Intestinal permeability after single dose gluten challenge in coeliac disease.

The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood.     

Complement studies in children with treated coeliac disease after gluten challenge

Changes of the complement components in the sera of 13 children with treated coeliac disease were studied after gluten challenge. The levels of C 1 and C 3-activator (factor B) were significantly decreased at 4 h after the challenge, as were the levels of total complement (CH 50) and the components C 1, C 4 and C 1-inactivator at 8 h. After 24 h most values returned to normal but there was another significant decrease in serum C 4 after 24 h, and for CH 50, C 1, C 2 and C 4 after 48 h.This study was supported by a grant from the Deutsche Forschungsgemeinschaft (Az. Op 12/11)     

Compliance with gluten free diet in coeliac disease.

Fifty two children in whom coeliac disease was confirmed by persistent enteropathy while they were taking gluten were monitored to assess the effects of compliance with a gluten free diet (GFD). Between the ages of 17.8 and 18.5 years height (in 45 patients followed up for a mean of 14.9 years) and weight (in 43 followed up for a mean of 15.2 years) were significantly lower in those complying poorly with a GFD compared with those complying well. Of the 37 patients still attending the clinic after a mean of 25 years, having been followed up for a mean of 18.4 years, 16 who had complied well with the diet had normal or only slightly abnormal mucosal morphology whereas all 10 who had not complied had abnormal morphology. In these 10 lactase, sucrase, and alkaline phosphatase activities were significantly less than values in those who complied well. Mucosal sucrase and alkaline phosphatase activities in those who complied well were no different from those in a control population, whereas lactase activity was significantly lower. It is concluded that failure to comply with a GFD during childhood results in decreased adult stature and in persisting active enteropathy with depressed brush border enzyme activity.     

Gluten challenge in treated coeliac disease.

Thirty-two children with a past diagnosis of coeliac disease were reinvestigated by means of gluten challenge. They had received a gluten-free diet for a mean period of 6-5 years (range 0-25-11-0) before gluten challenge, and had a mean age of 9-9 years (range 3-0-15-3) at the onset of challenge. Small intestinal biopsies were performed before and after the gluten challenge (at least 10 g natural gluten per day for 3 months in the majority) and, as judged by light microscopy and morphometric techniques, coeliac disease was confirmed in 25 (78%) of the 32 patients; challenge was continued in the remaining 7 for a total period of 2 years when biopsies were repeated in 6 children and all were normal. Serum and RBC folate, serum iron, Hb level, and clinical symptoms were unpredictable variables in identifying children who developed gluten-induced enteropathies. The social and emotional effects of gluten challenge are discussed. The results highlight the importance of gluten challenge and intestinal biopsy in the diagnosis of coeliac disease and strongly suggest that a normal biopsy after a 3-month gluten challenge (as described above) excludes coeliac disease.     

Short-term gluten challenge in children with coeliac disease does not impair spontaneous growth hormone secretion

BACKGROUND: Growth retardation in children with coeliac disease has been attributed to impaired growth hormone (GH) secretion observed in stimulation tests. OBJECTIVE: This study aimed at investigating the possible change in spontaneous GH secretion during a standardised gluten challenge. PATIENTS: Twelve children with previous enteropathy suggesting coeliac disease and a normal pre-challenge biopsy on a gluten-free diet were included; eight of them completed all parts of the study, including repeated 24-h GH sampling. METHODS: At the start and the end of a 5-6 weeks standardised gluten challenge, blood was drawn at a constant rate for 24 h and collected for GH analysis at 20-min intervals. The graph of plotted GH values was analysed by means of a computer program (PULSAR). RESULTS: No significant changes were seen in the measures of maximum GH peak, baseline GH values, area under the curve over the baseline (AUCb), the number of GH peaks or mean GH concentration. GH secretion rate (GHt) increased slightly. None of the characteristics of the 24-h profile was significantly correlated to the change of IGF-I. CONCLUSION: No impaired GH secretion was found. Thus, we speculate that decreased growth rate in celiac disease may not be primarily caused by changes in GH secretion. Instead it may be caused by changed peripheral sensitivity to GH.     

Genetic difference in HLA-DR phenotypes between coeliac disease and transitory gluten intolerance.

Genetic differences in HLA phenotypes were studied in coeliac disease to investigate why some patients do not react with mucosal damage after gluten challenge. Forty five children with coeliac disease and 16 with transitory gluten intolerance were typed; 76 subjects served as controls. HLA phenotypes in children with coeliac disease had significantly higher proportions of DR3/X and DR5/7 than controls (48.8% v 11.8% and 26.7% v 5.3%). Children with transitory gluten intolerance had lower DR3/X (43.8%) than children with coeliac disease and there were no DR5/7 phenotypes. Further analysis of similarly well defined cases might show whether genetic differences in the DR3/X and DR5/7 phenotypes can serve as a marker for the permanence of gluten intolerance.     

Two different doses of gluten show a dose-dependent response of enteropathy but not of serological markers during gluten challenge in children with coeliac disease

In order to study dose-dependency in histopathological reactions and in changes of serological markers of mucosal relapse, gluten challenge was performed with two defined amounts of gluten in 54 children with earlier enteropathy. Gluten was provided in the form of powder and the patients were randomly allotted to either 0.2 (group A, n = 27) or 0.5 (group B, n = 27) grams per kg body weight per day. At the start and after 4 wk of challenge a small intestinal biopsy was performed. Biopsy specimens were evaluated, in accordance with defined criteria, graded and summarized in an enteropathy score. Blood was sampled at the start and after 2 and 4 wk of challenge. Serum levels of anti-gliadin antibodies (AGA) and anti-endomysium antibodies (EmA) were measured. Within 4 wk of challenge, 24 out of 27 patients in group A and all patients in group B had relapsed. After increasing the gluten dose to 0.5 g/kg/d during the subsequent 4 wk, the three non-relapsing patients also relapsed. Conclusion: The severity of mucosal inflammation was significantly higher for group B (p = 0.04) indicating a dose-related severity of the enteropathy. No significant difference was found for maximum AGA level, or in the proportion of patients that converted to pathological values for AGA or EmA.     

Influence of infant feeding and gluten intake on coeliac disease

OBJECTIVES: To study the impact of infant feeding habits and actual gluten intake on gluten induced enteropathy. METHODS: A case-referent design, controlling for the HLA alleles conferring increased genetic risk, was used. All 164 siblings of 97 probands were investigated. Eighty five of the siblings, carrying the genes DQA1*0501-DQB1*02 conferring susceptibility for the disease, were investigated by interview, food recording, and taking a small intestinal biopsy sample. Eight cases of silent coeliac disease were found and these were compared with the 73 siblings in whom the diagnosis was excluded. RESULTS: No statistically significant differences were found between cases and referents in terms of duration of breast feeding, age at introduction of cows' milk products, frequency of breast feeding after gluten introduction, and gluten consumption. CONCLUSIONS: The studies factors may be of less importance for the development of gluten induced enteropathy.     

Confirming persistence of gluten intolerance in children diagnosed as having coeliac disease in infancy.

In young infants the clinical and investigative features of coeliac disease (CD) may be mimicked by other conditions such as cow's milk intolerance or secondary disaccharidase deficiency. It is therefore especially important to confirm a diagnosis of CD by later gluten challenge in such infants. Sixteen children in whom the diagnosis of CD had been made before the age of 12 months had an oral gluten challenge, after being treated with a gluten-free diet for periods of one month to 5 years. In 15 we showed intestinal xylose malabsorption by the one-hour blood xylose level within 1-28 days of starting ingestion of gluten. One child, with a persistently normal one-hour blood xylose test after gluten challenge for 3 months, had normal absorption and normal jejunal histology after 18 months on a gluten-containing diet; she is considered not to have CD. The one-hour blood xylose test before and after gluten challenge can help to confirm the diagnosis in coeliac patients diagnosed in infancy.     

Genetic difference in HLA-DR phenotypes between coeliac disease and transitory gluten intolerance

Genetic differences in HLA phenotypes were studied in coeliac disease to investigate why some patients do not react with mucosal damage after gluten challenge. Forty five children with coeliac disease and 16 with transitory gluten intolerance were typed; 76 subjects served as controls. HLA phenotypes in children with coeliac disease had significantly higher proportions of DR3/X and DR5/7 than controls (48.8% v 11.8% and 26.7% v 5.3%). Children with transitory gluten intolerance had lower DR3/X (43.8%) than children with coeliac disease and there were no DR5/7 phenotypes. Further analysis of similarly well defined cases might show whether genetic differences in the DR3/X and DR5/7 phenotypes can serve as a marker for the permanence of gluten intolerance.     

Incidence of coeliac disease and transient gluten intolerance in children in a Swedish urban community.

The incidence of coeliac disease in children in the city of Malm?, South Sweden, was 1 : 982 during 1966 to 1975. The diagnostic criteria were: flat intestinal mucosa on gluten-containing diet, free of symptoms, and improvement in mucosal morphology on gluten-free diet, and morphological and/or evident clinical relapse (three times) on gluten challenge. 6 (12%) of 49 children with initially a flat mucosa still had a normal mucosa on a gluten-containing diet for two years or longer, having so-called transient gluten intolerance.     

Early prediction of relapse during gluten challenge in childhood celiac disease

Thirty-seven children, in whom celiac disease had been diagnosed because of flat mucosa on a gluten-containing diet and recovery on a gluten-free diet, were challenged with gluten powder, 10 g/day, in addition to an otherwise gluten-free diet. A small intestinal biopsy was performed before the challenge; clinical symptoms, a 1-h blood xylose test, and gliadin antibody measurement were used to establish the timing of the confirmatory biopsy. All but one case relapsed within 205 days (mode, 60 days). In no case was the relapse clinically evident. Raised levels of gliadin antibodies, a fall in xylose absorption, or both predicted the relapse in 37%, 7%, and 57% of cases, respectively. Evaluated individually, each test gave a considerable rate of false negative results. Discriminant coefficients produced for each test were used to compute a score that allowed the classification of patients into relapse/no relapse categories with a good degree of accuracy. The discriminant score rose sharply after only 15 days of challenge, indicating that it is possible to predict the relapse long before any clinical symptom appears.     

IgA anti-gliadin antibodies in the monitoring of gluten challenge in celiac disease

The aim of this study was to evaluate the reliability of serum IgA anti-gliadin antibodies (IgA-AGA) in the monitoring of gluten challenge and in the prediction of mucosal relapse in children with celiac disease (CD) in order to reduce the challenging procedure to a minimum. Serial evaluations of serum IgA-AGA titers and 1-h blood xylose levels were performed in 17 children with celiac disease during gluten challenge. Jejunal biopsy was generally done after two consecutive measurements of positive IgA-AGA. The morphological appearance of the mucosa and intraepithelial lymphocyte infiltration were also evaluated. A serum positive for IgA-AGA was observed in 16 of 17 patients between the 15th and 35th day of challenge. The challenge was concluded in all children after 20-45 days from the introduction of a gluten-containing diet after histological confirmation of CD. Plasma xylose test was less reliable in this respect. We conclude that IgA-AGA measurement by gluten challenge is likely to simplify and allow earlier diagnostic confirmation of celiac disease in children, without intestinal biopsy.     

Urinary NOx:creatinine ratios during gluten challenge in children with celiac disease

OBJECTIVES: Celiac disease is a gluten-induced small bowel enteropathy. Inflammation is known to be associated with enhanced nitric oxide (NO) production. An increase in urinary nitrate and nitrite (NOx) reflects increased NO production. The urinary NOx:creatinine ratio can be used as an indicator of the endogenous NO production. The aim of the study was to determine whether the urinary NOx:creatinine ratio of celiac disease patients increases during gluten challenge. METHODS: The authors studied 20 patients with unconfirmed celiac disease who had been following a gluten-free diet for at least 1 year. These patients underwent an 80-day gluten challenge. Urinary samples were obtained before and 10, 20, 40, and 80 days after starting the gluten challenge. The Griess reagent method was used for measuring urinary NOx. RESULTS: Gluten challenge confirmed the diagnosis of celiac disease in 15 of 20 patients. The NOx:creatinine ratios (mmol:mmol) of the biopsy-confirmed celiac disease patients were significantly higher than those of the unconfirmed celiac disease patients (0.67 vs. 0.17 on day 10; 0.78 vs. 0.15 on day 20; 0.85 vs. 0.25 on day 40; and 0.85 vs. 0.17 on day 80). CONCLUSIONS: Gluten challenge resulted in an increased urinary NOx:creatinine ratio in patients with biopsy-confirmed celiac disease. The NOx:creatinine ratio could be useful for the serial evaluation of disease activity.     

Proctosigmoiditis and coeliac disease.

Of 80 children with proved coeliac disease, 2 presented with an associated disease of the distal portion of the large intestine. In one child the family history and the extension, localisation, and characteristics of intestinal lesions made us suspect ulcerative colitis; in the other we made a diagnosis of milk-induced colitis.