Causes
Celiac’s disease, previously also known
as sprue, is an autoimmune disorder in
genetically predisposed individuals associated with the ingestion of
gluten, a protein present in wheat, rye and
barley. Incompletely digested gluten, or
more specifically the gliadin protein
portion, leads to inflammatory reactions
predominantly in the small intestine. This
process may be enhanced by factors
increasing the leakiness of the intestinal
lining (increased intestinal permeability),
such as infections. Possible protective
factors may be breast-feeding and the
introduction of gluten only after the age
of 7 months, at the time of weaning.
Frequency in population
Approximately 1% of the population has
celiac’s disease, as detected by screening
methods, most of whom are asymptomatic.
The incidence may be even higher in 1st
(5-22%) and 2nd degree (2-15%) relatives
of individuals with manifest celiac’s
disease, as well as patients with diabetes
mellitus type 1 (2-8%), autoimmune
thyroiditis (2-7%), liver disease (2-9%),
Down’s (5%) and Turner’s (6%) syndromes,
unexplained infertility (4%), and
especially a skin disease known as
dermatitis herpetiformis (100%). Both
children and adults are affected by
celiac’s disease and almost all patients
have certain genetic markers (HLA-DQ2 or
HLA-DQ8). Negative markers virtually
exclude the disease, but positive markers
also occur in over 40% of unaffected
individuals. Twenty-five percent of
patients with newly diagnosed celiac’s
disease are now over 60 years old.
Symptoms
Symptoms and signs of celiac’s disease
range from unspecific, such as fatigue,
anemia, osteoporosis, malabsorption of
vitamins and minerals, dental enamel
malformations, skin, thyroid or liver
disease, growth retardation in children,
possibly infertility or miscarriages, and
neurologic symptoms, to classic
gastrointestinal, including diarrhea or
constipation, bloating / abdominal
distension, flatulence, increased
intestinal sounds, abdominal pain and
cramps, vomiting and weight loss. Diverse
rheumatologic dermatologic, neurologic autoimmune
disorders, as well as depression are
associated with celiac’s disease and there
is an increased incidence of small bowel
cancer in inadequately managed disease.
Over 35% of patients with subsequently
diagnosed celiac’s disease had earlier
received a diagnosis of irritable bowel
syndrome. Inflammation in the small
intestine due to celiac’s disease is a
common reason for so-called secondary
lactose (milk sugar) intolerance (see
Lactose intolerance), unexplained iron
deficiency or anemia and osteoporosis.
Testing and diagnosis
Diagnosis is possible using tissue
samples from the small intestine taken
during upper endoscopy and with blood
tests for specific antibodies (anti-transglutaminase,
aTGA) and genetic markers. Both children
and adults are affected by celiac’s
disease and almost all patients have
certain genetic markers (HLA-DQ2 or
HLA-DQ8). Negative markers virtually
exclude the disease, but positive markers
also occur in over 40% of unaffected
individuals. Twenty-five percent of
patients with newly diagnosed celiac’s
disease are now over 60 years old.
Exclusion of vitamin and other
deficiencies, as well as associated
diseases should be part of the diagnostic
procedure.
See
Tests.
Management
Treatment is via meticulous and
life-long dietary exclusion of gluten.
This requires long-term expert dietary
advice, support and medical surveillance.
Wheat, rye and barley must be excluded
from the diet and they occur in hidden
form in many processed foods, beverages
and medicines (see
Food tables). Oats are gluten-free,
but can be gluten-contaminated due to
processing procedures. They are tolerated
by most patients. A wide range of
gluten-free foods are now offered in many
countries and patient support
organizations offer useful support and
resources (See Links
below). The term ‘gluten-free’
actually implies gluten levels below a
certain limit, as defined by governments.
Some governments subsidize the special
dietary needs. Various novel therapies are
undergoing evaluation, including the
development of cereals free of the
causative proteins by genetic
modification, induction of immune
tolerance and ingestion of supplements
digesting the offending dietary proteins.
Repeated and long-term follow-up is
required in this multi-organ disease.
Adherence to the gluten-free diet and
disease regression should be periodically
assessed using blood antibody tests (e.g.
anti-transglutaminase antibody), or small
intestinal biopsies. With strict adherence
and a good clinical response, many of the
potential disease complications can be
prevented. However, due to an increased
incidence of some cancers and other
autoimmune disorders, follow-up at
reasonable intervals is recommended.
Vitamin and mineral supplements are often
necessary. Improvement in symptoms can
occur within 2 weeks of beginning the diet
and antibodies can revert to normal within
3-12 months. Lactose intolerance often
resolves naturally with time. Inadequate
responses to a gluten-free diet are most
commonly due to dietary errors, although
about 5% of patients do not respond
despite strict dietary adherence
(‘refractory celiac disease”). In the
latter case further diagnostic workup is
required. Refractory celiac’s disease may
respond to steroids or immunosuppressive
drugs.
Currently contentious issues include the
necessity of a gluten-free diet in
asymptomatic individuals testing positive
for celiac’s disease, the maximum amount
of gluten permitted in foods labeled as
‘gluten-free” and interpretation of cereal
or gluten sensitivity without evidence of
celiac’s disease. It should be noted not
all intolerances to grains constitute
celiac’s disease (gluten hypersensitivity). In case of
suggestive symptoms other cereal allergies and
intolerances should also be considered.
One such differential diagnosis is wheat
allergy, which is IgE-mediated and often
exercise induced (see
Food allergies) and fructose
intolerance via fructopolysaccharides (see
Fructose intolerance).
See
Food tables.
Links to
literature, including support organizations:
www.celiac.org
www.gluten.net
www.americanceliac.org
www.celiac.com
www.csaceliacs.org
www.celiachealth.org
http://celiac.nih.gov
http://www.celiaccentral.org
http://shepherdworks.com.au/disease-information/coeliac-disease
http://gflinks.com
www.coeliac.org.au
Gluten-free drugs
http://www.glutenfreedrugs.com/
and
http://www.foodintolerances.org/pdf/Plogsted-Article-Medications-and-Celiac-Disease.pdf