Celiac Disease Diagnosis and Testing

How Is Celiac Disease Diagnosed?

Diagnosing Celiac Disease can be difficult and frustrating for both the patient and the doctor because each person is affected individually and there are other disorders that share symptoms. With no definite set of symptoms to cause suspicion, the single most important step in getting a diagnosis of Celiac Disease is to recognize its myriad features.¹ Read more…Symptoms.

People With Any of These Situations Are at Higher Risk of Celiac Disease and Should be Evaluated:

• Symptoms indicating nutritional deficiencies.
• Unexplained digestive problems such as IBS, acid reflux, diarrhea/constipation, bloating, chronic abdominal pain.
• Chronic skin disorders, especially when itchy.
• Unexplained visual problems including poor night vision, dry eye, or cataracts.
• An auto-immune disease like Type 1 Diabetes Mellitus or Sjogrens Syndrome.
• A chronic disease like arthritis, migraine headache, or polyneuritis.
• A relative who has Celiac Disease.
• A relative who has Dermatitis Herpetiformis.
• Frequent or long bouts of colds, bronchitis, and other respiratory infections.
• Long recuperation from illness or surgery.
• A history of tuberculosis.
• Non-Hodgkin’s lymphoma.
• Cancer, especially of the digestive tract.

Very good diagnostic tests are available, but no one test can definitively diagnose or exclude Celiac Disease in every individual.² And, because all diagnostic tests look for harmful effects of gluten, you MUST be eating gluten in your diet when ANY diagnostic test is performed. Tests may be inconclusive if you strictly eliminate gluten for longer than two weeks.  So if you think you may have Celiac Disease or feel better going without gluten for a week to 10 days, go get tested before continuing.

Steps to Celiac Disease Diagnosis

Diagnosis is established by serological testing, small intestinal biopsy evidence of villous atrophy, and improvement of symptoms on a gluten-free diet.^1,3 Supporting methods include ultrasound procedure, genetic testing, sugar absorption test, rectal biopsy, and gluten-free diet trial.

1. Make Appointment with Your Doctor for an Examination and Symptom Check

When you visit your doctor, think carefully upon questioning. If you do not understand a question, ask your doctor to explain. Give an accurate history of all symptoms because seemingly irrelevant problems can be very meaningful. Your doctor will want to examine you for evidence of nutritional deficiencies or other problems.

2. Blood Testing for Abnormal Antibodies

Your doctor will order the following blood tests to detect if you have specific autoantibodies  for Celiac Disease circulating in your blood. Autoantibodies are antibodies against our body’s own tissues.

Based on very high sensitivities and specificities, the best available autoimmune antibody tests are the anti-tissue transglutaminase antibody (tTG) test and the anti-endomysial antibody (EMA) test.1 The newer anti-deamidated gliadin peptide antibody (DGP) test, also called Gliadin DP, is comparable to the tTG in identifying celiac disease in patients.

Many factors affect the results of serological tests and clinicians should be aware of their limitations. To avoid false negatives, combining two or more serology tests is preferable to one test. Because celiac screening tests detect IgA type antibodies, a serum IgA level should be included to determine adequate IgA antibody production. The inability to produce IgA antibodies negates all IgA test results.

Other necessary blood tests, called AGA-IgA and AGA-IgG, detect antibodies produced by the body against gliadin (the gluten in wheat) that is abnormally present in the blood, with or without celiac disease. AGA-IgA and AGA-IgG are tested at the same time in case there is an IgA deficiency. IgA deficiency means the body does not produce adequate antibodies.

Antigliadin (AGA) tests have lower sensitivity for detecting celiac disease (70 to 85%) and distinguishing celiac disease (70 to 90%) than the EMA, tTG or DGP tests, with exceptions.

For example, AGA is best in finding celiac disease in children younger than 18 months compared to tTG and EMA tests. Also, AGA has a high sensitivity for gluten exposure resulting from increased intestinal permeability in non-celiac gluten sensitivity.

Blood Results of Antibody Testing

Positive Antibody Results.

The presence of IgA antibodies for any antibody (tTG, EMA, AGA) demonstrate a short-term immune response, showing that gluten was ingested usually within two weeks preceding the test. The presence of IgG antibodies demonstrate long-term immune response, indicating ingestion of gluten in the six months to a year preceding the test.

Negative Antibody Results.

Blood tests that return negative results for both IgA and IgG antibodies would be considered negative, provided you have been regularly eating food with gluten.

Negative Antibody Results and Suggestive Symptoms. Three scenarios are possible.

1. You may have selective IgA deficiency, meaning you do not make these antibodies so they will always be negative.  A “Serum IGA” blood test would detect this condition.
2. The blood test itself may be a “false negative,” meaning the laboratory testing is defective. If this is suspected, the test could be repeated using a lab with better experience, an alternative blood test could be conducted, and/or a small intestinal biopsy could be performed.
3. You may not have Celiac Disease.²

3. Biopsy of the Proximal Small Bowel

If your blood tests suggest Celiac Disease, your doctor will want to know if your intestinal villi are damaged. He will send you to a gastroenterologist (doctor who specializes in gastro-intestinal disorders) who can obtain biopsies (tiny pieces of your intestinal lining) to check for villi damage.

An endoscopy procedure is useful for actually looking at the esophagus, stomach, and first part of the small intestine. The gastroenterologist passes an endoscope (a thin, lighted tube) through the mouth and down the throat, while viewing the images on screen. Although this procedure is painless, it is difficult for  patients to cooperate. Most people benefit by light sedation.

It is not helpful to have an endoscopic evaluation without biopsies. Only biopsies can confirm or exclude a diagnosis of Celiac Disease. Multiple biopsies should be obtained because the cell changes may be spotty.²

Celiac Disease is the most common disorder that a gastroenterologist would see.³ Nevertheless, it has been demonstrated that among diverse endoscopy sites, gastroenterologists do not perform small bowel biopsy for the majority of patients with anemia, iron deficiency, weight loss, and diarrhea (classic symptoms of Celiac Disease).⁴ This means you need to make certain that the doctor will take samples for biopsy.

Upper Endoscopy

Upper endoscopy enables the physician to look inside the esophagus, stomach, and duodenum (first part of the small intestine). The procedure might be used to discover the reason for swallowing difficulties, nausea, vomiting, reflux, bleeding, indigestion, abdominal pain, or chest pain. Upper endoscopy is also called EGD, which stands for esophagogastroduodenoscopy (eh-SAH-fuh-goh-GAS-troh-doo-AH-duh-NAH-skuh-pee).

For the procedure you will swallow a thin, flexible, lighted tube called an endoscope (EN-doh-skope). Right before the procedure the physician will spray your throat with a numbing agent that may help prevent gagging. You may also receive pain medicine and a sedative to help you relax during the exam. The endoscope transmits an image of the inside of the esophagus, stomach, and duodenum, so the physician can carefully examine the lining of these organs. The scope also blows air into the stomach; this expands the folds of tissue and makes it easier for the physician to examine the stomach.

The physician can see abnormalities, like inflammation or bleeding, through the endoscope that don’t show up well on x rays. The physician can also insert instruments into the scope to treat bleeding abnormalities or remove samples of tissue (biopsy) for further tests.

Possible complications of upper endoscopy include bleeding and puncture of the stomach lining. However, such complications are rare. Most people will probably have nothing more than a mild sore throat after the procedure.

The procedure takes 20 to 30 minutes. Because you will be sedated, you will need to rest at the endoscopy facility for 1 to 2 hours until the medication wears off.

Preparation

Your stomach and duodenum must be empty for the procedure to be thorough and safe, so you will not be able to eat or drink anything for at least 6 hours beforehand. Also, you must arrange for someone to take you home?you will not be allowed to drive because of the sedatives. Your physician may give you other special instructions.⁵

What Biopsy Specimens Show

There are three distinct patterns of mucosal cell abnormalities of the small intestine:

• Infiltration of the villous epithelium with lymphocytes and a normal villi and crypt architecture. This pattern is found in 40% of individuals with dermatitis herpetiformis and a portion of first degree relatives of celiacs who have no gastrointestinal symptomatology.
• A flat mucosa characterized by villous flattening and crypt elongation with inflammatory cells in the lamina propria. This pattern is classically found in individuals with CD who have gastrointestinal symptoms, but has also been reported in asymptomatic celiac relatives and individuals with dermatitis herpetiformis.
• A hypoplastic mucosa characterized by villous flattening and small crypts. This biopsy is found in the small group of patients with presumed severe celiac disease that does not improve on a gluten-free diet.¹

Celiac Disease can be associated with minimal mucosal changes on biopsy. The blood test may be positive and seemingly normal cells on biopsy. However, damage to the absorptive villi may be submicroscopic, meaning changes can not yet be seen through a microscope. This would imply a reduction of intestinal absorption is already occurring, even in this latent stage of the disease.  In these patients, alterations of the cells may develop at a later date.⁶

Biopsies are not fool proof. A negative report may result from poor technique in obtaining the tissue to be biopsied and/or from inaccurate determination by the pathologist who examines it.

Definitive Diagnosis

With both positive blood and biopsy results, a presumptive diagnosis of Celiac Disease can be made. Definitive diagnosis is confirmed when symptoms resolve subsequently with a gluten-free diet.

In the case of a positive blood test and normal biopsy result, the choices include additional small bowel biopsies, periodic monitoring with blood tests, or a trial of gluten-free diet.

Other Tests Used to Diagnose Celiac Disease

If blood tests and endoscopy with biopsy should prove unfeasible or inconclusive, these other tests may be performed.

Ultrasound

Ultrasound is especially useful for diagnosing Celiac Disease in children because it does not require needle sticks or anesthesia. An ultrasound uses sound waves to detect an abnormal appearance of the small bowel wall structure. Typical findings in fully developed celiac disease are fluid-filled distended intestinal loops and continuous peristalsis in the small bowel segments during fasting. With positive EMA serology, intestinal dilatation and increased peristalsis, finding increased gall bladder size, abdominal free fluid and enlarged mesenteric lymph nodes reliably and accurately predicts celiac disease. These findings disappeared with therapy but reappeared after exposure to gluten.⁹

Genetic Testing

More than 97% of people with Celiac Disease share the same genetic markers called HLA-DQ2 and HLA-DQ8.Checking for these markers is useful in determinig risk for Celiac Disease.²

It is useful to test blood for the HLA-DQ2 and HLA-DQ8 genetic markers in the following people:

• Relatives of diagnosed people with Celiac Disease.
• People with negative blood tests who exhibit manifestations of Celiac Disease.
• People with ambiguous biopsy results.
• People who started a gluten-free diet before diagnostic testing.

Sugar Absorption Test

This is a test used to determine if there is increased permeability (”leaky gut”) of the small intestine. Normal permeablity is a barrier system that does not allow harmful substances such as gliadin prolamines from gluten to pass into the bloodstream from the gut. Increased permeability is believed to contribute to the development of active Celiac Disease. The procedure simply involves drinking a dose of specific sugars and then having the urine examined later. If sugar is found in the urine, it means these sugars abnormally passed through the intestinal lining, into the blood and then were excreted in the urine.

Rectal Biopsy

A rectal biopsy can detect an immune response to Celiac Disease. It is done in the doctor’s office by a specialist trained in the procedure. A tiny sample of rectal tissue is removed to look under a microscope for an immune reaction. Rectal biopsy is useful for people who did not get tested before starting a gluten free diet and then want to definitely know if they really do have Celiac Disease.  The test is effective within 6 months of starting a gluten free diet.

Gluten-Free Diet Trial to Demonstrate Dependency of Symptoms

No test is 100% accurate. Serology tests and biopsies have returned negative results on one occasion and positive on another or negative on one test and positive on a different type of test. In particular, serology seems to be ineffective in detecting most patients affected by subclinical/silent disease. If tests are negative, yet symptoms are still being experienced, then the patient should be put on a strict gluten restrictive diet trial. Remission of symptoms would indicate gluten sensitivity.

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Sources:

1. National Institutes of Health,”National Institutes of Health Concensus Development Conference
   Statement, Celiac Disease,” August 9, 2004;1-14.
2. Murray, J.”The Widening Spectrum of Celiac Disease.” American Journal of Clinical Nutrition. Mar
   1999;69(3):354-365.
3. Schuppan D, Zimmer KP. The diagnosis and treatment of celiac disease. Dtsch Arztebl Int. 2013 Dec 6;110(49):835-46. doi: 10.3238/arztebl.2013.0835.
4. Korponay-Szabo IR, Szabados K, Pusztai J, et al. Population screening for celiac disease in primary care by district nurses using rapid antibody test: diagnosyic accuracy and feasibility study. BMJ. Dec 2007;335(7632): 1244-1247.
5. Horvath K.”Comments on Celiac Screening Test.” Pediatric Gastroenterology and Nutrition
   Laboratory, UMAB/Bressler Research Building, Baltimore, MD. 21201.
6. Harewood GC, Holub JL, Lieberman DA. ”Variation in small bowel biopsy performance among diverse endoscopy settings: results from a national endoscopic database.”American Journal of Gastroenterology.” Sep 2004;99(9):1790-4.
7. http://digestive.niddk.nih.gov/ddiseases/pubs/upperendoscopy/index.htm
8. Sbarbati A, Valletta E, Bertini M, Cipolli M, Morroni M, Pinelli L, Tato L. ”Gluten sensitivity and ’normal histology: is the intestinal mucosa really normal?” Digestive and Liver Disease:Official Journal of the Italian Society of Gastroenterology and the Study of the Liver. Nov 2003;35(11):768-73.
9. Nyland, K, Ødegaard S, Hausken T, et al. Sonography of the small intestine. World Gastroenterol. Mar 2009; 15(11):1319-1330.