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Indian Pediatr 2017;54: 723-725 |
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Inflammatory Bowel Disease—Unclassified: How
Much do we Know?
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*Ujjal Poddar and Aathira Ravindranath
From the Department of Pediatric Gastroenterology,
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow,
India.
Email: [email protected]
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I
nflammatory bowel disease (IBD) is no longer a
disease of the West as there are reports of increasing incidence of IBD
in general, and Crohn’s disease in particular, from India [1,2]. Though
IBD is less common in children than in adults, almost one-fifth to a
quarter of all cases are diagnosed in first two decades of life. There
are three entities under the umbrella of IBD: ulcerative colitis (UC),
Crohn’s disease (CD) and IBD-unclassified (IBD-U). Proportion of these
entities varies from country to country, and from region to region. In
the West, around 60% of all cases of IBD in children are CD, 32% UC, and
the remaining 8% IBD-U [3]. While in Northern India, UC is more common
than CD, the reverse is true in Southern India [2]. Though there are set
diagnostic criteria for CD and UC, IBD-U is basically a diagnosis of
exclusion (cases of colonic phenotype of IBD that lacks features which
will enable classification as CD or UC).
Understanding IBD-U assumes more importance in the
pediatric population as the prevalence of IBD-U is higher among children
than in adults (13% vs. 6%, respectively) [4]. The proportion of
IBD-U declines with increasing age as evidenced by a large study of 1370
cases of IBD, where IBD-U (n=179) accounted for one-third of all
IBD in children less than 2 years and the proportion dwindled to 9% in
those above 13 years [5]. Clinically, this entity is indistinguishable
from UC or CD with isolated colonic involvement. Nevertheless, the age
of presentation is shown to be younger and disease severity is milder in
IBD-U compared to UC or CD as evidenced by lower Physician Global
Assessment scores (PGA), lower use of steroids, immunomodulators and
colectomy rates in IBD-U [6].
The natural history suggests that IBD-U may be the early
manifestation of either UC or CD in a proportion of cases. In EUROKIDS
study, 38 of 117 (33%) cases of IBD-U were reclassified as UC (23, 60%)
or CD (14, 37%) within median (IQR) 2.7 (1.0, 4.0) years of diagnosis
[3]. Long-term follow-up studies in adults as well as in children have
shown that almost half of the cases of IBD-U turned out to be non-IBD
(non-specific colitis) [7,8]. Hence it is important to keep these
patients on regular follow-up for reclassification (early) and to rule
out IBD (in long run).
IBD is now diagnosed and classified according to the
revised Porto criteria [9], which mandates ileocolonoscopy,
esophagogastroduodenoscopy, histology and small bowel imaging in all
cases (except for typical cases of UC). Though there is an exhaustive
list of features to aid in classification of IBD, the picture gets
complicated when ambiguity creeps in a case with colitis phenotype (thus
labeled as IBD-U), like transmural inflammation without acute severe UC,
macroscopic and microscopic rectal sparing, nonspecific inflammation and
ulcers in upper gastrointestinal tract, ambivalent serological markers (pANCA,
ASCA), reverse gradient of mucosal inflammation (more severe in proximal
colon) and significant growth delay [9]. The importance of complete
diagnostic work-up and strict adherence to the Porto criteria before
labeling as IBD-U has been highlighted in a recent study that showed a
reduction of prevalence from 7.7% to 5.6% on follow-up with complete
re-investigation [3].
The study by Paul, et al. [10], published in
this issue of Indian Pediatrics, is commendable in its effort to
unveil the course of IBD-U in children. It emphasizes the importance of
thorough work-up at diagnosis as per the revised Porto criteria, and
also the readiness for repeat assessment and reclassification at
follow-up. The inherent drawback of a retrospective study is obvious
here as some information is missing. The detailed information about
three cases that were later reclassified in another center was not
available, and reasons for reclassification of these cases are unclear.
In the present study [10], 40% were reclassified; of these, 70% were
categorized as CD and 30% as UC, which is in contrast to previous
studies. In the EUROKIDS registry (n=3, 461 IBD cases), 33% of
IBD-U were reclassified out of which 60% were categorized as UC [3]. In
another large pediatric IBD cohort (n=210), 50% of IBD-U were
reclassified, within a median follow-up of 18.5 months, to UC (75%) or
CD (25%) [11]. The long-term outcomes of IBD-U in terms of treatment
response, remission and requirement of surgery are not clear from the
present study. More often remission is achieved and maintained in IBD-U
with aminosalicylates alone, and the remission rate is higher than in CD
or UC [6,7]. It has been suggested that aminosalicylates should be the
first line of treatment in active IBD-U [6]. In light of the paucity of
recommendations on treatment of IBD-U and exclusion of IBD-U from
clinical trials on treatment strategies for IBD, there is a dire need to
appraise treatment responsiveness and formulate evidence-based
recommendations for IBD-U.
In view of the variations in prevalence, natural
history, treatment response and a potential for reclassification of
IBD-U, there is a need for further exclusive studies on IBD-U to better
delineate this abstruse disease entity.
Funding: None; Competing interests: None
stated.
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