Incidence of inflammatory bowel disease across Europe: Is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD)

Abstract

It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe.
For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition.
Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age.
The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.

Full text

Gut
1996;
39:
690-697
Incidence
of
inflammatory
bowel
disease
across
Europe:
is
there
a
difference
between
north
and
south?
Results
of
the
European
collaborative
study
on
inflammatory
bowel
disease
(EC-IBD)
S
Shivananda,
J
Lennard-Jones,
R
Logan,
N
Fear,
A
Price,
L
Carpenter,
M
van
Blankenstein,
and
the
EC-IBD
Study
Group
(see
appendix
for
committees,
participants,
and
addresses)
Abstract
Background-It
has
been
suggested
that
the
incidence
of
inflammatory
bowel
disease
(IBD),
which
includes
ulcerative
colitis
(UC)
and
Crohn's
disease
(CD),
is
three
or
more
times
higher
in
northern
than
in
southern
Europe.
The
aim
of
this
EC
funded
study
was
to
investigage
this
apparent
variation
by
ascertaining
the
incidence
of
IBD
across
Europe.
Methods-For
the
period
1
October
1991
to
30
September
1993
all
new
patients
diagnosed
with
IBD
were
prospectively
identified
in
20
European
centres
ac-
cording
to
a
standard
protocol
for
case
ascertainment
and
definition.
Findings-Altogether
2201
patients
aged
15
years
or
more
were
identified,
of
whom
1379
were
diagnosed
as
UC
(including
proctitis),
706
as
CD,
and
116
as
in-
determinate.
The
overall
incidence
per
100000
at
ages
15-64
years
(standardised
for
age
and
sex)
of
UC
was
10.4
(95%
confidence
interval
(95%
CI)
7.6
to
13.1)
and
that
of
CD
was
5.6
(95%
CI
2.8
to
8.3).
Rates
of
UC
in
northern
centres
were
40%
higher
than
those
in
the
south
(rate
ratio
(RR)=1.4
(95%
CI
1-2
to
1.5))
and
for
CD
they
were
80%
higher
(RR=1.8
(95%
CI
1.5
to
2.1)).
For
UC
the
highest
reported
incidence
was
in
Iceland
(24.5,
95%
CI
17.4
to
31.5)
and
for
CD,
Maastricht
(The
Netherlands;
9.2,
95%
CI
6.5
to
11.8)
and
Amiens
(north
west
France;
9.2,
95%
CI
6.3
to
12.2).
The
lowest
incidence
of
UC
was
in
Almada
(southern
Portugal)
(1.6,
95%
CI
0.0
to
3.2)
and
of
CD
in
Ioannina
(north
west
Greece)
(0.9,
95%
CI
0.0
to
2.2).
An
unexpected
finding
was
a
differ-
ence
in
the
age
specific
incidence
of
UC
in
men
and
women
with
the
incidence
in
women
but
not
men
declining
with
age.
Interpretation-The
higher
overall
inci-
dence
rates
in
northern
centres
did
not
seem
to
be
explained
by
differences
in
tobacco
consumption
or
education.
Nevertheless,
the
magnitude
of
the
ob-
served
excess
for
both
conditions
is
less
than
expected
on
the
basis
of
previous
studies.
This
may
reflect
recent
increases
in
the
incidence
of
IBD
in
southern
Europe
whereas
those
in
the
north
may
have
stabilised.
(Gut
1996;
39:
690-697)
Keywords:
Crohn's
disease,
ulcerative
colitis,
epidemiology.
Ulcerative
colitis
(UC)
and
Crohn's
disease
(CD)
are
chronic
inflammatory
bowel
diseases
(IBDs)
of
unknown
aetiology.
Previous
studies
have
suggested
that
the
incidence
of
these
diseases
may
vary
greatly
across
Europe,
with
higher
rates
being
found
in
the
north
than
the
south.'-19
For
example,
the
incidence
of
UC
found
in
Copenhagen,
Denmark
(8
1
per
100
000)
was
four
times
that
in
Bologna,
Italy
(1.9
per
100000).2
5
For
CD,
the
rate
of
4.1
per
100
000
in
Copenhagen
was
five
times
that
in
Galicia,
north
west
Spain
(0-8
per
100
000).i8
Such
patterns
could
be
due
to
different
study
designs
(for
example,
criteria
for
case
definition,
methods
of
case
ascertain-
ment,
or
the
time
period
of
investigation)
or
they
could
represent
real
differences
which
might
reflect
environmental
factors,
lifestyle,
or
genetic
susceptibility.
In
1988,
around
50
European
gastroenterol-
ogists
and
other
experts
attended
a
meeting
in
Rotterdam
to
plan
a
study
to
investigate
these
patterns.20
The
primary
aim
of
the
resultant
EC-IBD
study
was
to
measure
the
incidence
of
UC
and
CD
in
centres
in
the
north
and
south
of
Europe
prospectively
using
a
standard
protocol
for
case
ascertainment
and
data
analysis.
We
report
here
the
epidemiological
findings
for
the
two
year
study
period
1
October
1991
to
30
September
1993.
Methods
IDENTIFICATION
OF
STUDY
CENTRES
Potential
participating
centres
for
the
study
were
identified
at
the
Rotterdam
meeting
and
from
enquiries
resulting
from
an
announcement
in
the
Lancet.
2
Investigators
interested
in
participating
were
invited
to
take
part
if
their
centre
satisfied
the
following
requirements:
firstly,
the
centre
had
a
defined
catchment
area
with
up
to
date
population
data;
secondly,
diagnostic
facilities
for
high
quality
endoscopy,
radiology,
and
pathology
were
available
in
the
catchment
area;
thirdly,
the
centre
was
part
of
a
healthcare
system
which
offered
universal
cover
for
primary
and
specialist
services
with
an
established
system
for
referral
from
primary
to
secondary
care.
Correspondence
to:
Dr
S
Shivananda,
Gastroenterology
Unit,
Department
of
Internal
Medicine,
University
Hospital
Maastricht,
MEMIC-P.Debyeplein
1,
Postbus
616,
6200
MD
Maastricht,
The
Netherlands.
Accepted
for
publication
11
June
1996
690
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

Incidence
of
inflammatory bowel
disease
across
Europe:
is
there
a
difference
between
north
and
south?
The
study
aimed
to
include
centres
across
Europe.
From
northern
Europe,
the
study
areas
comprised
all
of
Iceland,
south
east
Norway
(including
Oslo),
Copenhagen
County
(Denmark),
Eastern
Health
Board,
Ireland
(including
Dublin),
City
of
Leicester
(United
Kingdom),
South
Limburg
including
Maastricht
(The
Netherlands),
Cities
of
Essen
and
Mulheim/Ruhr
area
(Germany),
and
the
Department
of
Somme
including
Amiens
(north
west
France).
In
the
south,
study
areas
comprised
Unita'
Sanitaria
Locale
1
including
Varese
(northern
Italy),
Unita'
Sanitaria
Locale
51
and
53
including
Crema
and
Cremona
(northern
Italy),
Reggio
Emilia
(northern
Italy),
metropolitan
Florence
(central
Italy),
Vigo
health
area
(north
west
Spain),
Sabadell
health
area
(north
east
Spain),
District
of
Braga
(northern
Portugal),
Ioannina,
(north
west
Greece),
Almada,
Seixal,
Sesimbra
(southern
Portugal),
Palermo
(Sicily,
southern
Italy),
Heraklion
(Crete,
Greece),
and
Beer
Sheva
(Israel).
CASE
DEFINITION
Diagnosis
of
IBD
was
on
the
basis
of
endoscopic
or
radiological
evidence,
or
both,
supported
whenever
possible
by
mucosal
biopsy
or
examination
of
a
specimen
from
operation.
UC
was
defined
as
continuous
mucosal
inflammation
without
granulomata
(by
biopsy),
affecting
the
rectum
and
some
or
all
of
the
colon
in
continuity
with
the
rectum
(by
endoscopy
or
radiology).
Proctitis
was
defined
as
macroscopic
inflammation
with
a
clearly
marked
upper
border
within
15
cm
of
the
anal
margin
and
for
the
purposes
of
this
report
was
classified
with
more
extensive
UC.
CD
was
defined
by
both
macroscopic
and
microscopic
features
using
the
Lennard-Jones
criteria.`
A
diagnosis
of
indeterminate
colitis
was
used
when
there
was
clear
evidence
of
IBD
but
insufficient
evidence
to
make
a
definitive
diagnosis
of
either
UC
or
CD.
Incident
cases
were
defined
as
all
new
cases
which
met
the
standard
diagnostic
definition
(with
probable
or
definite
diagnosis)
who
were
diagnosed
between
1
October
1991
and
30
September
1993
in
the
resident
population
of
the
defined
study
areas.
The
date
of
diagnosis
(taken
as
the
date
the
patient
was
informed
of
the
diagnosis)
was
used
for
the
analysis
of
incidence
of
disease.
Asymptomatic
cases
and
cases
detected
as
a
result
of
any
screening
activities
were
excluded.
CASE
ASCERTAINMENT
For
each
participating
study
centre,
all
general
practitioners
and
hospital
and
medical
specialists
working
in
the
field
of
gastro-
enterology
were
informed
of
the
study.
They
were
asked
to
identify
all
new
patients
seen
during
the
study
period
with
symptoms
of
persistent
or
relapsing
diarrhoea
or
blood
or
mucus
in
their
stools
for
more
than
three
weeks
or
abdominal
pain
and
weight
loss
without
evident
cause.
To
achieve
as
complete
an
as-
certainment
of
incident
cases
as
possible,
investigators
in
each
centre
regularly
canvassed
general
practitioners
and
relevant
specialists
both
within
and
in
the
periphery
of
the
study
area
by
post,
telephone,
or
personal
visit.
Exact
methods
of
case
finding
varied
between
centres.
These
included
regular
searches
of
endoscopic,
radiological,
and
pathological
records
and
sometimes
reports
by
pharmacists
of
prescriptions
issued
for
drugs
used
to
treat
IBD.
Patient
self
help
groups
were
contacted
and
doctors
were
regularly
reminded
of
the
study
at
local
medical
meetings
and
in
local
medical
newsletters.
DATA
COT
L
CTION
To
achieve
consistency
of
methods
between
centres,
two
initial
meetings
of
investigators
from
all
centres,
and
three
follow
up
meetings
during
the
study
period,
were
held.
Most
centres
formed
multidisciplinary
teams
to
review
the
diagnostic
and
epidemiological
data
before
recording
them
on
the
incidence
data
form.
An
external
review
team
visited
Greek,
Iberian,
Italian,
and
Scandinavian
groups
for
regional
case
reviews
and
the
principal
Investigator
(SS)
went
on
'site
visits'
to
all
but
one
of
the
centres
to
review
the
local
study
protocol,
the
case
ascertainment
procedures,
and
the
quality
of
data
recorded
on
the
incidence
data
form
and,
when
necessary,
suggested
improvements.
Each
incidence
data
form
had
a
unique
identifying
number
and
contained
a
patient
consent
form.
Patient
data
were
collected
on
sociodemographic
character-
istics,
educational
attainment,
current
occupa-
tion,
smoking
habits,
oral
contraceptive
use,
main
symptoms
and
their
duration,
endoscopic
and
radiographical
investigations,
biopsies
taken
and
histological
abnormalities,
and
any
surgery
performed.
On
the
basis
of
the
initial
investigations
the
diagnosis
was
recorded
as
UC,
CD,
proctitis
only,
indeterminate
IBD,
or
other.
One
copy
of
the
data
form
was
then
sent
to
Rotterdam
for
data
processing.
One
year
after
diagnosis
the
data
form
was
updated
with
the
addition
of
data
referring
to
any
changes
in
diagnosis,
disease
extent,
further
surgery,
and
drug
use
for
IBD
in
that
year
and
sent
to
Rotterdam.
STATISTICAL
ANALYSIS
Age,
sex,
and
disease
specific
incidence
rates
(per
100
000)
for
each
study
area
were
calculated
by
dividing
the
numbers
of
new
cases
in
each
category
of
age
and
sex
by
the
corresponding
estimated
numbers
of
person-
years
at
risk
based
on
the
population
statistics
for
each
area.
Children
and
adolescents
under
the
age
of
15
were
excluded
as
there
were
doubts
about
completeness
of
ascertainment
in
this
age
group
in
some
centres.
Centre
specific
direct
age
and
sex
stan-
dardised
incidence
rates
were
obtained
by
applying
the
age
specific
rates
to
the
European
Standard
Population23
using
10
year
age
groups
(15-25,
25-34,
35-44,
45-54,
55-64).
Approximate
95%
confidence
intervals
(95/o
CIs)
were
derived
from
the
standard
error
for
691
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

Shivananda,
Lennard-Jones,
Logan,
Fear,
Price,
Carpenter,
van
Blankenstein
the
logarithm
of
the
directly
standardised
rate.24
Data
for
patients
aged
over
64
were
excluded
from
calculation
of
the
directly
standardised
rates
due
to
the
problems
associated
with
completeness
of
case
ascer-
tainment
among
the
oldest
members
of
the
population
and
because
age
specific
population
counts
were
not
available
for
older
ages
in
all
centres.
To
examine
the
hypothesis
of
a
north-south
difference
in
the
incidence
of
IBD,
age
adjusted
rate
ratios
(RRs)
for
northern
centres
relative
to
those
in
the
south
were
estimated
by
the
method
of
maximum
likelihood.
This
involved
fitting
a
log
linear
model
to
the
centre,
age,
and
sex
specific
cases
and
person-years
using
the
EGRET
computer
package.25
Approximate
x2
tests
of
significance
were
obtained
from
the
likelihood
ratio
and
95%
CIs
from
the
standard
errors
of
the
model
coefficients.
Because
of
previously
documented
higher
rates
of
IBD
in
the
immigrant
population
of
Leicester,
rates
were
provided
separately
for
the
immigrant
and
non-immigrant
popula-
tions.26
For
the
other
centre
with
a
substantial
number
of
immigrants
(Beer
Sheva),
rates
could
not
be
calculated
separately,
as
the
necessary
population
data
were
not
provided.
Data
for
Beer
Sheva
and
the
immigrant
population
of
Leicester
were
excluded
from
calculation
of
rate
ratios
for
the
northern
versus
southern
centres.
Rate
ratios
for
northern
versus
southern
centres
were
also
estimated
with
additional
adjustment
for
national
tobacco
consumption
(used
as
a
proxy
measure
of
smoking
status)
and
tertiary
education
(used
as
a
proxy
measure
for
social
class
and
access
to
health
care).
Data
for
these
factors
and
Gross
National
Product
(GNP)
were
obtained
from
the
1993
World
Development
Report.27
For
tobacco
consumption
and
tertiary
education,
three
groups
were
formed,
containing
roughly
equal
numbers
of
centres
in
each
category
for
the
analysis
(tertiles).
Rate
ratios
adjusted
for
these
factors
were
estimated
by
adding
terms
to
represent
their
categorical
effects
to
the
above
mentioned
log
linear
models.
Results
During
the
two
year
study
period
a
total
of
2201
patients
aged
15
years
and
older
were
diagnosed
with
IBD
in
the
20
centres
(due
to
relocation
of
investigators
in
Dublin,
cases
were
recruited
during
the
first
year
only)
with
one
year
follow
up
forms
available
for
98%
of
patients
by
December
1994.
Final
diagnosis
at
one
year
follow
up
was
UC
(including
proctitis)
in
1379
cases
(63%),
CD
in
706
cases
(32%),
and
indeterminate
colitis
in
the
remaining
116
(5%).
The
initial
diagnosis
was
unchanged
for
2119
(96%)
cases;
37
cases
with
an
initial
diagnosis
of
indeterminate
colitis
were
changed
to
UC,
and
20
to
CD;
16
cases
initially
diagnosed
as
UC
were
changed
to
CD
and
conversely
nine
were
changed
from
CD
to
UC.
The
diagnostic
methods
used
for
UC
were
endoscopy
in
99%
of
cases,
biopsy
in
95%,
and
radiology
in
31%;
for
CD
the
corresponding
figures
were
endoscopy
in
81%
of
cases,
biopsy
in
78%,
radiology
in
7
1O%,
and
examination
of
a
resection
specimen
in
16%.
Cases
with
a
final
diagnosis
of
indeterminate
colitis
are
not
considered
further.
Analysis
of
the
diagnostic
methods
used,
anatomical
site,
and
extent
of
disease
showed
little
overall
difference
between
centres
in
the
north
and
south
of
Europe
(data
not
shown).
Likewise,
analysis
of
the
presenting
symptoms
such
as
bowel
frequency,
occurrence
of
rectal
bleeding,
weight
loss,
and
abdominal
pain
suggested
no
systematic
differences
in
severity
of
symptoms
at
presentation
between
cases
in
the
northern
and
southern
centres.
INCIDENCE
BY
AGE
AND
SEX
Figure
1
shows
the
age
specific
incidence
rates
(per
100
000)
for
UC
including
proctitis
and
CD
for
all
20
centres
combined.
For
UC,
different
patterns
of
incidence
were
observed
for
men
and
women
aged
35
and
over,
with
the
rates
for
men
remaining
fairly
constant
with
increasing
age,
whereas
those
for
women
decreased.
Incidence
rates
for
CD
were
generally
lower
and
were
broadly
similar
for
men
and
women,
with
rates
for
both
sexes
declining
with
increasing
age.
Tables
I
and
II
show
the
age
and
sex
specific
incidence
for
UC
and
CD
for
each
study
centre
with
centres
ordered
according
to
degree
latitude.
Some
centre
specific
rates
(for
both
UC
and
CD)
were
based
on
very
few
cases
and
for
some
centres
no
cases
were
observed
in
certain
age
groups,
particularly
in
the
oldest
age
group
(65+
years)
for
women.
Tables
III
and
IV
show
the
crude
and
age
and
sex
adjusted
incidence
rates
for
ages
15
to
64,
for
UC
and
CD,
according
to
study
centre.
In
general,
the
crude
rates
were
similar
to
the
age
and
sex
adjusted
rates.
For
both
diagnostic
groups
there
seemed
to
be
a
large
degree
of
0
0
0
0
0
(L)
0
a)
,o
V
C
0
0
._
c
0
0
0
0
C.)
c
.5
c
16
14
12
10
8
6
4
A
2
a
VVoIXlen
0
15-24
25-34
35-44
45-54 55-64
.65
Age
groups
B
12
H
6
H
2
_
n
15-24
25-34
35-44
45-54
55-64
.65
Age
groups
Figure
1:
Age
specific
incidence
rates
per
100
000
for
ulcerative
colitis
including
procolitis
(UC)
and
Crohn
's
disease
(CD)
in
the
20
centres
included
in
the
EC-IBD
study.
692
1
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

Incidence
of
inflammatory
bowel
disease
across
Europe:
is
there
a
difference
between
north
and
south?
TABLE
I
Incidence
rates
(/100
000)
and
numbers
of
cases
(in
parentheses)
aged
15
years
or
overfor
ulcerative
colitis
(including
proctitis)
reported
in
the
20
centres
included
in
the
EC-IBD
study,
according
to
age
and
sex
Men
(age)
Women
(age)
Total
Centre
15-44
45-64
65
15-44
45-64
65
¢15
Northern
centres:
Reykjavik
(Iceland)
27-3
(34)
26-4
(12)
32-2
(8)
27-5
(33)
11.1
(5)
9-7
(3)
24-3
(95)
Oslo
(Norway)
18-7
(82)
14-1
(27)
22-3
(26)
17-5
(75)
8-7
(18)
9.9
(23)
15-6
(251)
Copenhagen
(Denmark)
8-3
(20)
8-3
(11)
10-6
(7)
11-4
(27)
9.7
(14)
13-3
(13)
10.0
(92)
Dublin
(Ireland)
16-2
(47)
22-0
(23)
22-1
(10)
13-8
(42)
7-1
(8)
9.7
(7)
14-8
(137)
Leicester
(United
Kingdom)
Non-immigrants
10.0
(8)
13-5
(5)
9-8
(3)
10
9
(9)
5-1
(2)
4-3
(2)
9-2
(29)
Immigrants
8-1
(3)
8-8
(1)
28-7
(1)
20-4
(8)
26-2
(3)
(0)
15-1
(16)
Maastricht
(Te
Netherlands)
15-1
(46)
17-1
(26)
8-8
(6)
14-3
(42)
9-2
(14)
5-9
(6)
13-1
(140)
Essen
(Germany)
3-5
(12)
3-2
(7)
4-2
(4)
5-8
(19)
4.0
(9)
4-6
(9)
4-3
(60)
Amiens
(NW
France)
6-3
(16)
9-6
(10)
(0)
5-2
(16)
5-5
(6)
1
1
(1)
5-6
(49)
All
northern
centres
12-7
(268)
12.2
(122)
12-7
(65)
13-0
(271)
7-6
(79)
7-3
(64)
11-4
(869)
Southern
centres:
Milan-Varese
(Italy)
15-4
(14)
6-1
(3)
28-8
(6)
6-6
(6)
3-8
(2)
8-5
(3)
10-0
(34)
Crema-Cremona
(Italy)
6-0
(9)
19-7
(15)
3-0
(1)
8-1
(10)
2-5
(2)
3-4
(2)
7-5
(39)
ReggioEmilia
(Italy)
9-3
(17)
10-2
(11)
2-9
(2)
9.1
(16)
5-5
(6)
4-1
(4)
7-5
(56)
Florence
(Italy)
10-3
(26)
11-4
(18)
11-7
(11)
7-9
(20)
4-6
(8)
2-7
(4)
8-1
(87)
Vigo
(NW
Spain)
5.9
(14)
11-3
(12)
8-6
(4)
9-5
(23)
1-7
(2)
3-8
(3)
7-0
(58)
Sabadell
(NE
Spain)
11-4
(20)
14-8
(11)
12-6
(4)
8-1
(14)
3.9
(3)
(0)
9.0
(52)
Braga
(N
Portugal)
5-8
(7)
6-7
(3)
(0)
8-0
(10)
3.9
(2)
(0)
5-5
(22)
Ioannina
(NW
Greece)
9.5
(10)
5.0
(3)
15.4
(5)
11-2
(12)
7-6
(5)
(0)
8-5
(35)
Almada
(SPortugal)
1-5
(2)
1.4
(1)
4.0
(1)
0-7
(1)
4-2
(3)
(0)
1-7
(8)
Palermo,
Sicily
(Italy)
15-6
(9)
17-0
(4)
(0)
7-7
(5)
2-9
(1)
(0)
8-5
(19)
Heraklion,
Crete
(Greece)
19-2
(18)
35-5
(18)
10.1
(3)
12-3
(12)
14-9
(8)
2-7
(1)
16-6
(60)
Beer
Sheva
(Israel)
12-0
(20)
8-6
(4)
5-3
(1)
6-1
(10)
9.9
(5)
(0)
8-5
(40)
All
southern
centres
9.5
(166)
11.9
(103)
8-6
(38)
7
9
(139)
5.0
(47)
2-6
(17)
8-0
(510)
All
centres
11.2
(434)
12-1
(225)
10-8
(103)
10-7
(410)
6-4
(126)
5-3
(81)
9-8
(1379)
variation
between
the
centre
specific
rates.
For
UC,
the
age
and
sex
adjusted
rate
ranged
from
24.5
per
100
000
in
Iceland,
to
1.6
per
100
000
in
Almada
(southern
Portugal).
For
CD,
the
highest
rate
was
9.2
per
100
000
in
both
Amiens
(north
west
France)
and
Maastricht
(The
Netherlands),
and
the
lowest
was
0.9
per
100
000
in
Ioannina
(north
west
Greece).
INCIDENCE
IN
NORTHERN
EUROPE
VERSUS
SOUTHERN
EUROPE
The
overall
age
and
sex
adjusted
rate
for
UC
in
all
northern
European
centres
combined
was
40°/
higher
than
that
of
all
southern
European
centres
and
that
for
CD
80%
higher
(Table
V).
For
UC
and
CD
there
was
some
suggestion
that
the
age
adjusted
RRs
differed
for
the
two
sexes,
with
slightly
higher
RRs
being
found
in
men
for
UC
and
in
women
for
CD
(X2
for
difference
in
RRs=4
2,
ldf,
p=004
for
UC
and
X2
for
difference
in
RRs=3.3,
ldf,
p=0.07
for
CD).
Additional
adjustment
for
both
national
tobacco
consumption
and
tertiary
education
tended
to
reduce
the
estimated
RRs
(Table
V).
After
adjustment
for
both
tobacco
consump-
tion
and
tertiary
education
significantly
increased
rates
in
northern
versus
southern
centres
were
still
found
for
UC
and
CD
in
women
and
for
both
sexes
combined,
whereas
for
both
conditions
in
men
the
difference
in
TABLE
ii
Incidence
rates
(/100
000)
and
numbers
of
cases
(in
parentheses)
aged
1
5years
or
over
for
Crohn
's
disease
reported
in
the
20
centres
included
in
the
EC-IBD
study,
according
to
age
and
sex
Men
(age)
Women
(age)
Total
Centre
15-44
45-64
2r65
15-44
45-64
'65
2
:15
Northern
centres:
Reykjavik
(Iceland)
10-4
(13)
4-4
(2)
8-0
(2)
10-0
(12)
2-2
(1)
6-4
(2)
8-2
(32)
Oslo
(Norway)
9-8
(43)
2-6
(5)
5-1
(6)
9-6
(41)
5-3
(11)
2-6
(6)
6-9
(112)
Copenhagen
(Denmark)
5-4
(13)
5-3
(7)
1-5
(1)
12.2
(29)
3-5
(5)
6-2
(6)
6-6
(61)
Dublin
(Ireland)
5-5
(16)
2-9
(3)
2-2
(1)
7-9
(24)
2-7
(3)
11.1
(8)
5.9
(55)
Leicester
(United
Kingdom)
Non-immigrants
2-5
(2)
(0)
(0)
9-7
(8))
(0)
(0)
3-2
(10)
Immigrants
5-4
(2)
17-5
(2)
(0)
2-5
(1)
(0)
(0)
4-7
(5)
Maastricht
(The
Netherlands)
10-2
(31)
4.0
(6)
(0)
13-9
(41)
2-6
(4)
(0)
7-7
(82)
Essen
(Germany)
4-1
(14)
1-4
(3)
3-1
(3)
6-7
(22)
3-1
(7)
(0)
3-5
(49)
Amiens
(NWFrance)
8-2
(21)
7-7
(8)
1-6
(1)
12-8
(32)
6-4
(7)
2-2
(2)
8-1
(71)
All
northern
centres
7-3
(155)
3-6
(36)
2-7
(14)
10-1
(210)
3-6
(38)
2-8
(24)
6-3
(477)
Southern
centres:
Milan-Varese
(Italy)
1-1
(1)
2-0
(1)
14-4
(3)
5-5
(5)
(0)
2-8
(1)
3-2
(11)
Crema-Cremona
(Italy)
0-7
(1)
5-3
(4)
3-0
(1)
4-1
(5)
1-2
(1)
3-4
(2)
2-7
(14)
Reggio
Emilia
(Italy)
5-4
(10)
3-7
(4)
5.9
(4)
5-1
(9)
1-8
(2)
1-0
(1)
4-0
(30)
Florence
(Italy)
3-6
(9)
0-6
(1)
1
1
(1)
4-4
(11)
3-4
(6)
0-7
(1)
2-7
(29)
Vigo
(NWSpain)
9-7
(23)
3-8
(4)
4-3
(2)
4-1
(10)
0.9
(1)
(0)
4-8
(40)
Sabadell
(NE
Spain)
5-7
(10)
(0)
3-2
(1)
7-5
(13)
5-2
(4)
(0)
4-9
(28)
Braga
(N
Portugal)
3-3
(4)
2-2
(1)
(0)
7-2
(9)
1
9
(1)
(0)
3-7
(15)
Ioannina
(NW
Greece)
1-0
(1)
1-7
(1)
3-1
(1)
0o-
(1)
(0)
(0)
1-0
(4)
Almada
(S
Portugal)
1-5
(2)
2-9
(2)
(0)
3-5
(5)
2-8
(2)
(0)
2-3
(11)
Palermo,
Sicily
(Italy)
10-4
(6)
(0)
6-4
(1)
7-7
(5)
2-9
(1)
(0)
5-8
(13)
Heraklion,
Crete
(Greece)
7-5
(7)
7.9
(4)
(0)
3-1
(3)
(0)
(0)
3-9
(14)
Beer
Sheva
(Israel)
1-8
(3)
4-3
(2)
(0)
6-1
(10)
7-9
(4)
4.3
(1)
4-3
(20)
All
southern
centres
4-4
(77)
2-8
(24)
3-2
(14)
4-9
(86)
2-3
(22)
0.9
(6)
3-6
(229)
All
centres
6-0
(232)
3-2
(60)
2-9
(28)
7-7
(296)
3.0
(60)
2-0
(30)
5-0
(706)
693
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

Shivananda,
Lennard-Jones,
Logan,
Fear,
Price,
Carpenter,
van
Blankenstein
TABLE
III
Incidence
rates
(/100
000)
and
numbers
of
cases
aged
15-64
years
for
ulcerative
colitis
(including
proctitis)
reported
in
the
20
centres
included
in
the
EC-IBD
study
Men
Women
Total
Age
adjusted
Age
adjusted
Age
and
sex
rate
rate
adjusted
rate
Centre
Crude
rate
(95%
CI)
Crude
rate
(95%
CI)
Crude
rate
(95%
CI)
Northern
centres:
Reykjavik
(Iceland)
27-1
(46)
26-9
(21-5-32-3)
23-0
(38)
21-9
(17-3-26-5)
25-1
(84)
24-5
(17-4-31-5)
Oslo
(Norway)
17-3
(109)
16-9
(14-7-19-1)
14-6
(93)
14-2
(12-3-16-1)
16-0
(202)
15-6
(12-7-18-5)
Copenhagen
(Denmark)
8-3
(31)
8-4
(6-4-10-4)
10-8
(41)
11-2
(9
0-13
5)
9-5
(72)
9-8
(6-8-12-8)
Dublin
(Ireland)
17-7
(70)
18-6
(15-5-21-6)
12-0
(50)
11-6
(9-5-13-8)
14-8
(120)
15-2
(11-5-18-9)
Leicester
(United
Kingdom)
Non-immigrants
11.1
(13)
11-5
(7-3-15-7)
9-0
(11)
8-4
(5-2-11-7)
10-0
(24)
10-0
(4-7-15-3)
Immigrants
8-3
(4)
8-3
(2-6-13-9)
21-7
(11)
22-8
(13-7-31-8)
15-1
(15)
15-3
(4.6-26.0)
Maastricht
(The
Netherlands)
15-8
(72)
15-6
(13-2-18-1)
12-6
(56)
12-6
(10-4-14-7)
14-2
(128)
14-1
(10-9-17-4)
Essen
(Germany)
3-4
(19)
3-3
(2.3-4.3)
5-1
(28)
5-0
(3
8-6-2)
4-2
(47)
4-1
(2.6-5.7)
Amiens
(NW
France)
7-2
(26)
7-3
(5-4-9-3)
6-1
(22)
6-1
(4-4-7-8)
6-7 (48) 6-7
(4
2-9-3)
All
northern
centres
12-6
(390)
12-5
(10-5-14-5)
11-2
(350)
11-1
(9-2-13-1)
11-9
(740)
11.8
(9
0-14
6)
Southern
centres:
Milan-Varese
(Italy)
12-1
(17)
12.5
(8-4-16-5)
5-6
(8)
5-7
(3-1-8-2)
8-8
(25)
9-1
(4-4-13-8)
Crema-Cremona
(Italy)
10.6
(24)
11.0
(8.0-14.0)
5.9
(12)
6.2
(3.9-8.4)
8.4
(36)
8.6
(4.8-12-4)
Reggio
Emilia
(Italy)
9-6
(28)
9.4
(7
0-11
9)
7-7
(22)
7-9
(5-7-10-0)
8-7
(50)
8-7
(5-5-11-9)
Florence
(Italy)
10-7
(44)
10-7
(8-5-12-8)
6-6
(28)
6-7
(5-1-8-4)
8-6
(72)
8-7
(6-0-11-4)
Vigo
(NW
Spain)
7-5
(26)
8-0
(6-0-10-1)
7-0
(25)
6-8
(5-1-8-6)
7-3
(51)
7-4
(4-7-10-1)
Sabadell
(NE
Spain)
12-4
(31)
12-9
(9-9-16-0)
6-8
(17)
6-7
(4-6-8-7)
9-6
(48)
9-8
(6-
13-5)
Braga
(N
Portugal)
6-1
(10)
6-7
(3-9-9-5)
6-8
(12)
6-6
(4-1-9-0)
6-4
(22)
6-6
(2-9-10-4)
Ioannina
(NW
Greece)
7-9
(13)
8-2
(5-2-11-2)
9-8
(17)
10-4
(7-2-13-7)
8-9
(30)
9-3
(4-9-13-7)
Almada
(S
Portugal)
1-5
(3)
1-4
(0.3-2.4)
1-9
(4)
1-9
(0-7-3-1)
1-7
(7)
1-6
(0
0-3.2)
Palermo,
Sicily
(Italy)
16.0
(13)
16-1
(10-2-22.0)
6-0
(6)
5-7
(2.7-8.7)
10-5
(19)
11-0
(4-3-17-8)
Heraklion,
Crete
(Greece)
24-9
(36)
25-0
(19.3-30-6)
13-3
(20)
13-3
(9-5-17-1)
19-0
(56)
19-3
(12
6-26
1)
BeerSheva(Israel)
11-3(24)
10-7(7-7-13-7)
7-0(15)
7-4(48-9-9)
9-1
(39)
9-1
(5-1-13-0)
All
southern
centres
10-3
(269)
10-3
(8-4-12-3)
6-9
(186)
6-9
(5
0-8-9)
8-6
(455)
8-7
(5.9-11-5)
All
centres
11-5
(659)
11-5
(10.9-12-1)
9-2
(536)
9-2
(8.7-9-7)
10-3
(1195)
10-4
(7-6-13-1)
incidence
of
disease
between
the
north
and
south
of
Europe
was
no
longer
statistically
significant.
The
relation
between
centre
specific
rates
and
GNP
was
examined.
Northern
centres
tended
to
have
higher
rates
of
UC
and
CD
and
higher
levels
of
GNP
(Fig
2).
As
a
consequence
of
the
strong
relation
between
incidence
of
disease,
GNP,
and
latitude,
it
was
not
possible
to
reliably
estimate
the
relative
incidence
in
northern
versus
southern
centres
independent
of
GNP.
Discussion
This
is
the
first
study
to
assess
the
incidence
of
UC
and
CD
across
Europe
prospectively
and
simultaneously.
The
overall
incidence
per
100
000
at
ages
15-64
years
was
104
for
UC
and
5.6
for
CD.
Rates
of
UC
in
northern
centres
were
40%
higher
than
those
in
the
south
(RR=
1.4,
95%
CI
1.2
to
1.5)
and
for
CD
they
were
80%
higher
(RR=1.8,
95%
CI
1.5
to
2.1).
The
observed
excess
in
incidence
of
UC
and
CD
in
northern
centres
did
not
seem
to
be
explained
by
differences
in
tobacco
TABLE
IV
Incidence
rates
(/100
000)
and
numbers
of
cases
aged
15-64
years
for
Crohn
's
disease
reported
in
the
20
centres
included
in
the
EC-IBD
study
Men
Women
Total
Age
adjusted
Age
adjusted
Age
and
sex
rate
rate
adjusted
rate
Centre
Crude
rate
(95%
CI)
Crude
rate
(95%
CI)
Crude
rate
(95%
CI)
Northern
centres:
Reykjavik
(Iceland)
8-8
(15)
8-4
(5-5-11-3)
7-9
(13)
7-2
(4.6-9-8)
8-4
(28)
7-8
(4-0-11-7)
Oslo
(Norway)
7-6
(48)
7-6
(6
1-9-1)
8-2
(52)
8-3
(6-8-9-7)
7-9
(100)
7-9
(5-8-9.9)
Copenhagen
(Denmark)
5-3
(20)
5-4
(3-8-7-1)
8-9
(34)
9-3
(7-3-11-4)
7-2
(54)
7-3
(4-7-10-0)
Dublin
(Ireland)
4-8
(19)
4-5
(3-1-5-9)
6-5
(27)
5-9
(4.5-7-4)
5-7
(46)
5-2
(3.2-7-2)
Leicester
(United
Kingdom)
Non-immigrants
1-7
(2)
1-6
(0-1-3-1)
6-6
(8)
6-1
(3.3-8-9)
4-2
(10)
3-8
(0.7-6-9)
Immigrants
8-3
(4)
9-4
(2-9-15-9)
2-0
(1)
1-7
(0-0-3-8)
5-0
(5)
5-6
(0-0
12-5)
Maastricht
(The
Netherlands)
8-1
(37)
8-3
(6-5-10-2)
10-1
(45)
10-1
(8-2-12-0)
9-1
(82)
9-2
(6-5-11-8)
Essen
(Germany)
3-1
(17)
3-2
(2-2-4-2)
5-3
(29)
5-6
(4.2-6-9)
4-2
(46)
4-4
(2-7-6-1)
Amiens
(NW
France)
8-1
(29)
8-0
(6-0-9-9)
10-8
(39)
10-6
(8-4-12-7)
9-5
(68)
9-2
(6-3-12-2)
All
northern
centres
6-2
(191)
6-2
(4-2-8-1)
7-9
(248)
7-9
(5-9-9-8)
7-0
(439)
7-0
(4-2-9-8)
Southern
centres:
Milan-Varese
(Italy)
1-4
(2)
1-4
(0
1-2-6)
3-5
(5)
3-6
(1-5-5-6)
2-5
(7)
2-5
(0-1-4-9)
Crema-Cremona
(Italy)
2-2
(5)
2-3
(0.9-3-6)
2-9
(6)
3-1
(1-5-4-7)
2-6
(11)
2-7
(0
6-4-8)
ReggioEmilia(Italy)
4-8(14)
4-8(3-1-6-5)
3-9(11)
4-1
(25-557)
4-3(25)
4-4(2-1-6-7)
Florence
(Italy)
2-4
(10)
2-6
(1-5-3-7)
4-0
(17)
4-1
(2.8-5-3)
3-2
(27)
3-3
(1-7-5-0)
Vigo
(NW
Spain)
7-8
(27)
7-3
(5-4-9-2)
3-1
(11)
2-8
(1-7-3-9)
5-4
(38)
5-1
(2-9-7-3)
Sabadell
(NE
Spain)
4-0
(10)
3-8
(2.2-5-4)
6-8
(17)
6-6
(4-6-8-7)
5-4
(27)
5-2
(2-6-7.7)
Braga
(N
Portugal)
3-0
(5)
2-7
(1-1-4-3)
5-7
(10)
5-7
(3-4-8-0)
4-4
(15)
4-2
(1-3-7-0)
Ioannina
(NW
Greece)
1-2
(2)
1-1
(0
1-2-2)
0-6
(1)
0-7
(0-0-1-5)
0-9
(3)
0-9
(0-0-2-2)
Almada
(S
Portugal)
1-9
(4)
1-9
(0
7-3-2)
3-3
(7)
3-3
(1-7-4-9)
2-6
(11)
2-6
(0-6-4-6)
Palermo,
Sicily
(Italy)
7-4
(6)
7-1
(3-2-11-0)
6-0
(6)
6-1
(2.9-9
3)
6-6
(12)
6-6
(1-6-11-5)
Heraklion,
Crete
(Greece)
7-6
(11)
7-5
(4-5-10-4)
2-0
(3)
2-1
(0.5-3-6)
4-7
(14)
4-8
(1-5-8-1)
Beer
Sheva
(Israel)
2-3
(5)
2-4
(0.9-3-8)
6-5
(14)
6-5
(4.2-8-9)
4-4
(19)
4-4
(1-7-7-2)
All
southern
centres
3-9
(101)
3-8
(1.9-5-8)
4-0
(108)
4-0
(2-0-6-0)
3-9
(209)
3-9
(1
1-6-7)
All
centres
5-1
(292)
5-1
(4-7-5-5)
6-1
(356)
6-1
(5
7-6-5)
5-6
(648)
5-6
(2.8-8
3)
694
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

Incidence
of
inflammatory
bowel
disease
across
Europe:
is
there
a
difference
between
north
and
south?
TABLE
V
Relative
rates
for
northern
European
centres
compared
with
southern
European
centres*,
95%
CIs,
and
the
corresponding
p
value
for
ages
15-64
Ulcerative
colitis
Crohn
's
disease
Factors
adjustedfor
Men
Women
Both
sexes
Men
Women
Both
sexes
Age
and
sex
1-23
(1-05-1-44)
1-57
(1-30-1-88)
1-37
(1-21-1-55)
1-53
(1-20-1-96)
2-09
(1-65-2-65)
1-81
(1-53-2-15)
p
Value
0-012
<0
001
<0-001
<0
001
<0
001
<0
001
Age,
sext,
tobacco
consumption,
and
tertiary
education
1-16
(0-95-1-41)
1-38
(1.10-1.74)
1-26
(1.08-1.46)
1-15
(0-85-1-55)
2-25
(1-63-3-09)
1-61
(1-30-2-00)
p
Value 0-152
0.004
0.003
0-370
<0
001
<0
001
*Data
for
Leicester
include
non-immigrant
population
only.
Beer
Sheva
excluded
from
data
for
southern
centres.
tAdjusted
for
sex
when
appropriate.
consurI
availabl
confou
For
inciden
previou
studies,
criteria
approa(
ment,
a
ing.
In
allowed
analysis
specific
may
pa
inciden
centres.
centres
represe:
than
pr
a
few
se
Desp
differen
and
sc
conside
diseaser
exampli
25
20
15
10
5
0
10
9
8
7
6
5
4
3
2
Figure
2:
rates
per
1
(UC)
anc
(GNP).
iption
and
education,
although
the
Iceland
and
Heraklion
(Crete,
Greece)
and
the
le
data
on
these
and
other
potential
low
incidence
of
CD
in
Ioannina
(north
west
nding
factors
were
limited.
Greece),
the
second
confirming
what
was
both
diseases,
the
observed
excess
found
previously
in
a
retrospective
study.28
To
ice
in
northern
centres
is
smaller
than
what
extent,
if
at
all,
can
these
findings
be
sly
suggested.
By
contrast
with
earlier
explained
by
differences
in
the
ascertainment
the
present
study
used
agreed
standard
of
cases
between
centres?
Case
ascertainment
for
case
definition,
and
a
uniform
is
dependent
on
the
symptom
threshold
at
ch
and
time
period
for
case
ascertain-
which
people
within
a
population
seek
medical
nd
a
common
protocol
for
data
record-
advice,
access
to
and
availability
of
specialist
l
addition,
the
pooled
data
analysis
care,
the
sensitivity
and
specificity
of
any
1
the
application
of
standard
methods
of
investigation,
and
the
completeness
of
search
s,
including
the
calculation
of
rates
for for
newly
diagnosed
cases.
The
severity
of
IBD
age
groups.
Together,
these
factors
varies
greatly
and
cases
with
few
or
no
irtly
explain
the
smaller
difference
in
symptoms
are
not
uncommon.29
For
this
Lce
between
northern
and
southern
reason,
patients
who
were
asymptomatic
or
The
inclusion
of
a
wide
range
of
study
diagnosed
as
a
result
of
any
screening
activity
is
likely
to
have
produced
a
more
were
excluded.
Analysis
of
the
presenting
ntative
picture
of
IBD
across
Europe
symptoms
such
as
bowel
frequency,
rectal
evious
comparisons
that
were
based
on
bleeding,
weight
loss,
and
abdominal
pain
flected
centres.
showed
little
overall
difference
in
severity
of
ite
the
relatively
modest
overall
disease
for
patients
in
the
northern
and
ice
in
incidence
rates
between
northern
southern
centres.
uthern
centres,
there
seems
to
be
Likewise
the
frequency
with
which
the
rable
variation
in
the
incidence
of
both
various
diagnostic
investigations
were
per-
s
across
Europe.
The
most
striking
formed
did
not
seem
to
vary
between
centres.
es
are
the
high
incidence
of
UC
in
Throughout
the
two
years
of
the
study
vigorous
efforts
were
made
to
recruit
all
eligible
patients;
to
this
end
all
centres
made
regular
contact
A
with
general
practitioners
and
other
specialists,
0
North
18
centres
arranged
meetings
for
their
general
0
*
South
practitioners,
and
17
carried
out
regular
_
0
0
O
searches
of
endoscopy
and
pathology
records.
o
Moreover,
major
differences
in
case
as-
_
0
certainment
do
not
readily
account
for
areas
*
*0
*
°
with
a
high
or
low
incidence
of
one
disease
in
_
*0
the
presence
of
an
average
incidence
of
the
0
other
as
was
found
in
Ioannina
(north
west
I
Greece),
Heraklion
(Crete,
Greece),
and
o
5000
10
000
15
000
20
000
25
000
Amiens
(north
west
France).
GNP
It
is
possible
that
the
smaller
than
expected
difference
in
north-south
incidence
of
IBD
-
B
found
in
the
present
study
results
from
rates
in
B
|o0
0
some
areas
of
Europe
increasing
more
rapidly
o
North
than
in
others.
Several
centres
in
northe
_
*
South
|
ff
Europe
reported
considerable
increases
in
incidence
of
CD
during
the
1950s
and
1960s
whereas
the
latest
studies
have
suggested
that
-
*
*
0
*
0
the
increase
in
incidence
of
CD
in
the
north
has
slowed
or
plateaued.16
19
3032
Until
re-
-
cently,
there
were
few
studies
from
southern
-
*
Europe
and
interpretation
of
these
have
been
X
I
500
loooo
15000
20200
2500
hampered
by
the
problems
mentioned
above.
5000
10
000
15
000
20
000
25
000
Two
studies
from
central
Italy
that
examined
GNP
the
incidence
of
IBD
during
the
1970s
and
Centre
specific
age
and
sex
adjusted
incidence
1
980s
found
a
roughly
threefold
increase
in
the
100
000
for
ulcerative
colitis
including
proctitis
dCrohn's
disease
versus
Gross
National
Product
incidence
of
both
UC
and
CD.14
33
3
In
addition.,
a
prospective
study
of
incidence
of
a)
C)
V
*
-
x
a,
(L)
:3
0
Cu0
X
0
cn
m
a)
0)
U)
B
(D
CD
L0
,o
a1)
zo
.
0
'00
xo
U)
-0
c
a)
CD
695
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

Shivananda,
Lennard-J7ones,
Logan,
Fear,
Price,
Carpenter,
van
Blankenstein
IBD
in
Zagreb
between
1980
and
1990
disclosed
an
extremely
low
annual
incidence
of
both
UC
(1-5
per
100
000)
and
CD
(0
7
per
100
000)
in
neighbouring
Yugoslavia.35
36
Further
evidence
that
might
support
the
suggestion
that
the
incidence
of
IBD
is
changing
across
Europe
is
the
emergence
of
differences
in
age
specific
incidence
of
UC
in
men
and
women.
Many
previous
studies
have
shown
that
in
both
sexes
incidence
of
UC
peaks
in
early
adult
life,
sometimes
with
a
second
lower
peak
around
the
age
of
65.37
38
However,
more
recent
studies
have
shown
less
pronounced
peaks
in
age
specific
incidence
in
men
but
not
women.6
16
17
39
In
the
present
study,
overall
age
specific
rates
of
UC
among
men
showed
little
variation
whereas
those
for
women
declined
with
increasing
age.
This
is
the
first
study
large
enough
to
show
this
difference
clearly
and
for
it
to
be
significant.
In
conclusion,
this
study
suggests
a
modest
excess
of
incidence
of
IBD
in
northern
Europe.
The
magnitude
of
the
observed
excess
for
both
conditions
is
less
than
expected
on
the
basis
of
previous
studies.
This
may
reflect
recent
increases
in
the
incidence
of
IBD
in
southern
Europe
whereas
those
in
the
north
may
have
stabilised.
The
aetiology
of
these
conditions
is
unclear
and
it
is
therefore
difficult
to
explain
the
patterns
found.
That
similar
north-south
gradients
in
incidence
have
also
been
documented
in
the
United
States40
suggests
that
several
factors
may
be
involved,
including
climate,
diet,
economic
wealth,
and
de-
velopment
or
genetic
susceptibility.
The
collaborative
network
and
the
baseline
data
established
under
this
study
provides
the
framework
for
further
studies
to
monitor
the
incidence
of
IBD,
particularly
in
the
low
incidence
areas,
and
to
examine
putative
environmental
factors
around
Europe.
Appendix
EC-IBD
STUDY
PARTICIPANTS
(CENTRE,
STUDY
AREA
AND
STUDY
AREA
POPULATION,
INVESTIGATORS):
Northern
Europe
1
Reykjavik
(Iceland
-
the
whole
country
-
population
195
467):
Dr
Sigurdur
Bj6rnsson,
Dr
J6hann
H
J6hannsson,
Dr
Einar
Oddsson,
Department
of
Medicine,
Reykjavik
City
and
University
Hospitals,
Iceland.
2
Oslo
(south
eastern
Norway
including
Oslo
-
population
806
898):
Dr
Bj0rn
Moum,
Dr
Morten
Vatn,
Dr
Erling
Aadland,
Dr
Olav
Fausa,
Dr
Idar
Lygren,
Dr
Jostein
Sauar,
Dr
Tom
Schulz,
Dr
Njaal
Stray,
Dr
Rolf
Stave,
Medical
Department
A,
Rikshospitalet
University,
UllevAl
University,
Telemark
Central,
Aust
Agder
Central,
Diakonhjemmets
and
Lovisenberg
Hospitals,
Norway.
3
Copenhagen
(Copenhagen
County
-
population
459
125):
Dr
Ebbe
Langholz,
Dr
Vibeke
Binder,
Dr
Peter
Vedtofte,
Dr
Jesper
Sonne,
Medical
Departm-ents
C
and
F,
Herlev,
Glostrup
and
Gentofte
Hospitals,
Copenhagen,
Denmark.
4
Dublin
(Eastern
Health
Board
including
Dublin
-
population
928
619):
Dr
Rosemary
Collins,
Professor
Colm
O'Morain,
Department
of
Gastroenterology,
Meath
and
Adelaide
Hospitals,
Dublin,
Ireland.
5
Leicester
(Leicester
City
-
population
211159):
Dr
John
Mayberry,
Mrs
Irene
Carr,
Department
of
Gastroenterology,
Leicester
General
Hospital,
Leicester,
UK.
6
Maastricht
(South
Limburg
-
population
535
683):
Dr
Maurice
Russel,
Professor
Reinhold
Stockbrugger,
Department
of
Gastroenterology,
Academisch
Zie-
kenhuis
Maastricht,
The
Netherlands.
7
Essen
(Cities
of
Essen
and
Miulheim-Ruhr
Area
-
population
698
784):
Professor
Harald
Goebell,
Dr
Bettina
Katschinski-Breuer,
Department
of
Gastro-
enterology,
Universitatsklinikum
Essen,
Germany.
8
Amiens
(Department
of
Somme
-
population
437
742):
Professor
Jean-Louis
Dupas,
Department
of
Hepatogastroenterology,
Centre
Hospitalier
Universi-
taire
Amiens,
France.
Southern
Europe
9
Milan
(Unita'
Sanitaria
Locale
1
including
Varese
-
population
169
830):
Professor
Paolo
Bianchi,
Dr
T
Ranzi,
Dr
M
C
Campanini,
Dr
M
Curzio,
Dr
R
Gullotta,
Department
of
Gastroenterology,
University
of
Milan,
Italy.
10
Milan
(Unita'
Sanitaria
Locale
51
and
53
including
Crema
-
Cremona
-
population
251
328):
Professor
Paolo
Bianchi,
Dr P
Bodoni,
Dr
P
Politi,
Dr
G
Lupinacci,
Dr
A
Zambelli,
Department
of
Gastro-
enterology,
Ospedale
di
Cremona
et
OM
Crema,
Italy.
11
Reggio
Emilia
(Reggio
Emilia
-
population
370
905):
Dr
Giovanni
Fornaciari,
Dr
Marina
Beltrami,
Dr
Maria
Grazia
Mortilla,
Dr
Franco
Nicoli,
Dr
Luigi
Serra,
3rd
Department
of
Internal
Medicine,
Arcispedale
S
Maria
Nuova,
Reggio
Emilia,
Italy.
12
Florence
(Metropolitan
Florence
-
population
539
833):
Dr
Giacomo
Trallori,
Dr
Andrea
Bonanomi,
Dr
Guiseppe
d'Albasio,
Professor
Franco
Pacini,
Division
of
Gastroenterology,
Policlinico
di
Careggi,
Firenze,
Italy.
13
Vigo
(Vigo
Health
Area
-
population
413
830):
Dr
Victor
Ruiz
Ochoa,
Dr
Ana
de
la
Fuente,
Dr
Francisco
Tardaguila,
Dra
Dolores
Rodriguez,
Dr
Santos
Pereira,
Dra
Mercedes
Butron,
Dra
Margarita
Cueto,
Dr
Luis
Alvarez-Cervea,
Dr
Juan
Clofent,
Dr
Juan
R
Pineda,
Departments
of
Digestive
Diseases,
Povisa
Policlinico
Vigo,
Hospital
Xeral-Cies
and
Hospital
Meixoeiro,
Vigo,
Spain.
14
Sabadell
(Sabadell
Health
Area
-
population
287
714):
Dr
Enric
Brullet,
Dr
Xavier
Bonfill,
Dr
Gerard
Urriutia,
Departments
of
Endoscopy
and
Epidemiology,
Consorci
Hospitalari
Parc
Tauli,
Sabadell,
Spain.
15
Porto
(District
of
Braga
-
population
200
156):
Professor
Fernando
Tavarela
Veloso,
Dr
Reinaldo
Noronha,
Department
of
Gastroenterology,
Hospital
S
Joao,
Porto
and
Hospital
de
San
Marcos,
Braga,
Portugal.
16
Ioannina
(Epirus
-
population
205
798):
Dr
Epameinondas
Tsianos,
Georgios
Dalekos,
Department
of
Internal
Medicine,
The
University
of
Ioannina,
Greece.
17
Lisbon
(Almada,
Seixal,
Sesimbra
-
population
238
729):
Professor
Estela
Monteiro,
Drs
Joao
Freitas,
Paula
Borralho,
F
Cunha
Leal,
C
Soares,
P
Martins,
M
Dupond,
Department
of
Medicine
II,
Hospital
Uni-
versitario
de
Santa
Maria,
Lisbon,
and
Department
of
Gastroenterology
and
Pathology,
Almada
Regional
Health
Department,
Portugal.
18
Palermo
(Palermo
-
population
111
894):
Dr
Mario
Cottone,
Dr
G
Filippazzo,
Dr
Rita
Ayala,
Department
of
Medicine,
Ospedale
"V
Cervello",
Palermo,
Italy.
19
Heraklion
(Heraklion
-
population
181
222):
Dr
Joanis
Mouzas,
Professor
Orestes
Manousos,
De-
partment
of
Gastroenterology,
University
General
Hospital
Heraklion,
Greece.
20
Beer
Sheva
(Beer
Sheva
-
population
234
500):
Professor
Selwyn
Odes,
Gastroenterology
Unit,
Soroka
University
Hospital,
Beer
Sheva,
Israel.
STUDY
COORDINATION
Study
coordinator
Dr
Mark
van
Blankenstein,
Division
of
Gastro-
enterology,
Department
of
Internal
Medicine
II,
Uni-
versity
Hospital,
Rotterdam
"Dijkzigt".
696
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

Incidence
of
inflammatory
bowel
disease
across
Europe:
is
there
a
difference
between
north
and
south?
697
Principal
investigator
and
scientific
director
Dr
Shiva
Shivananda,
Division
of
Gastroenterology,
Department
of
Internal
Medicine
II,
University
Hos-
pital,
Rotterdam
"Dijkzigt".
Data
manager
Dr
Ron
Brower,
Medical
Computing
Consultants,
Rotterdam.
Coordination
secretary
Ms
Jo-Anne
Campbell,
Division
of
Gastroenterology,
Department
of
Internal
Medicine
II,
University
Hospital,
Rotterdam
"Dijkzigt".
SCIENTIFIC
ADVISORS
Clinical
gastroenterology
Professor
John
E
Lennard-Jones,
Department
of
Gastroenterology,
St
Mark's
Hospital,
London.
Epidemiology
Sir
Richard
Doll,
Clinical
Trials
Service
Unit,
Radcliffe
Infirmary
Oxford.
Dr
Anders
Ekbom,
Cancer
Epi-
demiology
Unit,
University
Hospital
Uppsala.
Dr
Richard
F
Logan,
Department
of
Public
Health
and
Epidemiology,
Queen's
Medical
Centre,
Nottingham.
Pathology
Dr
Ashley
B
Price,
Department
of
Cellular
Pathology,
Northwick
Park
Hospital,
London.
Statistical
analysis
Dr
Lucy
Carpenter,
Department
of
Public
Health
and
Primary
Care,
University
of
Oxford.
Miss
Nicola
Fear,
ICRF
Cancer
Epidemiology
Unit,
Gibson
Building,
Radcliffe
Infirmary,
Oxford.
Coordination
of
the
EC-IBD
Study
was
financially
supported
by
Biomed
I
programme
of
the
Commission
of
the
European
Communities
with
additional
support
for
the
meetings
in
different
parts
of
Europe
from
Astra
(Sweden),
Bracco
(Italy),
Falk
Foundation
(Germany),
and
Pharmacia
(Sweden).
We
thank
Sir
Richard
Doll
and
Professor
Martin
Vessey
for
help
in
design
and
conduct
of
the
study,
and
for
their
review
with
Dr
Valerie
Beral
of
the
manuscript.
1
Orholm
M,
Munkholm
P,
Langholz
E,
Haagen
Nielsen
0,
Sorensen
TIA,
Binder
V.
Familial
occurrence
of
inflammatory
bowel
disease.
N
Engl
Y
Med
1991;
324:
84-8.
2
Lanfranchi
GA,
Mechelini
A,
Brignola
C,
et
al.
Uno
studio
epidemiologico
sulle
malattie
inflammatorie
intestinali
nella
provincia
de
Bologna.
Giornale
di
Clinica
Medica
1976;
57:
235-45.
3
Hellers
G.
Crohn's
disease
in
Stockholm
county
1955-74:
a
study
of
epidemiology,
results
of
surgical
treatment
and
long
term
prognosis.
Acta
Chir
Scand
1979;
(suppl
490):
1-84.
4
Paredes
JG,
Garcia
JMP.
Crohn's
disease
in
the
central
area
of
Spain.
In:
Pefia
AS,
Weterman
IT,
Booth
CC,
Strober
W,
eds.
Developments
in
gastroenterology.
1.
Recent
advances
in
Crohn's
disease.
The
Hague:
Martinus
Nijhoff,
1981;
168-73.
5
Binder
V,
Both
H,
Hansen
PK,
et
al.
Incidence
and
prevalence
of
ulcerative
colitis
and
Crohn's
disease
in
the
county
of
Copenhagen,
1962-78.
Gastroenterology
1982;
83:
563-8.
6
Sinclair
TS,
Brunt
PW,
Mowat
NAG.
Non-specific
proctocolitis
in
north-eastern
Scotland:
a
community
study.
Gastroenterology
1983;
85:
1-11.
7
Nordenvall
B,
Berglund
M,
Bostrom
D,
Berglund
M,
Monsen
U,
Nordenstrom
J,
et
al.
Epidemiology
of
ulcerative
colitis
in
Stockholm
County.
Scand
J
Gastroenterol
1985;
20:
783-90.
8
Ruiz
V,
Potel
J.
Crohn's
disease
in
Galicia,
Spain:
1968-1982.
Frontiers
in
Gastrointestinal
Research
1986;
11:
94-101.
9
Shivananda
S,
Pefla
AS,
Nap
M,
et
al.
Epidemiology
of
Crohn's
disease
in
Regio
Leiden,
The
Netherlands.
A
population
study
from
1979-83.
Gastroenterology
1987;
93:
966-74.
10
Shivananda
S,
Pefla
AS,
Mayberry
JF,
et
al.
Epidemiology
of
proctocolitis
in
the
region
of
Leiden,
The
Netherlands.
A
population
study
from
1979-83.
Scand
Jf
Gastroenterol
1987;
22:
993-1002.
11
Haug
K,
Schrumpf
E,
Barstad
5,
Fluge
G,
Halvorsen
JF,
and
the
Study
Group
of
Inflammatory
Bowel
Disease
mn
Western
Norway.
Epidemiology
of
ulcerative
colitis
in
western
Norway.
Scandjr
Gastroenterol
1988;
23:
517-22.
12
Bjornsson
S.
Inflammatory
bowel
disease
in
Iceland
during
a
30
year
period,
1950-79.
ScandJ3
Gastroenterol
1989;
24
(suppl
170):
47-9.
13
Roin
F,
Roin
J.
Inflammatory
bowel
disease
of
the
Faroe
Islands,
1981-8.
Scand
J
Gastroenterol
1989;
24
(suppl
170):
44-6.
14
Trallori
G,
d'Albasio
G,
Palli
D,
et
al.
Epidemiology
of
inflammatory
bowel
disease
over
a
10
year
period
in
Florence
(1978-87).
Ital
Jf
Gastroenterol
1991;
23:
559-63.
15
Cottone
M,
Cipolla
C,
Orlando
A,
et
al.
Epidemiology
of
Crohn's
disease
in
Sicily.
A
hospital
incidence
study
from
1987-9.
EurJrEpidemiol
1991;
7:
636-40.
16
Ekbom
A,
Helmick
C,
Zack
M,
Adami
HO.
The
epidemiology
of
inflammatory
bowel
disease:
a
large
population-based
study
in
Sweden.
Gastroenterology
199
1;
100:
350-8.
17
Langholz
E,
Munkholm
P,
Haagen
Nielsen
0,
Kreiner
S,
Binder
V.
Incidence
and
prevalence
of
ulcerative
colitis
in
Copenhagen County
from
1962-87.
Scand
J
Gastroenterol
1991;
26:
1247-56.
18
Kyle
J.
Crohn's
disease
in
the
northeastern
and
northern
isles
of
Scotland:
an
epidemiological
review.
Gastroenterology
1992;
103:
392-9.
19
Munkholm
P,
Langholz
E,
Haagen
Nielsen
0,
Kreiner
S,
Binder
V.
Incidence
and
prevalence
of
Crohn's
disease
in
the
County
of
Copenhagen,
1962-87:
a
sixfold
increase
in
incidence.
ScandJ3
Gastroenterol
1992;
27:
609-14.
20
Shivananda
S,
Hordijk
ML,
Pefia
As,
Mayberry
JF,
van
Blankenstein
M.
Proceedings
of
the
first
European
community
workshop
on
inflammatory
bowel
disease.
ScandJ3
Gastroenterol
1989;
24
(suppl
170):
1-101.
21
European
Community
initiative
on
inflammatory
bowel
disease.
Lancet
1988;
ii:
1321.
22
Lennard-Jones
JE.
Classification
of
inflammatory
bowel
disease.
ScandJr
Gastroenterol
1989;
24
(suppl
170):
2-6.
23
United
Nations.
World
population
prospects
1990.
New
York:
United
Nations,
1991.
24
Breslow
NE,
Day
NE.
Statistical
methods
in
cancer
research.
Vol
II.
The
design
and
analysis
of
cohort
studies.
Lyon:
International
Agency
for
Research
on
Cancer,
1987:
58-9.
(Sci
publ
No
82.)
25
EGRET
reference
manual.
Seattle:
Statistics
and
Epidemiology
Research
Corporation
and
Cytel
Software
Corporation,
1990.
26
Probert
CSJ,
Jayanthi
V,
Pinder
D,
Wicks
AC,
Mayberry
JF.
An
epidemiological
study
of
ulcerative
proctocolitis
in
Indian
migrants
and
the
indigenous
population
of
Leicestershire.
Gut
1992;
33:
687-93.
27
World
Development
Report.
Investing
in
health
-
world
development
indicators.
New
York:
Oxford
University
Press,
1993.
28
Tsianos
EV,
Masalas
CN,
Merkouropoulos
M,
Galekos
GN,
Logan
RFA.
Incidence
of
inflammatory
bowel
disease
in
north
west
Greece:
rarity
of
Crohn's
disease
in
an
area
where
ulcerative
colitis
is
common.
Gut
1994;
35:
369-72.
29
Mayberry
JF,
Ballantyne
KC,
Hardcastle
JD,
Mangham,
Pye
G.
Epidemiological
study
of
asymptomatic
inflammatory
bowel
disease:
the
identification
of
cases
during
a
screening
programme
for
colorectal
cancer.
Gut
1989;
30:
481-3.
30
Fellows
IW,
Freeman
JG,
Holmes
GKT.
Crohn's
disease
in
the
city
of
Derby,
1951-85.
Gut
1990;
31:
1262-5.
31
Lee
FI,
Nguyen-Van-Tam
JS.
Prospective
study
of
incidence
of
Crohn's
disease
in
northwest
England:
no
increase
since
the
late
1970s.
Eur
J
Gastroenterol
Hepatol
1994;
6:
27-31.
32
Thomas
GAO,
Millar-Jones
D,
Rhodes
J,
Roberts
GM,
Williams
GT,
Mayberry
JF.
Incidence
of
Crohn's
disease
in
Cardiff
over
60
years:
1986-90
an
update.
Eur
J
Gastroenterol
Hepatol
1995;
7:
401-5.
33
Trallori
G,
Bonanomi
AG,
Bardazzi
G,
et
al.
Incidence
and
prevalence
of
inflammatory
bowel
disease
in
Florence
from
1978-92.
Gastroenterology
1995;
108:
A930.
34
Tragnone
A,
Hanau
C,
Bazzocchi
G,
Lanfranchi
GA.
Epidemiological
characteristics
of
inflammatory
bowel
disease
in
Bologna,
Italy
-
incidence
and
risk factors.
Digestion
1993;
54:
183-8.
35
Vucelic
B,
Korac
B,
Sentic
M,
et
al.
Epidemiology
of
Crohn's
disease
in
Zagreb,
Yugoslavia:
a
10-year
prospective
study.
Int3
Epidemiol
1991;
20:
216-20.
36
Vucelic
B,
Korac
B,
Sentic
M
et
al.
Ulcerative
colitis
in
Zagreb,
Yugoslavia:
incidence
and
prevalence
1980-1989.
IntJ'Epidemiol
1991;
20:
1043-7.
37
Calkins
BM,
Mendeloff
AI.
Epidemiology
of
inflammatory
bowel
disease.
Epidemiol
Rev
1986;
8:
60-91.
38
Langman
MJS.
Chronic
non-specific
inflammatory
bowel
disease
-
ulcerative
colitis.
In:
Langman
MJS,
ed.
The
epidemiology
of
chronic
digestive
disease.
London:
Edward
Arnold,
1979:
91.
39
Gower-Rousseau
C,
Salomez
J-L,
Dupas
J-L,
et
al.
Incidence
of
inflammatory
bowel
disease
in
northern
France
(1988-90).
Gut
1994;
35:
1433-8.
40
Sonnenberg
A,
McCarty
DJ,
Jacobsen
SJ.
Geographic
variation
of
inflammatory
bowel
disease
within
the
United
States.
GastroenterologSy
1991;
100:
143-9.
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from

doi: 10.1136/gut.39.5.690
1996 39: 690-697Gut
S Shivananda, J Lennard-Jones, R Logan, et al.
Disease (EC-IBD).
Collaborative Study on Inflammatory Bowel
north and south? Results of the European
across Europe: is there a difference between
Incidence of inflammatory bowel disease
http://gut.bmj.com/content/39/5/690
Updated information and services can be found at:
These include:
References http://gut.bmj.com/content/39/5/690#related-urls
Article cited in:
service
Email alerting box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
Collections
Topic
(952 articles)Ulcerative colitis  (816 articles)Crohn's disease 
Articles on similar topics can be found in the following collections
Notes
http://group.bmj.com/group/rights-licensing/permissions
To request permissions go to:
http://journals.bmj.com/cgi/reprintform
To order reprints go to:
http://group.bmj.com/subscribe/
To subscribe to BMJ go to:
group.bmj.com on July 26, 2011 - Published by gut.bmj.comDownloaded from