Celiac Disease: More of the Story.

17 Sep 2017

Celiac Disease

When I wrote The Lyons Lifestyle, I mentioned that I had a much larger article than I wrote about in the book. This is the additional information not included in the book. I hope this gives you a better understanding about gluten and celiac disease.

Celiac disease (CD) is a chronic medical condition wherein a person develops an inflammatory immune reaction to the storage protein components (collectively called gluten) found most commonly in wheat, barley and rye. This immunologic reaction leads to damage to the intestinal lining in the first part of the small intestine known as the duodenum. In severe cases, the inflammation can be more extensive. If gluten is removed from the diet, a marked improvement in the damage to the intestine is seen and there is a recurrence of the damage with the renewed consumption of these grains.

Celiac disease occurs in about 1% of the population and affects children and adults alike. In the adult population, 20% of those diagnosed with this malady are over the age of 60 demonstrating that diagnosis may be delayed for decades. Classic clinical presentations of diarrhea or maldigestion will often lead to the diagnosis but many present with much more subtle medical conditions as will be discussed later in the article.

Epidemiology

Celiac disease occurs in most population groups in the world other than Central Africa, Japan and China. The whole of Europe, the rest of Asia, the Middle East, the Americas and all Caucasian populations are affected. Most reports suggest a female to male ratio of about 2-3:1. The prevalence of disease is reported at 0.5 to 1% however, many individuals are not diagnosed or delayed in their diagnosis because of atypical clinical presentations. Recent data suggest an increasing prevalence in CD. Recent data from the Mayo Clinic demonstrates that the prevalence of CD as increased by as much as 400% since the 1940-1950’s. Analyzing frozen blood samples from large populations of individuals from that era have been compared to modern population data revealing this insight. What is worse, prospective data on patients suffering from CD are at increased risk of developing cancer, heart disease and lung diseases by as much as 30-49% compared with those without CD.

Why the increasing prevalence of CD? Wheat has dramatically changed since the 1950’s. In the 1960’s to the present time, wheat has been hybridized through genetic modifications to dramatically increase crop yield. A consequence of this gene change has been a massive increase in the quantity of gluten and other compounds in wheat. A single slice of whole wheat bread today contains about as much gluten as 100 slices of bread from the 1950’s.

Clinical Presentations

As we have gained a better understanding about celiac disease, four different categories of CD have emerged. The first is typical or classic CD. These individuals present with predictive symptoms of diarrhea and weight loss. Depending on age of presentation, other issues such as short stature, delayed puberty, or failure to thrive may also be seen.

The second category is atypical CD. People in this group typically present with more vague complaints such as: abdominal bloating or distention, anemia, abnormal liver chemistries, thinned bones (osteoporosis), peripheral nerve damage, seizures, personality problems, skin problems, enamel loss from teeth, cold sores in the mouth, hair loss, recurrent vomiting or loss of appetite.

The third group is latent CD. These are individuals who were diagnosed with CD at a young age but now are no longer intolerant of gluten. The reason for this reversal of CD status is unclear but some of these individuals can subsequently revert back to active CD and need to be monitored.

The fourth group is potential CD. This is a frequent pattern that I see in my clinical practice today. These patients have circulating antibodies to gluten components but do not have microscopic damage seen in biopsies obtained from the small intestine. These individuals are also sometimes referred to as the third group of latent CD. These people have a significant intolerance to gluten but do not manifest the spectrum of disease seen in CD patients.

Finally, there are a group of individuals who become quite symptomatic when consuming gluten products but do not manifest any of the immunologic or microscopic findings seen with CD. These individuals cannot be given a diagnosis of CD but their gastrointestinal complaints dramatically improve when they reduce their gluten intake. This is a bit more complicated in these individuals as wheat contains fermentable carbohydrates that can induce many gastrointestinal symptoms that can mimic celiac disease. The cause of the symptoms is not the gluten; rather, it is from the fermentable carbohydrates creating gas, bloat and irritable bowel in the colon.

Pathogenesis

The storage proteins (gluten) found in wheat (gliadin), barley (hordein) and rye (secalin) interact with the lining of the small intestine and stimulate an inflammatory immune reaction in genetically susceptible individuals leading to the presentation of CD. Not all presentations are the same as can be seen above, but the pathogenesis of CD occurs in a similar fashion. Components of ingested gluten are taken up and presented to T lymphocytes (a type of white blood cell that helps regulate our immune system). These T cells then activate another population of lymphocytes known as B cells.

The B cells then produce antibodies directed against some of the protein components of gluten as well as antibodies directed against an enzyme thought to play a role in the pathogenesis of CD. This enzyme is named tissue transglutaminase or TTG and a valuable antibody marker against TTG is helpful in establishing the diagnosis of CD. Antibody production against TTG and components of gluten allow the clinician to test blood of individuals suspected of suffering from CD.

The CD-activated T cells also stimulate other populations of T cells that then release inflammatory chemicals (interferon, interleukins, tumor necrosis factor and tumor growth factor) that lead directly to tissue damage to the intestinal lining.

The disease tends to affect the first part of the small intestine; however, in more severe cases, the entire small bowel may be damaged. The inflammatory damage of the intestinal lining decreases digestion and absorption of nutrients because of flattening of the surface area. This flattening can be seen when the lining is biopsied and observed under the microscope.

Nutrients affected include iron and folic acid in proximal small bowel CD but with advanced disease involvement patients can develop: calcium, magnesium, vitamin D, vitamin B-12, and/or vitamin K deficiency. Because of flattening of the intestinal lining, total calorie, fat, carbohydrate and protein maldigestion can occur.

Antibodies seen in CD as well as microscopic damage seen in the lining of the small intestine are normalized in most individuals when they refrain from gluten in their diet. The antibodies return and damage recurs if they revert back to excessive gluten intake. When celiac disease is in remission, nutrition, absorption and health also return.

Associated Diseases

Celiac disease is now recognized to be associated with many medical conditions. One of the strongest associations is dermatitis herpetiformis (DH). This skin condition is an intensely itchy blistering disorder seen most frequently on the elbows and legs but can also occur on the buttocks, trunk, neck and scalp. A tissue diagnosis of the damaged skin area is easily established and withdrawal from gluten in the diet will usually cause the DH to go into remission.

CD is an autoimmune disease and it is not surprising that its presence is associated the occurrence of other autoimmune disorders in the same individual. Established associations include:
Type 1 diabetes
Autoimmune thyroid disease
Rheumatoid arthritis
Sjogren’s disease
Microscopic colitis
IgA deficiency
IgA nephropathy
Hyposplenism
Pancreatic insufficiency
Inflammatory bowel disease

Other diseases that have been reported to occur with CD but not as definitively as the above list are:
Down’s syndrome
Turner’s syndrome
Autoimmune hepatitis
Primary biliary cirrhosis
Myasthenia gravis
Systemic lupus erythematosus
Addison’s disease
Sarcoidosis
Systemic vasculitis
Polymyositis
Pulmonary hemosiderosis
Fibrosing lung disease
Cystic fibrosis
Recurrent pericarditis
Schizophrenia
Cavitary lung disease
Small bowel bacterial overgrowth
Idiopathic thrombocytopenic purpura
Macroamylasemia
Congenital heart disease
Epilepsy

Because CD is rather common, it is sometimes difficult to establish true associations and time will tell as to which ones are real or just published anecdotes.

Finally, CD is considered a premalignant condition, especially in chronically uncontrolled individuals. The strongest association with cancer and CD is small bowel lymphoma. A specific type of lymphoma called enteropathy-associated T-cell lymphoma (EATL) has a very high association with CD. Other cancers that have been reported with increased frequency with CD include: small bowel adenocarcinoma, esophageal carcinoma and oropharyngeal squamous cancer. Avoidance of gluten for five years in patients suffering from CD reduces that risk.

Differential Diagnosis

Many diseases can mimic various aspects of CD. As can be seen above, CD can present with different clinical components and this can cause difficulty in sorting out the diagnosis. As noted, associated ailments can be seen in patients with CD and in many individuals more than one diagnosis is often seen. Regardless, an open mind is needed to sort through the possible causes, associated diseases and CD. The differential diagnosis is as varied as:
Whipple’s disease
Peptic ulcer disease
Helicobacter pylori infection
Lactose intolerance
Pancreatic insufficiency
Gallbladder disease
Fructose malabsorption
Inflammatory bowel disease
Irritable bowel syndrome
Giardiasis
Cryptosporidiosis
Strongyloidiasis
Coccidiosis
Hookworm infection
Mycobacterium avium complex infection
Small intestine bacterial overgrowth
Tropical sprue
Collagenous sprue
Immune globulin deficiency
Kwashiorkor
Acquired Immune deficiency
Eosinophilic gastroenteritis
Graft versus host disease
Post viral gastroenteritis
Medication/chemotherapy-induced enteritis
Radiation enteropathy
Autoimmune enteropathy
Alpha chain disease
Specific food allergies

Diagnosis

As can be seen from the issues discussed above, the first step in diagnosing celiac disease is suspicion about the diagnosis. Additionally, many cases of CD are diagnosed later in life because of a lack of classic symptoms. Just as the intensity of the disease varies widely, so can the results of available tests performed to diagnose CD.

Several blood tests have been developed that measure antibodies to TTG and various components of gluten. No one antibody is diagnostic of the disease and the lack of detectable antibodies does not absolutely eliminate the diagnosis. Depending on the amount and duration of exposure to gluten prior to testing and the potential for underlying IgA deficiency can make the diagnosis problematic in some individuals. I had one patient who was so certain of her diagnosis that she would not challenge herself with gluten because of ensuing symptoms so I could not see if she would develop an immunologic response to gluten. A gluten challenge can be helpful in the difficult-to-diagnose case.

Upper endoscopy with small bowel biopsy is an integral and helpful addition to the establishment of CD. While very active disease reveals a classic flattening of the intestinal lining when viewed endoscopically, CD is often seen under the microscope even with a normal appearance to the eye.

Genetic testing is available but there are many false positive individuals as many people without clinical celiac disease carry the genetic markers that are associated with CD. The vast majority of those afflicted with CD will have positive genetic markers but most of those individuals are not easily diagnosed. In my clinical experience I have rarely found a situation where it would be helpful to spend the money on genetic testing. For the individual who is reluctant to embark on a gluten challenge, a positive genetic test result would support the diagnosis of CD but not establish it.

Treatment

The primary treatment for CD is adherence to a gluten free diet. This was a lot more problematic in years past but nearly all supermarkets and many specialty shops have developed a wide array of gluten free products. With the rising recognition of CD and many who have an intolerance to the levels of gluten now found in the western diet, the demand for these gluten free products has sustained production of many gluten free foods.

The biggest problem with the Western diet is that there are many foodstuffs and products that contain gluten without obvious wheat, barley or rye as a prime ingredient. Additionally, grains such as oats do not contain gluten but if they are ground in the same mill as gluten-containing grains, there can be significant contamination.

While I cannot find a complete list of products that contain gluten, I have compiled a list of items that may contain varying amounts of gluten. You should search out food labels, ask questions, and visit food, beverage or medication websites if you are unsure. Some items to consider include:
Bouillon
Soups
Beer, ales, lagers, stouts
Communion wafer
Breaded foods (fish sticks, cheese sticks, etc)
Ice cream
Vitamin preparations
Lipstick
Lip balm
Toothpaste
Play-Doh
Soy sauce
Prepared gravies, sauces
Precooked meals
Self-basting turkeys
Nutritional supplements
Medications
Cheese spreads
Imitation meats, seafood
Pasta
Sausages
Candy
Salad dressings

I am sure there are other items; and again, I would remind you to learn to read all labels and ask questions when in doubt.

The majority of individuals who suffer from CD respond promptly to a gluten free diet. Treatment requires a major lifestyle change for those who have been diagnosed later in life as they have grown accustomed to dietary habits and a tolerance to their symptoms. I have a patient who was diagnosed later in life and she had learned that she could consume gluten to maintain weight loss. No matter the effort to counsel her by me, her dietician or her hematologist no one could convince her to give up gluten in spite of suffering from bone wasting, anemia, chronic diarrhea and low body weight.

Counseling with a dietician well versed in CD is beneficial to many patients. Additionally, long-term follow up to assess for nutritional deficiencies and sustained immunologic remission is important. Finally, counseling the patient about associated medical conditions, especially the increased risk of cancer is important.

A couple websites that you may find beneficial include:
www.celiac.com
www.celiacsociety.com
www.celiac.org

I hope this synopsis is helpful for those of you who suffer from celiac disease or just have an interest in the disease. Regardless, I would entertain input and if I do not know the answer, I certainly know how to do the homework.

References:
Feldman: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 9th Ed, 2010
Gastroenterology Clinics 41: Sept 2012
Arch Intern Med 163:286, 2003
Current Problems in Pediatric and Adolescent Health Care 37, March 2007
Clinical Gastroenterology and Hepatology, 2005
Gastroenterology 137:88, 2009
Journal of the American Medical Association 302:1171, 2009
Gut 30:333, 1989