HOw tO apprOacH tHe patIent wItH cOlItIS, 139

How to approach the patient with colitis,
type-unclassified: Diagnosis and management options
Janneke van der Woude
The Netherlands
Learning objectives
1.The term indeterminate colitis (IC) is reserved for colectomy
2. The diagnosis of IC in a colectomy specimen may change to ulcerative colitis or Crohn’s disease.
3. The diagnosis colitis, type-unclassified or IC should not be regarded as a contra-indication for ileal pouch anal anastomosis.
After this course the participant is able to
1. Describe factors leading to the diagnosis of colitis, type-unclassified.
2. Describe the management in the patient group.
The management of patients with ulcerative colitis (UC) and
Crohn’s disease (CD) may differ in terms of medical treatment,
disease course and long-term prognosis and type of surgery. Most
complicated are those cases where a colectomy is needed and the
patient has rectal inflammation without a clear diagnosis of either
UC or CD, because an ileal pouch anal anastomosis (IPAA) in
CD is generally contraindicated due to a high risk of morbidity
related pouch complications (fistulas) and pouch failure. Definitions In approximately two-third to three quarter of newly diagnosed patients a correct diagnosis of inflammatory bowel disease
(IBD) can be made, and the additional endoscopic and clinical
data allow a final diagnosis in the vast majority of patients (1). In
1978, Price introduced the term indeterminate colitis (IC) to refer
to a subgroup of 10-15 % of IBD cases (mostly patients with severe
inflammatory activity) in which there was difficulty to distinguish
between UC and CD in the excised colon (2). After this publication the term IC was not only used for colectomy specimens but
also used by gastroenterologist in patients of whom the diagnosis
inflammatory bowel disease was clear but insufficient data was lacking to make a definite diagnosis. Because the term IC was originally proposed for colectomy specimens and not all diagnostic
microscopic features can be assessed on endoscopic biopsy samples
it was recommended to restrict the term IC to resected colon
specimens and to use IBD unclassified (IBDU) for all other cases
(3). Pathological features In the original description by Price, 90%
of the patients diagnosed with IC had undergone urgent surgery
and since this first publication others have also found that the dia-
gnosis of IC more often is associated with urgent surgery for acute
or fulminant colitis (4-6). In the acute phase pathological features
of UC and CD can overlap. For example the presence of fissures
can lead to confusion. The typical chronic fissures of CD are usually single serpiginous tract lined with inflammatory cells, but fissures can also be seen in fulminant disease. In Price’s IC paper, he
described in areas of severe ulceration the presence of multiple,
short, V-shaped fissures. Another paper described probably the
same pathological features as deep slit-like fissures (7). Transmural
inflammation which can be a feature of CD was present in most
cases of IC, but only related to areas of severe ulceration, this was
further specified by Lee et al (7). Transmural inflammation was
defined as lymphocytes in an aggregated pattern in all layers of the
colon, including the serosa. The presence of scattered mononuclear inflammatory cells in the muscularis mucosa adjacent to ulceration was regarded as a non-specific response of the colon, including the serosa. Serologic markers Serologic tests may be used for
diagnostic purposes; however data on the value of these tests are
conflicting. In a prospective study on patients with IBD unclassified, a 48% positive predictability of ASCA-/pANCA- was found
for sustained IC (8). In contrast in a large population based study
no substantial number of IC patients with this pattern was found
(9). Common reasons for diagnosing IBD unclassified The most
common reason for diagnosing IBD unclassified is in a patient
with a fulminant colitis, when there is insufficient clinical, radiologic or pathological information, which stretches the importance to
follow the guidelines for diagnosing IBD (10). Furthermore unu-
Medical & Surgical Gastroenerology II Medical / surgical scenarios in ulcerative colitis
Saturday, October 22
14:00 – 16:30
Key messages
Janneke van der Woude | How to approach the patient with colitis, type-unclassified:
Diagnosis and management options
Saturday, October 22
14:00 – 16:30
sual variants of UC and CD can be overlooked, such as UC patients demonstrating at endoscopy relative rectal sparing and backwash ileitis and at biopsies superficial fissures, granulomas related
to ruptured crypts, or even skip lesions due to therapy effect. Furthermore the presence of a secondary disease can lead to difficult
interpretation of biopsy specimens for example the UC patients
with an intestinal co-infection. Unusual variants of UC and CD
As depicted in the above paragraph there are different reasons leading to a diagnosis of IBD unclassified, some of these reasons are
listed below:
1. Effect of oral and topical therapy: in both UC and CD features
found in biopsies can be related to the effect of medical treatment. In UC patients followed over time endoscopic and histological patchiness of inflammation and rectal sparing was found
in 59% of the patients (11).
2.Children with a newly diagnosed IBD: especially in children
microscopic features used for the diagnosis of IBD are often not
present in the early stage of disease. Atypical lesions at initial
presentation of UC include absence of chronicity, mild active
disease, and microscopic skip areas (12).
3. Backwash ileitis: patients with severe pancolitis may show a mid
degree of active inflammation in the distal few centimetres of
the terminal ileum. Occasionally this inflammation is confused
with CD of the terminal ileum, also due to the fact that strict
histolopathologic criteria are lacking.
4.Upper gastrointestinal tract involvement: gastroduodenal involvement, which is often used to be diagnostic of CD, may also
occur in UC (13). Furthermore diffuse antral H pylori negative
gastritis is of no value to distinguish between UC and CD, with
diffuse acute duodenitis being more suggestive of UC (14, 15).
5. Perianal fistulas in UC: both low and high fistulas can be present in the absence of CD.
Frequency and natural history In approximately 5% of IBD cases,
a definite diagnosis of UC or CD cannot be established, it is estimated that the true nature of the patient’s underlying IBD usually
becomes apparent within a few years (17). A recent meta-analysis
found that in children more frequently the distinction between
UC and CD could not be made when compared to adults (12,7%
versus 6%, p<0.0001) (18). Large studies studying the natural history of IBD unclassified are scarce. In a study from Norway a large
proportion of patients initially diagnosed with IBD unclassified,
after one year were reclassified to UC, CD, and non-IBD (9, 18).
A review of IC patients that underwent restorative proctocolectomy showed that the percentage of patients that subsequently develop CD varies from 0-15%, whilst a significant number of patients
remain categorised as having IC (19). Management The medical
management of IBD unclassified resembles the management of
UC. This includes the initiation of 5-ASA in mild to moderate
cases to anti-TNF inhibitors in severe refractory cases (20). Surgery is usually performed in a 2-step procedure, after a subtotal colectomy the colon will be thoroughly reviewed by the pathologist and
in cases of persisted diagnosis of IBD unclassified (now IC) a
pouch construction can be performed (20). Outcome pouch Some
surgeons are reluctant to offer IPAA to IC patients due to the re-
ported risk of pouch failure compared to UC in early small case
series. However the general consensus is that there is no significant
difference in pouch failure and functional outcome between UC
and IC, but other postoperative complications such as pelvic sepsis
and fistulae are more often seen in IC patients (21). Colorectal
cancer It is known that colorectal cancer (CRC) can complicate
IBD unclassified. In the Netherlands of 149 cases of CRC complicating IBD only one patient was diagnosed with IC and in another
study conducted in a referral hospital with 57 IBD CRC patients
only 2 patients had the diagnosis of IC (22-23). Conclusions The
term IC should be reserved only for those cases where colectomy
has been performed and a definitive diagnosis of CD or UC cannot be made. The current term for uncertain cases is IBD unclassified. Management of patients with IBD unclassified resembles the
mangment of an UC patient, including undergoing an IPAA, although this can be related to postoperative complications such as
pelvic sepsis and the forming of fistulas. Case presentation In the
course a case of young male with unclassified will be presented and
some of the challenges in treating a patient with colitis, type-unclassified will be discussed.
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Medical & Surgical Gastroenerology II Medical / surgical scenarios in ulcerative colitis
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Policy of full disclosure
Herewith I disclose the participation in advisory board of the following companies: MSD, Abbott labaratories, Shire. Unrestricted
grant were obtained form: Ferring The netherlnad, Falk Benelux,
Medical & Surgical Gastroenerology II Medical / surgical scenarios in ulcerative colitis
Saturday, October 22
14:00 – 16:30
How to approach the patient with colitis, type-unclassified: | Janneke van der Woude Diagnosis and management options