Indian J Pediatr (December 2016) 83(12):14441451

DOI 10.1007/s12098-016-2091-5

REVIEW ARTICLE

Approach to a Child with Colitis

Sirish K. Palle 1,2 & Mahadev Prasad 1 & Subra Kugathasan 1,2,3

Received: 9 October 2015 / Accepted: 10 March 2016 / Published online: 15 April 2016
# Dr. K C Chaudhuri Foundation 2016

Abstract In this review, the authors discuss the etiology,

pathogenesis, and clinical presentations of colitis in children, and provide current recommendations for the approach to a child with colitis. In addition, they discuss
in detail one of the important and emerging causes of
chronic colitis in children; inflammatory bowel disease
(IBD). Diagnostic and management approaches to colitis
in children vary considerably based on several factors,
including if the colitis is acute in onset or chronic, the
age of the child, and the geographical region of the
affected child. Broader classification or differential diagnosis of colitis falls under infectious, inflammatory, allergic, and less commonly, immune-mediated and ischemic colitis. Recent epidemiologic reports have elucidated a shift in our understanding of ethnicities and geographic regions affected by IBD. The incidence and
prevalence of IBD has been steadily increasing in developing countries, including South-East Asia/India.
Also, the risk of developing IBD among the secondgeneration South-Asians immigrants has greatly increased, with rates approaching those in the Western
country to which they immigrated. Current research is
focusing on genetic, environmental, and dietary factors

* Subra Kugathasan
skugath@emory.edu

Department of Pediatrics, Emory University School of Medicine,

Atlanta, GA, USA

Childrens Healthcare of Atlanta, Atlanta, GA, USA

Division of Pediatric Gastroenterology, Department of Pediatrics,

Emory University School of Medicine, 2015 Upper gate Drive,
Room 248, Atlanta, GA 30322, USA

to understand the increased incidence of IBD in developing countries and immigrants from developing
nations.
Keywords Colitis . Crohns disease . Ulcerative colitis .
Children

Abbreviations
IBD
Inflammatory Bowel Disease
CD
Crohns Disease
UC
Ulcerative Colitis
MRE
Magnetic Resonance Enterography
CRP
C-Reactive Protein
ESR
Erythrocyte Sedimentation Rate
PCDAI Pediatric Crohns Disease Activity Index
PUCAI Pediatric Ulcerative Colitis Activity Index

Introduction
Colitis refers to inflammation of the mucosal lining of
the colon and can be associated with abdominal pain,
diarrhea, fever, tenesmus, urgency, and blood in the
stool. Colitis in children can have multiple causes such
as infection, inflammatory bowel disease, allergic,
ischemic/vascular or colitis secondary to immune deficiency disorders. Fortunately, most cases of colitis in
children are secondary to infection [1] (Table 1) which
is self-limiting in its course, can be managed by general
pediatricians, and do not typically require a referral to
pediatric gastroenterology with few exceptions such as
inflammatory bowel disease (IBD). In IBD, comanaging a child with pediatric gastroenterologists is
advisable. Specific diagnostic consideration for colitis

Indian J Pediatr (December 2016) 83(12):14441451

Table 1

1445

Clinical features and recommended laboratory workup for colitis due to infectious etiology

Etiology

Clinical features

Tests

Additional comments

Campylobacter jejuni [2, 3]

Acute bloody diarrhea and fever

Stool culture

Yersinia enterocolitica [4]

Acute bloody diarrhea, fever and

right lower quadrant pain, similar
picture to appendicitis
Acute watery diarrhea and fever

Stool culture

Can mimic Crohns disease clinically as

well as radiologically

Stool culture

Commonly occurs in children younger

than 5 y of age

Acute watery to bloody diarrhea,

fever and abdominal pain
Acute water to bloody diarrhea,
abdominal pain, fecal blood
and leucocytes
Fever, weight loss, bloody diarrhea,
abdominal pain, Ileocecal area,
fistula formation
History of antibiotic use, watery
to bloody diarrhea, pseudomembrane
on colonoscopy

Stool culture

Bacterial

Salmonella [5]
Shigella [6]
Escherichia coli
O157:H7 [6]
Mycobacterium
tuberculosis [7, 8]
Clostridium difficle [9]

Stool culture

Hemolytic-uremic syndrome, food

borne diarrheal illness

Culture, PPD, biopsy

Can mimic Crohns disease, both

clinically and radiologically

Stool for C.difficle toxin

(enzyme immune assay,
PCR or cytotoxin assay)

Nosocomial diarrhea, can cause

toxic megacolon

Acute bloody diarrhea, abdominal

pain, colonoscopy classic flask
shaped ulcers

Stool for ova and parasites,

serological tests

History of travel to endemic area,

can mimic chronic IBD

Abdominal pain, bloody diarrhea

Culture, biopsy for Immuno

stains and PCR

May occur in immunosuppressed

children, both in disease states
such as HIV or following organ
or bone marrow transplant

Parasites
Entamoeba histolytica [10]
Viral
Cytomegalovirus [11]

by age is shown in Table 2. IBD is an umbrella term

which refers to Crohns disease (CD) and Ulcerative
colitis (UC). These are the two commonest chronic digestive diseases. For decades, CD and UC were considered different entities since the clinical features and natural history of these diseases varied widely. However,
the recent developments and findings that CD and UC
can occur in the same families, share common genetic
susceptibility genes and pathways, and respond to therapies similarly have made clinicians and scientists think
of IBD as one entity with similar pathophysiology, clinical features, and outcome.

Epidemiology of Inflammatory Bowel Disease

Most epidemiology studies in IBD come from geographic
areas with higher rates of IBD, but many small series on
IBD epidemiology have been published recently from Asia,
Eastern Europe, and South America [1214]. These studies
suggest that the highest IBD disease rates occur in the western
or industrialized countries and that it has an uneven global
distribution [15, 16]. Recent epidemiologic surveys have also
suggested that IBD incidence rates have changed over the

second half of the 20th century, with a gradual increase in

CD and plateauing incidence in UC [17].

Table 2

Common causes of colitis categorized by different age groups

Neonates
Necrotizing enterocolitis
Cows milk protein induced allergic colitis
Hirschsprung associated enterocolitis
Congenital/primary immunodeficiency disorders
Infants and Toddlers
Cows milk protein-induced allergic colitis
Congenital/primary or acquired immunodeficiency disorders
Infantile (and toddler) onset inflammatory bowel disease
Preschool period
Henoch-Schnlein purpura
Acquired immunodeficiency disorders
Early onset inflammatory bowel disease
School aged and adolescents
Pediatric onset inflammatory bowel disease
Vascular-ischemic colitis (associated with rheumatologic disorders)
Microscopic colitis
Note: Infectious colitis can occur in any age group. Please refer Table 1

1446

Inflammatory Bowel Disease in the Pediatric

Population
There have been few systematic, population-based studies
performed regarding the true incidence of childhood IBD.
These studies estimate the incidence of IBD in the pediatric
age group to be 712 per 100,000 children [18]. Several studies and surveys estimate the prevalence of pediatric IBD at
100150,000 in North America (USA and Canada), while the
pediatric population in these countries is estimated to be
around 80 million. Based on these numbers, IBD is a rare
condition with about 1 in 600 children affected by IBD. But
on the other hand, IBD is chronic, and is the most common
chronic gastrointestinal disorder pediatricians and pediatric
gastroenterologists care for at any given time in USA/
Canada or in Europe. Precise epidemiological data from rest
of the world is lacking. While IBD can occur at any age, it
presents predominantly in late adolescence to young adulthood and its onset peaks in the second to third decades of life.
Although limited, clinical data suggests that childhood IBD
has more severe manifestations characterized by extensive
intestinal manifestations. Specifically, childhood CD presents
with greater incidence of fistulising ileal and colonic disease.
UC, however, presents more frequently with pancolitis and
decreased time to first surgery. Additionally, childhood CD
shows a trend toward male predominance, as opposed to UC
that seems to be gender neutral [19, 20].

Inflammatory Bowel Disease in India

As there are no population-based registries in India, most of
the available data is from case series across tertiary care centers. The incidence and prevalence rates reported for CD and
UC were 6.02 per 100,000 and 44.3 per 100,000 [21].
Published data from United Kingdom and Canada show an
increased incidence and prevalence of IBD in immigrants
from South Asia, particularly among the second and third
generation immigrants [22, 23]. Interestingly, recent
population-based cohort studies from Canada showed that
younger immigrants from less prevalent geographic regions
like South Asia are at greater risk of developing IBD [24, 25].

Etiology
The etiology of IBD is not completely understood.
Although there is overwhelming evidence that IBD is
a genetic disease in large part with over 200 genetic
loci been discovered, the changing epidemiology of
IBD implies that, in addition to a genetic susceptibility
for disease, environmental triggers such as diet and specific commensal microbiota signatures may likely

Indian J Pediatr (December 2016) 83(12):14441451

impact disease presentation and eventual phenotypic expression [26]. In regards to genetic susceptibility, many
GWAS (genome-wide association studies) in IBD have
implicated many genes and pathways that involve in
bacterial recognition and handling. The largest effect
was observed in gene nucleotide- binding oligomerization domain-containing protein 2 (NOD2) in CD and is
only found in Caucasians, indicating the genetic susceptibility may be related to populations [27]. Several
GWAS studies and a recent trans-ethnic mapping across
population including North Indians revealed that the
majority of risk-associated IBD loci are shared across
populations. However, a handful of loci including human leucocyte antigen (HLA) and tumor necrosis factor
ligand superfamily, member 15 (TNFSF15) demonstrate
heterogeneity of effect among Asian populations [28].
Taken together, genetic studies have great potential to
reveal important pathways that can be used to discover
treatments to ameliorate inflammation in patients with
IBD.

Clinical Features
Clinical features of both UC and CD are described in Table 3
[29]. Laboratory tests that should be ordered include complete
blood count (CBC), erythrocyte sedimentation rate (ESR), albumin, aminotransferases, C reactive protein (CRP), iron studies,
and stool calprotectin. The four lab tests that are most commonly
abnormal and good indicators of the presence of IBD are the
elevated ESR (>20 mm/h) or CRP, thrombocytosis (>400,000),

Table 3 Presenting features and physical examination findings in

children with inflammatory bowel disease
History

Physical examination

Abdominal pain
Abdominal pain distant from umbilicus
Pain that interferes with sleep
Discrete episodes of pain that are acute
in onset
Pain precipitated by eating
Dysphagia, odynophagia
Involuntary weight loss
Rectal bleeding
Nocturnal diarrhea
Extraintestinal manifestations
Unexplained low grade fevers
Erythema nodosum, pyoderma
gangrenosum
Joint pain/swelling
Jaundice
Severe eye pain or persistent conjunctivitis
Strong family history of IBD

Anemia
Decreased growth velocity
Delayed sexual maturation
Finger clubbing
Oral ulcerations
Abdominal tenderness
Abdominal mass
Perianal fistula, fissures,
skin tags

Indian J Pediatr (December 2016) 83(12):14441451

1447

decreased albumin level (2.03.5 g/dl), and decreased hemoglobin level indicating iron deficiency anemia [30, 31]. If any of
these labs are abnormal, referral to a specialist should be made in
a timely manner so that the diagnosis is confirmed with further
work up. Differentiating features of different types of colitis are
described in Table 4 (Figs. 1, 2 and 3).

salicylates, immunomodulators and biologics. These classes

have allowed practitioners to discontinue steroid use in some
cases. There is a recent increased focus on IBD pathways and
genetics which will ideally allow focussed targeting of those
pathways in the future, hopefully this targeting will lead to
better outcome with fewer adverse effects. Many treatment
medications overlap between UC and CD but there are some
clear indications that differ.

Serological Markers
Corticosteroids
Serologic markers such as anti-Saccharomyces cervisiae
(ASCA), pANCA (anti-neutrophil cytoplasmic antibodies),
antibody to outer membrane protein (Anti-OmpC) and others
are used by few clinicians to identify IBD subtypes in cases
where there is a significant overlap in the results after conventional diagnostic work up. Currently, there is insufficient evidence in the use of these serological markers for therapeutic
strategies or monitoring treatment response of IBD patients.

Management
Over the last 15 y, medical therapy has progressed. Before the
year 2000 the main therapy was corticosteroids, with few other options. Classes of drugs used to treat IBD include amino
Table 4

Corticosteroids remain the main therapy for the induction of

remission in moderate to severe CD and UC by providing
rapid improvement of inflammation [35]. No evidence suggests that they provide mucosal healing, and they should not
be used as maintenance therapy. They are typically started in
tandem with a maintenance therapy to induce remission; while
the maintenance drug takes effect, the steroids are gradually
weaned. IV steroids can be used in severe UC and CD to
induce remission. Rectal steroid enemas can be used for
proctitisand sigmoid disease with no systemic side effects.
The other formulations of steroids like oral budesonide, which
has first pass metabolism, can be used to minimize systemic
adverse effects [36]. Systemic steroids have many adverse
effects in children, particularly the effects on growth,

Differentiating features of different types of colitis

Clinical features

Endoscopic features

Infectious colitis

Acute onset of watery or

Patchy areas of erythema,
bloody diarrhea, abdominal
discreet ulcers/erosions,
pain and fever
loss of vascular pattern

Ulcerative colitis [32]

Diarrheal, rectal bleeding

and abdominal pain

Crohns colitis [32, 33] Abdominal pain, diarrhea,

poor appetite, weight loss
and growth failure

Tuberculous colitis
[7, 8, 34]

Fever, abdominal pain,

weight loss, bloody
diarrhea and change
in bowel habits

Histological features

Edematous mucosa, superficial ulcers

with exudates, cryptitis with abscesses
and increased cellularity of lamina
propria with predominant neutrophils
and lymphocytes
Chronic or chronic active colitis
Diffuse and continuous inflammation
(crypt architectural distortion, basal
beginning in rectum and extending
lymphocytosis, distal Paneth cell metaplasia)
proximally to a variable extent. Features
of inflammation as shown in Fig. 1
Inflammation limited to mucosa with only
colonic involvement
Chronic or chronic active colitis (colonic
Segmental distribution with occasional
findings similar to UC but commonly
pan colonic involvement, typically
patchy), ileitis, small, poorly organized
with rectal sparing
- Aphthous ulcers
non-caseating granulomas. Discontinuous
inflammation with zones of normal
- Linear ulcers (Fig. 2)
bowel in between
- Deep fissuring ulcers with
cobblestone mucosa
- Stricture (eccentric) and fistula formation
- Perianal disease
Confluent caseating granulomas in the
Ileocecal area is the most common
submucosa and positive acid-fast bacilli have
site of intestinal involvement but
been reported in one-third of positive cases
can also occur in any segment of colon.
Erythematous mucosal nodules and deep
serpiginous ulcers in a discreet segment
of colon (Fig. 3). Fissures and intestinal
strictures (eccentric) can occur

1448

Fig. 1 Endoscopic features of Ulcerative colitis: diffuse erythema,

friability, granularity and loss of vascular pattern in the colon

immunity and adrenal suppression. For these reasons, plus

lack of efficacy in maintenance of remission and mucosal
healing in IBD, they should be used only for short period of
time, ideally less than 3 mo.
Aminosalicylates (ASAs)
Aminosalicylates are a wide group of medications that all
contain a 5-aminosalicylate (5-ASA) moiety. These medications have shown to be effective in induction and maintenance
of remission in mild to moderate UC and are the first line of
therapy in these cases [37, 38]. They may also have some
benefit in maintenance of remission in mild CD. Because
ASAs have varying delivery systems which determine the
segment of bowel targeted, it is imperative to understand disease location prior to initiation of this therapy. In general,
these therapies are well tolerated.
Immunomodulators
6-Mercaptopurine and Azathioprine
Azathioprine and its metabolite 6-mercaptopurine (6-MP)
are used for steroid refractory CD for decades. They are

Indian J Pediatr (December 2016) 83(12):14441451

Fig. 3 Endoscopic features of tuberculous colitis: ascending colon

showing erythematous mucosa, nodularity and deep serpiginous ulcers

also used as maintenance of remission in moderate to

severe UC and CD [39, 40]. These drugs are not used
in the induction of remission because they act slowly
and may take up to 36 mo to reach maximal effect.
Most often they are started in conjunction with steroids
in moderate to severe disease and when used in this
way, can minimize the steroid use. Adverse effects of
these drugs are idiosyncratic and dose dependent.
Idiosyncratic adverse effects are pancreatitis, fevers, and
myalgias. Dose dependent adverse effects include infection, bone marrow suppression, and elevated liver enzymes
[41]. Patients must be monitored for these side effects.
Thiopurine methyl transferase activity (TPMT) is the enzyme that metabolizes these drugs and patients have different genotypes for this enzyme. A laboratory test to
check the enzyme levels or genotypes and therefore, how
a patient will respond to therapy, is commercially available
and should be done prior to starting therapy to help guide
dosing and prevent adverse effects. Patients who metabolize these drugs slowly are at higher risk for bone marrow
suppression and require decreased doses of the medication
[41]. These drugs are contraindicated in patients with no
TPMT activity, although this is rare. 6-thioguanine nucleotide (6-TG) levels can be used to optimize the dose or
check compliance.

Methotrexate

Fig. 2 Endoscopic features of colonic Crohns disease: deep fissuring

linear ulcers and exudates

Methotrexate has shown to be effective in inducing and maintaining remission in adult patients with CD [42]. So far, there
have been no controlled trials of methotrexate use in pediatric
CD but reports from retrospective reviews have shown good
remission rates in patients that fail 6-MP or are intolerant to
azathioprines [42]. Methotrexate is a known teratogen, so
birth control counseling must be given to all females of childbearing age who are started on this therapy.

Indian J Pediatr (December 2016) 83(12):14441451

1449

Biologic Therapies
Biologics have changed the treatment and management of
IBD dramatically. One class of these drugs is the anti-tumor
necrosis factor alpha (TNF) agents. Tumor necrosis factor
alpha is a cytokine involved in systemic inflammation and can
stimulate the acute phase reaction. Infliximab blocks the action of TNF by preventing it from binding to its receptor in
the cell. Infliximab, the first in this class to be approved in
pediatric IBD, is a chimeric (part mouse and part human)
monoclonal IgG1 antibody that is given intravenously. This
biologic is used in children with moderate to severe UC and
CD [40, 43]. Infliximab is also effective in fistulising and
perianal CD [43, 44]. Since infliximab is chimeric, it can cause
formation of antibodies against the drug and decrease efficacy.
The most common adverse effects for infliximab include infusion reactions, infections, and ALT elevations. Infusion reactions are usually mild and respond to antihistamine therapy.
Another anti-TNF agent, adalimumab, has been approved for
treatment of IBD in adults and recently approved for pediatric
CD [45]. Adalimumab is a recombinant human IgG1

Fig. 4 Approach to a child with

chronic colitis

monoclonal antibody. Adalimumab has decreased occurrence

of antibody formation and is given as a subcutaneous injection. Biologic therapies can reactivate latent Mycobacterium
tuberculosis and all patients must have a documented negative
PPD or quantiferon gold before starting the therapy.
Other more serious complications with anti-TNF
drugs are increased risk for malignancy. Infliximab has
a black box warning regarding hepatosplenic T-cell lymphoma [46], which is a rare and often fatal T-cell lymphoma that has been reported in approximately 12 US
cases. All patients had IBD and majority were young
males. All these patients had received infliximab in conjunction with azathioprine and 6-mercaptopurine. For
this reason, these agents should not be used concurrently in young males, until other options are exhausted and
the benefits outweigh the risks. Other malignancies that
have been associated with anti-TNF agents include lymphoma and leukemia (the risk is 24 times the general
population).
Overall medical approach to a child with chronic colitis is
summarized in Fig. 4.

Patient history and exam especially looking for red flags

(Bloody/nocturnal diarrhea, tenesmus, urgency, weight loss, anemia and growth failure)

Consider/exclude infections (such as bacterial, TB, C.difficle, CMV, HIV)

Consider/ exclude other causes of intestinal inflammation as per age

Labs- CBC, CRP, ESR, albumin, PPD, chest x-ray, stool culture, stool C.diff toxin and
stool O&P
If labs show low hemoglobin levels, decreased albumin, elevated ESR and
thrombocytosis

Referral to pediatric gastroenterologist

Extent, behavior and location of disease- Upper and lower GI endoscopy, MRE
and histology (If infection is strongly suspected send biopsy tissue- PCR and
culture for viral, TB and bacterial infections)

Ulcerative Colitis

Mild UC (PUCAI 10-30)

PO steroids & oral Aminosalicylates
Moderate UC (PUCAI 35-60)
PO steroids and Immunomodulators
Severe UC (PUCAI 65)
Admit, IV steroids, consider biologics
therapies

Crohns disease

Minimal symptoms, normal growth,

PCDAI < 30, inflammatory type- PO
steroids and Immunomodulators
Severe symptoms, PCDAI > 30,
growth failure, peri-pubertal,
structuring, internal penetrating or
perianal consider biologics and
surgery options

1450

Surgical Management
IBD first line treatment remains medical therapy. Indications
for surgery are relatively similar between ulcerative colitis and
Crohns disease, however, the approach and the outcomes
differ. Indications for surgery include fulminant colitis, massive hemorrhage, perforation, stricture, abscess, fistula (in
Crohns disease), toxic megacolon, failure of medical therapy,
steroid dependency, and dysplasia. Additional indications for
surgery in pediatric patients include growth and pubertal delay
as children often demonstrate post operative catch up growth.
When deciding to perform surgery for UC, the diagnosis
should be confirmed to the highest degree possible because
the approach, follow-up, and outcomes vary between UC and
CD. The current standard surgical procedure for UC is total
colectomy followed by ileoanal pull-through with anal anastomosis (IPAA) [47]. In this procedure, an ileal reservoir,
Bpouch^, is created which allows preservation of anorectal
function and avoids permanent ileostomy. This is typically a
staged surgery with 13 stages occurring over several months.
Typically, a patient has a temporary ileostomy prior to pouch
creation. These surgeries may be performed open or
laparoscopically. Complications include pouchitis, which is
inflammation of the pouch, obstruction of the small bowel,
anastomotic leak, strictures, fecal incontinence, fistula, and
anal transition zone dysplasia [48].
Majority of patients with Crohns disease will need surgery
during their life, although this number is decreasing due to
advances in medical therapy. As recurrence rates of CD are
very high within 5 y of surgery, the aim of the surgery is to
resect as little bowel as possible. This is also the reason CD is
a relative contraindication to IPAA. Postoperative recurrence
prevention is an area of debate and varies between physicians,
patients and families.

Conclusions
Inflammatory bowel disease is one of the chronic diseases
with a remitting and relapsing disease course. With effective
management, majority of the children with IBD can lead active normal lives. Management of IBD requires a multidisciplinary approach with pediatricians and sub-specialists. As the
incidence of pediatric IBD is increasing worldwide, and as
immigration and geographic trends are changing, IBD should
be considered in the differential diagnosis of chronic colitis in
children, even in countries with historically lower prevalence
such as India. If substantial differences exist in regards to
clinical features, response to therapy, and natural history
among Indian children with IBD compared to their western
counterparts, they have not yet been discovered. Well-defined,
epidemiologic studies are needed to address two important
aspects of IBD pertaining to Indian community: first to

Indian J Pediatr (December 2016) 83(12):14441451

characterize the true incidence and prevalence of IBD in stable

population residing in India or South Asia, and second to
identify epidemiological or other factors that put immigrant
children of south Asian living in western world at greatest risk
of developing IBD.
Acknowledgments The authors thank Jordan Weitzer, MD for critical
review of the manuscript.
Contributions SKP was critical in researching and assimilating the
required material for the manuscript. He was involved with the creation
writing of the manuscript. MP was responsible for citation search, literature review and bibliography. SK is the senior and corresponding author
responsible for the overall manuscript. He provided the critical input and
material for the development of this manuscript. He will act as guarantor
for the paper.
Compliance with Ethical Standards
Conflict of Interest None.
Source of Funding None.

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