Should relatives of coeliacs with mild clinical complaints undergo a small-bowel biopsy despite negative serology?

BACKGROUND AND OBJECTIVES: Small intestinal lesions in coeliac disease (CD) have a variable severity. Early diagnosis of CD is important because treatment allows a normal psycho-physical development, especially in children, and can avoid associated disorders. The aim of this study was to evaluate the predictive value of screening parameters for the detection and estimation of CD prevalence in first-degree relatives. METHODS: The screening was performed in 338 first-degree relatives of 134 coeliac families. Questionnaires and a physical examination followed by haematological analyses and serologyfor IgA anti-endomysium (EMA)/IgA antigliadin (AGA) antibodies were used in orderto selectthe candidates for small-bowel biopsy. The small-bowel biopsy was indicated on the basis of clinical complaints, laboratory tests and serology performed in 96 (28%) of the study group. RESULTS: CD was diagnosed in 17/96 cases. Six of the 17 showed total villous atrophy (VA) (Marsh IIIc), five subtotal VA (Marsh IIIb) and six partial VA (Marsh IIIa). EMA and AGA were strongly positive in the six patients whose intestinal biopsy showed total VA. However, only one coeliac out of the six patients with partial VA had positive EMA and AGA. CONCLUSION: A significant proportion of coeliacs may be missed if cases are screened by serology only. Although endomysial antibody assay has been reported as a highly sensitive and specific test for detection of CD, we argue that using only EMA and AGA in screening is not enough for investigation of the true prevalence of CD. A combination of clinical parameters as described in this study and laboratory/serological tests is an important and practical contribution to improving the detection rate of CD.

Clinical implications of the sugar absorption test: intestinal permeability test to assess mucosal barrier function.

BACKGROUND: Functional integrity as an aspect of the mucosal barrier function of the small bowel can be estimated by the intestinal permeability for macromolecules. In the first part of this paper, an overview of intestinal permeability and its measurement is given. METHODS: In the second part of the paper our own experience with the Sugar Absorption Test using lactulose and mannitol to assess mucosal barrier function of gastric, small and large bowel, respectively, is described. RESULTS AND CONCLUSIONS: The Sugar Absorption Test is not recommended as a predictor of NSAID-related upper gastrointestinal damage nor as a marker of disease activity in inflammatory bowel diseases. The Sugar Absorption Test is very useful in screening for small intestinal disease, in assessing the response to treatment, and in predicting the prognosis, especially in coeliac disease. In our opinion, the D-xylose test is obsolete.

The daily gluten intake in relatives of patients with coeliac disease compared with that of the general Dutch population.

BACKGROUND: It has been suggested that the amount of gluten intake in populations offers an explanation for differences in the epidemiology of coeliac disease. Investigations into first-degree relatives of coeliac disease patients have often shown that relatives exhibit intermediate features of coeliac disease, possibly due to a low gluten intake. AIMS: The aim of this study was to investigate the pattern of gluten consumption in the general Dutch population for different age and sex groups and for different product groups, and to investigate the daily gluten intake of first-degree relatives of coeliac disease patients. METHODS: Questionnaires concerning the gluten intake of 55 first-degree relatives of coeliac disease patients were analysed. To determine the gluten intake of the general Dutch population, the results of a mass investigation were used. The amount of gluten in the gluten-rich products was estimated by multiplying the amount of vegetable proteins by 0.8. RESULTS: The median daily gluten intake of the relatives was 12.9 g (range: 3.8-31.3). The mean daily gluten intake of the study population in the Netherlands was 1 3.1 g. CONCLUSION: The gluten intake of first-degree relatives of coeliac disease patients was the same as that of the general population. Thus, a low gluten intake apparently does not explain the aspecific presentation and prevalence of coeliac disease in first-degree relatives of coeliac disease patients.

Follow-up of treated coeliac patients: sugar absorption test and intestinal biopsies compared.

OBJECTIVE: To determine whether the sugar absorption test (SAT) during follow-up of patients with coeliac disease on a gluten-free diet (GFD) correlates with improvement of the villous architecture of the small intestine. METHODS: The SAT was performed in coeliacs at diagnosis and during follow-up with GFD. For the SAT, a solution of lactulose (L) and mannitol (M) was given to the fasting patient and the L-M ratio calculated in a 5-hour urine sample by gas chromatography: ratios > 0.089 are considered abnormal. The solution was made hyperosmolar by adding sucrose (1560 mmol/l). RESULTS: The L-M ratio was 2-3 times higher at diagnosis than either at 8 months to 2 years gluten free, or beyond 2 years gluten free, consecutively. The L-M ratio (mean, range) was significantly higher in cases of biopsies with (sub)total villous atrophy (VA) (0.388, 0.062-0.804, n = 28), partial VA (0.240, 0.062-0.841, n = 18) and villous irregularity (0.143, 0.017-0.322, n = 29) than in case of normalized histology after GFD (0.085, 0.021-0.230, n = 19). The rate of normalization of functional integrity was slower in adults than in children, demonstrated by a combination of histology and SAT. CONCLUSION: The SAT correlates well with the degree of VA. It is important for daily clinical practice that the simple and non-invasive SAT can be used as an indicator of intestinal damage, thus influencing need for and timing of intestinal biopsies.

[A new biscuit free of cow's milk, chicken egg protein, lactose and gluten for children with food hypersensitivity]. / Een nieuwe koek, vrij van koemelkeiwit, kippeëi-eiwit, lactose en gluten, voor kinderen met voedselovergevoeligheid.

OBJECTIVE: Evaluation of the clinical reaction of 10 children with food allergy, including allergy to cow's milk protein, to the introduction of a new biscuit, free of cow's milk protein, chicken egg protein, lactose and gluten. DESIGN: Descriptive prospective study. SETTING: Outpatient clinic, Beatrix Children's Hospital, University Hospital Groningen. METHOD: In 10 patients (mean age 28 months, range 13-78 months) with a proven cow's milk protein allergy the new biscuit (25 biscuits of 15.5 g each in 2 weeks) was introduced without otherwise changing the diet. The clinical symptoms, total serum IgE, the IgE radio-allergosorbent test (RAST), the skin test, the intestinal permeability (measured with the sugar absorption test), and energy and nutrient intake were determined before and after the introduction of the biscuits. Results were evaluated by the Wilcoxon test. RESULTS: Laboratory results were not significantly different between the groups. A recurrent clinical reaction was seen in one patient after consumption of a biscuit (probably due to a potato component). During the period of biscuit consumption energy and nutrient intake were increased in all children when a maximum of 1.5 biscuit per day was consumed. CONCLUSION: No problems were seen in 9/10 children following introduction of the new biscuit. Energy and nutrient intake were improved. An allergic reaction was seen in 1/10 children, probably due to the potato component.

Distribution of exogenous surfactant in rabbits with severe respiratory failure: the effect of volume.

The transient effect of surfactant therapy that is observed in some patients might, at least in part, be explained by a nonhomogeneous distribution. Therefore, we investigated the distribution of a surfactant preparation (Alvofact, 45 g/L) that is used clinically. Rabbits with severe respiratory failure were treated with this surfactant at a dose of 100 mg/kg body weight, and the distribution of surfactant was determined by the use of 141Ce-labeled microspheres that were mixed with the surfactant. Fifteen min after surfactant administration, the rabbits were killed, and the lungs were removed and divided into 200 pieces. The radioactivity per mg lung tissue was determined in each piece. We found that the endotracheal instillation of this surfactant preparation results in a nonhomogeneous distribution. However, a significantly improved distribution was obtained when this dose of surfactant (100 mg/kg body weight) was diluted with normal saline to a concentration of 6.25 g/L. The consequence of the administration of this dose was an intratracheal fluid administration of 16.0 mL/kg body weight. The distribution was also nonhomogeneous after the administration of a small-volume (2.4 mL/kg body weight), low-concentration surfactant preparation (6.25 g/L). We conclude that a surfactant preparation with clinical application is distributed nonhomogeneously in the lungs after endotracheal administration. The distribution can be significantly improved by increasing the fluid volume in which the surfactant is suspended.