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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/01.mpg.0000441934.92221.ca
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Gastrointestinal Food Allergy and Intolerance in Infants and Young Children

Heine, Ralf G.

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Department of Gastroenterology & Clinical Nutrition, Royal Children's Hospital, Melbourne, Australia.

Correspondence to Ralf G. Heine, MD, Department of Gastroenterology & Clinical Nutrition, Royal Children's Hospital Melbourne, Parkville 3052, Victoria, Australia (e-mail: ralf.heine@rch.org.au).

The author reports no conflicts of interest.

Infants and young children may present with a diverse range of gastrointestinal (GI) allergies and intolerances that are triggered by specific food proteins or other food constituents (eg, carbohydrates, fat). It may be clinically difficult to distinguish these conditions because there is significant overlap in symptoms. There are several well-characterized food allergic GI conditions that usually manifest in the first weeks to months of life and may even occur in exclusively breast-fed infants. GI food allergy needs to be distinguished from nonimmunological intolerance reactions to foods. Examples are carbohydrate or fat malabsorption, which presents with diarrhoea and abdominal pain following ingestion of the offending food. In addition, dietary factors may directly influence gut functioning and motility. For example, dietary long-chain triglycerides may delay gastric emptying, which predisposes to vomiting or upper abdominal pain. Because of the diverse spectrum of diseases and underlying mechanisms it may sometimes be difficult to define an exact diagnosis, and empirical treatment of suspected adverse reactions to foods with dietary manipulations is common practice.

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GI FOOD ALLERGY

With the rise in allergic disorders, GI food allergies have become a relatively common problem in infants and young children (1). Population-based studies on the epidemiology of challenge-proven immunoglobulin E (IgE)–mediated food allergy in 1-year-old Australian infants found a high prevalence of >10% (2). Although non-IgE-mediated food allergy is thought to be relatively common, its exact prevalence in infancy is not known. GI food allergy involves non-IgE-mediated, delayed GI reactions that may cause upper and lower GI pathologies, including mucosal inflammation, ulceration, small intestinal villous damage, changes in intestinal permeability, or motility abnormalities. Symptoms in young children include persistent vomiting/regurgitation, chronic diarrhoea, feeding difficulties, unsettled behaviours, and sleep pattern disturbance.

Relatively little progress has been made in developing diagnostic tests for cell-mediated GI food allergy. Because no single diagnostic test for non-IgE-mediated food allergy is available, the diagnosis relies on clinical improvement after food elimination and relapse upon challenge. GI biopsies may provide further important diagnostic clues. The cumbersome diagnostic process and lack of characteristic symptoms may lead to significant diagnostic delay and may result in adverse clinical outcomes, including growth impairment or nutritional deficiency states (eg, iron-deficiency anaemia). Early diagnosis and appropriate treatment are therefore crucial in preventing the nutritional complications of GI food allergy.

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Food Protein–Induced Enteropathy

Infants and young children with food protein–induced enteropathy typically present with chronic diarrhea and failure to thrive. Cow's milk and soy milk protein are considered the main offending food allergens. The prevalence of food protein–induced enteropathy appears to have decreased since the development of “humanized” cow's milk and soy formula. Current reliable prevalence figures are not available. Allergic inflammation in the small intestine causes mucosal damage with distortion of the villous architecture. Histological features share strong similarities with untreated coeliac disease, which is the closest differential diagnosis. Early studies in cow's-milk–sensitive enteropathy demonstrated that mucosal damage is mediated by eosinophils in the presence of vascular cell adhesion molecule-1 (3). Cow's-milk–specific lymphocytes were identified in biopsies of patients with duodenal eosinophilic gastroenteritis or food protein–induced enteropathy (4). In addition, localised production of IgE in the mucosa of the small intestine (in the absence of specific serum IgE) may be implicated in the pathogenesis of food allergic enteropathies (5).

The clinical presentation of infants with cow's-milk protein–induced enteropathy is similar to that of coeliac disease. These formula-fed infants present with chronic diarrhoea, vomiting, and poor weight gain and may develop associated micronutrient deficiencies (eg, iron deficiency, rickets). If treatment is delayed, infants may develop protein-energy malnutrition with growth impairment. Infants with cow's-milk enteropathy develop secondary lactose malabsorption resulting from reduced expression of brush border lactase in the shortened intestinal villi. Lactose, therefore, needs to be eliminated from the infant's diet until the normal villous architecture has been restored. Soy formula and extensively hydrolysed formulae are commonly used in the treatment of cow's-milk enteropathy (6). Strict cow's-milk protein elimination needs to be continued until tolerance develops, usually between 12 and 24 months of age. In a subset of patients, residual GI symptoms may persist to school age (7).

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Food Protein–Induced Enterocolitis Syndrome

Food protein–induced enterocolitis syndrome (FPIES) is characterized by potentially severe GI reactions with profuse vomiting and dehydration (8). In a population-based study, FPIES reactions occurred in 0.34% of infants (9). As with most cell-mediated food allergic disorders, the pathological mechanisms causing FPIES are poorly understood. The term enterocolitis may be misleading because direct evidence for allergic inflammation in the small intestine and colon is missing. Clinical symptoms include profuse vomiting and diarrhoea, with onset 2 to 4 hours after a meal. Protracted vomiting may lead to hypovolaemic shock, which is present in approximately 20% of patients with FPIES. These infants present with pallor, lethargy, and floppiness. Cutaneous signs are absent, which, apart from the timing of reactions, is an important distinguishing clinical feature against anaphylaxis. No diagnostic test, other than food challenge, is available to confirm the diagnosis. The diagnosis is therefore often not established at first presentation, and infants may develop recurrent FPIES reactions before this type of food allergy is recognized (10). FPIES may be mistaken for gastroenteritis, sepsis, or even intestinal obstruction (11). Cow's milk and soy are considered the main causative allergens (8). Solid foods, including rice, other cereals, and poultry meats also may cause FPIES reactions in infancy (12,13). FPIES to multiple food allergens is relatively common. The condition does not appear to occur in breast-fed infants. Maternal elimination diets in breast-fed infants are therefore not required (6). The treatment of FPIES involves strict avoidance of the offending food proteins. Tolerance usually is assessed by food challenge at approximately 2 years of age. Because of the risk of significant vomiting and dehydration during a challenge, these challenges usually are performed in hospital.

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Food Protein–Induced Proctocolitis

Food protein–induced proctocolitis is a relatively common and benign form of GI food allergy that manifests with low-grade diarrhoea and bright rectal bleeding in the first weeks of life (14). Infantile proctocolitis is the most common cause of low-grade rectal bleeding in infants younger than 3 months old (15). Exact prevalence figures in infancy are not available. Symptoms usually develop between 3 and 6 weeks of age, but they may be seen occasionally in older infants. Infantile proctocolitis occurs in both breast- and formula-fed infants (16). The clinical presentation is generally limited to low-grade diarrhoea containing small amounts of fresh blood. Infants are otherwise healthy. Because blood loss is usually minimal, clinically significant anaemia is uncommon. Endoscopic biopsies typically demonstrate an eosinophilic proctocolitis with the presence of >6 to 10 eosinophils per microscopic field at high power (16). Numbers of intraepithelial lymphocytes, predominantly CD8+ cells, also are increased (17). The differential diagnosis of allergic proctocolitis in infants includes bacterial gastroenteritis, anal fissures, juvenile polyps, or other nonallergic forms of colitis, such as chronic granulomatous disease or inflammatory bowel disease. The treatment of infantile allergic proctocolitis involves the dietary elimination of the offending food protein. In the majority of cases, elimination of cow's-milk protein is sufficient and can be achieved by a maternal elimination diet in breast-fed infants or the use of an extensively hydrolysed hypoallergenic formula. The prognosis of infantile allergic proctocolitis is excellent, and most infants outgrow the condition between 9 and 12 months of age (16).

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FOOD INTOLERANCES AND CARBOHYDRATE MALABSORPTION

Carbohydrate malabsorption in early childhood presents with intermittent, food-associated diarrhea, abdominal bloating, and pain. It is therefore one of the main differential diagnoses of GI food allergy. The diagnostic overlap is particularly close between non-IgE-mediated cow's-milk allergy and lactose malabsorption. Other forms of carbohydrate malabsorption, including congenital sucrase-isomaltase deficiency (18), also may masquerade as food allergy. Lactose and fructose malabsorption often are implicated in children with recurrent abdominal pain; however, clinical trials have demonstrated that these conditions are generally not associated with recurrent abdominal pain unless a clear history of intolerance to fruit or cow's milk is evident (19).

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Lactose Intolerance/Malabsorption

Lactose is a disaccharide that consists of 2 sugar molecules, glucose and galactose, that are linked via a β-1→4 glycosidic bond. Lactose is the main carbohydrate in human milk and occurs at a mean concentration of 56.8 g/L (range 43–65 g/L) (20). Lactose is converted to lactic acid by intestinal bacteria, including Streptococcus lactis(21). In addition, nonabsorbed lactase is fermented by colonic bacteria to short-chain fatty acids (eg, butyrate) and hydrogen (22). In breast-fed infants, low-grade lactose malabsorption is considered physiological (23). In this age group, lactose may act as a conditional prebiotic; however, the prebiotic effects of lactose on faecal biodiversity and early immune modulation are still poorly understood (22,24).

Lactose requires enzymatic hydrolysis before its subunits D-glucose and D-galactose can be absorbed (25). Lactase is a member of the β-galactosidase family, with a molecular weight of 150 kDa. The enzyme is encoded by a gene located on chromosome 2 (26). Lactase is expressed in the brush border of mature enterocytes's enzyme and has its highest expression in the mid-jejunum. Maximum lactase expression occurs during first months of life (27). Lactase transcription is gradually downregulated after weaning. There are significant genetic and ethnic differences in the rate of decline of lactase activity beyond infancy. In 65% to 70% of the world's population, lactase activity significantly declines by adult life (nonpersistence). Lactase nonpersistence is linked to 2 main single nucleotide polymorphisms upstream from the lactase gene, C/T-13910 and G/A-22018 (28,29). Heterozygotes have intermediate lactase levels and are more susceptible to secondary lactose intolerance during illness. Lactase persistence is more common in people of northern European, west African or Middle Eastern backgrounds (30).

Congenital (primary) lactose malabsorption is a rare genetic disorder that occurs in mainly Finland and western Russia (31). Infants present with severe diarrhoea and growth failure in the newborn period. Lactase activity is low or completely absent from an otherwise normal intestinal epithelium. Several mutations in the lactase gene have been identified. Secondary lactose malabsorption is relatively common in infancy and is the result of another underlying disorder, including infective gastroenteritis, cow's-milk protein–induced enteropathy, or rare epithelial dysplasia syndromes. Viral GI infection and cow's-milk enteropathy are by far the most common causes of secondary lactose malabsorption in infancy.

Lactose malabsorption in infancy presents with abdominal distension, diarrhea, and perianal excoriation caused by acidic stools. Depending on the underlying pathology and duration of symptoms, weight gain also may be slow (32). The treatment in formula-fed infants consists of lactose restriction, by shifting to a lactose-reduced, cow's-milk–based formula. In breast-fed infants, it is more difficult to limit the intake of lactose. Expressed breast milk can be incubated with lactase if symptoms are severe. The need for ongoing lactose restriction depends on the type of the underlying process. In infants with infective gastroenteritis, adequate lactase activity is usually restored within 2 to 4 weeks; however, in very young infants the recovery from gastroenteritis may be delayed. If cow's-milk enteropathy is suspected, the infant should be started on a hypoallergenic formula and dietary cow's-milk protein should be avoided. In breast-fed infants, a maternal cow's-milk–free diet may be beneficial.

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Fructose Malabsorption

Fructose is a monosaccharide that occurs naturally in fruit, honey, and some vegetables. Fructose is absorbed by glucose-facilitated absorption via the intestinal transporters GLUT2 and GLUT5 (33). Absorption is increased in the presence of equimolar amounts (1:1) of glucose (34). Patients with fructose malabsorption have a limited capacity to absorb fructose. Fructose malabsorption is common in young children and generally improves with age. The diagnosis of fructose malabsorption often can be made by taking a careful dietary history and by assessing the response to dietary fructose restriction. Alternatively, the diagnosis can be made objectively based on breath hydrogen testing after an oral fructose dose (35). Rates of fructose malabsorption (based on fructose breath hydrogen testing) were 88.2% in infants younger than 1 year of age, 66.6% in 1- to 5-year-olds, 40.4% in 6- to 10-year-olds, and 27.1% in 10- to 15-year-olds (36). These results most likely reflect the normal maturation of fructose absorption with age, and not all children show clinical symptoms during a positive breath hydrogen test. Debate, therefore, continues as to whether fructose malabsorption in children is a distinct disease state or a normal variant (37).

Fermentation of nonabsorbed fructose by intestinal bacteria causes intestinal gas production, flatulence, abdominal pain, and diarrhoea. In young children, fructose malabsorption may present as toddler's diarrhoea. These young children have a long-standing history of low-grade diarrhoea, but they generally achieve normal weight gain and linear growth. Older children may develop irritable bowel syndrome–like symptoms, with central abdominal pain and bloating. The dietary treatment involves the elimination of high-fructose foods (containing >3 g of fructose per serving). Elimination of high-fructose fruit (eg, apple, pear, watermelon, raisins, dried fruit), fruit juice, honey, and high-fructose corn syrup often is sufficient in young children (38,39). The role of fructans (nonabsorbable fructose polymers) in children with fructose malabsorption is less clear. There is increasing evidence that diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols are effective in the treatment of adults with irritable bowel syndrome (40); however, the use of low–fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diets in young children is still controversial. The extent of fructose and fructan elimination needs to be individualised in children. In general, the low-fructose diet can be relaxed over time. A paediatric dietitian should be involved to assess the nutritional adequacy of the diet and to monitor growth parameters.

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Coeliac Disease and Noncoeliac Gluten Sensitivity

Coeliac disease (CD) is a gluten-sensitive autoimmune disease that has returned to the scientific spotlight. CD is currently considered a common disorder. Population-based screening in Finland and Europe suggests a community prevalence of approximately 1% (41,42). During the past decade, there have been significant breakthroughs in the understanding of the pathophysiology of CD, particularly regarding the involvement of human leucocyte antigens (HLA-DQ2/DQ8) and tissue transglutaminase in the immune processing of gluten-derived peptides by antigen-presenting cells and T lymphocytes (43,44). Highly sensitive and specific serological markers such as serum IgA and IgG antibodies against tissue transglutaminase and deamidated gliadin peptides have become available in recent years (45,46). The combination of HLA-DQ2/DQ8 screening and antibody testing has significantly improved the diagnostic accuracy of the serological diagnosis of CD. Despite these advances, the diagnosis of CD still requires confirmation by small bowel biopsy (47–49).

The assessment of adverse reactions to wheat in children is complex. Apart from CD, there is increasing recognition of non-IgE-mediated wheat allergy (presenting with food protein–induced proctocolitis or enterocolitis) and noncoeliac gluten sensitivity (NCGS) (50). The pathophysiology of NCGS is still poorly understood. Infants and children with non-IgE-mediated wheat allergy or NCGS do not have evidence of CD but have reproducible GI reactions after gluten challenge. Fructans in wheat may contribute to GI symptoms, although children with fructose malabsorption often tolerate small amounts of wheat. From a practical perspective, it is important to rule out CD before wheat is eliminated from a child's diet. A CD serology and HLA-DQ2/DQ8 screen is a useful diagnostic tool to assess for possible CD. Slow reintroduction of increasing amounts of wheat into the diet, as tolerated, should be attempted in patients with non-IgE-mediated wheat allergy or NCGS; however, patients with CD need to remain on a lifelong, strict gluten-free diet.

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REFERENCES

1. Sicherer SH. Epidemiology of food allergy. J Allergy Clin Immunol 2011; 127:594–602.

2. Osborne NJ, Koplin JJ, Martin PE, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol 2011; 127:668–676.

3. Chung HL, Hwang JB, Kwon YD, et al. Deposition of eosinophil-granule major basic protein and expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the mucosa of the small intestine in infants with cow's milk-sensitive enteropathy. J Allergy Clin Immunol 1999; 103:1195–1201.

4. Beyer K, Castro R, Birnbaum A, et al. Human milk-specific mucosal lymphocytes of the gastrointestinal tract display a TH2 cytokine profile. J Allergy Clin Immunol 2002; 109:707–713.

5. Lin XP, Magnusson J, Ahlstedt S, et al. Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE. J Allergy Clin Immunol 2002; 109:879–887.

6. Allen KJ, Davidson GP, Day AS, et al. Management of cow's milk protein allergy in infants and young children: an expert panel perspective. J Paediatr Child Health 2009; 45:481–486.

7. Kokkonen J, Haapalahti M, Laurila K, et al. Cow's milk protein-sensitive enteropathy at school age. J Pediatr 2001; 139:797–803.

8. Leonard SA, Nowak-Wegrzyn A. Clinical diagnosis and management of food protein-induced enterocolitis syndrome. Curr Opin Pediatr 2012; 24:739–745.

9. Katz Y, Goldberg MR, Rajuan N, et al. The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: a large-scale, prospective population-based study. J Allergy Clin Immunol 2011; 127:647–653.

10. Mehr S, Kakakios A, Frith K, et al. Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics 2009; 123:e459–e464.

11. Jayasooriya S, Fox AT, Murch SH. Do not laparotomize food-protein-induced enterocolitis syndrome. Pediatr Emerg Care 2007; 23:173–175.

12. Nowak-Wegrzyn A, Sampson HA, Wood RA, et al. Food protein-induced enterocolitis syndrome caused by solid food proteins. Pediatrics 2003; 111 (4 Pt 1):829–835.

13. Mehr SS, Kakakios AM, Kemp AS. Rice: a common and severe cause of food protein-induced enterocolitis syndrome. Arch Dis Child 2009; 94:220–223.

14. Odze RD, Bines J, Leichtner AM, et al. Allergic proctocolitis in infants: a prospective clinicopathologic biopsy study. Hum Pathol 1993; 24:668–674.

15. Chang JW, Wu TC, Wang KS, et al. Colon mucosal pathology in infants under three months of age with diarrhea disorders. J Pediatr Gastroenterol Nutr 2002; 35:387–390.

16. Lake AM. Food-induced eosinophilic proctocolitis. J Pediatr Gastroenterol Nutr 2000; 30 (Suppl):S58–S60.

17. Ormala T, Rintala R, Savilahti E. T cells of the colonic mucosa in patients with infantile colitis. J Pediatr Gastroenterol Nutr 2001; 33:133–138.

18. McMeans AR. Congenital sucrase-isomaltase deficiency: diet assessment and education guidelines. J Pediatr Gastroenterol Nutr 2012; 55 (Suppl 2):S37–S39.

19. Gijsbers CF, Kneepkens CM, Buller HA. Lactose and fructose malabsorption in children with recurrent abdominal pain: results of double-blinded testing. Acta Paediatr 2012; 101:e411–e415.

20. Fusch G, Choi A, Rochow N, et al. Quantification of lactose content in human and cow's milk using UPLC-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2011; 879:3759–3762.

21. Thompson J, Chassy BM, Egan W. Lactose metabolism in Streptococcus lactis: studies with a mutant lacking glucokinase and mannose-phosphotransferase activities. J Bacteriol 1985; 162:217–223.

22. Francavilla R, Calasso M, Calace L, et al. Effect of lactose on gut microbiota and metabolome of infants with cow's milk allergy. Pediatr Allergy Immunol 2012; 23:420–427.

23. Mobassaleh M, Montgomery RK, Biller JA, et al. Development of carbohydrate absorption in the fetus and neonate. Pediatrics 1985; 75 (1 Pt 2):160–166.

24. Szilagyi A, Shrier I, Chong G, et al. Lack of effect of lactose digestion status on baseline fecal micoflora. Can J Gastroenterol 2009; 23:753–759.

25. Gupta SK, Chong SK, Fitzgerald JF. Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes. J Pediatr Gastroenterol Nutr 1999; 28:246–251.

26. Kruse TA, Bolund L, Grzeschik KH, et al. The human lactase-phlorizin hydrolase gene is located on chromosome 2. FEBS Lett 1988; 240:123–126.

27. Hamosh M. Digestion in the newborn. Clin Perinatol 1996; 23:191–209.

28. Bernardes-Silva CF, Pereira AC, de Fatima Alves da Mota, et al.Lactase persistence/non-persistence variants, C/T_13910 and G/A_22018, as a diagnostic tool for lactose intolerance in IBS patients. Clin Chim Acta 2007;386:7–11.

29. Enattah NS, Sahi T, Savilahti E, et al. Identification of a variant associated with adult-type hypolactasia. Nat Genet 2002; 30:233–237.

30. Itan Y, Jones BL, Ingram CJ, et al. A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evol Biol 2010; 10:36.

31. Savilahti E, Launiala K, Kuitunen P. Congenital lactase deficiency. A clinical study on 16 patients. Arch Dis Child 1983; 58:246–252.

32. Northrop-Clewes CA, Lunn PG, Downes RM. Lactose maldigestion in breast-feeding Gambian infants. J Pediatr Gastroenterol Nutr 1997; 24:257–263.

33. Jones HF, Butler RN, Brooks DA. Intestinal fructose transport and malabsorption in humans. Am J Physiol Gastrointest Liver Physiol 2011; 300:G202–G206.

34. Latulippe ME, Skoog SM. Fructose malabsorption and intolerance: effects of fructose with and without simultaneous glucose ingestion. Crit Rev Food Sci Nutr 2011; 51:583–592.

35. Mann NS, Cheung EC. Fructose-induced breath hydrogen in patients with fruit intolerance. J Clin Gastroenterol 2008; 42:157–159.

36. Jones HF, Burt E, Dowling K, et al. Effect of age on fructose malabsorption in children presenting with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr 2011; 52:581–584.

37. Kyaw MH, Mayberry JF. Fructose malabsorption: true condition or a variance from normality. J Clin Gastroenterol 2011; 45:16–21.

38. Muir JG, Shepherd SJ, Rosella O, et al. Fructan and free fructose content of common Australian vegetables and fruit. J Agric Food Chem 2007; 55:6619–6627.

39. Wintermeyer P, Baur M, Pilic D, et al. Fructose malabsorption in children with recurrent abdominal pain: positive effects of dietary treatment. Klin Padiatr 2012; 224:17–21.

40. Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: the FODMAP approach. J Gastroenterol Hepatol 2010; 25:252–258.

41. Maki M, Mustalahti K, Kokkonen J, et al. Prevalence of celiac disease among children in Finland. N Engl J Med 2003; 348:2517–2524.

42. Mustalahti K, Catassi C, Reunanen A, et al. The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med 2010; 42:587–595.

43. Sollid LM, Qiao SW, Anderson RP, et al. Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics 2012; 64:455–460.

44. Karell K, Louka AS, Moodie SJ, et al. HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease. Hum Immunol 2003; 64:469–477.

45. Alessio MG, Tonutti E, Brusca I, et al. Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease. J Pediatr Gastroenterol Nutr 2012; 55:44–49.

46. Zanini B, Magni A, Caselani F, et al. High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease. Dig Liver Dis 2012; 44:280–285.

47. Kurppa K, Salminiemi J, Ukkola A, et al. Utility of the new ESPGHAN criteria for the diagnosis of celiac disease in at-risk groups. J Pediatr Gastroenterol Nutr 2012; 54:387–391.

48. Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (“celiac sprue”). Gastroenterology 1992; 102:330–354.

49. Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 1999; 11:1185–1194.

50. Lundin KE, Alaedini A. Non-celiac gluten sensitivity. Gastrointest Endosc Clin N Am 2012; 22:723–734.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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