Ewa Grodzinsky

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.

Is small bowel biopsy necessary in adults with suspected celiac disease and IgA anti-endomysium antibodies? 100% positive predictive value for celiac disease in adults.

The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin antibodies in adults with histologically confirmed celiac disease is reported. Sera from 144 adult patients (without concurrent dermatitis herpetiformis or IgA deficiency) who underwent small bowel biopsy were analyzed for both IgA anti-endomysium and IgA anti-gliadin antibodies. Nineteen patients (13%) had celiac disease. The presence of IgA antiendomysium antibodies had a sensitivity of 74% and a specificity of 100%. The positive and negative predictive values were 100% and 96%, respectively, and the diagnostic accuracy was 97%. In contrast, IgA anti-gliadin antibodies had positive and negative predictive values of 28% and 96%, respectively, with a diagnostic accuracy of 71%. Based on these data, we suggest that small bowel biopsy is not necessary to diagnose celiac disease in symptomatic adults with IgA antiendomysium antibodies. Due to a negative predictive value of 96%, some symptomatic adults lacking anti-endomysium antibodies will not be correctly diagnosed without small bowel biopsy.

Familial Prevalence of Coeliac Disease: a Twenty-Year Follow-up Study

Background: The genetic predisposition of coeliac disease (CD) is well known. Previous studies of first-degree relatives of coeliac patients have shown that as many as 10% have the disease. In 1981, we published a study in which all first-degree relatives of 32 index patients with CD were investigated by small-bowel biopsy. We found 2 relatives (2%) with CD. The present study is a re-investigation of all first-degree relatives of the same index patients performed 20-25 years after the first study to reveal any new cases of CD in this high-risk population. Methods: All 120 first-degree relatives were screened for CD by means of serological markers of CD. The relatives with positive markers were submitted to small-bowel biopsy. Results: Eight new cases of CD were found among the relatives. Two had been investigated by small-bowel biopsy 20 years previously, when they had only minor mucosal changes not classified as CD. The other six new cases of CD were found among offspring of the index patients and were born after completion of the previous study. Thus no new case of CD was found among those relatives who had a completely normal small-bowel biopsy 20-25 years previously. Conclusions: The high prevalence of CD among first-degree relatives of coeliac patients (8.3% in this study) supports the need to screen for CD in this high-risk population. Even relatives with only mild enteropathy should be followed carefully, since some may subsequently develop CD.

Better dietary compliance in patients with coeliac disease diagnosed in early childhood

Background: In coeliac disease (CD) there is a permanent gluten intolerance requiring life-long adherence to a strict gluten-free diet (GFD). An inadequate diet increases the risk for long-term complications. Coeliac patients often have great difficulty in maintaining a strictly GFD. We aimed to study whether young adults with CD diagnosed before the age of 4 years have a better dietary compliance than patients diagnosed later in life. Method: Twenty-nine adults with CD diagnosed in childhood were studied. They had had CD for 17-24 (mean 20) years. Their compliance to GFD was assessed using a questionnaire and serological markers (IgA and IgG anti-endomysium antibodies and IgA anti-tissue transglutaminase antibodies). Results: At least 80% of the coeliac patients who had been diagnosed before the age of 4 years complied with the GFD compared to 36% of the CD patients older than 4 years at diagnosis ( P r < r 0.05). Conclusion: This is the first study to show that patients with CD diagnosed before 4 years of age keep to a GFD significantly better than patients diagnosed after 4 years. It is thus important to diagnose childhood CD as early as possible in order to minimize the risk for reduced well-being and other potentially serious complications in coeliac individuals on an inadequate diet.BACKGROUND In coeliac disease (CD) there is a permanent gluten intolerance requiring life-long adherence to a strict gluten-free diet (GFD). An inadequate diet increases the risk for long-term complications. Coeliac patients often have great difficulty in maintaining a strictly GFD. We aimed to study whether young adults with CD diagnosed before the age of 4 years have a better dietary compliance than patients diagnosed later in life. METHOD Twenty-nine adults with CD diagnosed in childhood were studied. They had had CD for 17-24 (mean 20) years. Their compliance to GFD was assessed using a questionnaire and serological markers (IgA and IgG anti-endomysium antibodies and IgA anti-tissue transglutaminase antibodies). RESULTS At least 80% of the coeliac patients who had been diagnosed before the age of 4 years complied with the GFD compared to 36% of the CD patients older than 4 years at diagnosis (P < 0.05). CONCLUSION This is the first study to show that patients with CD diagnosed before 4 years of age keep to a GFD significantly better than patients diagnosed after 4 years. It is thus important to diagnose childhood CD as early as possible in order to minimize the risk for reduced well-being and other potentially serious complications in coeliac individuals on an inadequate diet.

Anti-endomysium and anti-gliadin antibodies as serological markers for coeliac disease in childhood: a clinical study to develop a practical routine.

Anti‐gliadin and anti‐endomysium antibodies were analysed in 174 children with suspected or verified coeliac disease with the aim of developing a practical routine. The biopsy was performed without knowledge of the antibody levels. To screen for coeliac disease is children younger than 2 years, we suggest the use of IgA anti‐gliadin antibodies, giving a sensitivity of 100% and a specificity of 86%. In older children both tests should be used in parallel, i.e. a biopsy should be performed if at least one of the tests is positive, giving a sensitivity of 98% and a specificity of 81%. To avoid unnecessary biopsy before mucosal relapse can be demonstrated during gluten challenge in a child without clinical symptoms, we suggest that the tests are used as serial testing, i.e. a biopsy should be performed if both tests are positive.

Prevalence of celiac disease: before and after a national change in feeding recommendations.

Objective. A national change in infant feeding recommendations was proposed in 1996 in Sweden: a slow introduction to gluten during weaning was stressed, the recommendation being introduction at 4 instead of 6 months of age. The aim of the present study was to compare the prevalence of celiac disease in healthy young children born before and after the new feeding recommendations in 1996. Material and methods. Sera from 679 children at a median age of 2.9 years (range 2.5–4.2 years) born between January 1996 and November 1997 were investigated with IgA-antigliadin antibodies (AGA) and IgA-endomysial autoantibodies (EMA) and compared with 690 age-matched children born between July 1992 and June 1993. Children with a positive test for EMA and AGA or EMA only were re-tested, and if positive at follow up, investigated with intestinal biopsy. Results. At baseline, 2.2% (15/679) children were positive for EMA and another 0.6% (4/679) for both EMA and AGA. One child refused to be re-tested and eight children were still EMA positive at follow-up. Intestinal biopsy was performed in seven children (one declined biopsy), of whom three showed total villous atrophy. Two children with EMA titers 1:640, respectively, refused further participation in the study, but were strongly suspected to have celiac disease. In total, 0.7% (5/679) (95% confidence interval (CI) = 0.1–1.4%) were considered to have celiac disease compared with 1.3% (9/690) (95% CI = 0.4–2.2%) in the control group (p=0.4217). In addition, 0.3% of the children were diagnosed with symptomatic celiac disease compared with 0.7% in controls (p=0.0134). Conclusions. The prevalence of symptomatic celiac disease declined after the infant dietary recommendations were introduced in 1996, but we could not find any difference in undiagnosed celiac disease between the screened children born before and those born after 1996.

High prevalence rates of adult silent coeliac disease, as seen in Sweden, must be expected in Denmark.

Aim: To disclose the prevalence of adult “silent” coeliac disease in Denmark and Sweden. Experimental design: 1573 Danish and 1866 Swedish healthy blood donors were screened for the presence of serum anti‐gliadin antibodies (AGA) by enzyme‐linked immunosorbent assay. AGA‐positive serum samples were further analysed for IgA anti‐endomysium antibodies (EmA) by indirect immunofluorescence microscopy. Main results: The Danish donor population had a higher mean age than the Swedish (41.4 years versus 37.6 years) and a higher proportion of females (41% versus 32%), and had a lower mean level of AGA (17.3 units versus 20.6 units). Sixty‐one (3.9%) Danish donors had AGA above the cut‐off limit, and four of these also had positive EmA tests. Sixty (3.2%) Swedish donors had AGA above the cut‐off limit, and five of these also had positive EmA. Coeliac pathology was proven by biopsy in all five coeliac disease‐suspected Swedish donors. No small intestinal biopsy was performed in the coeliac disease‐suspected Danish donors. Conclusions: Based upon the finding of EmA in AGA‐positive serum samples, silent coeliac disease may be suspected in 1 per 394 Danish blood donors (2.5 per 1,000). A similar rate was proven in 1 per 373 Swedish blood donors (2.7 per 1,000), indicating no major differences in the prevalence of adult silent coeliac disease between the two neighbouring countries.

Coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres

Objective. Recent studies report negligible toxicity of oats in the majority of coeliac disease (CD) patients. It has previously been shown that children with untreated CD have circulating antibodies to oats avenin. In this study we performed serial assessments of anti-avenin antibodies in children under investigation for CD on a gluten-free diet with or without oats. Material and methods. The study involved 116 children, randomized to a standard gluten-free diet or a gluten-free diet supplemented with oats. Sera were obtained from 86 children, 48 in the standard gluten-free group and 38 in the gluten-free oats group, of which 33 consumed at least 10 g of oats daily. IgA and IgG anti-avenin antibodies were monitored at 0, 3, 6 and 12 months. Nitric oxide metabolites were measured in 7 patients, with deviating antibody results. Results. There was a significant decrease in anti-avenin antibodies in both groups at the end as compared to the beginning of the study, (p<0.001), but no difference was found between the two groups. IgA titres already declined after 3 months. IgG titres, although significantly decreased, remained high in the majority of patients in both groups. Nitric oxide levels were high in four of the analysed samples. Conclusions. Oats per se, do not seem to produce a humoral immune reaction in children with CD when given in an otherwise gluten-free diet, indicating that the reaction requires gluten challenge. Anti-avenin antibodies were equal in the two study groups, and these findings strengthen the clinical impression that oats can be tolerated by the majority of patients with CD.

Time for a change to assess and evaluate body temperature in clinical practice.

The definition of normal body temperature as 37 degrees C still is considered the norm worldwide, but in practice there is a widespread confusion of the evaluation of body temperature, especially in elderly individuals. In this paper, we discuss the relevance of normal body temperature as 37 degrees C and consequences in clinical practice. Our conclusion is that body temperature should be evaluated in relation to the individual variability and that the best approach is to use the same site, and an unadjusted mode without adjustments to other sites. If the baseline value is not known, it is important to notice that frail elderly individuals are at risk of a low body temperature. In addition, what should be regarded as fever is closely related to what is considered as normal body temperature. That is, as normal body temperature shows individual variations, it is reasonable that the same should hold true for the febrile range.

Screening for coeliac disease in apparently healthy blood donors

As gliadin is a common food antigen for large people, we have developed an ELIS A for the detection of class‐specific antigliadin antibodies (AGA), with which sera from a large population of apparently healthy blood donors was analysed. A very high prevalence (1/256) of positive AGA was found. However, the positive predictive value (+PV) was found to be very low, 20% for IgA‐AGA and 0% for IgG‐AGA alone. When screening large populations with no or few symptoms, it is desirable to have a high +PV to avoid unnecessary biopsies. IgA antiendomyisum antibodies (IgA‐EM A) were evaluated both as a single test and in combination with IgA‐AGA. When screening individuals for CD in a population with no or few symptoms the easy and cheap IgA‐AGA assay should be used as a first test and the IgA‐EMA to verify the diagnosis and avoid unnecessary biopsies.