Autistic enterocolitis; is it a histopathological entity?

AIMS: To review the literature on the histopathological diagnosis of the condition termed 'autistic enterocolitis'. METHODS AND RESULTS: We have reviewed all published works where mucosal biopsy specimens from autistic children have been examined histopathologically. Abstracts were excluded. Our review of the published works, nearly all from a single centre, identifies major inconsistencies between studies, lack of appropriate controls and misinterpretation of normal findings as pathology. Ileal lymphoid hyperplasia may be more prevalent in children with regressive autism but is also seen in children with food allergies and severe constipation, the latter being an extremely common finding in autistic children. CONCLUSION: The histopathological diagnosis of autistic enterocolitis should be treated with caution until a proper study with appropriate methodology and controls is undertaken.     

Virtual elimination of necrotising enterocolitis for 5 years - reasons?

A standardised feeding regimen was adopted in 1997 for guiding enteral feeding of neonates <32 weeks' gestation during clinical trials (18 months each) involving erythromycin (n=73) as a prokinetic and carboxymethylcellulose (n=70) as a laxative as well as for during 2 years (n=155) without any trials. Most aspects of the feeding regimen (e.g., milk increments-total volume/day, use of breast milk by choice, etc) were not significantly different from current practices. RESULTS: 298 neonates <32 weeks' gestation (<28 weeks; n=78) were enterally fed during the 5 years. Their demographic characteristics and median (interquartile) age in days at starting (AST) and days to reach full enteral feeds (FFT) of 150 ml/kg/day were not significantly different during these 5 years: [AST: 5 (3-7.5)], [FFT: 4 (3-7)] Only one case of definite NEC (> or =Stage II) occurred during the 5 years. The time to reach full feeds was also reduced by over 54% (including for neonates <28 weeks gestation) compared with a historical cohort. CONCLUSION: Sustained reduction in the time to reach full feeds with virtual elimination of > or =Stage II NEC for 5 years indicates continued benefits of a standardised feeding regimen as a simple preventive strategy to prevent NEC. Whether our specific policy of no enteral feeds in presence of hemodynamic instability associated with PDA requiring indomethacin, and/or sepsis played a role in achieving the significant results needs controlled trials.     

Food protein-induced enterocolitis syndrome oral food challenge: Time for a change?

ObjectiveFood protein-induced enterocolitis syndrome (FPIES) is typically diagnosed based on a characteristic clinical history; however, an oral food challenge (OFC) may be necessary to confirm the diagnosis or evaluate for the development of tolerance. FPIES OFC methods vary globally, and there is no universally agreed upon protocol. The objective of this review is to summarize reported FPIES OFC approaches and consider unmet needs in diagnosing and managing FPIES.Data SourcesPubMed database was searched using the keywords food protein-induced enterocolitis syndrome, oral food challenge, cow milk allergy, food allergy, non-immunoglobulin E–mediated food allergy and FPIES.Study SelectionsPrimary and review articles were selected based on relevance to the diagnosis of FPIES and the FPIES OFC.ResultsWe reviewed the history of FPIES and the evolution and variations in the FPIES OFC. A summary of current literature suggests that most patients with FPIES will react with 25% to 33% of a standard serving of the challenged food, there is little benefit to offering a divided dose challenge unless there is suspicion of specific immunoglobulin E to the food being challenged, reactions typically appear within 1 to 4 hours of ingestion, and reactions during OFC rarely result in emergency department or intensive care unit admission.ConclusionInternational standardization in the FPIES OFC approach is necessary with particular attention to specific dose administration across challenged foods, timing between the patient’s reaction and offered OFC to verify tolerance, patient safety considerations before the OFC, and identification of characteristics that would indicate home reintroduction is appropriate.     

Metabolic-hypoxic modulation of cytokine induction of intestinal endothelial adhesion molecules: Relevance to ischemic injury mediated necrotizing enterocolitis?

BackgroundNecrotizing enterocolitis (NEC) triggers an intense inflammatory response in the neonatal gut associated with cytokine activation, altered nutrient status and intracellular O₂-deprivation. Endothelial cell adhesion molecules (ECAMs) play critical roles in driving immune cell infiltration into inflamed gut. Currently, relationships between inflammation, metabolism and ECAM expression remain poorly understood in NEC. We studied the effects of metabolic depletion (aglycemia/ hypoxia) on TNF-α mediated ECAM expression including ICAM-1, MAdCAM-1, VCAM-1 and E-selectin, in vitro in intestinal microvascular endothelial cells (IMEC).MethodsTo study the effects of TNF-α, aglycemia and hypoxia (alone or in combination) IMECs expression of adhesion molecules was studied using cell surface ELISA and immunoblotting.ResultsTotal VCAM-1 expression was induced TNF-α and by hypoxia + TNF-α, cell surface expression was induced by hypoxia, TNF-α, TNF- α+hypoxia, and TNF- α+hypoxia and aglycemia. Total ICAM-1 increased following TNF- α, TNF- α+hypoxia, hypoxia + aglycemia, and TNF- α+hypoxia + aglycemia. Total MAdCAM-1 protein expression was significantly induced by a combination of TNF-α+hypoxia + aglycemia and cell surface expression induced by TNF- α+hypoxia. Surface expression of E-selectin was induced by TNF- α+aglycemia and TNF- α+hypoxia + aglycemia.ConclusionEnergy metabolism influences inflammation induced injury through mobilization of intestinal ECAMs, and may represent an important mechanism in NEC pathology.