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Why Celiac Disease is So Easy to Miss

Clinician Reviews. 2014 September;24(9):508-513

References

1. Sanders L. Hurt all over. New York Times Sunday Magazine. November 11, 2011:MM22.

2. Rubio-Tapia A, Ludvigsson JF, Brantner TL, et al. The prevalence of celiac disease in the United States. Am J Gastroenterol. 2012;107:1538-1544.

3. Fasano A, Catassi C. Clinical practice. Celiac disease. N Engl J Med. 2012;367:2419-2426.

4. Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357: 1731-1743.

5. 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.

6. Mustalahti K, Catassi C, Reunanen A, et al; Coeliac EU Cluster, Project Epidemiology. The prevalence of celiac disease in Europe: results of centralized, international mass screening project. Ann Med. 2010;42:587-595.

7. Farrel R, Kelly C. Celiac disease and refractory celiac disease. In: Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 9th ed. Philadelphia, PA: Saunders; 2010: 1797-1820.

8. Gujral N, Freeman HJ, Thomson Ab. Celiac disease: prevalence, diagnosis, pathogenesis and treatment. World J Gastroenterol. 2012;18:6036-6059.

9. Sleisenger MH. Diseases of malabsorption. In: Beeson PB, McDermott W. Cecil-Loeb Textbook of Medicine. 13th ed. Philadelphia, PA: WB Saunders Company; 1971:1285-1291.

10. Reilly NR, Green PH. Epidemiology and clinical presentations of celiac disease. Sem Immunopathol. 2012;34:473-478.

11. Kagnoff MF. Celiac disease. A gastrointestinal disease with environmental, genetic, and immunologic components. Gastroenterol Clin North Am. 1992;21:405-425.

12. Riddle MS, Murray JA, Porter CK. The incidence and risk of celiac disease in a healthy US adult population. Am J Gastroenterol. 2012;107:1248-1255.

13. Rampertab SD, Pooran N, Brar P, et al. Trends in the presentation of celiac disease. Am J Med. 2006;119:355.e9-355.e14.

14. Pietzak M. Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad. JPEN J Parenter Enteral Nutr. 2012;36(1 suppl):68S-75S.

15. Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012;10:13.

16. Rubio-Tapia A, Hill ID, Kelly CP, et al; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management celiac disease. Am J Gastroenterol. 2013;108:656-676.

17. Hill ID, Dirks MH, Liptak GS, et al; North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Guidelines for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroentertol Nutr. 2005;40:1-19.

18. Husby S, Koletsko S, Korponay-Szabó IR, et al; ESPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastoenterology 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.

19. Catassi C, Fasano A. Celiac disease diagnosis: simple rules are better than complicated algorithms. Am J Med. 2010;123:691-693.

20. US Food and Drug Administration. Foods labeled gluten-free must now meet FDA's definition. Available at: http://www.fda. gov/Food/NewsEvents/ConstituentUpdates/ucm407867.htm. Accessed August 13, 2014.

21. National Institutes of Health Consensus Development Conference on Celiac Disease. National Institutes of Health Consensus Development Conference Statement. Available at: http://consensus.nih.gov/2004/2004celiacdisease118html.htm. Accessed August 13, 2014.

22. Norris JM, Barriga K, Hoffenberg EJ, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA. 2005;293:2343-2351. 

23. Pozo-Rubio T, Olivares M, Nova E, et al. Immune development and intestinal microbiota in celiac disease. Clin Dev Immunol. 2012;2012:654143

24. Ivarsson A, Myléus A, Norström F, et al. Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics. 2013;131:687-694. 

25. Cataldo F, Montalto G. Celiac disease in the developing countries: a new and challenging public health problem. World J Gastroenterol. 2007;13:2153-2159.

The only proven treatment:  A gluten-free diet

Non-celiac gluten sensitivity is a distinct condition in which the body reacts adversely to gluten; it is not an autoimmune disease with an inflammatory response.Lifelong adherence to a gluten-free diet is the only effective treatment for CD.^14,16 Previously, patients with CD were advised to also avoid oats, but most evidence supports the safety of oats (<2 oz/d), provided there is no cross-contamination with gluten.¹⁴ Adhering to a strict gluten-free diet can be challenging because cereal flours are ubiquitous in western foods, and some foods may be cross-contaminated. The Celiac Disease Foundation (http://www.celiac.org) offers guidance on maintaining a gluten-free diet.

Because avoiding gluten has become popular even among people who don’t have CD, product labeling that includes information on gluten content has become pervasive. However, determining which items contain gluten depends on accurate labeling, a standard that often is not met in many countries; in the United States, such labeling began to be phased in starting in July 2014.²⁰ As a result, CD patients may unwittingly be exposed to gluten over the long term, which can result in greater morbidity and mortality. Unless a food is labeled “gluten-free," it is best to check with the manufacturer.

Compliance with a gluten-free diet can be monitored by following IgA tTG titers every 1 to 2 years, as these values normalize after a patient has been adhering to the diet for 6 to 24 months.^3,16

In addition to lifelong adherence to a gluten-free diet, a National Institutes of Health Consensus Development Conference recommended that management of patients with CD should include²¹:

consultation with a skilled dietitian 
education about the disease
 continuous long-term follow-up by a multidisciplinary team
 identification and follow-up of abnormalities found at baseline, such as abnormal liver function test results 
treatment of nutritional deficiencies.

The ACG also recommends that CD patients receive a dual energy x-ray scan for follow-up of osteopenia and a pneumococcal vaccine because functional hyposplenism is associated with CD, and pneumonia is a common complication of hyposplenism.^16,18

A link between infant feeding practices and the risk of CD?

Compared to infants who are breastfed and don’t receive gluten until ages 4 to 6 months, infants who are fed gluten in their first  3 months have a significantly increased risk of developing antibodies that are associated with celiac disease (CD).²² Recent studies suggest that the effects of breast milk on the microbiota composition of the intestine may help explain this difference. Breast milk selectively stimulates the growth of specific bacteria, including bifidobacteria, which are relatively depleted in children with CD.^23,24 Researchers believe breastfeeding and delaying introduction of gluten-containing foods until 4 to 6 months of age might protect against CD.²⁵

Should you recommend a gluten-free diet for other patients? Because avoiding gluten is now popular and many gluten-free products are marketed as “health food,” physicians may be reluctant to recommend a gluten-free diet for patients who have vague abdominal symptoms but negative CD test results. Despite the current popularity of “going gluten-free,” the reality is that in addition to CD, many other diseases may be helped by a gluten-free diet, such as dermatitis herpetiformis, irritable bowel syndrome, and neurologic diseases such as gluten-sensitive ataxia.¹⁹ In the end, whether to adopt a gluten-free diet is a decision that you and your patient will need to make together.

Researchers are searching  for additional treatments 

Because many patients find it difficult to adhere to a gluten-free diet, researchers are investigating several alternative treatments, including a derivative from cholera toxin that inhibits the opening of intestinal epithelial junctions, thereby reducing the resultant inflammatory response, and a desensitizing vaccine.^19,22,23 Another intriguing approach involves using the parasite Necator americanus to modulate the immune response to gluten.18 Finally, certain infant feeding practices, including breastfeeding and delaying introduction of gluten to the diet, may minimize the risk of developing CD. (See "A link between infant feeding practices and the risk of CD?" above.^22-25)

CORRESPONDENCE
Patrick T. Dowling, MD, MPH, Department of Family Medicine, 50-078 Center for Health Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1683; pdowling@mednet.ucla.edu