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Year : 2013  |  Volume : 2  |  Issue : 2  |  Page : 69-76

Coeliac disease: An under-recognized nutritional disorder

1 Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur, India
2 Department of Radio diagnosis, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India
3 Honorary Dietician, Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
4 Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication6-Jul-2013

Correspondence Address:
Salam Ranabir
Singjamei, Chingamakha, Liwa Road, Imphal - 795 008
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-019X.114725

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Celiac disease (CD) is an immune - mediated enteropathy caused by ingestion of gluten present in wheat, barley, and rye in genetically susceptible individuals. It was considered to be a disease of childhood, but now it is reported with an increasing frequency. Classically, it present with intestinal symptoms such as diarrhea. However, in recent studies more patients are diagnosed with extra-intestinal manifestations. A trend towards more extra-intestinal manifestations and diagnosis at later age reported from several countries. In developing countries, CD is a diagnostic dilemma because the histological changes may not be pathognomonic of the disease and several other common conditions such as persistent enteric infections, parasitic infestation, small bowel bacterial overgrowth or tropical sprue have similar mucosal abnormalities. Furthermore, interpretation of mucosal histology in the presence of severe malnutrition where similar changes may be seen is difficult. A highly sensitive and specific test as adjuncts to histology is required in diagnosing celiac disease. Delay in diagnosis may also be there mainly because of lack of awareness about this condition because the symptoms may have been attributed to many other more frequently occurring conditions such as gastrointestinal infections, infestations, and nutritional deficiencies. However, untreated CD may lead to several complications, some of which may be irreversible, so early diagnosis and prompt institution of gluten free diet is important.

Keywords: Extra-intestinal manifestations, gluten free diet, immune - mediated enteropathy

How to cite this article:
Singh O O, Devi RJ, Waikhom S, Ranabir S. Coeliac disease: An under-recognized nutritional disorder. J Med Nutr Nutraceut 2013;2:69-76

How to cite this URL:
Singh O O, Devi RJ, Waikhom S, Ranabir S. Coeliac disease: An under-recognized nutritional disorder. J Med Nutr Nutraceut [serial online] 2013 [cited 2024 Mar 3];2:69-76. Available from: http://www.jmnn.org/text.asp?2013/2/2/69/114725

  Introduction Top

Celiac disease (CD) is an immune - mediated enteropathy caused by ingestion of gluten present in wheat, barley, and rye in genetically susceptible individuals. It has long been considered a pediatric syndrome, in which classical intestinal symptoms such as diarrhea, steatorrhea and weight loss predominate. However, the disease has been increasingly diagnosed in older children and adults and has emerged to encompass a broad spectrum of clinical manifestations, which are associated with a large variety of changes in the mucosa of the small intestine. [1],[2] In developing countries, CD is a diagnostic dilemma because the histological changes may not be pathognomonic of the disease. Several other common conditions such as persistent enteric infections, parasitic infestation, small bowel bacterial overgrowth or tropical sprue have similar mucosal abnormalities. Furthermore, interpretation of mucosal histology in the presence of severe malnutrition where similar changes may be seen is difficult. A highly sensitive and specific test as adjuncts to histology is required in diagnosing celiac disease. [3] Whether it would be cost-effective to screen the general population for CD, or to restrict it to symptomatic or asymptomatic high-risk subjects is an issue. [4]

  Epidemiology Top

The prevalence of celiac disease in adults is approximately 1-2% in Europe. [5] In US, the prevalence of CD is 0.71%. [6] The risk is higher is first-degree relatives. But MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked genes are likely to be the stronger determinant of disease susceptibility. [7] There is usually a higher prevalence in females than males with a ratio of around 2:1, [8] possibly because the necessary HLA haplotypes, DQ2/DQ8, are more frequent in female than in male CD patients (i.e., 94% vs. 85%) [9] . With aging, however, this female predominant pattern disappears and in the elderly, the ratio of newly diagnosed males is equivalent to newly diagnosed females. [9]

In North India, the sero-prevalence of celiac disease is 1.44% and the prevalence of celiac disease is 1.04%. [10] In another study, Sood et al. reported a prevalence of celiac disease to be 1 in 310 based on a questionnaire based survey including 4347 school children (3-17 years). [11] Lal et al. in another study from Chandigarh (Northern part of India) reported a sero-prevalence of celiac disease to be 1:120 in healthy school children. [12] Based on these three communities based studies, 5-8 millions are expected to have celiac disease in India but only a few thousands have been diagnosed as having celiac disease and a large number of subjects are still undiagnosed.

The age of clinical onset (based on diagnosis) is often described as bimodal: The first peak is at 8-12 months of age, and the second during the third to fourth decades of life. [13] Whether diagnosing celiac disease at advanced age is the result of diagnostic delay or of a true late onset of the disease is still debated. Whereas several studies reported a diagnostic delay in the elderly population, [14] other reports suggest that celiac disease may indeed develop later in life. [15]

Poddar et al. (2006), evaluating 300 cases of CD, reported that CD in Indian children presents late with a significant delay in diagnosis. [16] The reason for the delayed onset of symptoms in Indian children could be prolonged breast feeding and delayed weaning. Delay in diagnosis is mainly caused by the lack of awareness about this condition because the symptoms may have been attributed to many other more frequently occurring conditions such as gastrointestinal infections, infestations, and nutritional deficiencies.


Hallmark of celiac disease (CD) is an autoimmune T-cell mediated chronic inflammatory reaction as a consequence of loss of tolerance to gluten. Gluten found in wheat grain is a mixture of proteins including gliadins and glutenins. Similar proteins, hordeins from barley and secalins from rye can also induced injury, however, gliadin peptide are the most immunogenic for celiac disease. These peptides resists complete digestion and likely to pass across the intestinal epithelial barrier via both transcellular and paracellular mechanisms. [17] Normal defensive intestinal barrier prevents spreading of bacteria and toxins of different origin from the lumen to systemic circulation. It consists of anatomical epithelial barrier and functional barrier constituted by mucus layer and other factors such as trefoil peptides, defensins, and secretory IgA. [18] The alteration of intestinal barrier of CD results in increased intestinal permeability. One of the proteins involved in controlling tight junction is zonulin. When gliadin binds to CXCR3 chemokine receptor, zonulin is released from intestinal cells leading to disassembly of tight junction structure and allows paracellular passage of macromolecules including the toxic fraction of gliadin. [19] Hydrophobicity, a surface biophysical property affecting the adhesion of macromolecules, bacteria, and toxin are also found to be decreased in the duodenal mucous layer. [19] Expression of zonulin mRNA is increased in individuals with active CD, suggesting that this protein is related to intestinal damage in patients with CD. [20]

Interplay between genetic predisposing factors, host immune response, and environmental factors are the key in the development of this disease. HLA-DQ2 and HLA-DQ8 are found virtually in all the patients with CD, however, though 30-35% of Caucasians carry these markers, only 2-5% developed CD and also less than 100% concordance in monozygous twins suggests the existence of both other genetic and environmental factors in the development of CD. In susceptible individual, substantial exposure of infants to dietary gluten, early infection with enteropathic viruses and change in bacterial flora of the gut are the factors implicated. Children exposed to gluten in the first 3 months of life have a five-fold increased risk compared with children exposed to gluten at between 4 and 6 months of age. Breast milk exerts its protective effect against the development of CD. Though the mechanism is unknown, it is postulated that breast milk may have immune-modulating properties that suppress T-cells, dilute the amount of ingested gluten, prevent gastrointestinal infections that would increase intestinal permeability and gluten exposure or decrease gliadin uptake because IgA antibodies in breast milk agglutinate with gliadin. Studies indicated children from lower socio-economic status may be protected against CD development more than from prosperous ones, reason could be possibly children in poorer ones may have been breastfed longer for financial reasons not strictly socio-economic status. [21] The small intestinal mucosa when exposed to gliadin peptides accumulates intraepithelial CD8+ cells and large numbers of lamina propria CD4+ T-cells, however, there is significant variability among epitopes of gliadin in the severity of their immunogenic responses. The α-gliadin epitopes are recognised by T-cells in nearly all patients with CD while the α-gliadin and glutenin epitopes are not as universally recognised. [22] The epitopes on gliadin undergo deamidation by enzyme transglutaminase, the neutral glutamate residue is converted into negatively charged glutamic acid residue. Deamidation significantly increased affinity to HLA-DQ2 and in some case to HLA-DQ8 molecule and leads to enhanced antigenic presentation of gliadin. [23] Binding of deamidated peptides activates gluten specific CD4+ Tcells in the lamina propria which results in intraepithelial lymphocytosis, crypt hyperplasia, cytokine (IFN-ϒ) interferon production damaging intestinal wall leading to villous atrophy, and expansion of B-cells producing antibodies to gliadin and tissue transglutaminase. It is unclear how CD8+ T-cells accumulate in the epithelium as they don't recognize gliadin, but seems to be in response to stress induced molecule on epithelial cells. The epithelial cells secrete large amounts of IL-5 that activates CD8+ cells.

Clinical presentation of CD

Clinical features of CD are often related to the manifestations of gastrointestinal tract symptoms due to intestinal mucosal damage. However, many patients may present with a variety non-gastrointestinal features. And some individuals with characteristic histological features may remain asymptomatic or minimally symptomatic. "Celiac iceberg" was described by Catassi et al. (1994), following their observation that clinically manifest cases represent only a small proportion of patients with the disease. [24] In 1999, Bottaro et al. reported an increased prevalence of subclinical or silent CD both in adults and children. [25] Varied clinical features of CD lead to delay in diagnosis unless the physicians appreciate it. [26]

The (NIH) National Institute of Health Consensus Development Conference on Celiac Disease recognized 4 different categories of CD.

  1. Classical celiac disease: It is dominated by symptoms and sequel of gastrointestinal malabsorption. Its diagnosis is established by serological testing, biopsy evidence of villous atrophy, and improvement of symptoms on a gluten-free diet.
  2. CD with atypical symptoms: This type is characterized by few or no gastrointestinal symptoms, with extra-intestinal manifestations predominating. Recognition of atypical features of celiac disease is responsible for much of the increased prevalence. This type now may be the most common presentation. As with the classical form, the diagnosis is established by serologic testing, biopsy evidence of villous atrophy, and improvement of symptoms on a gluten-free diet.
  3. Silent celiac disease: It refers to individuals who are asymptomatic but have a positive serologic test and villous atrophy on biopsy. They usually are detected via screening of high-risk individuals, or villous atrophy occasionally may be detected by endoscopy and biopsy conducted for another reason.
  4. Latent celiac disease: It is defined by a positive serology but no villous atrophy on biopsy. These individuals area symptomatic, but later may develop symptoms and/or histologic changes.

In younger children, the most common presenting features are diarrhea, irritability, and weight loss. However, in older children, abdominal pain is the most common presenting feature. Patient may also have oral ulceration. [27] Older children and adolescents may present mainly with extra-intestinal features such as short stature and anemia. Rickets is seen in 25% of children. [28] Patient may also present with ataxia. [29] In a study in Canadian children, abdominal pain was the most common symptom seen in 90%, weight loss (70%), diarrhea (65%), nausea/vomiting (53%) and constipation (30%) were the other prominent features. Extra-intestinal symptoms included growth failure, generalized weakness, anemia, mood swings, and depression. Short stature may be seen in 18%. [30] Cognitive impairment has also been described as a feature of CD. [31]

In adults, non-specific gastrointestinal symptoms are common. [8] However, most adults present with extra-intestinal features such as fatigue and malaise. [32] They may present with osteomalacia, skin lesions, bleeding diathesis or infertility. Sanders et al. (2002) [8} and Ravikumara et al. (2006) [33] have reported a changing trend in clinical presentation of CD with an increasing prevalence of atypical features like iron deficiency anemia. In a study of adult celiacs by Jones et al. (2006), anemia was the most common mode of presentation seen in 50%. Less than 50% patients had the classical symptoms of CD. Osteoporosis was present in 28% and osteopenia in 31%. [34]

Up to 10% of patients with CD have neurological symptoms ranging from polyneuropathy, epilepsy, myoclonus, multifocal leukoencephalopathy, dementia, chorea, migraine, memory/attention impairment and peripheral axonal, and demyelinating neuropathies as well as acetylcholine-antibody positive myasthenia gravis. [35] Autoimmunity may act as a mechanism triggering neurological dysfunction and anti-neuronal, anti-gliadin and (tTG) tissue transglutaminase antibodies may contribute to neurological impairment through Apaf-1 activation with Bax and cytochrome C translocation, leading to impairment of mitochondrial dependent apoptosis. [36]

Associated disorders

An increased prevalence of celiac disease is seen in association with autoimmune thyroiditis, [37] Down Syndrome, [38] Turner Syndrome, [39] Williams Syndrome, [40] Selective IgA deficiency [41] and among first degree relatives of patients with celiac disease. [42]

Type 1 diabetes mellitus have been shown to be associated with CD in several studies. Savilahti et al. (1986), found a celiac disease prevalence of 3.5% in patients with type 1 diabetes and reported an association with HLA-B8 and-DR3. [43] In another study, one-third of subjects with (T1DM) Type 1 diabetes mellitus homozygous for HLA-DQ2 are positive for tTG antibody compared to less than 2% of type 1 diabetics lacking DQ2 or DQ8. [44] Several studies from India showed a high prevalence of tTG antibody) positivity in patients with T1DM. [45],[46],[47],[48]

A six- to seven-fold increase in CD prevalence has been reported in subjects with autoimmune thyroid disease. [49] In children affected with Down syndrome, the reported prevalence of CD ranges between 3.2% and 10.3%. [50]

Asymptomatic CD is also seen in children and adults with autoimmune hepatitis and autoimmune biliary disease. [51] Patients with irritable bowel syndrome have a four-fold higher prevalence of CD. [52]


In the past, several serologic tests were used for the diagnosis of CD. Patients with untreated celiac disease have increased antibody titers to gluten. The abnormal humoral response in celiac disease is of two types:

  1. antibodies against wheat gluten extract, e.g. anti-gliadin antibodies
  2. connective tissue reactive auto antibodies induced by gluten, e.g., anti-endomysial antibodies, antireticulin antibodies and anti-tissue transglutaminase antibodies.

Anti-reticulin antibody in CD was first described by Seah et al. (1971). [53] They are no longer used because it has a sensitivity of 35-75% and specificity of 95%. Anti-gliadin antibody have also been detected in other gastroenterological disorders, including, esophagitis, gastritis, gastroenteritis, inflammatory bowel disease, cystic fibrosis and cow's milk protein intolerance. Sensitivity of 58-75% and specificity of 80-95% had been reported with crude gliadin as the antigen. NIH Consensus and State-of-the-Science Statements, 2004 no longer recommends anti-gliadin antibody test because of their lower sensitivity and specificity. [54] Anti-endomysial antibody which stains structures around the muscle fiber bundles is considered the gold standard for celiac serology because of its high specificity (nearly 100%). However, the drawback with this indirect immunofluorescence assay is that it is subjective and labour intensive. Furthermore, it requires either primate esophagus or human umbilical cord as tissue substrate. In a systematic review by Lewis and Scott (2006), the pooled sensitivity and specificity is estimated to be 94% and 98% respectively. [55]

Dieterich et al. (1997), identified tissue transglutaminase as the endomysial autoantigen by performing indirect immunofluorescence with celiac disease serum samples on monkey esophagus. [56] An enzyme-linked immunosorbent assay for the detection of IgA anti-tTG antibodies has been established and is now the current widely used serology test.

Those patients who are positive for antibodies have to be subjected to upper (GI) Gastrointestinal endoscopy for duodenal biopsy and histopathological confirmation. At least four to six endoscopic-biopsy specimens should be obtained from the duodenum given the patchy nature of the disease and the difficulty of orienting the small pieces of tissue taken during the biopsy for assessment of villous morphology. [57],[58]


The pathological changes are usually more marked in the proximal small intestine than in the distal as duodenum and proximal jejunum are exposed to highest concentration of dietary gluten. Biopsy specimen demonstrates diffuse enteritis with marked atrophy or total loss of villi. The surface epithelium show increased intraepithelial lymphocytes (IELs), vacuolar degeneration, and loss of brush border. The crypts are elongated, hyperplastic, tortuous, and exhibit increased mitotic activity. This is accompanied by increase number of lymphocytes and plasma cells in the lamina propria. The spectrum of pathology varies from mild characterized by an increased inflammation in the surface epithelium, so called intraepithelial lymphocytosis to severe with total villous atrophy and crypt hyperplasia.

Several schemes have been developed to describe the varying degree of injury. In the Marsh grading system, Marsh 0 is described as normal mucosal architecture without significant intraepithelial lymphocytic infiltration. Marsh I (lymphocytic enteritis) is normal mucosal architecture with a marked infiltration of villous epithelium by lymphocytes. Marsh II (lymphocytic enteritis with crypt hyperplasia) consists of intraepithelial lymphocytosis and elongation and branching of crypts in which there is an increased proliferation of epithelial cells. Marsh III comprises intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. In Marsh IIIA (partial villous atrophy) the villi are blunt and shortened. In Marsh IIIB (subtotal villous atrophy) villi are clearly atrophic, but still recognizable and in Marsh IIIC (total villous atrophy) villi are rudimentary or absent and the mucosa resemble colonic mucosa. The Oberhuber modification of the Marsh scheme is based on villous architecture, crypt height, and intraepithelial lymphocytosis. In this type 0, 1, and 2 have normal villous architecture. Crypt heights are normal in type 0 and 1 but hyperplasia in type 2. The number of IEL is <40 per 100 enterocytes in type 0 and other types have higher IELs. Increased crypt height, high IEL and villous flattening are the features in type 3. Depending on the degree of villous flattening it is subdivided into 3A, 3B and 3C with mild, marked and total flattening. In general, the greater the degree of injury, the more specific the changes are for CD. One criticism of using Marsh grading as a pathologic grading system is the decreased inter-observer and intra-observer agreement. [59],[60]

Definitive diagnosis requires demonstration of complete symptom resolution after treatment with a gluten-free diet. [26]

Role of radiology

Imaging techniques like barium examinations, ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) have role in the diagnosis of celiac disease and its complications such as intussusception, ulcerative jejunitis, osteomalacia, cavitating lymph node syndrome, etc., Radiological guided percutaneous biopsy helps in the diagnosis as well as in staging of lymphoma, squamous cell carcinoma, adenocarcinoma, which are the possible complications. [61] The classical feature of barium study is widely separated jejunal folds accompanied by paradoxical increase in ileal folds (ilealjejunisation), however, this classical feature may be often absent and more common finding is luminal dilatation. Fold thickening may occur because of oedema secondary to hypo-albunemia rather as the primary disease. Barium enema also plays a pivotal role in determining response to treatment. A significant reduction in the average number of jejunal folds and an increase in the number of ileal folds (reversal of the jejunoileal fold pattern) were found in eight of nine non-responsive coeliac patients, one of seven untreated coeliac patients and in none of the good responders or control subjects. This pattern identifies coeliac patients with a poor response to a gluten free diet (GFD) who are likely to suffer major complications. [62] Radiological criteria for adult CD diagnosis by small bowel barium examinations (follow-through and double-contrast enteroclysis) can be divided into four patterns: (1) Definite (reversal of jejuno-ileal fold pattern); (2) possible (malabsorption pattern and ileal jejunisation); (3) malabsorption (fluid, dilatation, moulage, flocculation); (4) complicated (irregular thickened nodular folds, wall thickening, masses). Small bowel double contrast enteroclysis is currently considered to be the most accurate examination though further imaging techniques are always needed in the cases with complications. [63]

Small intestinal ultrasonography with anechoic contrast agents (SICUS) has been shown to have significant diagnostic accuracy. The parameters considered diagnostic are liquid endoluminal content before contrast, increased loop diameter and peristaltic waves, Kerckring's folds, ileal jejunisation, mesenteric lymphadenomegaly, and Doppler resistance index (RI) of mesenteric superior artery. Doppler RI value is found to be significantly correlated with the histologic degree of damage. [64] CT is often the first medical examination performed in non-specific and doubtful cases of CD. The abnormalities in intestinal fold pattern, bowel dilatation, fluid and air excess, duodenal abnormalities, intestinal intussusception, bowel wall thickening, lymphadenopathy, ascites, intestinal stenosis, and mesenteric vascular changes are the common findings in CT. [65] MRI in CD also revealed similar findings such as bowel dilatation, increased number of ileal folds, reversed fold pattern abnormality, increased wall thickness, duodenal stenosis, intussusception, mesenteric lymphadenopathy, mesenteric vascular changes, and ascites. MRI features are reported to be highly specific and accurate though it is less sensitive (79%). [66]


Early diagnosis and treatment are important in CD, as some of the associated complications may be irreversible. [67] Growth retardation, osteoporosis and abnormal dentition will remain permanent if not treated early.

The mainstay of therapy in celiac disease is avoidance of gluten containing food stuffs (GFD). It is important to understand what is the definition of a GFD? Even the so-called "gluten-free" products may not be completely free of gluten. A 2008 systematic review tentatively concluded that consumption of <10 mg of gluten/day for celiac disease patients is unlikely to cause histological abnormalities, although it noted that few reliable studies had been conducted. [68]

The only currently available treatment for CD is GFD. Grains which contain gluten such as wheat, rye, barley, triticale, couscous, spelt, and kamut should be avoided. [69] Rice, maize, and buckwheat do not contain gluten and hence can be eaten. Potato, chestnut, tapioca, sorghum, millet teff, quinoa, and amaranth are safe. Oats were considered to be toxic to individuals with CD but many studies have shown that the ingestion of uncontaminated oats is not only safe but can also improve the quality of the diet in the majority of patients with CD. [70] Vegetables, salads, pulses, fruits, nuts, meat, fish, poultry, cheese, eggs, and milk can be consumed. A multicenter, double-blind, placebo-controlled trial, have established the safety threshold of prolonged exposure to trace amounts of gluten to be 50 mg/day. The threshold of 20 ppm (parts per million) keeps the intake of gluten well below the amount of 50 mg/day, which allows a safety margin for the variable gluten sensitivities and dietary habits of patients. [71]

Supportive nutritional care in the case of iron, calcium, and vitamin deficiencies is also recommended. [72] In the long-term, a GFD is associated with clinical, serologic, and histological remission and seems to reduce the risk of complications. [69]

However, it is almost impossible to maintain a diet with zero gluten content because gluten contamination is very common in food. "Hidden" gluten (used as protein filler) may be found in commercially available products, such as sausages, soups, soy sauces, and ice cream. Even products specifically, targeted to dietary treatment of CD may contain tiny amounts of gluten proteins, either because of the cross-contamination of originally gluten-free cereals during their milling, storage, and manipulation or because of the presence of wheat starch as a major ingredient.

Alternatives to a gluten free diet

There may be poor compliance with the GFD because it is not widely available in developing countries like India and gluten-free products are expensive. For these reasons, new approaches have been taken in the treatment of CD. Some of these include, orally administered endopeptidase, antagonists to S100B protein, IL-15 blockers, elemental diets and transamidation of wheat flour. Lactobacilli added to sourdough for fermentation are able to break down the proline-/glutamine-rich gluten peptide. This may play a role in the future treatment of CD. [73] Other therapeutic approaches would include the binding of gluten to HLA-DQ2 or HLA-DQ8, or blocking the gluten-reactive T-cells by immunotherapy (e.g., vaccination). [74] Intestinal permeability is increased in patients with CD, and is associated with alterations in tight junction proteins (e.g., zonulin). Addition of zonulin may prevent T-cell mediated stimulation in CD. In a double-blind randomized placebo-controlled study of milligram doses of AT-1001, an inhibitor of paracellular permeability derived from Vibrio cholera, prevented the expected increases in intestinal permeability in subjects with CD challenged with gluten. [75]

Sequela of celiac disease

Untreated CD may lead to growth failure in children, infertility, anemia, osteoporosis, small intestinal non-Hodgkin lymphoma, [76] and a 3.9-fold increased all-cause mortality rate. [77] Potentially, this may underscore the importance of diagnosing and treating even latent CD.

The adult height of children with classical CD (e.g., symptomatic with diarrhea) is influenced by their compliance to a GFD. Children diagnosed with CD after 4 years of age show a slower and less complete catch-up growth. A delayed diagnosis of CD may be associated with a shorter adult height in men, but not in women. [78]

Celiac patients were reported to have a 5.4-fold higher risk of non-Hodgkin's lymphoma, but no increased risk of Hodgkin's or chronic lymphatic leukemia. It remains controversial whether there is an increased risk of developing lymphoma in CD if the disease is asymptomatic. [79]

Adult patients with CD have an increased risk of sepsis, particularly pneumococcus infection. [80] In CD there is an increased prevalence of splenic hypofunction. [81] Increased risk of cardiovascular disease in CD in (EMA)Anti-endomysial antibody positive individuals. [82]

  Conclusion Top

CD is being increasingly diagnosed because of the recognition that the disease may be present without significant intestinal symptoms, may be associated with other autoimmune disorders and may be suspected from serological screening. Definition of the disease includes an intestinal biopsy before treatment with a GFD along with documentation of a definitive GFD response. In some patients, this may necessitate further intestinal biopsy after a period on a GFD. Serological testing may be useful in providing additional evidence that CD is present and may be useful in some patients to assess GFD compliance. Recent studies focused on the genetic basis and pathogenesis of CD has emerged to improve understanding of the complex molecular alterations that occur with CD.

  References Top

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