Secondary Hemophagocytic Lymphohistiocytosis and Iatrogenic Withdrawal Syndrome as Competing Causes of Seizures in a Child with Patent Ductus Arteriosus: A Case Report

Background. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can coexist with other complications of pediatric intensive care. When it overlaps with iatrogenic withdrawal syndrome (IWS), the cause of new seizures may be impossible to establish at the bedside. Case presentation. A 3-year-old girl with an unrepaired patent ductus arteriosus (PDA) was admitted on hospital day (HD) 1 with decompensated heart failure and influenza B pneumonia, and acute pulmonary edema led to invasive mechanical ventilation on HD16. On HD21–22 she developed refractory fever, splenomegaly, hyperferritinemia (4,332 ng/mL), hypertriglyceridemia (413.2 mg/dL, possibly confounded by a concurrent propofol infusion), a procalcitonin of 102.77 ng/mL, and bone marrow hemophagocytosis. She met 5 of 8 HLH-2004 criteria and received dexamethasone and intravenous immunoglobulin. The PDA was divided and suture-ligated on HD30, once she was hemodynamically stable. After prolonged multi-agent analgosedation she developed IWS (Sophia Observation withdrawal Symptoms [SOS] score 7/15 on HD35) and recurrent generalized seizures; two extubation attempts failed, and she required a tracheostomy (HD56) and an open gastrostomy (HD65) before discharge on HD86. Cerebrospinal fluid analysis, soluble CD25, natural killer cell activity, and conclusive brain magnetic resonance imaging reports were not available, so central nervous system (CNS) involvement by HLH could not be separated from IWS as the cause of the seizures. Conclusions. In critically ill children with systemic hyperinflammation, early protocolized weaning of analgosedation and a broad neurological differential diagnosis are essential.