eMedicine Specialties > Gastroenterology > Intestine

Celiac Sprue: Differential Diagnoses & Workup

Author: Jan-Michael A Klapproth, MD, Assistant Professor, Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine
Coauthor(s): Vincent W Yang, MD, PhD, R Bruce Logue Professor, Director, Division of Digestive Diseases, Department of Medicine, Professor of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine
Contributor Information and Disclosures

Updated: Sep 2, 2009

Differential Diagnoses

Bacterial Overgrowth Syndrome
Hypocalcemia
Collagenous and Lymphocytic Colitis
Hypokalemia
Crohn Disease
Hypomagnesemia
Cytomegalovirus
Hypothyroidism
Cytomegalovirus Colitis
Immunoglobulin A Deficiency
Eosinophilic Gastroenteritis
Inflammatory Bowel Disease
Gastroenteritis, Bacterial
Iron Deficiency Anemia
Gastroenteritis, Viral
Irritable Bowel Syndrome
Giardiasis
Malabsorption
Hypoalbuminemia
Protein-Losing Enteropathy

Other Problems to Be Considered

Enteropathy-type T-cell lymphoma
Jejunoileitis
Non-Hodgkin lymphoma

Workup

Laboratory Studies

  • Patients with diabetes mellitus type 1, Down syndrome, or Turner syndrome have an increased incidence of celiac disease.
  • Electrolytes and chemistries
    • Electrolyte imbalances, such as hypokalemia, hypocalcemia, hypomagnesemia, and metabolic acidosis, can develop.
    • Evidence of malnutrition, such as hypoalbuminemia, hypoproteinemia, hypocholesterolemia, and a low serum carotene level, might be present.
  • Hematologic tests  
    • Anemia due to deficiency in iron, folate, and, rarely, vitamin B-12 might be present.
    • A low serum iron level is common.
    • The prothrombin time (PT) might be prolonged because of malabsorption of vitamin K.
  • Stool examination  
    • The typical bulky, greasy appearance and rancid odor of stools often suggest malabsorption of fat.
    • Findings from a Sudan stain of the stool might reveal fat droplets.
    • For a more quantitative measurement of fat absorption, a 72-hour fecal fat collection is frequently helpful in documenting steatorrhea.
  • Oral tolerance tests  
    • Excretion of breath hydrogen, a product of bacterial fermentation of unabsorbed lactose, is often elevated in celiac sprue.
    • The oral D-xylose tolerance test can reveal carbohydrate malabsorption. D-xylose is absorbed preferentially in the proximal small intestine and excreted unmetabolized in the urine. In untreated celiac sprue, urinary D-xylose excretion and peak blood xylose levels are depressed.
    • Lactose tolerance is another oral tolerance test.
  • Serology 
    • The most sensitive and specific antibodies for the confirmation of celiac disease are tissue transglutaminase IgA, endomysial IgA, and reticulin IgA and correlate with the degree of mucosal damage. As the incidence of selective IgA deficiency is higher among patients with celiac disease, total IgA serum concentrations should be determined. If the patient is IgA deficient, tissue transglutaminase IgG can be measured.
    • The presence of serum IgA antibody to endomysium in untreated celiac sprue has higher sensitivity and higher specificity than antigliadin antibodies. However, serum IgA antiendomysial antibody often becomes undetectable after 6-12 months of gluten withdrawal. Persistently elevated IgA endomysial and tissue transglutaminase antibodies for 12 months usually indicate poor compliance with a gliadin-free diet.
    • Seronegative celiac disease has been reported in 6.4-9.1% of patients with normal IgA serum concentrations; however, these patients either were elderly or had severe disease.

Imaging Studies

  • Small bowel barium studies
    • Radiographic evaluation of the small bowel after barium ingestion is helpful in making a diagnosis of untreated celiac sprue.
    • Abnormal radiographic findings can include dilatation of the small intestine, a coarsening or obliteration of the normally delicate mucosal pattern, and fragmentation or flocculation of the barium in the gut lumen.

Procedures

  • Upper endoscopy with at least 6 duodenal biopsies is considered the criterion standard to help establish a diagnosis of celiac disease. Serology and endoscopy should be considered, especially in patients presenting with classical symptoms, evidence of malabsorption, and endoscopic findings, including mucosal fold scalloping, reduced mucosal folds, and mosaic pattern.

Histologic Findings

Celiac sprue primarily involves the mucosa of the small intestine. The submucosa, muscularis, and serosa are usually not involved. The villi are atrophic or absent with a decreased villous-to-crypt ratio (normal ratio, 4-5:1) and crypts are hyperplastic. The cellularity of the lamina propria is increased with a proliferation of plasma cells and lymphocytes. The number of intraepithelial lymphocytes per unit length of absorptive epithelium is increased (normal intraepithelial lymphocyte to epithelial cell ratio, 1:10).

Staging

Histologically, duodenal biopsies can be graded into the following 5 stages:

  • Stage 0 - Normal
  • Stage 1 - Increased percentage of intraepithelial lymphocytes (>30%)
  • Stage 2 - Characterized by an increased presence of inflammatory cells and crypt cell proliferation with preserved villous architecture
  • Stage 3 - Mild (A), moderate (B), and subtotal to total (C) villous atrophy
  • Stage 4 - Total mucosal hypoplasia

More on Celiac Sprue

Overview: Celiac Sprue
Differential Diagnoses & Workup: Celiac Sprue
Treatment & Medication: Celiac Sprue
Follow-up: Celiac Sprue
References
Further Reading
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References

  1. 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].

  2. Askling J, Linet M, Gridley G, et al. Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology. Nov 2002;123(5):1428-35. [Medline].

  3. Catassi C, Rätsch IM, Fabiani E, Rossini M, Bordicchia F, Candela F. Coeliac disease in the year 2000: exploring the iceberg. Lancet. Jan 22 1994;343(8891):200-3. [Medline].

  4. Collin P, Kaukinen K, Vogelsang H, et al. Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study. Eur J Gastroenterol Hepatol. Jan 2005;17(1):85-91. [Medline].

  5. Dieterich W, Ehnis T, Bauer M, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. Jul 1997;3(7):797-801. [Medline].

  6. Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med. Jan 17 2002;346(3):180-8. [Medline].

  7. 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. Feb 10 2003;163(3):286-92. [Medline].

  8. Ferguson A, Arranz E, O'Mahony S. Clinical and pathological spectrum of coeliac disease--active, silent, latent, potential. Gut. Feb 1993;34(2):150-1. [Medline].

  9. Godkin A, Jewell D. The pathogenesis of celiac disease. Gastroenterology. Jul 1998;115(1):206-10. [Medline].

  10. Greco L, Romino R, Coto I, et al. The first large population based twin study of coeliac disease. Gut. May 2002;50(5):624-8. [Medline].

  11. Green PH, Cellier C. Celiac disease. N Engl J Med. Oct 25 2007;357(17):1731-43. [Medline].

  12. Green PH, Jabri B. Coeliac disease. Lancet. Aug 2 2003;362(9381):383-91. [Medline].

  13. James MW, Scott BB. Coeliac disease: the cause of the various associated disorders?. Eur J Gastroenterol Hepatol. Sep 2001;13(9):1119-21. [Medline].

  14. Johnson TC, Diamond B, Memeo L, et al. Relationship of HLA-DQ8 and severity of celiac disease: comparison of New York and Parisian cohorts. Clin Gastroenterol Hepatol. Oct 2004;2(10):888-94. [Medline].

  15. Kagnoff MF. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Invest. Jan 2007;117(1):41-9. [Medline].

  16. Mention JJ, Ben Ahmed M, Begue B, et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology. Sep 2003;125(3):730-45. [Medline].

  17. Murray JA, Van Dyke C, Plevak MF, et al. Trends in the identification and clinical features of celiac disease in a North American community, 1950-2001. Clin Gastroenterol Hepatol. Jan 2003;1(1):19-27. [Medline].

  18. Murray JA, Van Dyke C, Plevak MF, et al. Trends in the identification and clinical features of celiac disease in a North American community, 1950-2001. Clin Gastroenterol Hepatol. Jan 2003;1(1):19-27. [Medline].

  19. Pietzak MM, Schofield TC, McGinniss MJ, Nakamura RM. Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles. Clin Gastroenterol Hepatol. Sep 2009;7(9):966-71. [Medline].

  20. Rashtak S, Murray JA. Celiac disease in the elderly. Gastroenterol Clin North Am. Sep 2009;38(3):433-46. [Medline].

  21. Rostami K, Malekzadeh R, Shahbazkhani B, et al. Coeliac disease in Middle Eastern countries: a challenge for the evolutionary history of this complex disorder?. Dig Liver Dis. Oct 2004;36(10):694-7. [Medline].

  22. 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].

  23. Salmi TT, Collin P, Korponay-Szabo IR, et al. Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits. Gut. Dec 2006;55(12):1746-53. [Medline].

  24. Sanders DS, Hurlstone DP, McAlindon ME, et al. Antibody negative coeliac disease presenting in elderly people--an easily missed diagnosis. BMJ. Apr 2 2005;330(7494):775-6. [Medline].

  25. Sategna-Guidetti C, Pulitanó R, Grosso S, et al. Serum IgA antiendomysium antibody titers as a marker of intestinal involvement and diet compliance in adult celiac sprue. J Clin Gastroenterol. Sep 1993;17(2):123-7. [Medline].

  26. Smedby KE, Akerman M, Hildebrand H, et al. Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut. Jan 2005;54(1):54-9. [Medline].

  27. Stojiljkovic V, Todorovic A, Pejic S, et al. Antioxidant status and lipid peroxidation in small intestinal mucosa of children with celiac disease. Clin Biochem. Sep 2009;42(13-14):1431-7. [Medline].

  28. Thompson T. National Institutes of Health consensus statement on celiac disease. J Am Diet Assoc. Feb 2005;105(2):194-5. [Medline].

  29. Trier JS. Diagnosis of celiac sprue. Gastroenterology. Jul 1998;115(1):211-6. [Medline].

  30. Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease. J Clin Gastroenterol. Mar 2003;36(3):219-21. [Medline].

  31. Yachha SK, Misra S, Malik AK, Nagi B, Mehta S. Spectrum of malabsorption syndrome in north Indian children. Indian J Gastroenterol. Oct 1993;12(4):120-5. [Medline].

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Further Reading

Related eMedicine Topics

Clinical Trials

National Guideline Clearinghouse

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Keywords

celiac sprue, celiac disease, gluten, gluten-sensitive enteropathy, coeliac disease, gluten allergy, food allergy, food allergies, gluten intolerance, gluten free diet, gluten-free diet, gliadin, gliadin free diet, gliadin-free diet, nontropical sprue, malabsorption, diarrhea, maldigestion

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Contributor Information and Disclosures

Author

Jan-Michael A Klapproth, MD, Assistant Professor, Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine
Jan-Michael A Klapproth, MD is a member of the following medical societies: American College of Gastroenterology, American Federation for Medical Research, American Gastroenterological Association, and Crohns and Colitis Foundation of America
Disclosure: Nothing to disclose.

Coauthor(s)

Vincent W Yang, MD, PhD, R Bruce Logue Professor, Director, Division of Digestive Diseases, Department of Medicine, Professor of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine
Vincent W Yang, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, American Society for Clinical Investigation, and Association of American Physicians
Disclosure: Nothing to disclose.

Medical Editor

Mounzer Al Al Samman, MD, Department of Internal Medicine, Division of Gastroenterology, Assistant Professor, Texas Tech University School of Medicine
Mounzer Al Al Samman, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine
James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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