Compliance of adolescents with coeliac disease with a gluten free diet.

A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state. Mucosal structure and lymphocytes were assessed in small intestinal biopsy specimens obtained from 36 subjects, by computerised image analysis. Of these adolescents with coeliac disease, 65% were adhering to a strict gluten free diet, 11.4% were on a gluten free diet but with occasional gluten intake, and 23.6% were on a gluten containing diet. Clinical symptoms occurred more frequently in patients on a gluten containing diet, but not in patients on a semi-strict diet. Occasional intake of small amounts (0.06-2 g/day) of gluten did not produce increased concentrations of antigliadin antibodies but resulted in an appreciably increased crypt epithelial volume and expanded crypt intraepithelial lymphocyte population.     

Malignancy in coeliac disease--effect of a gluten free diet.

Two hundred and ten patients with coeliac disease previously reported from this unit were reviewed at the end of 1985 after a further 11 years of follow up. The initial review at the end of 1974 could not demonstrate that a gluten free diet (GFD) prevented these complications, probably because the time on diet was relatively short. The same series has therefore been kept under surveillance with the particular aim of assessing the effects of diet on malignancy after a further prolonged follow up period. Twelve new cancers have occurred: of which one was a carcinoma of the oesophagus and two lymphomas. Thirty nine cancers developed in 38 patients and of 69 deaths, 33 were the result of malignancy. A two-fold relative risk (RR) of cancer was found and was because of an increased risk of cancer of the mouth and pharynx (RR = 9.7, p less than 0.01, 95% confidence interval (CI) = 2.0-28.3), oesophagus (RR = 12.3, p less than 0.01, CI = 2.5-36.5), and of non-Hodgkin's lymphoma (RR = 42.7, p less than 0.001, CI = 19.6-81.4). The results indicate that for coeliac patients who have taken a GFD for five years or more the risk of developing cancer over all sites is not increased when compared with the general population. The risk is increased, however, in those taking a reduced gluten, or a normal diet, with an excess of cancers of the mouth, pharynx and oesophagus (RR = 22.7, p < 0.001), and also of lymphoma (RR = 77.8, p < 0.001). A significant decreasing trend in the excess morbidity rate over increasing use of a GFD was found. The results are suggestive of a protective role for a GFD against malignancy in coeliac disease and give further support for advising all patients to adhere to a strict GFD for life.     

Reversal of osteopenia with diet in adult coeliac disease.

To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p < 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p < 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.     

Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet.

This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal.     

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet

BACKGROUND: Coeliac disease patients show a number of gastrointestinal motor abnormalities, including a decrease in lower oesophageal sphincter pressure. The prevalence of endoscopic oesophagitis in these subjects however is unknown. Aim: To evaluate whether untreated adult coeliac patients had an increased prevalence of reflux oesophagitis and, if so, to assess whether a gluten free diet exerted any beneficial effect on gastro-oesophageal reflux disease (GORD) symptoms. PATIENTS AND METHODS: We retrospectively studied 205 coeliac patients (females/males 153/52, median age 32 years) who underwent endoscopy for duodenal biopsy and 400 non-coeliac subjects (females/males 244/156, median age 37 years) referred for endoscopy for upper gastrointestinal symptoms. Each patient was given a questionnaire for evaluation of GORD symptoms prior to and 4-12 months after endoscopy. Coeliac patients were given a gluten free diet. Oesophagitis patients of both groups, following an eight week course of omeprazole, were re-evaluated for GORD symptoms at four month intervals up to one year. Significance of differences was assessed by Fisher's exact test. RESULTS: Oesophagitis was present in 39/205 (19%, 95% confidence interval (CI) 13.8-25.0%) coeliac patients and in 32/400 (8%, 95% CI 5.5-11.1%) dyspeptic subjects. At the one year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% CI 13-42.1%) coeliacs with oesophagitis and in 23/32 (71.8%, 95% CI 53.2-86.2%) non-coeliac subjects with oesophagitis. CONCLUSION: Coeliac patients have a high prevalence of reflux oesophagitis. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that coeliac disease may represent a risk factor for development of reflux oesophagitis.     

Beneficial effects of gluten free diet in potential coeliac disease in adult population

BackgroundTo date, potential coeliac disease (PCD) occurring in adults remains an almost unexplored condition.AimsTo explore the prognostic role of Marsh grade in adult PCD patients, and to evaluate the effects of gluten-containing diet (GCD) in asymptomatic PCD patients.MethodsWe retrospectively evaluated all consecutive adult PCD patients followed-up for at least 6 years. Patients were divided into: Group A (patients with Marsh 0 histology) and Group B (Marsh 1 patients). Symptomatic patients were started gluten-free diet (GFD), while asymptomatic subjects were kept on GCD and were followed-up.Results56 PCD patients were enrolled (21 in Group A and 35 in Group B). Forty-three patients were symptomatic and started GFD. Of these, none of 15 patients in Group A and 8 of 28 patients in Group B developed immune-mediated disorders (IMD) during follow-up (P = 0.03; OR = 4.2). The 13 asymptomatic PCD patients were kept on GCD. During the follow-up, 9 patients developed CD-related symptoms, 6 villous atrophy and 8 IMD. At the end, patients kept on GCD were at higher risk of developing IMD than those following a GFD (61% vs 18%, P = 0.03, OR = 3.3).ConclusionsAlthough PCD with normal mucosa seems to be a milder disease, the continuation of GCD places patients at a high risk of developing villous atrophy and IMD compared to commencement of GFD. Adult PCD patients should start GFD even if not symptomatic.     

Severe osteopenia in symptom-free adults with a childhood diagnosis of coeliac disease

The frequency of osteopenia in symptom-free adults diagnosed with coeliac disease during childhood and who resumed a normal diet during adolescence is unknown. Severe osteopenia (a bone mineral density below two standard deviations of the mean) was found in up to a third of symptom-free young adults on a normal diet. These patients should not be thought to be disease-free but should receive long-term follow-up and most of them should be advised to resume a gluten-free diet.     

Serum cholesterol precursor sterols in coeliac disease: effects of gluten free diet and cholestyramine.

Enhanced biliary secretion and high faecal excretion of cholesterol are associated with increased cholesterol synthesis in coeliac disease. We have further investigated cholesterol synthesis in coeliac disease by determining the concentrations of faecal steroids and cholesterol precursors in serum, with and without a gluten free diet and while taking cholestyramine. The levels of unesterified methyl sterols and free and esterified lathosterol, but not those of squalene and desmosterol, were increased in proportion to the level of cholesterol synthesis, as measured with the sterol balance technique. Serum esterified methyl sterol concentrations were also slightly higher but, unlike free methyl sterols or lathosterol, they were not significantly correlated with cholesterol synthesis. The gluten free diet decreased the level of cholesterol synthesis, and the levels of lathosterol and free methyl sterols. There was less decrease in the concentration of esterified methyl sterols, and an insignificant decrease in the concentrations of squalene and desmosterol. Cholestyramine lowered the serum cholesterol concentration and increased that of serum free methyl sterols less in the patients than in the controls, and the increase was proportionate to increase of cholesterol elimination (or synthesis). The increase of serum free methyl sterols per unit of the increase of cholesterol elimination (or synthesis) was three times higher in the bile acid malabsorption caused by cholestyramine than in the cholesterol malabsorption caused by gluten enteropathy. On the other hand, the decrease in the level of serum cholesterol relative to the increase in cholesterol elimination (or synthesis) was higher in cholesterol malabsorption due to coeliac disease than in cholestyramine induced bile acid malabsorption. Effective secretion of newly synthesised and/or absorbed cholesterol directly into the bile could be a factor in the marked decrease of the serum cholesterol concentration in coeliac disease.     

Reintroduction of gluten in adults and children with treated coeliac disease.

Twenty-eight patients, thought to have coeliac disease and on gluten free diets, were put on a normal diet to confirm their diagnoses. Nineteen had been diagnosed in adult life (ACD) and nine in childhood (CCD). Patients were assessed on jejunal, morphological, and symptomatic parameters. Eighteen patients with ACD relapsed within seven weeks. Nine patients with CCD relapsed at variable times but five took longer than seven weeks, the longest period beint 10 months. Seven patients had no symptoms despite morphological deterioration during challenge and one patient, with ACD, did not relapse and was HLA B8 negative. This patient with ACD had subtotal villous atrophy on two jejunal biopsies and later showed morphological improvement on a gluten free diet. There was no correlation between the relapse time and time spent on a gluten free diet.     

Non-responsive celiac disease in children on a gluten free diet

BACKGROUNDNon-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population.AIMTo determine the incidence, clinical characteristics and underlying causes of NRCD in children.METHODSRetrospective cohort study performed at Boston Children’s Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.RESULTSSix hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with Helicobacter pylori (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.CONCLUSIONNRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.     

Celiac disease: Alternatives to a gluten free diet

Celiac disease is a chronic inflammatory disorder of the small intestine caused by the ingestion of gluten or related rye and barley proteins. At present, the only available treatment is a strict gluten-exclusion diet. However, recent understanding of the molecular basis for this disorder has improved and enabled the identification of targets for new therapies. This article aims to critically summarize these recent studies.     

Oats to children with newly diagnosed coeliac disease: a randomised double blind study

BACKGROUND: Treatment of coeliac disease (CD) requires lifelong adherence to a strict gluten free diet (GFD) which hitherto has consisted of a diet free of wheat, rye, barley, and oats. Recent studies, mainly in adults, have shown that oats are non-toxic to CD patients. In children, only open studies comprising a small number of patients have been performed. Aim: To determine if children with CD tolerate oats in their GFD. PATIENTS AND METHODS: In this double blind multicentre study involving eight paediatric clinics, 116 children with newly diagnosed CD were randomised to one of two groups: one group was given a standard GFD (GFD-std) and one group was given a GFD with additional wheat free oat products (GFD-oats). The study period was one year. Small bowel biopsy was performed at the beginning and end of the study. Serum IgA antigliadin, antiendomysium, and antitissue transglutaminase antibodies were monitored at 0, 3, 6, and 12 months. RESULTS: Ninety three patients completed the study. Median (range) daily oat intake in the GFD-oats group (n = 42) was 15 (5-40) g at the six month control and 15 (0-43) g at the end of the study. All patients were in clinical remission after the study period. The GFD-oats and GFD-std groups did not differ significantly at the end of the study regarding coeliac serology markers or small bowel mucosal architecture, including numbers of intraepithelial lymphocytes. Significantly more children in the youngest age group withdrew. CONCLUSIONS: This is the first randomised double blind study showing that the addition of moderate amounts of oats to a GFD does not prevent clinical or small bowel mucosal healing, or humoral immunological downregulation in coeliac children. This is in accordance with the findings of studies in adult coeliacs and indicates that oats, added to the otherwise GFD, can be accepted and tolerated by the majority of children with CD.     

Analysis and clinical effects of gluten in coeliac disease.

The prolamin working group coordinates research on laboratory gluten analysis in food and on clinical evaluation of patient sensitivity to prolamins. As an observer organization to the Codex Alimentarius Commission, the group summarizes current data on analysis and effects of gluten in coeliac disease. All types of gliadin, the ethanol-soluble fraction of gluten, contain the coeliac-active factor. However, coeliac toxicity and immunogenicity (humoral and cellular) of various prolamins are not identical in coeliac patients. There are no conclusive data on the threshold of gluten sensitivity of coeliac patients. Information as to the long-term risk to coeliac patients exposed to small doses of gliadin is lacking. Therefore, every effort should be made to keep the diet of coeliac patients as gluten-free as possible. The prolamin group is currently evaluating a new enzyme-linked immunosorbent assay (ELISA) protocol for gluten analysis that could serve as a basis for further Codex regulations. The group recommends adherence to a single Codex limit for gluten-free foods. The current limit of 200 ppm gluten is questionable and requires reconsideration based on new information that will be available soon.     

Variability of gluten intolerance in treated childhood coeliac disease.

Fifty children consecutively attending a clinic for coeliac disease co-operated in a trial; 10 found to have flat mucosa were excluded. Forty children of mean age 9.8 years, whose duodenal or jejunal mucosa had returned to normal or near normal appearance after a mean of 5.8 years on gluten-free diets, were put back on normal diets. In 37, mucosal occurred in a mean of 16.9 months (four to 74 months). Four of the 37 had serial biopsies, in which mucosal enzymes (particularly lactase) fell and interepithelial lymphocyte counts rose before the mucosal morphology was regarded as definitely 'coeliac'. Three children had normal mucosal appearance after 58 to 73 months on normal diets, one of whom showed temporary mucosal abnormalities, another having occasionally low enzymes, in both suggesting underlying gluten sensitivity. Lactase suppression and raised IEL counts appear to be sensitive indicators of gluten intolerance. In our experience, a diagnosis of coeliac disease based on severe mucosal damage and a satisfactory response to a gluten-free but milk-containing diet implies a very strong likelihood of permanent or prolonged gluten intolerance, but with a striking variability in its expression.     

In vivo gluten ingestion in coeliac disease

Studies to determine the nature of the cereal component toxic to patients with coeliac disease have concentrated on wheat due to its nutritional importance. A number of in vitro studies have indicated the presence of one or more coeliac-disease-activating epitopes with the N terminus of the A gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acid 31-49 of A gliadin. Changes induced by this peptide included a decrease in the ratio of villous height to crypt depth, a decrease in enterocyte surface cell height and an increase in intra-epithelial lymphocyte count. There was evidence of mRNA for the pro-inflammatory cytokincs interferon gamma and interleukin 2 within 2 h of the in vivo challenge. We examined electron-microscopically biopsies from patients with coeliac disease challenged with gluten to determine the subcellular sites where gliadin co-localised with T-cell receptor subunits and HLA antigens. There were differences in co-localisation patterns between treated and untreated coeliac patients. These differences and the different patterns of gliadin staining within enterocytes of coeliac patients and controls, observed by others, suggest that gliadin may be metabolised via a different immunogenic pathway in coeliac disease. This might result in an abnormal presentation to the immune system, triggering a pathogenic, rather than a tolerogenic response.     

Effect of gluten-free diet on splenic hypofunction of adult coeliac disease.

Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, before and during a gluten-free diet. The basal percentage values of pitted cells decreased significantly during treatment but no correlation was observed between the duration of the gluten-free diet and the percentage of recovery of splenic function over basal values. Out of six coeliacs with pitted cell values consistent with splenic hypofunction, three showed a total recovery after gluten withdrawal. Our data suggest that, contrary to recent reports, hyposplenism in adult coeliac disease is improved by a gluten-free diet, and that environmental factors may be important in determining and maintaining this complication.     

Small intestinal bacterial overgrowth among patients with celiac disease unresponsive to a gluten free diet

Background/AimsLittle is known about the relationship between small intestinal bacterial overgrowth (SIBO) and celiac disease (CeD) in patients who are unresponsive to a gluten-free diet (GFD). This study aimed to determine the SIBO prevalence in patients with CeD who are unresponsive to a GFD.Materials and MethodsWe conducted a case-control study from July 2012 to September 2014. We included 32 patients with CeD who were unresponsive to a GFD and 52 healthy age- and sex-matched controls. Demographic, clinical, and laboratory data were obtained from patients’ medical records. Antitissue transglutaminase antibody determined by enzyme-linked immunosorbent assay was recorded, and lactulose hydrogen breath test (LHBT) was used to detect SIBO in all participants. Microbiological analysis, including jejunal aspirates obtained using upper endoscopy, was performed for only 20 patients with CeD.ResultsA total of 10 (31%) of 32 patients with CeD and 4 (7.7%) of 52 controls tested positive for LHBT, with a statistically significant difference (p=0.007). Of 20 cultures, 3 (15%) were positive with no statistically significant correlation between the cultures and LHBT (p=0.05). In a subgroup analysis of children who were 18 years old or younger, 7/24 (29.2%) patients with CeD had a positive LHBT compared with 3/32 (9.4%) controls, but this difference was not statistically significant (p=0.08).ConclusionThe prevalence of SIBO was 31% in unresponsive patients with CeD according to LHBT and 15% in the quantitative culture of the jejunal aspirate, which is comparable with the published Western literature