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Keywords:

  • adults;
  • coeliac disease;
  • population-based;
  • prevalence;
  • screening

Abstract.

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Objective. To determine the prevalence of coeliac disease in a population-based sample of Swedish adults.

Design. Population-based cross-sectional study.

Setting. Northern Sweden.

Subjects. A total of 1894 adults (76%) out of 2500 invited, randomly selected from the population register after stratification for age and sex.

Main outcome measures. Prevalence of biopsy verified coeliac disease, symptoms of undiagnosed cases, and results of antiendomysium and antigliadin serum antibody tests.

Results. Coeliac disease was confirmed by intestinal biopsy showing enteropathy in 10 individuals (seven women and three men), corresponding to a prevalence of 5.3 per 1000 (95% CI = 2.5–9.7). The majority of cases (eight out of 10) had not been diagnosed prior to the screening, although many had symptoms compatible with coeliac disease. All individuals with antiendomysium antibody positivity who were subjected to a small intestinal biopsy had enteropathy. Furthermore, all of them also had elevated levels of antigliadin antibodies type IgA and/or IgG.

Conclusions. Coeliac disease is common, albeit mostly undiagnosed, in Swedish adults. It is likely that the situation is no better in other countries. This highlights the importance of keeping coeliac disease in mind, and of promptly investigating individuals with unexplained, even mild, symptoms compatible with the disease. Serological markers, e.g. antigliadin and antiendomysium antibodies, are useful tools within this active case-finding strategy, although the final diagnosis should be based on an intestinal biopsy demonstrating enteropathy.


Introduction

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

From the early 1980s, the cumulative incidence of coeliac disease in Swedish children has increased from about 1 to 4 per 1000 births [ 1, 2], which makes childhood coeliac disease diagnosed in clinical practice more common than in any other country [ 3]. The causes of this unique increase are still unknown. It has been argued that changes in infant feeding practices, i.e. the introduction of gluten delayed until 6 months of age paralleled by increased amounts of gluten in the diet, may have provoked coeliac disease in genetically predisposed individuals who would otherwise have remained healthy until later in life, or perhaps for their entire life span [ 4–6].

The reported prevalence of coeliac disease in Swedish adults diagnosed in clinical practice is 1.0 per 1000 [ 7, 8], which supported the view that the lifetime risk of coeliac disease has indeed increased for children born in the 1980s and onwards. This view was, however, contradicted by a screening study of Swedish blood donors which surprisingly revealed a prevalence of 3.8 per 1000 [ 9], indicating that there is also a high prevalence of coeliac disease in age groups not affected by the change in infant feeding practices. Furthermore, this study suggested that, even in Sweden, most adult cases are undiagnosed. However, blood donors do not necessarily represent the population at large, and in Sweden as well as in most other countries population-based estimates of the prevalence have not been available. Therefore, the aim of the present study was to determine the prevalence of coeliac disease – previously diagnosed and undiagnosed – in a population-based sample of Swedish adults.

Subjects and methods

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

This cross-sectional study of coeliac disease amongst adults was performed in the two northernmost counties (Västerbotten and Norrbotten) of Sweden in conjunction with the 1994 WHO MONICA survey (The World Health Organization project of Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) [ 10]. The study population constituted all 318 359 inhabitants in the age range 25–74 years (December 1994). A sample of 2500 individuals was randomly selected from the population register stratified by age and sex. From each 10-year age cohort (25–34, 35–44, 45–54, 55–64 and 65–74 years), 250 men and 250 women were invited to participate. Calculated on the participation rate of 79% in the 1990 MONICA survey, the present study would be able to report a hypothetical prevalence of 4 per 1000 with a 95% confidence interval from 2 to 8 per 1000. Out of the 2500 individuals invited, 1921 agreed to participate in the survey at large, and complete data for the coeliac disease screening were obtained from 1894 individuals (76%), with a median age of 50 years and a male/female ratio of 1.0.

A questionnaire focusing on cardiovascular disease, but also including a question on previously diagnosed coeliac disease, was sent to the participants beforehand and brought to the health centre at the time of examination. Non-responders were reminded by telephone or mail. Later a telephone interview was performed with those participants who either responded positively to the question on already diagnosed coeliac disease or who fulfilled the criteria described below for being recommended to have a small intestinal biopsy. One individual who fulfilled the criteria had died before contact could be made and was excluded from the analysis. In the telephone interview, a semistructured questionnaire was used which aimed at symptoms indicative of untreated coeliac disease.

Blood samples were obtained by venipuncture and serum samples stored at –20 °C until analysis. A total of 1892 serum samples were analysed for levels of antigliadin antibodies of isotypes IgA and IgG and antiendomysial antibodies of isotype IgA. Serum samples were not analysed for the two individuals with previously diagnosed coeliac disease. To exclude IgA deficiency, total serum immunoglobulin A was analysed in all serum samples except the 79 samples in which elevated levels of antigliadin and/or antiendromysial antibodies type IgA were detected.

Antigliadin antibodies type IgA and IgG were analysed by enzyme-linked immunosorbent assay (ELISA) as described previously [ 11] but with minor modifications. Serum samples were diluted in phosphate-buffered saline (PBS), pH 7.4, 1/200 for IgA and 1/400 for IgG, and incubated in gliadin sensitized wells in microtitre plates for 1 h at 37 °C. Alkaline phosphatase-labelled IgA and IgG conjugates (Orion Diagnostica, Espo, Finland) were added and the plates incubated for 1 h at 37 °C.

Antiendomysial antibodies type IgA were analysed by immunofluorescence technique, using monkey oesophagus as antigen source (SciMedx, Denville, New Jersey, USA). Serum samples, diluted 1/20 in PBS, were incubated on the antigen-coated slides for 40 min at room temperature. The fluorescein-labelled antihuman IgA (F 204, DAKO A/S, Glostrup, Denmark) was diluted 1/30 in PBS containing Evan's blue counter stain, and incubated on the slides for 40 min at 37 °C. All slides were read by the same investigator under an Olympus fluorescence microscope at 100 times magnification. The presence of typical reticulin-like pattern was recorded. All positive samples were reanalysed using serial dilution (1/20, 1/80 and 1/320).

Serum IgA was analysed using a routine nephelometric method (Behring Nephelometer A, Behring Diagnostics, Marburg, Germany). Results below 1.0 g L−1 were reanalysed using a radioimmunodiffusion method (LC-Partigen Immunodiffusion Plates, Behring Diagnostics, Marburg, Germany). IgA deficiency was defined as values below 0.05 g L−1 [ 12].

Individuals who had elevated levels of antiendomysial antibodies type IgA or who were classified as IgA-deficient in combination with having elevated levels of antigliadin antibodies type IgG were recommended to have a small intestinal biopsy. When already diagnosed coeliac disease was reported in the questionnaire, the diagnosis was validated by information extracted from the medical records. The criterion for the diagnosis of coeliac disease was a biopsy from the small intestinal mucosa demonstrating enteropathy grade III to IV according to Alexander [ 13].

The study was approved by the Research Ethics Committee at Umeå University. Informed consent was obtained after the participants had received written and verbal information.

Results

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The results of the screening procedure are summarized in Fig. 1. Two participants reported previously diagnosed coeliac disease which, according to their medical records, had been confirmed by a small intestinal biopsy demonstrating enteropathy. IgA deficiency was found in 0.2% (4/1892), and those two individuals subjected to small intestinal biopsy both demonstrated a normal mucosa. Antigliadin antibodies type IgA and/or IgG were elevated in 23% (438/1892). Elevated levels of antiendomysial antibodies type IgA, with titres varying between 1/20 and 1/320, were found in 0.5% (9/1892). It should be noted that all nine individuals with elevated levels of antiendomysial antibodies type IgA also had elevated levels of antigliadin antibodies type IgA and/or IgG. All but one of the nine individuals with elevated levels of antiendomysial antibodies were subjected to intestinal biopsy, and the diagnosis of coeliac disease was confirmed in all of them. One woman with elevated levels of antiendomysial antibodies and symptoms compatible with coeliac disease, i.e. flatulence, diarrhoea and depression, refused biopsy.

image

Figure 1.  Results of the screening procedure for coeliac disease. The number of individuals in each group is given in italics. IgA deficiency was defined as total s-IgA < 0.05 g L−1. AGA, antigliadin antibodies; AEA, antiendomysial antibodies; IgA ,antibodies of type IgA; IgG, antibodies of type IgG; ±, above and below the cut-off level, respectively; ‘biopsy’, a small intestinal biopsy was performed; CD, coeliac disease confirmed with a biopsy from the mucosa of the small intestine showing enteropathy.

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Thus, coeliac disease had previously been confirmed or was confirmed as part of the study by intestinal biopsy in 10 individuals, corresponding to a prevalence of 5.3 per 1000 inhabitants (95% CI = 2.5–9.7) in the age interval 25–74 years. Coeliac disease was more common amongst women (seven women and three men) and in the older age groups, with the highest prevalence in the interval 55–64 years (five out of 10 cases). The majority of cases (eight out of 10) had not been diagnosed prior to the screening, although many had symptoms or other diseases compatible with coeliac disease ( Table 1) [ 14].

Table 1.   Mean plasma lipoprotein concentration and mean processed plasma volume with LDL apheresis during concomitant simvastatin and atorvastatin therapy Table 1 Characteristics of the coeliac disease cases Thumbnail image of

Discussion

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

This population-based screening study on coeliac disease prevalence amongst randomly selected Swedish adults, conducted in the northern part of Sweden, revealed a prevalence of 5.3 per 1000 with an overrepresentation of women in older age groups. The majority of cases were undiagnosed prior to the study, although many had symptoms compatible with coeliac disease. This prevalence may be an underestimation: (i) one woman with elevated levels of antiendomysial antibodies and symptoms suggestive of coeliac disease refused biopsy and was excluded; (ii) additional cases of coeliac disease might be present amongst those who only had elevated levels of antigliadin antibodies, and amongst those without elevated levels of any of the serological markers; and (iii) when inviting individuals to submit to health examinations, there is probably a selection bias towards the healthier part of the population [ 15]. However, it should be noted that the diagnostic criteria used in the present and other screening studies on coeliac disease may give some overestimation of prevalence, as the diagnosis should preferably be based on the demonstration of enteropathy followed by improvement of symptoms and histology on a gluten-free diet [ 14].

The study sample of 2500 adults was randomly selected after stratification for age within 10-year strata. As a consequence, the sample does not reflect the age and sex distribution of the Swedish adult population. Adjusting the recorded prevalence to the population structure would decrease the prevalence from 5.3 to 4.6 per 1000. Although the study was restricted to the northern part of Sweden, there is no reason to believe that the results would not be representative of the adult population at large.

Several studies based on coeliac disease cases diagnosed in clinical practice have shown an overrepresentation amongst women, especially in older age groups [ 16–18]. It has been questioned whether these sex- and age-specific differences in prevalence reflect a true difference or if they are simply the result of a higher case ascertainment in this group. Our results, which are based on a population-based screening, support the contention that there are real differences. These in turn may reflect the fact that autoimmune disorders are overrepresented in women of this age.

The prevalence found in our population-based study was higher than in the Swedish blood donor study [ 9], albeit that the 95% confidence limits are overlapping. The latter study revealed a biopsy-verified prevalence of 3.8 per 1000 (95% CI = 1.5–7.7), which most likely is an underestimation. A major reason for this is that blood donors are not representative of the population at large.

Previous Swedish studies on coeliac disease in adults diagnosed in clinical practice have shown an estimated prevalence of 1.0 per 1000 [ 7, 8]. This is not contradictory to the finding in the present study, as we found that only a minority of the coeliac disease cases had been diagnosed before the screening. Frequent reports of increased morbidity in individuals with untreated coeliac disease, e.g. diarrhoea, anaemia, psychiatric illness, osteopenia and even malignant disease [ 14], emphasize the importance of early and correct diagnosis followed by adherence to a gluten-free diet. Therefore, an active case-finding strategy has been suggested [ 19, 20], whilst screening of the general population is still under debate. In a screening situation the costs for analyses must be limited and unnecessary small intestinal biopsies avoided. Therefore our results would support a serial testing approach, i.e. the use of an antigliadin antibody test as a first step, and if positive, a follow-up with an antiendomysial antibody test [ 21]. The diagnosis of coeliac disease should be based on histology, although our study confirms the high specificity of antiendomysial antibodies type IgA.

That coeliac disease is common, albeit largely undiagnosed amongst adults, is not unique to Sweden ( Table 2). Thus, so far, all studies, with the exception of the one from Estonia [ 26], have discovered that coeliac disease is to a large extent undiagnosed.

Table 2.   Prevalence of coeliac disease in different countries according to screening studies Thumbnail image of

In conclusion, this study, which is one of the very first population-based studies on coeliac disease, reveals a high prevalence of the disease in Swedish adults. It should be noted that these adults were not affected by the change in feeding practices advocated to have caused the dramatic increase in childhood coeliac disease. An important observation is that the majority of these adult coeliac disease cases were undiagnosed prior to the screening, which is in agreement with other studies. This highlights the importance of keeping coeliac disease in mind, and of promptly investigating all individuals with unexplained, even mild, symptoms compatible with the disease. Serological markers, e.g. antigliadin and antiendomysium antibodies, are useful tools within this active case-finding strategy, although the final diagnosis should be based on an intestinal biopsy demonstrating enteropathy.

Acknowledgements

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

We thank Ms Carina Lagerqist for skilful laboratory analyses and our colleagues at the Departments of Medicine in northern Sweden for performing the intestinal biopsies. We gratefully acknowledge the assistance of the Northern Sweden MONICA Project. Financial support from The Swedish Council for Forestry and Agricultural Research, the Swedish Foundation for Health Care Sciences and Allergy Research, and the Swedish Foundation for Research on Asthma and Allergy, are gratefully acknowledged.

References

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
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Received 24 February 1998; accepted 15 May 1998.