eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Celiac Disease: Differential Diagnoses & Workup

Author: Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
Coauthor(s): Phyllis A Vallee, MD, Associate Program Director, Department of Emergency Medicine, Henry Ford Hospital
Contributor Information and Disclosures

Updated: Sep 2, 2009

Differential Diagnoses

Protein Intolerance

Workup

Laboratory Studies

  • Celiac disease (CD) is diagnosed as follows:
    • Duodenal mucosa histology changes are documented while on a gluten-containing diet and are characterized by a progressive deterioration of the villous architecture associated with a progressive increase in crypt length and density. Biopsy samples are now almost universally obtained by endoscopy. Multiple biopsy samples (at least 4) are recommended because celiac disease may be patchy and areas of villous atrophy may be adjacent to normal areas.16 Although endoscopically visible changes have been described (eg, scalloping or nodularity of the mucosa, sparse duodenal folds), such changes are neither constant nor specific, and a diagnosis of celiac disease should never be based on their presence or absence.
    • The clinical and laboratory response to a gluten-free diet is documented. In particular, the positive autoantibodies (anti-tTG or antiendomysium antibodies) must progressively normalize.
  • Substantial agreement is observed between the evidence-based guidelines introduced in 2005 by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and those published by the American Gastroenterological Association (AGA) in 2006.17,18  Both describe the diagnostic approach in great detail. In part, these guidelines follow previous, only partially evidence-based guidelines proposed by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) in 1990.19
  • The role of serology in the diagnosis of celiac disease is as follows:
    • In clinical practice, serologic tests for celiac disease are useful in identifying children who require intestinal biopsy findings to diagnose the condition. In addition, these serologic test findings are supportive of the diagnosis in those with characteristic histopathologic features of celiac disease on small intestinal biopsy findings and may have a role in monitoring response to treatment.
    • Numerous serologic tests are now commercially available.
    • Sensitivities and specificities for the antigliadin tests widely vary. Immunoglobulin (Ig)G-based antigliadin (AGA) tests are generally poor in both parameters, whereas the IgA-based test was poorly sensitive but more specific. Using AGA testing to screening for celiac disease is not currently recommended. The variability and generally lower accuracy associated with the AGA tests make them unsuitable for screening purposes; however, they can be used to monitor dietetic compliance because they are known to react more promptly to dietary transgression.
    • The IgA endomysium (EMA-IgA) and tissue transglutaminase (TTG-IgA) tests are both highly sensitive and highly specific, with values for both parameters exceeding 96% in most studies. No identifiable differences between adults and children are noted with respect to these tests.

Imaging Studies

  • Radiography of the GI tract with a barium swallow study and a small intestinal follow-through may show nonspecific changes because of the mucosal inflammation and possible concomitant protein-losing enteropathy (edema of the bowel walls, dispersion of the barium column).
  • The findings are clearly nonspecific, and radiographic investigation is not indicated.

Procedures

  • Most centers today include diagnostic duodenal biopsy during esophagogastroduodenoscopy (EGD). Obtaining at least 4 biopsy samples from the bulb and from the distal duodenum is highly recommended because mucosal changes in celiac disease may be patchy.
  • Colonoscopy may be indicated if bloody stools are reported or if symptoms of colitis are also present.

Histologic Findings

Mucosal biopsy of the duodenum shows the changes described above.

  • However, changes referred to as Marsh 1 or even Marsh 2 are nonspecific because they can also be found in food-allergic enteropathies, such as cow's milk allergy or soy allergy (especially in infancy). 
  • These changes are also observed in giardiasis and in autoimmune enteropathy.
  • Although also not pathognomonic for celiac disease, changes referred to as Marsh 3 are usually much more specific, especially if they are associated with supportive serology findings.
  • Evidence suggests that patients with Marsh type 1 changes who have a positive serology findings may develop more severe changes if they continue a gluten-containing diet; this challenges the idea that celiac disease is only observed in those who have more advanced findings.20

More on Celiac Disease

Overview: Celiac Disease
Differential Diagnoses & Workup: Celiac Disease
Treatment & Medication: Celiac Disease
Follow-up: Celiac Disease
Multimedia: Celiac Disease
References
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References

  1. Guandalini S, Setty M. Celiac disease. Curr Opin Gastroenterol. Nov 2008;24(6):707-12. [Medline].

  2. [Best Evidence] Rubio-Tapia A, Kyle RA, Kaplan EL, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology. Jul 2009;137(1):88-93. [Medline].

  3. Tang F, Chen Z, Ciszewski C, et al. Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15. J Exp Med. Feb 23 2009;[Medline].

  4. Marsh MN, Hinde J. Inflammatory component of celiac sprue mucosa. I. Mast cells, basophils, and eosinophils. Gastroenterology. Jul 1985;89(1):92-101. [Medline].

  5. Catassi C, Kryszak D, Louis-Jacques O, et al. Detection of Celiac disease in primary care: a multicenter case-finding study in North America. Am J Gastroenterol. Jul 2007;102(7):1454-60. [Medline].

  6. Lohi S, Mustalahti K, Kaukinen K, Laurila K, Collin P, Rissanen H, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther. Nov 1 2007;26(9):1217-25. [Medline].

  7. Kondrashova A, Mustalahti K, Kaukinen K, Viskari H, Volodicheva V, Haapala AM, et al. Lower economic status and inferior hygienic environment may protect against celiac disease. Ann Med. 2008;40(3):223-31. [Medline].

  8. Catassi C, Cobellis G. Coeliac disease epidemiology is alive and kicking, especially in the developing world. Dig Liver Dis. Oct 2007;39(10):908-10. [Medline].

  9. Silano M, Volta U, Vincenzi AD, Dessì M, Vincenzi MD. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci. Apr 2008;53(4):972-6. [Medline].

  10. Metzger MH, Heier M, Maki M, et al. Mortality excess in individuals with elevated IgA anti-transglutaminase antibodies: the KORA/MONICA Augsburg cohort study 1989-1998. Eur J Epidemiol. 2006;21(5):359-65. [Medline].

  11. Guandalini S, ed. Celiac Disease. In. Textbook of Pediatric Gastroenterology and Nutrition. London: Taylor & Francis;. 2004: 435-50.

  12. Pope R, Sheiner E. Celiac disease during pregnancy: to screen or not to screen?. Arch Gynecol Obstet. Jan 2009;279(1):1-3. [Medline].

  13. Akobeng AK, Ramanan AV, Buchan I, Heller RF. Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Arch Dis Child. Jan 2006;91(1):39-43. [Medline].

  14. Olsson C, Hernell O, Hornell A, Lonnberg G, Ivarsson A. Difference in celiac disease risk between Swedish birth cohorts suggests an opportunity for primary prevention. Pediatrics. Sep 2008;122(3):528-34. [Medline].

  15. Troncone R, Auricchio S. Rotavirus and celiac disease: clues to the pathogenesis and perspectives on prevention. J Pediatr Gastroenterol Nutr. May 2007;44(5):527-8. [Medline].

  16. Bonamico M, Mariani P, Thanasi E, et al. Patchy villous atrophy of the duodenum in childhood celiac disease. J Pediatr Gastroenterol Nutr. Feb 2004;38(2):204-7. [Medline].

  17. Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. Dec 2006;131(6):1981-2002. [Medline].

  18. [Guideline] Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. Jan 2005;40(1):1-19. [Medline].

  19. Walker-Smith JA, Guandalini S, Schmitz J, Shmerling DH, Visakorpi JK. Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child. 1990;65:909-911. [Medline].

  20. Kurppa K, Collin P, Viljamaa M, et al. Diagnosing mild enteropathy celiac disease: a randomized, controlled clinical study. Gastroenterology. Mar 2009;136(3):816-23. [Medline].

  21. [Best Evidence] Akobeng AK, Thomas AG. Systematic review: tolerable amount of gluten for people with coeliac disease. Aliment Pharmacol Ther. Jun 1 2008;27(11):1044-52. [Medline].

  22. Leffler DA, Dennis M, Edwards GJ, et al. A Simple Validated Gluten-Free Diet Adherence Survey for Adults With Celiac Disease. Clin Gastroenterol Hepatol. Jan 11 2009;[Medline].

  23. University of Chicago Celiac Disease Center. Available at www.celiacdisease.net.

  24. Isselbacher KJ, Braunwald E, Wilson JD. Harrison's Principles of Internal Medicine. 13th ed. New York, NY: McGraw Hill; 1994:1398-400.

  25. McCance KL, Huether SE. Pathophysiology: The Biologic Basis for Disease in Adults and Children. St Louis, MO: Mosby; 1990:1277-80.

  26. Saltzman JR, Russell RM. The aging gut. Nutritional issues. Gastroenterol Clin North Am. Jun 1998;27(2):309-24. [Medline].

  27. USP. United States Pharmacopeial Convention: Drug Information (USP DI) for the Health Care Professional. 16th ed. Rockville, MD: United States Pharmacopeial Convention; 1996:978-95.

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Further Reading

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Keywords

celiac sprue, celiac disease, gluten-sensitive enteropathy, nontropical sprue, wheat, potbelly, rye, barley, osteopenia, osteoporosis, short stature, delayed puberty, anemia, intestinal T-cell lymphoma, diarrhea, abdominal distension, malnutrition, celiac crisis, explosive watery diarrhea, dehydration, hypotension, hypokalemia, constipation, failure to thrive, dermatitis herpetiformis, dental enamel hypoplasia, iron-deficiency anemia, chronic hepatitis, hypertransaminasemia, arthritis, arthralgia, Down syndrome, Williams syndrome, Turner syndrome, diabetes mellitus type 1, alopecia, thyroiditis, rotavirus

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Contributor Information and Disclosures

Author

Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Coauthor(s)

Phyllis A Vallee, MD, Associate Program Director, Department of Emergency Medicine, Henry Ford Hospital
Phyllis A Vallee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, and Michigan State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Jorge H Vargas, MD, Professor of Pediatrics and Clinical Professor of Pediatric Gastroenterology, David Geffen School of Medicine, University of California at Los Angeles; Consulting Physician, Department of Pediatrics, University of California at Los Angeles Health System
Jorge H Vargas, MD is a member of the following medical societies: American Liver Foundation, American Society for Gastrointestinal Endoscopy, American Society for Parenteral and Enteral Nutrition, Latin American Society of Pediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

 
 
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