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. 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 who have any of the following situations should be evaluated for Celiac Disease:

• Symptoms indicating nutritional deficiencies.
• Unexplained digestive problems.
• 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. Here are steps to diagnosis:

1. MAKE APPOINTMENT WITH YOUR DOCTOR

When you visit your doctor, think carefully upon questioning. If you do not understand a question, ask him 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  

Your doctor will order the following blood tests to detect if you have specific autoantibodies for Celiac Disease circulating in your blood.  

The IGA Anti-Endomysium Antibody (EMA) test can detect antibodies in excess of 90% of people.  This test is the most costly because the actual lab work requires human evaluation.

The IGA Anti-tissue Transglutaminase Antibody (tTG) test is the newest antibody test.  It can detect antibodies in 98% of adults and 96% of children.  The tTG analysis is performed by a computer so that it is less costly than the EMA test.

Other blood testing involves the specific immune reaction to the gliadin component of gluten. These are inexpensive tests useful to screen for evidence of the abnormal presence of gliadin in the body.  

IGA Anti-Gliadin Antibody tests for Immunoglobulin A type antibodies that attack gliadin.   IGG Anti-Gliadin Antibody tests for Immunoglobulin G type antibodies that attack gliadin.

Antigliadin (AGA) tests have lower sensitivity for detecting celiac disease (70 to 85%) and distinguishing celiac disease (70 to 90%) than the EMA or tTG tests.  However, they have a high sensitivity for gluten exposure resulting from increased intestinal permeability.  Both IgA-AGA and IgG-AGA are advised.

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

What Biopsy Specimens can 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.

5. 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. 

6.  A 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.

7.  A 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.

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. 

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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. Horvath K. "Comments on Celiac Screening Test." Pediatric Gastroenterology and Nutrition 
   Laboratory, UMAB/Bressler Research Building, Room 10-047, 655 West Baltimore Street, Baltimore, MD. 21201.
4. 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.
5. http://digestive.niddk.nih.gov/ddiseases/pubs/upperendoscopy/index.htm
6. 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.