[guide.chat] Coeliac Disease
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Coeliac disease
From Wikipedia, the free encyclopedia
Coeliac disease
Classification and external resources
File:Coeliac_path
Biopsy of small bowel showing coeliac disease manifested by blunting of
villi, crypt hyperplasia, and lymphocyte infiltration of crypts
ICD-10
K90.0
ICD-9
579.0
OMIM
212750
DiseasesDB
2922
MedlinePlus
000233
eMedicine
med/308 ped/2146 radio/652
MeSH
D002446
Coeliac disease (play /'si?li.æk/; spelled celiac disease in North
America[1]) is an autoimmune disorder of the small intestine that occurs
in genetically predisposed people of all ages from middle infancy
onward. Symptoms include chronic diarrhoea, failure to thrive (in
children), and fatigue, but these may be absent, and symptoms in other
organ systems have been described. A growing portion of diagnoses are
being made in asymptomatic persons as a result of increased
screening;[2] the condition is thought to affect between 1 in 1,750 and
1 in 105 people in the United States.[3] Coeliac disease is caused by a
reaction to gliadin, a prolamin (gluten protein) found in wheat, and
similar proteins found in the crops of the tribe Triticeae (which
includes other common grains such as barley and rye). Upon exposure to
gliadin, and specifically to three peptides found in prolamins,[4] the
enzyme tissue transglutaminase modifies the protein, and the immune
system cross-reacts with the small-bowel tissue, causing an inflammatory
reaction. That leads to a truncating of the villi lining the small
intestine (called villous atrophy). This interferes with the absorption
of nutrients, because the intestinal villi are responsible for
absorption. The only known effective treatment is a lifelong gluten-free
diet.[5] While the disease is caused by a reaction to wheat proteins, it
is not the same as wheat allergy.
This condition has several other names, including: c?liac disease (with
? ligature), c(o)eliac sprue, non-tropical sprue, endemic sprue, gluten
enteropathy or gluten-sensitive enteropathy, and gluten intolerance. The
term coeliac derives from the Greek ?????a??? (koiliak?s, "abdominal"),
and was introduced in the 19th century in a translation of what is
generally regarded as an ancient Greek description of the disease by
Aretaeus of Cappadocia.[6][7]
Contents [hide]
1 Signs and symptoms
1.1 Gastrointestinal
1.2 Malabsorption-related
1.3 Miscellaneous
1.4 Other grains
2 Pathophysiology
2.1 Genetics
2.2 Prolamins
2.3 Tissue transglutaminase
2.4 Villous atrophy and malabsorption
2.5 Risk modifiers
3 Diagnosis
3.1 Blood tests
3.2 Endoscopy
3.3 Pathology
3.4 Other diagnostic tests
4 Screening
5 Treatment
5.1 Diet
5.2 Refractory disease
5.3 Experimental treatments
6 Epidemiology
7 Social and religious issues
7.1 Christian churches & the Eucharist
7.2 Roman Catholic position
7.3 Passover
8 History
9 References
10 External links
[edit]
Signs and symptoms
Severe coeliac disease leads to the characteristic symptoms of pale,
loose and greasy stool (steatorrhoea), and weight loss or failure to
gain weight (in young children). People with milder coeliac disease may
have symptoms that are much more subtle and occur in other organs rather
than the bowel itself. It is also possible to have coeliac disease
without any symptoms whatsoever.[5] Many adults with subtle disease only
have fatigue or anaemia.[2]
[edit]
Gastrointestinal
The diarrhoea that is characteristic of coeliac disease is (chronic)
pale, voluminous and malodorous. Abdominal pain and cramping,
bloatedness with abdominal distension (thought to be due to fermentative
production of bowel gas) and mouth ulcers[8] may be present. As the
bowel becomes more damaged, a degree of lactose intolerance may
develop.[5] Frequently, the symptoms are ascribed to irritable bowel
syndrome (IBS), only later to be recognised as coeliac disease; a small
proportion of patients with symptoms of IBS have underlying coeliac
disease, and screening for coeliac disease is recommended for those with
IBS symptoms.[9]
Coeliac disease leads to an increased risk of both adenocarcinoma (small
intestine cancer) and lymphoma of the small bowel
(enteropathy-associated T-cell lymphoma or EATL). This risk returns to
baseline with diet. Longstanding and untreated disease may lead to other
complications, such as ulcerative jejunitis (ulcer formation of the
small bowel) and stricturing (narrowing as a result of scarring with
obstruction of the bowel).[10]
[edit]
Malabsorption-related
The changes in the bowel make it less able to absorb nutrients, minerals
and the fat-soluble vitamins A, D, E, and K.[5][11]
? The inability to absorb carbohydrates and fats may cause weight loss
(or failure to thrive/stunted growth in children) and fatigue or lack of
energy.
? Anaemia may develop in several ways: iron malabsorption may cause iron
deficiency anaemia, and folic acid and vitamin B12 malabsorption may
give rise to megaloblastic anaemia.
? Calcium and vitamin D malabsorption (and compensatory secondary
hyperparathyroidism) may cause osteopenia (decreased mineral content of
the bone) or osteoporosis (bone weakening and risk of fragility fractures).
? A small proportion have abnormal coagulation due to vitamin K
deficiency and are slightly at risk for abnormal bleeding.
? Coeliac disease is also associated with bacterial overgrowth of the
small intestine, which can worsen malabsorption or cause malabsorption
despite adherence to treatment.[12]
[edit]
Miscellaneous
Coeliac disease has been linked with a number of conditions. In many
cases, it is unclear whether the gluten-induced bowel disease is a
causative factor or whether these conditions share a common predisposition.
? IgA deficiency is present in 2.3% of patients with coeliac disease,
and in turn, this condition features a tenfold increased risk of coeliac
disease. Other features of this condition are an increased risk of
infections and autoimmune disease.[13]
? Dermatitis herpetiformis; this itchy cutaneous condition has been
linked to a transglutaminase enzyme in the skin, features small-bowel
changes identical to those in coeliac disease, and may respond to gluten
withdrawal even if there are no gastrointestinal symptoms.[14][15]
? Growth failure and/or pubertal delay in later childhood can occur even
without obvious bowel symptoms or severe malnutrition. Evaluation of
growth failure often includes coeliac screening.[5]
? Recurrent miscarriage and unexplained infertility.[5]
? Hyposplenism (a small and underactive spleen);[16] this occurs in
about a third of cases and may predispose to infection given the role of
the spleen in protecting against bacteria.[5]
? Abnormal liver function tests (randomly detected on blood tests).[5]
Coeliac disease is associated with a number of other medical conditions,
many of which are autoimmune disorders: diabetes mellitus type 1,
autoimmune thyroiditis,[17] primary biliary cirrhosis, and microscopic
colitis.[18]
A more controversial area is a group of diseases in which anti-gliadin
antibodies (an older and non-specific test for coeliac disease) are
sometimes detected, but no small bowel disease can be demonstrated.
Sometimes, these conditions improve by removing gluten from the diet.
This includes cerebellar ataxia, peripheral neuropathy, schizophrenia
and autism.[19]
[edit]
Other grains
Wheat subspecies (such as spelt, semolina and durum) and related species
such as barley, rye, triticale and Kamut also induce symptoms of coeliac
disease.[20] A small minority of coeliac patients also react to oats.[5]
It is most probable that oats produce symptoms due to cross
contamination with other grains in the fields or in the distribution
channels. Generally, oats are therefore not recommended.[20] Other
cereals such as maize (corn), millet, sorghum, teff, rice, and wild rice
are safe for patients to consume, as well as non cereals such as
amaranth, quinoa or buckwheat.[20][21] Non-cereal carbohydrate-rich
foods such as potatoes and bananas do not contain gluten and do not
trigger symptoms.[20]
[edit]
Pathophysiology
Coeliac disease appears to be polyfactorial, both in that more than one
genetic factor can cause the disease and that more than one factor is
necessary for the disease to manifest in a patient.
Almost all coeliac patients have the variant HLA-DQ2 allele.[2] However,
about 20-30% of people without coeliac disease have inherited an HLA-DQ2
allele.[22] This suggests additional factors are needed for coeliac
disease to develop. Furthermore, about 5% of those people who do develop
coeliac disease do not have the DQ2 gene.[2]
The HLA-DQ2 allele shows incomplete penetrance, as the gene alleles
associated with the disease appear in most patients but are neither
present in all cases nor sufficient by themselves to cause the disease.
[edit]
Genetics
File:DQa2b5_da_gliadin
DQ a5-ß2 -binding cleft with a deamidated gliadin peptide (yellow),
modified from PDB 1S9V[23]
The vast majority of coeliac patients have one of two types of
HLA-DQ.[22] This gene is part of the MHC class II antigen-presenting
receptor (also called the human leukocyte antigen) system and
distinguishes cells between self and non-self for the purposes of the
immune system. The gene is located on the short arm of the sixth
chromosome and has been labelled CELIAC1.
There are seven HLA-DQ variants (DQ2 and DQ4-DQ9). Over 95% of coeliac
patients have the isoform of DQ2 or DQ8, which is inherited in families.
The reason these genes produce an increase in risk of coeliac disease is
that the receptors formed by these genes bind to gliadin peptides more
tightly than other forms of the antigen-presenting receptor. Therefore,
these forms of the receptor are more likely to activate T lymphocytes
and initiate the autoimmune process.[2]
Most coeliac patients bear a two-gene HLA-DQ2 haplotype referred to as
DQ2.5 haplotype. This haplotype is composed of two adjacent gene
alleles, DQA1*0501 and DQB1*0201, which encode the two subunits, DQ a5
and DQ ß2. In most individuals, this DQ2.5 isoform is encoded by one of
two chromosomes 6 inherited from parents. Most coeliacs inherit only one
copy of this DQ2.5 haplotype, while some inherit it from both parents;
the latter are especially at risk for coeliac disease, as well as being
more susceptible to severe complications.[24] Some individuals inherit
DQ2.5 from one parent and portions of the haplotype (DQB1*02 or DQA1*05)
from the other parent, increasing risk. Less commonly, some individuals
inherit the DQA1*05 allele from one parent and the DQB1*02 from the
other parent, called a trans-haplotype association, and these
individuals are at similar risk for coeliac disease as those with a
single DQ2.5-bearing chromosome 6, but in this instance, disease tends
not to be familial. Among the 6% of European coeliacs that do not have
DQ2.5 (cis or trans) or DQ8 (encoded by the haplotype
DQA1*03:DQB1*0302), 4% have the DQ2.2 isoform, and the remaining 2% lack
DQ2 or DQ8.[25]
The frequency of these genes varies geographically. DQ2.5 has high
frequency in peoples of North and Western Europe (Basque Country and
Ireland[26] with highest frequencies) and portions of Africa and is
associated with disease in India,[27] but is not found along portions of
the West Pacific rim. DQ8 has a wider global distribution than DQ2.5,
and is particularly common in South and Central America; up to 90% of
individuals in certain Amerindian populations carry DQ8 and thus may
display the coeliac phenotype.[28]
Other genetic factors have been repeatedly reported in CD, however,
involvement in disease has variable geographic recognition. Only the
HLA-DQ loci show a consistent involvement over the global
population.[29] Many of the loci detected have been found in association
with other autoimmune diseases. One locus, the LPP or lipoma-preferred
partner gene is involved in the adhesion of extracellular matrix to the
cell surface and a minor variant (SNP = rs1464510) increases the risk of
disease by approximately 30%. This gene strongly associates with celiac
disease(p < 10-39) in samples taken from a broad area of Europe and the
US.[29]
[edit]
Prolamins
The majority of the proteins in food responsible for the immune reaction
in coeliac disease are the prolamins. These are storage proteins rich in
proline (prol-) and glutamine (-amin) that dissolve in alcohols and are
resistant to proteases and peptidases of the gut.[2][30] Prolamins are
found in cereal grains with different grains having different but
related prolamins: wheat (gliadin), barley (hordein), rye (secalin),
corn (zein) and as a minor protein, avenin in oats. One region of
a-gliadin stimulates membrane cells, enterocytes, of the intestine to
allow larger molecules around the sealant between cells. Disruption of
tight junctions allow peptides larger than three amino acids to enter
circulation.[31]
File:A2-gliadin-33mer
Illustration of deamidated a-2 gliadin's 33mer, amino acids 56-88,
showing the overlapping of three varieties of T-cell epitope[32]
Membrane leaking permits peptides of gliadin that stimulate two levels
of immune response, the innate response and the adaptive (T-helper cell
mediated) response. One protease-resistant peptide from a-gliadin
contains a region that stimulates lymphocytes and results in the release
of interleukin-15. This innate response to gliadin results in
immune-system signalling that attracts inflammatory cells and increases
the release of inflammatory chemicals.[2] The strongest and most common
adaptive response to gliadin is directed toward an a2-gliadin fragment
of 33 amino acids in length.[2] The response to the 33mer occurs in most
coeliacs who have a DQ2 isoform. This peptide, when altered by
intestinal transglutaminase, has a high density of overlapping T-cell
epitopes. This increases the likelihood that the DQ2 isoform will bind
and stay bound to peptide when recognised by T-cells.[32] Gliadin in
wheat is the best-understood member of this family, but other prolamins
exist, and hordein (from barley) and secalin (from rye) may contribute
to coeliac disease.[2][33] However, not all prolamins will cause this
immune reaction, and there is ongoing controversy on the ability of
avenin (the prolamin found in oats) to induce this response in coeliac
disease.
[edit]
Tissue transglutaminase
File:Tissue_transglutaminase
Tissue transglutaminase, drawn from PDB 1FAU
Anti-transglutaminase antibodies to the enzyme tissue transglutaminase
(tTG) are found in an overwhelming majority of cases.[34] Tissue
transglutaminase modifies gluten peptides into a form that may stimulate
the immune system more effectively.[2] These peptides are modified by
tTG in two ways, deamidation or transamidation.[35] Deamidation is the
reaction by which a glutamate residue is formed by cleavage of the
epsilon-amino group of a glutamine side chain. Transamidation, which
occurs three times more often than deamidation, is the cross-linking of
a glutamine residue from the gliadin peptide to a lysine residue of tTg
in a reaction which is catalysed by the transglutaminase. Crosslinking
may occur either within or outside the active site of the enzyme. The
latter case yields a permanently, covalently linked complex between the
gliadin and the tTg.[36] This results in the formation of new epitopes
which are believed to trigger the primary immune response by which the
autoantibodies against tTg develop.[37][38][39]
Stored biopsies from suspected coeliac patients have revealed that
autoantibody deposits in the subclinical coeliacs are detected prior to
clinical disease. These deposits are also found in patients who present
with other autoimmune diseases, anaemia or malabsorption phenomena at a
much-increased rate over the normal population.[40] Endomysial
components of antibodies (EMA) to tTG are believed to be directed toward
cell-surface transglutaminase, and these antibodies are still used in
confirming a coeliac disease diagnosis. However, a 2006 study showed
that EMA-negative coeliac patients tend to be older males with more
severe abdominal symptoms and a lower frequency of "atypical" symptoms
including autoimmune disease.[41] In this study, the anti-tTG antibody
deposits did not correlate with the severity of villous destruction.
These findings, coupled with recent work showing that gliadin has an
innate response component,[42] suggests that gliadin may be more
responsible for the primary manifestations of coeliac disease, whereas
tTG is a bigger factor in secondary effects such as allergic responses
and secondary autoimmune diseases. In a large percentage of coeliac
patients, the anti-tTG antibodies also recognise a rotavirus protein
called VP7. These antibodies stimulate monocyte proliferation, and
rotavirus infection might explain some early steps in the cascade of
immune cell proliferation.[43] Indeed, earlier studies of rotavirus
damage in the gut showed this causes a villous atrophy.[44] This
suggests that viral proteins may take part in the initial flattening and
stimulate self-crossreactive anti-VP7 production. Antibodies to VP7 may
also slow healing until the gliadin-mediated tTG presentation provides a
second source of crossreactive antibodies.
[edit]
Villous atrophy and malabsorption
The inflammatory process, mediated by T cells, leads to disruption of
the structure and function of the small bowel's mucosal lining and
causes malabsorption as it impairs the body's ability to absorb
nutrients, minerals and fat-soluble vitamins A, D, E and K from food.
Lactose intolerance may be present due to the decreased bowel surface
and reduced production of lactase but typically resolves once the
condition is treated.
Alternative causes of this tissue damage have been proposed and involve
release of interleukin 15 and activation of the innate immune system by
a shorter gluten peptide (p31-43/49). This would trigger killing of
enterocytes by lymphocytes in the epithelium.[2] The villous atrophy
seen on biopsy may also be due to unrelated causes, such as tropical
sprue, giardiasis and radiation enteritis. While positive serology and
typical biopsy are highly suggestive of coeliac disease, lack of
response to diet may require these alternative diagnoses to be
considered.[10]
[edit]
Risk modifiers
There are various theories as to what determines whether a genetically
susceptible individual will go on to develop coeliac disease. Major
theories include infection by rotavirus[45] or human intestinal
adenovirus.[46] Some research has suggested that smoking is protective
against adult-onset coeliac disease.[47]
A 2005 prospective and observational study found that timing of the
exposure to gluten in childhood was an important risk modifier. People
exposed to wheat, barley, or rye before the gut barrier has fully
developed (within the first three months after birth) had five times the
risk of developing coeliac disease relative to those exposed at four to
six months after birth. Those exposed even later than six months after
birth were found to have only a slightly increased risk relative to
those exposed at four to six months after birth.[48] A study conducted
in 2006 showed that early introduction of grains was protective against
grain allergies; however, this study explicitly excluded any
participants found to have coeliac disease and therefore offers no help
in this regard.[49] Breastfeeding may also reduce risk. A meta-analysis
indicates that prolonging breastfeeding until the introduction of
gluten-containing grains into the diet was associated with a 52% reduced
risk of developing coeliac disease in infancy; whether this persists
into adulthood is not clear.[50]
[edit]
Diagnosis
There are several tests that can be used to assist in diagnosis. The
level of symptoms may determine the order of the tests, but all tests
lose their usefulness if the patient is already taking a gluten-free
diet. Intestinal damage begins to heal within weeks of gluten being
removed from the diet, and antibody levels decline over months. For
those who have already started on a gluten-free diet, it may be
necessary to perform a re-challenge with some gluten-containing food in
one meal a day over 2-6 weeks before repeating the investigations.[18]
Combining findings into a prediction rule to guide use of endoscopic
biopsy reported a sensitivity of 100% (it would identify all the cases)
in a population of subjects with a high index of suspicion for celiac
disease, with a concomitant specificity of 61% (a false positive rate of
39%). The prediction rule recommends that patients with high-risk
symptoms or positive serology should undergo endoscopic biopsy of the
second part of the duodenum. The study defined high-risk symptoms as
weight loss, anaemia (haemoglobin less than 120 g/l in females or less
than 130 g/l in males), or diarrhoea (more than three loose stools per
day).[51]
[edit]
Blood tests
Serological blood tests are the first-line investigation required to
make a diagnosis of coeliac disease. IgA antiendomysial antibodies can
detect coeliac disease with a sensitivity and specificity of 90% and 99%
according to a systematic review. The systematic review estimates that
the prevalence of coeliac disease in primary care patients with
gastrointestinal symptoms to be about 3%.[52] Serology for anti-tTG
antibodies was initially reported to have a high sensitivity (99%) and
specificity ( 90%) for identifying coeliac disease; however, the
systematic review found the two tests were similar.[52] Modern anti-tTG
assays rely on a human recombinant protein as an antigen.[53] tTG
testing should be done first as it is an easier test to perform. An
equivocal result on tTG testing should be followed by antibodies to
endomysium.[18]
Because of the major implications of a diagnosis of coeliac disease,
professional guidelines recommend that a positive blood test is still
followed by an endoscopy/gastroscopy and biopsy. A negative serology
test may still be followed by a recommendation for endoscopy and
duodenal biopsy if clinical suspicion remains high due to the 1 in 100
"false-negative" result. As such, tissue biopsy is still considered the
gold standard in the diagnosis of coeliac disease.[10][18][54]
Historically three other antibodies were measured: anti-reticulin (ARA),
anti-gliadin (AGA) and anti-endomysium (EMA) antibodies. Serology may be
unreliable in young children, with anti-gliadin performing somewhat
better than other tests in children under five.[55] Serology tests are
based on indirect immunofluorescence (reticulin, gliadin and endomysium)
or ELISA (gliadin or tissue transglutaminase, tTG).[56]
Guidelines recommend that a total serum IgA level is checked in
parallel, as coeliac patients with IgA deficiency may be unable to
produce the antibodies on which these tests depend ("false negative").
In those patients, IgG antibodies against transglutaminase (IgG-tTG) may
be diagnostic.[18][57]
Antibody testing and HLA testing have similar accuracies.[22] However,
widespread use of HLA typing to rule out coeliac disease is not
currently recommended.[18]
Blood HLA tests for coeliac disease[22]
Test
sensitivity
specificity
HLA-DQ2
94%
73%
HLA-DQ8
12%
81%
[edit]
Endoscopy
File:Celiac_endo
Endoscopic still of duodenum of patient with coeliac disease showing
scalloping of folds and "cracked-mud" appearance to mucosa
File:Coeliac_Disease
Schematic of the Marsh classification of upper jejunal pathology in
coeliac disease
An upper endoscopy with biopsy of the duodenum (beyond the duodenal
bulb) or jejunum is performed. It is important for the physician to
obtain multiple samples (four to eight) from the duodenum. Not all areas
may be equally affected; if biopsies are taken from healthy bowel
tissue, the result would be a false negative.[10]
Most patients with coeliac disease have a small bowel that appears
normal on endoscopy; however, five concurrent endoscopic findings have
been associated with a high specificity for coeliac disease: scalloping
of the small bowel folds (pictured), paucity in the folds, a mosaic
pattern to the mucosa (described as a "cracked-mud" appearance),
prominence of the submucosa blood vessels, and a nodular pattern to the
mucosa.[58]
Until the 1970s, biopsies were obtained using metal capsules attached to
a suction device. The capsule was swallowed and allowed to pass into the
small intestine. After x-ray verification of its position, suction was
applied to collect part of the intestinal wall inside the capsule.
Often-utilised capsule systems were the Watson capsule and the
Crosby-Kugler capsule. This method has now been largely replaced by
fibre-optic endoscopy, which carries a higher sensitivity and a lower
frequency of errors.[59]
[edit]
Pathology
The classic pathology changes of coeliac disease in the small bowel are
categorised by the "Marsh classification":[60]
? Marsh stage 0: normal mucosa
? Marsh stage 1: increased number of intra-epithelial lymphocytes,
usually exceeding 20 per 100 enterocytes
? Marsh stage 2: proliferation of the crypts of Lieberkuhn
? Marsh stage 3: partial or complete villous atrophy
? Marsh stage 4: hypoplasia of the small bowel architecture
Marsh's classification, introduced in 1992, was subsequently modified in
1999 to six stages, where the previous stage 3 was split in three
substages.[61] Further studies demonstrated that this system was not
always reliable and that the changes observed in coeliac disease could
be described in one of three stages-A, B1 and B2-with A representing
lymphocytic infiltration with normal villous appearance and B1 and B2
describing partial and complete villous atrophy.[5][62]
The changes classically improve or reverse after gluten is removed from
the diet. However, most guidelines do not recommend a repeat biopsy
unless there is no improvement in the symptoms on diet.[10][54] In some
cases, a deliberate gluten challenge, followed by biopsy, may be
conducted to confirm or refute the diagnosis. A normal biopsy and normal
serology after challenge indicates the diagnosis may have been
incorrect.[10]
[edit]
Other diagnostic tests
At the time of diagnosis, further investigations may be performed to
identify complications, such as iron deficiency (by full blood count and
iron studies), folic acid and vitamin B12 deficiency and hypocalcaemia
(low calcium levels, often due to decreased vitamin D levels). Thyroid
function tests may be requested during blood tests to identify
hypothyroidism, which is more common in people with coeliac disease.[11]
Osteopenia and osteoporosis, mildly and severely reduced bone mineral
density, are often present in people with coeliac disease, and
investigations to measure bone density may be performed at diagnosis,
such as dual energy X-ray absorptiometry (DXA) scanning, to identify
risk of fracture and need for bone protection medication.[10][11]
[edit]
Screening
Due to its high sensitivity, serology has been proposed as a screening
measure, because the presence of antibodies would detect previously
undiagnosed cases of coeliac disease and prevent its complications in
those patients.[10] There is significant debate as to the benefits of
screening. Some studies suggest that early detection would decrease the
risk of osteoporosis and anaemia. In contrast, a cohort study in
Cambridge suggested that people with undetected coeliac disease had a
beneficial risk profile for cardiovascular disease (less overweight,
lower cholesterol levels).[2] There is limited evidence that
screen-detected cases benefit from a diagnosis in terms of morbidity and
mortality; hence, population-level screening is not presently thought to
be beneficial.[5]
In the United Kingdom, the National Institute for Health and Clinical
Excellence (NICE) recommends screening for coeliac disease in patients
with newly diagnosed chronic fatigue syndrome[63] and irritable bowel
syndrome,[9] as well as in type 1 diabetics, especially those with
insufficient weight gain or unexplained weight loss.[18][64] It is also
recommended in autoimmune thyroid disease, dermatitis herpetiformis, and
in the first-degree relatives of those with confirmed coeliac disease.[18]
There is a large number of scenarios where testing for coeliac disease
may be offered given previously described associations, such as the
conditions mentioned above in "miscellaneous".[5][18]
[edit]
Treatment
[edit]
Diet
Main article: Gluten-free diet
At present, the only effective treatment is a life-long gluten-free
diet.[20] No medication exists that will prevent damage or prevent the
body from attacking the gut when gluten is present. Strict adherence to
the diet allows the intestines to heal, leading to resolution of all
symptoms in most cases and, depending on how soon the diet is begun, can
also eliminate the heightened risk of osteoporosis and intestinal cancer
and in some cases sterility.[65] Dietitian input is generally requested
to ensure the patient is aware which foods contain gluten, which foods
are safe, and how to have a balanced diet despite the limitations. In
many countries, gluten-free products are available on prescription and
may be reimbursed by health insurance plans.
The diet can be cumbersome; failure to comply with the diet may cause
relapse. The term gluten-free is generally used to indicate a supposed
harmless level of gluten rather than a complete absence.[66] The exact
level at which gluten is harmless is uncertain and controversial. A
recent systematic review tentatively concluded that consumption of less
than 10 mg of gluten per day is unlikely to cause histological
abnormalities, although it noted that few reliable studies had been
done.[66] Regulation of the label gluten-free varies widely by country.
In the United States, the FDA issued regulations in 2007 limiting the
use of "gluten-free" in food products to those with less than 20 ppm of
gluten.[67][68] The current international Codex Alimentarius standard
allows for 20 ppm of gluten in so-called "gluten-free" foods.[69]
Gluten-free products are usually more expensive and harder to find than
common gluten-containing foods.[70] Since ready-made products often
contain traces of gluten, some coeliacs may find it necessary to cook
from scratch.[71]
Even while on a diet, health-related quality of life (HRQOL) may be
lower in people with coeliac disease. Studies in the United States have
found that quality of life becomes comparable to the general population
after staying on the diet, while studies in Europe have found that
quality of life remains lower, although the surveys are not quite the
same.[72] Men tend to report more improvement than women.[73] Some have
persisting digestive symptoms or dermatitis herpetiformis, mouth ulcers,
osteoporosis and resultant fractures. Symptoms suggestive of irritable
bowel syndrome may be present, and there is an increased rate of
anxiety, fatigue, dyspepsia and musculoskeletal pain.[74]
Many people with coeliac disease also have one or more[75] additional
food allergies or food intolerances, which may include milk protein
(casein),[76] corn (maize),[77][78] soy,[75] amines,[75] or salicylates.[75]
[edit]
Refractory disease
A tiny minority of patients suffer from refractory disease, which means
they do not improve on a gluten-free diet. This may be because the
disease has been present for so long that the intestines are no longer
able to heal on diet alone, or because the patient is not adhering to
the diet, or because the patient is consuming foods that are
inadvertently contaminated with gluten. If alternative causes have been
eliminated, steroids or immunosuppressants (such as azathioprine) may be
considered in this scenario.[10]
[edit]
Experimental treatments
Various other approaches are being studied that would reduce the need of
dieting. All are still under development, and are not expected to be
available to the general public for a while:[2]
? Genetically engineered wheat species, or wheat species that have been
selectively bred to be minimally immunogenic. This, however, could
interfere with the effects that gliadin has on the quality of dough.
? A combination of enzymes (prolyl endopeptidase and a barley
glutamine-specific cysteine endopeptidase (EP-B2)) that degrade the
putative 33-mer peptide in the duodenum. This combination would enable
coeliac disease patients to consume gluten-containing products.[79]
? Inhibition of zonulin, an endogenous signalling protein linked to
increased permeability of the bowel wall and hence increased
presentation of gliadin to the immune system.[80]
? Other treatments aimed at other well-understood steps in the
pathogenesis of coeliac disease, such as the action of HLA-DQ2 or tissue
transglutaminase and the MICA/NKG2D interaction that may be involved in
the killing of enterocytes (bowel lining cells).
[edit]
Epidemiology
The disease is thought to affect between 1 in 1750 (with CD defined as
clinical cases including dermatitis herpetiformis) to 1 in 105 (CD
defined by presence of IgA TG in blood donors) people in the United
States.[3] The prevalence of clinically diagnosed disease (symptoms
prompting diagnostic testing) is 0.05-0.27% in various studies. However,
population studies from parts of Europe, India, South America,
Australasia and the USA (using serology and biopsy) indicate that the
prevalence may be between 0.33 and 1.06% in children (5.66% in one study
of Sahrawi children[81]) and 0.18-1.2% in adults.[2] People of African,
Japanese and Chinese descent are rarely diagnosed;[citation needed] this
reflects a much lower prevalence of the genetic risk factors. Population
studies also indicate that a large proportion of coeliacs remain
undiagnosed; this is due, in part, to many clinicians being unfamiliar
with the condition.[82]
Coeliac disease is more prevalent in women than in men.[83]
A large multicentre study in the U.S. found a prevalence of 0.75% in
not-at-risk groups, rising to 1.8% in symptomatic patients, 2.6% in
second-degree relatives of a patient with coeliac disease and 4.5% in
first-degree relatives. This profile is similar to the prevalence in
Europe.[84] Other populations at increased risk for coeliac disease,
with prevalence rates ranging from 5% to 10%, include individuals with
Down and Turner syndromes, type 1 diabetes, and autoimmune thyroid
disease, including both hyperthyroidism (overactive thyroid) and
hypothyroidism (underactive thyroid).[85]
Historically, coeliac disease was thought to be rare, with a prevalence
of about 0.02%.[85] Recent increases in the number of reported cases may
be due to changes in diagnostic practice,[86] but there is evidence that
coeliac disease may be becoming more common in the United States.[87]
[edit]
Social and religious issues
[edit]
Christian churches & the Eucharist
In the Christian Eucharist a wafer or small piece of wheat bread is
eaten (see Sacramental bread). A typical wafer weighs about half a
gram[88] Wheat flour contains around 10 to 13% gluten, so a single
communion wafer may have more than 50 mg of gluten, an amount which will
harm the health of many coeliac patients especially if consumed every
day (see Diet above). Many Christian churches offer their communicants
gluten-free alternatives, usually in the form of a rice-based cracker or
gluten-free bread. These include United Methodist, Christian Reformed,
Episcopal, Lutheran, Roman Catholic and The Church of Jesus Christ of
Latter-day Saints.[89]
[edit]
Roman Catholic position
Roman Catholic doctrine states that for a valid Eucharist, the bread
must be made from wheat. In 2002, the Congregation for the Doctrine of
the Faith approved German-made low-gluten hosts, which meet all of the
Catholic Church's requirements, for use in Italy; although not entirely
gluten-free, they were also approved by the Italian Celiac
Association.[90] Some Catholic coeliac sufferers have requested
permission to use rice wafers; such petitions have always been
denied.[91] The issue is more complex for priests. Though a Catholic
(lay or ordained) receiving under either form is receiving Christ "whole
and entire"-his body, blood, soul, and divinity-the priest, who is
acting in persona Christi, is required to receive under both species
when offering Mass-not for the validity of his Communion, but for the
fullness of the sacrifice of the Mass. On 22 August 1994, the
Congregation for the Doctrine of the Faith apparently barred coeliacs
from ordination, stating, "Given the centrality of the celebration of
the Eucharist in the life of the priest, candidates for the priesthood
who are affected by coeliac disease or suffer from alcoholism or similar
conditions may not be admitted to holy orders." After considerable
debate, the congregation softened the ruling on 24 July 2003 to "Given
the centrality of the celebration of the Eucharist in the life of a
priest, one must proceed with great caution before admitting to Holy
Orders those candidates unable to ingest gluten or alcohol without
serious harm."[92]
As of January 2004, an extremely low-gluten host became available in the
United States. The Benedictine Sisters of Perpetual Adoration in Clyde,
Missouri, produce low-gluten hosts safe for coeliacs and also approved
by the Catholic Church for use at Mass. The hosts are made and packaged
in a dedicated wheat-free, gluten-free environment. Gluten-content
analysis found no detectable amount of gluten, though the reported
gluten content is 0.01% as that was the lowest limit of detection
possible with the utilised analysis technique. In an article from the
Catholic Review (15 February 2004), Dr. Alessio Fasano was quoted as
declaring these hosts "perfectly safe for celiac sufferers."[93]
[edit]
Passover
The Jewish festival of Pesach (Passover) may present problems with its
obligation to eat matzo, which is unleavened bread made in a strictly
controlled manner from wheat, barley, spelt, oats, or rye. This rules
out many other grains that are normally used as substitutes for people
with gluten sensitivity, especially for Ashkenazi Jews, who also avoid
rice. Many kosher-for-Passover products avoid grains altogether and are
therefore gluten-free. Potato starch is the primary starch used to
replace the grains. Consuming matzo is mandatory on the first night of
Pesach only. Jewish law holds that a person should not seriously
endanger one's health in order to fulfil a commandment. Thus, a person
with severe coeliac disease is not required, or even allowed, to eat any
matzo other than gluten-free matzo. The most commonly used gluten-free
matzo is made from oats.[94]
[edit]
History
Humans first started to cultivate grains in the Neolithic period
(beginning about 9500 BCE) in the Fertile Crescent in Western Asia, and
it is likely that coeliac disease did not occur before this time.
Aretaeus of Cappadocia, living in the second century in the same area,
recorded a malabsorptive syndrome with chronic diarrhoea. His "C?liac
Affection" (coeliac from Greek ?????a??? koiliakos, "abdominal") gained
the attention of Western medicine when Francis Adams presented a
translation of Aretaeus's work at the Sydenham Society in 1856. The
patient described in Aretaeus' work had stomach pain and was atrophied,
pale, feeble and incapable of work. The diarrhoea manifested as loose
stools that were white, malodorous and flatulent, and the disease was
intractable and liable to periodic return. The problem, Aretaeus
believed, was a lack of heat in the stomach necessary to digest the food
and a reduced ability to distribute the digestive products throughout
the body, this incomplete digestion resulting in the diarrhoea. He
regarded this as an affliction of the old and more commonly affecting
women, explicitly excluding children. The cause, according to Aretaeus,
was sometimes either another chronic disease or even consuming "a
copious draught of cold water."[6][7]
The paediatrician Samuel Gee gave the first modern-day description of
the condition in children in a lecture at Hospital for Sick Children,
Great Ormond Street, London, in 1887. Gee acknowledged earlier
descriptions and terms for the disease and adopted the same term as
Aretaeus (coeliac disease). He perceptively stated: "If the patient can
be cured at all, it must be by means of diet." Gee recognised that milk
intolerance is a problem with coeliac children and that highly starched
foods should be avoided. However, he forbade rice, sago, fruit and
vegetables, which all would have been safe to eat, and he recommended
raw meat as well as thin slices of toasted bread. Gee highlighted
particular success with a child "who was fed upon a quart of the best
Dutch mussels daily." However, the child could not bear this diet for
more than one season.[7][95]
Christian Archibald Herter, an American physician, wrote a book in 1908
on children with coeliac disease, which he called "intestinal
infantilism." He noted their growth was retarded and that fat was better
tolerated than carbohydrate. The eponym Gee-Herter disease was sometimes
used to acknowledge both contributions.[96][97] Sidney V. Haas, an
American paediatrician, reported positive effects of a diet of bananas
in 1924.[98] This diet remained in vogue until the actual cause of
coeliac disease was determined.[7]
While a role for carbohydrates had been suspected, the link with wheat
was not made until the 1940s by the Dutch paediatrician Dr. Willem Karel
Dicke.[99] It is likely that clinical improvement of his patients during
the Dutch famine of 1944 (during which flour was scarce) may have
contributed to his discovery.[100] Dicke noticed that the shortage of
bread led to a significant drop in the death rate among children
affected by CD from greater than 35% to essentially zero. He also
reported that once wheat was again available after the conflict, the
mortality rate soared to previous levels.[101] The link with the gluten
component of wheat was made in 1952 by a team from Birmingham,
England.[102] Villous atrophy was described by British physician John W.
Paulley in 1954 on samples taken at surgery.[103] This paved the way for
biopsy samples taken by endoscopy.[7]
Throughout the 1960s, other features of coeliac disease were elucidated.
Its hereditary character was recognised in 1965.[104] In 1966,
dermatitis herpetiformis was linked to gluten sensitivity.[7][14]
May and October have been designated as "Coeliac Awareness Month".[105][106]
[edit]
References
1. ^ See American and British English spelling differences.
2. ^ a b c d e f g h i j k l m n van Heel D, West J (2006). "Recent
advances in coeliac disease". Gut 55 (7): 1037-46.
doi:10.1136/gut.2005.075119. PMC 1856316. PMID 16766754.
3. ^ a b Rewers, Marian J. (2005). "Epidemiology of Celiac Disease: What
Are the Prevalence, Incidence, and Progression of Celiac Disease?".
Gastroenterology (National Institute of Health) 128 (4 Suppl 1): S47-51.
doi:10.1053/j.gastro.2005.02.030. PMID 15825126
4. ^ Binning, D (2010). "Causes of gluten intolerance discovered".
Australian Life Scientist (July).
5. ^ a b c d e f g h i j k l Di Sabatino A, Corazza GR (April 2009).
"Coeliac disease". Lancet 373 (9673): 1480-93.
doi:10.1016/S0140-6736(09)60254-3. PMID 19394538.
6. ^ a b Adams F, translator (1856). "On The C?liac Affection". The
extant works of Aretaeus, The Cappadocian. London: Sydenham Society.
pp. 350-1. Retrieved 12 December 2009.
7. ^ a b c d e f Losowsky MS (2008). "A history of coeliac disease". Dig
Dis 26 (2): 112-20. doi:10.1159/000116768. PMID 18431060.
8. ^ Ferguson R, Basu M, Asquith P, Cooke W (1976). "Jejunal mucosal
abnormalities in patients with recurrent aphthous ulceration". Br Med J
1 (6000): 11-13. doi:10.1136/bmj.1.6000.11. PMC 1638254. PMID 1247715.
9. ^ a b National Institute for Health and Clinical Excellence. Clinical
guideline 61: Irritable bowel syndrome. London, 2008.
10. ^ a b c d e f g h i "American Gastroenterological Association
medical position statement: Celiac Sprue". Gastroenterology 120 (6):
1522-5. 2001. doi:10.1053/gast.2001.24055. PMID 11313323.
11. ^ a b c Presutti RJ, Cangemi JR, Cassidy HD, Hill DA (December
2007). "Celiac disease". Am Fam Physician 76 (12): 1795-802. PMID 18217518.
12. ^ Tursi A, Brandimarte G, Giorgetti G (2003). "High prevalence of
small intestinal bacterial overgrowth in celiac patients with
persistence of gastrointestinal symptoms after gluten withdrawal". Am J
Gastroenterol 98 (4): 839-43. doi:10.1111/j.1572-0241.2003.07379.x.
PMID 12738465.
13. ^ Cunningham-Rundles C (September 2001). "Physiology of IgA and IgA
deficiency". J. Clin. Immunol. 21 (5): 303-9.
doi:10.1023/A:1012241117984. PMID 11720003.
14. ^ a b Marks J, Shuster S, Watson A (1966). "Small-bowel changes in
dermatitis herpetiformis". Lancet 2 (7476): 1280-2.
doi:10.1016/S0140-6736(66)91692-8. PMID 4163419.
15. ^ Nicolas ME, Krause PK, Gibson LE, Murray JA (August 2003).
"Dermatitis herpetiformis". Int. J. Dermatol. 42 (8): 588-600.
doi:10.1046/j.1365-4362.2003.01804.x. PMID 12890100.
16. ^ Ferguson A, Hutton M, Maxwell J, Murray D (1970). "Adult coeliac
disease in hyposplenic patients". Lancet 1 (7639): 163-4.
doi:10.1016/S0140-6736(70)90405-8. PMID 4189238.
17. ^ Collin P, Kaukinen K, Välimäki M, Salmi J (2002).
"Endocrinological disorders and celiac disease". Endocr Rev 23 (4):
464-83. doi:10.1210/er.2001-0035. PMID 12202461.
18. ^ a b c d e f g h i National Institute for Health and Clinical
Excellence. Clinical guideline 86: Recognition and assessment of coeliac
disease. London, 2009.
19. ^ Schuppan D, Junker Y, Barisani D (December 2009). "Celiac disease:
from pathogenesis to novel therapies". Gastroenterology 137 (6):
1912-33. doi:10.1053/j.gastro.2009.09.008. PMID 19766641.
20. ^ a b c d e Kupper C (2005). "Dietary guidelines and implementation
for celiac disease". Gastroenterology 128 (4 Suppl 1): S121-7.
doi:10.1053/j.gastro.2005.02.024. PMID 15825119.
21. ^ Gallagher, Eimear (2009). Gluten-free Food Science and Technology.
Published by John Wiley and Sons,. pp. 320. ISBN 1405159154, 9781405159159.
22. ^ a b c d Hadithi M, von Blomberg BM, Crusius JB, et al. (2007).
"Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac
disease". Ann. Intern. Med. 147 (5): 294-302. PMID 17785484.
23. ^ Kim C, Quarsten H, Bergseng E, Khosla C, Sollid L (2004).
"Structural basis for HLA-DQ2-mediated presentation of gluten epitopes
in celiac disease". Proc Natl Acad Sci USA 101 (12): 4175-9.
doi:10.1073/pnas.0306885101. PMC 384714. PMID 15020763.
24. ^ Jores RD, Frau F, Cucca F, et al. (2007). "HLA-DQB1*0201
homozygosis predisposes to severe intestinal damage in celiac disease".
Scand. J. Gastroenterol. 42 (1): 48-53. doi:10.1080/00365520600789859.
PMID 17190762.
25. ^ Karell K, Louka AS, Moodie SJ, et al. (2003). "HLA types in celiac
disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer:
results from the European Genetics Cluster on Celiac Disease". Hum.
Immunol. 64 (4): 469-77. doi:10.1016/S0198-8859(03)00027-2. PMID 12651074.
26. ^ Michalski J, McCombs C, Arai T, Elston R, Cao T, McCarthy C,
Stevens F (1996). "HLA-DR, DQ genotypes of celiac disease patients and
healthy subjects from the West of Ireland". Tissue Antigens 47 (2):
127-33. doi:10.1111/j.1399-0039.1996.tb02525.x. PMID 8851726.
27. ^ Kaur G, Sarkar N, Bhatnagar S, et al. (2002). "Pediatric celiac
disease in India is associated with multiple DR3-DQ2 haplotypes". Hum.
Immunol. 63 (8): 677-82. doi:10.1016/S0198-8859(02)00413-5. PMID 12121676.
28. ^ Layrisse Z, Guedez Y, Domínguez E, Paz N, Montagnani S, Matos M,
Herrera F, Ogando V, Balbas O, Rodríguez-Larralde A (2001). "Extended
HLA haplotypes in a Carib Amerindian population: the Yucpa of the Perija
Range". Hum Immunol 62 (9): 992-1000. doi:10.1016/S0198-8859(01)00297-X.
PMID 11543901.
29. ^ a b Dubois et al.; Trynka, G; Franke, L; Hunt, KA; Romanos, J;
Curtotti, A; Zhernakova, A; Heap, GA et al. (2010). "Multipel common
variants for celiac diease influencing immune gene expression". Nature
Genetics 42 (4): 295-302. doi:10.1038/ng.543. PMC 2847618. PMID 20190752.
30. ^ Green PH, Cellier C (October 2007). "Celiac disease". N. Engl. J.
Med. 357 (17): 1731-43. doi:10.1056/NEJMra071600. PMID 17960014.
31. ^ Lammers KM, Lu R, Brownley J, et al. (July 2008). "Gliadin induces
an increase in intestinal permeability and zonulin release by binding to
the chemokine receptor CXCR3". Gastroenterology 135 (1): 194-204.e3.
doi:10.1053/j.gastro.2008.03.023. PMC 2653457. PMID 18485912.
32. ^ a b Qiao SW, Bergseng E, Molberg Ø, et al. (August 2004). "Antigen
presentation to celiac lesion-derived T cells of a 33-mer gliadin
peptide naturally formed by gastrointestinal digestion". J. Immunol. 173
(3): 1757-62. PMID 15265905.
33. ^ Shan L, Qiao SW, Arentz-Hansen H, et al. (2005). "Identification
and analysis of multivalent proteolytically resistant peptides from
gluten: implications for celiac sprue". J. Proteome Res. 4 (5): 1732-41.
doi:10.1021/pr050173t. PMC 1343496. PMID 16212427.
34. ^ Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken E,
Schuppan D (1997). "Identification of tissue transglutaminase as the
autoantigen of celiac disease". Nat Med 3 (7): 797-801.
doi:10.1038/nm0797-797. PMID 9212111.
35. ^ Skovbjerg H, Norén O, Anthonsen D, Moller J, Sjöström H (2002).
"Gliadin is a good substrate of several transglutaminases: possible
implication in the pathogenesis of coeliac disease.". Scand J
Gastroenterol 37 (7): 812-7. doi:10.1080/713786534. PMID 12190095.
36. ^ Fleckenstein B, Molberg 0, Qiao SW, Schmid DG, Mulbe E von der,
Elgstoen K, Jung G and Soflid ML. (2002). "Gliadin T cell epitope
selection by tissue transglutaminase in celiac disease. Role of enzyme
specificity and pH influence on the transamidation versus deamidation
process.". J Bio Chem 277 (37): 34109-34116. doi:10.1074/jbc.M204521200.
PMID 12093810.
37. ^ Koning, F.; Schuppan, D.; Cerf-Bensussan, N.; Sollid, M. (Jun
2005). "Pathomechanisms in celiac disease". Best practice & research.
Clinical gastroenterology 19 (3): 373-387.
doi:10.1016/j.bpg.2005.02.003. ISSN 1521-6918. PMID 15925843. edit
38. ^ Mowat AM. (2003). "Coeliac disease - a meeting point for genetics,
immunology, and protein chemistry". Lancet 361 (9365): 1290-1292.
doi:10.1016/S0140-6736(03)12989-3. PMID 12699968.
39. ^ Dewar D, Pereira SP and Ciclitira PJ (2004). "The pathogenesis of
coeliac disease". Int J Biochem Cell Biol 36 (1): 17-24.
doi:10.1016/S1357-2725(03)00239-5. PMID 14592529.
40. ^ Kaukinen K, Peraaho M, Collin P, Partanen J, Woolley N, Kaartinen
T, Nuuntinen T, Halttunen T, Maki M, Korponay-Szabo I (2005).
"Small-bowel mucosal tranglutaminase 2-specific IgA deposits in coeliac
disease without villous atrophy: A Prospective and radmonized clinical
study". Scand J Gastroenterology 40 (5): 564-572.
doi:10.1080/00365520510023422. PMID 16036509.
41. ^ Salmi T, Collin P, Korponay-Szabó I, Laurila K, Partanen J,
Huhtala H, Király R, Lorand L, Reunala T, Mäki M, Kaukinen K (2006).
"Endomysial antibody-negative coeliac disease: clinical characteristics
and intestinal autoantibody deposits". Gut 55 (12): 1746-53.
doi:10.1136/gut.2005.071514. PMC 1856451. PMID 16571636.
42. ^ Londei M, Ciacci C, Ricciardelli I, Vacca L, Quaratino S, and
Maiuri L. (2005). "Gliadin as a stimulator of innate responses in celiac
disease". Mol Immunol 42 (8): 913-918. doi:10.1016/j.molimm.2004.12.005.
PMID 15829281.
43. ^ Zanoni G, Navone R, Lunardi C, Tridente G, Bason C, Sivori S, Beri
R, Dolcino M, Valletta E, Corrocher R, Puccetti A (2006). "In celiac
disease, a subset of autoantibodies against transglutaminase binds
toll-like receptor 4 and induces activation of monocytes". PLoS Med 3
(9): e358. doi:10.1371/journal.pmed.0030358. PMC 1569884. PMID 16984219.
44. ^ Salim A, Phillips A, Farthing M (1990). "Pathogenesis of gut virus
infection". Baillieres Clin Gastroenterol 4 (3): 593-607.
doi:10.1016/0950-3528(90)90051-H. PMID 1962725.
45. ^ Stene L, Honeyman M, Hoffenberg E, Haas J, Sokol R, Emery L, Taki
I, Norris J, Erlich H, Eisenbarth G, Rewers M (2006). "Rotavirus
infection frequency and risk of celiac disease autoimmunity in early
childhood: a longitudinal study". Am J Gastroenterol 101 (10): 2333-40.
doi:10.1111/j.1572-0241.2006.00741.x. PMID 17032199.
46. ^ Kagnoff M, Paterson Y, Kumar P, Kasarda D, Carbone F, Unsworth D,
Austin R (1987). "Evidence for the role of a human intestinal adenovirus
in the pathogenesis of coeliac disease" (PDF). Gut 28 (8): 995-1001.
doi:10.1136/gut.28.8.995. PMC 1433141. PMID 2822550.
47. ^ Suman S, Williams E, Thomas P, Surgenor S, Snook J (2003). "Is the
risk of adult coeliac disease causally related to cigarette exposure?".
Eur J Gastroenterol Hepatol 15 (9): 995-1000.
doi:10.1097/00042737-200309000-00009. PMID 12923372.
48. ^ Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, Haas JE,
Emery LM, Sokol RJ, Erlich HA, Eisenbarth GS, Rewers M. (2005). "Risk of
celiac disease autoimmunity and timing of gluten introduction in the
diet of infants at increased risk of disease". JAMA 293 (19): 2343-2351.
doi:10.1001/jama.293.19.2343. PMID 15900004.
49. ^ Poole J, Barriga K, Leung D, Hoffman M, Eisenbarth G, Rewers M,
Norris J (2006). "Timing of initial exposure to cereal grains and the
risk of wheat allergy". Pediatrics 117 (6): 2175-82.
doi:10.1542/peds.2005-1803. PMID 16740862.
50. ^ Akobeng A, Ramanan A, Buchan I, Heller R (2006). "Effect of breast
feeding on risk of coeliac disease: a systematic review and
meta-analysis of observational studies". Arch Dis Child 91 (1): 39-43.
doi:10.1136/adc.2005.082016. PMC 2083075. PMID 16287899.
51. ^ Hopper A, Cross S, Hurlstone D, McAlindon M, Lobo A,
Hadjivassiliou M, Sloan M, Dixon S, Sanders D (2007). "Pre-endoscopy
serological testing for coeliac disease: evaluation of a clinical
decision tool". BMJ 334 (7596): 729. doi:10.1136/bmj.39133.668681.BE.
PMC 1847864. PMID 17383983.
52. ^ a b van der Windt DA, Jellema P, Mulder CJ, Kneepkens CM, van der
Horst HE (2010). "Diagnostic testing for celiac disease among patients
with abdominal symptoms: a systematic review.". JAMA 303 (17): 1738-46.
doi:10.1001/jama.2010.549. PMID 20442390.
53. ^ Sblattero D, Berti I, Trevisiol C, et al. (May 2000). "Human
recombinant tissue transglutaminase ELISA: an innovative diagnostic
assay for celiac disease". Am. J. Gastroenterol. 95 (5): 1253-7.
doi:10.1111/j.1572-0241.2000.02018.x. PMID 10811336.
54. ^ a b Hill ID, Dirks MH, Liptak GS, et al. (January 2005).
"Guideline for the diagnosis and treatment of celiac disease in
children: recommendations of the North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition". J. Pediatr. Gastroenterol.
Nutr. 40 (1): 1-19. doi:10.1097/00005176-200501000-00001. PMID 15625418.
55. ^ Hill ID (April 2005). "What are the sensitivity and specificity of
serologic tests for celiac disease? Do sensitivity and specificity vary
in different populations?". Gastroenterology 128 (4 Suppl 1): S25-32.
doi:10.1053/j.gastro.2005.02.012. PMID 15825123.
56. ^ Wong R, Steele R, Reeves G, Wilson R, Pink A, Adelstein S (2003).
"Antibody and genetic testing in coeliac disease". Pathology 35 (4):
285-304. PMID 12959764.
57. ^ Korponay-Szabó I, Dahlbom I, Laurila K, Koskinen S, Woolley N,
Partanen J, Kovács J, Mäki M, Hansson T (2003). "Elevation of IgG
antibodies against tissue transglutaminase as a diagnostic tool for
coeliac disease in selective IgA deficiency". Gut 52 (11): 1567-71.
doi:10.1136/gut.52.11.1567. PMC 1773847. PMID 14570724.
58. ^ Niveloni S, Fiorini A, Dezi R, Pedreira S, Smecuol E, Vazquez H,
Cabanne A, Boerr LA, Valero J, Kogan Z, Maurino E, Bai JC. (1998).
"Usefulness of videoduodenoscopy and vital dye staining as indicators of
mucosal atrophy of celiac disease: assessment of interobserver
agreement". Gastrointestinal Endoscopy 47 (3): 223-229.
doi:10.1016/S0016-5107(98)70317-7. PMID 9580349.
59. ^ Mee A, Burke M, Vallon A, Newman J, Cotton P (1985). "Small bowel
biopsy for malabsorption: comparison of the diagnostic adequacy of
endoscopic forceps and capsule biopsy specimens". Br Med J (Clin Res Ed)
291 (6498): 769-72. doi:10.1136/bmj.291.6498.769. PMC 1417146. PMID 3929934.
60. ^ Marsh M (1992). "Gluten, major histocompatibility complex, and the
small intestine. A molecular and immunobiologic approach to the spectrum
of gluten sensitivity ('celiac sprue')". Gastroenterology 102 (1):
330-54. PMID 1727768.
61. ^ Oberhuber G, Granditsch G, Vogelsang H (October 1999). "The
histopathology of coeliac disease: time for a standardized report scheme
for pathologists". Eur J Gastroenterol Hepatol 11 (10): 1185-94.
doi:10.1097/00042737-199910000-00019. PMID 10524652.
62. ^ Corazza GR, Villanacci V, Zambelli C, et al. (July 2007).
"Comparison of the interobserver reproducibility with different
histologic criteria used in celiac disease". Clin. Gastroenterol.
Hepatol. 5 (7): 838-43. doi:10.1016/j.cgh.2007.03.019. PMID 17544877.
63. ^ National Institute for Health and Clinical Excellence. Clinical
guideline 53: Chronic fatigue syndrome/myalgic encephalomyelitis.
London, 2007.
64. ^ National Institute for Health and Clinical Excellence. Clinical
guideline 15: Diagnosis and management of type 1 diabetes in children,
young people and adults. London, 2004.
65. ^ Treem W (2004). "Emerging concepts in celiac disease". Curr Opin
Pediatr 16 (5): 552-9. doi:10.1097/01.mop.0000142347.74135.73.
PMID 15367850.
66. ^ a b Akobeng AK, Thomas AG (June 2008). "Systematic review:
tolerable amount of gluten for people with coeliac disease". Aliment.
Pharmacol. Ther. 27 (11): 1044-52. doi:10.1111/j.1365-2036.2008.03669.x.
PMID 18315587.
67. ^ Section 206 of the Food Allergen Labeling and Consumer Protection
Act of 2004, Title II of Pub.L. 108-282, 118 Stat. 891, enacted
August 2, 2004
68. ^ 72 F.R. 2795-2817
69. ^ "Current Official Standards". FAO/WHO. Retrieved 26 June 2008.
70. ^ Lee AR, Ng DL, Zivin J, Green PH (October 2007). "Economic burden
of a gluten-free diet". J Hum Nutr Diet 20 (5): 423-30.
doi:10.1111/j.1365-277X.2007.00763.x. PMID 17845376.
71. ^ Troncone R, Ivarsson A, Szajewska H, Mearin ML (June 2008).
"Review article: future research on coeliac disease - a position report
from the European multistakeholder platform on coeliac disease
(CDEUSSA)". Aliment. Pharmacol. Ther. 27 (11): 1030-43.
doi:10.1111/j.1365-2036.2008.03668.x. PMID 18315588.
72. ^ Häuser W, Stallmach A, Caspary WF, Stein J (March 2007).
"Predictors of reduced health-related quality of life in adults with
coeliac disease". Aliment. Pharmacol. Ther. 25 (5): 569-78.
doi:10.1111/j.1365-2036.2006.03227.x. PMID 17305757.
73. ^ Goddard CJ, Gillett HR (November 2006). "Complications of coeliac
disease: are all patients at risk?". Postgrad Med J 82 (973): 705-12.
doi:10.1136/pgmj.2006.048876. PMC 2660494. PMID 17099088.
74. ^ Häuser W, Gold J, Stein J, Caspary WF, Stallmach A (July 2006).
"Health-related quality of life in adult coeliac disease in Germany:
results of a national survey". Eur J Gastroenterol Hepatol 18 (7):
747-54. doi:10.1097/01.meg.0000221855.19201.e8. PMID 16772832.
75. ^ a b c d Faulkner-Hogg et al.; Selby, WS; Loblay, RH (1999).
"Dietary analysis in symptomatic patients with coeliac disease on a
gluten-free diet: the role of trace amounts of gluten and non-gluten
food intolerances". Scand J Gastroenterol 34 (8): 784-9.
doi:10.1080/003655299750025714. PMID 10499479.
76. ^ Kristjánsson et al.; Venge, P; Hällgren, R (2007). "Mucosal
reactivity to cow's milk protein in coeliac disease". Clin Exp Immunol
147 (3): 449-55. doi:10.1111/j.1365-2249.2007.03298.x. PMC 1810502.
PMID 17302893.
77. ^ Kristjánsson et al.; Högman, M; Venge, P; Hällgren, R (2005). "Gut
mucosal granulocyte activation precedes nitric oxide production: studies
in coeliac patients challenged with gluten and corn". Gut 54 (6):
769-74. doi:10.1136/gut.2004.057174. PMC 1774524. PMID 15888782.
78. ^ Davidson et al.; Lloyd, RS; Whorwell, PJ; Wright, R (1979).
"Antibodies to maize in patients with Crohn's disease, ulcerative
colitis and coeliac disease". Clin Exp Immunol 35 (1): 147-8.
PMC 1537589. PMID 371884.
79. ^ Siegel M, Bethune M, Gass J, Ehren J, Xia J, Johannsen A, Stuge T,
Gray G, Lee P, Khosla C (2006). "Rational design of combination enzyme
therapy for celiac sprue". Chem Biol 13 (6): 649-58.
doi:10.1016/j.chembiol.2006.04.009. PMID 16793522.
80. ^ Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum S
(2000). "Zonulin, a newly discovered modulator of intestinal
permeability, and its expression in coeliac disease". Lancet 355 (9214):
1518-9. doi:10.1016/S0140-6736(00)02169-3. PMID 10801176.
81. ^ Catassi C, Rätsch I, Gandolfi L, Pratesi R, Fabiani E, El Asmar R,
Frijia M, Bearzi I, Vizzoni L (1999). "Why is coeliac disease endemic in
the people of the Sahara?". Lancet 354 (9179): 647-8.
doi:10.1016/S0140-6736(99)02609-4. PMID 10466670.
82. ^ Zipser R, Farid M, Baisch D, Patel B, Patel D (2005). "Physician
awareness of celiac disease: a need for further education". J Gen Intern
Med 20 (7): 644-6. doi:10.1007/s11606-005-0111-7. PMC 1490146.
PMID 16050861.
83. ^ Hischenhuber, C; Crevel, R; Jarry, B; Mäki, M; Moneret-Vautrin, D
A; Romano, A; Troncone, R; Ward, R (March 2006). "Review article: safe
amounts of gluten for patients with wheat allergy or coeliac disease".
Aliment. Pharmacol. Ther. 23 (5): 559-75.
doi:10.1111/j.1365-2036.2006.02768.x. PMID 16480395.
84. ^ Fasano A, Berti I, Gerarduzzi T, Not T, Colletti R, Drago S,
Elitsur Y, Green P, Guandalini S, Hill I, Pietzak M, Ventura A, Thorpe
M, Kryszak D, Fornaroli F, Wasserman S, Murray J, Horvath K (2003).
"Prevalence of celiac disease in at-risk and not-at-risk groups in the
United States: a large multicenter study". Archives of Internal Medicine
163 (3): 286-92. doi:10.1001/archinte.163.3.286. PMID 12578508.
85. ^ a b Barker JM, Liu E (2008). "Celiac disease: pathophysiology,
clinical manifestations, and associated autoimmune conditions". Adv
Pediatr 55: 349-65. doi:10.1016/j.yapd.2008.07.001. PMC 2775561.
PMID 19048738.
86. ^ Leeds JS, Hopper AD, Sanders DS (2008). "Coeliac disease". Br Med
Bull 88 (1): 157-70. doi:10.1093/bmb/ldn044. PMID 19073695.
87. ^ Rubio-Tapia et al.; Kyle, RA; Kaplan, EL; Johnson, DR; Page, W;
Erdtmann, F; Brantner, TL; Kim, WR et al. (2009). "Increased Prevalence
and Mortality in Undiagnosed Celiac Disease". Gastroenterology 137 (1):
88-93. doi:10.1053/j.gastro.2009.03.059. PMC 2704247. PMID 19362553.
88. ^ One on-line site sells 1200 wafers weighing a total of 523 g
89. ^ Jax Peter Lowell, The Gluten-Free Bible, p. 279.
90. ^ Scott Adams (2 August 2002). "Bishops in Italy Approve a
German-made Low Gluten Eucharistic Host". Celiac.com.
91. ^ Associated Press (8 December 2004). "Girl with digestive disease
denied Communion". MSNBC (Microsoft). Retrieved 30 May 2006.
92. ^ Ratzinger, Joseph (24 July 2003). Prot. 89/78-174 98. Congregation
for the Doctrine of the Faith. Full text at: "The Use of Mustum and
Low-Gluten Hosts at Mass". BCL Newsletter. United States Conference of
Catholic Bishops. November 2003. Retrieved 7 March 2007.
93. ^ McNamara, Father Edward (15 September 2004). "Liturgy: Gluten-free
Hosts". Catholic Online. Retrieved 17 June 2007.
94. ^ Rabbi Avraham Juravel. "Gluten Intolerance, Celiac, Allergies And
Pesach". Orthodox Union. Retrieved 3 September 2006.
95. ^ Gee, SJ (1888). "On the coeliac affection". St Bartholomew's
Hospital Report 24: 17-20.
96. ^ Herter, CA (1908). On infantilism from chronic intestinal
infection; characterized by the overgrowth and persistence of flora in
the nursing period. New York: Macmillan & Co. as cited by WhoNamedIt
97. ^ Ole Daniel Enersen. "Christian Archibald Herter". Who Named It?.
Retrieved 20 March 2007.
98. ^ Haas SV (1924). "The value of the banana in the treatment of
coeliac disease". Am J Dis Child 24: 421-37.
99. ^ van Berge-Henegouwen G, Mulder C (1993). "Pioneer in the gluten
free diet: Willem-Karel Dicke 1905-1962, over 50 years of gluten free
diet" (PDF). Gut 34 (11): 1473-5. doi:10.1136/gut.34.11.1473.
PMC 1374403. PMID 8244125.
100. ^ Dicke WK (1950) (in Dutch). Coeliakie: een onderzoek naar de
nadelige invloed van sommige graansoorten op de lijder aan coeliakie,
PhD thesis. Utrecht, the Netherlands: University of Utrecht.
101. ^ Fasano A (2009). "Celiac Disease Insights: Clues to Solving
Autoimmunity". Scientific American (August): 49-57.
102. ^ Anderson C, French J, Sammons H, Frazer A, Gerrard J, Smellie J
(1952). "Coeliac disease; gastrointestinal studies and the effect of
dietary wheat flour". Lancet 1 (17): 836-42.
doi:10.1016/S0140-6736(52)90795-2. PMID 14918439.
103. ^ Paulley JW (1954). "Observation on the aetiology of idiopathic
steatorrhoea; jejunal and lymph-node biopsies". Br Med J 4900 (4900):
1318-21. doi:10.1136/bmj.2.4900.1318. PMC 2080246. PMID 13209109.
104. ^ Macdonald W, Dobbins W, Rubin C (1965). "Studies of the familial
nature of celiac sprue using biopsy of the small intestine". N Engl J
Med 272 (9): 448-56. doi:10.1056/NEJM196503042720903. PMID 14242522.
105. ^ "Buy Me Some Gluten-Free Peanuts, Cracker Jacks". QSR magazine
(Journalistic). May 11, 2010. Retrieved December 30, 2010.
106. ^ Black, Rosemary (October 6, 2008). "Eating gluten-free will help
combat celiac disease". New York Daily News. Retrieved December 29, 2010.
[edit]
External links
Wikibooks Cookbook has a recipe/module on
Gluten-Free
? Coeliac disease at the Open Directory Project
? Celiac Disease Awareness Campaign from the National Institutes of Health
? Celiac Disease practice guideline from the World Gastroenterology
Organisation (WGO)
? Outcomes of 2004 consensus development conference, U.S. National
Institutes of Health
? GeneReviews/NCBI/NIH/UW entry on Celiac Disease
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Digestive system · Digestive disease · Gastroenterology (primarily
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