Celiac Disease
Introduction: Celiac disease is a small bowel disorder characterized by
mucosal inflammation, villous atrophy, and crypt hyperplasia, which
occur upon exposure to dietary gluten and demonstrates improvement
after withdrawal of gluten from the diet.
Suggestive gastrointestinal symptoms : Gastrointestinal symptoms
include chronic or recurrent diarrhea or constipation, malabsorption,
unexpected weight loss, abdominal pain, distension, or bloating. Testing
should therefore be performed in patients with symptoms suggestive of
irritable bowel syndrome or refractory lactose intolerance.
Extraintestinal signs/symptoms suggestive of celiac disease :
Patients with extraintestinal symptoms, signs, or laboratory evidence for
which celiac disease is a treatable cause. This includes patients without
other explanations for iron deficiency anemia, folate or vitamin B12
deficiency, persistent elevation in serum aminotransferases, dermatitis
herpetiformis, fatigue, recurrent headaches, recurrent fetal loss, low
birthweight offspring, reduced fertility, persistent aphthous stomatitis,
dental enamel hypoplasia, metabolic bone disease and premature
osteoporosis, idiopathic peripheral neuropathy, or nonhereditary
cerebellar ataxia.
DIAGNOSTIC APPROACH:
The diagnostic approach is based on the risk for celiac disease and
whether the patient is on a gluten-containing diet. All testing for celiac
disease should ideally be performed while patients are on a gluten-
containing diet.
All celiac disease blood tests require that you be on a gluten-containing
diet to be accurate. Tissue Transglutaminase Antibodies (tTG-IgA) –
The tTG-IgA test will be positive in about 98% of patients with celiac
disease who are on a gluten-containing diet. This is called the test's
sensitivity.
Contain Gluten Do Not Contain Gluten
Wheat Amaranth
Barley Buckwheat
Rye Corn
Bran Flax
Graham flour Millet
Spelt Potato flour
Wheat germ Quinoa
Triticale Rice
Oats Sorghum
Soybeans
Tapioca
Teff
Certain infectious agents and other compounds may contribute to the
development of celiac disease. Both adenovirus and hepatitis C viruses
are thought to act as triggers, whereas other agents, including
Campylobacter jejuni, Giardia lamblia, rotavirus, and enterovirus
infections, have been described in case reports as associated with celiac
disease.
Pathophysiology:
Enterocytes release the protein zonulin in response to the presence of
indigestible fragments of gluten in the intestine
Zonulin loosens the intercellular tight junctions
Abundant quantities of gluten fragments cross the intestinal lining and
accumulate under the enterocytes (epithelial cells)
Gluten induces the enterocytes to secrete interleukin-15 (IL-15)
IL-15 induces an immune response of intraepithelial lymphocytes
against the enterocytes
The damaged cells release the enzyme tissue transglutaminase (tTG),
which modifies the gluten
Antigen-presenting cells of the immune system join the modified gluten
to human leukocyte antigen (HLA) molecules and display the resulting
complexes to other immune cells (i.e., helper T cells)
Helper T cells that recognize the complexes secrete molecules that
attract other immune cells, which may result in damage to the
enterocytes
Helper T cells spur killer T cells that directly attack the enterocytes
B cells release antibody molecules that are targeted to gluten and tTG
(the role that these antibodies play remains to be further clarified;
however, they may cause further damage when they contact their targets
on or near the enterocytes)
Enterocytes are disabled or killed
Signs and Symptoms:
Children Adults
Symptoms Symptoms
o Fatigue o Abdominal pain
o Bloating o Chronic diarrhea
o Constipation o Abdominal distension
o Abdominal pain o Recurrent spontaneous abortion
o Chronic diarrhea o Peripheral neuropathy
o Irritability o Depression
o Vomiting o Fatigue/malaise
Signs o Ataxia
o Muscle wasting
Signs
o Failure to thrive/weight loss o Weight loss
o Short stature o Infertility
o Delayed puberty o Dermatitis herpetiformis
o Osteopenia/osteoporosis o Hepatitis
o Hepatitis o Anemia
o Dental anomalies o Aphthous ulcers
o Anemia o Alopecia
o Malignancy
o Seizures
o Osteopenia/osteoporosis
o Arthritis
Treatment:
Overall goals of treatment include relieving symptoms, healing the
intestine, and reversing the consequences of malabsorption while
enabling the patient to adhere to a healthy, interesting, and practical
gluten-free diet.
Non-Pharmacological:
Strict lifelong adherence to a gluten-free diet is the only proven
treatment for celiac disease.
Oral prescription drugs, nonprescription drugs, vitamin and mineral
supplements, and health and beauty aids and cosmetics that have oral
ingestion potential must not be overlooked as sources of gluten due to its
presence in their formulation or due to contamination or contact.
Although clinicians have concluded that as little as 10 to 50 mg/day of
gluten is the minimum dose required to produce measurable damage to
the small intestinal mucosa, it is difficult to set a universal threshold
given the individual variability among patients.
Pharmacological:
Dietary avoidance of gluten remains the mainstay of treatment of celiac
disease. Novel pharmacologic treatment modalities are under
investigation. Most reports related to pharmacotherapy for celiac disease
focus on the treatment of refractory disease.
In case reports, corticosteroids, azathioprine, cyclosporine, tacrolimus,
infliximab, and alemtuzumab have been reported as effective treatments
for refractory celiac disease.
