Home Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow’s milk allergy in toddlers
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Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow’s milk allergy in toddlers

  • Nicolas Kalach , Nathalie Kapel EMAIL logo , Anne-Judith Waligora-Dupriet , Marie-Christine Castelain , Marie Odile Cousin , Christine Sauvage , Fatimata Ba , Ioannis Nicolis , Florence Campeotto , Marie José Butel and Christophe Dupont
Published/Copyright: May 11, 2012

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., α1-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.


Corresponding author: Pr. Nathalie Kapel, Laboratoire de Coprologie Fonctionnelle, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Boulevard de l’Hôpital, 75013 Paris, France Phone: +33 1 42162652, Fax: +33 1 42162654

This scientific work was supported by a scientific grant from Bayer Schering® laboratory allocated to the Faculté Libre de Médecine de Lille, Catholic University-Lille, France. This grant was mainly used to cover laboratory analysis expenses for urinary and fecal markers.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Vandenplas Y, Koletzko S, Isolaurie E, Hill D, Orange AP, Brueton M, et al. Guidelines for the diagnosis and management of cow’s milk protein allergy in infants. Arch Dis Child 2007; 10:902–8.10.1136/adc.2006.110999http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000249707600022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed PubMed Central

2. Rancé F, Deschildre A, Villard-Truc F, Gomez SA, Paty E, Santos C, et al. Oral food challenge in children: an expert review. Position paper of the section of Pediatrics French Society of Allergology and Clinical Immunology (SFAIC) and the Pediatric Society of Pulmunology and Allergology (SP2A). Eur Ann Allergy Clin Immunol 2009;41:35–49.Search in Google Scholar

3. Nowak-Wegrzyn A, Assa’ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS, et al. On behalf of the adverse reactions to food committee of the American Academy of Allergy, Asthma and Immunology. Work group report: oral food challenge testing. J Allergy Clin Immunol 2009;S365–8.10.1016/j.jaci.2009.03.042Search in Google Scholar PubMed

4. Sicherer SH, Sampson HA. Food allergy. J Clin Allergy Immunol 2010;125(2 Suppl 2):S116–25.10.1016/j.jaci.2009.08.028Search in Google Scholar PubMed

5. Sampson HA. Update on food allergy. J Allergy Clin Imunol 2004;113:805–19.10.1016/j.jaci.2004.03.014Search in Google Scholar PubMed

6. Niggemann B, Reibel S, Wahn U. The atopic patch test (APT) – a useful tool for the diagnosis of food allergy in children with atopic dermatitis. Allergy 2000;55:281–5.10.1034/j.1398-9995.2000.00464.xSearch in Google Scholar PubMed

7. de Boissieu D, Waguet JC, Dupont C. The atopy patch tests for detection of cow’s milk allergy with digestive symptoms. J Pediatr 2003;142:203–5.10.1067/mpd.2003.92Search in Google Scholar PubMed

8. Kalach N, Soulaines P, de Boissieu D, Dupont C. A pilot study of the usefulness and safety of a ready-to-use atopy patch test (Diallertest) versus a comparator (Finn Chamber) during cow’s milk allergy in children. J Allergy Clin Immunol 2005;116:1321–6.10.1016/j.jaci.2005.08.033Search in Google Scholar PubMed

9. Dupont C, Goutail-Flaud MF. Alterations of intestinal permeability to sugars in infants following neonatal surgery. J Pediatr Gastroenterol Nutr 1990;11:66–71.10.1097/00005176-199007000-00014Search in Google Scholar PubMed

10. Isolauri E, Juntunen M, Wiren S, Vuorinen P, Koivula T. Intestinal permeability changes in acute gastroenteritis: effects of clinical factors and nutritional management. J Pediatr Gastroenterol Nutr 1989;8:466–73.10.1097/00005176-198905000-00008Search in Google Scholar PubMed

11. Carratù R, Secondulfo M, de Magistris L, Iafusco D, Urio A, Carbone MG, et al. Altered intestinal permeabiliy to mannitol in diabetes mellitus type I. J Pediatr Gastroenterol Nutr 1999;28:264–9.10.1097/00005176-199903000-00010Search in Google Scholar PubMed

12. Dupont C, Barau E, Molkhou P, Raynaud F, Barbet JP, Dehenin L. Food-induced alterations of intestinal permeability in children with cow’s milk-sensitive enteropathy and atopic dermatitis. J Pediatr Gastroenterol Nutr 1989;8:459–65.10.1097/00005176-198905000-00007Search in Google Scholar

13. Kalach N, Rocchiccioli F, de Boissieu D, Benhamou PH, Dupont C. Intestinal permeability in children: variation with age and reliability in the diagnosis of cow’s milk allergy. Acta Paediatr 2001;90:499–504.10.1080/080352501750197610Search in Google Scholar

14. Tibble J, Teahon K, Thjodleifsson B, Roseth A, Sigthorsson G, Bridger S, et al. A simple method for assessing intestinal inflammation in Crohn’s disease. Gut 2000;47:506–13.10.1136/gut.47.4.506Search in Google Scholar PubMed

15. McLoughlin RM, Mills KH. Influence of gastrointestinal commensal bacteria on the immune responses that mediate allergy and asthma. J Allergy Clin Immunol 2011;127:1097–107.10.1016/j.jaci.2011.02.012http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000290018600002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

16. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009;9:313–23.10.1038/nri2515Search in Google Scholar PubMed

17. Kapel N, Roman C, Caldari D, Sieprath F, Canioni D, Khalfoun Y, et al. Fecal tumor necrosis factor-alpha and calprotectin as differential diagnostic markers for severe diarrhea of small infants. J Pediatr Gastroenterol Nutr 2005;41:396–400.10.1097/01.mpg.0000178437.87546.06Search in Google Scholar PubMed

18. Mangin I, Suau A, Magne F, Garrido D, Gotteland M, Neut C, et al. Characterization of human intestinal bifidobacteria using competitive PCR and PCR-TTGE. FEMS Microbiol Ecol 2006;55:28–37.10.1111/j.1574-6941.2005.00005.xSearch in Google Scholar PubMed

19. Furet JP, Firmesse O, Gourmelon M, Bridonneau C, Tap J, Mondot S, et al. Comparative assessment of human and farm animal faecal microbiota using real-time quantitative PCR. FEMS Microbiol Ecol 2009;68:351–62.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000265770900009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1111/j.1574-6941.2009.00671.xSearch in Google Scholar PubMed

20. Klappenbach JA, Saxman PR, Cole JR, Schmidt TM. rrndb: the ribosomal RNA operon copy number database. Nucleic Acids Res 2001;29:181–4.10.1093/nar/29.1.181Search in Google Scholar PubMed

21. Mullié C, Odou MF, Singer E, Romond MB, Izard D. Multiplex PCR using 16S rRNA gene-targeted primers for the identification of bifidobacteria from human origin. FEMS Microbiol Lett 2003;222:129–36.10.1016/S0378-1097(03)00245-3Search in Google Scholar

22. Adlerberth I, Strachan DP, Matricardi PM, Ahrné S, Orfei L, Aberg N, et al. Gut microbiota and development of atopic eczema in 3 European birth cohorts. J Allergy Clin Immunol 2007;120:343–50.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000248654900019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.jaci.2007.05.018Search in Google Scholar PubMed

23. Waligora-Dupriet AJ, Campeotto F, Romero K, Mangin I, Rouzaud G, Ménard O, et al. Diversity of gut Bifidobacterium species is not altered between allergic and non-allergic French infants. Anaerobe 2011;17:91–6.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000293430600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.anaerobe.2011.04.003Search in Google Scholar

24. Björkstén B, Sepp E, Julge K, Voor T, Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001;108:516–20.10.1067/mai.2001.118130Search in Google Scholar PubMed

25. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010;107:12204–9.10.1073/pnas.0909122107Search in Google Scholar

26. Grönlund MM, Arvilommi H, Kero P, Lehtonen OP, Isolauri E. Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0-6 months. Arch Dis Child Fetal Neonatal Ed 2000;83:F186–92.10.1136/fn.83.3.F186Search in Google Scholar

27. Isolaurie E, Turjanmaa K. Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis. J Allergy Clin Immunol 1996;97:9–15.10.1016/S0091-6749(96)70277-4Search in Google Scholar

28. Majamaa H, Moisio P, Holm K, Kautianen H, Turjanmaa K. Cow’s milk allergy: diagnostic accuracy of skin prick and patch tests and specific IgE. Allergy 1999;54:346–51.10.1034/j.1398-9995.1999.00834.xSearch in Google Scholar

29. Jalonen T. Identical intestinal permeability changes in children with different clinical manifestations of cow’s milk allergy. J Allergy Clin Immunol 1991;88:737–42.10.1016/0091-6749(91)90180-VSearch in Google Scholar

30. Majamaa H, Laine S, Miettinen A. Eosinophil protein X and eosinophil cationic protein as indicators of intestinal inflammation in infants with atopic eczema and food allergy. Clin Exp Allergy 1999;29:1502–6.10.1046/j.1365-2222.1999.00666.xSearch in Google Scholar PubMed

31. Saarinen KM, Sarnesto A, Savilahti E. Markers of inflammation in the feces of infants with cow’s milk allergy. Pediatr Allergy Immunol 2002:13:188–94.10.1034/j.1399-3038.2002.01027.xSearch in Google Scholar PubMed

32. Kim KW, Lee KE, Kim ES, Song TW, Sohn MH, Kim KE. Serum eosinophil-derived neurotoxin (EDN) in diagnosis and evaluation of severity and bronchial hyperresponsiveness in childhood asthma. Lung 2007;185:97–103.10.1007/s00408-006-0054-8Search in Google Scholar PubMed

33. Goto T, Morioka J, Inamura H, Yano M, Kodaira K, Igarashi Y, et al. Urinary eosinophil derived neurotoxin concentrations in patients with atopic dermatitis: a useful clinical marker for disease activity. Allergol Int 2007;56:433–8.10.2332/allergolint.O-07-489Search in Google Scholar PubMed

34. Morita H, Nomura I, Shoda T, Saito H, Matsumoto K. Fecal eosinophil-derived neurotoxin is significantly elevated in non-IgE dependent gastrointestinal allergies, especially in subtypes showing bloody stool [abstract]. J Allergy Clin Immunol 2012;129:A353.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000301133400353&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar

Received: 2011-12-22
Accepted: 2012-04-19
Published Online: 2012-05-11
Published in Print: 2013-02-01

©2013 by Walter de Gruyter Berlin Boston

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