Dr. Pastore is a practitioner, consultant and researcher in biomedicine and human nutrition. In all his efforts he strives to develop novel methods using an amalgam of biomedical and clinical informatics data, encompassing biological observations to solve or assist in resolving a problem.

USA Today

The Washington Post

Forbes

The Morning Call

Celiac disease is a serious autoimmune disease that is not receiving the attention it should by many medical professionals and even the National Institutes of Health. It can act as a clinical chameleon, eluding diagnosis, and this has resulted in the average time to diagnosis being ten years, which I refer to as the “decade to diagnosis.” Here are some startling facts.

Data suggests 83% of those with celiac disease are undiagnosed.

Prevalence in the general population is 1 out of 100 but increases to 1 out of 10 if there is a relative with the disease.

The incidence in the United States has doubled every 15 years since 1974.

There is a 2 to 4 times increased risk in coronary artery disease and small intestinal cancer for those with celiac disease over the general population.

There is an increase in all-cause mortality for those who are undiagnosed.

Currently, the ONLY accepted treatment is a strict life-long gluten free diet, but data is indicating inadvertent exposure to gluten from certain prescription medications, cross-contamination and the contamination of foods routinely thought of as being gluten free.

While those facts can be alarming, for me the true story goes back to the clinical aspects of the disease, the delay in diagnosis and how it presents to the medical professional in practice. Often symptoms are vague, outside of the gastrointestinal tract, and cause the physician or even specialist to either not consider celiac disease as a possibility, or an incomplete diagnostic panel is undertaken, which can result in misdiagnosis.

Deepening this story is the strong potential that the physician may not be fully aware of the nuances of celiac disease testing and result in continued patient suffering and the decade to diagnosis. McCormick and colleagues presented this potential issue at an American College of Gastroenterology conference and Assiri and colleagues and Zipser and colleagues discovered similar findings.

 For example, for many doctors an IgA tissue transglutaminase antibody analysis could be the first and only blood test used to determine risk in a patient. Yet, a selective IgA deficiency has a rate of occurrence 10 to 15 times more frequent in celiac disease patients than their non-celiac counterparts.

 With that in mind, if testing a single IgA based gluten test, it is wise for physicians to measure total serum IgA first, because that should dictate the correct testing course of action. An IgA deficiency renders the most popular initial blood test screening moot and physicians should consider other serology, measuring gliadin DGGL gliadin deaminated IgG antibodies.

There are some options for serology testing for the potential celiac disease and should be selected on unique requirements of the individual patient. These tests include tissue transglutaminase IgA and IgG, DGLDN gliadin deaminated antibodies IgG and IgA, endomysial antibodies IgA as well as celiac associated HLA-DQ alpha 1 and DQ beta 1 medium high-resolution DNA typing.

 The goal of any tests for celiac disease risk is to identify if a biopsy is required, which is the gold standard for celiac disease diagnosis in the United States.

In other cases, uncommon symptoms may actually be the dominant ones presenting in clinical practice. They were for me and contributed in my more than a decade to diagnosis. Referencing the aforementioned work by McCormick, Assiri, Zipser and their respective colleagues, not all health care practitioners may be aware of all the associated symptomatology. Take a look at an example of classic symptoms and non-classic symptoms and manifestations below.

Now look at an example of sIgA deficiency symptoms and imagine how this can present to a physician without experience in celiac disease diagnostics.

Incomplete or incorrect medical decision-making and my personal experience was the catalyst for my work in enhancing diagnostic knowledge and the understanding of the symptomatology, culminating in the creation, study and publication of a clinical decision-making expert system for celiac disease assessment.

Regarding treatment being a life-long gluten free diet, data collected by researchers from the pharmaceutical company Takeda and the Celiac Disease Foundation reported 74% of individuals with celiac disease claimed they were exposed to gluten within the past 30 days.

 If you really think about it that is not a shocking piece of information when gluten is omnipresent and cross contamination risk is so high. In 2010, Thompson and colleagues had twenty-two gluten free grains and seeds sent to a lab for gluten analysis.

 Seven of the products were contaminated with gluten.

 These products were considered gluten free by default because they are naturally gluten free and therefore were not labeled gluten free. Products studied included millet flour, millet grain, buckwheat, soy, brown rice, amaranth and flaxseed.

 These are gluten free foods by nature, but obviously gluten contamination occurred via processing.

 Strict gluten free labeling and testing is required to assure a product is gluten free.

Moreover, there are known current conditions and diseases that have been linked to celiac disease in multiple studies in peer-reviewed literature.

 Any of these diseases below should alert a physician to test for celiac disease risk.

It can take a village for a proper diagnosis to transpire. Celiac disease encompasses many different diseases, leaving signs to alert practitioners to start the diagnostic process. The Canadian Dental Association released a clinical diagnosis guide for dentists based on the oral manifestations of celiac disease, which include chronic dental carries, weak enamel and aphthous stomatitis, in an effort to screen patients for further testing.

 The American Journal of Clinical Dermatology published a guide for dermatologists to enhance the recognition of cutaneous manifestations of celiac disease, with dermatitis herpetiformis being the primary sign.

 Turco and colleagues noted an increase in anxiety and depression in children with celiac disease and functional intestinal disorders.

Due to the fact that celiac disease can present as a clinical chameleon, alter the microbiome, is implicated in other autoimmune diseases, and can present with signs and symptoms that will most likely be seen by many different specialists in health care, a focus on obtaining an accurate diagnosis is key. If all these specialists are up to date in their knowledge of the many ways celiac disease can present in clinical practice and linked together in a health care information system, and sharing data via an electronic health record, may create an environment for a more accurate and prompt diagnosis, and improved continuity of care.

Celiac disease is a serious autoimmune disease that is not receiving the  attention it should by many medical professionals and even the National Institutes of Health. It can act as a clinical chameleon, eluding diagnosis, and this has resulted in the average time to diagnosis being ten years, which I refer to as the “decade to diagnosis."

Celiac Disease: A Clinical Chameleon

There are three interesting facts about sleep deprivation and immunity that are based on scientific study.

Lack of quality sleep is associated with a higher likelihood of getting sick after being exposed to a virus.

Lack of quality sleep negatively impacts how fast you recover if you do get sick.

Long-term poor-quality sleep increases the risk of specific diseases that in and of themselves are risk factors for an increased risk of infection and those are cardiovascular disease, diabetes and obesity.

The goal for adults should be to obtain 7 to 9 hours of uninterrupted sleep per night. For teens the ideal range is 8 to 10 hours per night. Raise your hand if you hit your target.

Why does sleep deprivation equate with truncated immune functioning?

The governing concept is that sleep is believed to support the initiation of an adaptive immune system response. So, a good night sleep on a regular basis supports the following: if exposed to an invading antigen the human immune system takes up that antigen with antigen presenting cells and presents fragments of the antigen to cells called T helper cells. The T helper cells release a cytokine called IL-12 and that calls in the squad known as a T helper cell 1 response which supports the work of antigen-specific T cells and starts the production of antibodies by another type of cell called B cells. It’s this antigen/antibody response that initiates long lasting immunity. Sleep helps foster this adaptive immune response in lymph nodes. Disrupting sleep, disrupts the adaptive immune system response [1].

Of course the first question you should ask if you are experiencing a major deviation from the recommending amount of sleep is are there any medical reasons behind your poor-quality sleep that need to be addressed?

The following can interfere with quality sleep.

•	Gastrointestinal problems such as reflux

•	Neurological conditions such as Parkinson's disease

•	Prescription medications – birth control, cold and flu medicines, drugs for asthma, hypertension medication, thyroid medication, etc. There are many prescription medications that can interfere with sleep. Please talk to your doctor about any concerns.

•	Restless leg syndrome – a neurological condition causing discomfort and the need to move one’s legs, strongly linked to iron deficiency anemia.

•	Sleep apnea – (main types are obstructive, central and complex).

Let’s hypothesize that’s all covered. What about prescription sleep medications?

As I mentioned on a previous podcast, “I’ve spoken with many sleep experts over the years and none of them believe these drugs are sleep saviors. On the contrary they do not believe a human obtains true restorative sleep on these medications.” I also stated, “All of these aforementioned prescription drugs and OTC medications have a risk of side effects including but not limited to drug tolerance, rebound insomnia, headaches, dizziness, nausea, difficulty swallowing or breathing, worsening depression, suicidal ideation and even a potential link to dementia and increased mortality.” Please listen to that episode for more info. While there are many physicians that recommend these medications, I’m certain none would recommend them for chronic use every single night for the rest of your life.

Address stress in the best way that works for you – meditation, exercise, cognitive behavioral therapy, psychotherapy, etc.

Do not consume caffeine late in the day. Some people are so sensitive that any more than one cup in the morning disrupts their sleep and for others they are fine having more, including late in the day. Learn your tolerance and stick with it.

Napping too late in the day can disrupt sleep in the evening.

Exposure to artificial light late in the evening, or prior to sleep. It disrupts normal neurological signaling required for sleep from taking place, such as the formation and release of melatonin, and the upregulation of excitatory neurotransmitters.

Adjust room temperature – too warm of a temperature can have negative affect on sleep

Alcohol is a sedative. It can make you fall asleep initially but may disrupt your sleep later in the night.

Nicotine from vaping or smoking – it’s a stimulant and disrupts sleep. Nicotine is a neurotoxin. Seek help to stop if you use it.

Eating too close to bed is a problem as well, keeping you up digesting instead of sleeping.

Consider trying something natural. I’m always asked about melatonin. So, let me explain that for a moment before I tell you what I personally take every night before bed.

Melatonin elicits its effects on the suprachiasmatic nucleus (SCN), an area of the brain the controls our circadian timing system, via at least two high-affinity melatonin receptors, MT1/MT1a and MT2/MT1b. Two distinct functional roles for melatonin on SCN physiology have been identified. Firstly, melatonin acts to promote sleep through the acute inhibition of SCN neuronal firing, a mechanism mediated by MT1/MT1a receptors. Secondly, melatonin has a phase-shifting effect which entrains the circadian rhythms within the environment and is mediated in part by MT2/MT1b receptors. The impact of these efforts are initiating sleep.

Unfortunately, many people experience negative side effects from melatonin, even at the standard lowest over the counter dose. In my early days in practice I successfully found a dose that had 500mcg, which is exactly half of the standard 1mg dose. Currently, I see 3mg to 5mg as a starting dose and I couldn’t imagine taking those. The feeling I had was akin to others reporting side effects such as a groggy feeling the next day, something I called a “melatonin hangover.” While we all know melatonin plays a crucial role in sleep, I always desired the tiniest dose possible. I also believe in a multifactorial approach to assisting sleep. As a dad, I absolutely need something. I cannot just turn off my brain at night and sleep. Every night I take an over the counter supplement called 

, that contains nine ingredients to help foster sleep. I co-authored a paper on each of these ingredients with Dr. Jennifer Newson, a PhD in neuroscience from Oxford. I have found it to be a game changer.

There are three interesting facts about sleep deprivation and immunity that are based on scientific study. 

Poor Sleep Quality and Immunity

Should you just immediately go gluten free and skip any diagnosis? No, and I’ll explain in a bit. The goal is to find out if you have this lifelong disease. 

 and schedule an appointment with your doctor. All the testing I’m about to recommend (except for genetic testing) requires gluten being in your diet.

It may help to bring this article to your doctor. I’m going to do my best to simplify this process, but please note things can get a bit complicated.

Start with a request for a total serum IgA and a tissue transglutaminase IgA. Many doctors prefer to get both tests done at the same time once you provide the reasoning. As mentioned above, there is a risk for a total IgA insufficiency and that could render any IgA test moot. If your total IgA is low, ask your doctor to order a tissue transglutaminase IgG and Gliadin (deaminated) IgG serum blood test. If any of those results are positive, proceed to a biopsy.

Providing another scenario, let’s say your total IgA is normal or elevated and your tissue transglutaminase is between 4.0 and 10U/mL. In that circumstance it would be wise to have additional blood work done including a Gliadin (deaminated) antibody IgA and Endomysial antibodies IgA (both are serum analyses). If the Endomysial antibodies are negative and the deaminated gliadin blood test is less than 20.0 units, request celiac disease associated HLA-DQ Alpha 1 and DQ Beta 1 Medium-High Resolution DNA typing via blood test. If this is negative, we can rest assured it is not celiac disease. If the result is positive for DQ2A1 or DQ8B1, this is a risk for celiac disease and a biopsy would be recommended.

Let’s go back to receiving a normal or elevated IgA but now your tissue transglutaminase result is greater than 10.0U/mL. If that is the case, you should be making sure you are being scheduled for a biopsy. In the event your biopsy is not consistent with your serology, meaning your biopsy is not revealing evidence of celiac disease, definitely request the aforementioned genetic testing. If the biopsy is in dispute with the serology and the genetics are present, you should be followed up for future celiac disease as your risk is extremely high.

Now let’s examine a case where the result of the IgA is normal or elevated, but this time the tissue transglutaminase is less than 4.0U/mL. While this does indicate celiac disease is unlikely, make sure you and your doctor know 10% of patients with celiac disease can present as being seronegative (meaning they do not show any indication in their blood). In that case the doctor should order the DNA testing mentioned above and make a decision based on those results.

Now let’s go back to the beginning of my recommendation for blood tests and look at the results of a total IgA test and imagine the result is below the age-matched value or a little over 1mg/dL or equal to 1mg/dL. In that case the course of action would be to run dual antibodies for celiac disease testing, such as tissue transglutaminase IgA and IgG and Gliadin (deaminated) antibodies IgA and IgG. Granted, this scenario really only works if the physician only ordered an IgA total alone as the initial line of testing. If your doctor combined it with a tissue transglutaminase IgA, and the result is as described in this paragraph, definitely request the IgG versions of each test as written above.

When looking at the results of the tissue transglutaminase IgA and IgG and the Gliadin (deaminated) IgA and IgG, please note any result that is positive OR equivocal should lead to a biopsy. IF the results are normal, request the celiac disease DNA testing I describe herein as 10% of celiac disease patients may present as being seronegative.

Let’s throw a monkey wrench into the mix. Imagine you believe you have celiac disease, stumbled across this article, print it and give it to your doctor and request starting testing as I discuss above. What if the response you receive is something akin to *“let me ignore all of this and just order an IgA Endomysial antibody test as it has a specificity of almost 100%?”* Kindly remind your doctor that about 5 to 10% of people with celiac disease do NOT have a positive Endomysial antibody test and that it is NOT as sensitive as the tissue transglutaminase test.

 Also note, this test is more expensive than other testing, may not be covered by insurance if it is the first test chosen and could leave you just as lost if you are low or deficient in total IgA. I favor Endomysial antibody testing at the right juncture, for the right reasoning, justifying the medical coding, all while progressing toward a diagnosis.

Additionally, perhaps you just had genetic testing done on your own and it states you are positive for one or both of the HLA-DQ genes associated with celiac disease. That doesn’t mean you have celiac disease. Approximately 30% of the population carry one or both of the genes for celiac disease. All that means is their risk increased from what is currently believed to be 1% of the population, up to 3% of the population. Your genetic test results should initiate a conversation with your doctor and that should initiate correct serology for celiac disease that can lead to a biopsy for a proper diagnosis.

As a scientist and individual with celiac disease, I am equally concerned for those that are unaware and remain undiagnosed as I am for people that believe they may have celiac disease and decide to just stop eating gluten instead of speaking with their doctor to start the diagnostic process. This is risky behavior for many reasons, but just on the surface, imagine never really knowing if you have the disease or not. Will you really be 100% militant ALL the time for the rest of your life with your gluten free diet? Including speaking with your doctor and pharmacist about every medication (prescription or OTC) to be certain it is gluten free? Will you speak with your server and chef at every restaurant every time you go out to eat? Will you have the willpower at a holiday party or birthday celebration to not partake in any gluten containing foods, even the tiniest crumb? What about after a night of drinking with colleagues or out with friends? Will you have the resolve not consume the gluten containing foods all around you? Are you aware that you cannot be properly tested for celiac disease risk if you are not consuming gluten? I can go on and on with just these small examples.

The big picture is you could have a disease that can cause many other diseases, increase your cost of living, and increase the risk for your offspring. For me, and the many people I have spoken with who have celiac disease, a formal diagnosis was a concrete and permanent life changing event that fostered extreme discipline in my dietary choices and will for the rest of my life. I have never met a person that decided to go gluten free and has remained as militant as a diagnosed celiac.

If the circumstance arises that your healthcare practitioner recommends saliva testing or stool analysis to “test for celiac disease” please note these tests are not accepted by the American College of Gastroenterology for the diagnosis of celiac disease at this time. Research into saliva tests for pediatrics are underway and such tests will receive rigorous scientific evaluation for their efficacy and FDA approval. The accuracy of stool tests for tissue transglutaminase antibodies is as low as 10%.

 Stick with solid science for the true path to diagnosis.

If you think you have celiac disease, this is the process I would recommend. You should not immediately go gluten-free and skip any diagnosis – instead, do not stop eating gluten and schedule an appointment with your doctor and follow the testing process I describe in this article. 

What do you do if you think you may have celiac disease?

In this episode, Dr. Pastore covers infertility in men and women could be caused by Celiac Disease. If you have the HLADQ2 or HLADQ8 Celiac gene but do not have Celiac disease, your child still could be born with or develop Celiac disease. If one of the biological parents are a gene carrier or are a diagnosed Celiac, a gluten-free diet should be followed during pregnancy

Dr. Robert Pastore, PhD, CNS

Dr. Pastore is a practitioner, consultant and researcher in biomedicine and human nutrition. In all his efforts he strives to develop novel methods using an amalgam of biomedical and clinical informatics data, encompassing biological observations to solve or assist in resolving a problem.

Dr. Pastore in the Press

Popular Articles & Podcasts

Celiac Disease: A Clinical Chameleon

Poor Sleep Quality and Immunity

What do you do if you think you may have celiac disease?

#051 - On Pregnancy & Celiac Disease