Normal Gluten-containing Diet Research Articles

Microbiota profile of new-onset celiac disease in children in Saudi Arabia

BackgroundIntestinal dysbiosis has been reported to be associated with celiac disease (CeD) in Western populations but little is known in other populations who have different dietary lifestyle and genetic background. The purpose of this study was to determine whether a different microbiota profile is associated with CeD in children in Saudi Arabia.ResultsForty children with CeD, 20 healthy controls, and 19 non-CeD controls were enrolled. The median age at diagnosis was 10.3, 11.3 and 10.6 years in children with CeD, fecal, and mucosal control groups, respectively. Significant differences in microbial composition between children with CeD and controls both at fecal and mucosal level were identified. Fecal samples were more diverse and richer in bacteria as compared with mucosal samples. Proteobacteria were more abundant in duodenal mucosal samples and Firmicutes and Bacteroides were more abundant in stools. The abundance of many taxa was significantly different between children with CeD and non-CeD controls. In mucosal samples, Bifidobacterium angulatum (unadjusted p = 0.006) and Roseburia intestinalis (unadjusted p = 0.031) were examples of most significantly increased species in children with CeD and non-CeD controls, respectively. In fecal samples, there were 169 bacterial species with significantly different abundance between children with CeD and non- CeD controls.ConclusionsTo our knowledge, this is the first report on the microbial profile in a non-Western population of children with new onset CeD. The fact that mucosal and fecal samples were collected from newly diagnosed children with CeD on normal gluten-containing diet suggests strong association between the identified bacteria and CeD. The identification of many unreported bacterial species significantly associated with CeD, indicates the need for further studies from different populations to expand our understanding of the role of bacteria in the pathogenesis of CeD, hopefully leading to the discovery of new adjuvant treatment options.

Anti-gliadin antibodies in breast milk from celiac mothers on a gluten-free diet.

To analyze the presence of total IgA and anti-gliadin antibodies (AGA) in BM from CD mothers who follow a gluten-free diet (GFD) and from mothers on a normal gluten-containing diet (ND). 218 samples of mature milk were obtained at different months of lactation (1-6) from 83 mothers (2 or more samples per mother) from Italy (Naples), The Netherlands (Leiden) and Spain (Madrid, Valencia and Reus): 42 CD mothers on GFD for more than 2years and 41 non-CD mothers on a ND. Whey samples were analyzed for AGA-IgA by an indirect homemade ELISA and for total IgA (g/L) by a commercial ELISA kit. AGA-IgA was detected in BM, both in mothers on a GFD and mothers on a ND. AGA-IgA levels in both groups of mothers, CD and non-CD, show the same trend towards decreasing slightly along the months of lactation (p=0.91). A different trend is observed for total IgA levels, decreasing markedly in CD mothers from the first month of lactation onwards but remaining stable in non-CD mothers (p=0.048). A statistically significant association was found between the means of total IgA and AGA-IgA (p<0.001). AGA-IgA is present in BM from mothers on a ND as well as in BM from mothers who had been on a GFD for years. This reflects the existence of a long-lasting immunological memory independent of the mother's diet. If the presence of these antibodies has any role in promoting the acquisition of gluten tolerance in the infant, our study shows that children of CD mothers would be on equal conditions as children of non-CD mothers.

Celiac disease evolving into dermatitis herpetiformis in patients adhering to normal or gluten-free diet

Objective. Dermatitis herpetiformis (DH) is a cutaneous form of celiac disease affecting ∼17% of celiac disease patients. The aim was to determine how often celiac disease precedes the development of DH, and what is the impact of gluten-free diet (GFD) in this phenotype change. Material and methods. Our prospectively collected DH series from 1970 comprised 514 patients. We analyzed all DH patients who at least 2 years earlier had been diagnosed with celiac disease. DH diagnosis was confirmed by showing immunoglobulin A deposits in dermis. Serological and small bowel mucosal findings were analyzed, and the strictness of GFD treatment before and after the diagnosis of DH was evaluated. Results. Twenty (4%) DH patients had a prior diagnosis of celiac disease. The median time interval between celiac disease and DH detection was 9.5 years. Before DH appeared 4 patients had been on a normal gluten-containing diet, 10 had dietary lapses on a GFD, and 6 were on a strict GFD. Celiac autoantibodies were positive in 7 out of 19 patients, and 5 out of 7 undergoing small bowel biopsy had partial villous atrophy. Following DH diagnosis the rash was controlled after a median of 6 months on a strict GFD. Conclusions. Patients with celiac disease may develop DH by time. This is most often an indicator of poor adherence to GFD, and a rigorous dietary intervention is necessary. In the majority of cases, DH will be detected without prior celiac disease diagnosis, but the physicians should recognize this phenotype alteration.

Celiac Disease Presenting as a Cecal Bascule

Background: The prevalence of celiac disease is as high as 1%, but many cases remain undiagnosed. In a large European survey, the ratio of diagnosed to undiagnosed was as high as 1 to 7, demonstrating the largely accepted “celiac iceberg” effect. Rarely, celiac disease can present as obstruction caused by malignancy, ulcerative jejuno-ileitis, intussusception or pseudo-obstruction. Such clinical presentations require high clinical suspicion. To improve diagnosis and prevent complications of celiac disease, it is imperative that we increase awareness of the disease and its varied presentations. We present a case of a cecal bascule requiring operative management and complicated by multiple partial small bowel obstructions, preceding a diagnosis of celiac disease. Results: A twenty-eight year-old Caucasian woman with recently diagnosed iron deficiency anemia (Hgb 8.2, Ferritin 2, MCV 65) of unknown etiology on oral iron therapy presented to the emergency room with diffuse abdominal pain of acute onset. She reported a few month history of mild abdominal cramps and episodes of bloating after meals, in addition to ongoing fatigue despite oral iron therapy. CT scan revealed a cecal bascule for which the patient underwent a right hemi-colectomy. The patient developed an ileus on post-op day five requiring nasogastric decompression for forty-eight hours. She was discharged home on post-op day eight, tolerating a regular diet. Further work-up performed for the previously identified iron deficiency anemia revealed positive celiac serologies. The patient continued a normal gluten-containing diet pending endoscopy. Two weeks later, she developed a partial bowel obstruction which was managed conservatively with bowel rest. Endoscopy performed after resolution of the obstruction confirmed the diagnosis of celiac disease. Despite compliance with a gluten-free diet, she developed another partial bowel obstruction which was again managed conservatively with bowel rest. At the time of this case report, the patient is now seven months post-op, maintaining a strict gluten-free diet and doing well. Conclusion: The clinical presentations of celiac disease are highly variable, some cases presenting as clinically silent to more serious cases such as obstruction requiring surgical intervention. Diagnostic delay can result in significant complications, unnecessary hospitalizations, and emergent surgical procedures. To prevent complications, clinicians should have a high index of suspicion for celiac disease when evaluating patients with obstructive bowel symptoms, especially in cases where the etiology of obstruction is unknown.

Point-of-care testing for coeliac disease: primary care diagnostic technology update

#### Clinical Question In primary care patients with suspected coeliac disease, what is the accuracy and utility of point-of-care (POC) testing for coeliac disease compared to standard practice? Coeliac disease is a malabsorption syndrome precipitated by gluten ingestion, and characterised by inflammation of the small intestine. Serological tests for IgA anti-tissue transglutaminase antibody (tTGA) and anti-endomysial antibody (EMA) have high sensitivity and specificity for coeliac disease.1,2 In patients with IgA deficiency, the IgG class of the tTGA and EMA tests are recommended. Anti-gliadin antibodies are no longer used for the detection of coeliac disease, except in children younger than 18 months.2 Conventional serological tests are performed in central laboratories, whereas the point-of-care (POC) test can be performed in practice or at home. Both the POC and conventional serological tests require patients to be on a normal gluten-containing diet at the time of testing, since IgA-tTGA titres diminish on a gluten-free diet. Two POC devices available on the market were identified. ### Biocard Coeliac Test Kit (Ani Biotech, Finland; UK Distributor: BHR Pharmaceuticals Ltd) There are two versions of the test, a home test and a professional test; a ‘total IgA measuring system’ is included in the professional kit. The Biocard requires a drop of whole blood (finger-prick) and provides results within 10 minutes. Anti-tTG IgA antibodies bind to antigen in the test strip to form a visible line. A positive test result shows two lines, while only one line appears if the test is negative. If there is no line, IgA deficiency should be suspected. ### Stick CD1 and CD2 (Operon SA, Zaragoza, Spain) Both are one-step tests detecting IgA, IgG, and IgM antibodies against human tTG; and the CD2 test also detects anti-gliadin antibodies. The tests use serum instead of whole blood, which limits …

Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces

Background: Certain immunotoxic peptides from gluten are resistant to gastrointestinal digestion and can interact with celiac-patient factors to trigger an immunologic response. A gluten-free diet (GFD) is the only effective treatment for celiac disease (CD), and its compliance should be monitored to avoid cumulative damage. However, practical methods to monitor diet compliance and to detect the origin of an outbreak of celiac clinical symptoms are not available.Objective: We assessed the capacity to determine the gluten ingestion and monitor GFD compliance in celiac patients by the detection of gluten and gliadin 33-mer equivalent peptidic epitopes (33EPs) in human feces.Design: Fecal samples were obtained from healthy subjects, celiac patients, and subjects with other intestinal pathologies with different diet conditions. Gluten and 33EPs were analyzed by using immunochromatography and competitive ELISA with a highly sensitive antigliadin 33-mer monoclonal antibody.Results: The resistance of a significant part of 33EPs to gastrointestinal digestion was shown in vitro and in vivo. We were able to detect gluten peptides in feces of healthy individuals after consumption of a normal gluten-containing diet, after consumption of a GFD combined with controlled ingestion of a fixed amount of gluten, and after ingestion of <100 mg gluten/d. These methods also allowed us to detect GFD infringement in CD patients.Conclusions: Gluten-derived peptides could be sensitively detected in human feces in positive correlation with the amount of gluten intake. These techniques may serve to show GFD compliance or infringement and be used in clinical research in strategies to eliminate gluten immunotoxic peptides during digestion. This trial was registered at clinicaltrials.gov as NCT01478867.

Gluten-free diet and autoimmune thyroiditis in patients with celiac disease. A prospective controlled study

Objective. Early diagnosis and dietary treatment with a gluten-free diet might slow down the progression of associated autoimmune diseases in celiac disease, but the data are contradictory. We investigated the course of autoimmune thyroid diseases in newly diagnosed celiac disease patients before and after gluten-free dietary treatment. Material and methods. Twenty-seven consecutive adults with newly diagnosed celiac disease were investigated at the time of diagnosis and after 1 year on gluten-free diet. Earlier diagnosed and subclinical autoimmune thyroid diseases were recorded and examined. Thyroid gland volume and echogenicity were measured by ultrasound. Autoantibodies against celiac disease and thyroiditis, and thyroid function tests were determined. For comparison, 27 non-celiac controls on normal gluten-containing diet were examined. Results. At the time of diagnosis, the celiac disease patients had more manifest (n = 7) or subclinical (n = 3) thyroid diseases than the controls (10/27 vs. 3/27, p = 0.055). During the follow-up, the thyroid volume decreased significantly in the patients with celiac disease compared with the controls, indicating the progression of thyroid gland atrophy despite the gluten-free diet. Conclusions.Celiac patients had an increased risk of thyroid autoimmune disorders. A gluten-free diet seemed not to prevent the progression of autoimmune process during a follow-up of 1 year.

A gluten metabolism study in healthy individuals shows the presence of faecal glutenasic activity

To study the gluten metabolism in healthy individuals and its effect over the intestinal microbial activity. The faeces of eleven healthy subjects were analysed under 4 diet regimens: their normal gluten diet, a strict gluten-free diet (GFD), a GFD with a supplemental intake of 9g gluten/day and a GFD with a supplemental intake of 30g gluten/day. Gluten content, faecal tryptic activity (FTA), short-chain fatty acids (SCFAs) and faecal glutenasic activity (FGA) were analysed in faecal samples. Faecal gluten contents, FTA, SCFAs and FGA varied significantly with different levels of gluten intake in the diet. When high gluten doses (30g/day) were administered in the diet, SCFA concentrations (70.5mmoles/kg faeces) were significantly different from those from the GFD period (33.8mmoles/kg faeces) of the experiment. However, the FTA showed significant differences between the GFD (34 units) and the normal gluten-containing diet (60 units) and also between the GFD and the GFD+30g of gluten/day (67 units). When gluten was present in the diet, gluten was detected in the faeces, showing that at least a portion of the gluten ingested is eliminated in the large intestine, providing a substrate for intestinal microbial proteases. We have also shown the presence of faecal glutenasic activity that increased proportionally with the gluten intake in the diet, showing an enzymatic activity of 993 units in DSG, 2,063 units in DSG+9g and 6,090 units in DSG+30g. The activity of the intestinal microbiota is modified by gluten intake in the diet. The incorporation of gluten in the diet increases the activity of a gluten proteolytic activity in the faeces.

Successful Treatment of Coeliac Disease by Allogeneic Haematopoietic Stem Cell Transplantation

Successful Treatment of Coeliac Disease by Allogeneic Haematopoietic Stem Cell Transplantation

Dietary compliance and health-related quality of life in patients with coeliac disease

Coeliac disease is treated with a lifelong gluten-free diet (GFD). The aim of our study was to investigate whether the dietary (nondietary) compliance is associated with health-related quality of life (HRQoL) of coeliac patients. Patients from our hospital, known with coeliac disease for more than 10 years, were invited to participate in a study on possible gluten tolerance. HRQoL was assessed by the Short Form-36 health survey, symptoms by the Gastrointestinal Symptom Rating Scale and dietary compliance by a food frequency questionnaire. HRQoL of coeliac patients was compared with that of the general population. Fifty-three biopsy-confirmed coeliac patients were divided into three groups according to gluten consumption: GFD (n = 33), gluten transgression (<10 g gluten/day; n = 8) and normal gluten-containing diet (>10 g gluten/day; n = 12). Compared with the general population, coeliac patients scored significantly worse on general health perception but significantly better on bodily pain and limitations due to physical problems. The results of the Gastrointestinal Symptom Rating Scale and the Short Form-36 health survey were similar in all three dietary groups. Although adhering to the GFD is strictly important to prevent future complications, patients who stop following GFD do exist and patients with partial or nonadherence report similar HRQoL compared with patients with strict adherence in this group of adult coeliac patients.

Long-term Health and Quality-of-Life Consequences of Mass Screening for Childhood Celiac Disease: A 10-Year Follow-up Study

Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.

Gut Microflora Associated Characteristics in Children with Celiac Disease

The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls. The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups. This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient.

Density of gamma/delta+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age.

Increased density of gamma/delta T cell receptor (TCR)+ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial gamma/delta and alpha/beta TCR+ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial gamma/delta T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of gamma/delta+ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P < 0.0001). In controls, the density of gamma/delta+ cells remained low throughout the age-range studies, from age 0.6-57 years. In controls, alpha/beta+ cells increased with age (r = 0.57, P < 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation.

Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes.

Removal of gluten from the diet can attenuate the intensity of autoimmunity and reduces the incidence of diabetes in the nonobese diabetic mouse. In this study, we tested whether a gluten-free diet could reduce autoimmunity in human preclinical type 1 diabetes. A trial consisting of 6 months of a gluten-free diet followed by another 6 months of normal gluten-containing diet was performed in 17 first-degree relatives with at least 2 antibodies among islet cell antibodies, glutamic acid decarboxylase autoantibodies, protein tyrosine islet antigen-2 autoantibodies, and insulin autoantibodies. Treatment effect was measured as autoantibody titers and acute insulin response to iv glucose tolerance test. Two subjects dropped out for lack of compliance to diet restrictions. Of the remaining 15 subjects, 3 developed diabetes. Autoantibody titers did not show significant changes after 6 months of gluten-free diet and again after return to normal diet. Acute insulin response to iv glucose tolerance test significantly increased in 12 of 14 subjects after the first 6 months of gluten deprivation (P = 0.04) and decreased in 10 of 13 subjects during the following 6-month period of normal diet (P = 0.07). Insulin sensitivity (homeostasis model assessment-insulin resistance) nonsignificantly improved after the gluten-free diet and subsequently decreased (P < 0.005) after 6 months of normal diet. These findings indicate that 6 months of gluten deprivation do not influence humoral autoimmunity, but may have a beneficial effect on preservation of beta-cell function in subjects at risk for type 1 diabetes.

Gluten challenge in borderline gluten-sensitive enteropathy

OBJECTIVES: In patients with signs and symptoms of malabsorption, suggestive of gluten-sensitive enteropathy, small intestinal biopsies sometimes only reveal infiltration of lymphocytes into the mucosal epithelium. This infiltrative lesion (Marsh I) is not a definite proof for gluten-sensitive enteropathy. However, in the present study, we aimed to show that a subgroup of these patients could ultimately be identified as being gluten sensitive. METHODS: A total of 38 patients with a Marsh I lesion were subjected to a gluten challenge comprising 30 g of gluten added daily to a normal gluten-containing diet for 8 wk. Before and after the challenge, small intestinal biopsies were taken, and symptoms and signs of malabsorption were scored. RESULTS: In 12 patients we demonstrated a significant change in mucosal histopathology, i.e., subtotal villous atrophy (Marsh IIIB, n = 1), partial villous atrophy (Marsh 3A, n = 6) or infiltrative-crypthyperplastic lesions (Marsh II, n = 5). In the other 26 patients, the small intestinal mucosa remained unchanged. After initiation of a gluten-free diet, follow-up small intestinal biopsies in 12 patients who initially had progressive mucosal pathology after gluten challenge showed normalization of mucosal pathology in seven cases, regression to a Marsh I lesion in four, and to a Marsh II lesion in one. Symptom relief was seen in all 12 patients. Ten of 26 patients without histological response to the gluten challenge were motivated to adhere to a gluten-free diet. Follow-up biopsies revealed unchanged Marsh I lesions in eight patients and normalization (Marsh 0) in two patients. Three patients had follow-up biopsies while on a normal diet. All had unchanged Marsh I lesions. CONCLUSIONS: In the present study we demonstrated that a gluten challenge might be useful in identifying patients as being sensitive to gluten if initial small intestinal biopsies reveal only minor abnormalities.

Gluten challenge in borderline gluten-sensitive enteropathy.

In patients with signs and symptoms of malabsorption, suggestive of gluten-sensitive enteropathy, small intestinal biopsies sometimes only reveal infiltration of lymphocytes into the mucosal epithelium. This infiltrative lesion (Marsh I) is not a definite proof for gluten-sensitive enteropathy. However, in the present study, we aimed to show that a subgroup of these patients could ultimately be identified as being gluten sensitive. A total of 38 patients with a Marsh I lesion were subjected to a gluten challenge comprising 30 g of gluten added daily to a normal gluten-containing diet for 8 wk. Before and after the challenge, small intestinal biopsies were taken, and symptoms and signs of malabsorption were scored. In 12 patients we demonstrated a significant change in mucosal histopathology, i.e., subtotal villous atrophy (Marsh IIIB, n = 1), partial villous atrophy (Marsh 3A, n = 6) or infiltrative-crypthyperplastic lesions (Marsh II, n = 5). In the other 26 patients, the small intestinal mucosa remained unchanged. After initiation of a gluten-free diet, follow-up small intestinal biopsies in 12 patients who initially had progressive mucosal pathology after gluten challenge showed normalization of mucosal pathology in seven cases, regression to a Marsh I lesion in four, and to a Marsh II lesion in one. Symptom relief was seen in all 12 patients. Ten of 26 patients without histological response to the gluten challenge were motivated to adhere to a gluten-free diet. Follow-up biopsies revealed unchanged Marsh I lesions in eight patients and normalization (Marsh 0) in two patients. Three patients had follow-up biopsies while on a normal diet. All had unchanged Marsh I lesions. In the present study we demonstrated that a gluten challenge might be useful in identifying patients as being sensitive to gluten if initial small intestinal biopsies reveal only minor abnormalities.

Tissue transglutaminase and endomysial antibodies-diagnostic markers of gluten-sensitive enteropathy in dermatitis herpetiformis.

The association of Durhing's disease, commonly referred to as dermatitis herpetiformis (DH), with gluten-sensitive enteropathy (GSE) is supported by the presence of villous atrophy and endomysial antibodies (EMA). EMA are found to be a marker of GSE both in celiac disease (CD) and in DH. Since tissue transglutaminase (tTG) is believed to be the major autoantigen in GSE, the aim of our study was to determine the specificity and sensitivity of anti-tTG antibody ELISA compared to the EMA indirect immunofluorescence test. We studied 44 cases of DH, confirmed by the presence of IgA immune deposits in the dermal papillae, and 58 cases of CD conforming to the International Criteria of Diagnosing CD. The control group comprised 161 sera from patients with vesiculobullous disorders other than DH and 106 sera from normal healthy blood donors. Anti-tTG antibodies were detected in 36 of 44 DH (79%) and in 32 of 58 CD (55%) patients. EMA were positive in 33 of 44 DH (74%) and in 36 of 58 CD (62%) patients. Both the EMA and the antibodies to tTG were present in the majority of patients with DH and CD when they were on a normal gluten-containing diet and were absent when on a gluten-free diet for an extended period of time. There were, however, small discrepancies in positivity and negativity in tTG antibody-positive and EMA-negative patients and vice versa. There seems to be a correlation between the EMA titers and the anti-tTG antibody levels. This study confirms the high specificity and sensitivity of anti-tTG antibody ELISA for GSE and its strong correlation with EMA both in CD and in DH. The results of anti-tTG antibody and EMA assays were comparable; however, in DH, tTG was somewhat more sensitive than the EMA test. For screening of DH, it is advisable to perform both EMA and anti-tTG antibody tests.

GLUTEN-SENSITIVE ENTEROPATHY

Gluten-sensitive enteropathy is induced by dietary wheat gliadin and related proteins in genetically susceptible individuals. Most evidence suggests that the mucosal lesion represents an immunologically mediated injury triggered by gluten in the context of a particular assortment of major histocompatibility complex genes. The amino acid residues of gliadin and related proteins responsible for toxicity have not been identified; in vitro systems are available, but definitive conclusions must rely on in vivo jejunal challenges. At a conservative estimate, symptomatic gluten-sensitive enteropathy affects approximately 1 in 1000 individuals in Europe; however, it is now becoming clear that a greater proportion of individuals has clinically silent disease, and probably many others have a minor form of the the enteropathy. In most countries, the clinical presentation has changed over the past few years coming closer to the adult type of the disease, and the age of onset of symptoms is shifting upward. Liver, joint, hematologic, dental, and neurologic symptoms are increasingly being recognized. Several diseases are associated the gluten-sensitive enteropathy, such as IgA deficiency, insulin-dependent diabetes mellitus, and a range of other autoimmune diseases. Tests based on the measurement of antigliadin and antiendomysium antibodies have gained success as noninvasive screening tests; however, the ultimate diagnosis still is based on the finding of a severe histologic lesion of the jejunum while the patient is on a gluten-containing diet and on its disappearance once the gluten is excluded from the diet. A lifelong, strict GFD is mandatory for celiac children. Among other long-term problems, an increased risk of intestinal lymphoma has been reported in patients on a normal gluten-containing diet.

Malabsorption syndrome with cow's milk intolerance. Clinical findings and course in 54 cases.

Fifty-four infants with the malabsorption syndrome and cow's milk intolerence seen during 1962-1971 were investigated. All had diarrhoea and failed to thrive. Most had vomiting and about 20% had atopic eczema and recurrent respiratory infections. Laboratory investigations revealed malabsorption, raised serum IgA, and precipitins to cow's milk. Biopsies showed that the jejunal mucosa was damaged, and in about half the cases was flat. The patient did well on human milk but reacted clinically to cow's milk challenge, either in a few hours or gradually during 3-4 weeks. Some patients showed first a quick, but later a slow, reaction. Clinical symptoms of cow's milk intolerance disappeared at the age of about one year. At that time 81% had normal faecal fat, but only 29% had a normal proximal jejunal mucosa. Many of the patients developed intolerances to other food proteins, such as soya and wheat, if these were given during the sensitive period. Forty-two patients have been followed up for 2 years on a normal gluten-containing diet. Of these, 37 have a normal or nearly normal jejunal mucosa and 5 (12%) have subtotal villous atrophy indicative of coeliac disease. It is concluded that the malabsorption syndrome with cow's milk intolerance is a clear-cut clinical entity. However, the symptomatology, results of laboratory tests, and jejunal biopsy findings closely resemble those of other entities where damage to the intestinal mucosa causes a malabsorption snydrome. Follow-up studies showed that the disease is transient, but about 10% of the patients have coeliac disease, regarded in such cases as the primary disorder.

Latent Celiac Sprue

This study shows that patients with dermatitis herpetiformis (DH) and morphologically normal small intestinal mucosa may have a latent form of celiac sprue. Two patients with DH and one normal volunteer, all of whom had morphologically normal small intestinal mucosa, were placed on a high gluten diet for 22 to 30 weeks. Moderately abnormal and severe flat mucosal lesions were induced in both patients with DH, but not in the normal volunteer. Neither patient with DH developed clinical or laboratory evidence of malabsorption. On completion of the high gluten diet, 1 patient with DH was studied on a normal gluten-containing diet, and his intestinal mucosa reverted toward normal by 16 weeks. Latent celiac sprue may be defined as a condition in which the intestinal mucosa becomes unequivocally abnormal in response to increased dietary gluten.