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Diagnosis and Testing of Celiac Disease

How is celiac disease diagnosed?
How is celiac disease treated?
What healthcare providers should I see?
What happens when I eat gluten?
Are the villi permanently damaged in celiac disease? If not, how long will they take to recover?
Is it important to have repeat blood tests or biopsies to confirm that I have celiac disease?
What is a gluten challenge? Do I need one?
How often should a patient or family member of a patient have a repeat blood test if their test was negative?
What is the meaning of HLA-DQ2 and HLA-DQ8?
What are the recommended blood tests to determine whether or not I have celiac disease?
How accurate are the blood tests?
Is there a stool test to determine whether or not I have celiac disease?
I think I have celiac disease, but I had a negative blood test. How do I know if I have it?
My doctor told me I have celiac disease, but I feel fine. What should I do?

How is celiac disease diagnosed?

Celiac disease is diagnosed by a gastroenterologist. A patient who is suspected to have celiac disease will first have a blood test for either EMA or tTG, as well as a total IgA count. The first two of these tests look for auto antibodies (i.e., antibodies directed to a self antigen; here tTG) found only in patients with celiac disease. A total IgA count is performed to check for a harmless disease called IgA deficiency. If someone is IgA deficient, they may have a false negative result to their EMA or tTG tests, requiring different tests. TTG tests are more commonly used, but both EMA and tTG tests are very accurate in the diagnosis of celiac disease. These tests are described in a separate section below. These tests will determine if there are specific antibodies in the blood that are only found in patients with celiac disease.

There are occasional individuals whose IgA-tTG results may be misleading. In this case, we recommend using a newer test, anti-DGP (IgG and IgA antibodies to deamidated gliadin peptide). It is similarly accurate to IgA-tTG and is useful for patients w/ IgA deficiency.

If the blood test is positive, the patient will have an endoscopy and a biopsy of the small intestine performed by a gastroenterologist. During the procedure, the physician uses a flexible device with a camera (endoscope) to remove a small amount of tissue from the small intestine. A doctor will look at the tissue under a microscope to determine whether there is damage to the intestine that is characteristic of celiac disease. A biopsy is the gold standard for the diagnosis of celiac disease and is a necessary part of diagnosis.

It is important that all these tests be done BEFORE starting a gluten-free diet, as they will all be expected to become normal once there is no gluten exposure. Starting a gluten-free diet without first confirming the diagnosis of celiac disease using blood tests and endoscopy with biopsy of the small intestine is not recommended. The reason is that celiac disease is a lifelong illness, not only necessitating keeping a gluten free diet indefinitely, but also involving multiple parts of the body. A number of other tests including nutritional status and bone density may need to be performed. If testing is done AFTER a gluten free diet is initiated, blood tests can normalize and the intestine may have a chance to fully heal, thus, your doctor will be unable to accurately diagnose celiac disease.

This is problematic because other illnesses responsible for symptoms may be missed if you are diagnosed incorrectly with celiac disease based on resolution of symptoms alone. Thus, an important diagnosis may be missed and/or you may be following a difficult diet that is not improving your health. In the past, the diagnosis of celiac disease was confirmed with what is known as a gluten challenge, where after resolution of symptoms on a gluten free diet, the individual was instructed to consume gluten again. If symptoms recurred, this was further evidence for celiac disease. Currently, with the advent of accurate diagnostic tests, this is no longer routinely necessary.

Depending on the patient's particular symptoms and medical history, a number of physical examinations and lab studies may be carried out to help identify nutritional deficiencies, electrolyte abnormalities or other health concerns.

Physical Exam findings could include:

Examination of the abdomen may reveal a bloated stomach due to distention of intestinal loops with fluids and gas
Evidence of weight loss such as muscle atrophy (loss of muscle mass) or loose skin folds
Orthostatic hypotension (a decrease in blood pressure when going from a seated or lying position to standing)
Peripheral edema (a collection of fluids in the arms and legs)
Bruising
Dermatitis Herpetiformis (DH) (see section on DH)
Cheilosis (severely reddened and cracked lips; mostly commonly seen at the corners of the mouth)
Glossitis (inflammation of the tongue with formation of ulcers in the mouth)
Peripheral neuropathy (decreased sensation or numbness in the fingers and toes)
Physical exam findings related to hypocalcemia
- Chvostek's sign- tapping on a specific area of the face results in twitching of the facial muscle
- Trousseau's sign- inflation of a blood pressure cuff on either arm results in a "carpal spasm", seen as flexing of the wrist

Blood tests:

· Low iron levels are common. Ferrritin is generally the best test to measure iron stores.
B12 and folate: Anemia due to deficiency in iron, folate, and in rare cases vitamin B12 may be present.
Vitamin D (25-OHD)

Other tests that clinicians may order depending on your condition include:
• Zinc
• Parathyroid hormone
• TSH (thyroid stimulating hormone)
• Potassium
• Serum calcium
• Magnesium
• Albumin (protein stores) is suspected of malnutrition
• Cholesterol panel

Stool examination:

Looking for bulky, greasy appearance and foul-smelling stools that might suggest improper absorption of fat
Tests that actually measure the amount of fat in the stool can also help to determine if this condition is present.

Immunologic testing/serology:

Measurement of antibody levles to
- Tissue Transglutaminase (tTG)
- Endomysium
- Gliadin

Imaging studies:

Imaging studies including x-rays, CT scans and a variety of other tests are rarely necessary in the diagnosis of celiac disease; however they may be needed to rule out other disorders in cases where the diagnosis is uncertain or to assess for complications of celiac disease.

X-rays of the small bowel can be taken after the patient swallows a substance known as barium. On the X-ray, the physician may observe dilatation of the small intestine or an absence of the normal pattern of the small intestine due to destruction of the villi. Similarly, abdominal ultrasound has also been used to suggest the diagnosis of celiac disease but, at this time, imaging studies are not routinely recommended in the diagnosis and follow up of celiac disease.
Bone density studies (also referred to as a DEXA scan) should be performed in those recently diagnosed with celiac disease. DEXA scans are usually recommended after 12 months of strictly following a gluten free diet.

Procedures:

In the initial workup of celiac disease, an endoscopic biopsy of the small intestine is usually performed. This procedure involves a small tube with a video camera on the tip being placed down the throat and into the stomach and small intestine. The gastroenterologist takes samples of tissue from the small intestine, which can then be looked at under the microscope for evidence of celiac disease.

The tests and procedures listed above are not to be taken as all-inclusive. Depending on the extent of disease, further testing or referral to other specialists may be necessary. Nonetheless, these are some of the common tests and results you might find carried out in an individual suspected of having celiac disease. Finally, improvement of symptoms upon the removal of gluten from the diet provides further clinical evidence of celiac disease.

How is celiac disease treated?

Celiac disease is treated with a strict, lifelong, gluten-free diet. Once gluten is removed from the diet, healing and regeneration of the intestine begins. Young children respond very well to the diet, and usually heal completely within a year. Adults generally take longer, and some may never fully heal on the gluten-free diet, even though their symptoms are usually alleviated. At this time, there are no medications or treatments other than the gluten-free diet for celiac disease.

One way to remember the treatment of celiac disease is by the acronym C.E.L.I.A.C.:

Consultation with a skilled dietician
Education about celiac disease
Lifelong adherence to a gluten-free diet
Identification and treatment of nutritional deficiencies
Access to an advocacy group
Continuous long-term follow-up by a multidisciplinary team.1

What healthcare providers should I see?

Once diagnosed with celiac disease, it is important to maintain life-long follow up with a physician regarding your condition. This follow-up is especially important since there are several manifestations of the disease that are not related to the gastrointestinal tract.

Specifically, you should see your primary care physician (PCP) for any initial problems you may have. Your PCP or another specialist may make or suspect the initial diagnosis of celiac disease; however, a referral to a gastroenterologist and nutritionist skilled in the diagnosis and management of celiac disease is usually needed to confirm the initial diagnosis and plan further management including:

Arranging for consultation(s) with a celiac dietitian
Evaluation for nutritional deficiency states
Initial education regarding dietary treatment of the disease
Counseling regarding the test results and screening of family members
Evaluation for associated disorders
Initiation of nutritional supplements, as indicated
Monitoring of the response to the gluten-free diet
Adjustment of diet, as well as nutritional supplements, according to clinical and immunologic response

If an associated disorder is discovered, such as thyroid disease, you may be referred to another specialized physician for management of the problem. In the case of celiac patients, an endocrinologist may be seen for thyroid problems, diabetes, or management of bone health.

The Celiac Center at Beth Israel Deaconess Medical Center has a listing of "Celiac Skilled" gastroenterologists and dietitians to assist you with your needs. These individuals will aid in the diagnosis of the disease if you or your primary doctor suspects celiac disease and will also provide long- term specialized care for individuals already diagnosed with celiac disease. Please see the left legend for links to contact these healthcare providers.

What happens when I eat gluten?

Currently, it is believed that proteins derived from the digestion of gluten, (the component of grains toxic to individuals with celiac disease) including gliadin, are able to pass into the wall of the intestine. Once inside the intestinal wall (in the submucosa), an enzyme known as tissue transglutaminase, or tTG, changes the shape of the small gliadin proteins. The modified gliadin is then processed by antigen presenting cells. These cells are specialized to present many different kinds of substances to the immune cells so that the immune system may decide what is harmful and what is not. After processing by the antigen presenting cell, the gliadin in its new shape is able to activate the immune system through binding to T cells, causing inflammation and the release of chemicals that can affect the entire body. Only people that have the HLA-DQ2 or HLA-DQ8 genes have T cells that bind gluten proteins (mostly gliadin). The ability of these cells to bind to gluten-derived peptides is inherited and seems to be the main reason why some people get celiac disease and others do not. 2

The small intestine is lined with finger-like projections called villi (see the image below on the left). The villi are necessary to produce digestive enzymes and aid in the absorption of nutrients. When a patient with celiac disease eats gluten, these villi become shorter or flattened, and they will have a diminished ability to make enzymes. The shortening of the villi decreases the surface area available to absorb nutrients. The overall result of eating gluten is decreased digestion and nutrient absorption, leading to malnutrition and symptoms such as diarrhea and fatigue.

The images above are from biopsies taken from the small intestine of two patients. The image on the left is of the villi of a healthy patient. The image on the right is from the intestine of a patient with celiac disease. You can see that the villi are absent in the picture on the right as a result of damage to the intestine caused by celiac disease.

Are the villi permanently damaged in celiac disease? If not, how long will they take to recover?

The villi are not permanently damaged in celiac disease, although in older individuals it may take years for the villi to fully regenerate. The intestine is capable of regenerating every three days, but the amount of time it takes for the villi to return to normal varies from person to person. In general, the intestine is expected to heal over a period of weeks to months on a gluten-free diet.

Is it important to have repeat blood tests or biopsies to confirm that I have celiac disease?

It is important to be securely diagnosed with blood tests and a biopsy before going on a gluten-free diet. After starting the diet, follow-up tests are individualized based on your age, symptoms and other health problems. Routine follow-up with a nutritionist skilled in celiac disease and a gastroenterologist is strongly recommended. In most cases, blood tests are performed on a regular basis, while repeat biopsies are not usually necessary. Your doctor will determine which specific tests you need.

What is a gluten challenge? Do I need one?

A gluten challenge is recommended when an individual is on a gluten-free diet, but his/her physician is unsure of whether or not he/she has celiac disease. In this case, gluten is reintroduced into the diet slowly, over a period of 4-6 weeks. At the end of this time period, the patient is given a repeat blood test and biopsy. If the individual experiences symptoms before 4 weeks, he/she may be advised to see the physician earlier to have a blood test and biopsy performed. Unfortunately, in this case, there is a greater risk of obtaining a false negative result. Individuals with confirmed celiac disease do not need to have a gluten challenge.

Note that patients should ONLY undergo a gluten challenge if instructed to do so by their physician. Patients who have been following a gluten-free diet should not reintroduce gluten into their diet without talking to their physician.

How often should a patient or family member of a patient have a repeat blood test if their test was negative?

If your physician has a strong suspicion that you have celiac disease, even with a negative blood test s/he may perform an endoscopy with biopsy, as up to 5% of patients with celiac disease may have a falsely negative blood test. If the blood test and biopsy are normal then you do not have celiac disease and there is no need for repeat testing unless your symptoms change. For an adult relative of a patient with celiac disease, there is no need to repeat a blood test unless the relative starts to develop symptoms of celiac disease. Children, however, may need to be tested regularly, and should see a pediatric gastroenterologist.

What is the meaning of HLA-DQ2 and HLA-DQ8?

These are the names of two genes which are part of the immune system and are able to stick to the gluten proteins. Every patient with celiac disease has at least one of these genes. If your doctor is unsure as to whether or not you have celiac disease, s/he can perform a simple blood test to determine whether or not you have one or both of these genes. If you do not have one of these two genes, your doctor can rule out celiac disease. If you DO have one of these genes, it is possible that you have celiac disease, and your doctor will need to perform more tests. You do not need to eat gluten in order to have the gene testing.

What are the recommended blood tests to determine whether or not I have celiac disease?

Currently, the most frequently used test is IgA anti-tTG, or tissue transglutaminase. Your doctor may additionally check your total IgA level to determine if you have an IgA deficiency, which is a harmless condition that is associated with celiac disease. If you have an IgA deficiency, your doctor can order an IgG anti-tTG test instead, although this is slightly less accurate than IgA anti-tTG. Another blood test that your doctor may order is an EMA, or endomysial antibody test. This test is used less frequently than the IgA anti-tTG, but since it detects the same target antigen on a tissue section it can be just as accurate. Anti-gliadin antibodies, or AGA, were used in the past, but are typically not done now because they are much less accurate than tTG or EMA.

If your doctor is still uncertain as to whether or not you have celiac disease, s/he may order an HLA-DQ2 or HLA-DQ8 blood test. This is a genetic test that will help her/him determine whether or not you have celiac disease.

How accurate are the blood tests?

These blood tests are very accurate, especially when the tTG and EMA levels are elevated, as in patients with celiac disease. In a small number of cases, though, a patient with celiac disease may have a negative blood test.

Is there a stool test to determine whether or not I have celiac disease?

Stool tests have not been proven to be effective in screening for celiac disease in patients. Blood tests remain the most effective and reliable way of screening for celiac disease.

I think I have celiac disease, but I had a negative blood test. How do I know if I have it?

If you are on a gluten-containing diet, and had a negative blood test for celiac disease, you can elect to have a biopsy taken. Approximately up to 5% of patients with celiac disease have a negative blood test. If your biopsy is negative, you can conclude that you do not have celiac disease.

Some patients without celiac disease may find that they experience discomfort after ingesting gluten. These patients may feel better on a gluten-reduced diet. This condition is called gluten intolerance, and is not the same as celiac disease.

My doctor told me I have celiac disease, but I feel fine. What should I do?

There is no evidence that strongly supports recommending a gluten-free diet if you had a positive blood test for celiac disease, but no symptoms of the disease. Your doctor should check other lab values, though, to determine whether celiac disease has had other effects on your body. You should be aware of symptoms of celiac disease that do not affect your gastrointestinal system that you may be experiencing. Talk to a celiac disease specialist about the pros and cons of treatment for celiac disease.

References:

1. National Institutes of Health Consensus Development Conference Statement on Celiac Disease, June 28-30, 2004. Gastroenterology 2005; 128 (4 Suppl 1):S1-9

2. Dietrich W, Ehnis T. Bauer M, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801.