Being the health and wellness researcher that I am, I have been digging deep into research from the last 30 years pertaining to Celiac Disease. I found an extract of a document that highlights some very important items in a presentation made by Dr. Alesio Fasano to the Celiac Disease Foundation back in May of 99. This is a must read if you or someone you know has Celiac Disease.
Here are a few points worth noting:
For those intrigued by their medical family tree, Dr. Fasano reports a 15% incidence of villous atrophy in first degree relatives of persons with celiac disease. If a (monozygotic) twin has CD, there is a 75% chance that the other twin does too.
If you’ve ever wondered how our genes may be programmed for celiac disease, European research shows a high recurrence of certain HLA types (“genetic fingerprints”) in celiacs, but–and here’s the big question mark–there are some celiacs who don’t test positive for these “fingerprints.” Keep an eye on the medical literature for the rest of that story.
Celiacs who became symptomatic after having the flu, might be interested in reports of adenovirus 12 which may be more common in persons with celiac disease. Is adenovirus a trigger for CD onset? Another development to watch.
Have your friends ever asked you what the prevalence of CD is? If you didn’t know, you’re not to blame. U.S. research is so sparse that there are no statistics here. In Europe, where screening for CD is more common, epidemiologists report incidence rates as high as 1 in 300.
Anyone diagnosed as an adult might recall having an assortment of health complaints before ever experiencing the classic gastrointestinal or dermatological symptoms. Dr. Fasano’s main emphasis seemed to be that there must be a change in the perception of how celiac disease presents itself. In one of his slides, a pyramid illustrated a new way of perceiving celiac disease clinical presentation. (The data is based on European immunological studies.)
The celiac disease that physicians in this country are trained to recognized is the typical form which in Europe occurs in approximately 1 in 2500. Dr. Fasano defined the atypical form as that found in those who have latent onset of the disease (typical + atypical = 1 in 1500). Asymptomatic celiacs are discovered when relatives of celiacs are tested. Latent celiacs are defined as those who have one of the companion diseases (other autoimmune disorders such as diabetes, arthritis, Sjogren’s syndrome, thyroid disease, collagen vascular disease, and liver disease). When combined, these various presentations of CD reach as high as 1 in 300.
Celiacs interested in the amazing interconnectedness of various bodily systems will want to watch for research that studies these connections. Dr. Fasano mentioned how toxins pass through the intestinal wall to affect the mouth, kidneys, skin and joints. In his work with children, Dr. Fasano has looked for gliadin antibodies in children with problems as varied as short stature, dental enamel defects, epilepsy and erratic behavior. He presented a theory on how gliadin may interfere with the normal binding of casomorphine in the brain. (think: endorphins).
Those interested in how testing has changed since their biopsy learned how blood tests are used. Each year, Dr. Fasano uses the IgA antibody test on his pediatric patients to see if they are complying with their diet.
It is clear that Dr. Fasano’s goal is that even celiacs without severe symptoms will someday be diagnosed promptly so that they may avoid chronic ill health, a host of long- and short-term health problems, as well as increased health care costs. He reminded CDF members that at the five-year gluten-free mark, their risk for intestinal lymphoma becomes the same as the general population.
The two major components of the disease are:
1. A genetic background. You have to be predisposed to have the disease. The genetic background plays a major role, as I will show you.
2. You have to have also some environmental factors that will trigger the disease to a full expression that can be typical or atypical.
What is the poison? Gliadin is chemically a prolamin, the alcohol soluble part of grains. So, gliadin is the alcohol soluble fraction of wheat. So, (prolamin) is the more appropriate way to define the entire family of alcohol soluble prolamins that are dangerous to celiacs.
Environmental factors are not end of the story. The genetic background is crucial. This is data that we generated years ago in Europe. Unfortunately, the data available in the States is very limited. There is no scientific interest in the States, because there is a general belief among our physicians, a gut feeling, I should say, that celiac is not here.
Looking at the general population, there is a 2 to 5% risk of developing classical (overt) celiac disease. The rate it occurs can be as much as 10% to-in the latest reports-up to 15% of first degree relatives of a patient with typical celiac disease, with villous atrophy. In other words, 1.5 out of 10 people that belong to your family may be celiac and they don’t know that.
HLA [Human Leukocyte Antigens] is a genetic fingerprint. What is being described in Europe is a high occurrence of certain HLA types in those with celiac disease. In Class I, between 70 and 80% are positive for HLA-B 8. In Class II, 70 to 80% are positive for HLA-DR 7, while HLA-DQx2 appears I about 95% of those with celiac disease. But since there are a certain proportion of biopsy-proven persons with celiac disease who do not test positive for these antigens, there must be more to the story.
The genetics are crucial, because what we believed were the landmarks of the disease are not the reality anymore. Chronic diarrhea, weight loss, etc. is not the only way that celiac disease can express itself. The severity of the disease is also variable. There are people who were exposed to gluten, and in a matter of a few weeks or a month have the full expression of the disease. Other people have to be exposed to gluten for years and years and years. (Of course, you have to understand, that if you ‘became’ celiac at age 65, that does not mean that you’ve been healthy for the previous sixty years.)
The HLA is not just a fingerprint. There is a reason why people with a particular HLA develop the disease. The enterocytes, the cells on the lining of the small intestine have some receptors which are ‘programmed’ by the Class II antigens to recognize gluten. The gluten will bind to HLA receptors that are present on enterocytes. When this binding occurs, there is a kind of migration to the other side of the cells. This receptor-gluten complex will reach cells in the bloodstream. They are like lymphocytes. They are responsible for the production of toxic compounds that are ultimately responsible for tissue damage in the intestine. The HLA Class II profile plays a major role, because it’s kind of a gate through which gluten can reach inflammatory cells that eventually will turn on an auto-immune process. The T-cells work so well that they are not able to discriminate between external substances (that they are intended to attack to protect our body) and internal substances. Gluten triggers an auto-immune attack. (Note that part of the energy that normally is there to produce antibodies against flu, for example, is not available.)
What is the prevalence of the disease in the United States? With sporadic reports from a very limited area, you can’t make any kind of global statement in terms of prevalence, unless you go for a multi-center study.
In Europe, there are changes in the past ten or twelve years in terms of prevalence of the disease there because of the awareness of the total presentation of the disease. There’s a way to classify the total presentation of celiac disease. You have symptomatic cases with typical presentation (diarrhea), and atypical (short stature, anemia, for example). Unless the endocrinologist or pathologist has knowledge to think about celiac disease, the diagnosis will be missed for years.
There are also asymptomatic patients with celiac disease who have no symptoms whatsoever, but already have tissue damage in the small intestine. Then, there is a latent form where the tissue damage has not occurred yet, but which can be discovered biochemically. This latent form will later develop into typical or atypical form of celiac disease. [Dr. Fasano mentioned delayed exposure to gluten in infancy in study of Danish prevalency statistics as a possible cause of missed diagnoses.]
The typical form is just the tip of the iceberg. In Italy, when we counted just the typical (classical) form of celiac disease, we were diagnosing 1 in 2,500 people with celiac disease. When screening programs became available with the anti-gliadin and anti-endomysial antibodies, and we looked at all forms of celiac disease, the incidence is more like 1 in 300 to 500. [Cumulative Prevalence Pyramid: Typical: 1 in 2500; add atypical: 1 in 1500; add the asymptomatic form: 1 in 1000; all presentations of celiac disease including latent form: 1 in 300-500.]
By crossing through the intestinal wall, celiac disease affects many other organs: the mouth, with stomatitis; the kidney, with nephropathy; the joints and bones; and the skin, with dermatitis herpetiformis (DH). It is universally understood in Europe that dermatitis herpetiformis equals celiac disease. About 5% of those with celiac disease have the skin lesions, too. Immunocomplexes with gliadin antibodies are present in the skin of those with DH. The erythematacous blisters tend to be symmetrical in distribution, and located on the elbows, buttocks, knees, back and/or face. [Dr. Fasano later mentions cracked lips as a possible celiac disease symptom.]
Affects on the hematological system include: Anemia (Iron, Folate/B-12 deficiency); Leukopenia; Thrombocyotopenia; Vitamin K deficiency.
Another type of clinical presentation that should be considered atypical is short stature. In Europe, reports have been published which state that up to 20% of short stature is due to celiac disease. At the University of Maryland, we have a serum bank where 20 years of serum samples are stored. I took advantage of this serum bank and had my colleagues pull samples from all those children who were diagnosed with growth hormone deficiency and who were followed in the growth failure clinic. These serum samples were analyzed for IgG anti-gliadin antibody. Their medical records were examined to see what their growth pattern was. Two populations were seen: ‘good growers’ and ‘poor growers.’ The ‘good growers’ who responded well to growth hormone therapy, all had antibody levels within normal range. Among those who did not respond to growth hormone, a large proportion had high titers of anti-gliadin antibodies. Of those in the high antibody group who consented to undergo small intestinal biopsy, all were found to have celiac disease. Now, at the University of Maryland, children admitted for growth failure are routinely tested for anti-gliadin antibodies.
Osteoporosis starts in childhood with Calcium and Vitamin D deficiencies. The potential health implications include needless bone fractures.
Enamel dysplasia is also common among those with celiac disease. This discoloration is due to gliadin antibodies along with gliadin in the matrix of the teeth. You can actually follow the evolution of celiac disease by following the lines in the teeth, especially in those who have undergone gluten challenge.
The central nervous system may also be affected. Epilepsy occurs twenty times more often in persons with celiac disease than those in the general population. Calcium deposits form in the brain because of a deficiency of folic acid. In one child, the calcifications disappeared after 1 to 2 years on a gluten-free diet. Other ailments include schizophrenia, dementia, and cerebellar degeneration.
The more we study celiac disease, the more we realize that it is an immunological disorder which is associated with other immune-based disorders. Some of these are: diabetes mellitus (Type I), thyroid disease, Sjogren’s syndrome, rheumatoid arthritis, collagen vascular disease, and liver disease. The genes responsible for diabetes, for example, travel back-to-back on the same gene.
In pediatrics, another very dramatic presentation is mood changes. One of our studies suggests that gliadin may actually act on the brain by interfering with the binding sites [opiate receptors] for B-casomorphine [endorphins].
Persons with asymptomatic celiac disease complicate the problem. Since they feel fine, they are difficult to find. One source is among the first-degree relatives of those who have been diagnosed. About 10% of them will show small intestinal damage. First, we screen parents, siblings and children of those with celiac disease using the anti-gliadin and anti-endomysial antibody blood tests. Those who test positive are biopsied. Any who show damage to the lining of the small intestine are diagnosed with celiac disease and place on a gluten-free diet. It is crucial to treat these people as true celiacs!
The diagnosis protocol has changed over the years. Even though the antibody screening is not totally reliable (still produces false negatives), it has reduced the need for multiple biopsies, permeability tests, etc. The new protocol: If you are positive for both the IgA and IgG anti-gliadin and the IgG anti-endomysial antibodies, your chance of having celiac disease is about 99.6% (positive predictive value).
For pediatric diagnosis of celiac disease:
- If the patient has:
- a history and clinical picture suggesting celiac disease
- laboratory data (including antibodies) consistent with celiac disease
- a clear histological picture of crypt hyperplasia and subtotal villous
- obvious clinical and laboratory response to a gluten-free diet
- an age of more than two years
- possibility of having cow milk protein sensitivity has been eliminated
- responds to gluten-free diet
then, the patient has gluten sensitivity enteropathy for life.
Antibodies can easily be used to check for compliance to the gluten-free diet. At our clinic, we now check IgA antibodies every year.
Why is it so critical to make a diagnosis and keep people free of gluten, even if they are asymptomatic?
Chronic ill health and increased health care costs. Permanent stunted growth. Skeletal disorders, such as osteoporosis. Infertility. The mortality rate is twofold greater in persons with untreated celiac disease. I am sure you are also aware of the increased risk of malignancy in those with celiac disease who continue to be exposed to wheat, rye, oats or barley. The incidence of intestinal lymphoma is much higher in celiacs chronically exposed to gluten than persons in the general population. Those who strictly follow their gluten-free diet, however, can expect a reduction in their risk, so that at the five-year gluten-free mark, their risk factors are the same as the general population.
- What is Celiac Disease – Must See Video (glutenfreemommyandme.com)
- What Foods are Bad for You with Celiac Disease? (glutenfreemommyandme.com)
- Probiotics: New Hope for People with Celiac Disease (glutenfreemommyandme.com)