Pediatric veno-arterial extracorporeal membrane oxygenation in fulminant hemophagocytic lymphohistiocytosis.

To the Editor, Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease, which may be difficult to timely diagnose because the clinical presentation mimics other conditions like severe sepsis, hepatic failure, meningitis, and malignancies (1). Extracorporeal life support/extracorporeal membrane oxygenation (ECLS/ECMO) in the pediatric population for short-term bridge to recovery and decision or for long-term bridge to transplantation has become standard of care. The need to perform differential diagnosis of potentially recoverable conditions (myocarditis, sepsis, other) is imperative during fatal evolution of an unknown disease. However, the use of ECLS/ECMO as bridge to diagnosis is not well established (unclear risk/benefit, unclear cost-effectiveness). A 4-year-old male presenting with circulatory collapse and lethargy, in the absence of a reliable working diagnosis and with the possibility of a fulminant myocarditis episode with secondary central nervous system involvement, was transferred to our Pediatric Cardiac-Surgery Unit for emergent ECLS. Via left femoral artery and left internal jugular vein cannulation, veno-arterial ECMO was started using a pediatric magnetic levitation pump (Levitronix LLC, Waltham, MA, USA), a polymethylpentene-coated oxygenator (EOS ECMO, Sorin-Group, Mirandola, Italy), and biocompatible circuits (A.g.i.l.e. Eurosets, Medolla, Italy). In line with the hypothesis of viral myocarditis or encephalitis, steroid pulse therapy with dexamethasone was administered. After 24 h of ECMO support and wash out of sedative drugs, neurological evaluation was compatible with nonreactive mydriasis. Considering the need for electroencephalogram (EEG) examination and the risk of electrical interference with the ECMO device, echocardiographic assessment was repeated to establish feasibility of weaning from mechanical life support. Given the evidence of slight improvement in biventricular function, gradual weaning from ECMO was completed (Fig. 1A). At first, hemodynamic parameters were stable, cardiac rhythm was 70/bpm, stable lactate, with marked polyuria. EEG tracing was isoelectric and compatible with brain death. After a few hours, multiple organ failure had progressed, and the patient died on the same day due to III-grade AV heart block followed by asystole on second day of hospital stay. Autopsy was performed to define the diagnosis. Histopathologic analysis of specimens taken during autopsy of bone marrow and lymph nodes determined the diagnosis of HLH. Bone marrow showed infiltrating histiocytes with abundant cytoplasm and oval or lobulated nuclei with prominent nucleoli. Most of the histiocytes showed phagocytosis of red blood cell (Fig. 1B). Widespread infiltration of histiocytes and marked hypocellularity of other cellular elements were even shown in the lymph nodes and bone marrow. HLH incidence is reported to be 1.2 cases-permillion persons per year with a male to female ratio 1:1. Virus-associated HLH (VAHS), first described by Risdall et al. (2), is related to herpes viruses, cytomegalovirus, human parvovirus B19, human herpes virus type 6, adenovirus, rubella virus, HIV, and influenza virus. A prognostically unfavorable form of VAHS is associated with Epstein–Barr virus (EBV), called EBV-HLH, which develops mostly in children and young adults and shows fulminant and fatal manifestations. Although the VAHS occurs most commonly in children and adolescents living in Asian counties, for unclear reasons, it has also been reported to occur sporadically in Western countries (3). It is uniformly fatal without treatment and mortality remains significant for patients treated in accordance with the HLH-94 protocol (2.5-year survival rates, range 10–85%). Intensive supportive care is crucial during the acute phase of illness to prevent the numerous lifethreatening complications that may develop, but is not always a sufficient condition to prevent fatal evolution. In this setting, ECMO support offers a chance to stabilize circulatory and respiratory function thereby allowing for recovery of ventricular function. HLH is a systemic disease and, without suitable therapy, there is no possibility to modify the prognosis. Unfortunately, HLH is difficult to diagnose, because it mimics other fatal disease processes (myocarditis, meningoencephalitis, sepsis), which doi:10.1111/aor.12115 bs_bs_banner