title: Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow's milk allergy in toddlers.
abstract: BACKGROUND
  Food allergy is a common problem in France involving 4%-6% of toddlers. As opposed to IgE-mediated cow's milk allergy (CMA), delayed-onset CMA, mostly, non-IgE-mediated, remains difficult to diagnose in toddlers. Our study assessed the diagnostic performances of intestinal permeability and of fecal markers, in comparison with the standard allergic work-up in children referred for CMA diagnosis.
  
  
  METHODS
  Twenty-five consecutive children, mean age (standard deviation) 6.3 months (4.8) with digestive and/or extra-digestive manifestations suggesting CMA, were prospectively studied based on a standardized allergic work-up (specific cow's protein IgE and IgG, skin prick test, atopy patch test and oral open cow's milk challenge) and digestive work-up including fecal microbiota analysis, intestinal permeability determination (urinary lactitol/mannitol ratio) and fecal markers measurement, i.e., α(1)-antitrypsin, tumor necrosis factor-α, calprotectin, β-defensin2, secretory IgA and eosinophil-derived neurotoxin (EDN). Receiver operating characteristic (ROC) curves were calculated for all markers in order to define cut-off levels.
  
  
  RESULTS
  The cow's milk challenge was positive in 11 children and negative in 14. The global test performances, i.e., the number of true positive+negative cases/the total number of cases, were 76% for intestinal permeability; 72% for fecal EDN; contrasting with atopy patch test, 68%; IgE, 60%; skin prick test, 55% and IgG, 52%.
  
  
  CONCLUSIONS
  In this routine diagnosis allergy work-up for CMA in toddlers, the best efficacy was seen for intestinal permeability compared to IgE, IgG, skin prick test and atopy patch test. Moreover, fecal EDN in a single spot sample displayed a similar performance.
authors.affiliation: Clinique Pediatrique Saint Antoine, Hopital Saint Vincent de Paul, Groupe Hospitalier de L'institut Catholique de Lille, Universite Catholique, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kalach
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kapel
authors.forename: Anne-Judith
authors.initials: AJ
authors.lastname: Waligora-Dupriet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Castelain
authors.forename: Marie Odile
authors.initials: MO
authors.lastname: Cousin
authors.forename: Christine
authors.initials: C
authors.lastname: Sauvage
authors.forename: Fatimata
authors.initials: F
authors.lastname: Ba
authors.forename: Ioannis
authors.initials: I
authors.lastname: Nicolis
authors.forename: Florence
authors.initials: F
authors.lastname: Campeotto
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Butel
authors.forename: Christophe
authors.initials: C
authors.lastname: Dupont
mesh_terms: D015415:Biomarkers / Q000032:analysis; D002675:Child, Preschool; D047208:Eosinophil-Derived Neurotoxin / Q000032:analysis*; D005243:Feces / Q000737:chemistry* / Q000382:microbiology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007223:Infant; D008297:Male; D016269:Milk Hypersensitivity / Q000175:diagnosis* / Q000276:immunology; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D007073:Immunoglobulin E; D047208:Eosinophil-Derived Neurotoxin