Celiac Sprue 2006 An Update by Enest Stanley, MD

What is Celiac Sprue?
Celiac Sprue, or Celiac for short, is an allergic reaction to ingested wheat and wheat-containing products that damages the delicate lining of the small intestine. Few people realize that over seventy percent of the body's immune system lies in the digestive tract, mostly within the walls of the small intestine. One of your small intestine's jobs is to absorb the water and nutrients that you need from your diet. At the same time, it must ward off foreign invaders (such as bacteria) as they try to cross the intestinal wall and enter your blood stream. It's a big job, and sometimes the small intestine gets confused. One such instance is Celiac sprue, a disorder in which the small intestine mistakenly believes that wheat, often called the staff of life, is harmful.

When a person with Celiac eats a slice of bread, a specific protein component in wheat, called gluten, crosses the intestinal lining and causes the gut's immune system to be activated. (Gluten is also found in rye and barley.) Once activated, a battle begins. The immune system attacks and destroys the invading protein. Like all wars, collateral damage often occurs and the fine absorptive structures of the gut, called villi, become flattened causing a decreased absorption of nutrients and a myriad of clinical symptoms.

What are the symptoms?
Undiagnosed or untreated Celiac can manifest as abdominal pain, bloating, excess gas, diarrhea or constipation and lactose (milk sugar) intolerance. Outside the digestive tract symptoms may include unexplained fatigue, persistent anemia, premature softening of the bones (osteoporosis), headaches, infertility, skin rashes etc. Because of the vague nature of these symptoms the diagnosis is often missed. The average patient seeks medical care for over five years before an accurate diagnosis is made. See our past newsletter Celiac-When Bread is Poison for a more detailed review.

Increasing incidence - Tip of the iceberg
Celiac is a much under-recognized and under-diagnosed condition. Until a few years ago the estimated number of affected Americans was 1 in 5000. This really didn't make a whole lot of sense, as our European ancestors had a 10 fold higher estimated risk. In a landmark study, Dr. Alessio Fasano, a professor of pediatrics at the University of Maryland School of Medicine, showed the true rate of Celiac sprue in Americans to be closer to 1 in 250. This is certainly much higher than previously thought and in keeping with what was being observed in Europe. Recent studies from the Mayo Clinic and John Hopkins estimate the rate even higher at approximately 1 per 100. With that high of an incidence there should be many more diagnosed Celiacs than we are currently seeing in clinical practice. Essentially this means that there is a silent epidemic out there with 97% of Celiac going undiagnosed, and all of the negative health consequences that go with untreated Celiac.

Current Treatment Strategies
If you are lucky enough to have Celiac correctly diagnosed there is good news - it can be treated and put in remission by going on a gluten free diet. There is also bad news as a gluten free diet is difficult to maintain and must be lifelong. Re-ingestion of wheat, barley or rye either intentionally or unintentionally results in recurrent symptoms and disease. It is very important that patients with Celiac realize that they must become their own advocate. They must educate themselves with the many resources available on Celiac disease. Becoming familiar with what is allowed and what is forbidden is overwhelming at first - but once one learns to read and understand contents on labeling it really becomes second nature! Unfortunately, there is NO CHEATING on a gluten-free diet. It must become a way of life.

The response to treatment should be monitored with blood tests which detect the body's immune response to wheat ( so-called tTG-Iga antibodies). These antibodies gradually decrease in amount once a gluten free diet has been established and allow the doctor to follow success and compliance with the diet. I recommend checking them once yearly.

Once the intestinal damage heals, absorption of calories and nutrients returns to normal with the symptoms of Celiac resolving over a 3 to 6 month time period. Bone density and anemia should be closely monitored to document normalization especially in females. Vitamin, calcium and iron supplements are in order. At one year out from treatment, if bone density remains below normal, then medications for osteoporosis (Fosamax, Actonel, etc) should be considered. First degree relatives (parents, siblings, children) have between a 1:10 and 1:20 incidence and should be screened with blood testing for tTG-Iga antibodies.

Future Treatment Strategies

1. Prevention
Celiac Sprue occurs when three factors combine to cause a clinical disease:
(1) the predisposing genes (haplotypes DQ2 and/or DQ8),
(2) have been sensitized or exposed to gluten and
(3) continue to ingest gluten which maintains the immune response and damage.

The second factor is very important in regards to preventive intervention. The timing of the introduction of wheat into a baby's diet appears to make a difference to future risk of Celiac. In the early 1980's there was an epidemic of new Celiac diagnosis in Swedish infants. A five fold increase in the number of cases was linked to a lack of breast feeding and large amounts of gluten added to infant formulas at that time. National guidelines (gluten free formulas and increased breast feeding) were introduced which resulted in a marked reduction in the number of new cases. A recent study confirmed the findings and treatment strategy. Norris et al publishing in "Nature Practice Gastroenterology and Hepatology" Oct 05 showed that children fed gluten containing foods within 3 months of age had a five fold increase in Celiac compared to those fed gluten between 4-6 months of age. Somewhat unexpected was that waiting longer, (greater than 7 months), to introduce wheat was associated with a slight increase in the risk of disease.

2. Enzyme Therapy
An exciting development on the treatment front has been the identification of an enzyme developed for commercial food processing which turns out to quickly and nearly-completely break down gluten molecules that cause Celiac disease. The enzyme AN-PEP operates best in the acidic enviorment of the stomach and works 60 times faster than an earlier promising enzyme, breaking down gluten molecules within 4 minutes. "On the basis of our results, there now is a realistic chance that oral supplementation with an enzyme can ensure gluten degradation in the stomach before reaching the small intestine, where it causes problems for people with Celiac disease," according to Frits Koning, researcher at the Leiden University Medical Center, The Netherlands, who headed the team that has published a new research paper on its work. Of course, this would be the Holy Grail for Celiacs, but further studies are needed ultimately in human subjects since Celiac lacks an animal model.

3. Stopping the leaky gut
AT-1001 from Alba pharmaceuticals is a novel approach directed at preventing gluten from damaging the intestines. Part of the mechanism allowing gluten to do its damage is leaky gaps between the cells lining the gut. When gluten leaks through these gaps it activates the immune system causing the damage that leads to Celiac. If you could make these gaps tighter or keep them closed, gluten would not have access to the gut immune system. AT-1001 does just that by decreasing a protein called Zonulin which is released with food and gluten ingestion. Zonulin, which opens the cell gaps are found in higher levels in Celiac and Type1 diabetics - a closely related disease. The drug has shown success and has been fast tracked by the FDA and now is in Phase II trials. Active patient recruitment is under way.

Summary
The increasing number of people suffering from Celiac has lead to a spotlight on this previously thought to be rare disease. The effect has been an improvment in physician recognition, patient advocacy groups, and reseach. The potential for prevention and improved management strategies other than gluten-free diets are giving hope to Celiac suffers.