Celiac Disease (Gluten-Sensitive Enteropathy)

The prevalence of celiac disease (CD) has been underesti-mated in the past and now is
considered to affect at least 1 in 141 persons in the United States and varies by race and ethnic-
ity, with a marked predominance among non-Hispanic whites (Rubio-Tapia et al, 2012). The
onset and first occurrence of symptoms may appear any time from infancy to adulthood, but
the peak in diagnosis occurs between the fourth and sixth decade. The disease may become
apparent when an infant be-gins eating gluten-containing cereals. In some, it may not ap-pear
until adulthood, when it may be triggered or unmasked during GI surgery, stress, pregnancy, or
viral infection. It may be discovered as a result of evaluation for another suspected problem.
Approximately 20% of cases are diagnosed after the age of 60 years.
Etiology
The presentation in young children is likely to include the more “classic” GI symptoms of
diarrhea, steatorrhea, malodorous stools, abdominal bloating, apathy, fatigue, and poor weight
gain. Although GI-related symptoms often are thought to be most common, an increasing
number of patients present without symptoms. Fifty percent of celiac patients have few or no
obvi-ous symptoms, and some are overweight at presentation (Phatak and Pashankar, 2015).
CD frequently is misdiagnosed as irritable bowel syndrome (IBS), lactase deficiency, gallblad-der
disease, or other disorders not necessarily involving the GI tract, because the presentation and
onset of symptoms vary so
greatly.Patients may present with one or more of a host of condi-tions associated with CD:
anemias, generalized fatigue, weight loss or failure to thrive, osteoporosis, vitamin or mineral
defi-ciencies, and (although rare) GI malignancy. Dermatitis her-petiformis, yet another
manifestation of CD, presents as an itchy skin rash; its presence is diagnostic of CD. Box 28-6
lists conditions associated with CD. Persons who are diagnosed late in life, who cannot or will
not comply with the diet, or who were diagnosed as children, but told they would grow out of
it, are at a higher risk for experiencing long-term complications
from CD (Nachman et al, 2010).
Pathophysiology
CD, or gluten-sensitive enteropathy, is characterized by a combination of four factors: (1)
genetic susceptibility, (2) ex-posure to gluten, (3) an environmental “trigger,” and (4) an
autoimmune response. Gluten refers to specific peptide frac-tions of proteins (prolamines)
found in wheat (glutenin and gliadin), rye (secalin), and barley (hordein). These peptides are
generally more resistant to complete digestion by GI en-zymes and may reach the small
intestine intact. In a normal, healthy intestine, these peptides are harmless as the intestinal
barrier is intact and prevents translocation from the intestine. However, in persons with CD
these peptides travel from the intestinal lumen, across the intestinal epithelium, and into the
lamina propria, where they can trigger an inflammatory re-sponse that results in flattening of
intestinal villi and elonga-tion of the crypt cells (secretory cells), along with a more general
systemic immune response (Sams and Hawks, 2014) (see Figure 28-2).The term gluten
sensitivity is used commonly to describe persons with nonspecific symptoms, without the
immune re-sponse characteristic of CD or the consequential intestinal damage. Gluten
intolerance describes individuals who have symptoms and who may or may not have CD. These
two terms are used to describe symptoms such as nausea, abdominal cramps, or diarrhea after
ingesting gluten. Patients who experi-ence these symptoms generally should be advised against
following a gluten-free (GF) diet without having a workup to exclude or confirm a diagnosis of
CD because (1) there may be an underlying medical condition for which a GF diet is not the
treatment; (2) after following a GF diet for months or years, it is difficult to diagnose CD; and (3)
although generally a healthy way to eat, a GF diet can be expensive and restrictive.The
“triggers” of CD are not well understood, but stressors (e.g., illness, inflammation) are thought
to play a role. When CD remains untreated, the immune and inflammatory re-sponse
eventually results in atrophy and flattening of villi.
Symptoms and Conditions Associated with Celiac Disease
Nutritional
Anemia (iron or folate, rarely B12)
Osteomalacia, osteopenia, fractures (vitamin D deficiency, inadequate
calcium absorption)
Coagulopathies (vitamin K deficiency)
Dental enamel hypoplasia
Delayed growth, delayed puberty, underweight
Lactase deficiency
Extraintestinal
Lassitude, malaise (sometimes despite lack of anemia)
Arthritis, arthralgia
Dermatitis herpetiformis
Infertility, increased risk of miscarriage
Hepatic steatosis, hepatitis
Neurologic symptoms (ataxia, polyneuropathy, seizures); may be partly
nutrition related
Psychiatric syndromes
Associated Disorders
Autoimmune diseases: type 1 diabetes, thyroiditis, hepatitis, collagen
vascular disease
Gastrointestinal malignancy
IgA deficiency

Assessment
The diagnosis of CD is made from a combination of clinical, laboratory, and histologic
evaluations. Persons suspected of having CD should be evaluated for the overall pattern of
symptoms and family history. Biopsy of the small intestine is the gold standard for diagnosis. An
intestinal biopsy positive for CD generally shows villous atrophy, increased intraepithe-lial
lymphocytes, and crypt cell hyperplasia. However, biopsy is not used for initial screening
because of its cost and inva-siveness.Elevated blood levels of certain autoantibodies are found
in people with celiac disease. To screen for celiac disease several serologic tests are evaluated.
These tests identify the presence of antibodies in the blood, such as anti-tissue
transglutaminase (anti-TTG), and antiendomysial antibodies, and deaminated gliadin peptide.
The sensitivity and specificity of these tests are 90% to 99% (Schyum and Rumessen, 2013).
There is a higher incidence of immunoglobulin A (IgA) deficiency in patients with CD; thus
physiciansoften measure IgA levels when sero-logic findings are normal, but the overall clinical
picture suggests CD (see Clinical Insight: Antibody Testing for Celiac Disease and Gluten
Sensitivity). Using video capsule endoscopy to image the entire intestinal mucosa can show
inflammation related to CD but is not currently used in the initial diagnosis (Bouchard et al,
2014). Because dietary change alters diagnostic results, initial evaluation should be done before
the person has eliminated gluten-containing foods from his or her diet. Sero-logic tests also
may be used to monitor the response of a newly diagnosed patient treated with a GF diet.
CLINICAL INSIGHT
Antibody testing for Celiac Disease and Gluten Sensitivity by Ruth Leyse-Wallace, PhD,
RDNThere are two different types of antibodies considered in celiac dis-ease diagnosis: those
which are “anti-gluten”, and those which are “anti-self” (auto-immune). “Anti-gluten”
antibodies are the anti-gliadin IgG and IgA. Ig stands for “immunoglobulin” or “antibody”. “Anti-
self” antibodies are anti-endomysial IgA and anti-tissue transglutaminase IgA (tTg IgA).
Antigliadin antibodies IgG and IgA recognize a small piece of the gluten protein called gliadin.
Antigliadin IgG has good sensitivity, while antigliadin IgA has good specificity. Their combined
use provides a screening test for celiac disease. Many normal individuals without celiac disease
will have an elevated antigliadin IgG. It is estimated that 0.2-0.4% of the general popu-lation
has selective IgA deficiency, while 2 to 3% or more of celiacs are IgA deficient.
If a celiac panel is only positive for antigliadin IgG, this is not highly sugges-tive for celiac disease
if the patient has a normal total IgA level. An antigliadin IgG level 3 to 4 times the upper limit of
normal for that lab is highly suggestive of a condition where the gut is abnormally permeable
(“leaky”) to gluten. This can happen with food allergies, cystic fibrosis, parasitic infections,
Crohn’s disease, and other types of autoimmune GI diseases. These antibodies may also be
slightly elevated in individuals with no obvious disease.The tTG IgA test is highly sensitive and
specific. It correlates well with biopsy, is inexpensive, not subjective, and can be performed on
a single drop of blood. However, it can be falsely positive in a patient who has other
autoimmune conditions, such as type 1 diabetes. For those with a negative tTG IgA test, IgA
deficiency should be considered. http://americanceliac.org/celiac-disease/diagnosis/)Lifelong,
strict adherence to a GF diet is the only known treat-ment for CD (see Box 28-7 for a list of safe,
questionable, and un-safe choices on the GF diet). The GF diet greatly diminishes the
autoimmune process, and the intestinal mucosa usually reverts to normal or near normal.
Within 2 to 8 weeks of starting the GF diet, most patients report that their clinical symptoms
have abated. Histologic, immunologic, and functional improvements may take months to years,
depending on the duration of the disease, age of the subject, and degree of dietary compliance.
With strict dietary control, levels of the specific antibodies usually become undetect-able within
3 to 6 months in most persons. In some individuals, recovery may be slow or incomplete.A
small percentage of patients are “nonresponders” to diet therapy. Inadvertent gluten intake is
the most common of-fender, but another coexisting disorder may be present (such as
pancreatic insufficiency, IBS, bacterial overgrowth, fructose in-tolerance, other GI maladies, or
unknown causes). For nonre-sponders, intensive interviewing to identify a source of gluten
contamination or treatment of another underlying disease may resolve the symptoms.
Diagnosis of refractory celiac disease is made when patients do not respond or respond only
temporar-ily to a GF diet, and all external causes have been ruled out, including inadvertent
gluten ingestion. Patients with refractory disease may respond to steroids, azathioprine,
cyclosporine, or other medications classically used to suppress inflammatory or immunologic
reactions.Several novel treatments for CD are being studied for their potential as alternative
therapies. Researchers seek to treat CD by reducing gluten exposure (by digestion with added
en-zymes), decreasing uptake of gluten (by tightening junctions between intestinal epithelial
cells), altering the immune re-sponse to gluten, or repairing intestinal injury.

Medical Nutrition Therapy

Elimination of gluten peptides from the diet is the only treat-ment for CD presently. The diet
omits all dietary wheat, rye, and barley, which are the major sources of the prolamin
fractions.In general, patients should be assessed for nutrient deficien-cies before
supplementation is initiated. In all newly diagnosed patients, the clinician should consider
checking levels of ferri-tin, red blood cell folate, and 25-OH vitamin D. If patients pres-ent with
more severe symptoms, such as diarrhea, weight loss, malabsorption, or signs of nutrient
deficiencies (e.g., night-blindness, neuropathy, prolonged prothrombin time), other vitamins
such as fat-soluble
The healing of the intestinal mucosa that occurs after initia-tion of a GF diet improves nutrient
absorption, and many patients who eat well-balanced GF diets do not need nutritional
supplementation. However, most specialty GF products are not fortified with iron, folate, and
other B vitamins like other grain products, so the diet may not be as complete without at least
partial supplementation. Anemia should be treated with iron, folate, or vitamin B12, depending
on the nature of the anemia. Patients with malabsorption may benefit from a bone density scan
to assess for osteopenia or osteoporosis. Calcium and vita-min D supplementation are likely to
be beneficial in these pa-tients. Electrolyte and fluid replacement is essential for those
dehydrated from severe diarrhea.Those who continue to have malabsorption should take a
general vitamin-mineral supplement to at least meet DRI rec-ommendations. Lactose and
fructose intolerance sometimes occur secondary to CD, and sugar alcohols are not well ab-
sorbed, even in a healthy gut. A low-lactose or low-fructose diet may be useful in controlling
symptoms, at least initially. Once the GI tract returns to more normal function, lactase activity
also may return, and the person can incorporate lactose and dairy products back into the diet.In
general, many fruits, vegetables, non–gluten containing grains, meats, and dairy products that
are plain and unseasoned are safe to eat. Oats were once thought to be questionable for
persons with CD; however, extensive studies have shown that they are safe in the GF diet as
long as they are pure, uncon-taminated oats (Garsed and Scott, 2007). However, a very small
population of patients with CD may not tolerate even pure oats. In general, patients do not
need to be advised against including GF oats in their diet unless they have demonstrated
intolerance to GF oats.Flours made from corn, potatoes, rice, soybean, tapioca, ar-rowroot,
sorghum, garbanzo beans, nuts (such as almond flour), amaranth, quinoa, millet, teff, and
buckwheat can be substituted in recipes. Patients can expect differences in textures and flavors
of common foods using the substitute flours, but new recipes can be palatable once the
adjustment is made. In GF baked goods, gums such as xanthan, guar, and cellulose (from
nongluten grains) can be used to provide the elasticity needed to trap leavening gases in baked
goods.A truly GF diet requires careful scrutiny of the labels of all bakery products and packaged
foods. Gluten-containing grains are not only used as primary ingredients in many products but
also may be added during processing or preparation of foods. For example, hydrolyzed
vegetable protein can be made from wheat, soy, corn, or mixtures of these grains.In the US
there is now a gluten-free labeling law that went into effect in September, 2014.
(https://www.federalregister.gov/articles/2013/08/05/2013-18813/food-labeling-gluten-free-
labeling-of-foods). This law states that all food carrying a gluten-free claim also must contain
less that 20 ppm gluten (i.e., below 20 mg gluten per kg of food), including from cross-contact.
Thompson discusses the law in detail (Thompson, 2015). Recent studies on the gluten content
of labeled gluten-free food in the US showed that 95 – 99% of the products tested contained
less than 20 ppm gluten (Sharma et al, 2015).The diet for the person with CD requires a major
lifestyle change because of the change from traditional grains in the diet. A tremendous
number of foods made with wheat (in par-ticular breads, cereals, pastas, and baked goods) are
a common part of a Western diet. However, there is increasing awareness among food
companies and restaurants of the expanding de-mand for GF foods, and food businesses are
responding. The individual and family members should be taught about label reading, safe food
additives, food preparation, sources of cross-contamination (such as toasters, condiment jars,
bulk bins, and buffets), and hidden sources of gluten (such as medications and communion
wafers) to be compliant with the diet. Box 28-8provides sources of hidden gluten and cross-
contamination. Eating in cafeterias, restaurants, vending outlets, street markets, at friends’
homes, and at social events can be challenging, espe-cially initially.To avoid misinterpretation of
information, newly diagnosed patients should be started with an in-depth instruction from a
RDN on a GFD.