Diagnosing Celiac Disease

Today’s topic is about the proper testing for celiac disease. Celiac disease is an immune-mediated condition that can occur in a genetically susceptible individual at any age with the consumption of gluten. In those with celiac disease, the consumption of gluten, a protein found in the grains, wheat, rye and barley, initiates a cascade of effects including small intestinal inflammation and flattening of the fingerlike villi that line the small intestine. The small intestine is where nutrients are absorbed to nourish our body and therefore, flattened villi can lead to a reduction in nutrient absorption. Although non-celiac gluten sensitivity (also known as non-celiac wheat sensitivity) is another condition that may benefit from a gluten free diet, I will not be reviewing this topic today.

In my clinical practice, most patients have been screened accurately for celiac disease, however, occasionally, I find two other possibilities:

1. Testing for celiac disease was incomplete and the patient was told they do not have celiac disease.
2. Testing for celiac disease was incomplete and the patient was told they do have celiac disease.

More practitioners are initiating specific serology (blood) testing for celiac disease to screen for this immune mediated condition. In my opinion, screening for celiac disease is important for those who have been diagnosed with irritable bowel syndrome.

Celiac disease is estimated to occur in about 1:133 Americans and the prevalence of celiac is increasing. Although most assume an individual with celiac disease will present with gastrointestinal symptoms, celiac disease really does not have a set clinical presentation. In fact, some individuals present with what is called silent celiac disease and have no symptoms whatsoever! Some symptoms that may occur in celiac disease include:

• Weight gain or weight loss
• Constipation and/or diarrhea
• Bloating
• Anxiety or depression
• Fatigue
• Neurological issues: unsteady of the feet, numbness is extremities
• Anemia
• Osteoporosis
• Brittle hair or nails
• Hypothyroidism
• Type 1 Diabetes
• Gerd
• Infertility

The treatment of celiac disease is a life long gluten free diet. And let me stress here, individuals with celiac disease require a strict gluten free diet. This means, no sharing of toaster ovens that may contain wheat bread crumbs or going to a salad bar as gluten containing ingredients may cross contaminate gluten free options. Careful vigilance to the gluten free diet is a must. Meeting with a registered dietitian with celiac and gluten free diet expertise is very important.

Lori Welstead, MS, RD, LDN, a University of Chicago digestive health dietitian expert with a recent diagnosis of celiac disease emphasizes, “Living gluten free and not having to would be horrible! It’s truly important to get a baseline endoscopy testing on anyone with elevated TTG (Anti-tissue Transglutaminase Antibody tested via blood). It is important to definitively diagnose celiac disease.”

Is blood testing alone enough to diagnose celiac disease in adults? No. Unfortunately, I am seeing patients that report a diagnosis of celiac disease without proper screening. There is the potential for error here! For one, blood testing and the follow up endoscopy should be evaluated while an individual is still ingesting gluten. And a positive blood test, should be followed up with an endoscopy to confirm the celiac diagnosis! For more specifics about how much gluten is necessary to consume for accurate testing, see Lori Welstead’s comments in How to Properly Diagnose Celiac Disease below.

Alessio Fasano, MD,  Chief of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children in Boston, MA, stresses, “the celiac diagnosis algorithm is based on a blood screening test (TTG antibodies) performed in cases of suspected celiac disease, followed by confirmation of the diagnosis by an upper endoscopy with biopsy showing the typical celiac enteropathy (flattening of the villi in the small intestine).  Therefore, while strongly indicative, the single positivity of the TTG test is not enough to confirm the diagnosis, given the rare but possible false positivity of the test, particularly for borderline positive results. The combination of a positive TTG and villous atrophy, even if mild, is strongly indicative of a diagnosis of celiac disease.”

Genetic Markers for Celiac Disease

Checking genetic markers for celiac disease may be considered in an individuals already following a gluten free diet due to self-determined intolerance to gluten. The genetic markers are are called DQ2 and DQ8. Each case of celiac disease has been found to show these genes; therefore, a negative gene test indicates that celiac disease cannot develop in that individual.

Genetic testing is most useful when the results are negative as it rules out celiac disease. If positive for the celiac genetic markers, you may never develop celiac disease, but you are at risk. If positive to the genetic markers for celiac and you exhibit celiac symptoms, your practitioner may instruct you to embark on a gluten challenge and then evaluate your TTG blood markers and perform an endoscopy.

Could you have an elevated TTG in the absence of celiac? It’s possible, but unlikely.

Ciaran Kelly, MD, Medical Director of the Celiac Center, BIDMC in Boston notes, “An elevated serum IgA-TTG has a high specificity for celiac disease. However, an elevated IgA-TTG can rarely be seen in the absence of celiac disease. When might this happen: 

1.  False positive TTGs in congestive heart failure and in liver disease may occur but are now are far less common since most assays use human TTG (not rodent TTG) as the capture antigen.
2. TTG auto-antibodies might be elevated and can be associated with autoimmune disorders (lupus, RA, MS and others)

Lori Welstead, notes additionally, “an elevated TTG may be a false positive in some cases of liver disease and other autoimmune diseases such as Type 1 DM, Crohn’s disease, thyroid disease.” Again, reinforcing the importance of both serology and endoscopy testing!

Duodenal biopsy AND serology testing is the gold standard for diagnosis of celiac disease in adults.

Interestingly, I have also seen elevated TTG levels in small intestinal bacterial overgrowth in rare cases–but more research on the cause and effect is needed!

How to Properly Diagnose Celiac Disease

Lori Welstead, MS, RDN, LDN provides the run down:

The University of Chicago Celiac Disease Center has useful information for patients and professionals with regard to proper diagnosis of celiac disease¹.

Patient must be eating gluten for TTG (Anti-tissue Transglutaminase Antibody) tests to be accurate. Standard testing includes: Total IgA and TTG IgA. If the Total IgA is deficient, then the TTG IgA is invalid. Total IgG and TTG IgG can then be drawn to assess for celiac disease. I find many practitioner’s forget to measure quantitative IgA! If you don’t make IgA, then measuring an antibody that requires its presence, will be inaccurate. 

Patient must be eating gluten prior to endoscopy for proper diagnosis. If  the TTG is elevated, then an endoscopy is indicated. During the endoscopy, there will be multiple biopsies done in the duodenum; with a goal of 2 biopsies in the duodenal bulb, and 4-6 in the distal duodenum, as villous atrophy is often patchy.²   I find, that many patients forget to tell their doctor they are already following a gluten free diet at the time of testing, which makes both the antibody and endoscopy testing inaccurate.

Fortunately, Dr. Dan Leffler (at Boston’s Beth Israel Deaconess Hospital) found in a study³ that 75% of adults will meet criteria for gluten challenge with a low dose of gluten (2 slices of wheat bread/day) versus higher dose of gluten (5 pieces of bread/day) in only two weeks. This is important, as not many are able to tolerate high doses of gluten for 4-8 weeks, which was historically recommended in adults.

Testing for celiac disease has come a long way due to better understanding of the antibodies and genetic markers for this condition. Untreated celiac disease may increase health risks (e.g. osteoporosis, anemia and in rare cases, intestinal cancer). You can develop celiac disease at any time. Work closely with your primary care doctor or gastroenterologist to ensure proper screening for this condition as warranted given your personal and family history.

References:

1. University of Chicago Celiac Disease Center: diagnosis of Celiac disease. http://www.cureceliacdisease.org/diagnosis/
2. Iacucci, M., & Ghosh, S. (2013). Routine duodenal biopsies to diagnose celiac disease.Canadian Journal of Gastroenterology, 27(7), 385.
3. Leffler, D. A., Schuppan, D., Pallav, K., Najarian, R., Goldsmith, J. D., Hansen, J., Kelly, C. P. (2013). Kinetics of the histologic, serologic and symptomatic responses to gluten challenge in adults with coeliac disease.Gut,62(7), 996–1004. http://doi.org/10.1136/gutjnl-2012-302196