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| Journal of the New Zealand Medical Association,
20-February-2004, Vol 117 No 1189
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A thirty-year (1970–1999) study of coeliac disease in
the Canterbury region of New Zealand
Bramwell Cook, Robert Oxner, Bruce Chapman, Martin Whitehead
and Michael Burt
Coeliac disease (CD) is an enteropathy, affecting mainly the
proximal small intestine. It can be defined as an intolerance in genetically
susceptible people to certain storage proteins found in the cereals wheat,
barley and rye.
Incidence and prevalence studies of clinically recognised
CD, mostly from Europe and the United Kingdom, have shown significant changes
over the years, with both rising and falling trends
reported.1–11
This paper presents an experience of CD in the Canterbury
region of New Zealand over 30 years from 1970 to 1999, and demonstrates an
increase in the incidence of clinically recognised CD during the latter half of
this period.
MethodsFor this study, CD was defined
by small-intestine biopsy histology showing crypt hyperplastic villous atrophy
with intra-epithelial lymphocytosis consistent with the destructive Type 3
lesion as described by Marsh.12 For
consistency, subjects with histology of Marsh Types 1 and 2 were excluded, as
these lesions were not fully appreciated in the earlier years of the study.
Subjects with dermatitis herpetiformis were included in the study if an
intestinal biopsy had shown histologic findings compatible with a diagnosis of
CD. The age of diagnosis of CD was deemed to be the subject’s age at the
time of the first intestinal biopsy supporting the diagnosis.
Biopsies were obtained by capsule (Baker-Hughes or
Watson) or by Quinton-Rubin tube from the region of the duodenojejunal flexure
or distal to this point in all patients up to 1989. In 1989 endoscopic biopsies
from as far around the duodenal loop as possible became standard practice for
adults.13 For children endoscopic biopsies
replaced capsule biopsies (Paediatric Watson) during the period 1992 to
1994.
Anti-gliadin antibody (AGA) and anti-endomysial
antibody (EMA) tests were introduced in 1987 and 1994 respectively. The accepted
normal range in our laboratory for AGA IgG was 0–70 units, and for AGA IgA
0–15 units. EMA was detected by indirect immunofluorescence using primate
oesophagus as the substrate with sera tested at a dilution of 1:5. Anti-tissue
transglutaminase antibody tests (TTG) were introduced in 2000 after completion
of this study.
The period covered in this study was 1 January 1970 to
31 December 1999. A database commenced during 1969 by one author formed the
basis for the study. Records held by all gastroenterologists in public and
private practice, and by the paediatric, pathology and dietary departments in
the region, were reviewed to identify patients in whom a diagnosis of CD had
been considered. A population prevalence study performed in 1996–1997
identified 10 subjects who were also included in this
study.14 The authors estimate that greater than
95% of cases of CD diagnosed in the region were ascertained in this
study.
To be included in the study patients were required to
be resident in the Canterbury region at the date the first intestinal biopsy
consistent with a diagnosis of CD was obtained. Population demographics for the
Canterbury region over the study period were calculated using published,
five-yearly census data. In 1971 and 1996 the populations were respectively 341
141 and 386 792, with 38.7% and 27.5% under the age of 20 years, and 13.7% and
16.8% aged 60 years and over. The female to male sex ratios were 0.96:1 for
those under 20, and 1.32:1 for those aged 60 and over. In the Canterbury region
there were approximately 146 700 births in the period 1970–1999. Incidence
figures were calculated using population data abstracted from these census
reports and from birth statistics.
ResultsOver the 30-year study period, 416
patients fulfilled the criteria for a diagnosis of CD as defined in this study.
Fifteen subjects (aged 4–46 years) had been commenced on a gluten-free
diet for periods of less than one year up to ten years before the diagnosis was
confirmed by gluten challenge studies and by small-bowel biopsy histology. Of 15
subjects with dermatitis herpetiformis who had small biopsies, 11 showed
histology consistent with CD. These 11 are included in the study.
EMA testing was introduced in 1994. Of 214 subjects tested
at the time of diagnosis, 195 (91%) were positive, 6 weak positive, 2 atypical
positive, and 11 negative (5%). Of the 11 subjects with a negative test, two
were reported on a subsequent test to be positive. Of the remaining nine
subjects with a negative test serum, IgA levels were known for six, three (50%)
of whom proved to be serum IgA deficient (<0.1 g/l). Selective IgA deficiency
is associated with CD and is a recognised explanation for a negative EMA test
based on an IgA antibody.15
For the 195 subjects with a positive EMA, parallel AGA tests
were available for 164. AGA IgG levels were elevated (>70) in 106 (65%) of
these and AGA IgA levels elevated (>15) in 106 (65%). AGA tests were
available for 10 of the 11 subjects with a negative EMA test. AGA IgG was
elevated in seven (70%) and AGA IgA in four (40%). In the three subjects with
selective IgA deficiency, AGA IgG was elevated and AGA IgA not detected. Seventy
one subjects were recognised to have CD between the introduction of AGA in 1987
and EMA in 1994. AGA results were known for 41 subjects. AGA IgG levels were
elevated in 26 (63%), and AGA IgA levels elevated in 27 (66%).
Table 1 presents by year from 1970 to 1999 the numbers of
subjects recognised to have CD. The overall incidence was 2.2/100 000/year
rising from 1.4/100 000/year (1970 to 1972) to 12.9/100 000/year (1997 to 1999).
From 1970 to 1983 the number of new cases recognised each year showed no
detectable trend (range 1–7/year, average 4.8/year). Thereafter the
numbers recognised each year showed a progressive rise (range
5–55/year).
Table 1. Numbers of subjects diagnosed as having
coeliac disease between 1970 and 1999
*incidence
figures have been calculated using census data
Sixty two children (age 0–12 years) were found to have
CD, 27 in the last four years of the study period, giving a cumulative incidence
of 0.40/1000 births. The numbers of children recognised each year to have CD
began to rise in the 1990s, ten years later than the rise recorded in adults.
Thirteen children were in their second year of life, the youngest child
identified being 13.5 months of age.
Table 2. Number of diagnoses of coeliac disease made
during each decade of life
F = female; M = male
*this group is presented for the calculation of
population-adjusted ratios, as census statistics are recorded for the age groups
0–4 years, 5–14 years, and 15–19 years, thereafter by decade,
20–29 years, 30–39 years, etc
The age and sex distributions of the study population are
given in Table 2. Females numbered 283 and males 133 giving a female to male
ratio of 2.1:1. The female to male ratio of the subjects in the first two
decades of life was 1.3:1, 1.4:1 corrected for the population at risk. In the
third decade this ratio rose to 3.4:1, 3.3:1 corrected for the population at
risk, and thereafter fell. For those over 60 years at the time of diagnosis the
female to male ratio was 1.55:1, 1.15:1 corrected for the population at
risk.
The incidence of newly recognised CD over the 30-year study
period, corrected for the populations at risk, was 2.3/100 000/year for those
under 20 years of age, and 2.9/100 000/year for those aged 60 years and
over.
DiscussionIn our study the incidence of newly
diagnosed CD showed no detectable trend between 1970 and the mid 1980s.
Thereafter the incidence of adult CD steadily increased followed in the early
1990s by a rise in childhood CD. Possible explanations for the increasing
incidence are an increased awareness of the disease and its wide spectrum of
clinical manifestations,16 replacement of
capsule biopsies by endoscopic biopsies (adults 1989, children 1992–1994),
and the introduction of AGA (1987) and EMA (1994) testing.
Greater awareness of CD and of its more subtle
presentations, both by medical practitioners and by the public have undoubtedly
contributed to the increased recognition of CD during the study period.
Small-bowel biopsies were initially obtained by capsule techniques, but with
advances in technology, endoscopic small-bowel biopsy became widely available
and acceptable.13 Furthermore, endoscopists
learned to recognise the macroscopic appearances of CD in the
duodenum,17 and some later cases were diagnosed
during endoscopy performed for other clinical reasons.
The development of specific and reliable antibody tests such
as AGA and EMA antibody tests, have almost certainly contributed to the
increased diagnosis of CD during the study period. EMA was positive in over 90%
of subjects. Both IgG and IgA AGA have significantly lower sensitivities
(60–70%) and are known to be less specific than
EMA.16 This study clearly indicates that,
because of its greater sensitivity, EMA is the screening test of choice if only
a single assay is performed. Despite this, serological screening will miss
10–20% of cases of CD,18,19 and
small-bowel biopsy should still be performed in subjects in whom there is a
strong clinical suspicion of CD.
A true rise in the incidence of CD during the study period
cannot be excluded. CD has a clear genetic
predisposition,20 but there is no suggestion
that changes in population genetics occurred during the study. Exposure to wheat
with a higher gluten content following the deregulation of the wheat industry in
1987 is a possible factor, but this remains speculative. Trigger factors, as yet
poorly identified, have also been postulated to explain observed variations in
the incidence of CD.4
Three studies in New Zealand have shown a low cumulative
incidence of CD in childhood (0–12 years): 0.35/1000 births in
Otago,21 0.1/1000 births in
Wellington,22 and in our study 0.40/1000 births
(1.40/1000 births in the last three years). In our study the youngest child at
the time of diagnosis was 13.5 months old. Much higher incidence figures for
childhood CD have been reported,1,4,8,9,23
although significant fluctuations, both rising and
falling,1–11 have occurred over the
years. In Sweden a steady increase in the incidence of childhood CD has been
observed,9,10 reaching 2.93/1000 births, with
many children diagnosed before their first
birthday.9 In a more recent study the annual
incidence of CD in children below the age of two years, from 1985 to 1987,
increased fourfold to 200–240 cases per 100 000 person years, followed
from 1995 by a sharp decline to the previous
level.11 In neighbouring Denmark the incidence
of CD in childhood is considerably lower at 0.10/1000 births, and the diagnosis
is made at an older age.24 The officially
recommended diets of the two countries differ substantially, in Sweden
containing over 40 times more gliadin than in Denmark at the age of eight
months, and four times more at the age of 12
months.24 However, the prevalence of CD in
blood donors is similar in both countries.25
These findings suggest that the clinical presentation of childhood CD is
affected by the age at which gluten is introduced into the diet. The Paediatric
Society of New Zealand has recommended that wheat be withheld from infants until
at least nine months of age, and until twelve months in those with a family
predisposition to allergies.26,27
Our study shows a female to male ratio of 2.1:1 (Table 2), a
female predominance in keeping with published
studies.4,28 For people diagnosed during the
first two decades of life the female to male ratio was 1.4:1. During the fourth
decade the number of females greatly outnumbered males by 3.3:1, thereafter
gradually declining until the seventh decade and older when this ratio fell to
1.15:1. Similar findings have been recorded by
others.28 The excess of females over males in
the third and fourth decades is best explained by the extra nutritional demand
sustained by women as a result of menstruation, pregnancies and lactation, which
precipitates symptoms and diagnosis.
Hankey and Holmes drew attention to CD being as much a
disease of the elderly as of children, finding that 16% of their patients with
CD (19% of those aged 15 years and over) were diagnosed in their seventh decade
and beyond.28 We agree, finding in our study
that 12% (15% of those aged 15 years and over) were into their seventh decade
and beyond at time of diagnosis. Twenty per cent were under the age of 20 years
at the time of diagnosis. In our study, adjusting for the population at risk,
the diagnosis of CD was similar in those aged 60 years and over (2.9/100
000/year) and those under 20 years of age (2.3/100 000/year).
Of 703 patients with CD reported by Logan et al, 10.5% had
dermatitis herpetiformis.4 In our study of 416
subjects only 3% had dermatitis herpetiformis. We suspect that, in our region,
there are a significant number of subjects with dermatitis herpetiformis in whom
the possibility of CD has not been entertained or not confirmed by
biopsy.
The prevalence of adult CD in Christchurch has been reported
as 1:83,14 consistent with reported prevalence
rates in adults of between 1:83 and
1:200.29–33 In children, prevalence rates
of 1:85 and 1:184 have been reported.34,35 With
a population of about 350 000 in the Canterbury region there could be as many as
4000 subjects with CD, of whom about 600 are presently known. While many will be
free of significant symptoms and/or medical consequences there remain a
considerable number who may benefit from a gluten-free diet.
In summary, this 30-year experience of CD has demonstrated
an increasing incidence of biopsy-proven cases of CD in the Canterbury region of
New Zealand. CD is more common in females, especially during the reproductive
years, but may be found in either sex and at all ages of life. Possible reasons
for the observed increase include a greater awareness of CD, the use of
endoscopic rather than capsule biopsies and the introduction of sensitive and
specific serological tests for CD.
Author information:
H Bramwell Cook, Gastroenterologist, Department of Gastroenterology,
Christchurch Hospital; Robert B Oxner, Physician, Thames Hospital; Bruce A
Chapman, Gastroenterologist, Department of Gastroenterology; Martin R Whitehead,
Anatomical Pathologist, Department of Pathology; Michael Burt,
Gastroenterologist, Department of Gastroenterology, Christchurch
Hospital
Acknowledgements: We
thank Drs GD Abbott, ML Barclay, AG Ross, PF Sheppard, and WD Troughton, and
members of the Paediatric and Dietary Departments, Christchurch Hospital, for
assistance in the enrolment of subjects.
Correspondence: Dr
Michael Burt, Department of Gastroenterology, Christchurch Hospital, PO Box
4710, Christchurch. Fax: (03) 364 0419; email: michael.burt@cdhb.govt.nz
References:
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