(Redirected from Celiac)
'Coeliac disease' or 'celiac disease' is an
autoimmune disorder of the
small bowel that occurs in
genetically predisposed individuals in all age groups after early infancy. Symptoms may include chronic
diarrhoea,
failure to thrive (in children) and
fatigue, but these may be absent and associated symptoms in all other organ systems have been described. It affects approximately 1% of
Indo-European populations, though it is significantly underdiagnosed. A growing portion of diagnoses are being made in asymptomatic persons as a result of increasing screening.
[ Recent advances in coeliac disease, van Heel D, West J, , , Gut, 2006 ]
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, which
interferes with the absorption of nutrients. The only effective treatment is a lifelong
gluten-free diet.
This condition has several other names, including: 'cœliac 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 κοιλιακος (''koiliakos'', 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.
[1]
Signs and symptoms
Classic symptoms of coeliac disease include
diarrhoea,
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.
[ Interim Guidelines for the Management of Patients with Coeliac Disease ] Many adults with subtle disease only have fatigue or
anaemia.
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[2] 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.[ Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analysis, Spiegel BM, DeRosa VP, Gralnek IM, Wang V, Dulai GS, , , Gastroenterology, 2004 ]
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).[ American Gastroenterological Association medical position statement: Celiac Sprue, , , , Gastroenterology, 2001 ]
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.
★ 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 (10%) have abnormal coagulation due to deficiency of vitamin K, 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 after treatment.[ High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal, Tursi A, Brandimarte G, Giorgetti G, , , Am J Gastroenterol, 2003 ]
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% of patients with coeliac disease, and in turn this condition features a tenfold increased risk of coeliac disease.[3][4] Other features of this condition are an increased risk of infections and autoimmune disease.
★ 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[ Small-bowel changes in dermatitis herpetiformis, Marks J, Shuster S, Watson A, , , Lancet, 1966 ] and occurs more often (in 2%) in patients with coeliac disease.
★ Neurological associations: epilepsy, ataxia (coordination problems), myelopathy and peripheral neuropathy have all been linked with coeliac disease, but the strength of these associations and the causality is still subject of debate.[5]
★ 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.
★ Miscarriage and infertility.
★ Hyposplenism (a small and underactive spleen) - it is unclear whether this actually increases infection risk in the same way as in other people without a functioning spleen.[ Adult coeliac disease in hyposplenic patients, Ferguson A, Hutton M, Maxwell J, Murray D, , , Lancet, 1970 ]
★ Other auto-immune disorders: diabetes mellitus type 1,[ Coeliac disease and Type 1 diabetes mellitus - the case for screening, Holmes G, , , Diabet Med, 2001 ] autoimmune thyroiditis,[6] primary biliary cirrhosis[7] and microscopic colitis.[8]
Role of other grains
Wheat varieties or subspecies containing gluten such as spelt and Kamut®, and the rye/wheat hybrid triticale, also trigger symptoms.[9]
Barley and rye also induce symptoms of coeliac disease.[ There is at least one oat vendor (McCann's) which, while not claiming to be gluten-free, points out that the risk of contamination is low due to the processes they use.[12] Other cereals, such as maize (corn), quinoa, millet, sorghum, rice are safe for a patient to consume. Other carbohydrate-rich foods such as potatoes and bananas do not contain gluten and do not trigger symptoms.]
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.
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).[13]
Blood tests
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.
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.
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.[Hill ID. "What are the sensitivity and specificity of serological tests for celiac disease? Do sensitivity and specificity vary in different populations?" In: ''NIH Consensus Development Conference on Celiac Disease''. Bethesda, Md.: U.S. National Institutes of Health, 2004;27–31. PDF.] Serology tests are based on indirect immunofluorescence (reticulin, gliadin and endomysium) or ELISA (gliadin or tissue transglutaminase).[14]
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.[15]
Endoscopy
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, it would result in false negative results.
Most patients with coeliac disease have a small bowel that appears normal on endoscopy; however, five endoscopic findings have been associated with a high specificity for coeliac disease when all are found: 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.[16]
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 much utilized capsule system is the Watson capsule. This method has now been largely replaced by fiberoptic endoscopy, which carries a higher sensitivity rate and a lower error frequency.[17]
Pathology
The classic pathology changes of coeliac disease in the small bowel are categorized by the "Marsh classification":[18]
★ 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
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.
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.[ Patients are warned that one does not "outgrow" coeliac disease in the same way as childhood food intolerances.]
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.
Some professional guidelines[ recommend screening of all patients for osteoporosis by DXA/DEXA scanning.]
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).
Clinical scenarios in which screening may be justified include type 1 diabetes,[ unexplained iron-deficiency anemia,[19][20] Down's syndrome, Turner's syndrome, irritable bowel syndrome,][ lupus, and autoimmune thyroid disease.[21]]
Pathophysiology
Genetics
The vast majority of coeliac patients have one of two types of HLA DQ, a gene that 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.
Coeliac disease 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 cause the disease. 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 is more likely to activate T lymphocytes and initiate the autoimmune process.
Most coeliac patients bear a two-gene HLA-DQ haplotype refered 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.[22] 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.[23]
About 20–30% of people carry HLA-DQ2 but most of them do not have coeliac disease, suggesting 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.[ The frequency of these genes varies geographically. DQ2.5 has high frequency in peoples of North and Western Europe (Basque Country, Ireland,[24] with highest frequencies), portions of Africa, and is associated disease in India[25], 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).[26] ]
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 and gene have been found to be linked to coeliac disease and other autoimmune diseases.[27][28] Two additional loci on chromosome 4, 4q27 (IL2 or IL21 locus) and 4q14, have been found to be linked to coeliac disease.[29][30]
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.[ However, not all prolaminins 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.]
Tissue transglutaminase
Anti-transglutaminase antibodies to the enzyme tissue transglutaminase (tTG) are found in an overwhelming majority of cases.[ Identification of tissue transglutaminase as the autoantigen of celiac disease, Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken E, Schuppan D, , , Nat Med, 1997 ] Tissue transglutaminase modifies gluten peptides into a form that may stimulate the immune system more effectively.[ ]
Stored biopsies from suspected coeliac patients has revealed that autoantibody deposits in the 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.[ Small-bowel mucosal tranglutaminase 2-specific IgA deposits in coeliac disease without villous atrophy: A Prospective and radmonized clinical study, Kaukinen K, Peraaho M, Collin P, Partanen J, Woolley N, Kaartinen T, Nuuntinen T, Halttunen T, Maki M, Korponay-Szabo I, , , Scand J Gastroenterology, 2005 ] 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.[ Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits, Salmi T, Collin P, Korponay-Szabó I, Laurila K, Partanen J, Huhtala H, Király R, Lorand L, Reunala T, Mäki M, Kaukinen K, , , Gut, 2006 ] 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,[ Gliadin as a stimulator of innate responses in celiac disease, Londei M, Ciacci C, Ricciardelli I, Vacca L, Quaratino S, and Maiuri L., , , Mol Immunol, 2005 ] suggests that gliadin may be more responsible for the primary manifestations of coeliac disease whereas as tTG is a bigger factor in secondary effects such as allegic 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.[ In celiac disease, a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes, Zanoni G, Navone R, Lunardi C, Tridente G, Bason C, Sivori S, Beri R, Dolcino M, Valletta E, Corrocher R, Puccetti A, , , PLoS Med, 2006 ] Indeed, earlier studies of rotavirus damage in the gut showed this causes a villous atrophy.[31] 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.
Villous atrophy and malabsorption
The inflammatory process, mediated by T cells, leads to disruption of the structure and function of the small bowel's mucous 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.[ 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.]
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[32] or human intestinal adenovirus[33] Some research has suggested that smoking is protective against adult onset coeliac disease.[34]
A 2005 prospective and observational study found that timing of the exposure to gluten in childhood was important risk modifier. Early exposure to wheat, barley, or rye before the gut barrier has developed fully over the first three months after birth. People exposed during this period 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 4–6 months.[35] However a 2006 study with similar numbers, found just the reverse, that early introduction of grains was protective.[36] 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.[37]
Treatment
Diet
Main articles: Gluten-free diet
Presently, the only effective treatment is a life-long gluten-free diet.[38] 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.[39] 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; while young children can be kept compliant by their parents, teenagers may wish to hide their problem or rebel against the dietary restrictions, risking 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.[40]
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.
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:
★ 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.[41]
★ 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.[42]
★ 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).
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[43]) and 0.18–1.2% in adults.[ 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.[44]]
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.[45]
Social and religious issues
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.[46] Some Catholic coeliac sufferers have requested permission to use rice wafers; such petitions have always been denied.[47] 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."[48]
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."
[49]
Coeliacs and Passover
The Jewish festival of Pesach (Passover) may present problems with its obligation to eat matzo. Matzo is normally made from wheat or other gluten-containing grains, so oat matzo is used. Many products prepared for Passover are free of wheat, barley, spelt, oats, and rye, as many Orthodox (especially Hasidic) Jews avoid non-matzo wheat products (''gebroks'') altogether. Potato starch is the primary starch used to replace the grains.[50]
History
Aretaeus of Cappadocia, living in the second century, recorded a malabsorptive syndrome with chronic diarrhoea. His "Cœliac Affection" is a translation of the Greek κοιλιακος (''koiliakos'', abdominal). It gained the attention of Western medicine when Francis Adams presented a translation of Aretaeus' work at the Sydenham Society in 1856. 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 resulted in loose stools that were white, malodorous and flatulent. The patient had stomach pain and was atrophied, pale, feeble and incapable of work. The disease was intractable and liable to periodic return. 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".
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 acknowledges earlier descriptions and terms for the disease and adopts the same term as Aretaeus. Unlike Aretaeus, he includes children in the scope of the affection, particularly those between one and five years old. Gee finds the cause to be obscure and fails to spot anything abnormal during post-mortem examination (the lining of the small bowel quickly deteriorates on death).[ History of coeliac disease ] He perceptively states "if the patient can be cured at all, it must be by means of diet." Gee recognises that milk intolerance is a problem with coeliac children and that highly starched foods should be avoided. He forbids rice, sago, fruit and vegetables, which all would have been safe to eat. Raw meat is recommended as are thin slices of toasted bread. Gee highlights particular success with a child "who was fed upon a quart of the best Dutch mussels daily". However, the child cannot bear this diet for more than one season.[51]
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.[ On infantilism from chronic intestinal infection; characterized by the overgrowth and persistence of flora in the nursing period, , CA, Herter, Macmillan & Co, 1908, as cited by WhoNamedIt][ Christian Archibald Herter Ole Daniel Enersen ] Sydney V. Haas, an American paediatrician, reported positive effects of a diet of bananas in 1924.[52] 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 1950 by the Dutch paediatrician Dr Willem Dicke.[53] 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.[54] The link with the gluten component of wheat was made in 1952 by a team from Birmingham, England.[55] Villous atrophy was described by British physician John W. Paulley in 1954.[56] Paulley was able to examine biopsies taken from patients during abdominal operations.[ 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.[57]]
Throughout the 1960s other features of coeliac disease were elucidated. Its hereditary character was recognized in 1965.[58] In 1966 dermatitis herpetiformis was linked to gluten sensitivity.[ The link with tissue transglutaminase was not made until 1997.]
References
1. The extant works of Aretaeus, The Cappadocian, , , Adams F, translator, Sydenham Society, 1856, See also Google Books entry
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9. Grain toxicity
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12. McCann's FAQ
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★ 0201 homozygosis predisposes to severe intestinal damage in celiac disease, Jores RD, Frau F, Cucca F, ''et al'', , , Scand. J. Gastroenterol., 2007
23. HLA types in celiac disease patients not carrying the DQA1
★ 05-DQB1
★ 02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease, Karell K, Louka AS, Moodie SJ, ''et al'', , , Hum. Immunol., 2003
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25. Pediatric celiac disease in India is associated with multiple DR3-DQ2 haplotypes, Kaur G, Sarkar N, Bhatnagar S, ''et al'', , , Hum. Immunol., 2002
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36. Timing of initial exposure to cereal grains and the risk of wheat allergy, Poole J, Barriga K, Leung D, Hoffman M, Eisenbarth G, Rewers M, Norris J, , , Pediatrics, 2006
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38. Dietary guidelines and implementation for celiac disease, Kupper C, , , Gastroenterology, 2005
39. Emerging concepts in celiac disease, Treem W, , , Curr Opin Pediatr, 2004
40. Health-related quality of life in adult coeliac disease in Germany: results of a national survey, Häuser W, Gold J, Stein J, Caspary W, Stallmach A, , , Eur J Gastroenterol Hepatol, 2006
41. Rational design of combination enzyme therapy for celiac sprue, Siegel M, Bethune M, Gass J, Ehren J, Xia J, Johannsen A, Stuge T, Gray G, Lee P, Khosla C, , , Chem Biol, 2006
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44. Physician awareness of celiac disease: a need for further education, Zipser R, Farid M, Baisch D, Patel B, Patel D, , , J Gen Intern Med, 2005
45. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study, 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, , , Archives of Internal Medicine, 2003
46. Bishops in Italy Approve a German-made Low Gluten Eucharistic Host Scott Adams
47. Girl with digestive disease denied Communion
48. Ratzinger, Joseph (July 24, 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
49. Liturgy: Gluten-free Hosts
50. Gluten Intolerance, Celiac, Allergies And Pesach Rabbi Avraham Juravel
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52. Haas SV (1924). The value of the banana in the treatment of coeliac disease. ''Am J Dis Child'' '24': 421–37.
53. Pioneer in the gluten free diet: Willem-Karel Dicke 1905–1962, over 50 years of gluten free diet, van Berge-Henegouwen G, Mulder C, , , Gut, 1993
54. Dicke WK. ''Coeliakie: een onderzoek naar de nadelige invloed van sommige graansoorten op de lijder aan coeliakie'' [PhD thesis]. Utrecht, the Netherlands: University of Utrecht, 1950.
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56. Observation on the aetiology of idiopathic steatorrhoea; jejunal and lymph-node biopsies, Paulley JW, , , Br Med J,
57. Duodenal biopsy, Shiner M, , , Lancet, 1956
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External links
★ National Digestive Diseases Clearinghouse - page on coeliac disease
★ Coeliac UK - leading UK charity
★ Celiac.com - U.S. resource
★ Celiac Disease Foundation - U.S.
★ Celiac Sprue Association - U.S.
★ National Foundation for Celiac Awareness - U.S.
★ NIH Celiac Disease Awareness Campaign
★ Outcomes of 2004 consensus development conference, U.S. National Institutes of Health
★
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