Skip to main content

Advertisement

SpringerLink
Log in

Extraintestinal manifestations of celiac disease

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Celiac disease is an autoimmune disorder that occurs in genetically predisposed individuals as the result of an immune response to gluten. It is present in approximately 1% of the population. Diarrhea has become a less common mode of presentation (< 50% of cases) than it once was. Other presentations include iron-deficiency anemia, osteoporosis, dermatitis herpetiforme, and neurologic disorders, mainly peripheral neuropathy and ataxia. Arthritis is commonly found in patients with celiac disease when systematically sought. Overall, autoimmune diseases occur more frequently (three to ten times more) in those with celiac disease than in the general population. A gluten-free diet is the standard of treatment, although its effect on some of the extraintestinal manifestations remains to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Louka AS, Sollid LM: HLA in coeliac disease: unravelling the complex genetics of a complex disorder. Tissue Antigens 2003, 61:105–117. A valuable review of the mechanism of disease.

    Article  PubMed  CAS  Google Scholar 

  2. Bingley PJ, Williams AJ, Norcross AJ, et al.: Undiagnosed coeliac disease at age seven: population based prospective birth cohort study. BMJ 2004, 328:322–323.

    Article  PubMed  Google Scholar 

  3. Fasano A, Berti I, Gerarduzzi T, et al.: Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003, 163:286–292. The first study showing prevalence of celiac disease in the United States.

    Article  PubMed  Google Scholar 

  4. Green PHR, Stavropoulos SN, Panagi SG, et al.: Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol 2001, 96:126–131. Describes clinical features of celiac disease in the adult US population.

    Article  PubMed  Google Scholar 

  5. Rostom A, Dube C, Cranney A, et al.: The diagnostic accuracy of serologic tests for celiac disease: A systematic review. Gastroenterology 2005, 128:S38-S46. A valuable comprehensive review.

    Article  PubMed  Google Scholar 

  6. Abrams JA, Brar P, Diamond B, et al.: Utility in clinical practice of immunoglobulin anti-tissue transglutaminase antibody for the diagnosis of celiac disease. Clin Gastroenterol Hepatol 2006, 4:726–730.

    Article  PubMed  CAS  Google Scholar 

  7. Rampertab SD, Pooran N, Brar P, et al.: Trends in the presentation of celiac disease. Am J Med 2006, 119:355:9–14.

    Google Scholar 

  8. Green PH, Alaedini A, Sander HW, et al.: Mechanisms underlying celiac disease and its neurologic manifestations. Cell Mol Life Sci 2005, 62:791–799.

    Article  PubMed  CAS  Google Scholar 

  9. Cicarelli G, Della Rocca G, Amboni M, et al.: Clinical and neurological abnormalities in adult celiac disease. Neurol Sci 2003, 24:311–317.

    Article  PubMed  CAS  Google Scholar 

  10. Pynnonen PA, Isometsa ET, Aronen ET, et al.: Mental disorders in adolescents with celiac disease. Psychosomatics 2004, 45:325–335.

    Article  PubMed  Google Scholar 

  11. Zelnik N, Pacht A, Obeid R, Lerner: Range of neurologic disorders in patients with celiac disease. Pediatrics 2004, 113:1572–1676.

    Article  Google Scholar 

  12. Chapman RW, Laidlow JM, Colin-Jones D, et al.: Increased prevalence of epilepsy in coeliac disease. BMJ 1978, 2:250–251.

    PubMed  CAS  Google Scholar 

  13. Hadjivassiliou M, Grunewald RA, Davies-Jones GA: Idiopathic cerebellar ataxia associated with celiac disease: lack of distinctive neurological features. J Neurol Neurosurg Psychiatry 1999, 67:257.

    PubMed  CAS  Google Scholar 

  14. Pellecchia MT, Scala R, Perretti A, et al.: Cerebellar ataxia associated with subclinical celiac disease responding to gluten-free diet. Neurology 1999, 53:1606–1608.

    PubMed  CAS  Google Scholar 

  15. Hadjivassiliou M, Maki M, Sanders DS, et al.: Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia. Neurology 2006, 66:373–377.

    Article  PubMed  CAS  Google Scholar 

  16. Sander HW, Magda P, Chin RL, et al.: Cerebellar ataxia and coeliac disease. Lancet 2003, 362:1548.

    Article  PubMed  Google Scholar 

  17. Chin RL, Sander HW, Brannagan TH, et al.: Celiac neuropathy. Neurology 2003, 60:1581–1585.

    PubMed  CAS  Google Scholar 

  18. Brannagan TH III, Hays AP, Chin SS, et al.: Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings. Arch Neurol 2005, 62:1574–1578.

    Article  PubMed  Google Scholar 

  19. Alaedini A, Green PH, Sander HW, et al.: Ganglioside reactive antibodies in the neuropathy associated with celiac disease. J Neuroimmunol 2002, 127:145–148.

    Article  PubMed  CAS  Google Scholar 

  20. Dalgic B, Dursun I, Serdaroglu A, Dursun A: Latent and potential celiac disease in epileptic Turkish children. J Child Neurol 2006, 21:6–7.

    PubMed  Google Scholar 

  21. Pengiran Tengah DS, Holmes GK, Wills AJ: The prevalence of epilepsy in patients with celiac disease. Epilepsia 2004, 45:1291–1293.

    Article  Google Scholar 

  22. Mavroudi A, Karatza E, Papastavrou T, et al.: Successful treatment of epilepsy and celiac disease with a gluten-free diet. Pediatr Neurol 2005, 33(4):292–295.

    Article  PubMed  Google Scholar 

  23. Gobbi G, Bouquet F, Greco L, et al.: Coeliac disease, epilepsy, and cerebral calcifications. The Italian Working Group on Coeliac Disease and Epilepsy. Lancet 1992, 340:439–443.

    Article  PubMed  CAS  Google Scholar 

  24. Gabrielli M, Cremonini F, Fiore G, et al.: Association between migraine and celiac disease: results from a preliminary case-control and therapeutic study. Am J Gastroenterol 2003, 98:625–629.

    Article  PubMed  Google Scholar 

  25. Zelnik N, Pacht A, Obeid R, Lerner A: Range of neurologic disorders in patients with celiac disease. Pediatrics 2004, 113:1672–1676.

    Article  PubMed  Google Scholar 

  26. Siniscalchi M, Iovino P, Tortora R, et al.: Fatigue in adult coeliac disease. Aliment Pharmacol Ther 2005, 22:489–494.

    Article  PubMed  CAS  Google Scholar 

  27. Carta MG, Hardoy MC, Usai P, et al.: Recurrent brief depression in celiac disease. J Psychosom Res 2003, 55:573–574.

    Article  PubMed  Google Scholar 

  28. Eaton W, Mortensen PB, Agerbo E, et al.: Coeliac disease and schizophrenia: population based case control study with linkage of Danish national registers. BMJ 2004, 328:438–439.

    Article  PubMed  Google Scholar 

  29. Pynnonen PA, Isometsa ET, Verkasalo MA, et al.: Untreated celiac disease and development of mental disorders in children and adolescents. Psychosomatics 2002, 43:331–334.

    Article  PubMed  Google Scholar 

  30. Verkasalo MA, Raitakari OT, Viikari J, et al.: Undiagnosed silent coeliac disease: A risk for underachievement? Scand J Gastroenterol 2005, 40:1407–1412.

    Article  PubMed  Google Scholar 

  31. Lo W, Sano K, Lebwohl B, et al.: Changing presentation of adult celiac disease. Dig Dis Sci 2003, 48:395–398.

    Article  PubMed  Google Scholar 

  32. Oxentenko AS, Grisolano SW, Murray JA, et al.: The insensitivity of endoscopic markers in celiac disease. Am J Gastroenterol 2002, 97:933–938.

    Article  PubMed  Google Scholar 

  33. Karnam US, Felder LR, Raskin JB: Prevalence of occult celiac disease in patients with iron-deficiency anemia: a prospective study. South Med J 2004, 97:30–34.

    Article  PubMed  Google Scholar 

  34. Kosnai I, Kuitunen P, Siimes MA: Iron deficiency in children with coeliac disease on treatment with gluten-free diet. Role of intestinal blood loss. Arch Dis Child 1979, 54:375–378.

    PubMed  CAS  Google Scholar 

  35. Mant MJ, Bain VG, Maguire CG, et al.: Prevalence of occult gastrointestinal bleeding in celiac disease. Clin Gastroenterol Hepatol 2006, 4:451–454.

    Article  PubMed  Google Scholar 

  36. Logan RF, Howarth GF, West J, et al.: How often is a positive faecal occult blood test the result of coeliac disease? Eur J Gastroenterol Hepatol 2003, 15(10):1097–1100.

    Article  PubMed  Google Scholar 

  37. Annibale B, Severi C, Chistolini A, et al.: Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients. Am J Gastroenterol 2001, 96:132–137.

    Article  PubMed  CAS  Google Scholar 

  38. Dickey W: Low serum vitamin B12 is common in coeliac disease and is not due to autoimmune gastritis. Eur J Gastroenterol Hepatol 2002, 14:425–427.

    Article  PubMed  CAS  Google Scholar 

  39. Di Sabatino A, Rosado MM, Cazzola P, et al.: Splenic hypofunction and the spectrum of autoimmune and malignant complications in celiac disease. Clin Gastroenterol Hepatol 2006, 4:179–186.

    Article  PubMed  Google Scholar 

  40. Hervonen K, Vornanen M, Kautiainen H, et al.: Lymphoma in patients with dermatitis herpetiformis and their firstdegree relatives. Br J Dermatol 2005, 152:82–86.

    Article  PubMed  CAS  Google Scholar 

  41. Smecuol E, Sugai E, Niveloni S, et al.: Permeability, zonulin production, and enteropathy in dermatitis herpetiformis. Clin Gastroenterol Hepatol 2005, 3:335–341.

    Article  PubMed  Google Scholar 

  42. Ojetti V, Aguilar Sanchez J, Guerriero C, et al.: High prevalence of celiac disease in psoriasis. Am J Gastroenterol 2003, 98:2574–2575.

    Article  PubMed  CAS  Google Scholar 

  43. Zone JJ: Skin manifestations of celiac disease. Gastroenterology 2005, 128:S87-S91.

    Article  PubMed  Google Scholar 

  44. Corazza GR, Andreani ML, Venturo N, et al.: Celiac disease and alopecia areata: report of a new association. Gastroenterology 1995, 109:1333–1337.

    Article  PubMed  CAS  Google Scholar 

  45. Bardella MT, Marino R, Barbareschi M, et al.: Alopecia areata and coeliac disease: no effect of a gluten-free diet on hair growth. Dermatology 2000, 200:108–110.

    Article  PubMed  CAS  Google Scholar 

  46. Meneghetti R, Gerarduzzi T, Barbi E, Ventura A: Chronic urticaria and coeliac disease. Arch Dis Child 2004, 89:293.

    Article  PubMed  CAS  Google Scholar 

  47. Patinen P, Aine L, Collin P, et al.: Oral findings in coeliac disease and Sjogren’s syndrome. Oral Dis 2004, 10:330–334.

    Article  PubMed  CAS  Google Scholar 

  48. Aine L: Permanent tooth dental enamel defects leading to the diagnosis of coeliac disease. Br Dent J 1994, 177:253–254.

    Article  PubMed  CAS  Google Scholar 

  49. Finizio M, Quaremba G, Mazzacca G, Ciacci C: Large forehead: a novel sign of undiagnosed coeliac disease. 2005 37:659–664.

    CAS  Google Scholar 

  50. Dickey W, McMillan SA, Collins JS, et al.: Liver abnormalities associated with celiac sprue. How common are they, what is their significance, and what do we do about them? J Clin Gastroenterol 1995, 20:290–292.

    Article  PubMed  CAS  Google Scholar 

  51. Volta U, De Franceschi L, Lari F, et al.: Coeliac disease hidden by cryptogenic hypertransaminasaemia. Lancet 1998, 352:26–29.

    Article  PubMed  CAS  Google Scholar 

  52. Lawson A, West J, Aithal GP, Logan RF: Autoimmune cholestatic liver disease in people with coeliac disease: a population-based study of their association. Aliment Pharmacol Ther 2005, 21:401–405.

    Article  PubMed  CAS  Google Scholar 

  53. Kaukinen K, Halme L, Collin P, et al.: Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure. Gastroenterology 2002, 122:881–888.

    Article  PubMed  Google Scholar 

  54. Rabsztyn A, Green PH, Berti I, et al.: Macroamylasemia in patients with celiac disease. Am J Gastroenterol 2001, 96:1096–1100.

    Article  PubMed  CAS  Google Scholar 

  55. Ciacci C, Cirillo M, Giorgetti G, et al.: Low plasma cholesterol: a correlate of nondiagnosed celiac disease in adults with hypochromic anemia. Am J Gastroenterol 1999, 94:1888–1891.

    Article  PubMed  CAS  Google Scholar 

  56. Bai D, Brar P, Holleran S, et al.: Effect of gender on the manifestations of celiac disease: evidence for greater malabsorption in men. Scand J Gastroenterol 2005, 40:183–187.

    Article  PubMed  Google Scholar 

  57. Brar P, Kwon G, Holleran S, et al.: Change in lipid profile in celiac disease: beneficial effect of gluten free diet. Am J Medicine, 2006, in press.

  58. Meyer D, Stavropolous S, Diamond B, et al.: Osteoporosis in a north american adult population with celiac disease. Am J Gastroenterol 2001, 96:112–119.

    PubMed  CAS  Google Scholar 

  59. Stenson WF, Newberry R, Lorenz R, et al.: Increased prevalence of celiac disease and need for routine screening among patients with osteoporosis. Arch Intern Med 2005, 165:393–399.

    Article  PubMed  Google Scholar 

  60. Sanders DS, Patel D, Khan FB, et al.: Case-finding for adult celiac disease in patients with reduced bone mineral density. Dig Dis Sci 2005, 50:587–592.

    Article  PubMed  Google Scholar 

  61. Gonzalez D, Sugai E, Gomez JC, et al.: Is it necessary to screen for celiac disease in postmenopausal osteoporotic women? Calcif Tissue Int 2002, 71:141–144.

    Article  PubMed  CAS  Google Scholar 

  62. Lubrano E, Ciacci C, Ames PR, et al.: The arthritis of coeliac disease: prevalence and pattern in 200 adult patients. Br J Rheumatol 1996, 35:1314–1318.

    Article  PubMed  CAS  Google Scholar 

  63. Luft LM, Barr SG, Martin LO, et al.: Autoantibodies to tissue transglutaminase in Sjogren’s syndrome and related rheumatic diseases. J Rheumatol 2003, 30:2613–2619.

    PubMed  CAS  Google Scholar 

  64. Rensch MJ, Szyjkowski R, Shaffer RT, et al.: The prevalence of celiac disease autoantibodies in patients with systemic lupus erythematosus. Am J Gastroenterol 2001, 96:1113–1115.

    Article  PubMed  CAS  Google Scholar 

  65. Sategna Guidetti C, Solerio E, Scaglione N, et al.: Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders. Gut 2001, 49:502–505.

    Article  Google Scholar 

  66. Dickey W, McMillan SA, Callender ME: High prevalence of celiac sprue among patients with primary biliary cirrhosis. J Clin Gastroenterol 1997, 25:328–329.

    Article  PubMed  CAS  Google Scholar 

  67. Talal AH, Murray JA, Goeken JA, Sivitz WI: Celiac disease in an adult population with insulin-dependent diabetes mellitus: use of endomysial antibody testing. Am J Gastroenterol 1997, 92:1280–1284.

    PubMed  CAS  Google Scholar 

  68. Iltanen S, Collin P, Korpela M, et al.: Celiac disease and markers of celiac disease latency in patients with primary Sjogren’s syndrome. Am J Gastroenterol 1999, 94:1042–1046.

    PubMed  CAS  Google Scholar 

  69. O’Leary C, Walsh CH, Wieneke P, et al.: Coeliac disease and autoimmune Addison’s disease: a clinical pitfall. QJM 2002, 95:79–82.

    Article  PubMed  CAS  Google Scholar 

  70. Fonager K, Sorensen HT, Norgard B, Thulstrup AM: Cardiomyopathy in Danish patients with coeliac disease. Lancet 1999, 354:1561.

    Article  PubMed  CAS  Google Scholar 

  71. Frustaci A, Cuoco L, Chimenti C, et al.: Celiac disease associated with autoimmune myocarditis. Circulation 2002, 105:2611–2618.

    Article  PubMed  Google Scholar 

  72. Gasbarrini A, Torre ES, Trivellini C, et al.: Recurrent spontaneous abortion and intrauterine fetal growth retardation as symptoms of coeliac disease. Lancet 2000, 356:399–400.

    Article  PubMed  CAS  Google Scholar 

  73. Kolho KL, Tiitinen A, Tulppala M, et al.: Screening for coeliac disease in women with a history of recurrent miscarriage or infertility. Br J Obstet Gynaecol 1999, 106:171–173.

    PubMed  CAS  Google Scholar 

  74. Sher KS, Jayanthi V, Probert CS, et al.: Infertility, obstetric and gynaecological problems in coeliac sprue. Dig Dis 1994, 12:186–190.

    PubMed  CAS  Google Scholar 

  75. Lee SK, Green PH: Celiac sprue (the great modern-day imposter). Curr Opin Rheumatol 2006, 18:101–107.

    Article  PubMed  Google Scholar 

  76. Curione M, Barbato M, De Biase L, et al.: Prevalence of coeliac disease in idiopathic dilated cardiomyopathy. Lancet 1999, 354:222–223.

    Article  PubMed  CAS  Google Scholar 

  77. Gillett HR, Cauch-Dudek K, Jenny E, et al.: Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis. Can J Gastroenterol 2000, 14:672–675.

    PubMed  CAS  Google Scholar 

  78. Volta U, De Franceschi L, Molinaro N, et al.: Frequency and significance of anti-gliadin and anti-endomysial antibodies in autoimmune hepatitis. Dig Dis Sci 1998, 43:2190–2195.

    Article  PubMed  CAS  Google Scholar 

  79. Sjoberg K, Lindgren S, Eriksson S: Frequent occurrence of non-specific gliadin antibodies in chronic liver disease. Endomysial but not gliadin antibodies predict coeliac disease in patients with chronic liver disease. Scand J Gastroenterol 1997, 32:1162–1167.

    Article  PubMed  CAS  Google Scholar 

  80. Lepore L, Martelossi S, Pennesi M, et al.: Prevalence of celiac disease in patients with juvenile chronic arthritis. J Pediatr 1996, 129:311–313.

    Article  PubMed  CAS  Google Scholar 

  81. Bonamico M, Bottaro G, Pasquino AM, et al.: Celiac disease and Turner syndrome. J Pediatr Gastroenterol Nutr 1998, 26:496–499.

    Article  PubMed  CAS  Google Scholar 

  82. Agardh D, Nilsson A, Carlsson A, et al.: Tissue transglutaminase autoantibodies and human leucocyte antigen in Down’s syndrome patients with coeliac disease. Acta Paediatr 2002, 91:34–38.

    Article  PubMed  CAS  Google Scholar 

  83. Ventura A, Martelossi S: Dental enamel defects and coeliac disease. Arch Dis Child 1997, 77:91.

    Article  PubMed  CAS  Google Scholar 

  84. Rutherford RM, Brutsche MH, Kearns M, et al.: Prevalence of coeliac disease in patients with sarcoidosis. Eur J Gastroenterol Hepatol 2004, 16:911–915.

    Article  PubMed  Google Scholar 

  85. Patel RS, Johlin FC Jr, Murray JA: Celiac disease and recurrent pancreatitis. Gastrointest Endosc 1999, 50:823–827.

    Article  PubMed  CAS  Google Scholar 

  86. Yang A, Chen Y, Scherl E, et al.: Inflammatory bowel disease in patients with celiac disease. Inflammatory Bowel Dis 2005, 11:528–532.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Columbia University College of Physicians and Surgeons, Harkness Pavillion, 180 Fort Washington Avenue, Suite 936, 10032, New York, NY, USA

    Peter H. Green MD

Authors
  1. Lincoln Hernandez MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter H. Green MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter H. Green MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hernandez, L., Green, P.H. Extraintestinal manifestations of celiac disease. Curr Gastroenterol Rep 8, 383–389 (2006). https://doi.org/10.1007/s11894-006-0023-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-006-0023-7

Keywords

Search

Navigation