Lars Danielsson

Epidemic of coeliac disease in Swedish children.

Coeliac disease has emerged as a public health problem. The aim of the present study was to analyse trends in the occurrence of symptomatic coeliac disease in Swedish children from 1973 to 1997, and to explore any temporal relationship to changes in infant dietary patterns. We established a population‐based prospective incidence register of coeliac disease in 1991, and, in addition, retrospective data from 1973 were collected. A total of 2151 cases fulfilled the diagnostic criteria. Furthermore, we collected national data on a yearly basis on duration of breastfeeding, intake of gluten‐containing cereals and recommendations on when and how to introduce gluten into the diet of infants. From 1985 to 1987 the annual incidence rate in children below 2 y of age increased fourfold to 200‐240 cases per 100 000 person years, followed from 1995 by a sharp decline to the previous level of 50‐60 cases per 100 000 person years. This epidemic pattern is quite unique for a chronic disease of immunological pathogenesis, suggesting that prevention could be possible. The ecological observations made in this study are compatible with the epidemic being the result, at least in part, of a change in and an interplay among three factors within the area of infant feeding, i.e. amount of gluten given, age at introduction of gluten, and whether breastfeeding was ongoing or not when gluten was introduced. Other factor(s) may also have contributed, and the search for these should be intensified.

Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic

Objective: Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12-year-olds born during the epidemic (1993), including both symptomatic and screening detected cases. Patients and Methods: All sixth-grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)-IgA (Celikey), and serum-IgA, and some for tTG-IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease. Results: Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7–11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17–23). The total prevalence was 29/1000 (95% CI 25–33). Conclusions: The celiac disease prevalence of 29/1000 (3%)—with two thirds of cases undiagnosed before screening—is 3-fold higher than the usually suggested prevalence of 1%. When these 12-year-olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast-feeding, which might have contributed to this unexpectedly high prevalence.

Prevalence of Childhood Celiac Disease and Changes in Infant Feeding

OBJECTIVES: Between 1984 and 1996, Sweden experienced an “epidemic” of clinical celiac disease in children <2 years of age, attributed partly to changes in infant feeding. Whether infant feeding affects disease occurrence and/or the clinical presentation remains unknown. We investigated and compared the total prevalence of celiac disease in 2 birth cohorts of 12-year-olds and related the findings to each cohort’s ascertained infant feeding. METHODS: A 2-phase cross-sectional screening study was performed in which 13 279 children from 2 birth cohorts participated: children born during the epidemic (1993) and children born after the epidemic (1997). Previously diagnosed cases were reported and confirmed. Blood samples were analyzed for serological markers and children with positive values were referred for small intestinal biopsy. Infant feeding practices in the cohorts were ascertained via questionnaires. Prevalence comparisons were expressed as prevalence ratios. RESULTS: The total prevalence of celiac disease was 29 in 1000 and 22 in 1000 for the 1993 and 1997 cohorts, respectively. Children born in 1997 had a significantly lower risk of having celiac disease compared with those born in 1993 (prevalence ratio: 0.75; 95% confidence interval: 0.60–0.93; P = .01). The cohorts differed in infant feeding (specifically, in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding). CONCLUSIONS: A significantly reduced prevalence of celiac disease in 12-year-olds indicates an option for disease prevention. Our findings suggest that the present infant feeding recommendation to gradually introduce gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding, is favorable.

Increasing incidence of childhood coeliac disease in Sweden. Results of a national study

A survey of the incidence of coeliac disease was carried out by asking all 43 paediatric departments in Sweden to report the number of children born between 1978 and 1987 in whom coeliac disease had been diagnosed. Thirty‐four departments representing a population of 7.18 million reported 1944 cases of coeliac disease among 804935 children born between 1978 and 1987. The cumulative incidence of coeliac disease was 1.7 per 1000 live births in children born between 1978 and 1982 and doubled to 3.5 per 1000 live births in children born after 1982. The highest incidence was found in the southern and south‐eastern regions of the country. The observed increase may have been influenced by changes in infant feeding practices such as the postponed age of introduction of gluten from four to six months of age and an increase in gluten content of proprietary baby foods.

How do Swedish paediatric clinics diagnose coeliac disease? Results of a nationwide questionnaire study

Background and aim: Diagnosis of coeliac disease is based on the demonstration of enteropathy in a small bowel biopsy. Correct diagnosis is of utmost importance, since the need for dietary management is life long, and inadequate treatment may lead to potentially serious complications. The Swedish Working Group for Paediatric Coeliac Disease has published guidelines for the diagnosis of childhood coeliac disease. The present questionnaire was designed in order to create the basis for revision of those guidelines. Methods: In 2004, a nationwide questionnaire concerning current diagnostic routines was sent to all 45 paediatric clinics performing small bowel biopsy. All clinics responded. Results: All clinics base their diagnosis on small bowel biopsy findings at presentation. Furthermore, in 24 (53%) of the clinics, children with suspected coeliac disease are investigated by small bowel biopsy both at presentation and follow‐up while on a gluten‐free diet. Eighteen (40%) of the clinics employ a different diagnostic routine for children under 2 y of age than for those older than 2 y. All clinics use coeliac serological testing at various stages of the diagnostic procedure.

Accuracy in Celiac Disease Diagnostics by Controlling the Small-bowel Biopsy Process.

Objectives:In a Swedish celiac disease screening study (Exploring the Iceberg of Celiacs in Sweden), we systematically reviewed the clinical diagnostic procedures with the aim to evaluate the diagnostic accuracy and to take advantage of lessons learned for improving diagnostic routines. Materials and Methods:A school-based celiac disease screening study involving 5 Swedish centers, with 10,041 invited 12-year-olds with 7567 consenting participation. All 192 children with elevated serological markers were recommended to undergo small-bowel biopsy, performed and evaluated according to local clinical routines. All of the mucosal specimens were reevaluated by 1 and, when needed, 2 expert pathologists to reach diagnostic consensus. Results:Small-bowel biopsies were performed in 184 children: 130 by endoscopy and 54 by suction capsule. Endoscopic biopsies were inconclusive in 0.6%, compared with 7.4% of biopsies by suction capsule. A patchy enteropathy was found in 9.1%. Reevaluation by the expert pathologist resulted in 6 additional cases with celiac disease and 1 cleared. Sixteen children with normal or inconclusive biopsies, 4 after endoscopy, and 12 after suction capsule were endoscopically rebiopsied, resulting in another 8 cases. The celiac disease prevalence of 30 of 1000 (95% confidence interval 26–34) was not statistically different from that previously reported. Conclusions:The present review revealed the importance of controlling each step of the diagnostic procedure. Several cases would have been missed by relying only on local routines. To improve the quality of childhood celiac disease diagnostics, we recommend multiple endoscopic biopsies from both proximal and distal duodenum and standardized evaluation by a pathologist with good knowledge of celiac disease.

Health-related quality-of-life in children with coeliac disease, measured prior to receiving their diagnosis through screening

Objective To compare the health-related quality-of-life (HRQoL) of children with screening-detected coeliac disease (CD), before they learned of their diagnosis, with that of children without CD and in those previously diagnosed with CD. Methods In a cross-sectional CD screening study (‘ETICS’: Exploring the Iceberg of Coeliacs in Sweden), of 10,041 Swedish 12-year-olds invited, 7567 (75%) consented to participate, and 7208 (72%) children without previously diagnosed CD had serological markers analysed. Before the screening results were known, 7218 children (72%) and 6524 of their parents (65%) answered questionnaires. Questionnaires included the Swedish child-friendly pilot version of the EQ-5D instrument and proxy version of the EQ-5D instrument, which are generic tools used to describe HRQoL. Results We found no significant difference in HRQoL between the groups of children with screening-detected CD, without CD, and those previously diagnosed with CD. Conclusion The HRQoL reported by 12-year-olds with screening-detected CD, before they learned of their diagnosis, was not worse than that of the children without CD or those previously diagnosed with CD. Thus, mass screening for CD should not be justified on the basis that children with unrecognized CD have a poor HRQoL. However, because these children rated their HRQoL before diagnosis and treatment, they may not have recognized or perceived symptoms as severe enough to seek medical attention which demonstrates how difficult clinical/active case finding can be. Mass screening may still, therefore, be considered if the aim is early detection and prevention of future complications.

Serum zinc in small children with coeliac disease.

In coeliac disease (CD) there is a gluten‐induced small bowel enteropathy leading to malabsorption of various nutrients, vitamins and trace elements. Low levels of serum zinc have been reported in adults with untreated CD. In the present study we related the serum concentration of zinc to the morphology of the small bowel mucosa in 58 children, all under 4 years of age and under investigation for coeliac disease. The mean serum concentration of zinc (mean ± SD; μmol/L) was significantly lower in children with untreated CD (9.7 ± 2.0) (n = 11) compared to non‐coeliac children without enteropathy (15.1 ± 2.3) (n = 16) (p < 0.001), coeliac children on a gluten‐free diet without enteropathy (14.2 ± 1.6) (n = 14) (p < 0.001), coeliac children on gluten challenge with enteropathy (14.1 ± 2.1) (n = 12) (p < 0.001) and coeliac children on gluten challenge without enteropathy (13.8 ± 1.9) (n = 6) (p < 0.005).

Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine.

Aim:  Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening‐detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern.

Small bowel biopsy in Swedish paediatric clinics

AIM A correct diagnosis of coeliac disease, one of the most common chronic diseases in Swedish children, demands small bowel biopsy, which can be performed endoscopically or by means of a peroral capsule. Recently there was a debate among Swedish paediatric gastroenterologists, with some advocating the cessation of capsule biopsy in favour of endoscopic biopsies. To gain information on which to base a recommendation for which technique to use, the Swedish Working Group for Childhood Coeliac Disease was commissioned to carry out a national questionnaire study on current small bowel biopsy routines in Swedish paediatric clinics. METHODS A questionnaire concerning biopsy routines in the year 2000 was sent to all paediatric clinics performing biopsies. A reply was obtained from 39 of 40 clinics, covering 98% of the Swedish population. RESULTS Some 1400 biopsies were performed, 64% of which were capsule biopsies and 36% endoscopic. Three clinics performed all biopsies endoscopically and 11 clinics all via a capsule. At endoscopy all children were under deep sedation or full anaesthesia, while most children undergoing capsule biopsy were under light or deep sedation. The oxygen saturation was monitored during endoscopy but less often or never during routine capsule biopsy. The presence of the parents during biopsy varied according to the degree of sedation: at 97% of the clinics performing capsule biopsy on children under light sedation, the parents were present during the whole procedure, whereas no parents were present at clinics where the biopsy was performed endoscopically under anaesthesia. CONCLUSION Compared with the results of a similar questionnaire concerning biopsy routines performed in the early 1990s, children are now more effectively sedated. Furthermore, there is an obvious trend from capsule towards endoscopic biopsy. Both the endoscopic and the capsule biopsy techniques are useful and satisfactory for obtaining small bowel mucosal samples providing that the children are effectively sedated. For practical and economic reasons the capsule biopsy technique will probably continue to be used, although to a lesser extent than today.