Celiac Disease
·
Celiac disease is an immune-mediated
enteropathy that results from increased sensitivity to and intolerance of
gluten proteins. The immunologic reaction to gluten proteins promotes injury to
the intestinal mucosa, resulting in diarrhea, steatorrhea, bloating,
flatulence, and fatigue in adults. In children, the condition presents as
irritability and failure to thrive. Enteropathy is its most common
presentation, though celiac disease can affect other organ systems
·
Celiac disease is genetically
transmitted and affects 0.5% to 1% of the people in the western hemisphere and
Europe
·
Presence of class II human leukocyte
antigen DQ2 and DQ8 confers an increased risk of developing celiac disease
·
Serologic detection of
immunoglobulin A (IgA) anti-endomysial antibodies during a gluten–non-deprived
diet is a useful screening test in suspected individuals
·
The sine qua non of
diagnosis in celiac disease is small intestinal biopsy obtained during a
gluten–non-deprived diet
·
A gluten-free diet is the mainstay
of treatment
·
Celiac disease is a lifelong
intolerance to gluten, causing autoimmune injury to the mucosa of the upper small
intestine. Damaged intestinal epithelium subsequently impairs digestion and
absorption of nutrients, producing the clinical signs and symptoms of the
disease
·
The condition may be classified as
asymptomatic, classic, and atypical:
o Asymptomatic patients present with no clinical disease
manifestations
o Classic presentation symptoms include diarrhea, steatorrhea,
bloating, flatulence, and ensuing nutrient and mineral deficiencies.
o Atypical patients present with predominantly extraintestinal
manifestations with absent or minimal gastrointestinal manifestations.
Extraintestinal manifestations include anemia, dermatitis herpetiformis,
aphthous stomatitis, neurologic dysfunction, osteopathy, and diabetes mellitus
·
Synonyms include gluten-sensitive
enteropathy and nontropical sprue
·
Celiac disease affects 0.5% to 1% of
the population
·
Its prevalence is decreased among
blacks and those of Hispanic or Asian ethnicity
·
The incidence of symptomatic celiac
disease in adults is estimated at 2 to 13 per 100,000 per year
·
Gliadins and glutenins in the
presence of CD4+ T cells with HLA-DQ2 and HLA-DQ8 activate cytokine production
and clonal expansion of antibody-producing B cells, which lead to
lymphocyte-mediated destruction of the epithelium and mucosa. This is termed
the adaptive response. The resulting injury impairs villous function and
absorption of nutrients, producing the clinical signs and symptoms of celiac
disease. In addition, there is an innate response, which involves interleukin-15
expressed by enterocytes
·
Celiac disease affects predominantly
the mucosa of the proximal small intestine, which receives the majority of
dietary gluten. Distal parts of the small intestine are less affected because
gluten has generally been absorbed by the time the enteric bolus reaches these
areas
Risk factors
Geographic:
·
The highest incidence of celiac
disease is found in western Europe and the U.S.
Age:
·
Peaks in diagnosis occur in
childhood (when approximately 6% of the cases are diagnosed) and between the
fifth and seventh decades of life
Female
gender:
·
The female-to-male ratio in celiac
disease is about 2:1
Heredity:
·
Celiac disease is an inherited
condition with a concordance rate of 70% to 100% between monozygotic twins
·
The concordance rate among siblings
is 7% to 30%. The rate increases up to 40% if the sibling has the same HLA risk
haplotype as the index case
·
Risk is higher among first-degree
relatives of those with the condition, with a 1:22 ratio, compared with the
risk among second-degree relatives (1:29)
·
At lease 11% of first-degree
relatives of index cases have celiac disease
Infant
diet:
·
If gluten-containing foods are
brought into the diet within the first 3 months or after 7 months of life, the
risk of developing celiac disease increases five-fold
·
The risk is higher in the first 3
months because of the infant's underdeveloped intestinal mucosal barrier, which
allows immunogenic peptides to cross the epithelium
Absent
breastfeeding:
·
Breastfeeding protects against the
development of celiac disease in childhood. Gradual introduction of
gluten-containing foods while breastfeeding decreases the risk by 48%. Its
benefit in preventing the disease later in adulthood, however, is unknown
·
Breastfeeding may have the following
protective effects:
o Continuation of breastfeeding limits the amount of gluten a
child receives
o Breast milk protects against gastrointestinal infections
that increase the permeability of the intestinal mucosa to gluten
o IgA in breast milk agglutinates with antigen, preventing the
antigen's uptake to the mucosa
o Breast milk has T-cell–specific suppressive effects
Inflammatory
bowel disease:
·
A few studies have shown an
increased prevalence of celiac disease in patients with Crohn disease and, to a
lesser extent, ulcerative colitis
Comorbid
risk factors:
·
Lymphocytic colitis (increases risk
of celiac disease 15%-27%)
·
Down syndrome (increases risk 12%)
·
Type 1 diabetes mellitus (increases
risk 5%-6%)
·
Autoimmune thyroid disease
(increases risk 5%)
·
Chronic fatigue syndrome (increases
risk 2%)
Screening for celiac disease is
essential to avoid unnecessary loss of growth potential in children at risk for
the disease (eg, those children with a family history) and untreated
progression of disease or complications in adults similarly at risk (eg,
those with autoimmune disease). In these instances, testing for the disease
even in asymptomatic patients should be strongly considered.
·
Screening for celiac disease is
recommended for individuals with certain autoimmune and comorbid disorders (eg,
lymphocytic colitis, Down syndrome, type 1 diabetes mellitus, autoimmune
thyroid disease, and chronic fatigue syndrome) who are at increased risk for
celiac disease. Screening is also recommended for first-degree relatives of
patients with celiac disease. Screening of the general population for celiac
disease is not recommended
·
Screening for celiac disease is also
advised for patients with the following conditions:
o Unexplained iron-deficiency anemia
o Early-onset or unexplained osteopenia or osteoporosis
o Unexplained elevated hepatic transaminases
o Dermatitis herpetiformis
o Unexplained epilepsy
o Failure to thrive, developmental delay, growth retardation,
and other unexplained nutritional problems (pediatric patients)
o Poor glucose control, lactose intolerance, diarrhea, and
bloating (diabetic patients)
o Recurrent pancreatitis and no clear etiology
o Unexplained infertility, recurrent spontaneous abortion,
stillbirth, perinatal death, and intrauterine growth retardation in women
o Unexplained chronic diarrhea
·
According to a population-based
cohort study of 111 index cases and their family members from southeast
Minnesota, the prevalence of celiac disease in family members was estimated to
be 11%. All affected family members carried the at-risk HLA-DQ genotype. Occult
intestinal villous atrophy was present in more than half of the cases. High
risk factors for celiac disease include carrying HLA-DQ2 (OR = 16.1) and being
a sibling (OR = 2.5).[1]Level
of evidence: 3
·
A multicenter, prospective study was
conducted from 2002 to 2004 on 976 adult subjects who attended a participating
primary care practice. Those with symptoms or conditions known to be associated
with celiac disease were tested. Of these, 30 (3.07%) had a positive anti-tTG
test, and celiac disease was diagnosed in 22 patients (18 women). Prevalence of
celiac disease in the serologically screened sample was 2.25%. Diagnostic rate
was 0.27 cases/1000 visits at baseline and 11.6/1000 after active screening.[2]Level
of evidence: 3
·
Serologic testing for the detection
of IgA antiendomysial antibodies is the preferred method of screening for
individuals suspected of having celiac disease because it has high sensitivity and
specificity (approaching 100%)
·
A total serum IgA level is preferred
as patients deficient in IgA may be unable to produce the antibodies on which
further screening tests depend
Celiac
disease in susceptible individuals can only be successfully prevented by strict
avoidance of all gluten-containing foods.
Infants
with a family history of celiac disease are at increased risk and may benefit
from delayed introduction of gluten in the diet and prolonged breastfeeding.
·
Introduction of gluten-containing
food within the first 3 months of life increases the risk of celiac disease. At
the time of weaning, gluten-containing food products should not be introduced
in large amounts
·
Breastfeeding is encouraged to
decrease the risk of celiac disease; however, the optimum duration of
breastfeeding is not known
No comments:
Post a Comment