- 1. JPGN Journal of Pediatric Gastroenterology and Nutrition
Publish Ahead of PrintDOI : 10.1097/MPG.0000000000000239The ESPGHAN
Revised Porto Criteria for the Diagnosis of Inflammatory Bowel
Disease inChildren and AdolescentsArie Levine MD1**, Sibylle
Koletzko MD2**, Dan Turner MD, PhD3*, Johanna C EscherMD, PhD4* ,
Salvatore Cucchiara MD, PhD5*, Lissy de Ridder MD, PhD*4,
Kaija-LeenaKolho MD, PhD6, Gabor Veres MD, PhD7, Richard K Russell
MB, PhD8, AndersPaerregaard DMS9, Stephan Buderus MD10, Mary-Louise
C Greer MBBS11, Jorge AmilDias MD12, Gigi Veereman-Wauters MD,
PhD13, Paolo Lionetti MD, PhD14, MalgorzataSladek MD, PhD15, Javier
Martin de Carpi PhD16, Annamaria Staiano MD17, Frank MRuemmele MD,
PhD18 , David C Wilson MB, MD19**Affiliations:(1) Pediatric
Gastroenterology and Nutrition Unit, Wolfson Medical Center,
Sackler Schoolof Medicine, Tel Aviv University, Israel(2) Dr. v.
Hauner Childrens Hospital, Ludwig Maximilians University, Munich,
Germany(3) Pediatric Gastroenterology Unit, Shaare Zedek Medical
Center, The Hebrew Universityof Jerusalem, Israel(4) Pediatric
Gastroenterology, Department of Pediatrics, Erasmus MC-Sophia
ChildrensHospital, Rotterdam, the Netherlands.(5) Pediatrica
Gastroenterology and Liver Unit, Sapienza University of Rome,
Italy(6) Childrens Hospital, University of Helsinki, Helsinki,
FinlandCopyright ESPGHAN and NASPGHAN. All rights reserved.
2. (7) Semmelweis University, Budapest, Hungary(8) Department of
Paediatric Gastroenterology and Nutrition, Yorkhill Childrens
Hospital,Glasgow, Scotland.(9) Department of Paediatrics, Hvidovre
University Hospital, Copenhagen, Denmark(10) St.-Marien-Hospital,
Department of Pediatrics, Bonn, Germany(11) Diagnostic Imaging, The
Hospital for Sick Children, Toronto, Canada; Department ofMedical
Imaging, University of Toronto, Canada(12) Hospital S. Joo, Porto,
Portugal(13) Pediatric Gastroenterology and Nutrition, UZ Brussels,
Brussels, Belgium(14) Departement Neurofarba, University of
Florence, Meyer Children Hospital, Florence,Italy(15) Department of
Pediatrics, Gastroenterology and Nutrition, Jagiellonian
UniversityMedical College, Cracow, Poland.(16) Department of
Pediatric Gastroenterology, Hepatology and Nutrition, Hospital
SantJoan de Du, Barcelona, Spain(17) Department of Pediatrics,
University of Naples "Federico II".(18) Universit Sorbonne Paris
Cit, Universit Paris Descartes, INSERM U989, AP-HP,Hpital Necker
Enfants Malades, Service de Gastroentrologie pdiatrique, Paris,
France.(19) Child Life and Health, University of Edinburgh,
Scotland, UK*Steering committee members** Contributed equally as
senior authorsCopyright ESPGHAN and NASPGHAN. All rights reserved.
3. Address for correspondence:Professor David C Wilson,Child Life
and Health, University of Edinburgh, 20 Sylvan Place, Edinburgh EH9
1UW,Scotland, UKPhone: +44 131 5360710Fax: +44 131 5360052Email:
[email protected] of interest and source of funding:AL
has received consultation fees, speakers fees, meeting attendance
support or honoraria fromMSD, Abbott, Ferring, Falk and Nestle.SK
has received consultation fees, speakers fees, meeting attendance
support or research supportfrom MSD, Abbott, Immundiagnostik,
Danone, Janssen and Nestle.DT has received consultation fees,
speakers fees, meeting attendance support, research support
orhonoraria from MSD, Abbott, Ferring, Nestle, Shire and
Centocor.JCE has received consultation fees, speakers fees, meeting
attendance support or research supportfrom MSD and Janssen.SC has
received consultation fees from MSD and Pfizer.LdR has received
consultation fees, speakers fees, meeting attendance support or
researchsupport from MSD, Abbott and Shire.KLK has received
consultation fees, speakers fees or meeting attendance support from
MSD,Abbott, Biocodex, and Tillotts Pharma.GV has declared no
conflicts of interest.RKR has received consultation fees, speakers
fees, meeting attendance support or researchsupport from MSD,
Ferring, Dr Falk and Nestle.Copyright ESPGHAN and NASPGHAN. All
rights reserved. 4. AP has received consultation fees and/or
speaker from MSD, Nestl and BioCare.SB has received consultation
fees, speakers fees or meeting attendance support from
Falk-Foundation, MSD, Nestle, Norgine and Pfrimmer.MCG has declared
no conflicts of interest.JAD has declared no conflicts of
interest.GV-W has received consultation fees from MSD, Abbott, Mead
Johnson and Novalac.PL has received consultation fees, speakers
fees, meeting attendance support form Abbvie,Danone Reearch, Nestl,
MSD, FerringMS has received consultation fees, speakers fees,
meeting attendance support from MSD, Abbott,Ferring, Ewopharma,
Nutricia and Nestle.JMdC has received consultation fees, speaker's
fees, meeting attendance support or researchsupport from MSD,
Abbott, Ferring, Nestle, Otsuka, and Fresenius Kabi.AS reports the
following - Movetis (Advisory board); Valeas (Speaker Bureau);
D.M.G. Italy(Consultant); Mead Johnson (Speaker Bureau).FR reports
the following - Advisory Board Member or Speaker for MSD, Jansen
and Jansen,Nestl, Meadjohnson, Danone, Biocodes.DCW has received
consultation fees, speakers fees, meeting attendance support or
researchsupport from MSD, Abbott, Ferring, Shire, Warner Chilcott,
Pfizer and Nestle.Word Count, Tables and Figures:Abstract 250
words, text 7290 words, 4 tables, 1 figure.Copyright ESPGHAN and
NASPGHAN. All rights reserved. 5. AbstractBackground: The diagnosis
of pediatric-onset IBD (PIBD) can be challenging in choosing
themost informative diagnostic tests and correctly classifying PIBD
into its different subtypes.Recent advances in our understanding of
the natural history and phenotype of PIBD, increasingavailability
of serological and fecal biomarkers, and the emergence of novel
endoscopic andimaging technologies taken together have made the
previous Porto criteria for the diagnosis ofPIBD obsolete.Methods:
We aimed to revise the original Porto criteria utilizing an
evidence-based approach andconsensus process to yield specific
practice recommendations for the diagnosis of PIBD. Theserevised
criteria are based on the Paris classification of PIBD and the
original Porto criteria whilstincorporating novel data, such as for
serum and fecal biomarkers. A consensus of at least 80%
ofparticipants was achieved for all recommendations and the summary
algorithm.Results: The revised criteria depart from existing
criteria by defining two categories of ulcerativecolitis (UC;
typical and atypical); atypical phenotypes of UC should be treated
as UC. A novelapproach based on multiple criteria for diagnosing
IBD-unclassified (IBDU) is proposed.Specifically, these revised
criteria recommend upper GI endoscopy and ileocolonscopy for
allsuspected PIBD patients, with small bowel imaging (unless
typical UC after endoscopy andhistology) by magnetic resonance
enterography (MRE) or wireless capsule endoscopy.Conclusions: These
revised Porto criteria for the diagnosis of PIBD have been
developed to meetcurrent challenges and developments in PIBD and
provide up to date guidelines for the definitionand diagnosis of
the IBD spectrum.Keywords: Inflammatory Bowel Disease; Crohn's
disease; ulcerative colitis; IBD unclassified;diagnosis.Copyright
ESPGHAN and NASPGHAN. All rights reserved. 6. IntroductionUntil
recently, the diagnosis of inflammatory bowel disease (IBD) in
childhood, whose subtypescomprise Crohn's disease (CD), ulcerative
colitis (UC), and IBD unclassified (IBDU; a form ofcolonic IBD
whose features make it impossible to define as either colitis of CD
or UC atdiagnosis) seemed straightforward. The diagnosis of IBD
required chronic inflammation in thegastrointestinal tract and
exclusion of other causes of inflammation. Differentiation of CD
fromUC, and both of these from infectious diseases, allergic
diseases or primary immunodeficiencydisorders with similar
presentations, was based largely upon clinical suspicion, ruling
out otherdiagnoses, endoscopic and histological evaluation of the
mucosa, and small bowel follow-through(which has limited
sensitivity for detecting small bowel inflammation) (1). Larger and
morerecent data sets of pediatric-onset IBD (PIBD) patients have
highlighted several atypicalphenotypes of all 3 forms of PIBD which
have led to frequent mislabeling of patients, andrecognition of the
need for more accurate definitions of each subset of disease (2-8).
The Parisclassification (8) was a significant step forward in
standardization of definitions and classificationof PIBD. Advances
in diagnostic imaging modalities, capsule endoscopy and
comprehensiveserological and fecal biomarkers, have also advanced
our ability to detect and characterize thesediseases whilst
reducing radiation exposure in children, but have themselves
presented newchallenges. These modalities increased not only the
sensitivity of mucosal lesion detection butalso increased the
uncertainty in some children with the isolated colitis phenotype
who haveperceived overlapping features. Thus the accurate diagnosis
of PIBD depends not only on anindex of suspicion and choice of
tests, but the appropriate interpretation of the results of
theworkup. This current revision of the original Porto Criteria of
2005 (1) utilizes an evidence-basedapproach to meet our goals - to
facilitate not only the diagnosis of PIBD, but also to
enableclinicians to properly diagnose each individual subtype based
on current evidence The newcriteria integrate the most recent
evidence regarding the recommended methods for diagnosis
ofCopyright ESPGHAN and NASPGHAN. All rights reserved. 7. IBD,
clearly define the disease subtypes of PIBD based on the Paris
phenotypic classification, andhighlight the diagnostic pitfalls in
order to provide reliable diagnosis, assessment, and
prognosisleading to the best individualized care for a new
generation of PIBD patients. Using a novel,evidence-based approach,
we have confronted in particular the difficult issue of defining
andevaluating IBDU. Although esophagogastroduodenoscopy (EGD) and
ileocolonoscopy are teststhat are within the broad consensus for
the initial evaluation of PIBD irrespective of disease type,the
choice of additional tests depends on phenotypes and interpretation
of endoscopic data. Thusthese revised Porto criteria start with a
description of phenotypes and pitfalls in interpretation ofthe data
in order to guide the physician or surgeon in choice of
investigations.MethodsAn international group of European experts in
PIBD, mainly from the Porto IBD WorkingGroup of ESPGHAN, wished to
construct a revised, methodologically robust,
consensus-basedclinical guideline for the diagnosis of PIBD,
including full facets of the assessment by allinvestigative
modalities, and interpretation of these results. This was to build
on and update theearlier work which has become known as the Porto
Criteria (1), and aimed to comprise the bestrecent available
evidence from the PIBD literature, relevant methodologically high
quality datafrom the adult IBD literature, together with clinical
expertise from PIBD specialists, based uponwork in their
multi-disciplinary IBD teams. A major reference point was the Paris
classification(8), a recent expert consensus document providing a
pediatric-specific modification of theMontreal classification of
IBD (9), and which specifically has highlighted those
phenotypiccharacteristics which are either more common in or are
unique to pediatric-onset rather than adult-onsetCopyright ESPGHAN
and NASPGHAN. All rights reserved.IBD. 8. A list of 12 topics
addressing the diagnosis of PIBD (age at diagnosis 80% consensus.
Key new evidence published in 2012 had beenconsidered for inclusion
in relevant sections in autumn 2012. The final manuscript has
beenapproved by all participants. The guidelines include not only
recommendations but also practicepoints which reflect common
practice where evidence is lacking.Copyright ESPGHAN and NASPGHAN.
All rights reserved. 9. Part I: Diagnosis of
IBDRecommendationsAccurate diagnosis of inflammatory bowel disease
(IBD) should be based on a combination ofhistory, physical and
laboratory examination, esophagogastroduodenoscopy (EGD)
andileocolonoscopy with histology, and imaging of the small bowel.
It is critical to exclude entericinfections. [EL2b, RG C]We
recommend performing small bowel imaging in all suspected cases of
IBD at diagnosis; thismay be deferred in typical UC, based on
endoscopy and histology. Imaging is particularlyimportant in
suspected Crohn's disease ,in patients whose ileum could not be
intubated, inpatients with apparent ulcerative colitis with
atypical presentations, and in patients with IBD-Unclassified.[EL3,
RG D]Practice Points1. The most important reliable feature of
typical UC is continuous mucosal inflammation of thecolon, starting
distally from the rectum, without small bowel involvement other
than backwashileitis, and without epithelioid granulomas on biopsy.
Disturbed crypt architecture and focal ordiffuse basal
plasmacytosis are characteristic.2. Pediatric-onset UC may present
with atypical phenotypes such as macroscopic rectal
sparing,isolated non-serpiginous gastric ulcers, normal crypt
architecture, absence of chronicity inbiopsies, or a cecal patch.
Patients with acute severe colitis may have transmural
inflammation.These individual phenotypes in isolation should not
lead to reclassification to CD.3. Patients with disease limited to
the colon with class 1 findings (Table 3) should be classified
asCD.Copyright ESPGHAN and NASPGHAN. All rights reserved. 10. 4.
IBD-U should be the preferential classification for patients with
colitis and highly atypicalfindings (defined as class 2 or class 3
findings in Table 3) for either CD or UC, or a combinationof
findings presented below.IBD should be suspected when patients
appear with the appropriate symptoms, which may be verydiverse
(10-13). Bloody diarrhea is the most common presenting symptom in
UC while CD maypresent with vague abdominal pain, diarrhea,
unexplained anemia, fever, weight loss, or growthretardation as
frequently reported symptoms. The classic triad of abdominal pain,
diarrhea andweight loss, occurs in only 25% of CD patients (14).
Extraintestinal manifestations may present atdiagnosis in 6-23% of
children with a higher frequency in those older than 6 years of age
(3, 12,15). It is beyond the scope of this paper to report the
complete list of luminal or extraintestinalsymptoms or
presentations of IBD.The classification of IBD is complex, and
characterized by many rare phenotypes that are atypicalor unusual.
It requires recognizing the typical features of CD and UC,
recognition of atypicalphenotypes which are still consistent with a
diagnosis of CD or UC, as well as knowledge of thosefactors that
preclude a diagnosis of one or the other.Copyright ESPGHAN and
NASPGHAN. All rights reserved. 11. Diagnosis and classification of
UCThe diagnosis of UC relies primarily upon identifying a typical
phenotype of chronicinflammation of the colon upon colonoscopy and
colonic biopsies, and the exclusion of both CDand infectious causes
of colitis. However there is no single set of macroscopic or
microscopiccriteria that can accurately diagnose UC, and there are
multiple atypical phenotypes which do notfit into this category.
Features of typical and 5 atypical variants of pediatric UC appear
in Table 1.This discussion will therefore focus initially on the
typical phenotype, and then delineate thefeatures of atypical UC in
children.The most reliable feature to diagnose UC is continuous
mucosal inflammation of the colon,starting from the rectum, without
small bowel involvement, and without granulomas on biopsy (2,6,
16). Typical macroscopic features of UC include erythema,
granularity, friability, purulentexudates and ulcers which usually
appear as superficial small ulcers (16). The inflammation mayeither
end at a transition zone anywhere in the colon or involve the whole
colon continuously. Themost distal part of the terminal ileum may
show non-erosive erythema or edema if pancolitis ispresent and the
ileocecal valve is involved (termed backwash ileitis), but should
be normal in allother circumstances. Disturbed crypt architecture
and focal or diffuse basal plasmacytosis aresigns of chronicity and
thus are good predictors of IBD occurring in 70% of adult patients
withIBD and
