Do you have celiac disease or gluten sensitivity?

Celiac disease affects between 1% and 5% of the population. Estimates regarding the incidence of gluten sensitivity vary widely, with conservative estimates placing it similarly at 1% to 6%. It will likely be some time before we know the incidence for sure but ask anyone who clearly suffers from the effects of gluten and they’ll tell you how miraculous it was when they eliminated it from their diet.

I authored the book The Gluten Effect several years ago, and since that time I get requests from around the world from individuals and parents asking for help interpreting their blood results.

• Do I have celiac disease or don’t I?
• Do I have gluten sensitivity?
• How do I know for sure?

Criteria for Celiac Diagnosis

In 2010 a paper was published in the American Journal of Medicine entitled “Celiac disease diagnosis: simple rules are better than complicated algorithms”.  It was well named and clearly laid out a brand new way of thinking about diagnosing celiac disease. The authors called it the “4 out of 5” Rule where a celiac diagnosis could be made if 4 out of 5 criteria were met.

The criteria to be met are as follows:

1. symptom typical of celiac disease
2. strongly positive blood test for celiac disease autoantibodies (IgA)
3. positive genetic test for celiac (HLA)-DQ2 or DQ8 genotypes)
4. positive small bowel biopsy indicative of the disease
5. feeling symptomatic improvement on a gluten-free diet.

https://www.ncbi.nlm.nih.gov/pubmed/20670718

Despite being published 8 years ago, there are still doctors insisting a biopsy is a gold standard for celiac diagnosis. Dr. Alessio Fasano, a world-renowned expert in the disease and one of the authors of the paper, states considering the biopsy as a diagnostic gold standard has been questioned as not necessarily reliable and conclusive in every case. The authors’ reasoning takes into consideration the “wide variability of celiac disease-related findings” and “the clinical complexity of this disease”.

Instead, they put forth the quantitative approach of the “4 out of 5” Rule, endeavoring to make diagnosis simpler and hopefully more accurate. Any doctor you meet with regarding gluten sensitivity or celiac disease should be familiar with this rule.

What is a “strongly positive” blood test?

As you can see above with the “4 out of 5” Rule, one of the criteria is a strongly positive blood test. How should that be defined?

A variety of studies put various values on the positive predictive value, or PPV, of the tTG blood test.

In pediatric populations, it’s been shown that a tTG over 100 U/mL is predictive of severe villous atrophy of the lining of the small intestine. This severity is called a Marsh 3 classification after the British doctor who established it. We’ll talk more about that in a moment.

Studies looking at patients older than 15 years put the PPV at 100% when tTG tested at over 30 U/mL. https://academic.oup.com/ecco-jcc/article/6/8/861/371107

The researchers noted a discrepancy however with strongly positive tTG values with normal or near-normal small intestinal linings, or Marsh 1 findings. Did that mean those patients did not have celiac disease? Not necessarily.

Is biopsy analysis being done currently?

Dr. Marsh himself, the founder of the classification system, states that patients in Marsh 1 and 2 can benefit from a gluten-free diet. In other words, Dr. Marsh himself doesn’t believe in waiting until severe destruction of the lining of the small intestine (Marsh 3 and 4) has occurred. There may not yet be destruction but there is inflammation, indicating immune system involvement, and therefore the condition should be taken seriously and evaluated for the presence of celiac.

Marsh 1 and 2 can be seen in other inflammatory and infectious diseases of the small bowel, including the parasite giardia, certain autoimmune disorders, acute disease, and those using NSAIDs. It is worth noting that parasites and autoimmune diseases go hand in hand with celiac disease.

Typically, if a biopsy finds anything less than a Marsh 3 level of destruction of your small intestine, you’re told you don’t have celiac disease, or that you should come back in 6 months to a year to see if your condition has worsened. Again, Dr. Marsh himself disagrees.

http://www.thedr.com/healthnetwork/

https://www.cureceliacdisease.org/wp-content/uploads/0909CeliacCtr_News_v3final.pdf

Who should be tested

There are many symptoms associated with celiac disease and gluten sensitivity; in fact, gluten has been called the “great masquerader” due to its ability to cause symptoms and conditions potentially involving every organ and system in the human body.

If you have any of the following symptoms or conditions you should consider ruling out whether gluten is a problem for you:

• Celiac disease in your family
• Autoimmune conditions, you or in your family
• Chronic diseases, especially thyroid or liver disease
• Infertility or miscarriage
• Skin conditions including eczema, cold sores, rashes
• Fatigue, lethargy
• Anxiety, depression
• Moodiness or irritability
• Anemia
• Headaches or migraines
• Joint or bone pain
• Heartburn or indigestion
• Bloating, Gas
• Diarrhea or constipation
• Congestion, allergies
• Seizures, neuropathy, ataxia
• Chronic iron, folate, or B12 deficiency
• Other vitamin and mineral deficiencies including calcium, vitamins A, D, E, K.
• Elevated liver enzymes

Additional pediatric symptoms:

• Irritability and behavioral changes
• Concentration and learning difficulties
• Failure to thrive (short stature/delayed growth)
• Delayed pubertal
• Dental enamel abnormalities

Why is it so difficult to receive a diagnosis?

In medicine, there are many things that aren’t totally clear-cut. Doctors must use judgment and evaluate your symptoms along with lab test results to come to the best diagnosis.

Yes, sometimes the results are obvious; there’s no argument what is occurring, but more often there are some gray areas and one needs to compile evidence and findings to best help one’s patient.

Laboratory tests for celiac disease are no different. Sometimes they are obvious; other times not. But the time involved to receive a celiac diagnosis “stands out” for the ridiculously lengthy period it takes. When the “why” for someone’s symptoms is celiac disease, the average diagnosis time is close to a decade.

The varied presentations of celiac disease and similarities of its symptoms with other diseases often lead to misdiagnoses such as irritable bowel syndrome, diverticular disease, gastric ulcers, allergies, chronic fatigue syndrome, or fibromyalgia.

Individuals frequently see numerous physicians before receiving a correct diagnosis. Published in Digestive Diseases and Sciences, The Canadian Celiac Health Survey revealed 37% of respondents had consulted two or more family physicians, 27% saw three or more physicians and 14% consulted two or more gastroenterologists before reaching a diagnosis of celiac disease. The mean delay in diagnosis was 11.7 years after the onset of the symptoms. https://www.ncbi.nlm.nih.gov/pubmed/17318390

What about gluten sensitivity?

Gluten sensitivity, or non-celiac gluten sensitivity, as it has come to be known, is more troublesome because there isn’t an agreed-upon method of diagnosis – there is no accepted lab test that definitively diagnoses it.

Further, many traditional doctors and gastroenterologists do not realize that a patient testing negative for celiac disease could still be suffering from gluten sensitivity.

Gluten sensitivity has been placed in the category of diagnosis by exclusion. Meaning, a patient who demonstrates the symptoms of the condition is only diagnosed with gluten sensitivity once it has been successfully ruled out that they do not have celiac disease or a wheat allergy.

Many doctors use the AGA- IgG test to evaluate for gluten sensitivity, but it may not be the best approach. A 2015 study published in Clinica Chimica Acta; The International Journal of Clinical Chemistry found the test to not work very well. They compared blood test results from people with suspected non-celiac gluten sensitivity, people with celiac disease, and those with neither condition.

They concluded that the AGA-IgG blood test isn’t sensitive for non-celiac gluten sensitivity, meaning it misses some who actually do have the condition. Their conclusion was the AGA-IgG test results can help with diagnosis, the researchers said, but only if the results are combined with other factors.  https://www.researchgate.net/publication/282342884

In diagnosis, never leave this step out

I am practical about diagnosing both conditions. Here at my clinic, we see many, many patients who are curious about gluten or have obvious symptoms that could be related to either celiac or gluten sensitivity. For those individuals, we utilize tests we feel are the current “best on the market” to give clarity to whether a gluten reaction is contributing to their ill-health.

With that said, we never fail to utilize an elimination diet where all the most common reactive foods are eliminated for a span of a few weeks and then reintroduced scientifically.

Dr. Amy Meyers says “the single best way to determine if you have an issue with gluten is with an elimination diet”. https://www.amymyersmd.com/2018/10/test-gluten-intolerance-celiac-disease/

I agree; I can’t tell you how many times an elimination diet has revealed a problem with gluten that a lab test has missed.

Why do we “bother” with labs then?

Mostly because we don’t want to perform a reintroduction if we have a positive lab test.

When it comes to evaluating for a problem with gluten, along with an elimination diet we typically also perform a complete blood test, which if positive precludes the need for a reintroduction. Similarly, if the patient feels “convinced” gluten is problematic, we discourage a reintroduction. It’s not unusual for patients to feel such clarity about their gluten reaction that they state they would no more eat gluten again than they would rat poison.

There are too many negative repercussions involved with gluten, including the triggering of autoimmune disease, for us to take lightly a reintroduction when the patient strongly feels they are reacting.

Adults with false-positive lab test

In some cases, people who have type 1 diabetes, thyroid disease, or autoimmune liver disease can test falsely positive on the tTG-IgA test. If this is your situation you would need to have a doctor who understands the other testing available to you to ensure a celiac or gluten sensitivity diagnosis isn’t missed.

Celiac, an autoimmune disease, frequently occurs along with diabetes, thyroid, and liver disease, making it vital to discern if celiac is also causing you problems.

Children with false-positive lab tests

A 2010 study published in Clinical and Experimental Immunology looked at over 200 children who were given the classic tTG antibody test for celiac disease. Nine tested positives or 4%. One child was clearly suffering from celiac disease as was supported by an additional celiac blood test and a biopsy. Two other children had positive genetics for the disease. But the rest of the children had their tTG blood test return to normal despite eating gluten.

What happened? The children with the positive test were ill at the time of testing. The researchers determined that an infection can trigger anti-transglutaminase (tTG test) antibodies but it is only temporary during the infection.

The takeaway is to ensure if you are testing a child for celiac that you do not perform a blood test while they’re ill so as to avoid any false positives.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810390/

How should you begin to discover if you have a problem?

The first step, unfortunately, often involves trying to “convince” your doctor to perform blood testing. Our healthcare model doesn’t like to pay for tests unless they are absolutely necessary, and if your doctor doesn’t agree with your suspicion you may find yourself in the dilemma of not being permitted to find out if you have a gluten problem.

If you cannot convince your doctor, yet you are very suspicious and concerned, you can find a doctor like myself who can help you to get tested. It will be without the financial support of your insurance company, but the testing is not financially prohibitive for most.

If you are fortunate enough to have the backing of your doctor, the next step is to confirm that a full panel is being run and not a single test. As we discussed above, there is more than one piece of data required to make a diagnosis and you need to ensure you are receiving a complete analysis.

What does a complete panel entail?

• tTG (anti-tissue transglutaminase) – IgA. This test is positive in about 98% of patients with advanced celiac disease who are consuming gluten, this is its sensitivity. Similarly, it will be negative in about 95% of those who do not have celiac, this is known as its specificity. One caveat is that if the person has an IgA deficiency, the test won’t be accurate. Request to add IgG as well.
• EMA (anti-endomysial antibodies)-IgA Request to add IgG as well.

• AGA (antigliadin antibodies)-IgA. AGA is less sensitive and less specific than both EMA and tTG when it comes to diagnosing celiac disease. Sensitivity is 46-87% and specificity is 70 – 98%. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3088693/

• AGA-IgG
• Total serum IgA

As you can see the panel involves 5 tests, and I recommend an additional two, the IgG versions of the top two. Why? If the total serum IgA is deficient, the tTG and EMA tests have the potential to be falsely negative. Those with celiac disease suffer from IgA deficiency ten to fifteen times more frequently than the general population so this is a valid concern.

IgG is another aspect of your immune system, unaffected by a deficient IgA, leaving you with a more complete picture of your risk rather than having to go back for additional testing after learning of an IgA deficiency.

Considering tTG and EMA are THE classic celiac tests, omitting to test the IgG version of reality makes no sense. Research agrees with me. The American Society for Microbiology Journals in  2004 had this to say: Taken together, our results indicate that the specificity of IgG-tTG is comparable to that of IgA-tTG. Detection of IgG-tTG is highly compatible with the presence of IgG-EmA and may improve the possibility of identification of celiac disease in patients with IgA deficiency. https://cvi.asm.org/content/12/2/254

I can’t tell you how often someone sends me their test results and the only test run is a tTG IgA. There’s no total serum IgA and no other tests. Certainly, if it was positive there would be some value, but if it’s negative it really doesn’t tell you anything. It was a waste of your money and blood.

Is there more you can do to receive a correct diagnosis?

Yes. If you do the above panel and all is negative, does that mean you’re in the clear? No, it doesn’t. Your risk of having celiac disease is fairly low, but the panel does not completely eliminate it nor does it negate gluten sensitivity as a possibility.

A truly complete panel would include the following:

    1. Deamidated Gliadin – Deamidated gliadin antibodies showed higher diagnostic accuracy for coeliac disease than gliadin antibodies in infancy (< 2 yrs old) per 2018 research.

https://www.ncbi.nlm.nih.gov/pubmed/23558824

2. Gliadin sub-classifications

Gliadin makes up 50% of gluten. It has four different sub-classifications, known as alpha, beta, gamma, and omega. Typical gliadin antibody tests measure only one of the four – alpha-gliadin. Needless to say, if you are reacting to one of the other three sub-classifications that will be missed by the traditional test.

3. Glutenin

Gluten is 50% gliadin and 50% glutenin. Thought once to be an innocent part of gluten, it has since been established that glutenin too can cause an inflammatory response in the body.    http://www.ncbi.nlm.nih.gov/pubmed/16772825

4. Gluteomorphins

If you’ve ever felt addicted to gluten, or the mere thought of eliminating it from your diet gives you an anxious feeling, you may very well suffer from a gluteomorphin reaction. Gluteomorphins are opiate-like compounds that can literally cause gluten to act like an addictive drug. When initially removed from your diet, those reacting to gluteomorphins can suffer irritability, headaches, brain fog, and fatigue. Working with a clinician who understands these reactions is therefore critical.

5. Prodynorphin

The building block of gluteomorphins are the opioid hormones prodynorphins. If your body is producing antibodies to prodynorphins, it’s called an opioid sensitivity, and removing gluten from your diet can result in severe withdrawal symptoms lasting from days to weeks. A lab test will reveal this sensitivity. [Huebner FR, Lieberman KW, Rubino RP, Wall JS. Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates. Peptides. 1984 Nov-Dec;5(6):1139-47. PMID: 6099562]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658803/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207593/

6. tTG 3 and 6

The classic celiac panel only tests tTG2. This can be very accurate for the typical small intestinal destruction, the hallmark of celiac disease, but there are other aspects of tTG known to affect the nervous system and the skin. Once thought to be exclusively a digestive disease, we now appreciate that celiac disease has a close association with skin and nervous system reactions including Dermatitis Herpetiformis, rashes, seizures, neuropathy, and depression, to name just a few.

7. Gluten Cross-Reactivity

This last one is its own unique test but it can be extremely valuable for those who are diligent about eating gluten-free but continue to experience “gluten” symptoms.

Especially when you are either new to gluten-free or if your gut hasn’t healed for whatever reason, cross-reactive foods can cause a “gluten-like” reaction despite the food having no gluten.

It sounds confusing, not to mention frustrating, but the reaction tends to be short-lived once intestinal healing and immune system normalization has occurred. The mechanism is similar to that of autoimmune disease. An overwhelmed, overtaxed immune system “sees” a protein similar to gluten, and in its overtaxed state cannot discern a difference so reacts to the food just as if it was gluten.

Some common gluten cross-reactive foods are rice, soy, corn, quinoa, oats, and buckwheat. Personally I had several positive cross-reactive foods positive on this test that I am now able to eat with zero problems since I have healed my gut and immune system.

The real importance of learning about the presence of such foods is that, unfortunately, they can be the reason you’re not fully healing. This is a test we utilize often because it is so very impactful.

Are you frustrated with your health?

If you’re frustrated with how you feel and don’t know where to start, let us help you. Whether you have a gluten problem or not, it’s important to realize that your body is designed to function optimally. Your body is strong and it can heal with the right help.

Our programs are tailored to you; they address the exact imbalances creating your symptoms.

If you’re not feeling your best, don’t put up with it. You’re not “too old” or “destined” because of your genetics. Let us help you.