3 Nutritional Challenges in Special Conditions and Diseases Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
3.10 Celiac Disease Riccardo Troncone Marco Sarno
Celiac disease · Gluten-free diet · Oats · Prevention · Gluten-related disorders
Key Messages • Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals • CD offers a wide range of clinical presentations from severe gastrointestinal symptoms (diarrhea, vomiting and failure to thrive) and extraintestinal symptoms (iron deficiency anemia, neurological problems, alterations in liver function tests, enamel defects and osteoporosis) to asymptomatic cases. The nutrition status at diagnosis depends mostly on the extent of the intestinal damage • All CD patients should be treated with lifelong gluten-free diet (GFD) irrespective of symptoms • An experienced dietician should be involved in order to evaluate the patient’s current nutritional status, to assess macronutrient and/or micronutrient intake, to detect deficiencies, to educate patients to the GFD and to monitor dietary compliance • Alternative therapies and strategies of prevention can now be envisaged © 2015 S. Karger AG, Basel
Introduction
Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines (from wheat, barley and rye) in genetically susceptible individuals. It is characterized by the presence of a variable combination of glutendependent clinical manifestations, CD-specific antibodies [antibodies to endomysium (EMA), tissue transglutaminase 2 (TG2) and deamidated gliadin peptides (DGP)], HLA-DQ2 or HLADQ8 haplotypes and enteropathy [1]. The accuracy of identifying and estimating the real prevalence of CD has been improved in recent years by the introduction of serological screening tests: 0.6–1.0% of the European general population is affected, with some regional differences (0.3% in Germany, 0.9% in Italy and 2.4% in Finland) [2]. CD is also common in North and South America, North Africa and the Middle East. The prevalence of CD is increasing because of a westernization of diets, changes in wheat production and increased awareness of the disease. CD offers a wide range of clinical presentations from severe gastrointestinal symptoms (diarrhea, vomiting and failure to thrive) and Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
Key Words
Table 1. Fundamentals of the GFD
Grains that should be avoided
Wheat (including spelt, Kamut, semolina and triticale), rye and barley (including malt)
Safe grains (gluten free)
Rice, amaranth, buckwheat, corn, millet, quinoa, sorghum, teff (an Ethiopian cereal grain) and oats (?)
Sources of gluten-free starches that can be used as flour alternatives
Cereal grains: rice, amaranth, buckwheat, corn, millet, quinoa, sorghum and teff Tubers: potato, arrowroot, jicama, taro and tapioca Legumes: chickpeas, lentils, kidney beans, navy beans, pea beans, peanuts and soybeans Nuts: almonds, walnuts, chestnuts, hazelnuts and cashews Seeds: sunflower, flax and pumpkin
tomatic child or adolescent with CD-associated conditions, duodenal biopsies are still advocated in all cases.
Gluten-Free Diet
The only treatment for CD is lifelong strict adherence to a gluten-free diet (GFD; table 1). GFD consist of the dietary exclusion of grains containing gluten (wheat, rye, barley, triticale, couscous, spelt and Kamut). Rice, corn and buckwheat do not contain gluten and can be eaten. Potato, chestnut, tapioca, sorghum, quinoa and amaranth are also tolerated. Although there is now a large body of clinical evidence suggesting oats lacking toxicity for CD patients, there are still some important aspects to consider [6]. There are documented cases of oat-dependent villous atrophy in patients with oat-specific mucosal T cell reactivity. Furthermore, there is also the possibility that symptoms are related to wheat proteins contaminating oats during the harvesting and milling process. Another issue that warrants further investigation is related to the great heterogeneity of oat cultivars. On the other hand, the incorporation of oats into a GFD provides high fiber and vitamin B content, increased palatability and beneficial effects on cardiovascular health. However, it seems wise to add oats only when the
Celiac Disease
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
191
3
Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
extraintestinal symptoms (iron deficiency anemia, neurological problems, alterations in liver function tests, enamel defects and osteoporosis) to asymptomatic cases [3]. Also, the small intestinal lesions may range from epithelial lymphocyte infiltration with preserved villous architecture to severe villous atrophy [4]. The nutrition status at diagnosis depends mostly on the extent of the intestinal damage. The classic presentation is accompanied by steatorrhea and fatsoluble vitamin deficiency. Malabsorption of iron, calcium and folic acid is also frequent, as these are absorbed in the proximal small intestine [5]. The diagnostic approach has recently been revised [1]. Children found positive for CD-specific antibodies (anti-TG2, EMA and anti-DGP) should undergo duodenal biopsies unless certain conditions are fulfilled which allow the option to omit the confirmatory biopsies. In children and adolescents with signs or symptoms suggestive of CD and very high anti-TG2 (or anti-DGP) titers with levels exceeding 10 times the upper limit of normal, the likelihood for villous atrophy (Marsh score 3) is high. In this situation, the pediatric gastroenterologist may discuss with the parents and patient (as appropriate for the patient’s age) the option of performing further laboratory testing (EMA, HLA) in order to make the diagnosis of CD without biopsies. In the case of an asymp-
GFD is well established, so that possible adverse reactions can be readily identified by a strict clinical follow-up. There is a general consensus that all CD patients should be treated with a GFD irrespective of the presence of symptoms. However, while it is relatively easy to assess the health improvement after treatment of CD in patients with clinical symptoms of the disease, it proves difficult in persons with asymptomatic CD. A high rate of osteoporosis/osteopenia (60%) was observed in asymptomatic patients with villous atrophy; this finding suggests that, in CD, clinical tolerance does not reflect tolerance to gluten and that, in silent cases, the increased risk of osteoporosis substantiates the need for a GFD. There are no guidelines concerning the need for a GFD in subjects with ‘potential’ CD (patients with positive CD-associated serology but without enteropathy). Most of the ‘potential’ cases are left on gluten-containing diet and strictly monitored for the appearance of complications. While a risk of osteoporosis also for this group of patients has been reported in the past [7], no significant differences have recently been found between CD patients on a long-term GFD and ‘latent’ patients (patients with a clear previous diagnosis of CD and no clinical/histological relapse after a long period of GFD) as far as biological tests of malabsorption and the overall nutritional status, including bone mass density, are concerned. Similarly, we did not observe any major nutritional problem in our cohort of potential CD subjects [8].
Alternative Therapies
Compliance with GFD It is important that an experienced dietician with specific expertise in CD counseling educates the family and the child about dietary restrictions. An expert dietician should be consulted in order to evaluate the patient’s current nutritional status, to assess macronutrient and/or micronutrient intake, to detect deficiencies, to educate the patient to the GFD and to monitor dietary compliance. Compliance with a GFD can be difficult, especial-
Breeding programs and transgenic technology may lead to the production of wheat that is devoid of biologically active peptide sequences. Recently, new, alternative approaches to GFD have been investigated (table 2) [12]. As gliadin peptides are highly resistant to digestive processing, prolyl endopeptidase produced by probiotic microorganisms has been shown to promote digestion of gliadin. Clinical trials have already started. Other approaches include restoring intestinal permea-
Limits More information is needed on the daily gluten amount that may be tolerated by CD patients. The data available so far seem to suggest that, although individual variability makes it difficult to set a universal threshold, this should be set below 50 mg/day, a level unlikely to cause significant histological abnormalities. The regulations on the composition and labeling of food suitable for CD patients have recently changed. In 2008, the Codex Alimentarius revised the previous standard indicating 2 thresholds: 20 ppm for products to be labeled gluten free and 100 ppm for products with very low gluten content. The 20-ppm threshold is considered a safe option for CD patients, considering the overall consumption of gluten-free products [11].
Troncone Sarno Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
192
ly in adolescents [9]. It is recommended that children with CD be monitored with periodic visits for assessment of symptoms, growth, physical status and adherence to GFD. Periodic measurements of tissue TG antibody levels to document reductions in antibody titers can be helpful as indirect evidence of adherence to a GFD, although they are inaccurate in detecting slight dietary transgressions. Recently, methods based on the detection of a 33-mer gliadin peptide in feces have been proposed to assess compliance with the GFD [10].
1. Intraluminal therapies Wheat varieties (Ancient) wheat variants with low immunogenicity Genetically modified wheat variants or deletion lines of common wheat with lower immunogenicity Flour/dough treatment Pretreatment with lactobacilli Transamidation of gliadin Ingested gliadin peptide modifications Prolyl endopeptidases from Aspergillus niger or Sphingomonas capsulata Intraluminal gliadin binding by polymers 2. Transepitelial uptake Epithelial tight junctions ZOT receptor antagonist AT1001 3. Adaptive immune response TG2 TG inhibitors HLA-DQ2 Blocking DQ2 analogs 4. Immune modulators Gluten vaccination 5. Biologicals (T cell or cytokine blockers)
bility with anti-zonulin antibodies, preventing gliadin presentation to T cells by blocking HLA binding sites and the use of tissue TG inhibitors. The efficacy of these approaches needs to be assessed in more in vivo studies.
Prevention
Evidence suggests that the first months of life are crucial for CD development; breastfeeding has a protective role, and indeed there is a negative correlation between its duration and the development of CD. Moreover, the age at introduction of gluten to the diet is important: exposure to gluten in the first 3 months significantly increases the risk of CD in genetically susceptible individuals.
One study has suggested the existence of a window of opportunity as the late introduction of gluten to the diet (after the 7th month of life) has been found to be associated with a higher risk. On the basis of the present evidence, breastfeeding should be strongly encouraged and gluten should not be introduced before the 4th month of life, preferably while the baby is still breastfed [13]. Finally, increasing attention is being devoted to the possible role of viruses, which could trigger CD autoimmunity in genetically susceptible children by increasing intestinal permeability and activating innate immune pathways linked to CD pathophysiology.
Other Conditions Requiring GFD
The spectrum of gluten-related disorders also includes wheat allergy (WA) and nonceliac gluten sensitivity (NCGS). WA is defined as an adverse immunologic reaction to wheat proteins. Depending on the allergen exposure and the immunologic mechanisms, WA is classified into (1) classic food allergy affecting the skin, gastrointestinal tract or respiratory tract, (2) wheat-dependent, exercise-induced anaphylaxis, (3) occupational asthma (baker’s asthma) and rhinitis as well as (4) contact urticaria. IgE antibodies play a central role in the pathogenesis of these diseases. WA is treated by GFD, and the same limits as discussed for CD seem to apply to WA [14]. NCGS refers to individuals who show distress when eating gluten and improvement when following a GFD. CD autoantibodies are absent, the small intestine is usually normal, and allergy tests are negative. Thus, NCGS is a diagnosis by exclusion criteria. However, many suggest caution, as there is a noticeable lack of controlled studies unequivocally demonstrating the role of gluten. Other food components (fermentable oligo-, di- and monosaccharides and polyols or FODMAPs) have been suspected to be responsible for symptoms attributed to NCGS. Further caution is required due
Celiac Disease
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
193
3
Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
Table 2. Alternative therapies for CD
to the fact that unmotivated GFD is dangerous not only because of the costs imposed upon the community but also because it may affect the health of incorrectly classified patients [15].
Conclusions
• CD patients should be treated with GFD irrespective of the presence of symptoms. There is still uncertainty as to whether to treat ‘potential’ CD or not
• It is important that an experienced dietician with specific expertise educates the family and the child about dietary restrictions • It seems wise to add oats only when the GFD is well established, so that possible adverse reactions can be readily identified • The 20-ppm threshold is considered a safe option for CD patients • To prevent CD, breastfeeding should be strongly encouraged; gluten should not be introduced before the 4th month of life, preferably while the baby is still breastfed
References
194
5 Garcia-Manzanares A, Lucendo JA: Nutritional and dietary aspects of celiac disease. Nutr Clin Pract 2011;26:163– 173. 6 Pulido O, Gillespie Z, Zarkadas M, et al: Introduction of oats in the diet of individuals with celiac disease: a systematic review. Adv Food Nutr Res 2009;57: 235–285. 7 Kaukinen K, Mäki M, Partanen J, Sievänen H, Collin P: Celiac disease without villous atrophy: revision of criteria called for. Dig Dis Sci 2001;46:879–887. 8 Tosco A, Salvati VM, Auricchio R, Maglio M, Borrelli M, Coruzzo A, Paparo F, Boffardi M, Esposito A, D’Adamo G, Malamisura B, Greco L, Troncone R: Natural history of potential celiac disease in children. Clin Gastroenterol Hepatol 2011;9:320–325. 9 Errichiello S, Esposito O, Di Mase R, Camarca ME, Natale C, Limongelli MG, Marano C, Coruzzo A, Lombardo M, Strisciuglio P, Greco L: Celiac disease: predictors of compliance with a glutenfree diet in adolescents and young adults. J Pediatr Gastroenterol Nutr 2010;50:54–60. 10 Comino I, Real A, Vivas S, Síglez MÁ, Caminero A, Nistal E, Casqueiro J, Rodríguez-Herrera A, Cebolla A, Sousa C: Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr 2012;95:670–677.
11 Gilbert A, Kruizinga AG, Neuhold S, Haoben GF, Canela MA, Fasano A, Catassi C: Might gluten traces in wheat substitutes pose a risk in patients with celiac disease? A population-based probabilistic approach to risk estimation. Am J Clin Nutr 2013;97:109–116. 12 Gianfrani C, Auricchio S, Troncone R: Possible drug targets for celiac disease. Expert Opin Ther Targets 2006;10:601– 611. 13 Szajewska H, Chmielewska A, PieścikLech M, Ivarsson A, Kolacek S, Koletzko S, Mearin ML, Shamir R, Auricchio R, Troncone R; PREVENTCD Study Group: Systematic review: early infant feeding and the prevention of coeliac disease. Aliment Pharmacol Ther 2012;36:607– 618. 14 Hischenhuber C, Crevel R, Jarry B, Mäki M, Moneret-Vautrin DA, Romano A, Troncone R, Ward R: Review article: safe amounts of gluten for patients with wheat allergy or coeliac disease. Aliment Pharmacol Ther 2006;23:559–575. 15 Di Sabatino A, Giuffrida P, Corazza GR: Still waiting for a definition of nonceliac gluten sensitivity. J Clin Gastroenterol 2013;47:567–569.
Troncone Sarno Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
1 Husby S, Koletzko S, Korponay-Szabó IR, et al; ESPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastroenterology Committee; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition: European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54: 136–160. 2 Mustalahti K, Catassi C, Reunanen A, Fabiani E, Heier M, McMillan S, Murray L, Metzger MH, Gasparin M, Bravi E, Mäki M; Coeliac EU Cluster, Project Epidemiology: The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med 2010;42:587–595. 3 Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PH, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KE, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C: The Oslo definitions for coeliac disease and related terms. Gut 2013;62:43–52. 4 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.
3.10 Celiac Disease Riccardo Troncone Marco Sarno
Celiac disease · Gluten-free diet · Oats · Prevention · Gluten-related disorders
Key Messages • Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals • CD offers a wide range of clinical presentations from severe gastrointestinal symptoms (diarrhea, vomiting and failure to thrive) and extraintestinal symptoms (iron deficiency anemia, neurological problems, alterations in liver function tests, enamel defects and osteoporosis) to asymptomatic cases. The nutrition status at diagnosis depends mostly on the extent of the intestinal damage • All CD patients should be treated with lifelong gluten-free diet (GFD) irrespective of symptoms • An experienced dietician should be involved in order to evaluate the patient’s current nutritional status, to assess macronutrient and/or micronutrient intake, to detect deficiencies, to educate patients to the GFD and to monitor dietary compliance • Alternative therapies and strategies of prevention can now be envisaged © 2015 S. Karger AG, Basel
Introduction
Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines (from wheat, barley and rye) in genetically susceptible individuals. It is characterized by the presence of a variable combination of glutendependent clinical manifestations, CD-specific antibodies [antibodies to endomysium (EMA), tissue transglutaminase 2 (TG2) and deamidated gliadin peptides (DGP)], HLA-DQ2 or HLADQ8 haplotypes and enteropathy [1]. The accuracy of identifying and estimating the real prevalence of CD has been improved in recent years by the introduction of serological screening tests: 0.6–1.0% of the European general population is affected, with some regional differences (0.3% in Germany, 0.9% in Italy and 2.4% in Finland) [2]. CD is also common in North and South America, North Africa and the Middle East. The prevalence of CD is increasing because of a westernization of diets, changes in wheat production and increased awareness of the disease. CD offers a wide range of clinical presentations from severe gastrointestinal symptoms (diarrhea, vomiting and failure to thrive) and Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
Key Words
Table 1. Fundamentals of the GFD
Grains that should be avoided
Wheat (including spelt, Kamut, semolina and triticale), rye and barley (including malt)
Safe grains (gluten free)
Rice, amaranth, buckwheat, corn, millet, quinoa, sorghum, teff (an Ethiopian cereal grain) and oats (?)
Sources of gluten-free starches that can be used as flour alternatives
Cereal grains: rice, amaranth, buckwheat, corn, millet, quinoa, sorghum and teff Tubers: potato, arrowroot, jicama, taro and tapioca Legumes: chickpeas, lentils, kidney beans, navy beans, pea beans, peanuts and soybeans Nuts: almonds, walnuts, chestnuts, hazelnuts and cashews Seeds: sunflower, flax and pumpkin
tomatic child or adolescent with CD-associated conditions, duodenal biopsies are still advocated in all cases.
Gluten-Free Diet
The only treatment for CD is lifelong strict adherence to a gluten-free diet (GFD; table 1). GFD consist of the dietary exclusion of grains containing gluten (wheat, rye, barley, triticale, couscous, spelt and Kamut). Rice, corn and buckwheat do not contain gluten and can be eaten. Potato, chestnut, tapioca, sorghum, quinoa and amaranth are also tolerated. Although there is now a large body of clinical evidence suggesting oats lacking toxicity for CD patients, there are still some important aspects to consider [6]. There are documented cases of oat-dependent villous atrophy in patients with oat-specific mucosal T cell reactivity. Furthermore, there is also the possibility that symptoms are related to wheat proteins contaminating oats during the harvesting and milling process. Another issue that warrants further investigation is related to the great heterogeneity of oat cultivars. On the other hand, the incorporation of oats into a GFD provides high fiber and vitamin B content, increased palatability and beneficial effects on cardiovascular health. However, it seems wise to add oats only when the
Celiac Disease
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
191
3
Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
extraintestinal symptoms (iron deficiency anemia, neurological problems, alterations in liver function tests, enamel defects and osteoporosis) to asymptomatic cases [3]. Also, the small intestinal lesions may range from epithelial lymphocyte infiltration with preserved villous architecture to severe villous atrophy [4]. The nutrition status at diagnosis depends mostly on the extent of the intestinal damage. The classic presentation is accompanied by steatorrhea and fatsoluble vitamin deficiency. Malabsorption of iron, calcium and folic acid is also frequent, as these are absorbed in the proximal small intestine [5]. The diagnostic approach has recently been revised [1]. Children found positive for CD-specific antibodies (anti-TG2, EMA and anti-DGP) should undergo duodenal biopsies unless certain conditions are fulfilled which allow the option to omit the confirmatory biopsies. In children and adolescents with signs or symptoms suggestive of CD and very high anti-TG2 (or anti-DGP) titers with levels exceeding 10 times the upper limit of normal, the likelihood for villous atrophy (Marsh score 3) is high. In this situation, the pediatric gastroenterologist may discuss with the parents and patient (as appropriate for the patient’s age) the option of performing further laboratory testing (EMA, HLA) in order to make the diagnosis of CD without biopsies. In the case of an asymp-
GFD is well established, so that possible adverse reactions can be readily identified by a strict clinical follow-up. There is a general consensus that all CD patients should be treated with a GFD irrespective of the presence of symptoms. However, while it is relatively easy to assess the health improvement after treatment of CD in patients with clinical symptoms of the disease, it proves difficult in persons with asymptomatic CD. A high rate of osteoporosis/osteopenia (60%) was observed in asymptomatic patients with villous atrophy; this finding suggests that, in CD, clinical tolerance does not reflect tolerance to gluten and that, in silent cases, the increased risk of osteoporosis substantiates the need for a GFD. There are no guidelines concerning the need for a GFD in subjects with ‘potential’ CD (patients with positive CD-associated serology but without enteropathy). Most of the ‘potential’ cases are left on gluten-containing diet and strictly monitored for the appearance of complications. While a risk of osteoporosis also for this group of patients has been reported in the past [7], no significant differences have recently been found between CD patients on a long-term GFD and ‘latent’ patients (patients with a clear previous diagnosis of CD and no clinical/histological relapse after a long period of GFD) as far as biological tests of malabsorption and the overall nutritional status, including bone mass density, are concerned. Similarly, we did not observe any major nutritional problem in our cohort of potential CD subjects [8].
Alternative Therapies
Compliance with GFD It is important that an experienced dietician with specific expertise in CD counseling educates the family and the child about dietary restrictions. An expert dietician should be consulted in order to evaluate the patient’s current nutritional status, to assess macronutrient and/or micronutrient intake, to detect deficiencies, to educate the patient to the GFD and to monitor dietary compliance. Compliance with a GFD can be difficult, especial-
Breeding programs and transgenic technology may lead to the production of wheat that is devoid of biologically active peptide sequences. Recently, new, alternative approaches to GFD have been investigated (table 2) [12]. As gliadin peptides are highly resistant to digestive processing, prolyl endopeptidase produced by probiotic microorganisms has been shown to promote digestion of gliadin. Clinical trials have already started. Other approaches include restoring intestinal permea-
Limits More information is needed on the daily gluten amount that may be tolerated by CD patients. The data available so far seem to suggest that, although individual variability makes it difficult to set a universal threshold, this should be set below 50 mg/day, a level unlikely to cause significant histological abnormalities. The regulations on the composition and labeling of food suitable for CD patients have recently changed. In 2008, the Codex Alimentarius revised the previous standard indicating 2 thresholds: 20 ppm for products to be labeled gluten free and 100 ppm for products with very low gluten content. The 20-ppm threshold is considered a safe option for CD patients, considering the overall consumption of gluten-free products [11].
Troncone Sarno Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
192
ly in adolescents [9]. It is recommended that children with CD be monitored with periodic visits for assessment of symptoms, growth, physical status and adherence to GFD. Periodic measurements of tissue TG antibody levels to document reductions in antibody titers can be helpful as indirect evidence of adherence to a GFD, although they are inaccurate in detecting slight dietary transgressions. Recently, methods based on the detection of a 33-mer gliadin peptide in feces have been proposed to assess compliance with the GFD [10].
1. Intraluminal therapies Wheat varieties (Ancient) wheat variants with low immunogenicity Genetically modified wheat variants or deletion lines of common wheat with lower immunogenicity Flour/dough treatment Pretreatment with lactobacilli Transamidation of gliadin Ingested gliadin peptide modifications Prolyl endopeptidases from Aspergillus niger or Sphingomonas capsulata Intraluminal gliadin binding by polymers 2. Transepitelial uptake Epithelial tight junctions ZOT receptor antagonist AT1001 3. Adaptive immune response TG2 TG inhibitors HLA-DQ2 Blocking DQ2 analogs 4. Immune modulators Gluten vaccination 5. Biologicals (T cell or cytokine blockers)
bility with anti-zonulin antibodies, preventing gliadin presentation to T cells by blocking HLA binding sites and the use of tissue TG inhibitors. The efficacy of these approaches needs to be assessed in more in vivo studies.
Prevention
Evidence suggests that the first months of life are crucial for CD development; breastfeeding has a protective role, and indeed there is a negative correlation between its duration and the development of CD. Moreover, the age at introduction of gluten to the diet is important: exposure to gluten in the first 3 months significantly increases the risk of CD in genetically susceptible individuals.
One study has suggested the existence of a window of opportunity as the late introduction of gluten to the diet (after the 7th month of life) has been found to be associated with a higher risk. On the basis of the present evidence, breastfeeding should be strongly encouraged and gluten should not be introduced before the 4th month of life, preferably while the baby is still breastfed [13]. Finally, increasing attention is being devoted to the possible role of viruses, which could trigger CD autoimmunity in genetically susceptible children by increasing intestinal permeability and activating innate immune pathways linked to CD pathophysiology.
Other Conditions Requiring GFD
The spectrum of gluten-related disorders also includes wheat allergy (WA) and nonceliac gluten sensitivity (NCGS). WA is defined as an adverse immunologic reaction to wheat proteins. Depending on the allergen exposure and the immunologic mechanisms, WA is classified into (1) classic food allergy affecting the skin, gastrointestinal tract or respiratory tract, (2) wheat-dependent, exercise-induced anaphylaxis, (3) occupational asthma (baker’s asthma) and rhinitis as well as (4) contact urticaria. IgE antibodies play a central role in the pathogenesis of these diseases. WA is treated by GFD, and the same limits as discussed for CD seem to apply to WA [14]. NCGS refers to individuals who show distress when eating gluten and improvement when following a GFD. CD autoantibodies are absent, the small intestine is usually normal, and allergy tests are negative. Thus, NCGS is a diagnosis by exclusion criteria. However, many suggest caution, as there is a noticeable lack of controlled studies unequivocally demonstrating the role of gluten. Other food components (fermentable oligo-, di- and monosaccharides and polyols or FODMAPs) have been suspected to be responsible for symptoms attributed to NCGS. Further caution is required due
Celiac Disease
Koletzko B, et al. (eds): Pediatric Nutrition in Practice. World Rev Nutr Diet. Basel, Karger, 2015, vol 113, pp 190–194 DOI: 10.1159/000367874
193
3
Downloaded by: Univ. of California San Diego 198.143.33.33 - 8/19/2015 4:44:31 AM
Table 2. Alternative therapies for CD
to the fact that unmotivated GFD is dangerous not only because of the costs imposed upon the community but also because it may affect the health of incorrectly classified patients [15].
Conclusions
• CD patients should be treated with GFD irrespective of the presence of symptoms. There is still uncertainty as to whether to treat ‘potential’ CD or not
• It is important that an experienced dietician with specific expertise educates the family and the child about dietary restrictions • It seems wise to add oats only when the GFD is well established, so that possible adverse reactions can be readily identified • The 20-ppm threshold is considered a safe option for CD patients • To prevent CD, breastfeeding should be strongly encouraged; gluten should not be introduced before the 4th month of life, preferably while the baby is still breastfed
References
194
5 Garcia-Manzanares A, Lucendo JA: Nutritional and dietary aspects of celiac disease. Nutr Clin Pract 2011;26:163– 173. 6 Pulido O, Gillespie Z, Zarkadas M, et al: Introduction of oats in the diet of individuals with celiac disease: a systematic review. Adv Food Nutr Res 2009;57: 235–285. 7 Kaukinen K, Mäki M, Partanen J, Sievänen H, Collin P: Celiac disease without villous atrophy: revision of criteria called for. Dig Dis Sci 2001;46:879–887. 8 Tosco A, Salvati VM, Auricchio R, Maglio M, Borrelli M, Coruzzo A, Paparo F, Boffardi M, Esposito A, D’Adamo G, Malamisura B, Greco L, Troncone R: Natural history of potential celiac disease in children. Clin Gastroenterol Hepatol 2011;9:320–325. 9 Errichiello S, Esposito O, Di Mase R, Camarca ME, Natale C, Limongelli MG, Marano C, Coruzzo A, Lombardo M, Strisciuglio P, Greco L: Celiac disease: predictors of compliance with a glutenfree diet in adolescents and young adults. J Pediatr Gastroenterol Nutr 2010;50:54–60. 10 Comino I, Real A, Vivas S, Síglez MÁ, Caminero A, Nistal E, Casqueiro J, Rodríguez-Herrera A, Cebolla A, Sousa C: Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr 2012;95:670–677.
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