Efficacy of sildenafil and high-dose anakinra in an MIS-C patient with pulmonary vasculitis: A case report

Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a newly identified clinical entity still not very well known in terms of epidemiology, pathogenesis, and long-term outcome. Pulmonary involvement with acute respiratory failure is an unusual life-threatening complication of MIS-C, often a reason for admission to the pediatric intensive care unit (PICU) and the use of mechanical ventilation. We present a case of a 7-year-old male patient, previously healthy, hospitalized for MIS-C, treated with intravenous immunoglobulins (IVIG), high dose methylprednisolone, and anakinra. After 2 days of the aforementioned therapy, the patient presented with hypoxia (SatO2: 85% in ambient air room) and breathing difficulties. A chest computed tomography (CT) scan showed the presence of multiple bilateral basal parenchymal thickening and small basal pleural effusion and an arterial blood gas analysis revealed severe hypoxia (PaO2/FiO2 ratio, 170 mmHg). Because of a worsening of respiratory distress, the patient was transferred to the PICU, where invasive mechanical ventilation and a continuous infusion of anakinra (12 mg/kg/day) were started. An echocardiogram was performed, which showed an increase in pulmonary pressure (40 mmHg) with normal heart ejection fraction (55%), and the hypothesis of pulmonary vasculitis involving the pulmonary arterioles was made. Therefore, therapy with sildenafil (0.15 mg/kg/day) was promptly set up, with an immediate improvement of the clinical picture of respiratory failure, reduction of pulmonary pressure (23 mmHg), and subsequent extubation at 36 h with a regular clinical course until discharge. As far as we know, our case represents the first report of pulmonary vasculitis in an MIS-C patient. The use of sildenafil and high-dose continuous anakinra may represent a rescue therapy in cases of MIS-C with pulmonary vasculitis or with difficulty in extubation, allowing a short-term hospitalization in intensive care and improving the long-term outcome in these patients.

Multi-Inflammatory Syndrome in Children (MIS-C) in 2023: Is It Time to Forget about It?

“…In the same recommendations, the use of biologics is suggested in patients with refractory disease. Indeed, biologics—and IL-1-blocking agents in particular—have been used anecdotally in patients with MIS-C with good results [ 74 , 75 , 76 , 77 ]. Interestingly, there is now mounting evidence of the role of IL-1 in driving the inflammatory process and the presence of neutralizing anti-IL1RA antibodies (that lead to increased secretion of IL-1 by inflammatory cells) in patients with MIS-C [ 78 ].…”

Incidence and Prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C) in Southern Italy

“…The use of anakinra, an IL-1 receptor antagonist, has been indicated by ACR in cases of refractory MIS-C despite IVIG and steroids, or in case of severe myocarditis or MAS [29,32]. Many papers have shown the efficacy of anakinra in MIS-C patients [33][34][35]. Nevertheless, due to the severe inflammation, higher doses of intravenous anakinra (>4 mg/kg/day, up to 10 mg/kg/day, in divided doses) are usually considered, particularly when there is evidence of MAS or a severe systemic involvement [29,33,34].…”

“…Many papers have shown the efficacy of anakinra in MIS-C patients [33][34][35]. Nevertheless, due to the severe inflammation, higher doses of intravenous anakinra (>4 mg/kg/day, up to 10 mg/kg/day, in divided doses) are usually considered, particularly when there is evidence of MAS or a severe systemic involvement [29,33,34]. A significant proportion of patients required intensive care (31-85%), and some of them needed mechanical ventilation and extracorporeal membrane oxygenation [9,14,16,36].…”