cyclophosphamide at 2 mg/kg/day orally; prednisone was gradually tapered to 1.5 and subsequently to 1 mg/kg per day over 1 month.

Fig. 2
figure 2

Schematic representation of treatments. CMV, Conventional mechanical ventilation; HFOV, high-frequency oscillatory ventilation; V–V, venovenous; V–A, venoarterial; ECMO, extracorporeal membrane oxygenation; MPDN, metylpredisolone)

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Four months after admission she was discharged in good general condition. In particular she was breathing normally and was oxygen independent; results of her neurological examination and her cognitive status were normal. Immunosuppressive treatment was definitively stopped after 4 months. At the present time, after 5 years follow-up, her pulmonary function tests including the diffusing capacity for carbon monoxide are normal. Her neurological and cognitive status, periodically checked, has always been normal and appropriate for her age. She has been extensively investigated for long-term ECMO neurological side effects by both neurophysiological (electroencephalography, brainstem auditory, visual, and somatosensory evoked potentials) and neuroimaging tools (cerebral magnetic resonance imaging), which show normal results.

Discussion

Severe pulmonary involvement, mainly characterized by ILD, is rare in JDM, and despite the progress achieved over recent years in the general treatment, including pulse metylprednisolone, intravenous immunoglobulin, cyclophosphamide, cyclosporin A, and heavy mechanical ventilation, mortality is still close to 50% (Table 1) [5–9].

Table 1 Pediatric patients with severe JDM-related interstitial lung disease reported to date. (IPF, interstitial pulmonary fibrosis; IP, interstitial pneumonia; BOOP, bronchiolitis obliterans organizing pneumonia; AFOP, acute fibrinous organizing pneumonia; PDN, prednisone; MPDN, metylprednisolone; MTX, methotrexate; CPM, cyclophosphamide; CYA, cyclosporine A; PP, plasmapheresis; IVIG, intravenous immunoglobulin; HFVO, high-frequency oscillatory ventilation; ECMO, extracorporeal membrane oxygenation)
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In our patient ECMO support for as long as 5 weeks, associated with immunosuppressive treatment, was able to reverse the severe life-threatening respiratory complication. ECMO is a direct extension of cardiopulmonary bypass to provide temporary life support in patients with potentially reversible heart and/or respiratory failure unresponsive to maximal conventional therapies [11].

Over the past few years ECMO has undergone significant changes with better technical equipments and decreased complications. Although in the past the presence of a chronic systemic disease was considered an exclusion criterion for ECMO, more recently this procedure has been successfully employed for the treatment of pulmonary hemorrhage secondary to systemic vasculitis, systemic lupus erythematosus, or microscopic polyangiitis [12–16]. Kolovos et al. [13] reported a case series of eight pediatric patients who were successfully treated with ECMO after developing respiratory failure secondary to diffuse alveolar hemorrhage; although the presence of systemic disease is generally considered a contraindication to ECMO, two patients had Wegener's granulomatosis and two systemic lupus erythematosus. This therapy has been used successfully in adults patients with diffuse alveolar hemorrhage secondary to anti-neutrophil cytoplasmic antibody associated vasculitis and Wegener's granulomatosis [14, 15] and in one child with microscopic polyangiitis [16].

To our knowledge, this is the first report of a child with severe JDM-related ILD successfully managed with ECMO. Although this is a highly invasive procedure with a significant risk of bleeding complications, it may be life saving in acute respiratory failure refractory to conventional mechanical ventilation. It is especially effective when used early in patients with potentially reversible pathology as in JDM. The efficacy of ECMO treatment in overcoming a critical but reversible phase of disease and the low rate of short and long-term side effects make this procedure a possible option for further treatment in the case of relapse, although, at least in children, this event has not yet been reported. On the other hand, it should be also underlined that ECMO can be performed only in a tertiary care academic center where a multidisciplinary approach of medical and nursing staff can deal properly with the various ethical and technical issues that a life-threatening condition such as this warrants. The family of our patient was aware from the early steps of ECMO procedure that the risk of death for their daughter was very high but, supported by the medical and psychosocial teams, reacted appropriately to such extreme clinical course.

In conclusion, ECMO, associated with an adequate immunosuppression treatment, should be considered for supportive therapy in children with JDM-related ILD, when conventional mechanical ventilation has failed, and may represents a valid tool to improve survival for this rare and potentially fatal complication.