Evaluation of Diagnostic Criteria For Crohn's Disease in Japan
Evaluation of Diagnostic Criteria For Crohn's Disease in Japan
Evaluation of Diagnostic Criteria For Crohn's Disease in Japan
DOI 10.1007/s00535-013-0798-x
Received: 17 January 2013 / Accepted: 14 March 2013 / Published online: 3 April 2013
Springer Japan 2013
Abstract
Background In Japan, Crohns disease (CD) is diagnosed
according to a single, well-established set of diagnostic
criteria. However, no nationwide attempt has been made to
determine which specific criteria within these diagnostic
criteria are used to make diagnoses.
Methods A questionnaire-based survey was conducted of
patients given a definitive or suspected diagnosis of CD before
January 2011 according to the Japanese Diagnostic Criteria
for Crohns Disease. The survey included 579 patients with a
definitive diagnosis of CD and 59 patients with a suspected
diagnosis of CD at 34 Japanese medical institutions.
Results A total of 87.4 % of definitive diagnoses of CD were
based on the criterion in the definite category: major finding A
longitudinal ulcer (LU) or B cobblestone-like appearance
(CSA). A total of 30.4 % of definitive diagnoses were based
on the criterion: major finding C non-caseating epithelioid
cell granuloma (NCEG) with minor finding a irregularshaped and/or quasi-circular ulcers or aphthous ulcerations
found extensively in the gastrointestinal tract or b characteristic perianal lesions. Finally, 7.1 % of definitive diagnoses were made according to the criterion: all minor findings
Introduction
Crohn et al. [1] were the first to report subacute or chronic
ileitis invading the terminal ileum as regional ileitis. This
condition, Crohns disease (CD), was subsequently established as a distinct pathological entity comprising lesions
throughout the gastrointestinal tract, from the mouth to the
anus. CD is a well-known type of refractory inflammatory
bowel disease of unknown etiology, and the number of
affected patients is growing in Japan [2]. CD causes both
symptoms attributable to gastrointestinal lesions and
complications throughout the body, appearing with many
clinical manifestations, so accurate diagnosis of CD in the
early stages is very important. No single gold standard for
the diagnosis of CD is currently available. The diagnosis is
therefore confirmed by clinical evaluation and a combination of endoscopic, histological, radiological, and/or
biochemical investigations [3].
In 1976, the Japanese Society of Gastroenterology
(Nippon Shokakibyo Gakkai Zasshi 1976;73:146778)
became the first Japanese organization to propose diagnostic criteria for CD. The criteria have been repeatedly
revised to reflect the continually advancing understanding
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Methods
A questionnaire on the diagnosis of CD was sent to each
participating medical institution of the Research Group of
Intractable Inflammatory Bowel Disease. These institutions
were asked to base their responses on the 20 most recent
consecutive cases of CD, as of January 2011, diagnosed
according to the CD diagnostic criteria [4, 6] (Table 1).
The survey also asked about suspected cases of CD identified during the period over which the 20 most recent cases
were diagnosed. The respondents were asked to identify the
sex, age, and symptoms of the patients as well as the
particular criterion on which the diagnosis was based, the
test methods used, and the time required to reach the
diagnosis.
Results
The survey included 579 patients given a definitive diagnosis of CD and 59 patients given a suspected diagnosis of
CD at the 34 responding medical institutions (Table 2).
Definite cases of CD
Mean age at the time of diagnosis for patients given a
definitive diagnosis of CD was 27.8 13.7 years. A mean
interval of 3.1 10.0 months passed between initial
examination and definitive diagnosis. Abdominal pain was
the most common clinical manifestation (414 patients,
71.5 %), followed by diarrhea (366 patients, 63.2 %) and
weight loss (201 patients, 34.7 %). Ileocolonic type was
the most common disease location (305 patients, 52.7 %),
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Suspected cases of CD
Mean age at the time of diagnosis of patients given a
suspected diagnosis of CD was 36.3 18.6 years.
Abdominal pain was the most common clinical manifestation (41 patients, 69.5 %), followed by diarrhea (35
patients, 59.3 %). The most common disease location was
colonic type (25 patients, 42.4 %) followed by ileal type
(20 patients, 33.9 %) and ileocolonic type (13 patients,
22.0 %) (Table 6).
The particular criteria used to make suspected diagnoses
are listed in Table 7. Of the suspected diagnoses of CD,
74.6 % were based on Suspected 4 (S4): One or two minor
findings. Moreover, 16.9 % of suspected diagnoses were
based on Suspected 2 (S2): major finding A LU or B
CSA, but cannot be differentiated from ischemic colitis
or ulcerative colitis. Among patients given a suspected
diagnosis of CD, the pathology could not be differentiated
from ulcerative colitis (11 patients), Behcets disease/
simple ulcer (9 patients), intestinal tuberculosis (5
patients), ischemic colitis (2 patients), infectious enterocolitis (2 patients), sarcoidosis (1 patient), and collagenous
colitis (1 patient).
95
In the small intestine, the ulcer occurs more commonly on the mesentery side
The rate of detection of this granuloma is improved by creating serial sections. It is advisable that a pathologist familiar with the gastrointestinal tract examine a specimen of it
In typical cases, the ulcers are arranged longitudinally, but this does not occur in some cases. It is necessary that they persist for at least
3 months. With regard to this condition, it is necessary to exclude enteric tuberculosis, intestinal Behcets disease, simple ulcers, nonsteroidal
anti-inflammatory drug (NSAID)-induced ulcers, and infectious enterocolitis
These lesions consist of anal fissures, cavitating ulcers, anal fistulas, perianal abscesses, and edema-like anal skin tags. Preferably, colorectal
surgeons familiar with Crohns disease are consulted to examine such lesions, referring to the Atlas of findings by visual observation of lesions in
anus Crohns disease
e
These lesions have a bamboo joint-like appearance, with notch-like depressions. Preferably, specialists familiar with Crohns disease are
consulted to examine such lesions
f
In cases with only longitudinal ulcers, it is necessary to exclude ischemic intestinal lesions and ulcerative colitis. In cases with only a
cobblestone-like appearance, it is necessary to exclude ischemic intestinal lesions
Discussion
The present survey represents the first nationwide attempt
to determine which specific criteria in the Japanese diagnostic criteria for CD were used to make diagnoses.
Physical examination, laboratory tests, and gastrointestinal
investigations should be conducted when CD is suspected
from the medical interview, and the definitive diagnosis of
CD is made based on the Japanese diagnostic criteria of CD
[4]. The Japanese diagnostic criteria of CD consist mainly
of morphological findings from the gastrointestinal tract
[6]. The criteria provide some supplemental information
about these findings. LU and CSA, two of the criterias
three major findings, have long been considered characteristic of CD [3, 710]. The criteria define a LU as an
ulcer C5 cm that runs longitudinally along the gastrointestinal tract and further state that LU encountered in
ischemic and infectious enterocolitis rarely display a CSA.
In CD, CSA is described as involving dense protrusions
of mucous membrane of uneven sizes, large or small,
surrounded by LU and smaller ulcers. The criteria further
state, This appearance may be seen in ischemic colitis, but
in ischemic colitis the protrusions are smaller and redness
is more intense. NCEG [1114] is an important histopathological finding, but also associated with intestinal
tuberculosis. The criteria recommend creating serial sections and assigning assessment to a pathologist familiar
with the gastrointestinal tract to improve diagnostic accuracy. Irregular-shaped and/or quasi-circular ulcers or aphthous ulcerations found extensively in the gastrointestinal
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96
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because primarily IBD specialist institutions were surveyed. In the survey, 87.4 % of definitive diagnoses of CD
were made based on D1. The vast majority of these
definitive diagnoses were made based on the presence of
LU and CSA are the first findings listed in the definite
category of the criteria. As these findings are characteristic
of CD, it follows that they would serve as the basis for
many diagnoses. A total of 30.4 % of definitive diagnoses
were based on D2. Finally, 7.1 % of definitive diagnoses
were made according to D3. We can think of several reasons why D2 and D3 in the definite category did not
contribute as substantially to the diagnoses. Even non-IBD
specialists are capable of diagnosing CD based on fullblown, typical lesions such as LU and CSA. The expertise
of an IBD specialist, however, is required to identify the
three minor findings in the criteria list, and differentiating
97
Male/female
459/120
Male/female
37/22
27.8 13.7
36.3 18.6
3.1 10.0
22.2 17.7
Clinical manifestations
Clinical manifestations
Abdominal pain
414
Abdominal pain
41
Diarrhea
366
Diarrhea
35
Weight loss
Fever
201
189
Intestinal obstruction
Fever
8
7
Perianal disease
167
Weight loss
Intestinal obstruction
32
Bleeding
Intestinal perforation
14
Perianal disease
Bleeding
19
Fistulas
Arthritis
19
Asymptomatic
Asymptomatic
14
Extent of lesions
Fistulas
10
Extent of lesions
Ileal type
20
Colonic type
25
Ileal type
153
Ileocolonic type
13
Colonic type
121
Ileocolonic type
305
115
SD standard deviation
SD standard deviation
Suspected 1
Major finding C
with minor finding c
Suspected 2
Major finding A or B,
but cannot be differentiated
from ischemic colitis
or ulcerative colitis
Definite 1
Major finding A or B
506/579 (87.4 %)
473/579 (81.7 %)
238/579 (41.1 %)
Definite 2
Major finding C with minor finding a or b
176/579 (30.4 %)
C?a
148/579 (25.6 %)
C?b
71/579 (12.3 %)
Definite 3
All minor findings a, b and c
B
Suspected 3
Suspected 4
10/59 (16.9 %)
9/59 (15.3 %)
1/59 (1.7 %)
8/59 (13.6 %)
44/59 (74.6 %)
40/59 (67.8 %)
2/59 (3.4 %)
6/59 (10.2 %)
41/579 (7.1 %)
0/59 (0 %)
Radiography
(n = 346)
Upper
gastrointestinal
tract
115
Small intestine
161
Colon
416
Biopsy
(n = 152)
Resected
specimen
(n = 46)
10
311
46
38
67
116
18
CD from other diseases can be difficult in patients presenting with these findings. General practitioners would
sometimes be unable to diagnose CD based on perianal
lesions, which should be examined by a proctologist
familiar with CD. The somewhat low biopsy-based detection rate of NCEG (26.3 %) identified in the survey is
likely another reason.
Several facilities and guidelines in the United States and
Europe have proposed diagnostic criteria, many of which
are composed of clinical symptoms and image-based,
surgical, and histopathological findings [3, 2330]. The
European Crohns and Colitis Organisation (ECCO) [3]
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98
123
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