Celiac Disease

Is gluten-free really enough?

Celiac disease is an autoimmune disorder that impairs a person’s ability to absorb nutrients due to inflammation in the small intestines.1

In recent decades, the diagnosis of celiac disease has more than doubled, however it is still one of the most misdiagnosed diseases worldwide, which ultimately leads to a greater risk of developing celiac related complications.2 With about 1% of the American population suffering from celiac disease, it is imperative to have early detection and a strict gluten-free diet in order to prevent intestinal damage.1

What is Celiac Disease?

Celiac disease is a multifactorial disease that predisposes an individual to mucosal damage of the small intestine.2 Mucosal damage is inflammation that occurs as a result of ingesting gluten, which is a storage protein found in products such as wheat, barley and rye.3

The exact cause of celiac disease has yet to be determined, however, it known that some individuals are genetically predisposed to the condition. Individuals with the human lymphocyte antigen HLA-DQ2 or HLA-DQ8 and the celiac disease autoantigen, tissue transglutaminase, TG2, are prone to an inappropriate immunological response to the ingestion of gluten which causes the intestinal inflammation.3

Gluten contains a glutamic-rich peptide that attaches to the DQ2 or DQ8 molecule, which then activates T-cells in the intestinal submucosa and destroys mucosal enterocytes leading to mucosal damage and inflammation.4

Continuous mucosal damage to the small intestine can be described as villous atrophy, hypertrophy of intestinal crypts, and atrophy of duodenal folds.4 All of these changes to the small intestine can lead to malabsorption problems and vitamin deficiencies. Continuous damage to the intestines can eventually lead to gastrointestinal related cancers.5

Clinical Presentation

With the varying symptoms present in celiac disease, it is often very difficult to diagnose. Over 83% of people with celiac disease are undiagnosed or misdiagnosed, taking an average of 6-10 years to be properly diagnosed.1

Typical symptoms of celiac disease are related to malabsorption, which include symptoms such as diarrhea, flatulence, steatorrhea, weight loss, bloating, fatigue, muscle atrophy and growth retardation.4 Because nutrients are not absorbed due to intestinal damage, the patient is at risk for vitamin deficiencies leading to symptoms such as pallor due to anemia, bone pain due to calcium deficiency, and easy bruising due to vitamin K deficiency.4 Neurological symptoms may also be present such as headaches, numbness and tingling, and ataxia due to B12 and vitamin E deficiency.4

Not every patient presents with typical malabsorption symptoms. Approximately 40% of patients with positive serological tests consistent with sprue have no symptoms of the disease.4

If patients with celiac disease do not present with any symptoms it is known as “asymptomatic celiac disease.” These patients are asymptomatic because only a small portion of their small intestine is damaged, allowing the undamaged portion to absorb the proper nutrients. However, just because patients do not present with symptoms does not mean they are immune to the complications of celiac disease.1

There is conflicting data as to whether or not undiagnosed celiac disease increases an individual’s risk of cancer, however, it has been confirmed that undiagnosed celiac disease increases an individual’s risk of developing osteoporosis.6


Celiac disease can be diagnosed in several different ways and at any age. It is recommended that patients with malabsorption symptoms, patients with a first degree relative with confirmed celiac disease, and patients with Type I diabetes mellitus with malabsorption symptoms should all be tested for the condition.7 Patients should remain on a gluten-rich diet while being evaluated for celiac disease in order to prevent false-negative results.7


The first diagnostic test that should be performed in all patients with suspected celiac disease is a serological evaluation of the IgA endomysial antibody and the IgA tTg antibody.4 A >90% sensitivity and >95% specifies a diagnosis of celiac disease.4 If an individual is under the age of two, then the IgA antibody and the DGP antibody should be tested.7 About 2-3% of individuals diagnosed with celiac disease are IgA deficient. Therefore, if an individual is identified as IgA deficient on serological exam, then a TTG IgG antibody should be evaluated.4,7 All antibody levels should be undetectable after 6-12 months of a gluten-free diet and therefore can be used to evaluate compliance of a gluten-free diet.4

The gold-standard for diagnosis of celiac disease is an endoscopic mucosal biopsy in patients with a positive serological test.4 An intestinal biopsy should still be performed if a patient has negative serological testing and there is a high suspicion of celiac disease.7

A biopsy should be taken from the duodenal bulb and an additional biopsy should be obtained from the distal duodenum or the proximal jejunum.4 When biopsies are histologically examined, they can appear in several different fashions. They can present with increased intraepithelial lymphocytes, total mucosal atrophy, complete loss of villi, epithelial apoptosis, or hyperplasia.5 A normal biopsy excludes the diagnosis of celiac disease but diagnosis is confirmed with positive serology results and abnormal mucosal biopsy findings.4


If celiac disease is properly diagnosed and the patient maintains a strict gluten-free diet, then the vast majority of individuals with the disease have an excellent prognosis.

The main reason individuals diagnosed with celiac disease don’t respond to a gluten-free diet is because of the continual ingestion of gluten. This is either from accidental ingestion of gluten due to the “hidden” gluten found in commercially available products, or deliberate ingestion of gluten due to the difficulty of compliance.

However, there are a small percentage of patients that are truly refractory to a gluten-free diet and have continuous symptoms despite elimination of gluten from the diet. These individuals have a poor prognosis and continuous damage can ultimately lead to T-cell lymphoma.4

Several observational studies have been performed that have compared the overall mortality of those with celiac disease to the general population. Several studies concluded that those with celiac disease had an overall increased risk of gastrointestinal cancer, non-Hodgkin lymphoma, cardiovascular disease and malignancy compared to the general population. Another study concluded that those with undiagnosed celiac disease have about a four-fold increase in all-cause mortality compared to the general population.5

Overall, it is imperative to correctly and quickly diagnose an individual with celiac disease to improve the rate of intestinal damage and further complications.

Treatment & Assessment

The only effective treatment for celiac disease is a completely gluten-free diet.1

Once an individual eliminates gluten from their diet, they should start seeing an improvement in their symptoms within a few weeks. The elimination of gluten in the diet can help improve the intestinal inflammation, which improves morphology and ultimately leads to increased nutritional absorption.

However, is a complete gluten-free diet really enough? A long term gluten-free diet has been known to cause clinical, serologic and histologic remission, however even those with a complete gluten-free diet have been shown to still have minor small-intestinal morphology due to the unknown trace amounts of gluten in the diet.8

According to a study published by the American Journal of Gastroenterology, an individual can incidentally be exposed to up to 2g of gluten a day.9 This exposure can occur through commercial foods that are contaminated with wheat or barley during processing. Gluten can also be an additive in medications, making it very difficult to avoid.4

In a study published by the American Journal of Clinical Nutrition, a “safety-threshold” was evaluated to determine the amount of gluten that can be tolerated by an individual with celiac disease. A randomized control trial was done to test different amounts of daily gluten (10mg, 50mg, and placebo) and their effects on patients with celiac disease. Overall, responses were variable. Some individuals were not able to tolerate any amount of gluten and therefore had to drop out of the study because of recurring symptoms, whereas some did not experience any symptoms.8 Overall, the study showed that as little as 50mg of gluten per day can cause intestinal damage that can lead to malabsorption.8 This consistent exposure to gluten can eventually lead to vitamin deficiencies, osteoporosis, anemia, decreased fertility, and numerous other problems.4

Due to the rise in celiac disease diagnoses over the last few years, gluten-free diets have become more popular. The National Foundation for Celiac Awareness has predicted that gluten-free sales will exceed more than $5 billion by 2015.1 Recently, there have been increased efforts to ensure that “gluten-free” foods really are in fact gluten-free. In order to help decrease the amount of “hidden” gluten found in commercially available food products and restaurants, the FDA passed the “Food Allergen Labeling and Consumer Protection Act in 2004.”10 In 2013, they passed a ruling to define “gluten-free”. It reads as followed:

“The final rule defines ‘gluten-free’ as meaning that the food either is inherently gluten free; or does not contain an ingredient that is: 1) a gluten-containing grain (e.g., spelt wheat); 2) derived from a gluten-containing grain that has not been processed to remove gluten (e.g., wheat flour); or 3) derived from a gluten-containing grain that has been processed to remove gluten (e.g., wheat starch), if the use of that ingredient results in the presence of 20 parts per million (ppm) or more gluten in the food. Also, any unavoidable presence of gluten in the food must be less than 20 ppm.” 10

Therefore, when educating patients on treatment of celiac disease it is imperative to educate them on the possibilities of “hidden” gluten in the products they are eating. Even minor ingestion of daily gluten causes consistent damage to the small intestine, predisposing patients to malabsorption problems, vitamin deficiencies, osteoporosis, etc.

Continual ingestion of gluten in someone with celiac disease could again lead to T-cell lymphoma and other gastrointestinal related cancers due to continuous intestinal damage.4,5 Patients should ensure all of the food products they buy are gluten-free. Also, when eating out in restaurants, they should ensure the chef is preparing food that is truly gluten-free.

A gluten-free diet can be challenging, however, with a little extra effort patients can improve their symptoms and live normal lives.


1. National Foundation for Celiac Awareness. Celiac Disease Symptoms List. http://www.celiaccentral.org/Celiac-Disease/Celiac-Symptoms/32/.
2. Marild K, et al. Antibiotic exposure and the development of coeliac disease: a nationwide case-control study. BMC Gastroenterol. 2013;13:109. doi: 10.1186/1471-230X-13-109.
3. Junker Y, et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med. 2012; 209(13):2395-2408.
4. Mcphee SJ, et al. Gastrointestinal Disorders. In: Current medical diagnosis and treatment. New York: The McGraw Hill Companies; 2012.
5. Kelly CP. Diagnosis of celiac disease. Up-To-Date. 2013. http://www.uptodate.com/contents/diagnosis-of-celiac-disease-in-adults
6. Godfrey JD, et al. Morbidity and mortality among older individuals with undiagnosed celiac disease. Gastroenterology. 2011;139(3):763-769.
7. Rubio-Tapia A, et al. Diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5):656-76. doi: 10.1038/ajg.2013.79.
8. Catassi C, et al. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr. 2007;85(1):160-166.
9. Leffler DA, et al. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterology. 2012;107:1554-62.
10. MassGeneral Hospital. Food Allergen Labeling and Consumer Protection Act. http://www.massgeneral.org/children/services/celiac-disease/falcpa.aspx.

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