Diagnostic challenges in a child with familial hemophagocytic lymphohistiocytosis type 3 (FHLH3) presenting with fulminant neurological disease.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessively inherited multisystem disease characterized by fever, rash, splenomegaly, cytopenias, and variable central nervous system (CNS) manifestations. CASE HISTORY: We report the case of a 3-year-old boy who presented with splenomegaly and normocytic anemia 4 months after returning to the US from a region endemic for Leishmania infection. The child later developed progressive neurological impairment and had radiologic evidence of widespread demyelinating disease. Gene studies showed homozygosity for a mutation at Munc13-4, confirming FHLH type 3. DISCUSSION: The diagnostic uncertainty that accompanies FHLH was compounded by our patient's travel history and CNS disease mimicking acute disseminated encephalomyelitis (ADEM). Diagnostic criteria for hemophagocytic lymphohistiocytosis were not consistently met, despite aggressive disease. CONCLUSIONS: FHLH may present with fulminant demyelinating disease, mimicking ADEM, and without necessarily meeting previously defined clinical and laboratory criteria. We strongly recommend expeditious molecular testing and genetic counseling for FHLH mutations in cases of undiagnosed inflammatory CNS disease in the pediatric population.

Hyperglycemia and outcome in the pediatric intensive care unit.

OBJECTIVE: To identify the frequency of hyperglycemia in children who are nondiabetic and critically ill and assess the independent effect of hyperglycemia on outcome. STUDY DESIGN: Consecutive admissions to the pediatric intensive care unit (PICU) were reviewed. The Pediatric Risk of Mortality III score (PRISM) measured patient acuity. Because maximum glucose level in the first day of PICU admission (GLFD) >200mg/dL contributes to PRISM, 200 mg/dL was used to differentiate high glucose (HG) from normal glucose. RESULTS: Of 1550 patients, 221 (14.3%) had HG. GLFD correlated with PRISM (r = 0.39, P < .001). Without controlling for PRISM, the HG group had more mechanical ventilation days (MVD; P < .001), longer PICU length of stay (PLOS; P < .001) and lower percent survival (P < .001) than the normal glucose group. Controlling for PRISM in survivors, GLFD was not associated with PLOS (P = .75) or with MVD (P = .06). GLFD was not significantly associated with survival (P = .76). In nonsurvivors, GLFD was not associated with PLOS (P = .19) or MVD (P = .31). CONCLUSION: When controlling for disease severity, hyperglycemia within 24 hours of PICU admission was not independently associated with increased mechanical ventilation time, length of stay, or mortality. Prospective evaluation of glycemic control in critically ill children is needed to elucidate its effects on outcome.

Hyperglycemia in the pediatric intensive care unit.

PURPOSE OF REVIEW: Studies on critically ill adults demonstrate the benefits of glycemic control. There is a paucity of data, however, in pediatric intensive care settings. This review summarizes sentinel papers in the adult literature, outlines mechanisms by which hyperglycemia mediates its effects in the critically ill, highlighting those described in pediatrics, and discusses studies that associate hyperglycemia with negative outcome in critically ill children. RECENT FINDINGS: Retrospective studies and prospective cohort studies have linked hyperglycemia to worse outcome in critically ill children. Investigations in small, homogenous groups, such as trauma, sepsis, burn and neonatal patients, have shown negative associations between hyperglycemia and injury-specific outcomes and have elucidated previously proposed mechanisms of tissue injury in children. In addition, certain properties of hyperglycemia, such as duration, peak, and excursion, may be more relevant than absolute levels of glucose. Larger studies generalize findings to heterogeneous pediatric intensive care populations, across ages and diagnoses. Further, in studies accounting for insulin administration, no obvious increases in hypoglycemia-related morbidity have been noted. SUMMARY: Glucose control in pediatric intensive care has been receiving increasing attention. Large, prospective studies are needed to address certain issues in pediatrics, such as differences in diseases, target values, complications of disease, risks and sequelae of hypoglycemia and logistical challenges.