Coeliac disease

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Coeliac disease
Classification and external resources
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 (pronounced /ˈsiːliːˌæk/), also spelled celiac disease, is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy. Symptoms include chronic diarrhoea, failure to thrive (in children), and fatigue, but these may be absent and symptoms in all other organ systems have been described. It is estimated to affect about 1% of all Indo-European populations, but is thought to be significantly underdiagnosed. A growing portion of diagnoses are being made in asymptomatic persons as a result of increased screening.[1]

Coeliac disease is caused by a reaction to gliadin, a gluten protein found in wheat (and similar proteins of the tribe Triticeae which includes other cultivars such as barley and rye). Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the bowel tissue, causing an inflammatory reaction. That leads to flattening of the lining of the small intestine (called villous atrophy). This interferes with the absorption of nutrients because the intestinal villi are responsible for absorption. The only effective treatment is a lifelong gluten-free diet. 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: cœliac disease (with "œ" 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 κοιλιακός (koiliakόs, 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.[2]

Contents

[edit] Signs and symptoms

This article is part of
the Gluten sensitivity
series.
Coeliac disease
Wheat allergy
Gluten-sensitive idiopathic neuropathies
Triticeae glutens
Gluten-free diet
GSE associated conditions
Anti-gliadin antibodies
Anti-transglutaminase antibodies
HLA-DQ2, HLA-DQ8

Classic symptoms of coeliac disease include diarrhea, weight loss (or stunted growth in children), and fatigue, but while coeliac disease is primarily a bowel disease, bowel symptoms may also be limited or even absent. Some patients are diagnosed with symptoms related to the decreased absorption of nutrients or with various symptoms which, although statistically linked, have no clear relationship with the malfunctioning bowel. Given this wide range of possible symptoms, the classic triad is no longer a requirement for diagnosis.

Children between 9 and 24 months tend to present with bowel symptoms and growth problems shortly after first exposure to gluten-containing products. Older children may have more malabsorption-related problems and psychosocial problems, while adults generally have malabsorptive problems.[3] Many adults with subtle disease only have fatigue or anaemia.[1]

[edit] Gastrointestinal

The diarrhoea characteristic of coeliac disease is pale, voluminous and malodorous. Abdominal pain and cramping, bloatedness with abdominal distention (thought to be due to fermentative production of bowel gas) and mouth ulcers[4] may be present. As the bowel becomes more damaged, a degree of lactose intolerance may develop. However, the variety of gastrointestinal symptoms that may be present in patients with coeliac disease is great, and some may have a normal bowel habit or even tend towards constipation. 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 may be justified.[5]

Coeliac disease leads to an increased risk of both adenocarcinoma and lymphoma of the small bowel, which returns to baseline with diet. Longstanding disease may lead to other complications, such as ulcerative jejunitis (ulcer formation of the small bowel) and stricturing (narrowing as a result of scarring).[6]

[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.[3]

[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.

[edit] Other grains

Wheat varieties or subspecies containing gluten and related species such as barley and rye also induce symptoms of coeliac disease.[18] A small minority of coeliac patients also react to oats.[19][20] It is most probable that oats produce symptoms due to cross contamination with other grains in the fields or in the distribution channels.[3] Generally, oats are therefore not recommended.[18] Other cereals, such as maize (corn), quinoa, millet, sorghum, and rice are safe for patients to consume. Non-cereal carbohydrate-rich foods such as potatoes and bananas do not contain gluten and do not trigger symptoms.

[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 10 g of gluten (four slices of bread) per day over 2–6 weeks before repeating the investigations. Those who experience severe symptoms (e.g. diarrhoea) earlier can be regarded as sufficiently challenged and can be tested earlier.[3]

Combining findings into a prediction rule to guide use of endoscopy reported a sensitivity of 100% (it would identify all the cases) and specificity of 61% (it would be incorrectly positive in 39%). The prediction rule recommends that patients with high risk symptoms or positive serology should undergo endoscopy. The study defined high risk symptoms as weight loss, anaemia (haemoglobin less than 120 g/l in females and less than 130 g/l in males), or diarrhoea (more than three loose stools per day).[21]

[edit] Blood tests

[edit] Antibody testing

Serology by blood test is useful both in diagnosing coeliac disease (high sensitivity of about 98%, i.e. it misses 2 in 100 cases) and in excluding it (high specificity of over 95%, i.e. a positive test is most likely confirmative of coeliac disease rather than another condition). 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. A negative test may still prompt a biopsy if the suspicion remains very high; this would pick up the remaining 2% undiagnosed cases, as well as offering alternative explanations for the symptoms. As such, endoscopy with biopsy is still considered the gold standard in the diagnosis of coeliac disease.[3][6]

Blood antibody tests for coeliac disease[22]
Test sensitivity specificity
AGA IgA 50% 98%
AGA IgA 25% 98%
Anti-EMA 81% 99%
ATA (Anti-TTG) 81% 99%

Four serological blood tests exist for coeliac disease. The most widely used ones detect an antibody of the IgA type against particular antigens in the small bowel. Older tests detected antibodies against reticulin (ARA) or gliadin (AGA), but recent evidence supports the use of the more modern tests, namely those detecting IgA antibodies against endomysium (EMA) or tissue transglutaminase (TTG). Generally, serology may be unreliable in young children, with anti-gliadin performing somewhat better than other tests in children under five.[23] Serology tests are based on indirect immunofluorescence (reticulin, gliadin and endomysium) or ELISA (gliadin or tissue transglutaminase).[24]

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.[25]

Blood HLA tests for coeliac disease[22]
Test sensitivity specificity
HLA-DQ2 94% 73%
HLA-DQ8 12% 81%

[edit] HLA genetic typing

Antibody testing and HLA testing have similar accuracies.[22]

[edit] Endoscopy

Endoscopic still of duodenum of patient with coeliac disease showing scalloping of folds.
Endoscopic still of duodenum of patient with coeliac disease showing scalloping of folds.
Schematic of the Marsh classification of upper jejunal pathology in 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.[6]

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 submucosal blood vessels, and a nodular pattern to the mucosa.[26]

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. One often-utilized capsule system is the Watson capsule. This method has now been largely replaced by fibre-optic endoscopy, which carries a higher sensitivity and a lower frequency of errors.[27]

[edit] Pathology

The classic pathology changes of coeliac disease in the small bowel are categorized by the "Marsh classification":[28]

The changes classically improve or reverse after gluten is removed from the diet, so many official guidelines recommend a repeat biopsy several (4–6) months after commencement of gluten exclusion.[3]

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.[3] Patients are warned that one does not "outgrow" coeliac disease in the same way as childhood food intolerances.

[edit] Other diagnostic tests

Other tests that may assist in the diagnosis are blood tests for a full blood count, electrolytes, calcium, renal function, liver enzymes, vitamin B12 and folic acid levels. Coagulation testing (prothrombin time and partial thromboplastin time) may be useful to identify deficiency of vitamin K, which predisposes patients to hemorrhage. These tests should be repeated on follow-up, as well as anti-tTG titres.[3]

Some professional guidelines[3] recommend screening of all patients for osteoporosis by DXA/DEXA scanning.

[edit] Pathophysiology

Coeliac disease appears to be polyfactorial, both in that more than one abnormal factor can cause the disease and also more than one factor is necessary for the disease to manifest in a patient.

Almost all coeliac patients have an abnormal HLA DQ2 allele.[1] However, about 20–30% of people without coeliac disease have inherited an abnormal 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.[1]

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

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. There are 7 HLA DQ variants (DQ2 and DQ4 through 9). Two of these variants—DQ2 and DQ8—are associated with coeliac disease. The gene is located on the short arm of the sixth chromosome, and as a result of the linkage this locus has been labeled CELIAC1.

Over 95% of coeliac patients have an isoform of DQ2 (encoded by DQA1*05 and DQB1*02 genes) and DQ8 (encoded by the haplotype DQA1*03:DQB1*0302), 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.[1]

DQ α5-β2 -binding cleft with a deamidated gliadin peptide (yellow), modified from PDB 1S9V
DQ α5-β2 -binding cleft with a deamidated gliadin peptide (yellow), modified from PDB 1S9V[29]

Most coeliac patients bear a two-gene HLA-DQ haplotype referred to as DQ2.5 haplotype. This haplotype is composed of 2 adjacent gene alleles, DQA1*0501 and DQB1*0201, which encode the two subunits, DQ α5 and DQ β2. 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.[30] 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 celiacs that do not have DQ2.5(cis or trans) or DQ8, 4% are DQ2 and 2% DQA1*05, 0.4% cannot be linked to DQ8, DQA1*05, or DQB1*02.[31]

The frequency of these genes varies geographically. DQ2.5 has high frequency in peoples of North and Western Europe (Basque Country, Ireland,[32] with highest frequencies), portions of Africa, and is associated disease in India,[33] but is not found along portions of the West Pacific rim. DQ8, spread more globally than DQ2.5, is more prevalent from South and Central America (up to 90% phenotype frequency).[34]

In addition to the CELIAC1 locus, CELIAC2 (5q31-q33 - IBD5 locus), CELIAC3 (2q33 - CTLA4 locus), CELIAC4 (19q13.1 - MYOIXB locus), have been linked to coeliac disease. The CTLA4 and myosin IXB genes have been found to be linked to coeliac disease and other autoimmune diseases.[35][36] Two additional loci on chromosome 4, 4q27 (IL2 or IL21 locus) and 4q14, have been found to be linked to coeliac disease.[37][38]

[edit] Prolamins

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 pepsin and chymotrypsin, the two main digestive proteases in the gut. 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.[1] 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

Tissue transglutaminase, drawn from PDB 1FAU.
Tissue transglutaminase, drawn from PDB 1FAU.

Anti-transglutaminase antibodies to the enzyme tissue transglutaminase (tTG) are found in an overwhelming majority of cases.[39] Tissue transglutaminase modifies gluten peptides into a form that may stimulate the immune system more effectively.[1]

Stored biopsies from suspected coeliac patients has 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, anemia or malabsorption phenomena at a much increased rate over the normal population.[40] Endomysial component 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 recognize a rotavirus protein called VP7. These antibodies stimulate monocytes 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.[1] 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.[6]

[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 (three months after birth) had five times the risk of developing coeliac disease over those exposed at 4 to 6 months. Those exposed later had a slightly increased risk relative to those exposed at 4 to 6 months.[48] However a 2006 study with similar numbers found just the reverse, that early introduction of grains was protective.[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] Treatment

[edit] Diet

Main article: Gluten-free diet

Presently, the only effective treatment is a life-long gluten-free diet.[18] 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 the vast majority of cases and, depending on how soon the diet is begun, can also eliminate the heightened risk of osteoporosis and intestinal cancer.[51] Dietician 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. More manufacturers are producing gluten-free products, some of which are almost indistinguishable from their gluten-containing counterparts.

The diet can be cumbersome; failure to comply with the diet may cause relapse. Many food products contain traces of gluten even if apparently wheat-free. Gluten-free products are usually more expensive and harder to find than common wheat-containing foods.

Even while on a diet, health-related quality of life (HRQOL) may be decreased in people with coeliac disease. Some have persisting digestive symptoms or dermatitis herpetiformis, mouth ulcers, osteoporosis and fractures. Symptoms suggestive of irritable bowel syndrome may be present, and there is an increased rate of anxiety, fatigue, dyspepsia and musculoskeletal pain.[52]

[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.[6]

[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:[1]

  • 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.[53]
  • Inhibition of zonulin, an endogenous signaling protein linked to increased permeability of the bowel wall and hence increased presentation of gliadin to the immune system.[54]
  • 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] Screening and case finding

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 studied in Cambridge suggested that people with undetected coeliac disease had a beneficial risk profile for cardiovascular disease (less overweight, lower cholesterol levels).[1]

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. Serology may also be used to monitor adherence to diet: in those who still ingest gluten, antibody levels remain elevated.[3][6]

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[55] and irritable bowel syndrome.[56]

Other clinical scenarios in which screening may be justified include type 1 diabetes,[14] unexplained iron-deficiency anemia,[57][58] Down's syndrome, Turner's syndrome, lupus, and autoimmune thyroid disease.[59]

[edit] Epidemiology

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 Saharawi children[60]) and 0.18–1.2% in adults.[1] People of African, Japanese and Chinese descent are rarely diagnosed; 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 to many clinicians being unfamiliar with the condition.[61]

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.[62]

[edit] Social and religious issues

[edit] Christian churches & the Eucharist

With exception of the Roman Catholic Church, most mainline Christian churches offer their communicants gluten-free alternatives to the sacramental bread, usually in the form of a rice-based cracker or gluten-free bread. These include United Methodist, Christian Reformed, Episcopal, Lutheran, The Church of Jesus Christ of Latter-day Saints, and many others.[63]

[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.[64] Some Catholic coeliac sufferers have requested permission to use rice wafers; such petitions have always been denied.[65] The issue is more complex for priests. Though a Catholic (lay or ordained) receiving under either form is considered to have received Christ "whole and entire", 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 August 22, 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."[66]

As of January 2004, an extremely low-gluten host became available in the United States. The Benedictine Sisters of Perpetual Adoration in Clyde, MO, after ten years of perseverance, trial, and error, have produced a low-gluten host safe for celiacs and also approved by the Catholic Church for use at Mass. Each host is made and packaged in a dedicated wheat-free / gluten-free environment. The hosts are made separately by hand, unlike the common host which is stamped out of a long thin sheet of bread by a cutter. Therefore, each host is a slightly different size and shape. Most importantly, the finished hosts have been analyzed for gluten content. The gluten content of these hosts is reported as 0.01 %. In actuality, the gluten content is probably less than 0.01%. Sister Lynn, OSB, said that the result of the analysis of the finished host revealed "no gluten detected". The hosts are labeled as 0.01 % since the lowest limit of detection of this analysis was 0.01 %. In an article from the Catholic Review (February 15, 2004) Dr. Alessio Fasano was quoted as declaring these hosts "perfectly safe for celiac sufferers." [67]

[edit] Coeliacs and 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 fulfill 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.[68]

[edit] History

Aretaeus of Cappadocia, living in the second century, recorded a malabsorptive syndrome with chronic diarrhoea. His "Cœliac Affection" (coeliac from Greek κοιλιακός koiliakos, abdominal) gained the attention of Western medicine when Francis Adams presented a translation of Aretaeus' work at the Sydenham Society in 1856. The patient 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".[2]

The paediatrician, Samuel Gee, gave the first modern-day description of the condition 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). Unlike Aretaeus, he included children in the scope of the affliction, particularly those between one and five years old. Gee found the cause to be obscure and failed to spot anything abnormal during post-mortem examination (the lining of the small bowel quickly deteriorates on death).[69] 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.[70]

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.[71][72] Sydney V. Haas, an American paediatrician, reported positive effects of a diet of bananas in 1924.[73] This diet remained in vogue until the actual cause of coeliac disease was determined.

While a role for carbohydrates had been suspected, the link with wheat was not made until the 1940s by the Dutch paediatrician Dr Willem Dicke.[74] It is likely that clinical improvement of his patients during the Dutch famine of 1944 (during which flour was sparse) may have contributed to his discovery.[75] The link with the gluten component of wheat was made in 1952 by a team from Birmingham, England.[76] Villous atrophy was described by British physician John W. Paulley in 1954.[77] Paulley was able to examine biopsies taken from patients during abdominal operations.[69] Dr Margo Shiner, working on Prof Sheila Sherlock's team at the Postgraduate Medical School in London, described the principles of small bowel biopsy in 1956.[78]

Throughout the 1960s other features of coeliac disease were elucidated. Its hereditary character was recognized in 1965.[79] In 1966 dermatitis herpetiformis was linked to gluten sensitivity.[10]

[edit] References

  1. ^ a b c d e f g h i j k van Heel D, West J (2006). "Recent advances in coeliac disease". Gut 55 (7): 1037–46. PMID 16766754. 
  2. ^ a b Adams F, translator (1856). "On The Cœliac Affection", The extant works of Aretaeus, The Cappadocian. London: Sydenham Society. Retrieved on 2006-09-04.  See also Google Books entry
  3. ^ a b c d e f g h i j k Ciclitira, P (2002). Interim Guidelines for the Management of Patients with Coeliac Disease. British Society of Gastroenterology. Retrieved on 2007-03-07.
  4. ^ 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. PMID 1247715.  Full text at PMC: 1638254
  5. ^ Spiegel BM, DeRosa VP, Gralnek IM, Wang V, Dulai GS (Jun 2004). "Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analysis". Gastroenterology 126 (7): 1721–32. PMID 15188167. 
  6. ^ a b c d e f "American Gastroenterological Association medical position statement: Celiac Sprue" (2001). Gastroenterology 120 (6): 1522–5. PMID 11313323. 
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