Skip to main content
SpringerLink
Log in

A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies

Clinical Reviews in Allergy & Immunology volume 57, pages 226–243 (2019)Cite this article

Abstract

Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and “at risk” populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease. Simple algorithms for care based on a comprehensive multidisciplinary approach are proposed. Refractory and non-responsive celiac diseases in the setting of a gluten-free diet are examined as are novel non-dietary therapies. Finally, the association of other disease states including psychiatric illness, infertility, lymphoproliferative malignancy, and mortality is explored with special attention paid to autoimmune and atopic disease.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Dowd B, Walker-Smith J (1974) Samuel Gee, Aretaeus, and the coeliac affection. Br Med J 2(5909):45–47

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Yan D, Holt PR (2009) Willem Dicke. Brilliant clinical observer and translational investigator. Discoverer of the toxic cause of celiac disease. Clin Transl Sci 2(6):446–448

    PubMed  PubMed Central  Google Scholar 

  3. Meeuwisse GW (1970) Round table discussion. Diagnostic criteria in coeliac disease. Acta Paediatr 59:461–463

    Google Scholar 

  4. Ludvigsson JF, Leffler DA, Bai JC, Biagi F, Fasano A, Green PHR, Hadjivassiliou M, Kaukinen K, Kelly CP, Leonard JN, Lundin KEA, Murray JA, Sanders DS, Walker MM, Zingone F, Ciacci C (2013) The Oslo definitions for coeliac disease and related terms. Gut 62(1):43–52

    PubMed  Google Scholar 

  5. van Heel DA et al (2007) A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat Genet 39(7):827–829

    PubMed  PubMed Central  Google Scholar 

  6. Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, de Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Cartenì M, Riegler G, de Magistris L, Fasano A (2011) Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med 9:23

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Potter M, Walker MM, Talley NJ (2017) Non-coeliac gluten or wheat sensitivity: emerging disease or misdiagnosis? Med J Aust 207(5):211–215

    PubMed  Google Scholar 

  8. DiGiacomo DV, Tennyson CA, Green PH, Demmer RT (2013) Prevalence of gluten-free diet adherence among individuals without celiac disease in the USA: results from the continuous National Health and Nutrition Examination Survey 2009-2010. Scand J Gastroenterol 48(8):921–925

    PubMed  Google Scholar 

  9. Skodje GI, et al. (2017) Fructan, rather than gluten, induces symptoms in patients with self-reported non-celiac gluten sensitivity. Gastroenterology

  10. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR (2013) No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 145(2):320–8 e1–3

    CAS  PubMed  Google Scholar 

  11. Aziz I, Peerally MF, Barnes JH, Kandasamy V, Whiteley JC, Partridge D, Vergani P, Cross SS, Green PH, Sanders DS (2017) The clinical and phenotypical assessment of seronegative villous atrophy; a prospective UK centre experience evaluating 200 adult cases over a 15-year period (2000-2015). Gut 66(9):1563–1572

    CAS  PubMed  Google Scholar 

  12. Silano M, Vincentini O, De Vincenzi M (2009) Toxic, immunostimulatory and antagonist gluten peptides in celiac disease. Curr Med Chem 16(12):1489–1498

    CAS  PubMed  Google Scholar 

  13. Shan L, Molberg Ø, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C (2002) Structural basis for gluten intolerance in celiac sprue. Science 297(5590):2275–2279

    CAS  PubMed  Google Scholar 

  14. Matysiak-Budnik T, Moura IC, Arcos-Fajardo M, Lebreton C, Ménard S, Candalh C, Ben-Khalifa K, Dugave C, Tamouza H, van Niel G, Bouhnik Y, Lamarque D, Chaussade S, Malamut G, Cellier C, Cerf-Bensussan N, Monteiro RC, Heyman M (2008) Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J Exp Med 205(1):143–154

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Visser J, Rozing J, Sapone A, Lammers K, Fasano A (2009) Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci 1165:195–205

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Leonard MM, Sapone A, Catassi C, Fasano A (2017) Celiac disease and nonceliac gluten sensitivity: a review. JAMA 318(7):647–656

    PubMed  Google Scholar 

  17. Picarelli A et al (1999) 31-43 amino acid sequence of the alpha-gliadin induces anti-endomysial antibody production during in vitro challenge. Scand J Gastroenterol 34(11):1099–1102

    CAS  PubMed  Google Scholar 

  18. Nilsen EM, Jahnsen FL, Lundin KEA, Johansen F–E, Fausa O, Sollid LM, Jahnsen J, Scott H, Brandtzaeg P (1998) Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology 115(3):551–563

    CAS  PubMed  Google Scholar 

  19. Hadjivassiliou M, Aeschlimann P, Sanders DS, Maki M, Kaukinen K, Grunewald RA, Bandmann O, Woodroofe N, Haddock G, Aeschlimann DP (2013) Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology 80(19):1740–1745

    CAS  PubMed  Google Scholar 

  20. Taylor TB, Schmidt LA, Meyer LJ, Zone JJ (2015) Transglutaminase 3 present in the IgA aggregates in dermatitis herpetiformis skin is enzymatically active and binds soluble fibrinogen. J Investig Dermatol 135(2):623–625

    CAS  PubMed  Google Scholar 

  21. Abadie V, Jabri B (2014) IL-15: a central regulator of celiac disease immunopathology. Immunol Rev 260(1):221–234

    CAS  PubMed  Google Scholar 

  22. Liu E, Lee HS, Aronsson CA, Hagopian WA, Koletzko S, Rewers MJ, Eisenbarth GS, Bingley PJ, Bonifacio E, Simell V, Agardh D, TEDDY Study Group (2014) Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med 371(1):42–49

    PubMed  Google Scholar 

  23. Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, Thorsby E, Sollid LM (1993) Gliadin-specific, HLA-DQ(alpha 1*0501,beta 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med 178(1):187–196

    CAS  PubMed  Google Scholar 

  24. Karell K, Louka AS, Moodie SJ, Ascher H, Clot F, Greco L, Ciclitira PJ, Sollid LM, Partanen J, European Genetics Cluster on Celiac Disease (2003) 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 64(4):469–477

    CAS  PubMed  Google Scholar 

  25. Trynka G et al (2011) Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat Genet 43(12):1193–1201

    CAS  PubMed  Google Scholar 

  26. Katz KD, Rashtak S, Lahr BD, Melton LJ, Krause PK, Maggi K, Talley NJ, Murray JA (2011) Screening for celiac disease in a North American population: sequential serology and gastrointestinal symptoms. Am J Gastroenterol 106(7):1333–1339

    PubMed  Google Scholar 

  27. Rubio-Tapia A et al (2009) Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology 137(1):88–93

    PubMed  PubMed Central  Google Scholar 

  28. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PHR, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K (2003) Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 163(3):286–292

    PubMed  Google Scholar 

  29. Ivarsson A, Myleus A, Norstrom F, van der Pals M, Rosen A, Hogberg L, Danielsson L, Halvarsson B, Hammarroth S, Hernell O, Karlsson E, Stenhammar L, Webb C, Sandstrom O, Carlsson A (2013) Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics 131(3):e687–e694

    PubMed  Google Scholar 

  30. Kuja-Halkola R, Lebwohl B, Halfvarson J, Wijmenga C, Magnusson PKE, Ludvigsson JF (2016) Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins. Gut 65(11):1793–1798

    PubMed  Google Scholar 

  31. Nistico L et al (2006) Concordance, disease progression, and heritability of coeliac disease in Italian twins. Gut 55(6):803–808

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Marild K et al (2017) Maternal and neonatal vitamin D status, genotype and childhood celiac disease. PLoS One 12(7):e0179080

    PubMed  PubMed Central  Google Scholar 

  33. Vriezinga SL, Auricchio R, Bravi E, Castillejo G, Chmielewska A, Crespo Escobar P, Kolaček S, Koletzko S, Korponay-Szabo IR, Mummert E, Polanco I, Putter H, Ribes-Koninckx C, Shamir R, Szajewska H, Werkstetter K, Greco L, Gyimesi J, Hartman C, Hogen Esch C, Hopman E, Ivarsson A, Koltai T, Koning F, Martinez-Ojinaga E, te Marvelde C, Pavic A, Romanos J, Stoopman E, Villanacci V, Wijmenga C, Troncone R, Mearin ML (2014) Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med 371(14):1304–1315

    CAS  PubMed  Google Scholar 

  34. Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, Barbato M, Barbera C, Barera G, Bellantoni A, Castellano E, Guariso G, Limongelli MG, Pellegrino S, Polloni C, Ughi C, Zuin G, Fasano A, Catassi C, SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk (2014) Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med 371(14):1295–1303

    PubMed  Google Scholar 

  35. Lebwohl B, Blaser MJ, Ludvigsson JF, Green PHR, Rundle A, Sonnenberg A, Genta RM (2013) Decreased risk of celiac disease in patients with Helicobacter pylori colonization. Am J Epidemiol 178(12):1721–1730

    PubMed  PubMed Central  Google Scholar 

  36. Whyte LA, Kotecha S, Watkins WJ, Jenkins HR (2014) Coeliac disease is more common in children with high socio-economic status. Acta Paediatr 103(3):289–294

    CAS  PubMed  Google Scholar 

  37. Oza SS, Akbari M, Kelly CP, Hansen J, Theethira T, Tariq S, Dennis M, Leffler DA (2016) Socioeconomic risk factors for celiac disease burden and symptoms. J Clin Gastroenterol 50(4):307–312

    PubMed  Google Scholar 

  38. Marild K et al (2015) Infections and risk of celiac disease in childhood: a prospective nationwide cohort study. Am J Gastroenterol 110(10):1475–1484

    PubMed  Google Scholar 

  39. Kemppainen KM, Lynch KF, Liu E, Lönnrot M, Simell V, Briese T, Koletzko S, Hagopian W, Rewers M, She JX, Simell O, Toppari J, Ziegler AG, Akolkar B, Krischer JP, Lernmark Å, Hyöty H, Triplett EW, Agardh D, TEDDY Study Group (2017) Factors that increase risk of celiac disease autoimmunity after a gastrointestinal infection in early life. Clin Gastroenterol Hepatol 15(5):694–702 e5

    PubMed  Google Scholar 

  40. Riddle MS, Murray JA, Cash BD, Pimentel M, Porter CK (2013) Pathogen-specific risk of celiac disease following bacterial causes of foodborne illness: a retrospective cohort study. Dig Dis Sci 58(11):3242–3245

    PubMed  Google Scholar 

  41. Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, Emery L, Taki I, Norris JM, Erlich HA, Eisenbarth GS, Rewers M (2006) Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol 101(10):2333–2340

    CAS  PubMed  Google Scholar 

  42. Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA, Costes LMM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S, McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker HC, Kupfer SS, Guandalini S, Semrad CE, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A, Dermody TS, Jabri B (2017) Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science 356(6333):44–50

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Walker WA (2013) Initial intestinal colonization in the human infant and immune homeostasis. Ann Nutr Metab 63(Suppl 2):8–15

    CAS  PubMed  Google Scholar 

  44. Sanchez E et al (2011) Influence of environmental and genetic factors linked to celiac disease risk on infant gut colonization by Bacteroides species. Appl Environ Microbiol 77(15):5316–5323

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L (2014) Long term effect of gut microbiota transfer on diabetes development. J Autoimmun 53:85–94

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, Troncone R, Giersiepen K, Branski D, Catassi C, Lelgeman M, Mäki M, Ribes-Koninckx C, Ventura A, Zimmer KP, ESPGHAN Working Group on Coeliac Disease Diagnosis, ESPGHAN Gastroenterology Committee, European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2012) European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 54(1):136–160

    CAS  PubMed  Google Scholar 

  47. Rubio-Tapia A, Ludvigsson JF, Brantner TL, Murray JA, Everhart JE (2012) The prevalence of celiac disease in the United States. Am J Gastroenterol 107(10):1538–1544 quiz 1537, 1545

    PubMed  Google Scholar 

  48. Gasbarrini G, Miele L, Malandrino N, Grieco A, Addolorato G, Gasbarrini A, Cammarota G, Bonvicini F (2009) Celiac disease in the 21st century: issues of under- and over-diagnosis. Int J Immunopathol Pharmacol 22(1):1–7

    CAS  PubMed  Google Scholar 

  49. Hagopian W, Lee HS, Liu E, Rewers M, She JX, Ziegler AG, Lernmark Å, Toppari J, Rich SS, Krischer JP, Erlich H, Akolkar B, Agardh D, the TEDDY Study Group (2017) Co-occurrence of type 1 diabetes and celiac disease autoimmunity. Pediatrics 140(5):e20171305

    PubMed  PubMed Central  Google Scholar 

  50. Choung RS, Ditah IC, Nadeau AM, Rubio-Tapia A, Marietta EV, Brantner TL, Camilleri MJ, Rajkumar SV, Landgren O, Everhart JE, Murray JA (2015) Trends and racial/ethnic disparities in gluten-sensitive problems in the United States: findings from the National Health and Nutrition Examination Surveys from 1988 to 2012. Am J Gastroenterol 110(3):455–461

    PubMed  Google Scholar 

  51. Mardini HE, Westgate P, Grigorian AY (2015) Racial differences in the prevalence of celiac disease in the US population: National Health and Nutrition Examination Survey (NHANES) 2009-2012. Dig Dis Sci 60(6):1738–1742

    PubMed  Google Scholar 

  52. Mustalahti K, Catassi C, Reunanen A, Fabiani E, Heier M, McMillan S, Murray L, Metzger MH, Gasparin M, Bravi E, Mäki M, the members of the Coeliac EU Cluster, Epidemiology (2010) The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med 42(8):587–595

    PubMed  Google Scholar 

  53. Ramakrishna BS, Makharia GK, Chetri K, Dutta S, Mathur P, Ahuja V, Amarchand R, Balamurugan R, Chowdhury SD, Daniel D, Das A, George G, Gupta SD, Krishnan A, Prasad JH, Kaur G, Pugazhendhi S, Pulimood A, Ramakrishna K, Verma AK (2016) Prevalence of adult celiac disease in India: regional variations and associations. Am J Gastroenterol 111(1):115–123

    CAS  PubMed  Google Scholar 

  54. Unalp-Arida A, Ruhl CE, Choung RS, Brantner TL, Murray JA (2017) Lower prevalence of celiac disease and gluten-related disorders in persons living in southern vs northern latitudes of the United States. Gastroenterology 152(8):1922–1932 e2

    PubMed  PubMed Central  Google Scholar 

  55. Volta U, Caio G, Stanghellini V, de Giorgio R (2014) The changing clinical profile of celiac disease: a 15-year experience (1998-2012) in an Italian referral center. BMC Gastroenterol 14:194

    PubMed  PubMed Central  Google Scholar 

  56. Kalkan, C., F. Karakaya, and I. Soykan (2017) Similarities and differences between older and young adult patients with celiac disease. Geriatr Gerontol Int

  57. Vivas S, Ruiz de Morales JM, Fernandez M, Hernando M, Herrero B, Casqueiro J, Gutierrez S (2008) Age-related clinical, serological, and histopathological features of celiac disease. Am J Gastroenterol 103(9):2360–2365 quiz 2366

    PubMed  Google Scholar 

  58. Reilly NR, Aguilar K, Hassid BG, Cheng J, Defelice AR, Kazlow P, Bhagat G, Green PH (2011) Celiac disease in normal-weight and overweight children: clinical features and growth outcomes following a gluten-free diet. J Pediatr Gastroenterol Nutr 53(5):528–531

    PubMed  Google Scholar 

  59. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA, American College of Gastroenterology (2013) ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 108(5):656–676 quiz 677

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Casella S, Zanini B, Lanzarotto F, Villanacci V, Ricci C, Lanzini A (2012) Celiac disease in elderly adults: clinical, serological, and histological characteristics and the effect of a gluten-free diet. J Am Geriatr Soc 60(6):1064–1069

    PubMed  Google Scholar 

  61. Rashtak S, Ettore MW, Homburger HA, Murray JA (2008) Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin Gastroenterol Hepatol 6(4):426–432 quiz 370

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Lee SK, Green PH (2005) Endoscopy in celiac disease. Curr Opin Gastroenterol 21(5):589–594

    PubMed  Google Scholar 

  63. Kivela L, Kurppa K (2017) USPSTF celiac disease screening recommendations. J Pediatr 188:308–311

    PubMed  Google Scholar 

  64. Hadithi M, von Blomberg B, Crusius JB, Bloemena E, Kostense PJ, Meijer JW, Mulder CJ, Stehouwer CD, Peña AS (2007) Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Ann Intern Med 147(5):294–302

    PubMed  Google Scholar 

  65. Frost AR, Band MM, Conway GS (2009) Serological screening for coeliac disease in adults with Turner’s syndrome: prevalence and clinical significance of endomysium antibody positivity. Eur J Endocrinol 160(4):675–679

    CAS  PubMed  Google Scholar 

  66. Lenhardt A, Plebani A, Marchetti F, Gerarduzzi T, Not T, Meini A, Villanacci V, Martelossi S, Ventura A (2004) Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency. Dig Liver Dis 36(11):730–734

    CAS  PubMed  Google Scholar 

  67. Rubio-Tapia A et al (2008) Predictors of family risk for celiac disease: a population-based study. Clin Gastroenterol Hepatol 6(9):983–987

    PubMed  PubMed Central  Google Scholar 

  68. Sattar N, Lazare F, Kacer M, Aguayo-Figueroa L, Desikan V, Garcia M, Lane A, Chawla A, Wilson T (2011) Celiac disease in children, adolescents, and young adults with autoimmune thyroid disease. J Pediatr 158(2):272–5 e1

    PubMed  Google Scholar 

  69. Volta U, Tovoli F, Caio G (2011) Clinical and immunological features of celiac disease in patients with type 1 diabetes mellitus. Expert Rev Gastroenterol Hepatol 5(4):479–487

    CAS  PubMed  Google Scholar 

  70. Wouters J, Weijerman ME, van Furth AM, Schreurs MWJ, Crusius JBA, von Blomberg BME, de Baaij LR, Broers CJM, Gemke RJBJ (2009) Prospective human leukocyte antigen, endomysium immunoglobulin A antibodies, and transglutaminase antibodies testing for celiac disease in children with Down syndrome. J Pediatr 154(2):239–242

    CAS  PubMed  Google Scholar 

  71. Deora V, Aylward N, Sokoro AR, el-Matary W (2017) Serum vitamins and minerals at diagnosis and follow-up in children with celiac disease. J Pediatr Gastroenterol Nutr 65(2):185–189

    CAS  PubMed  Google Scholar 

  72. Alwitry A (2000) Vitamin A deficiency in coeliac disease. Br J Ophthalmol 84(9):1079–1080

    CAS  PubMed  Google Scholar 

  73. Abdalla A, Saifullah SM, Osman M, Baniya R, Sidahmed S, LaChance J, Bachuwa G (2017) Prevalence of occult celiac disease in females with iron deficiency in the United States: an NHANES analysis. J Community Hosp Intern Med Perspect 7(6):347–350

    PubMed  PubMed Central  Google Scholar 

  74. Beniwal N, Ameta G, Chahar CK (2017) Celiac disease in children with severe acute malnutrition (SAM): a hospital based study. Indian J Pediatr 84(5):339–343

    PubMed  Google Scholar 

  75. Collin P, Salmi TT, Hervonen K, Kaukinen K, Reunala T (2017) Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med 49(1):23–31

    CAS  PubMed  Google Scholar 

  76. Dohan FC (1983) More on celiac disease as a model for schizophrenia. Biol Psychiatry 18(5):561–564

    CAS  PubMed  Google Scholar 

  77. Ross-Smith P, Jenner FA (1980) Diet (gluten) and schizophrenia. J Hum Nutr 34(2):107–112

    CAS  PubMed  Google Scholar 

  78. West J et al (2006) Risk of schizophrenia in people with coeliac disease, ulcerative colitis and Crohn’s disease: a general population-based study. Aliment Pharmacol Ther 23(1):71–74

    CAS  PubMed  Google Scholar 

  79. Hauser W et al (2010) Anxiety and depression in adult patients with celiac disease on a gluten-free diet. World J Gastroenterol 16(22):2780–2787

    PubMed  PubMed Central  Google Scholar 

  80. Carta MG, Hardoy MC, Boi MF, Mariotti S, Carpiniello B, Usai P (2002) Association between panic disorder, major depressive disorder and celiac disease: a possible role of thyroid autoimmunity. J Psychosom Res 53(3):789–793

    PubMed  Google Scholar 

  81. Zylberberg HM, Demmer RT, Murray JA, Green PHR, Lebwohl B (2017) Depression and insomnia among individuals with celiac disease or on a gluten-free diet in the USA: results from a national survey. Eur J Gastroenterol Hepatol 29(9):1091–1096

    PubMed  PubMed Central  Google Scholar 

  82. Fasano A, Sapone A, Zevallos V, Schuppan D (2015) Nonceliac gluten sensitivity. Gastroenterology 148(6):1195–1204

    CAS  PubMed  Google Scholar 

  83. Janatuinen EK, Kemppainen TA, Julkunen RJ, Kosma VM, Mäki M, Heikkinen M, Uusitupa MI (2002) No harm from five year ingestion of oats in coeliac disease. Gut 50(3):332–335

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Thompson T (2004) Gluten contamination of commercial oat products in the United States. N Engl J Med 351(19):2021–2022

    CAS  PubMed  Google Scholar 

  85. Lee AR, Ng DL, Zivin J, Green PHR (2007) Economic burden of a gluten-free diet. J Hum Nutr Diet 20(5):423–430

    CAS  PubMed  Google Scholar 

  86. Panagiotou S, Kontogianni M (2016) The weekly economic burden of a gluten-free diet. Clin Nutr ESPEN 13:e56

    Google Scholar 

  87. Shah S, Akbari M, Vanga R, Kelly CP, Hansen J, Theethira T, Tariq S, Dennis M, Leffler DA (2014) Patient perception of treatment burden is high in celiac disease compared with other common conditions. Am J Gastroenterol 109(9):1304–1311

    PubMed  PubMed Central  Google Scholar 

  88. Murray JA, Kelly CP, Green PHR, Marcantonio A, Wu TT, Mäki M, Adelman DC, Ansari S, Ayub K, Basile A, Behrend C, Bercik P, Bressler B, Byrnes V, Chandan VS, Cheekati V, Chipps B, Coates A, Collatrella A, Condemi J, Corder C, Corren J, Curtis C, DeMeo M, Desta T, Devereaux C, DiMarino A, DuPree M, Ennis C, Fedorak R, Fogel R, Freeman S, Freilich B, Friedenberg K, Geenen D, Gill K, Goldsobel A, Goldstein J, Goldstein M, Gordon G, Hardi R, Harris L, Holmes R, Jagarlamundi K, James G, Kaplan M, Kirstein J, Knoll A, Kotfila R, Krause R, Kravitz A, Kreines M, Lähdeaho ML, Lamet M, Laskin K, Lebwohl B, Leffler D, Lewis S, Liakos S, Lundin K, Marks K, Merkes K, Minton S, Moussa S, Narayen V, Nehra V, Newton E, Nyberg A, Oosthuizen J, Otrok T, Patel D, Pepin C, Phillips R, Pyle G, Reichelderfer M, Reid B, Ritter T, Saini S, Sanders D, Schulman M, Semrad C, Shah S, Stockwell D, Strout C, Suez D, Tatum H, Torbenson MS, Turner M, Varunok P, Vazquez-Roque M, Vento A, Welton T, Wohlman R, Wood M, Woods S, Yousef K (2017) No difference between latiglutenase and placebo in reducing villous atrophy or improving symptoms in patients with symptomatic celiac disease. Gastroenterology 152(4):787–798 e2

    CAS  PubMed  Google Scholar 

  89. Syage JA, Murray JA, Green PHR, Khosla C (2017) Latiglutenase improves symptoms in seropositive celiac disease patients while on a gluten-free diet. Dig Dis Sci 62:2428–2432

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Leffler DA, Kelly CP, Green PHR, Fedorak RN, DiMarino A, Perrow W, Rasmussen H, Wang C, Bercik P, Bachir NM, Murray JA (2015) Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology 148(7):1311–9 e6

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Szaflarska-Poplawska A (2015) Non-dietary methods in the treatment of celiac disease. Prz Gastroenterol 10(1):12–17

    PubMed  PubMed Central  Google Scholar 

  92. Leffler DA, Dennis M, Hyett B, Kelly E, Schuppan D, Kelly CP (2007) Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol 5(4):445–450

    PubMed  Google Scholar 

  93. Roshan B, Leffler DA, Jamma S, Dennis M, Sheth S, Falchuk K, Najarian R, Goldsmith J, Tariq S, Schuppan D, Kelly CP (2011) The incidence and clinical spectrum of refractory celiac disease in a north american referral center. Am J Gastroenterol 106(5):923–928

    PubMed  Google Scholar 

  94. Burkhardt JG, Chapa-Rodriguez A, Bahna SL (2017) Gluten sensitivities and the allergist: threshing the grain from the husks. Allergy

  95. Pillon R, Ziberna F, Badina L, Ventura A, Longo G, Quaglia S, de Leo L, Vatta S, Martelossi S, Patano G, Not T, Berti I (2015) Prevalence of celiac disease in patients with severe food allergy. Allergy 70(10):1346–1349

    CAS  PubMed  Google Scholar 

  96. Pallav K, Xu H, Leffler DA, Kabbani T, Kelly CP (2016) Immunoglobulin A deficiency in celiac disease in the United States. J Gastroenterol Hepatol 31(1):133–137

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Venhoff N, Emmerich F, Neagu M, Salzer U, Koehn C, Driever S, Kreisel W, Rizzi M, Effelsberg NM, Kollert F, Goldacker S, Voll RE, Warnatz K, Thiel J (2013) The role of HLA DQ2 and DQ8 in dissecting celiac-like disease in common variable immunodeficiency. J Clin Immunol 33(5):909–916

    CAS  PubMed  Google Scholar 

  98. Jorgensen SF et al (2016) A cross-sectional study of the prevalence of gastrointestinal symptoms and pathology in patients with common variable immunodeficiency. Am J Gastroenterol 111(10):1467–1475

    PubMed  Google Scholar 

  99. Denham JM, Hill ID (2013) Celiac disease and autoimmunity: review and controversies. Curr Allergy Asthma Rep 13(4):347–353

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Ress K, Annus T, Putnik U, Luts K, Uibo R, Uibo O (2014) Celiac disease in children with atopic dermatitis. Pediatr Dermatol 31(4):483–488

    PubMed  Google Scholar 

  101. Enroth S, Dahlbom I, Hansson T, Johansson Å, Gyllensten U (2013) Prevalence and sensitization of atopic allergy and coeliac disease in the Northern Sweden Population Health Study. Int J Circumpolar Health. 72

  102. Peroni DG et al (2010) Chronic urticaria and celiac disease: a case report. Pediatr Dermatol 27(1):108–109

    PubMed  Google Scholar 

  103. Mery A (2004) Celiac disease presenting as urticaria. Allergy Asthma Proc 25(2):97–99

    PubMed  Google Scholar 

  104. Ciacci C, Cavallaro R, Iovino P, Sabbatini F, Palumbo A, Amoruso D, Tortora R, Mazzacca G (2004) Allergy prevalence in adult celiac disease. J Allergy Clin Immunol 113(6):1199–1203

    PubMed  Google Scholar 

  105. Assa A, Frenkel-Nir Y, Tzur D, Katz LH, Shamir R (2017) Large population study shows that adolescents with celiac disease have an increased risk of multiple autoimmune and nonautoimmune comorbidities. Acta Paediatr 106(6):967–972

    CAS  PubMed  Google Scholar 

  106. Ludvigsson JF, Hemminki K, Wahlström J, Almqvist C (2011) Celiac disease confers a 1.6-fold increased risk of asthma: a nationwide population-based cohort study. J Allergy Clin Immunol 127(4):1071–1073

    PubMed  Google Scholar 

  107. Hommeida S, Alsawas M, Murad MH, Katzka DA, Grothe RM, Absah I (2017) The association between celiac disease and eosinophilic esophagitis: Mayo experience and meta-analysis of the literature. J Pediatr Gastroenterol Nutr 65(1):58–63

    PubMed  Google Scholar 

  108. Johnson JB, Boynton KK, Peterson KA (2016) Co-occurrence of eosinophilic esophagitis and potential/probable celiac disease in an adult cohort: a possible association with implications for clinical practice. Dis Esophagus 29(8):977–982

    CAS  PubMed  Google Scholar 

  109. Dharmaraj R, Hagglund K, Lyons H (2015) Eosinophilic esophagitis associated with celiac disease in children. BMC Res Notes 8:263

    PubMed  Google Scholar 

  110. Jensen ET, Eluri S, Lebwohl B, Genta RM, Dellon ES (2015) Increased risk of esophageal eosinophilia and eosinophilic esophagitis in patients with active celiac disease on biopsy. Clin Gastroenterol Hepatol 13(8):1426–1431

    PubMed  PubMed Central  Google Scholar 

  111. Ari A, Morgenstern S, Chodick G, Matar M, Silbermintz A, Assa A, Mozer-Glassberg Y, Rinawi F, Nachmias-Friedler V, Shamir R, Zevit N (2017) Oesophageal eosinophilia in children with coeliac disease. Arch Dis Child 102(9):825–829

    PubMed  Google Scholar 

  112. Dhalwani NN et al (2014) Women with celiac disease present with fertility problems no more often than women in the general population. Gastroenterology 147(6):1267–74 e1 quiz e13–4

    PubMed  Google Scholar 

  113. Zugna D, Richiardi L, Akre O, Stephansson O, Ludvigsson JF (2010) A nationwide population-based study to determine whether coeliac disease is associated with infertility. Gut 59(11):1471–1475

    PubMed  Google Scholar 

  114. Tata LJ, Card TR, Logan RFA, Hubbard RB, Smith CJP, West J (2005) Fertility and pregnancy-related events in women with celiac disease: a population-based cohort study. Gastroenterology 128(4):849–855

    CAS  PubMed  Google Scholar 

  115. Askling J, Linet M, Gridley G, Halstensen TS, Ekström K, Ekbom A (2002) Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology 123(5):1428–1435

    PubMed  Google Scholar 

  116. Catassi C, Fabiani E, Corrao G, Barbato M, de Renzo A, Carella AM, Gabrielli A, Leoni P, Carroccio A, Baldassarre M, Bertolani P, Caramaschi P, Sozzi M, Guariso G, Volta U, Corazza GR, Italian Working Group on Coeliac Disease and Non-Hodgkin’s-Lymphoma (2002) Risk of non-Hodgkin lymphoma in celiac disease. JAMA 287(11):1413–1419

    PubMed  Google Scholar 

  117. Green PH et al (2003) Risk of malignancy in patients with celiac disease. Am J Med 115(3):191–195

    PubMed  Google Scholar 

  118. Smedby KE, Akerman M, Hildebrand H, Glimelius B, Ekbom A, Askling J (2005) Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut 54(1):54–59

    CAS  PubMed  PubMed Central  Google Scholar 

  119. West J, Logan RFA, Smith CJ, Hubbard RB, Card TR (2004) Malignancy and mortality in people with coeliac disease: population based cohort study. BMJ 329(7468):716–719

    PubMed  PubMed Central  Google Scholar 

  120. Ilus T, Kaukinen K, Virta LJ, Pukkala E, Collin P (2014) Incidence of malignancies in diagnosed celiac patients: a population-based estimate. Am J Gastroenterol 109(9):1471–1477

    PubMed  Google Scholar 

  121. Lebwohl B, Granath F, Ekbom A, Smedby KE, Murray JA, Neugut AI, Green PHR, Ludvigsson JF (2013) Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 159(3):169–175

    PubMed  PubMed Central  Google Scholar 

  122. Elfstrom P, Granath F, Ekstrom Smedby K, Montgomery SM, Askling J, Ekbom A, Ludvigsson JF (2011) Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease. J Natl Cancer Inst 103(5):436–444

    PubMed  Google Scholar 

  123. Tio M, Cox MR, Eslick GD (2012) Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy. Aliment Pharmacol Ther 35(5):540–551

    CAS  PubMed  Google Scholar 

  124. Abdul Sultan A, Crooks CJ, Card T, Tata LJ, Fleming KM, West J (2015) Causes of death in people with coeliac disease in England compared with the general population: a competing risk analysis. Gut 64(8):1220–1226

    PubMed  Google Scholar 

  125. Godfrey JD, Brantner TL, Brinjikji W, Christensen KN, Brogan DL, van Dyke CT, Lahr BD, Larson JJ, Rubio–Tapia A, Melton LJ III, Zinsmeister AR, Kyle RA, Murray JA (2010) Morbidity and mortality among older individuals with undiagnosed celiac disease. Gastroenterology 139(3):763–769

    PubMed  PubMed Central  Google Scholar 

  126. Zanini B, Lanzarotto F, Mora A, Bertolazzi S, Turini D, Cesana B, Donato F, Ricci C, Lonati F, Vassallo F, Scarcella C, Lanzini A (2010) Five year time course of celiac disease serology during gluten free diet: results of a community based “CD-Watch” program. Dig Liver Dis 42(12):865–870

    PubMed  Google Scholar 

  127. Rubio-Tapia A, Rahim MW, See JA, Lahr BD, Wu TT, Murray JA (2010) Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. Am J Gastroenterol 105(6):1412–1420

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Wahab PJ, Meijer JW, Mulder CJ (2002) Histologic follow-up of people with celiac disease on a gluten-free diet: slow and incomplete recovery. Am J Clin Pathol 118(3):459–463

    PubMed  Google Scholar 

  129. Kalayci AG, Kansu A, Girgin N, Kucuk O, Aras G (2001) Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood. Pediatrics 108(5):E89

    CAS  PubMed  Google Scholar 

  130. McFarlane XA, Bhalla AK, Robertson DA (1996) Effect of a gluten free diet on osteopenia in adults with newly diagnosed coeliac disease. Gut 39(2):180–184

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Kemppainen TA, Heikkinen MT, Ristikankare MK, Kosma VM, Julkunen RJ (2010) Nutrient intakes during diets including unkilned and large amounts of oats in celiac disease. Eur J Clin Nutr 64(1):62–67

    CAS  PubMed  Google Scholar 

  132. Kamycheva E, Goto T, Camargo CA Jr (2017) Blood levels of lead and mercury and celiac disease seropositivity: the US National Health and Nutrition Examination Survey. Environ Sci Pollut Res Int 24(9):8385–8391

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, Mail Code HU33, 500 University Drive, UPC Suite 2400, Hershey, PA, 17033-0850, USA

    Brian P. McAllister, Emmanuelle Williams & Kofi Clarke

Authors
  1. Brian P. McAllister
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emmanuelle Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kofi Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kofi Clarke.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest. However, for full disclosure, Dr. Clarke is on the speakers bureau for AbbVie, Takeda, and Janssen. In addition, he has served on an Ad Board for Pfizer.

Ethical Approval and Informed Consent

This is a review article, no patients were involved and informed consent was not required. Permission was obtained for all images used and appropriate attribution/acknowledgement stated.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McAllister, B.P., Williams, E. & Clarke, K. A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies. Clinic Rev Allerg Immunol 57, 226–243 (2019). https://doi.org/10.1007/s12016-018-8691-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-018-8691-2

Keywords

search

Navigation