Management of Acute Severe

Colitis in Children With Ulcerative

Colitis in the Biologics Era
Claudio Romano, MD,a Sana Syed, MD,b Simona Valenti, MD,a Subra Kugathasan, PhDb

BACKGROUND AND OBJECTIVE: Approximately one-third of children with ulcerative

abstract

colitis will experience at least 1 attack of acute severe colitis (ASC) before
15 years of age. Severe disease can be defined in children when Pediatric
Ulcerative Colitis Activity Index is >65 and/or 6 bloody stools per
day, and/or 1 of the following: tachycardia, fever, anemia, and elevated
erythrocyte sedimentation rate with or without systemic toxicity. Our
aim was to provide practical suggestions on the management of ASC in
children. The goal of medical therapy is to avoid colectomy while preventing
complications of disease, side effects of medications, and mortality.
METHODS: A systematic search was carried out through Medline via PubMed

to identify all articles published in English to date, based on the following

keywords ulcerative colitis, pediatric ulcerative colitis, biological
therapy, and acute severe colitis. Multidisciplinary clinical evaluation is
recommended to identify early nonresponders to conventional treatment
with intravenous corticosteroids, and to start, if indicated, second-line
therapy or rescue therapy, such as calcineurin inhibitors (cyclosporine,
tacrolimus) and antitumor necrosis factor molecules (infliximab).
RESULTS: Pediatric Ulcerative Colitis Activity Index is a valid predictive tool
that can guide clinicians in evaluating response to therapy. Surgery should
be considered in the case of complications or rapid clinical deterioration
during medical treatment.
CONCLUSIONS: Several pitfalls may be present in the management of ASC, and

a correct clinical and therapeutic approach is recommended to reduce

surgical risk.

typical mucosal vascular pattern.

Histologic features include crypt
architectural distortion, cryptitis, and
crypt abscesses.4 Many patients with
UC present with acute severe colitis
(ASC) requiring inpatient admission.5
Treatment can include intravenous
(IV) steroids, but 29% of adults and
33% of children are refractory.6,7 In
the past, when no other treatments
were available, emergency colectomy
was the only option. In general, a
step-up approach based on disease
severity and subsequent response to

Ulcerative colitis (UC) causes

significant morbidity in children.1
The course of the disease in children
tends to be more severe than in
adults, and localization is more
extensive.2 UC is a chronic, idiopathic,
inflammatory disease limited to the
colon. Inflammation involves the
rectum in the majority of patients,
extending proximally in a continuous
and circumferential way.3 Endoscopic
features include contiguous mucosal
ulceration from the rectum with
erythema, friability, and loss of

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PEDIATRICS Volume 137, number 5, May 2016:e20151184

aInammatory Bowel Disease Unit, Pediatric Department,

University of Messina, Messina, Italy; and bDivision of
Pediatric Gastroenterology, Hepatology and Nutrition,
Department of Pediatrics, Emory University School of
Medicine, Atlanta, Georgia

To cite: Romano C, Syed S, Valenti S, et al.

Management of Acute Severe Colitis in Children
With Ulcerative Colitis in the Biologics Era.
Pediatrics. 2016;137(5):e20151184

STATE-OF-THE-ART REVIEW ARTICLE

therapy is recommended, with close

collaboration between medical and
surgical teams.8 The multidisciplinary
approach (surgeon, pediatric
gastroenterologist, infectious
diseases physician, nutritionist) is
an important issue for appropriate
management. Adequate knowledge
and proper use of the major
categories of immunosuppressant
medications (corticosteroids
[CS], thiopurines, biologics, and
calcineurin inhibitors) with details
including indications, typical doses,
and efficacy are essential. Often the
risk of surgery or complications is
related to the improper use of these
agents, with mistakes in route of
administration, timing, and dosages
used. We present a review of current
literature along with a synthesis on
the ASC management in hospitalized
pediatric patients.

METHODS
The aim of the current review is to
present an update of the definition,
clinical presentation, and therapy of
ASC in hospitalized pediatric patients.
A systematic search was carried out
through Medline via PubMed (http://
www.ncbi.nlm.nih.gov/pubmed)
to identify all articles published in
English, to date, on the basis of the
following keywords: ulcerative
colitis, pediatric ulcerative colitis,
biological therapy, and acute
severe colitis.

RESULTS
Disease Denition
By adapting the 1955 Truelove
and Witts criteria,9 the European
Crohns and Colitis Organization
statement has defined ASC in adults
as an exacerbation with at least
6 bloody daily stools and 1 of the
following: tachycardia (>90 beats/
min), temperature >37.8C, anemia
(hemoglobin <10.5 g/dL), or an
elevated erythrocyte sedimentation
rate (>30 mm/h).10 For pediatric

patients, a new score of clinical

disease, the Pediatric Ulcerative
Colitis Activity Index (PUCAI) has
recently been validated.11 An acute
attack may manifest severely with
onset of clinical relapse of disease,12
accompanied by local or systemic
complications such as massive
hemorrhage, toxic megacolon, and
multiorgan failure; in some cases,
this condition is defined as fulminant
colitis.13 The presence of metabolic
alkalosis, gaseous distension of
the small intestine (signaling
incumbent megacolon), and deep
ulcers visible on endoscopy are poor
prognostic factors.14 Finally, the
persistence of elevated C-reactive
protein (CRP) levels (>45 mg/L),
and diarrhea (>3 evacuations/
day) in the third day of an intensive
regimen may be associated with
a high risk (85%) of colectomy in
the short-term.15 UC with ASC is
defined in children as PUCAI score
>65. Abdominal examination should
include palpation for abdominal
tenderness, organomegaly, rebound,
or guarding. Rectal examination with
investigation of the perianal region
and/or the presence of blood in the
rectum after digital examination
is an important part of the initial
evaluation. Common pitfalls in the
initial workup of ASC include lack
of evaluation for exclusion of acute
infections or toxic megacolon before
use of anti-inflammatory agents.
Clostridium difficile infection is more
common in inflammatory bowel
disease (IBD) patients than in the
normal population, with a reported
increase in the incidence of infection
in individuals with IBD.16 In a singlecenter study, Ananthakrishnan
et al17 found an increase in the
incidence of Cdifficile infection in
hospitalized adult patients with UC
(18.4/1000 in 1998 vs 57.6/1000 in
2004). Furthermore, in the setting
of Cdifficile infection, there is a
reported 6.6-fold increase in the risk
of colectomy compared with those
with Cdifficile infection but no IBD.18
Hence, it is crucial that stool samples
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be assayed for Cdifficile cytotoxin

(both A and B) and cultured for
bacterial pathogens.
The pathogenic role of the
cytomegalovirus (CMV) in UC is
unclear. The prevalence of CMV in
intestinal tissue (ie, CMV disease)
and not in blood (ie, CMV infection)
varies in ASC from 5% to 81%,
depending on the population being
studied and the laboratory methods
used for viral detection.19 Clinical
suspicion of CMV viremia should
be directly suspected when IBD
patients present with prominent
systemic symptoms, especially fever,
lymphadenopathy, splenomegaly,
leucopenia, and mild hepatitis.20
However, CMV colitis need not
present such features. Criscuoli et al
reported that CMV may be a cause of
refractory UC in an adult population,
with detection in histologic
specimens of 11 patients (46%) with
toxic megacolon compared with 2
(9%) severe UC matched controls
(P = .0078) and 7 (14%) unmatched
controls (P = .003).21 For instance,
CMV infection does not need to be
excluded in all children with ASC
but only those with PUCAI >45 on
the third day after presentation.
Diagnosis requires demonstrating
CMV in colonic tissue with processed
biopsies for hematoxylin-eosin
and immunohistochemistry and/
or, if available, CMV DNA real-time
polymerase chain reaction. The
cutoff value for CMV DNA has yet
to be identified, but values >250
copies/mg tissue seem to predict
resistance to steroids. The treatment
recommended is IV ganciclovir 5
mg/kg twice daily for 14 days, with
remission rates from 67% to 100%.22
Therapy with appropriate antiviral
drugs can be considered in addition
to immunosuppressive therapy in
ASC. Toxic megacolon is defined as
the presence of symptoms such as
severe pain, abdominal distention,
altered level of consciousness,
guarding or rigidity, fever,
tachycardia, dehydration, electrolyte

ROMANO et al

disturbance (hypokalemia), or shock.

Plain radiographs are therefore
recommended as part of the baseline
evaluation instead of initial computed
tomography scans. Radiographic
evidence of colon dilatation 56 mm
in patients 10 years, or >40 mm
in patients <10 years of age can
be considered the most important
diagnostic criteria.15 Supportive
therapy in the initial clinical
approach can include prophylactic
subcutaneous heparin to reduce the
risk of thromboembolism, and blood
transfusions to maintain hemoglobin
>10 g/dL. In hospitalized children
and adolescents with IBD, there is an
increased risk for thromboembolism.
In a multivariable analysis, this risk
persists after adjusting for common
risk factors for thromboembolism.
The increased risk is for
thrombophlebitis, intracranial
venous sinus thrombosis, BuddChiari syndrome, and portal vein
thrombosis in patients with Crohn
disease and thrombophlebitis and
intracranial venous sinus thrombosis
in patients with UC.23
Clinical monitoring in this first
phase should include assessment
of symptoms, frequency of
bowel movements, presence of
blood in stools, abdominal pain,
temperature, pulse, abdominal
tenderness, biochemical testing
(blood count, inflammatory markers,
biochemistry), and radiologic
monitoring.24

Steroid Therapy
The use of CS for the induction of
remission in UC was first described
in 19559 and since then has been
the mainstay for induction of
remission in moderate to severe UC.
Methylprednisolone is used more
frequently than hydrocortisone for
minor mineralocorticoid effects
with a suggested dosage of 1 to
2 mg/kg, up to a maximum of
60 mg/day.25,26 Approximately
one-third of patients with ASC are
unresponsive to first-line therapy

PEDIATRICS Volume 137, number 5, May 2016

with IV CS; identifying predictive

factors of nonresponse is still a
diagnostic clinical challenge. Adult
randomized controlled trials of IV
steroids are lacking, but average
colectomy rate is low.6,27 To date,
4 small retrospective studies
(44 patients in total) and 1 large
prospective study of 128 children
have reported the short-term
response rate to CS therapy in
pediatric severe colitis.6,7 Similar to
adults, in prospective studies, IV CS
are also considered first-line therapy
for ASC in the pediatric population.28
Despite the predominance of
extensive disease in children with
UC, data concerning severe pediatric
UC are sparse. Turner et al6 reviewed
rates and predictor factors of response
to IV CS therapy in a single-center
cohort with long-term follow-up.
In their study, 99 children were
evaluated for treatment of severe
UC with measurement of associated
clinical, laboratory, and radiographic
data. Predictors of CS response
were analyzed using univariate
and multivariate analyses at days
3 and 5 of therapy. In this cohort of
patients from the prebiologics era,
53% did not respond to therapy, with
associated nocturnal stools and high
PUCAI of >45 at 3-day follow-up.
These were considered important
predictors and were associated
with CS failure.28 In clinical practice,
patient response is assessed by
improvement in symptoms (reduced
bowel frequency, reduced urgency,
improved stool constituency, reduced
abdominal pain and rectal bleeding)
and in blood test parameters (CRP,
erythrocyte sedimentation rate, and
platelet count). It was suggested
that at day 5, careful assessment be
made of the clinical response, and
in cases of clear nonresponders,
the decision should be made to
consider step-up therapy.29 Steroids,
especially in a pediatric population,
carry a significant side-effect profile
and can distort metabolic activity in a
multitude of organ systems. While on
high-dose steroid therapy, there is a
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high risk of developing opportunistic

infections and other side effects;
hypernatremia, hyperlipidemia, and
metabolic bone disease have been
reported.8 Common pitfalls in steroid
therapy include the use of low doses
<1 mg/kg/day to induce remission,
or giving prolonged therapy beyond
5 to 7 days, despite poor clinical
response (PUCAI >70 at 5 days of
therapy). In these cases, second-line
therapy with immunomodulators
should be started immediately. There
is no evidence supporting bowel rest
in patients with ASC nor regarding
elimination diets. In a small adult
study in UC patients, McIntyre et
al showed no differences in clinical
outcome between patients receiving
parenteral or enteral nutrition.30

Second-Line or Rescue Therapy

In patients who are nonresponsive
to IV CS, initiation of second-line/
rescue therapy is indicated. This
generally consists of various medical
therapeutic options including
calcineurin-inhibitors (cyclosporine,
tacrolimus) and antitumor necrosis
factor (TNF)- (infliximab) agents.
These therapies can induce a
response in 70% of patients.31 The
increased use of second-line therapy
is due not only to the effectiveness of
these drugs but also to the fact that
many surgeons prefer to control an
acute attack of colitis with medical
therapy and intervene at a later
time.32 A child with a PUCAI >45
after 3 to 5 days from starting IV CS
is defined as a nonresponder and
should be prepared for second-line
therapy. In this case, it is necessary
to discuss treatment options with the
family, have a surgical consultation
and tuberculosis screening, perform
sigmoidoscopy (on the third or fourth
day) to exclude infection (CMV and
Cdifficile), and search for chronic
changes along with granulomatous
inflammation. CRP values should
be monitored because high values
have some predictive value26 for
disease outcome and poor treatment

response. PUCAI >65 on day 5 of IV

CS predicts nonresponse to therapy
with a specificity of 94% and a
positive predictive value of 100%,
representing an indication to start
second-line therapy.33 In patients
with PUCAI scores between 35 and
64 on day 5 of treatment with IV
CS, rescue therapy should always
be considered; however, many
clinicians wait another 2 to 3 days
before assessing response to IV
steroid therapy. Those with PUCAI
<35 points on day 5 are unlikely
to require second-line therapy by
discharge26 (Fig 1).

Iniximab
Infliximab is a chimeric monoclonal
antibody to human TNF- that is
known to play an important role
in the inflammatory pathogenesis
of UC. It is constructed by linking
the variable regions of a mouse
antihuman TNF monoclonal antibody
to human immunoglobulin G1 with
light k-chains.34 Six case series have
reported the use of infliximab in
children with ASC (126 in total),
with pooled short- and long-term
response rates of 75% and 64%,
respectively. Short-term and 1-year
colectomy rates have declined since
the use of infliximab in children with
ASC to 9% on discharge and 19% by
1 year.7 Initial infliximab dosage is 5
mg/kg over 2 to 4 hours; subsequent
doses are given 2 and 6 weeks after
the initial infusion. Some centers
use higher doses (10 mg/kg) or
infuse the second dose after 7 to 10
days (maintenance therapy can be
given every 8 weeks after induction,
if clinically indicated).26 Before
treatment, it is important to perform
infectious disease screening as
follows: documentation of negative
tuberculosis testing (via tuberculin
skin testing or the QuantiFERON-TB
Gold assay) and chest radiograph
(if indicated by equivocal/positive
results on tuberculosis testing),
varicella immune status, and
hepatitis B and C infection status via

FIGURE 1
Treatment approach for hospitalized pediatric UC patients with ASC. AZA, azathioprine.

serology. It is necessary to evaluate

vital signs frequently during the
duration of infusion.26 If a patient has
previously failed an adequate trial of
thiopurine therapy, then infliximab
may be preferred, as indicated in
Fig 1, because it can be used as
a maintenance regimen, unlike
cyclosporine or tacrolimus, which are
both typically given for 3 to 4 months
to bridge therapy to thiopurines.
Eidelwein et al35 showed an initial
short-term response to infliximab
in pediatric UC: 75% had complete
resolution of symptoms, and 25%
improved after initial infusion;
many of these patients continued to
respond in the subsequent 6 months,
but one-third of children underwent
colectomy. The authors concluded
that infliximab is a valid alternative
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therapy to cyclosporine or colectomy

in patients requiring chronic CS
therapy or not responding to 6-MP
or azathioprine. In the pediatric
population, time of response can
be considered at the second week
mark. One of the common pitfalls
in the use of infliximab is starting
anti-TNF- therapy before excluding
CMV, hepatitis B and C, tuberculosis
infection, and toxic megacolon.
Additionally, it is important to avoid
underdosing of infliximab (initial
recommended dose of at least
5mg/kg) or improper use of
infliximab therapeutic regimen
during maintenance.

Cyclosporine
Cyclosporine acts mainly by binding
to the cytosolic protein cyclophilin

ROMANO et al

of T-lymphocytes, thereby inhibiting

calcineurin, which is responsible
for activating the transcription
of interleukin-2.36 Pediatric
cyclosporine data come from 8
retrospective case series (total of
94 children) in which the rate and
adverse events were similar to those
reported in adults.7,37 The pooled
short-term response was 81%, but
only 39% avoided colectomy in
the long-term.7 Heterogeneity in
the definition of disease activity,
concomitant therapies, follow-up
period (15 years), dose, and route
of administration (half started with
oral therapy) limit interpretation of
these combined studies. The better
long-term success rates were, in
part, related to the introduction
of azathioprine. Treem et al38
evaluated 14 patients in a pediatric
study with fulminant colitis treated
with cyclosporine; short-term
response was 78%, similar to adult
studies, but for 7 of 11 patients
initially responding to cyclosporine,
colectomy was necessary after
1 year. Recommended initial dose
is 2 mg/kg/day continuous IV
infusion. Once remission is achieved,
conversion to oral therapy 5 to
8 mg/kg/day is suggested, stopping
the medication after 3 to 4 months.26
The trough levels used for monitoring
range from 150 to 300 ng/mL.
Before treatment, it is important to
carry out the following: measure
blood pressure; perform blood
tests such as creatinine, glucose,
electrolytes, liver profile; and test
for and treat hypomagnesemia to
decrease risk of neurotoxicity.26
Widespread use of cyclosporine
has been tempered by potentially
serious side effects, including
nephrotoxicity, neurotoxicity
(manifested as paresthesias, tremors,
and seizures), serious infections
(dose and hypocholesterolemia
dependent), hypomagnesemia (if
serum magnesium <1.5 mg/dL,
the dose of cyclosporine should
be reduced), hypertension (can
be seen in up to 40% of subjects

PEDIATRICS Volume 137, number 5, May 2016

and usually responds to calcium

channel blockers), hypertrichosis,
headache, hyperkalemia, and, rarely,
death.39 The use of cyclosporine or
combination immunosuppressive
agents is associated with reports of
Pneumocystis jiroveci pneumonia,
and therefore, routine use of
trimethoprim-sulfamethoxazole
for prophylaxis is recommended.40
The most adverse events secondary
to cyclosporine use appear to be
less frequent if oral administration
is used.41 Monitoring should be
carried out every second day
during induction, weekly for the
first month, and then monthly. This
should consist of the following: drug
levels (starting after the third dose),
creatinine, glucose, electrolytes
(including magnesium), lipid levels,
blood pressure, and neurologic
symptoms.26 Common problems in
the administration of cyclosporine
therapy in children with ASC include
not using initial parenteral therapy
(oral therapy can be started when
remission is achieved) and failure to
monitor and maintain therapeutic
blood levels of cyclosporine.

Tacrolimus
There are few data available in the
current literature on the use of
oral tacrolimus in the short-term
treatment of pediatric steroiddependent/refractory UC. Watson
et al retrospectively reviewed the
results of 46 children with steroidrefractory colitis treated with
tacrolimus. Oral tacrolimus was
initiated at a dose of 0.1 mg/kg twice
a day and titrated to yield trough
levels of 10 to 15 ng/mL for induction
and 5 to 10 ng/mL once in remission.
Ninety-three percent of patients
were discharged without undergoing
surgery and the probability of
avoiding colectomy after starting
tacrolimus was 40% at 26 months.42
We report the published experience
from our group of 6 pediatric steroidrefractory patients with moderate/
severe UC who were treated with
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tacrolimus (0.1 mg/kg/dose twice

daily) achieving blood levels between
7 and 10 ng/mL. Response was
evaluated by using PUCAI scores, and
all patients responded within 1 to 2
weeks. Subsequently, the patients
were switched to thiopurine.43

Iniximab Versus Cyclosporine

No pediatric trials comparing
cyclosporine and infliximab in ACS
have been published to date. Adult
data suggest that any therapeutic
decision should be individualized.44
The CYcloSporine versus InFliximab
(CYSIF) trial has randomized 111
thiopurine-naive patients with severe
UC after 5 days of IV steroids to IV
cyclosporin (2 mg/kg/day followed
by 4 mg/kg/day orally) and infliximab
(5 mg/kg IV infusion at 0, 2, and 6
weeks). Patients who responded at
day 7 received oral azathioprine and
tapered steroids from day 8. Response
to treatment at day 7 was reported
in 85% patients in both groups.
Colectomy rates at day 98 were also
similar between cyclosporin and
infliximab (18% vs 21%, P = .66).
Treatment failure at day 98 was also
similar, seen in 60% patients in the
cyclosporin group versus 54% in
the infliximab group. There was no
clear evidence of superiority of either
therapy over the other.45 We suggest
that in patients naive to thiopurine
therapy, initiation of IV cyclosporine
should be followed by 3 months of oral
therapy, with subsequent introduction
of azathioprine. In patients who
present with severe episodes of UC
during azathioprine maintenance
therapy, the use of infliximab may be
considered as maintenance therapy.
A recent retrospective, single-center
study from Asia46 demonstrated, in
an adult population, that infliximab
seems to be more effective than
cyclosporine in terms of colectomy
rate in the univariate analysis. At 12
months, the rate of colectomy was
30% and 3% in cyclosporine and
the infliximab groups, respectively
(P = .034). The strategy of switching

TABLE 1 Drugs Used in Rescue Therapy for Pediatric UC Patients With ASC
Cyclosporine

Tacrolimus

Mechanism of action
Dose

Calcineurin inhibitor
IV 2 mg/kg/day. Once remission is achieved,
convert to oral therapy 58 mg/kg/day.
Stop medication after 34 mo.

Calcineurin inhibitor
Oral 0.1 mg/kg/day. Stop medication
after 34 mo.

Drug levels

Trough drug levels used for monitoring range

from 150 to 600 ng/mL.

Initial trough drug levels of 1015

ng/mL, and then 510 ng/mL once
remission achieved.

Toxicity/side effects

Nephrotoxicity, paresthesias, tremors

and seizures in the setting of
hypocholesterolemia (<120 mg/dL) and
hypomagnesemia (<1.5 mg/dL), serious
infections, hypertension, hypertrichosis,
headache, hyperkalemia, and, rarely, death.
Measure blood pressure and blood tests
including creatinine, glucose, electrolytes,
liver prole, lipid levels, and drug levels.

Hyperglycemia, hypomagnesemia,
neurotoxicity, and hypertension.

Tests before and

during treatment

between cyclosporine and infliximab

or vice versa can be considered highly
risky in a pediatric population because
of the significant risk of severe
infections.47

Surgery and a Time-Limited

Approach
A time-limited approach with
assessment of predictors of response
to therapies and close collaboration
between gastroenterologists and
surgeons is necessary to ensure
optimal management with reduced
risks of mortality. It is important
to consider colectomy in patients
with PUCAI scores >65 at 11 to 14
days after start of rescue therapy
(Fig 1). Surgery is unavoidable in
these patients, and time delay in
nonresponders to medical therapy
is associated with an increased risk
of postoperative complications.35
Indications for surgery, other than
ASC, include toxic megacolon,
perforation, severe hemorrhage,
or significant clinical deterioration
during medical therapy. Although
in general, medical rescue therapy
should be considered as first-line
treatment in steroid-refractory ASC,
colectomy is still a cornerstone of any
proposed management algorithm.48

Iniximab
Anti-TNF-
Initial dosage is IV 5 mg/kg over 24 h;
subsequent doses given 2 wk and 6 wk
later. Maintenance therapy can be given
every 8 wk after induction, if clinically
indicated.
A cutoff value of 0.5 g/mL was dened as
clinically relevant. Less than 0.5 g/mL was
associated with a sensitivity of 86% and a
specicity of 85% for identifying patients
with a loss of response.51
Infusion reactions, increased infection rate,
rare opportunistic infections.

Measure blood pressure and blood

tests including creatinine, glucose,
electrolytes, liver prole, lipid
levels, and drug levels.

The easiest classification scheme

divides indications for surgery
into 2 categories: emergency and
elective surgery. Emergency surgery
is performed in patients with toxic
megacolon, perforation, massive
hemorrhage, sepsis, or fulminant
disease without adequate control
with intense medical therapy.49 In
emergency conditions, the primary
surgical strategy is to address the
complications of disease by removing
the diseased colon and constructing
an ileostomy while leaving the
rectum in situ. This procedure is
known as subtotal colectomy with
end ileostomy. By leaving the rectum
in situ, a future restorative procedure
(ileal pouch-anal anastomosis) is
required.50 A 3-stage procedure
should be considered in a pediatric
population with protective ileostomy,
with anastomotic leaks being
the most important short-term
complications reported.26

CONCLUSIONS
Between 15% to 30% of pediatric
UC patients will have an ASC attack,
often at the time of disease onset.
This condition requires hospital
admission and standard intensive
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Documentation of negative tuberculosis

testing and chest radiograph and immunity
against varicella and hepatitis B and C.

therapy. A lack of response to firstline therapy after 3 to 5 days should

induce consideration of secondline/rescue medical therapy along
with consideration of surgery if
indicated. Management of ASC is
multidisciplinary, with intensive
steroid treatment being the mainstay
of medical therapy (Table 1). The
use of a specific salvage therapy in
pediatric ASC still depends on many
factors with no specific guidance
currently reported. Delaying
surgery, especially in early-onset
UC (in children <3 years of age) is
associated with increased mortality.
Close collaboration between
pediatric gastroenterologists and
surgeons is needed to ensure the best
management of patients with ASC.

ABBREVIATIONS
ASC:acute severe colitis
CMV:cytomegalovirus
CRP:C-reactive protein
CS:corticosteroid
IBD:inflammatory bowel disease
IV:intravenous
PUCAI:Pediatric Ulcerative
Colitis Activity Index
TNF:tumor necrosis factor
UC:ulcerative colitis

ROMANO et al

Drs Romano, Syed, Valenti, and Kugathasan conceptualized this study, contributed to data acquisition and interpretation, drafted the article, and approved the
nal manuscript as submitted.
DOI: 10.1542/peds.2015-1184
Accepted for publication Nov 19, 2015
Address correspondence to Claudio Romano, MD, IBD Unit, Pediatric Department, University of Messina, Viale Consolare Valeria, 98122 Messina, Italy. E-mail:
[email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of interest to disclose.

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Management of Acute Severe Colitis in Children With Ulcerative Colitis in the

Biologics Era
Claudio Romano, Sana Syed, Simona Valenti and Subra Kugathasan
Pediatrics 2016;137;; originally published online April 27, 2016;
DOI: 10.1542/peds.2015-1184
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
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Management of Acute Severe Colitis in Children With Ulcerative Colitis in the

Biologics Era
Claudio Romano, Sana Syed, Simona Valenti and Subra Kugathasan
Pediatrics 2016;137;; originally published online April 27, 2016;
DOI: 10.1542/peds.2015-1184

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/137/5/e20151184.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2016 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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