Jjy 113

Journal of Crohn's and Colitis, 2019, 144–164K
doi:10.1093/ecco-jcc/jjy113
Advance Access publication August 23, 2018
ECCO Guideline/Consensus Paper
ECCO Guideline/Consensus Paper
ECCO-ESGAR Guideline for Diagnostic

Assessment in IBD Part 1: Initial diagnosis,
monitoring of known IBD, detection of
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complications
Christian Maaser,a Andreas Sturm,b Stephan R. Vavricka,c Torsten Kucharzik,d
Gionata Fiorino,e Vito Annese,f Emma Calabrese,g Daniel C. Baumgart,h
Dominik Bettenworth,i Paula Borralho Nunes,j, Johan Burisch,k,
Fabiana Castiglione,l Rami Eliakim,m Pierre Ellul,n Yago González-Lama,o
Hannah Gordon,p Steve Halligan,q Konstantinos Katsanos,r Uri Kopylov,m
Paulo G. Kotze,s Eduards Krustiņš,t Andrea Laghi,u Jimmy K. Limdi,v
Florian Rieder,w Jordi Rimola,x Stuart A. Taylor,y Damian Tolan,z
Patrick van Rheenen,aa Bram Verstockt,bb, Jaap Stokercc; on behalf of the
European Crohn’s and Colitis Organisation [ECCO] and the European Society
of Gastrointestinal and Abdominal Radiology [ESGAR]
a
Outpatients Department of Gastroenterology, Hospital Lüneburg, Lüneburg, Germany bDepartment of Gastroenterology,
DRK Kliniken Berlin I Westend, Berlin, Germany cGastroenterology and Hepatology Center, Zurich, Switzerland
d
Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany eDepartment of
Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy fDepartment of Gastroenterology, Valiant Clinic
& American Hospital, Dubai, UAE gDepartment of Systems Medicine, University of Rome, Tor Vergata, Italy hDivision
of Gastroenterology, University of Alberta, Edmonton, AB, Canada iDepartment of Medicine B, Gastroenterology
and Hepatology, University Hospital Münster, Münster, Germany jDepartment of Anatomic Pathology, Hospital Cuf
Descobertas; Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal kDepartment of Gastroenterology,
North Zealand University Hospital; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg
Hospital, Frederiksberg, Denmark lDepartment of Clinical Medicine and Surgery, “Federico II” University of Naples,
Naples, Italy mDepartment of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
n
Department of Medicine, Mater Dei Hospital, Msida, Malta oDepartment of Gastroenterology, University Hospital
Puerta De Hierro, Majadahonda [Madrid], Spain pDepartment of Gastroenterology, Royal London Hospital, London, UK
q
Centre for Medical Imaging, University College London, London, UK rDepartment of Gastroenterology and Hepatology,
University and Medical School of Ioannina, Ioannina, Greece sColorectal Surgery Unit, Catholic University of Paraná
[PUCPR], Curitiba, Brazil tDepartment of of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical
University Hospital, Riga, Latvia uDepartment of Clinical and Surgical Translational Medicine, Sapienza University of
Rome, Rome, Italy vDepartment of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester; Manchester
Academic Health Sciences Centre, University of Manchester, UK wDepartment of Gastroenterology, Hepatology &
Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA xDepartment of Radiology,
Hospital Clínic Barcelona, Barcelona, Spain yCentre for Medical Imaging, University College London, London, UK
z
Clinical Radiology, St James’s University Hospital, Leeds, UK aaDepartment of Paediatric Gastroenterology, Hepatology
and Nutrition, University Medical Center Groningen, Groningen, The Netherlands bbDepartment of Gastroenterology
and Hepatology, University Hospitals Leuven and CHROMETA - Translational Research in Gastrointestinal Disorders,
Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.
144
For permissions, please email: [email protected]
ECCO-ESGAR Guideline for Diagnostic Assessment in Inflammatory Bowel Disease 145
KU Leuven, Leuven, Belgium ccDepartment of Radiology and Nuclear Medicine, Academic Medical Center [AMC],
University of Amsterdam, Amsterdam, The Netherlands
Corresponding author: Christian Maaser, gastroenterologist, Outpatients Department of Gastroenterology, Hospital

Lüneburg, Lüneburg, Germany. Email: [email protected]
Introduction of CD or UC is based on a combination of clinical, biochemical, stool,

endoscopic, and histological investigations. When CD is suspected,
This new diagnostic consensus guideline is a joint project of the
it may be necessary to visualise [radiologically] the small intestine.
European Crohn’s and Colitis Organisation [ECCO] and the European
Infectious colitis, including Clostridium difficile, should be excluded.
Society of Gastrointestinal and Abdominal Radiology [ESGAR] that
now merges the former ECCO-ESGAR Imaging Guideline and the
former ECCO Endoscopy Guideline, also including laboratory param- Statement 1.2. ECCO-ESGAR Diagnostics GL [2018]
eters. It has been drafted by 30 ECCO and ESGAR members from 17

European countries. All the authors recognise the work of and are Genetic or serological testing is currently not recom-
grateful to previous ECCO and ESGAR members who contributed to mended for routine diagnosis of CD or UC [EL3]
creating the earlier consensus guidelines on imaging and endoscopy.
The former guidelines have been condensed into this new diagnos-
tic consensus guideline which consists of two papers: the first detailing Statement 1.3. ECCO-ESGAR Diagnostics GL [2018]
assessment at initial diagnosis, to monitor treatment and for the detec-
tion of complications; the second dealing with the available scoring sys- On diagnosis, complementary investigations should
tems and general considerations regarding the different diagnostic tools. focus on markers of disease activity [EL2], malnutrition,
The strategy to define consensus was similar to that previously or malabsorption [EL5]. Immunisation status should be
described in other ECCO consensus guidelines [available at: www. assessed. Consider screening for latent tuberculosis [EL5]
ecco-ibd.eu]. Briefly, an open call for participants was made, with
ECCO participants selected by the Guidelines’ Committee of ECCO
At diagnosis, every patient should have a biochemical assessment
[known as GuiCom] on the basis of their publication record and a
with full blood count, inflammatory markers (C-reactive protein
personal statement, and ESGAR participants nominated by ESGAR.
[CRP]), electrolytes, liver enzymes, and a stool sample for microbio-
The following working parties were established: diagnostics at ini-
logical analysis, including C. difficile.1,2 The full blood count may
tial diagnosis, diagnostics for monitoring treatment in patients with
reveal thrombocytosis [due to an inflammatory response], anaemia,
known IBD, diagnostics for the detection of complications, scores
and leukocytosis. The presence of raised inflammatory markers
for IBD, and general principles and technical aspects.
[CRP] broadly correlates with clinical severity in CD1 but less so
Provisional guideline statements and supporting text were writ-
in UC except in the case of acute severe colitis.2 However, labora-
ten following a comprehensive literature review, then refined follow-
tory markers of chronic inflammation may be normal in both UC
ing two voting rounds. The first voting round introduced a more
and CD.3,4 As raised CRP, leukocytosis, or both are not IBD-specific,
comprehensive voting procedure, in which each guidelines partici-
their presence cannot differentiate IBD from infectious [or other
pant voted on all statements by explicitly reviewing those statements
causes of] colitis. Apart from biochemical evidence of malnutrition,
together with their respective supporting text and references.
hypoalbuminaemia can reflect severe inflammation; however this is
The second voting round included optional national representa-
not superior to CRP.4
tive participation of ECCO’s 36 member countries and ESGAR’s 28
Faecal calprotectin [FC], a neutrophil-derived protein, appears
member countries. The level of evidence was graded according to
to be the most sensitive marker of intestinal inflammation in IBD.
the Oxford Centre for Evidence-Based Medicine [www.cebm.net].
Other neutrophil-derived proteins are elastase, lysozyme, and lacto-
The ECCO statements were finalised by the authors at a face-to-face
ferrin.3,5–10 Calprotectin values correlate well with endoscopic indices
meeting in Barcelona in October 2017, and represent consensus with
of disease activity and are thus important in various clinical settings,
agreement of at least 80% of the present participants. Consensus
including initial diagnosis, diagnosis of relapse, and response to
statements are intended to be read in context with their qualifying
treatment.11–15
comments, and not in isolation. The supporting text was then finalised
In the initial investigations of a patient with gastrointestinal
under the direction of each working group leader [SV, TK, GF, VA,
symptoms and a raised stool marker of inflammation, an ileocolo-
EC], before being integrated by the consensus leaders [CM, JS, AS].
noscopy should be performed. An exact cut-off value that distin-
guishes between IBD and functional bowel diseases does not exist.16,17
Chapter 1: Initial diagnosis However, good diagnostic accuracy can potentially be obtained at a
cut-off value of 150 µg/g, as recently suggested in a meta-analysis.18
Statement 1.1. ECCO-ESGAR Diagnostics GL [2018] However, FC lacks the specificity to discriminate between IBD and
other causes of intestinal inflammation.7
A single reference standard for the diagnosis of Crohn’s
During the diagnostic process of IBD, gastrointestinal infections
disease [CD] or ulcerative colitis [UC] does not exist.
should always be excluded.1,2 Loose stools for more than 6 weeks
The diagnosis of CD or UC is based on a combination of
usually discriminate IBD-associated colitis from most cases of infec-
clinical, biochemical, stool, endoscopic, cross-sectional
tious diarrhoea.19 Stool specimens should be obtained to exclude
imaging, and histological investigations [EL5]
common pathogens and specifically assayed for C difficile toxin.
Additional tests may be tailored according to medical history, such
A single reference standard for the diagnosis of Crohn’s disease [CD] as for those who have travelled abroad. This may include assessment
or ulcerative colitis [UC] does not exist. At a minimum, the diagnosis for ova, cysts, and parasites.20
146 C. Maaser et al.
Serological markers may be used to support a diagnosis, though

the accuracy of the best available tests [pANCA and ASCAs] is rather Statement 1.6. ECCO-ESGAR Diagnostics GL [2018]
limited and hence ineffective at differentiating colonic CD from
For suspected IBD, ileocolonoscopy with biopsies from
UC.21,22 Similarly, the additional diagnostic value of antiglycan and
inflamed and uninflamed segments are required to estab-
antimicrobial antibodies, such as anti-OmpC and CBir1, is small.3,4,23,24
lish diagnosis [EL1], except in the case of acute severe col-
Likewise, although more than 250 IBD-associated susceptibility single
itis in which sigmoidoscopy may be sufficient [EL3]
nucleotide polymorphisms [SNPs] have been identified, genetic testing
for common variants does not allow diagnosis of IBD.25
Some infections are preventable, and the risk for severe infec- Statement 1.7. ECCO-ESGAR Diagnostics GL [2018]
tions during immunosuppression can be decreased or eliminated if
the patient is adequately vaccinated. Vaccination is best given before No endoscopic feature is specific for CD or UC. The most
initiating immunomodulatory therapy. The following should be useful endoscopic features of UC are considered to be
assessed before vaccination: hepatitis B surface antibody, hepatitis B continuous and confluent colonic involvement with clear
antigen, hepatitis B core antibody, hepatitis A IgG, measles serology, demarcation of inflammation and rectal involvement
and varicella serology. Additional baseline tests recommended at diag- [EL2]. The most useful endoscopic features in CD are dis-

nosis include hepatitis C serology, EpsteinBarr serology and human continuous lesions, presence of strictures and fistulae,
immunodeficiency virus serology, after appropriate counselling.26 and perianal involvement [EL2]
Statement 1.4. ECCO-ESGAR Diagnostics GL [2018] For a reliable diagnosis of UC and CD, ileocolonoscopy with
a minimum of two biopsies from the inflamed regions should be
[ECCO Anaemia Guideline: statement 1D in Dignass et al.] obtained.37–40 Additional biopsies from uninflamed regions and every
Diagnostic criteria for iron deficiency depend on the level colonic segment [including the rectum, especially in UC] may be help-
of inflammation. In patients without clinical, endoscopic, ful in the diagnostic process and to diagnose microscopic pathology.
or biochemical evidence of active disease, serum ferritin The distinction of infectious colitis from IBD is usually characterised
<30 μg/L is an appropriate criterion [EL2]. In the presence by preserved crypt architecture and acute inflammation.41 However,
of inflammation, serum ferritin up to 100 μg/L may still be in very early disease the architecture can be preserved. Other differ-
consistent with iron deficiency [EL4] ential diagnoses include segmental colitis associated with diverticuli-
tis [SCAD] and ischaemic colitis.42–45
Granulomas and focal crypt architectural abnormalities, in con-
Statement 1.5. ECCO-ESGAR Diagnostics GL [2018]
junction with focal or patchy chronic inflammation [defined by the
[ECCO Anaemia Guideline: statement 1E in Dignass et al.] presence of lymphocytes and plasma cells], or mucin preservation at
In the presence of biochemical or clinical evidence of active sites, are CD-related histological features. The patchy nature
inflammation, the diagnostic criteria for anaemia of of the inflammation is only diagnostic in untreated adult patients.46–50
chronic disease are serum ferritin >100 μg/L and transfer- One single feature is not considered to be diagnostic, though there
rin saturation <20%. If the serum ferritin level is between are no data available as to how many features must be present in an
30 and 100 μg/L, a combination of true iron deficiency and endoscopically derived biopsy before a firm diagnosis can be made.40
anaemia of chronic disease is likely [EL2] On surgical samples, a diagnosis of CD should be made when at least
three histological features suggestive of CD [segmental crypt archi-
tectural abnormalities and mucin depletion, mucin preservation at
One of the most frequent complications of IBD is anaemia (hae- the active sites, and focal chronic inflammation without crypt atro-
moglobin [Hb] <13 g/dL for men and <12 g/dL for women), which phy] are present in the absence of granulomas, or when an epithe-
may affect patients’ quality of life and should hence be evaluated lioid granuloma is present with one other feature.39,40
at initial diagnosis.27–29 In cases of documented anaemia, further Focal or diffuse basal plasmacytosis has been recognised as the
workup should start from the evaluation of mean corpuscular vol- earliest feature with the highest predictive value for UC diagnosis.
ume [MCV]. Microcytic anaemia is usually the most common type This can be identified in 38% of patients within 2 weeks after symp-
of anaemia in IBD, which usually indicates iron deficiency anaemia.30 tom presentation. During this period, the distribution pattern of
Macrocytosis may indicate vitamin B12 or folate deficiency and is basal plasmacytosis is focal but may eventually change into a diffuse
also commonly seen during thiopurine therapy, whereas normocy- pattern throughout the disease course. Only about 20% of patients
tosis may suggest anaemia of chronic disease [ACD].31 The distinc- show crypt distortion within 2 weeks of the first symptoms of colitis.
tion between iron deficiency anaemia and ACD or a mixed picture The distinction from infectious colitis is therefore a major concern.
of micro- and macrocytosis is important, as treatment is different Widespread mucosal or crypt architectural distortion, mucosal atro-
between these conditions. phy, and an irregular or villous mucosal surface appear later, at least
The diagnosis of iron deficiency depends on the level of inflam- 4 weeks after presentation.41,51 Not all microscopic features found
mation. In patients without clinical, endoscopic, or biochemical evi- in UC are observed in early disease. A correct diagnosis of UC is
dence of active disease, the diagnosis is made when serum ferritin is reached in approximately 75% of cases where two or three features
<30 µg/L.32,33 In the presence of inflammation, serum ferritin up to are present. However, the exact number of features needed for UC
100 µg/L may still be compatible with iron deficiency.34,35 Other mark- diagnosis has not been established.37
ers suggestive of iron deficiency anaemia are low mean corpuscular Due to the increased risk of bowel perforation, complete ileoco-
volume [MCV], raised red cell distribution width [RDW], microcytic lonoscopy is not usually recommended in case of acute severe coli-
hypochromic pencil red cells on blood film, low serum iron, raised tis.52 However, a study by Terheggen et al. demonstrated that there
total iron-binding capacity, and transferrin saturation of <16%.36 was no relationship between complication rate and disease activity.53
Flexible sigmoidoscopy can be safely performed to establish the if the decision to administer SBCE was based on imaging and not
diagnosis of UC. Phosphate enema preparation before flexible sig- on patency capsule results, at least 40% of the patients would not
moidoscopy has been reported to be safe in this setting,54 though it have undergone SBCE.57 Questions about optimal bowel preparation,
is generally advised to avoid purgatives, especially fleet enemas and selection of patients, and the optimal reading protocol remain to be
oral sodium phosphate preparations.55 clarified73 and are discussed in more detail later in part 2.
Statement 1.8. ECCO-ESGAR Diagnostics GL [2018] Statement 1.9. ECCO-ESGAR Diagnostics GL [2018]
Patients with clinical suspicion of CD and with normal Upper GI endoscopy is recommended in patients with CD
endoscopy should be considered for small bowel capsule with upper GI symptoms, but not for asymptomatic newly
endoscopy [SBCE] evaluation or cross-sectional imaging diagnosed adult IBD patients [EL5]
[EL2]. If stenotic disease is suspected, risk of retention
should be assessed [EL2] CD involving the upper GI tract [oesophagus, stomach, and duo-
denum] is almost invariably accompanied by small or large bowel
Small bowel capsule endoscopy [SBCE] is a sensitive tool to detect involvement.74–76 Patients who have upper gastrointestinal symptoms

mucosal abnormalities in the small bowel. There are currently two such as nausea, dyspepsia, and vomiting will benefit from upper GI
validated indexes available, namely the Capsule Endoscopy Crohn’s endoscopy.77 Whether asymptomatic adult CD patients should rou-
Disease Activity Index [CECDAI] and the Lewis Score, which assess the tinely undergo oesophago-gastroduodenoscopy is still debated.
disease location and activity of small bowel involvement. Both will be However, a prospective registry reported a higher prevalence of upper
discussed further in part 2. The diagnostic yield of SBCE is comparable GI involvement in asymptomatic CD patients than initially expected,77
to other modalities (MR enterography, small intestine contrast ultra- suggesting a place for a standard gastroscopy at CD diagnosis to cor-
sound [SICUS]), apart from proximal small bowel involvement for rectly evaluate disease extent. When it is difficult to obtain a histologi-
which SBCE seems superior.56 As proximal small bowel involvement is cal diagnosis of CD, upper GI endoscopy may support the diagnosis,
associated with a higher risk of surgery,57 this superior accuracy might as focal gastritis may be a feature of CD.74 Finally, upper GI endoscopy
have prognostic value.56 Data from small, prospective cohorts suggest is mandatory in patients with suspected concomitant coeliac disease.78
that the diagnostic yield of SBCE is highest in patients with sugges- The sensitivity and specificity of radiological imaging techniques
tive CD symptoms and increased inflammatory markers,58,59 although in the assessment of upper GI CD are unclear, with publications
this was not replicated in larger retrospective cohorts.60,61 However, the limited to case reports and small series. Radiological assessment
likelihood of positive diagnosis is very low in patients with suspected of patients should be reserved only for those patients with CD and
CD with FC <50 μg/g.62 Additionally, all patients with unclassified IBD upper GI symptoms in whom endoscopic assessment has failed or is
at diagnosis could also be considered for SBCE. incomplete. Radiological assessment of the upper GI tract should not
Similarly, as normal imaging tests such as intestinal ultrasound form part of routine diagnostic workup.
[IUS] and MR enterography of the small bowel cannot entirely
exclude small bowel involvement, CD patients with normal radio- Statement 1.10. ECCO-ESGAR Diagnostics GL [2018]
logical tests can be considered for additional SBCE, for example in
patients with clinical signs suspicious of small bowel Crohn´s disease All newly diagnosed CD patients should undergo small
and elevated calprotectin and/or otherwise unexplained iron defi- bowel assessment [intestinal ultrasound, MR enterogra-
ciency anaemia. Contraindications for SBCE include gastrointestinal phy and/or capsule endoscopy] [EL2]
obstruction, strictures, and swallowing disorders.63–65 The risk of
capsule retention in patients with suspected CD without obstructive The ileocaecal region is usually visualised adequately endoscopi-
symptoms and without history of small bowel resection or known cally. The proximal ileum and jejunum can be more difficult to
stenosis is low and comparable to that of obscure gastrointestinal assess. A study by Samuel et al. evaluated CD patients with com-
[GI] bleeding.66–69 Data on retention rates in patients with CD varies puted tomography [CT] enterography and ileocolonoscopy. Among
from 2% to 13% in patients with established CD, to approximately the group of patients with normal results from ileoscopy, 53.7% had
1.5% in patients with suspected CD.70 If small bowel stenosis is not active, small bowel CD. Ileoscopic examination can thus miss CD of
firmly excluded, a patency capsule can be used to confirm small bowel the terminal ileum, as the disease can skip the distal ileum or may be
patency before performing SBCE. All patency capsules are dissolved confined to the intramural portion of the bowel wall and mesentery.79
within 72 h. SBCE is considered safe if the patency capsule is excreted CT and MRI are both used to assess the small intestine. Both
before 30 h, an intact capsule is excreted after 30 h, or passage to the techniques can establish disease extent and activity based on wall
colon of an intact patency capsule has been radiologically confirmed.71 thickness and increased intravenous contrast enhancement.80
Yadav et al. demonstrated that the negative predictive value [NPV] for A direct comparison of CT and MRI for the diagnosis of a variety
patency capsules and radiological tests were not significantly differ- of small intestinal lesions demonstrates high sensitivity and specific-
ent.72 Thus, if either test is negative before SBCE, the patient will most ity, similar for both techniques.81–83 Due to the absence of radiation,
likely pass the capsule without incident. Radiological tests have the MRI should be preferred over CT, particularly in young patients.81
advantage of eliminating false-positive results, as they do not depend A study by Messaris et al. demonstrated that routine use of MR
on intestinal motility. However, cross-sectional imaging is significantly enterography can alter the management of patients with ileal or
less accurate in the evaluation of functional small bowel patency, fre- ileocolonic CD. In this study, 64 [53%] of patients had additional
quently overestimating the risk of obstruction. In a recent study evalu- medical management for active inflammation, and 16% underwent
ating the accuracy of MRI for prediction of patency capsule retention an operation for complicated CD or medical intractability. The
in patients with established small bowel CD, the sensitivity and speci- intraoperative findings were consistent with the MRI diagnosis in all
ficity of MR enterography were 92.3% and 59%, respectively. Thus, surgically treated patients.84 Similarly, Mendoza et al. demonstrated
that MRI influenced a change in treatment [medical or surgical] in exclude CD, the presence of small bowel pathology that is consistent
83 [55.3%] patients. The change in management even affected those with CD enables reclassification.90–95 In a study by Mow et al., mul-
patients who were already diagnosed with ileal or ileocolonic CD.85 tiple ulcerations [≥3 ulcerations] were considered diagnostic for CD
A direct comparison of intestinal ultrasound [IUS] and MRI per- and were observed in 26% of cases.90 Similar data have been reported
formed in 234 consecutive suspected CD patients showed a similar by Monteiro et al.; 25% of patients with unclassified IBD were found
diagnostic accuracy in detecting small bowel CD. Sensitivity, specifi- to have small bowel involvement consistent with CD. Still, 37% of
city, positive predictive value [PPV], and NPV for CD diagnosis were patients remained IBD unclassified during further follow-up.95
94%, 97%, 97%, and 94% for IUS and 96%, 94%, 94%, and 96%
for MR enterography, respectively. IUS was less accurate than MR Statement 1.13. ECCO-ESGAR Diagnostics GL [2018]
enterography in defining CD extent [r = 0.69], whereas the concord-
ance in terms of CD location between the two procedures was high Patients with unexplained perianal abscesses or complex
[κ = 0.81]. MR enterography also showed a fair concordance with fistulae should be investigated for CD [EL4]
IUS regarding strictures [κ = 0.82] and abscesses [κ = 0.88], with
better detection of enteroenteric fistulas [κ = 0.67].86 Perianal manifestations result in fistula and abscess formation in
A UK multicentre trial of 284 newly diagnosed or suspected 21% to 54% of CD patients96–99 and more frequently [up to 41%] in

relapsed Crohn’s disease patients showed that MRE had significantly patients with isolated colonic involvement compared with isolated
greater sensitivity for small bowel disease extent [presence and loca- ileal disease [12%].97 A thorough baseline clinical examination of
tion] compared with IUS [80% versus 70%, respectively]. MRE the perianal area should to be performed in all newly diagnosed
also had significantly greater specificity than IUS [95% versus 81%, patients at ileocolonoscopy, as symptoms can be initially very mild.
respectively]. For detecting the presence of small bowel disease irre- Diagnosis and classification of perianal disease are usually
spective of location, IUS sensitivity was 92%, compared with 97% achieved via a combination of both clinical and imaging findings.100
for MRE. Sensitivity for active small bowel [SB] disease was signifi- Fistulae can be considered ‘simple’ if they are low [of superficial or low
cantly greater for MRE than IUS (96% versus 90% [82 to 95]).87 intersphincteric or low transsphincteric origin], have a single external
A review by Calabrese et al. reported that IUS had a 79.7% sen- opening, and lack evidence of abscesses, rectovaginal fistulas, or ano-
sitivity and 96.7% specificity for the diagnosis of suspected CD, and rectal strictures. ‘Complex’ fistulas are high [of high intersphincteric or
an 89% sensitivity and 94.3% specificity in assessment of patients high trans-sphincteric or extrasphincteric or suprasphincteric origin],
with known CD with lower accuracy for detecting proximal small may have multiple external openings, and can be associated with the
bowel lesions. Administration of an oral contrast agent improved the presence of abscesses, rectovaginal fistulae, or anorectal strictures.101
sensitivity and specificity in determining CD lesions.88 A perianal abscess may be the first presentation of CD in a healthy
In a systematic review, the diagnostic yield of SBCE is compar- individual.102 Patients with an unexplained fistula and suspicion of
able to MR enterography and IUS, apart from proximal small bowel CD should therefore undergo ileocolonoscopy to assess mucosal
involvement for which SBCE seems to be superior. The odds ratio inflammation in the ileum or colon that may indicate CD.103 In case of
[OR] for diagnosis via SBCE versus MR enterography was 0.56 a negative conventional workup including ileocolonoscopy, capsule
(95% confidence interval [CI] 0.28–1.13; p = 0.1] and the OR for endoscopy can provide an incremental diagnostic yield of 24%.104
SBCE had superior diagnostic yield for proximal small bowel disease Proctosigmoidoscopy or ileocolonoscopy [if the proximal colon
with an OR of 2.62 [95% CI 1.10–6.53; p = 0.03].56 also needs evaluation] should be performed routinely in all patients
A range of factors, including local availability and expertise, with perianal CD to assess disease extent, severity of luminal inflam-
determines the choice of small bowel imaging modality. For initial mation, and presence of internal openings, and to exclude complica-
assessment and exclusion of CD, SBCE, IUS, MR enterography, tions such as strictures and cancer.103,105 Proctitis is a known risk factor
and CT enterography are superior to small bowel follow-through of persistent non-healing fistula tracts and increased proctectomy
[SBFT].83,89 Cross-sectional imaging of the small bowel should be rates,106 and often indicates complex fistulae and associated complica-
performed in preference to SBCE where clinical symptoms indicate tions such as abscesses.100 Undiagnosed extensions and abscesses are
obstructive or stricturing small bowel CD. major causes of recurrent disease after attempted surgical cure.100
Statement 1.11. ECCO-ESGAR Diagnostics GL [2018] Chapter 2: Monitoring known IBD

The presence of at least three small intestine ulcers in SBCE 2.1. Monitoring therapeutic success
highly suggests a diagnosis of CD, provided the patient
has not been using non-steroidal anti-inflammatory drugs Statement 2.1.1. ECCO-ESGAR Diagnostics GL [2018]
[NSAIDs] for at least 1 month before the test [EL4]
Response to treatment in active ulcerative colitis [UC]
should be determined by a combination of clinical
Statement 1.12. ECCO-ESGAR Diagnostics GL [2018] parameters, endoscopy, and laboratory markers such as
C-reactive protein [CRP] and faecal calprotectin [EL1]
In patients with negative endoscopy and suspicion of CD
on MRI or small bowel capsule endoscopy, device-assisted
enteroscopy may be performed if diagnosis needs to be Statement 2.1.2. ECCO-ESGAR Diagnostics GL [2018]
confirmed endoscopically and histologically [EL3]
In patients with UC who clinically respond to medical ther-
apy, mucosal healing [MH] should be determined endo-
Several small studies have evaluated the utility of SBCE for reclassi-
scopically or by faecal calprotectin [FC] approximately 3
fication of patients with UC and with unclassified IBD, and reported
to 6 months after treatment initiation [EL5]
varying reclassification rates. Although a normal SBCE cannot
recent study of 83 patients with moderate-to-severe UC, endoscopic

Statement 2.1.3. ECCO-ESGAR Diagnostics GL [2018] and IUS severity were graded 0 to 3 at entry according to validated
scores.116 Of the recruited patients, 74 patients who were clinically
Endoscopic reassessment in UC should be considered in
responsive to steroids were followed up with repeated colonoscopy
case of severe relapse, persistent disease activity, new
and IUS at 3, 9, and 15 months from recruitment. A high and con-
unexplained symptoms, and before switch of therapy [EL5].
sistent concordance was demonstrated between endoscopic and IUS
Sigmoidoscopy might be sufficient in most patients [EL5]
scores [weighted κ between 0.76 and 0.90]. Thus, IUS may be a
potential alternative to endoscopy to assess response to treatment
There is no gold standard in determination of therapeutic success in of severe UC.
ulcerative colitis [UC]. For follow-up of active disease in UC, endos- As IUS has significant limitations in detecting rectal disease, proc-
copy remains the reference standard. As UC involves the mucosa titis cannot be assessed by IUS as an alternative to sigmoidoscopy.
continuously from the rectum, colonoscopy with biopsies is still the Whereas FC has been shown to be useful for follow-up of procti-
reference standard for assessment of disease extent. However, flex- tis during treatment with mesalamine suppositories 8 weeks after
ible sigmoidoscopy is adequate for assessment of disease activity in treatment, the absolute levels of FC in ulcerative proctitis are low.118
most patients. Transrectal endosonography studies show that mucosal thickness

Several studies determined the benefit of mucosal healing [MH] correlates with endoscopic disease activity and a decline in bowel
in patients with UC. In a prospective Norwegian cohort, MH wall thickness, which can be determined a few weeks after treatment
was associated with reduced risk of colectomy in UC and lower in patients with active UC.119
inflammation at 5 years.107 These findings could be confirmed by a No study has compared the combination of different parameters
recent meta-analysis.108 In this meta-analysis, patients with MH had such as IUS plus FC in active UC, even though it is conceivable that
a pooled odds ratio of 4.50 for achieving long-term [after at least 52 combinations might enhance sensitivity. MR colonography [MRC]
weeks] clinical remission (95% confidence interval [CI] 2.12–9.52), can also assess inflammation with relatively high accuracy. In the
4.15 for remaining free of colectomy [95% CI 2.53–6.81], 8.40 largest series of 50 patients who underwent both MRC and endos-
for achieving long-term MH [95% CI 3.13–22.53], and 9.70 for copy, the segmental simplified MRC index strongly correlated with
achieving long-term corticosteroid-free clinical remission [95% CI the modified Baron score [r = 0.81, p < 0.001]. MRC was also able
0.94–99.67], compared with patients without MH. In accordance to detect endoscopic inflammation and severe lesions with high
with these findings, an international consensus panel recently recom- diagnostic accuracy [sensitivity 87% and 83%, specificity 88% and
mended MH as an important therapeutic goal for UC.109 82%, area under the curve 0.95 and 0.91, p < 0.001, respectively].
There is no evidence-based consensus of when best to reassess MRI may provide useful information on wall thickening, oedema,
disease activity after a change in therapy. However, in most induc- polyps, and extraluminal complications.120–122 MRI, especially when
tion studies MH has been determined approximately 2 to 3 months implemented with diffusion-weighted sequences, has high diagnostic
after starting treatment.110 Although this appears to be an appropri- accuracy in detecting active inflammation. Oussalah et al. investi-
ate time point to reassess, the exact timing will depend upon clinical gated 35 patients with UC, and reported a sensitivity and specificity
necessity and the chosen therapy. of 89.47% and 86.67%, respectively.123 Moreover, the accuracy of
There is a growing need to replace invasive diagnostics by surro- the diffusion-weighted imaging hyperintensity for detecting colonic
gate non-invasive markers. Blood parameters are convenient. However, inflammation was greater in UC than in CD [p = 0.004].
C-reactive protein [CRP] has low sensitivity in determining active
mucosal disease in UC, with serum levels frequently within normal
limits even in active disease.111 The exception is in patients with ele- Statement 2.1.4. ECCO-ESGAR Diagnostics GL [2018]
vated CRP levels during disease flare, for whom CRP might be used
as a suitable follow-up. A more accurate surrogate marker of MH is Clinical and biochemical response to treatment of Crohn’s
faecal calprotectin [FC]. There is a strong correlation between endo- disease [CD] should be determined within 12 weeks fol-
scopic inflammation and FC in UC. In a study with 52 patients, FC lowing initiation of therapy [EL2]. Endoscopic or trans-
correlated with clinical Mayo score [r = 0.63; p < 0.0001].112 This cor- mural response to therapy should be evaluated within
relation was strengthened by adding the endoscopic subscore [r = 0.90; 6 months following initiation of therapy [EL5]
p < 0.0001]. The endoscopic subscore also correlated independently
with FC [r = 0.96; p < 0.0001]. The use of FC as a surrogate marker for
MH in UC has also been demonstrated in several other studies.113,114 Statement 2.1.5. ECCO-ESGAR Diagnostics GL [2018]
Another potential non-invasive alternative for monitoring active Endoscopic or cross-sectional reassessment in CD should
UC is intestinal ultrasound [IUS]. In four studies that assessed the be considered in cases of relapse, persistent disease
diagnostic accuracy of IUS in a total of 74 patients, sensitivities activity, new unexplained symptoms, and prior to switch
ranged from 48% to 100% and specificities ranged from 82% to of therapy [EL5]
90%. Current evidence indicates that the diagnostic accuracy of IUS
in UC is also related to disease site, as sensitivity is high for sigmoid
or descending colonic disease [reaching 97%]115 but low for rectal Mucosal healing
disease.116 The utility of IUS for assessing activity has been assessed
in a study including 38 IBD patients [12 UC] and six controls.117 The There is no reference standard for determining therapeutic success in
mean colonic wall thickness was 3.2 mm in both Crohn’s disease CD. Clinical symptoms as scored by the CD Activity Index [CDAI] are
[CD] and UC, being higher in moderately [n = 46; p < 0.001] or not a reliable measure of the underlying inflammation. An increasing
severely inflamed bowels [n = 20; p < 0.001] compared with normal body of evidence suggests that MH may change the natural course of
segments [n = 58]. There are only few studies that address the use of CD by decreasing relapse rates, hospitalisation rates, and the need for
IUS for follow-up of patients with active UC under treatment. In a surgery124–126; as such, evaluation should be aimed at detecting this
endpoint, or at least at assessing a reliable surrogate marker of MH. treatment and 2 weeks thereafter. Anti-TNF therapy led to a signifi-
MH can be directly visualised endoscopically. Cross-sectional imaging cant reduction in bowel wall thickness [p = 0.005] and Doppler flow
and non-invasive serological and faecal surrogate markers may how- [p = 0.02], leading to the disappearance of IUS changes in 50% of
ever provide an indication, especially important when assessing parts the patients. However, sonographic normality was only achieved in
of the bowel that are difficult to reach endoscopically. five out of 17 patients [29%] with a clinical and biological response,
The time interval of when to evaluate MH endoscopically can and could not differentiate between those with and without clini-
be inferred somewhat from trial data. However, studies have seldom cal and biological response [p = 0.27]. A more recent prospective
been designed to directly evaluate the best point for reassessment and, trial evaluated IUS features in patients with CD after treatment
as such, inferences regarding optimal timing for re-evaluation must with biologics, using ileocolonoscopy as a reference standard.142 In
be taken with care. Any recent change in therapy must also be consid- this trial, normalisation of the IUS parameters could be observed in
ered. For example, it is recognised that the anti-integrin antibody ved- 62.8% of the patients, with a significant correlation compared with
olizumab takes longer than steroids or anti-TNFs for MH to occur. ileocolonoscopy [κ = 0.76; p < 0.001]. Some authors suggest that
A sub-study of the SONIC trial demonstrated that MH along with Contrast-enhanced ultrasound (CEUS) might be useful to determine
steroid-free clinical remission at Week 26 was strongly predictive of treatment outcome shortly after initiating treatment with biolog-
steroid-free clinical remission at Week 50 [82%].127 The EXTEND ics.133 In a study on 133 CD patients, transmural healing could be

trial demonstrated that MH at 12 weeks correlated well with MH at observed in approximately 25% of patients.134 Most of the patients
52 weeks.126 Thus, it appears that 12 to 24 weeks is a sensible time received anti-TNF therapy. In a paediatric CD study, 32 patients
scale for re-evaluation of MH. were included and followed up by IUS and ileocolonoscopy 9 to
The degree of mucosal inflammation may differ between segments 12 months after treatment initiation. Patients with MH showed a
of the digestive tract128; the need for panenteric evaluation remains to significant decrease of bowel wall thickness and disease extension.135
be determined. In a retrospective analysis of the SONIC trial, CDAI In a prospective multicentre longitudinal study of 51 patients with
scores and CRP values at baseline and at Week 26 were analysed from active CD, all patients underwent a clinical assessment and sono-
188 CD patients who had evaluable ileocolonoscopy with evidence graphic examination at baseline, 12 weeks after treatment initiation,
of mucosal ulceration at baseline.129 Half of the patients treated with and after 1 year of treatment.136 Improvement at 52 weeks was more
azathioprine or infliximab [or both] in clinical remission had endo- frequent in patients with improvement at the end of induction [12
scopic or CRP evidence [or both] of residual active CD, whereas other weeks] compared with patients who did not improve [85% versus
patients with endoscopic and CRP normalisation had persistent clini- 28%; p < 0.0001]. The authors concluded that sonographic response
cal symptoms. In a retrospective study of 201 patients with CD, the after 12 weeks of therapy predicts 1-year sonographic response.
predictors of medium-term clinical efficacy and MH during adali- A large multicentre trial including 243 patients from 50 centres in
mumab therapy were evaluated.130 Clinical efficacy and normalised Germany has recently been conducted to determine the role of IUS
CRP at Week 12 were associated with medium-term clinical efficacy for monitoring treatment response.132 In this trial, CD patients with
and mucosal healing during adalimumab therapy, whereas need for an acute disease flare received anti-inflammatory treatment. Almost
combined immunosuppression at induction and smoking status were all sonographic parameters determined during IUS [including bowel
predictors for non-response. Thus, correlation between CRP and wall thickness, vascularisation parameters, fibro-fatty proliferation]
MH is variable. Several studies indicate that FC correlates well with showed a highly significant decrease [p < 0.001 in all groups] at dif-
colonic inflammation in CD and might therefore be used as a surro- ferent sites. Interestingly, reduction of bowel wall thickness was more
gate marker.62,112 Importantly, although initial studies suggested that pronounced in the colon compared with the ileum. Improvement of
FC may be less sensitive in isolated small bowel disease, a recent meta- ultrasound parameters correlated with laboratory parameters such as
analysis demonstrated that the diagnostic yield of FC is significant for CRP.132 Based on current studies, IUS seems to be a valuable method
detection of active disease in the small bowel, with a negative predic- to determine transmural healing in CD, with bowel wall thickness
tive value [NPV] of 90% for the cut-off value of 50 µg/mL.62 and vascularisation appearing to be the most relevant parameters.143
The value of CT was assessed in a retrospective North American
study on 63 infliximab-treated patients with CD.137 Of 105 lesions,
Transmural healing – Role of MRI, CT, and IUS 21 [20%] were colonic. Poor-to-fair correlation was found between
There is no reference standard for CD activity, and any kind of diag- CT enterography features of response and improved clinical symp-
nostic modality [including endoscopy, MRI, laboratory parameters, toms [κ 0.26], improved endoscopic appearance [κ 0.07], and reduc-
or IUS] can only be used as a surrogate marker in this situation. CD tion of CRP [κ 0.30]. When comparing responders [complete and
is a transmural process; thus full-thickness bowel healing or remod- partial] with non-responders, only the presence of the ‘comb sign’ on
elling could be important endpoints. the index CT enterography was predictive of radiological response
Various studies have assessed the value of cross-sectional imaging [p = 0.024]. Even though CT in principle might be a suitable method
techniques for therapeutic monitoring in CD affecting the small and to determine disease activity in CD, it should be noted that CT, due
large bowel. These studies assessed IUS,131–136 CT,137 or MRI.138–140 to radiation safety, should not usually be used for monitoring disease
The role of IUS as a non-invasive and inexpensive imaging modal- activity if MRI or IUS is available.
ity for determining the treatment response of transmural inflam- In terms of responsiveness and reliability, different studies have
mation in CD has been evaluated in different studies. The utility shown that MRI has a high accuracy for monitoring therapeutic
of IUS for assessing activity and drug response has been compared responses using endoscopy as a reference standard.138–140 In a recent
with colonoscopy,116 with high concordance [weighted κ between study, 48 patients with ileocolonic CD were prospectively evalu-
0.76 and 0.90]. For example, a prospective study performed on 24 ated with MR enterography in comparison with ileocolonoscopy.138
consecutive patients with CD used IUS to assess changes induced MR enterography determined ulcer healing with 90% accuracy and
by anti-TNF therapy and its relationship with clinical and biologi- endoscopic remission with 83% accuracy. The mean CD Endoscopic
cal response.141 Parameters were measured 1 week before induction Index Of Severity [CDEIS] and Magnetic Resonance Index Of Activity
[MaRIA] scores significantly changed at Week 12 in segments with The other variables did not improve significantly. In another study,
ulcer healing, based on endoscopic examination [CDEIS, 21.28 ± 9.10 the CECDAI index was used to assess ileitis severity. All parameters
at baseline versus 2.73 ± 4.12 at 12 weeks; p < 0.001; and MaRIA, were reassessed at Week 52. In total, 108 capsule procedures were
18.86 ± 9.50 at baseline versus 8.73 ± 5.88 at 12 weeks; p < 0.001]. performed on 43 patients. Based on the CECDAI, 39 patients [90%]
The authors concluded that the MaRIA score is a valid, responsive, exhibited active small bowel CD at baseline, with 28 patients [65%]
and reliable index assessing response to therapy in patients with CD. undergoing assessment at 52 weeks. In total, 12 patients [42%]
In a retrospective study with 50 patients, MRI inflammation scores achieved complete MH and deep remission at the 52-week assess-
during anti-TNF therapy improved in 29 of 64 lesions [45.3%], ment [95% CI -0.62 to -0.22; p < 0.0001].148 SBCE has a significant
remained unchanged in 18 of 64 lesions [28.1%], or deteriorated in impact on disease management; in the largest retrospective series
17 of 64 lesions [26.6%] over time. In the anti-TNF responder group, of patients with established CD that were evaluated with SBCE, a
the mean intestinal inflammation score of all lesions improved from change in management was suggested in 52% of 187 patients.60
5.19 to 3.12 [p < 0.0001]. The mean inflammation scores in sten-
otic lesions in anti-TNF responders also improved significantly, from Statement 2.1.6. ECCO-ESGAR Diagnostics GL [2018]
6.33 to 4.58 [p = 0.01]. In contrast, the mean inflammation scores
did not change significantly [5.55–5.92; p = 0.49] in non-responders. In the absence of credible evidence to support the best

Diagnostic accuracy of anti-TNF response on MRI was 68%.139 The modality to assess response to treatment in upper GI dis-
authors conclude that MRI can be used to guide the optimal use of ease of CD, endoscopy is recommended as the preferred
TNF antagonists in daily clinical practice. In a prospective single- method [EL5]
centre trial with 27 patients treated with anti-TNF [infliximab or
adalimumab], the mean SES-CD and MaRIA scores significantly Data on imaging in upper GI CD and in particular on monitoring
changed at Week 26 [SES-CD: 14.7 ± 8.9 at baseline versus 4.4 ± 4.6 disease are sparse and sizeable series are unavailable, with essen-
at 26 weeks; p < 0.001; MaRIA: 41.1 ± 14.8 at baseline versus. tially absent data for the stomach. Cross-sectional imaging may
32.8 ± 11.7 at 26 weeks; p < 0.001]. The overall MaRIA correlated reveal ulcers or strictures in oesophageal CD, but superficial lesions
with endoscopic score and with clinical activity [CDAI] both at base- are difficult to detect, underscoring the importance of endoscopy in
line and at Week 26 [p < 0.05]. The authors conclude that the MaRIA the diagnosis of oesophageal CD. Endoscopy with tissue biopsy is
has a good correlation with SES-CD, a high accuracy for prediction of useful to exclude other common oesophageal disorders. The most
endoscopic mucosal healing, and is a reliable indicator to monitor the commonly described findings on endoscopy include aphthous ulcers,
use of TNF antagonists in patients with CD.140 superficial erosions, and late-stage stricture development and cobble-
In a systematic review and analysis to identify MRE variables stoning of the mucosa.151,152 One study discussed the application of
used to describe inflammation and damage wall enhancement, various methods to diagnose various inflammatory conditions of the
mucosal lesions and wall T2 hyperintensity were the most consist- oesophagus.153
ently useful for inflammation [most sensitivities >80% and specifici- Although IUS and MRI seem to be feasible tools to determine
ties >90%].144 disease activity of CD in the duodenum and stomach, there are no
In addition, in a retrospective analysis of 150 CD patients, hav- convincing data that prove their value in disease monitoring. Upper
ing either had a pre- and post-therapy CTE or MRE radiological GI involvement should therefore be primarily monitored by the ref-
response to medical therapy was associated with significant reduc- erence standard endoscopy.
tions in long-term risk of hospitalisation, surgery, or corticosteroid
usage among small bowel CD patients.145 Statement 2.1.7. ECCO-ESGAR Diagnostics GL [2018]
As MR enterography and IUS appear to be of similar value for
Extramural complications in CD [such as fistulae and
monitoring transmural healing in CD during treatment, which imag-
abscesses] should be monitored by cross-sectional
ing modality to use depends on local availability and expertise.
imaging, including intestinal ultrasound [IUS] [EL2] or MRI
[EL2] [or both] in combination with clinical and laboratory
Video-capsule endoscopy parameters [EL5]
As endoscopic access of the small bowel is more difficult, response to

treatment should either be determined by IUS or MR enterography or Whereas a variety of studies have shown good sensitivity and speci-
by capsule endoscopy. The superiority of small bowel capsule endos- ficity of cross-sectional imaging to assess fistulae and abscesses, there
copy [SBCE] compared with other imaging modalities to determine are only few studies that address the follow-up of these extramu-
small bowel disease in CD has been described in different studies.146 ral complications after treatment. The sensitivity of cross-sectional
Recent clinical trials have evaluated the potential role of SBCE for imaging modalities such as MRI, IUS, and CT to determine extramu-
assessment of MH in the small bowel.147–149 These trials used quan- ral complications has been shown to be high in a recent meta-anal-
titative scores such as the Lewis Score150 or the Capsule Endoscopy ysis, with sensitivity between 84% and 93% and specificity between
CD Activity Index [CECDAI], analogous to the application to ile- 90% and 93%, as discussed above.81,154 Although CT is accurate for
ocolonoscopy of the CDEIS or the simple endoscopic score for CD. follow-up of mural and extramural complications in CD patients,
In a case-control study, 40 patients with known or suspected CD CT is not recommended for monitoring patients with active disease
were included and underwent SBCE.147 When patients achieved clini- under treatment, due to radiation safety.155 Although the dose can
cal response [after at least 1 month of treatment] they underwent a be reduced substantially with state-of-the-art low-radiation-dose CT
second SBCE, with evaluation of the same parameters. The numbers scanners, the use of non-ionizing radiation techniques is preferable,
(mean ± standard error of the mean [SEM]) of large ulcers before considering the usually young age of these patients. Thus, CT should
and after treatment were 8.3 ± 1.4 and 5 ± 0.8, respectively (mean be used judiciously, ideally only in the emergency setting and if IUS
difference 3.3 ± 1.2, 95% confidence interval [CI] 0.8–5.9; p = 0.01). and MRI are unavailable.
Statement 2.1.8. ECCO-ESGAR Diagnostics GL [2018] Statement 2.1.9. ECCO-ESGAR Diagnostics GL [2018]
Perianal CD should be reassessed by clinical evaluation in Therapeutic drug monitoring might be beneficial in CD
combination with endoscopic examination of the rectum and UC in patients with non-response to thiopurines [EL3]
plus MRI [EL1]. Transrectal ultrasonography [TRUS] in the or anti-TNF therapy [EL2]. Drug level monitoring is man-
absence of anal stenosis [EL1] or transperineal ultrason- datory during treatment with calcineurin inhibitors [EL2]
ography [TPUS] [EL2] might be used instead of MRI
TRUS were correctly classified by TPUS in 45 cases, reaching a sen-
Evaluation of perianal CD and fistula closure is primarily achieved sitivity of 84.9%.173
with clinical evaluation. The definition of fistula healing varies in the Primary non-response and secondary loss of response are common
literature and there is no consensus on when a first or definitive evalu- problems during anti-TNF therapy. Loss of response [LOR] to anti-
ation of fistula healing should be performed.156 The Perianal Disease TNF has been shown to be as high as 20% to 40% after the first year
Activity Index [PDAI]157 is a clinical scoring system that has been of treatment174 and about 10% in the following years.
used and validated in clinical studies both at diagnosis and to meas- In a recent study on 247 patients, it was shown that therapeu-

ure treatment response. Fistula drainage assessment has been used in tic drug monitoring by measurement of anti-TNF trough levels and
several clinical trials of medical therapy,158–160 but is very much inves- antidrug antibodies in IBD patients with secondary LOR may lead to
tigator-dependent and has not been validated in large studies. A single therapeutic changes in more than 70% of patients.175 Several studies
retrospective study has evaluated the PDAI scoring system, where high have demonstrated that low trough levels and detectable antidrug
scores predicted short-term surgical outcome, but this has not since antibodies are associated with LOR.176–178 In a recent meta-analysis
been validated.161 of 22 trials with 3483 patients, it was shown that high infliximab
MRI classifications of fistula severity have been proposed, such as trough levels correlate with good clinical response and low CRP lev-
the system published by Van Assche et al.162 Thus far, this system is of els.179 Similar results have been shown for golimumab180 and adali-
limited use outside clinical trials. MRI is increasingly used to assess fis- mumab.181 Even though the primary endpoint of the TAXIT trial
tula healing, particularly during medical therapies.162–164 Various MRI [treatment guidance via infliximab trough level concentration meas-
classifications have been proposed, including the Van Assche Score,162 urements] was not achieved, it was shown that dose escalation in
which considers the number of fistulae, localisation, extensions, T2 patients with sub-therapeutic levels improved clinical response.182 The
hyperintensity, abscesses, and rectal involvement. Assessment of optimal trough level concentration in this study was defined as 3–7
dynamic contrast enhancement has also been proposed as a means µg/mL. A cohort of 60 CD patients treated with adalimumab has
to monitor fistula activity.165 It has been shown that fistulae may re- been investigated retrospectively.183 Higher adalimumab trough levels
open after therapy cessation, and studies using MRI findings as a more were significantly associated with MH [median 14.7 µg/mL in those
stringent endpoint of deep fistula healing suggest that MRI162,164,166 with MH versus 3.4 µg/mL in those without; p < 0.001]. This study
and endo-anal ultrasound167,168 may be useful for identification of fis- suggests that attaining MH alone or a combined outcome of clinical
tulae that show external closure but retain an internal fistula tract. and endoscopic remission is more likely to occur in those patients
This suggests that imaging assessment of deep healing is superior to who achieve an adalimumab trough level of at least 8.14 µg/mL.
simple clinical evaluation, although long-term comparative studies are In a recent study, primary non-response to anti-TNF therapy
lacking. in patients with severe UC was associated with faecal loss of inf-
Despite the lack of relevant studies evaluating the role of MRI for liximab.184 However, the optimal time points and cut-off levels for
the specific assessment of patients during and after therapy, several trough level measurements to determine primary non-response must
comparative studies have been performed evaluating ultrasound and still be determined.
MRI in perianal fistula diagnosis in CD. In most of these studies, Different studies have shown that measurement of thiopurine
MRI seems to be the method of choice. Schwartz et al. compared metabolites, such as 6-mercaptopurine [6-MMP] and 6-thioguanine
examination under anaesthesia [EUA], MRI, and transrectal ultra- [6-TGN], might be beneficial in patients with suboptimal response to
sonography [TRUS], and demonstrated a diagnostic accuracy of thiopurines. In a recent study, determination of 6-TGN and 6-MMP
91%, 87%, and 91%, respectively.169 Buchanan et al. performed a levels identified patients with reduced compliance in 11% and raised
large prospective clinical trial comparing preoperative digital rectal 6-MMP levels in 10%. Treatment improvement could be achieved in
examination, endoscopic ultrasound, and body-coil MRI for the pre- 87% of patients after optimising thiopurine usage.185
operative assessment of anal fistulae. According to their results, MRI It is likely that as vedolizumab and ustekinumab drug monitor-
was superior to both methods for abscess detection and accuracy in ing becomes more easily available, this will also form part of man-
fistula classification [90% of patients correctly classified by MRI, agement strategies when treating patients with these agents.
81% by TRUS, and 61% by EUA].170 In a recent meta-analysis, the
sensitivity of MRI and of TRUS to determine perianal CD was 87% 2.2. Monitoring clinically asymptomatic patients
for both imaging modalities, and specificity was 69% versus 43%,
respectively.171 A recent consensus suggested a combination of dif-
Statement 2.2.1. ECCO-ESGAR Diagnostics GL [2018]
ferent imaging modalities for diagnostic use during perianal CD.172
MRI may therefore be slightly superior to TRUS for determin- In patients with IBD who have reached clinical and bio-
ing perianal disease activity. However, use of the adequate imaging chemical remission, monitoring is aimed at early recog-
modality also depends on local availability and expertise. nition of a disease flare [EL5]. The interval of monitoring
If MRI is not available and TRUS is either not available or unfea- should be between 3 to 6 months depending upon dur-
sible due to pain, transperineal ultrasonography [TPUS] is an alter- ation of remission and current therapy [EL5]. Relapse can
native, although its sensitivity is lower than TRUS. In a recent study be detected with FC before clinical symptoms [EL2]
investigating 46 patients with perianal CD, 53 fistulae detected by
Figure 1 shows a simplified disease progression pathway in IBD from monitoring in this phase is to detect deviations from the target range,
risk factors to irreversible intestinal fibrosis. The practicality of a indicating the start of phase IV. In phase IV, therapy is adjusted to re-
given test for IBD monitoring decreases further downstream in the establish disease control and bring FC levels back to the target range.
pathway, as the disease becomes more resistant to standard therapy. When the FC concentration is in the target range, the patient is
The ideal monitoring test is non-invasive, simple to conduct, and reassured and advised to retest in 3 months. When the FC concentra-
easily interpretable. Such a test should detect an imminent disease tion is in the action range, the treatment plan is adjusted and re-testing
flare [often undetectable by symptom-based reporting alone] and is advised for the next month. In the uncertain range, a test interval of
make provision for proactive treatment optimisation [Table 1]. 1 month is advised before progressing to a treatment decision.
Faecal calprotectin C-reactive protein

The utility of FC monitoring in patients with quiescent disease Serum CRP is an acute-phase reactant that has been used in clini-
was evaluated in a recently published systematic review.186 Electronic cal practice for many years as a general measure of inflammation. In
searches up to April 2016 identified six prospective studies [mostly a meta-analysis of cohort and case-control studies that compared the
in UC patients] that met the selection criteria. Since then, an addi- diagnostic accuracy of CRP [index test] with endoscopy [reference

tional five prospective studies in both UC and CD patients were standard] in patients with symptomatic IBD, a CRP concentration of
published.118,187–190 ≥5 mg/L appeared to have a high specificity for detecting endoscopic
Two consecutively elevated FC levels were the best predictor for disease activity.111 However, the sensitivity was very poor and a nega-
clinical relapse, but this was investigated systematically in only one tive test does not exclude the presence of a flare. Almost two-thirds
study.191 In one of the more recently published studies, patients with of the asymptomatic patients with normalised CRP still had active
both UC and CD provided faecal samples every third month and endoscopic lesions, and consequently an isolated fall in CRP was
were prospectively followed until the first clinical relapse.188 This insufficient reassurance of endoscopic remission.201 Repeated CRP
study revealed that FC levels start rising approximately 3 months measurements in the detection of early postoperative recurrence
before a relapse becomes clinically apparent, and confirmed the of CD,202 or in the follow-up of small bowel CD,203 are inferior to
observations of the aforementioned systematic review. These findings repeated FC measurements.
support the biological implausibility that a single FC measurement
at baseline can predict the clinical course over a 12-month period, as
suggested in a meta-analysis192 and more recently by Theede et al.193
Currently, there is no consensus on the ideal cut-off point for Asymptomatic patients with abnormal biochemical
FC monitoring. In clinical trials where response to a new treatment parameters may have an imminent disease flare. After
is monitored, a low cut-off point [e.g. 100 μg/g] is frequently used excluding infection, endoscopic or cross-sectional imag-
to demarcate the upper limit of the normal FC range. Conversely, in ing [or both] should be performed [EL5]
real-life studies, a higher cut-off point is advocated [e.g. 250 μg/g]
as an action threshold for adjusting treatment.194–197 A prospective
evaluation of a monitoring strategy is needed, namely a planned and Capsule endoscopy
organised system of repeated FC assessments and subsequent deci- Recent prospective studies have shown that stool markers such as FC
sions about starting, modifying, or de-escalating therapy, as has been are useful in monitoring inflammation in the small bowel. Increased
part of the recently published CALM study.198 FC levels with negative findings on conventional endoscopy should
A general construct for FC-based disease monitoring in patients trigger further investigations into the presence of active small bowel
with IBD is shown in Figure 2, which illustrates the four phases of disease.204 Small bowel CD is in many cases located proximal to the
disease monitoring.199,200 Repeated FC measures are used to longitu- terminal ileum and is therefore inaccessible to conventional ileocolo-
dinally track changes in a patient’s condition over time. In phase I, noscopy. In a considerable proportion of asymptomatic patients with
IBD is suspected but is neither endoscopically confirmed nor treated. CD, previously unknown new proximal involvement and progression
In phase II, induction therapy is introduced to achieve disease con- to stricturing or penetrating disease were demonstrated with capsule
trol, resulting in patient response. Phase III begins with disease endoscopy,61 leading to modifications in the original Montreal classi-
remission with continuation of maintenance therapy. The goal of fication and consequently to treatment escalation.205 In a prospective
IBD susceptibility Intestinal Irreversible

inflammation intestinal fibrosis
– Genetics
– Gut microbiome
– Environment
– Immune response
Early targets: Intermediate: Late targets:

– Calprotectin – CRP – Weight
– Endoscopy – Symptom- – Bone health
– MRI based scores – Hospitalizations
– Intestinal US – Hematinic – Surgery
indices
Figure 1. Targets along the disease progression pathway in IBD.

observational cohort of patients with asymptomatic or mildly active

small bowel CD, tolerance and preference to MR enterography versus Statement 2.2.3. ECCO-ESGAR Diagnostics GL [2018]
capsule endoscopy were compared. Pre-examination and procedural Before de-escalation or withdrawal of maintenance IBD
discomfort was perceived more favourable in capsule endoscopy. therapy, it is necessary to assess disease activity using
The superior tolerability of capsule endoscopy, along with diag- a combination of clinical and biochemical markers and
nostic features, should be considered when choosing between these endoscopic and/or cross-sectional imaging, balancing the
two modalities for long-term follow-up.205 A negative FC result in risks and benefits of withdrawal [EL5]
an asymptomatic CD patient should deter the clinician from using
additional small bowel imaging techniques.204
In a recent meta-analysis of 18 studies, stopping immunomodu-
latory monotherapy after a period of remission was associated
MR enterography with approximately 75% of patients experiencing a relapse
MR enterography is not a suitable technique for early recog- within 5 years after therapy discontinuation.210 Approximately
nition of disease recurrence, since aphthoid ulcerations cannot be 50% of patients who discontinued anti-TNF therapy after com-
assessed. As disease severity progresses, MR enterography manifes- bination therapy in this systematic review maintained remission

tations become more apparent. Several studies have evaluated the 24 months later, but the proportion decreased over time.210 Similar
ability of MR enterography to quantify therapeutic response to results have been reported in other meta-analyses.211,212 The fac-
immunosuppressive therapy, especially in children.206 tors that predict relapse after discontinuation of therapy remain
controversial.
In a placebo-controlled study by the GETAID group, which
Intestinal ultrasound included 83 patients in clinical remission under azathioprine, neither
the presence of ulcerations nor a CDEIS >0 at ileocolonoscopy before
IUS is a non-invasive, widely available technique that does not
azathioprine discontinuation was predictive of clinical relapse.213 In
use ionising radiation and is well accepted and tolerated by patients.
contrast, in another GETAID trial, Louis et al. assessed the risk of
Most parts of the large bowel [with the exception of the rectum] and
clinical relapse after discontinuation of infliximab in 109 patients
major parts of the small bowel [with the exception of the proximal
with CD who were in clinical remission under combined mainte-
jejunum] can be visualised by IUS. The advantages of IUS include
nance therapy with infliximab and an immunomodulatory agent.214
rapid evaluation of bowel wall thickness and direct visualisation of
In their multivariate analysis, the absence of MH was among the fac-
bowel vascularisation and motility.88,207,208 The role of this technique
tors strongly associated with an increased risk of clinical relapse after
in monitoring patients with asymptomatic CD or UC is not yet clear.
infliximab withdrawal [hazard ratio 2.6]. In this study, immunosup-
More is known about the role of IUS in monitoring response to
pression with azathioprine or methotrexate was continued after inf-
treatment in CD patients. In a prospective trial that followed 234
liximab withdrawal. In a recent meta-analysis, the relapse rate 1 year
CD patients with bowel wall alterations in the terminal ileum or in
after discontinuation of anti-TNF therapy was 42%, which decreased
the colon, follow-up every 3 months showed significant improve-
to 26% when endoscopic remission was also required.211 Assessment
ments in nearly all ultrasound parameters.132 There is good concord-
of endoscopic activity in patients with quiescent CD is recommended
ance between ultrasound and MR enterography for disease location
before discontinuation of treatment is considered.
and activity, and fewer technical difficulties with IUS.209
Table 1. Markers of disease activity for monitoring asymptomatic IBD patients.
Validity [correlation Responsiveness to changes in Signal-to-noise ratio [ability to dif- Practicality

with gold standard] condition ferentiate changes in condition from
background variability]
Endoscopy Gold standard Gold standard Gold standard Low

Requires bowel preparation and
general anaesthesia in children
Faecal calprotectin Good Good Moderate High
Rises quickly in case of relapse; Risk of false-positive results Possible reluctance of patients
falls rapidly with successful for repeated stool collection
treatment
C-reactive protein Moderate Moderate Moderate High
Late position in disease Risk of false-positive results [acute Quick result; but requires
progression pathway infections and other inflammatory venepuncture
conditions] and false-negative results
[normal CRP despite active disease]
Capsule endoscopy Good Good Moderate Moderate
Potential over-interpretation of in- Requires bowel preparation, but
significant mucosal lesions is generally well tolerated
MR enterography Moderate Moderate Unknown Moderate
Late position in disease Requires oral preparation for
progression pathway bowel distention, and in children
preparation through a nasoduo-
denal tube
Intestinal ultrasound Unknown Good Unknown High
Non-invasive, widely available,
and well tolerated
I II III IV III
Selection for Achieve Detect drift from Bring Detect drift from
endoscopy control target range value target range
back
FECAL CALPROTECTIN LEVEL

within
target
range
ACTION RANGE
Action threshold
UNCERTAIN RANGE

Target threshold
TARGET RANGE
PRIOR
DIAGNOSIS 0 3 6 9 12 15 18 21 24 27 30 33
TIME SINCE DIAGNOSIS

(months)
Figure 2. Conceptual model of FC-based monitoring in IBD patients [Copyright 2017 by the Wolters Kluwer Health, Inc. Used with permission].
2.3. Monitoring clinically symptomatic patients colectomy rate.222 Corticosteroid and thiopurine exposure are
associated with reactivation of latent CMV.223 However, tissue
Statement 2.3.1. ECCO-ESGAR Diagnostics GL [2018] damage following exposure to immunomodulators is rare.224 Anti-
TNF agents and cyclosporine also do not appear to be associated
All patients with a suspected new flare of IBD should
with adverse outcomes in CMV-positive patients.225 Therefore,
be investigated for infection, including exclusion of
the ECCO guidance on opportunistic infections recommends that
Clostridium difficile infection [EL3]
testing for CMV should be reserved for steroid-resistant disease.26
Bacterial infection and Clostridium difficile should be excluded in all Statement 2.3.2. ECCO-ESGAR Diagnostics GL [2018]
patients. Diagnostic workup is recommended according to test avail-
Cytomegalovirus [CMV] should be tested in immunosup-
ability and local practice. Available tests include glutamate dehydroge-
pressant-resistant UC as CMV is associated with adverse
nase antigen and toxin A/B enzyme immunoassays, bacterial cultures,
outcomes, including reduced efficacy of therapy and
cytotoxicity assay, and nucleic acid amplification technology tests.
increased colectomy rates [EL3]
This is particularly important in patients with colonic disease
where the diagnostic yield is higher; in one series of paediatric
patients with UC [n = 354 stool tests], 1.8% of tests were positive CMV disease is most commonly assessed via detection of CMV
for Salmonella serotype typhi and 13.6% were positive for C. dif- DNA through PCR or immunohistochemistry of tissue biopsies and
ficile toxin.215 Patients with CD have comparatively lower rates of blood. The second European evidence-based consensus on oppor-
C. difficile infection.216 tunistic infection in IBD provides more detailed information on the
In UC, C difficile is associated with poorer outcome, including diagnosis and management of CMV infection.26
increased colectomy rates217 and increased postoperative complica-
tions218,219; detection is thus of direct clinical relevance. Additional Statement 2.3.3. ECCO-ESGAR Diagnostics GL [2018]
interrogation of faeces with polymerase chain reaction [PCR] should
not be performed routinely as there is a high rate of detection of Colonoscopy is the modality of choice to assess disease
bacteria that may not be of clinical significance, even in healthy activity of symptomatic colonic CD or UC [EL5]. Cross-
controls.220 sectional imaging is complementary to assess phenotype
Parasitic infections are found in about 12% of patients with UC [EL2], and may be used as an alternative to evaluate dis-
who reside in endemic areas.221 If travel history is suggestive, stool ease activity. Sigmoidoscopy should be considered in UC
examination for ova cysts and parasites and Strongyloides serology if symptoms suggest an acute severe flare
should be performed before therapy is escalated. Local protocols
regarding testing and transport of stool samples should be followed. Ileocolonoscopy provides direct mucosal visualisation of the colon
Further guidance on management of opportunistic infection can be and terminal ileum and allows histological assessment and therapeu-
found in the second European evidence-based consensus on the pre- tic intervention. As such it is the gold standard investigation of large
vention, diagnosis, and management of opportunistic infections in bowel disease.
inflammatory bowel disease.26 If assessment of disease location or behaviour is not necessary,
A recent meta-analysis revealed that cytomegalovirus [CMV] FC can be used to evaluate activity from the colon to the small
infection in IBD may be associated with longer disease dura- bowel.62,204,226–229 Studies have shown good correlation [r > 0.8] with
tion, reduced efficacy of corticosteroid therapy, and increased endoscopic disease activity in both CD and UC.230,231
If acute severe UC is suspected, endoscopic evaluation should be lim- Most studies show the diagnostic accuracy of SBCE to be compa-
ited to flexible sigmoidoscopy, as discussed previously in this guideline. rable to MR enterography, CT enterography, and IUS in CD,56,263–267
MR enterography232–237 of the colon, capsule endoscopy,238–240 although a 2017 meta-analysis demonstrated superior detection of
and IUS115 can also be considered for assessment of disease extent proximal small bowel disease compared with MR enterography (odds
and phenotype in individuals reluctant to undergo endoscopic evalu- ratio [OR] 2.79, 95% CI 1.2–6.48).56 This is in comparison with MR
ation. In a UK multicentre trial, IUS had superior sensitivity com- enterography, CT enterography, barium studies, and IUS.89 Clinically, the
pared with MRE for colonic disease presence in newly diagnosed use of SBCE is associated with earlier escalation of therapy.268 However,
patients [67% versus 47%, respectively].87 the benefits of this investigation are somewhat offset by a small risk of
capsule retention; even with use of patency capsule in patients deemed to
Statement 2.3.4. ECCO-ESGAR Diagnostics GL [2018] be at risk, the rates of capsule retention range from 1.5% to 2.1%.60 The
outcome of the retained capsule varies between studies; approximately
Symptomatic small bowel disease can be investigated 85% are asymptomatic and 15% result in partial or complete small
with MR enterography, IUS, and/or small bowel capsule bowel obstruction. The latter generally requires surgical management.
endoscopy [SBCE] [EL2] The former can sometimes be retrieved with small bowel enteroscopy
or managed conservatively.269 Routine use of a patency capsule has not

MR enterography, IUS, and SBCE are all sensitive and specific been shown to reduce the risk of retention in the absence of risk factors.
investigations of symptomatic small bowel disease. The decision on Patients who benefit from patency capsules include those with stricturing
which investigation is ‘first line’ is based upon local availability and or penetrating disease phenotypes.270 Cost analyses suggest that SBCE is
expertise. cost-effective271 and frequently leads to changes in therapy.272
MR enterography allows assessment of the small bowel with- Barium studies, in particular barium follow-through, are still
out radiation exposure.241 The presence of wall oedema, contraction used in some centres for suspected active small bowel CD.273,274
frequency,242 ulcers, and extramural signs such as fat stranding and However, sensitivity and specificity are less than those of MR enter-
lymphadenopathy, make MR enterography somewhat informative ography, IUS, or SBCE. Furthermore, radiation exposure also makes
of whether the abnormalities detected are more inflammatory or barium studies less appealing.275 This is particularly true in paedi-
fibrotic.242–245 However, it should be noted that no imaging modal- atric assessment.276 Accordingly, ECCO-ESGAR discourages barium
ity can fully assess whether a stricture is inflammatory or fibrotic in studies unless local facilities preclude alternatives.
nature. MR enterography is also safe and well tolerated in paediatric CT should largely be reserved for the emergency setting due
populations.246–248 A recent meta-analysis of 27 studies [19 included to radiation exposure. However, low-radiation CT enterography
in pooled analysis] showed MRI to have a sensitivity of 0.88 [95% CI yields results comparable to full-dose CT when evaluating CD.
0.86–0.91] and a specificity of 0.88 [95% CI 0.84–0.91].249 The stud- Accordingly, low-radiation CT enterography may be an alternative
ies included both MR with oral contrast solution [MR enterography] when local resources preclude alternatives or in older patients where
or contrast administered by nasojejunal tube insertion [MR enterocl- radiation exposure is of less concern. When considering the efficacy
ysis]. MRI is perhaps superior to IUS in assessing disease extent86 and of CT, the diagnostic yield of CT enterography is similar to that
leads to changes in clinical management following investigation250; of MR enterography.80,277,278 Indeed, several studies comment that
MRI increases scores of disease location [L] and disease behaviour CT yields images of higher spatial resolution279–281 and that there is
[B] of the Montreal classification in over 20% of patients.251 greater agreement between radiologists when interpreting CT.277 CT
MR enteroclysis is not significantly more sensitive or specific is often the only cross-sectional abdominal imaging modality avail-
than MR enterography.252 MR enteroclysis is also less well tolerated able outside standard working hours, and as such is widely used in
than MR enterography253 and requires minimal radiation exposure the emergency setting. CT has a high detection rate of complications,
for fluoroscopic nasojejunal placement.254 Accordingly, MR entero- including perforation, strictures, and abscesses.281
clysis is not routinely recommended. Studies of positron emission topography [PET] are limited. At
IUS may be available immediately within the clinical setting; if this present, PET does not appear to detect significantly more lesions
investigation is sufficient to confirm active disease it may preclude the than CT enterography282 or MR enterography alone.283 Leukocyte
need for further investigation. The sensitivity and specificity of IUS can scintigraphy has been shown to detect inflammatory lesions not oth-
be enhanced with contrast studies. Small intestine contrast ultrasound erwise shown prior to laparotomy. However, there is insufficient evi-
[SICUS] entails administering oral contrast and enables a greater rate dence to routinely include this test in clinical practice.284
of detection of small bowel lesions than by standard IUS,255,256 and in Non-invasive evaluation of symptomatic IBD includes measurement
particular enables greater detection of strictures and associated dilata- of blood and stool inflammatory markers and measurement of param-
tion. SICUS shows sensitivity and specificity comparable to MR enter- eters indicative of malabsorption. The use of non-invasive markers to
ography and CT enterography.257–259 In one study, SICUS was shown assess disease activity is largely covered elsewhere. In brief, FC is a more
to be more sensitive in the proximal small bowel [92% versus 75%], sensitive marker of disease activity than haemoglobin, CRP, or albu-
similar within the proximal and mid ileum, and less specific within min.285,286 In symptomatic disease, FC can be used to evaluate activity
the terminal ileum.260 One study showed SICUS to be more sensitive from the colon to the small bowel.62,204,226–229 Studies have shown good
and specific than CT enteroclysis.261 The rates of detection of small correlation [r > 0.8] with endoscopic disease activity in both CD and
bowel complications [such as strictures] are comparable to MR enter- UC.230,231 One of the main drawbacks of indirect markers is their limited
ography.258 CEUS may facilitate differentiation between inflammatory information on disease phenotype and potential complications.
and fibrotic strictures.262 In the recently published METRIC trial, both
MRE and IUS had a high sensitivity for detecting small bowel disease
presence. However, the sensitivity of MRE for small bowel disease
extent (80% [95% CI 72–86]) and presence [97%91–99] were signifi- Balloon-assisted enteroscopy can be used for diagnostic
cantly greater than that of IUS [70%62–78 for disease extent, 92%84–96 evaluation or endoscopic intervention [or both] through-
for disease presence]: a 10% [95% CI 1–18; p = 0·027] difference for out the small bowel [EL3]
extent, and 5% [1–9; p = 0·025] difference for presence.87
Balloon-assisted enteroscopy allows direct mucosal visualisation of follow-up after supplementation does not show a clear beneficial
the entire small bowel. Unlike other imaging modalities, balloon- impact in disease course.300 Nevertheless, ECCO suggests measuring
assisted enteroscopy also enables the taking of biopsies, therapeutic vitamin D in symptomatic patients, then re-evaluating after treat-
intervention throughout the small bowel,287–289 and interventions ment to verify that levels are replete.
to manage bleeding. One study showed a change in management Other micronutrient deficiencies to be considered in IBD patients
in 75% of patients who underwent this investigation.290 However, include vitamin K, selenium, vitamin A, vitamin C, zinc, vitamin B6,
this examination is time-consuming and requires patient sedation. and vitamin B1.301,302 All patients with symptomatic IBD do not rou-
The risk of perforation is 0.12% without therapeutic intervention tinely require evaluation of all of the above. However, testing should
but 1.74% with therapeutic intervention, the majority of which be considered in patients with small bowel CD, in those who have
occurred after stricture dilatation.291 Bleeding occurs in approxi- undergone resection, and in those receiving nutritional supplementa-
mately 2.5%,292 although one series demonstrated four out of six tion [in particular parenteral nutrition] or if the specific clinical sce-
significant bleeds occurring following polypectomy.293 It is worth nario lends suspicion to a deficiency [such as poor wound healing].
noting that real-world data on both the benefits and complications
are skewed by selection bias, as at present this test is usually reserved 2.4. Imaging after surgery [including
for patients where other imaging modalities have been inconclusive ileo-anal pouch]

or in scenarios when therapeutic intervention is a key aim.
Statement 2.4.1 ECCO-ESGAR Diagnostics GL [2018]
Ileocolonoscopy is the reference standard in the diagno-
Malabsorption parameters should be assessed at regular sis of postoperative recurrence after ileocolonic resec-
intervals in all patients with IBD [EL5] tion. Endoscopy is recommended within the first 6 to
12 months after surgery [EL3]
Nutritional deficiencies are frequently associated with sympto-
matic IBD. The reason for this is 2-fold. First, the discomfort and
anorexia associated with disease flares preclude adequate intake. Statement 2.4.2. ECCO-ESGAR Diagnostics GL [2018]
Second, inflammatory or fibrotic change to the bowel directly hin-
FC, IUS, MR enterography, and SBCE can be considered
ders absorption.
as non-invasive alternatives to detect postoperative recur-
In all patients with IBD, weight should be recorded at each clinic
rence, in particular after small bowel resection [EL2]
review with the aim of early dietetic support when unintentional
weight loss is noted. Anaemia is common and should be screened
for in all IBD patients; this topic is covered in full in Chapter 1 of In the natural history of CD, intestinal resection is unavoidable in
this guideline. Patients with symptoms suggestive of active disease a significant proportion of patients. A majority of patients develop
should be screened for anaemia every 3 months. Initial screening disease recurrence at or above the anastomosis, and endoscopic
should include complete blood count, ferritin, and CRP. There is no recurrence precedes the development of clinical symptoms. Data
evidence on optimal screening intervals for any of the parameters from endoscopic follow-up of patients after resection of ileocaecal
used for malabsorption. Common practice in patients with small disease have shown that in the absence of treatment, the postop-
bowel disease or previous resection is to measure vitamin B12 and erative endoscopic recurrence rate is approximately 65% to 90%
folic acid every 3 to 6 months. Judicious care must be taken when within 12 months and 80% to 100% within 3 years of the opera-
interpreting ferritin results in symptomatic patients; the ECCO anae- tion.303,304 The rates of recurrence are also significant in patients
mia guideline recommends ferritin values of up to 100 µg/L may still after total proctocolectomy and permanent ileostomy. In a recent
be consistent with iron deficiency in active disease, especially with meta-analysis of 18 cohort studies, the risk of clinical recurrence
a transferrin saturation of <20%. If low haemoglobin is confirmed, was 28.0%, with a 5-year and 10-year median cumulative rate of
a more extensive workup should be undertaken as per the anaemia 23.5%.305 Identification and treatment of early mucosal recurrence
guideline. may therefore prevent clinical recurrence.
Low albumin is common in active IBD, as it is an acute phase Ileocolonoscopy is the reference standard in the diagnosis
protein. Active IBD itself may lead to malabsorption, and low albu- of postoperative recurrence by defining the presence and sever-
min in IBD may correlate with nutritional status. However, the use ity of morphological recurrence. Data from endoscopic follow-up
of albumin as a direct marker of malabsorption is tenuous. In a of patients after resection of ileocaecal disease have shown that in the
meta-analysis of 63 studies, albumin did not correlate with nutri- absence of treatment, the postoperative recurrence rate is approxi-
tional status in calorie-restricted but otherwise healthy individu- mately 65% to 90% within 12 months.303,304 Ileocolonoscopy is
als.294 Longitudinal follow-up of serum albumin in patients with therefore recommended within the first year after surgery where
anorexia nervosa and in healthy controls also failed to yield signifi- treatment decisions may be affected. The Rutgeert´s score may be
cant differences.295 As such, albumin is not an appropriate test for used for detailed description [see Chapter 4 of this guideline].
malabsorption and ECCO does not recommend albumin measure- Non-invasive modalities may also be accurate and efficient in
ments for this reason. detection of postoperative recurrence.
Low vitamin D has been observed in between 16% to 95% of FC can accurately identify postoperative recurrence.306,307 In a
IBD patients, depending upon the study.296,297 Deficiency is associ- meta-analysis of 10 studies that evaluated the accuracy of FC for
ated with active disease, female gender, and non-Caucasian ethnicity, detection of endoscopic recurrence, the pooled sensitivity and speci-
with one recent study suggesting higher prevalence in CD.298 A retro- ficity values for assessing suspected endoscopic recurrence were 0.82
spective analysis has also linked low vitamin D with more frequent and 0.61, respectively.308 In a more recent prospective study, FC lev-
flares and lower quality-of-life scores.299 Unfortunately, prospective els >100 μg/g indicated endoscopic recurrence [defined as Rutgeerts
score ≥i2] with 89% sensitivity and 58% specificity and an NPV
of 91%; the authors suggested that colonoscopy could have been Statement 2.4.3. ECCO-ESGAR Diagnostics GL [2018]
avoided in 47% of patients. In an additional prospective study from
Endoscopy with biopsies should be performed in the
the GETAID group, FC levels >100 μg/g were associated with a posi-
assessment of pouch-related symptoms [EL2]
tive predictive value and NPV of 93% and 77%, respectively, for
prediction of endoscopic recurrence.309
Several imaging modalities are available to reliably diagnose The ileo-anal pouch is a well-established option for patients who
post-surgical recurrence, including IUS, small bowel follow-through, require surgery for chronic UC. Despite excellent functional results,
CT enteroclysis or CT enterography including virtual colonoscopy, the short-term and long-term outcome of ileal pouch with anal anas-
MR enteroclysis or MR enterography, SBCE, and white blood cell tomosis [IPAA] are determined by the occurrence of complications.
scintigraphy. These may be directly related to the surgery or may occur over the
Several authors have previously emphasised the value of IUS in long term. Immediate postoperative complications include leak-
postoperative follow-up, and confirmed the observation of bowel age, abscess formation, pelvic sepsis, and fistula formation. More
wall thickening as an indicator for recurrence.310–312 SICUS has chronic disorders following IPAA are pouchitis, cuffitis, irritable
shown an excellent correlation with the endoscopic Rutgeerts score pouch syndrome, pouch stricture, pouch sinus, afferent loop syn-

[r = 0.67; p = 0.0001], reaching 87.5% accuracy for detecting CD drome, or small bowel obstruction.324 Following surgery, up to 40%
recurrence.313 SICUS is also considered to be superior to standard of patients have a single episode of pouchitis [a non-specific inflam-
IUS in detecting postoperative CD recurrence after ileocaecal resec- matory condition at the ileal pouch reservoir]325 within 12 months,
tion.314 Bowel wall thickening was defined by thickness of >3.5 mm. whereas 19% and 5% experience intermittent episodes and chronic
SICUS prediction of recurrence was found to be correct in 100% of pouchitis, respectively.326–328 The incidence of pouch failure is up to
cases and confirmed by endoscopy.314 In a recent retrospective series 7% at 3 years and 9% at 5 years.329,330
from Italy, the absolute incidence of new surgical intervention is Endoscopy plays a significant role in diagnosing and guiding
13% in patients with bowel thickness of 3 mm and 40% in patients therapy in patients with pouch complications.324,331–334 Importantly,
with bowel thickness >6 mm.315 the severity of symptoms does not always correlate with endoscopic
CT enterography or CT enteroclysis are alternatives to endos- or histological findings.335,336 Therefore, a cumulative clinical, endo-
copy for assessing postoperative recurrence of CD activity.316 In a scopic, and histological assessment is needed. Several diagnostic cri-
prospective series that included 32 postoperative patients from teria are available and the most common in clinical use is the Pouch
China, a significant correlation between endoscopic and CT recur- Disease Activity Index.337 Furthermore, it is valuable to classify the
rence [r = 0.782; p < 0.0001] was demonstrated.317 Due to false- phenotype of pouchitis before initiating therapy, to provide guidance
negative findings, CT colonography has been tested for assessing the regarding treatment modalities and duration of treatment.338 In case
postoperative recurrence of CD with inconclusive results. However, of antibiotic-refractory pouchitis, endoscopic evaluation can facili-
CT colonography represents an alternative to conventional colonos- tate exclusion of contributory factors such as ischaemic pouchitis
copy in non-compliant post-surgical patients with a rigid stenosis and infections.339 Pouch endoscopy is essential in the diagnosis of
that does not allow passage of the endoscope.318 However, due to CD of the pouch and prepouch ileitis.324,334,335
concerns regarding cumulative radiation exposure, imaging modali- FC levels are significantly elevated in cases of pouchitis. In a
ties not associated with radiation [such as MR enterography or IUS] study that included 56 pouch patients, FC concentrations corre-
are preferable to CT enterography. lated closely with the objective pouchitis score, the Pouch Disease
MR enterography may be an alternative to endoscopy as a diag- Activity Index, and endoscopic and histological inflammatory scores
nostic tool in postoperative recurrence evaluation in CD patients. [Spearman rank test, p-values < 0.0001]; FC levels ≥92.5 µg/g had a
Similar to the endoscopic Rutgeerts score for assessing postoperative sensitivity of 90% and a specificity of 76.5% for detection of pouch
recurrence, one study showed an objective evaluation using an MRI- inflammation.340 Other potential biomarkers of pouch inflammation,
based index of activity and severity for postoperative recurrence. This such as faecal matrix metalloprotease-9341 and serum alpha-1 anti-
score achieved a high correlation with the endoscopic index, which trypsin,342 are also being evaluated but are currently not in routine
allowed differentiation between mild and severe lesions319 and predic- clinical practice.
tion of the risk of clinical postoperative recurrence in CD patients.320
Although the Rutgeerts score has been used to evaluate the
Chapter 3: Detection of complications
efficacy of several drugs, there is a lack of information on whether
mural healing changes seen by cross-sectional imaging techniques 3.1. Detection of strictures
are in parallel to endoscopic MH.
Capsule endoscopy can also be used to access postoperative Statement 3.1.1. ECCO-ESGAR Diagnostics GL [2018]
recurrence.321,322 A fair correlation between the modalities [r2 = 0.54–
Cross-sectional imaging should be used to detect small
0.64; p < 0.05] was observed in a small pilot study that compared the
bowel strictures [EL2]. Due to radiation exposure with
Rutgeerts score calculated by capsule endoscopy and ileocolonos-
CT, the preferred methods are MRI and/or intestinal ultra-
copy.322 An important advantage of capsule endoscopy is the ability
sound [IUS]. No imaging technique is currently able to
to detect proximal small bowel recurrence. However, data on the use
determine the degree of fibrosis [EL3]
of capsule endoscopy for this indication are currently very limited,
and patency capsule evaluation should be recommended before cap-
sule endoscopy to minimize the risk of retention. Despite wide heterogeneity in the definitions for strictures, the accu-
In a recent meta-analysis, MR enterography, IUS, and SBCE had racy of intestinal ultrasound [IUS], CT enterography, and MR enter-
excellent accuracy [area under the curve >0.9 for all modalities] for ography is high for diagnosis of stenosis affecting the small bowel.81
detection of endoscopic recurrence as defined by a Rutgeerts score ≥2.323 IUS is an accurate technique for detection of small bowel stenosis.
Based on pooled data using surgery as a reference standard, the sen- Consistent with the observation that patients with ulcerative coli-
sitivity and specificity of IUS are 79% and 92%, respectively.81 Use tis [UC] and patients with colonic CD are at an increased risk of
of oral contrast agents, such as small intestine contrast ultrasound developing colorectal cancer [CRC],363–365 detection of a new colonic
[SICUS], can improve the accuracy of IUS in detecting the presence stricture should lead to a careful diagnostic workup to exclude
and number of small bowel stenosis; sensitivity increased from 74% malignancy. A recently published population-based study suggested
to 89% in one study.131 The sensitivity of CT enterography for ste- that colonic strictures at diagnosis or during follow-up are associ-
nosis detection was 92% and specificity was 100% when CT was ated with a 3.6% and 4.9% probability of CRC at 5 and 10 years,
compared with ileocolonoscopy.343–345 Studies using endoscopy and respectively.366 According to the ECCO evidence-based consensus for
surgery as a reference standard reported a sensitivity of 85% and endoscopy in IBD, patients with strictures detected within 5 years
90%, respectively, with a specificity of 100%.82,346 MRI studies with should be considered ‘high risk’ and receive surveillance colonos-
an adequate reference standard [endoscopy, surgery, or both] for copy yearly. Malignancy is more frequent in the CD-affected colon
diagnosis of stenosis showed a sensitivity of 89% and a specificity and the incidence is comparable to UC.367,368 In a GETAID study,
of 94%.81 The accuracy had a tendency to improve using enterocly- dysplasia or cancer was detected in 3.5% of patients with IBD
sis [i.e. enteric contrast introduced via nasojejunal intubation rather who underwent surgery for colonic strictures.369 In addition, small
than oral] as compared with enterography [sensitivity of 100% ver- bowel adenocarcinoma is rare but can be fatal if overlooked.370

sus 86% and specificity of 100% versus 93%, respectively].253 Direct The endoscopist should therefore have a low threshold for taking
comparison of CT and MRI for diagnosis of stenosis indicated a a biopsy before endoscopic balloon dilatation.370 In addition, the
similar sensitivity [85% versus 92%] and specificity [100% versus use of paediatric endoscopes with a smaller diameter may permit
90%].82 The use of luminal contrast and anti-peristaltic agents is stricture traversal. Cross-sectional imaging should be considered as
recommended for CT enterography and MR enterography.347 a complementary diagnostic modality. Currently, there is no method
Strictures in Crohn’s disease [CD] are transmural and con- [including histology] that can definitively rule out malignancy in a
tain variable proportions of inflammatory and fibrotic tissue.348 patient with IBD and colonic strictures.
Quantification of active inflammation versus fibrosis is challeng-
ing. With regards to current techniques used in clinical practice, no 3.2. Detection of fistulae and abscesses
technique is sufficiently accurate to assess the degree of fibrosis in
a stricture with adequate precision to guide clinical decisions. The 3.2.1. Detection of intra-abdominal fistulae and abscesses
stratified echo pattern of the different layers of the intestinal wall
components of a stricture has been associated with collagen deposi- Statement 3.2.1. ECCO-ESGAR Diagnostics GL [2018]
tion, but this approach lacks consistency.349 On CT enterography,
Cross-sectional imaging [IUS, MRI, and CT] can detect
the presence of fibrosis was linked to stenotic lesions, but could not
internal penetrating disease and intra-abdominal
distinguish inflammation from fibrosis.350 Conventional-sequence
abscesses with varying accuracy [EL1]. MRI is preferable
MR enterography revealed conflicting results for fibrosis characteri-
to ultrasound for deep-seated fistulae or abscesses or pel-
sation.351,352 Rimola et al. developed a technique using gadolinium
vic fistulae [EL4]
enhancement between 70 s and 7 min on MR enterography. This
approach was able to distinguish mild or moderate fibrosis from
severe fibrosis irrespective of the degree of inflammation.353 This In a systematic review for the diagnosis of intra-abdominal fistulising
approach awaits external validation. lesions, cross-sectional imaging showed the following accuracy: for
Although several novel imaging techniques have been proposed, CT with surgery and endoscopy as reference standard, the sensitivity
data are limited, acquisition methods are unstandardised, and there was 70% and specificity 97%; MRI with surgery or endoscopy as the
is limited evidence to support external validity. These techniques reference standard showed a sensitivity of 76% and specificity of 96%
include MR with dynamic contrast-enhanced technique,354 magneti- for fistula diagnosis; IUS with surgery, barium studies, and colonos-
sation-transfer MR,355,356 ultrasound elastography,357,358 or contrast- copy as the reference standard showed a sensitivity of 74% and speci-
enhanced ultrasound [CEUS].359,360 While stenosis can be detected ficity of 95%.81 Oral contrast agents do not improve accuracy of IUS
by endoscopy, most investigators use the ability to pass the endo- for detection of internal fistulae.131 If available, CT or MRI is prefera-
scope as a measure of stenosis. The proportion of fibrosis cannot be ble for detection of intra-abdominal or pelvic fistulae over ultrasound;
evaluated precisely by biomarkers, endoscopy, or histology. There is MRI has the advantage of no radiation exposure.80,81 Cross-sectional
no consistent approach regarding strategy for monitoring strictures imaging has a pivotal role in the assessment of penetrating complica-
over time or with which method. tions of CD. In one study, there was no clinical fistula or abscess suspi-
Although not the preferred technique, ileocolonoscopy can be used cion from pre-CT examination in half of patients with penetrating CD
for stricture diagnosis. The commonly used definition is a narrowing complications. Cross-sectional imaging changed management in more
that cannot be passed with an endoscope.361 An ileocolonoscopy is not than three-quarters of these patients.371 White blood cell scintigraphy
necessary in all cases after a stricture has been detected on cross-sec- is not indicated for diagnosis and characterisation of fistulae.
tional imaging, but should be considered if endoscopic therapy through A systematic review revealed the following point estimates for
endoscopic balloon dilatation is a valid therapeutic approach362 and in diagnosis of abscesses: using surgery as a reference standard, IUS had
case of colonic strictures when malignancy cannot be excluded. a sensitivity of 84% and a specificity of 93%, which was dependent
on disease location in CD.81 Detection of intra-abdominal abscesses
via CT, with surgery as the reference standard, revealed a sensitivity
of 86% and a specificity of 88%.350 One prospective study showed a
sensitivity of 85% and specificity of 95% of CT for intra-abdominal
Any colonic stricture should be carefully surveyed due to abscesses.372 CT and ultrasound showed an overall high and compa-
risk of carcinoma [EL4]; surgery should be considered rable accuracy in the detection of intra-abdominal abscesses, although
CT showed a slightly greater positive predictive value than ultrasound.
CEUS has been shown to differentiate between an intra-abdominal the effect of preoperative MRI on clinical outcome after surgical
phlegmon and abscess with high accuracy.373 The accuracy of MRI treatment for perianal fistulising disease.376,377 Both studies showed
for abscess detection, using surgery as the reference standard, showed that MRI revealed additional and clinically relevant information to
sensitivities ranging from 86% to 100% and specificities from 93% the surgeon performing EUA. A prospective comparison of modali-
to 100%.352,374,375 A systematic review of these three studies showed ties using a robust outcome-based reference standard found MRI
a sensitivity of 86% and a specificity of 93% for MRI detection of superior to TRUS for fistula classification and detecting abscesses.170
abscesses.81 Endoscopy is not used for evaluation of internal penetrat- In general, MRI is preferred in CD, especially in recurrent or sus-
ing disease, due to an inability to image extramural structures. pected complex disease.
Endoscopy can facilitate detection of perianal disease and has a
role in assessing the degree of inflammation in the rectum, which may
3.2.2 Detection of fistulae and abscesses affect management.105 Endoscopy has not been shown to be useful in
monitoring perianal disease or assessing response to fistula therapy.
Transperineal ultrasound [TPUS] has been evaluated in small
MRI is the most accurate imaging modality for diagnosis studies for the documentation of perianal disease and may have
and classification of perianal CD and is the recommended clinical utility.387,388

first-line test [EL1]. Transrectal ultrasonography [TRUS] is
superior to clinical examination and is an alternative to MRI 3.3 Detection of pouch complications
[EL2]. Combining any modality of MRI, examination under
anaesthesia [EUA], or TRUS improves accuracy [EL2] Statement 3.3.1. ECCO-ESGAR Diagnostics GL [2018]
Cross-sectional imaging and endoscopy are complemen-

tary methods for assessing suspected structural compli-
cations after ileal pouch anal anastomosis [IPAA] [EL4].
Examination under anaesthesia [EUA] with drainage is Pouchography can be used additionally to assess func-
recommended if a perianal abscess is suspected, and tional disorders and other complications [EL3]
should not be postponed if pelvic imaging is not immedi-
ately available [EL2] Inflammatory and non-inflammatory complications of the ileal
pouch anal anastomosis [IPAA] are common and include strictures,
abscesses, fistulae, and sinus tracts culminating in pouch failure in
Statement 3.2.4. ECCO-ESGAR Diagnostics GL [2018] up to 9% of cases at 5 years.329,330,332,389 These complications can be
immediately postoperative or long-term. In the cases of IPAA ste-
Endoscopic evaluation of the rectum is essential to deter- nosis, fistulae, abscesses, and sinuses, EUA by an experienced IBD
mine the most appropriate management strategy for peri- surgeon is important for diagnosis and timely treatment of most
anal CD [EL2] pathologies. The choice of diagnostic modality depends on the clini-
cally suspected disorder, local expertise, and availability. Endoscopy
Three diagnostic tests are commonly used alone or in combination for is essential to obtain information on mucosal status and for diag-
the diagnosis and classification of perianal disease, namely examina- nosis of intraluminal or anastomotic complications, such as stric-
tion under anaesthesia [EUA], MRI, or transrectal ultrasonography tures. Endoscopic balloon dilatation can be used to treat pouch
[TRUS]. Both TRUS [with and without hydrogen peroxide] and MRI stricture.390,391 For suspected extraluminal complications, such as
can identify and classify fistulous tracts with a diagnostic accuracy for abscesses, fistulae, or sinus tracts,392,393 pelvic CT, MRI, and TRUS or
MRI ranging from 80% to 100% in most reported studies. The diag- TPUS are sensitive methods that allow the identification and char-
nostic accuracy of TRUS is more variable and ranges from 50% to acterisation of septic problems170; use of these modalities depends
100%.165,170,376–385 MRI is the recommended first-line test, as TRUS is on local availability and experience level. Unfortunately, the propor-
hindered by patient discomfort, cannot be performed in the presence tion of fibrosis versus inflammation cannot be assessed precisely by
of stenosis, and has a smaller field of view. EUA by an experienced any currently available diagnostic tool.394–396 Contrast pouchography
surgeon has long been considered the reference standard for assess- can assist in assessment of pouch strictures, pouch fistulae, and leak-
ment of perianal CD. However, a prospective blinded study comparing age100 but is only used in a limited number of centres. A correlation
EUA, MRI, and TRUS found diagnostic accuracies of 91%, 87%, and of pelvic CT, MRI, pouch endoscopy, and retrograde pouchography
91%, respectively, with 100% accuracy when any two of the tests were findings with clinical outcome revealed a reasonable accuracy for
combined.169 A larger prospective clinical trial compared preoperative diagnosis of strictures, fistulae, sinuses, and pouch leaks, with all
digital rectal examination [33% sensitivity], TRUS [75% sensitivity], methods.397 CT had the lowest accuracy for small bowel strictures
and body-coil MRI [85% sensitivity]. MRI may change management [74%]; MRI had the lowest accuracy for pouch sinuses [68%].
in patients with perianal CD by detecting an abscess not suspected clin- A combination of two imaging tests increased diagnostic accuracy
ically,376,386 and should therefore precede EUA unless there is a need for to 100%. In the acute postoperative setting, complications of IPAA
immediate drainage of sepsis. Although the use of EUA may be limited include anastomotic leaks and abscesses. Leaks from the tip of
by luminal stenosis, dilatations during the procedure can be performed. the J-pouch and the pouch-anal anastomosis often result in pelvic
Undiagnosed fistula extensions and abscesses are major causes abscesses. Detection of anastomotic dehiscence after IPAA is pos-
of recurrent disease after attempted surgical cure.377 Furthermore, sible using transanal ultrasound and TPUS, although pelvic CT or
full knowledge of the presence and extent of these secondary tracts MRI scanning is usually required to outline the full extent of the
is required for appropriate medical therapy, particularly with anti- complication and guide drainage.396,398 Complications of the pouch
TNF agents.166 Accurate classification of perianal fistulae is thus should be discussed in a multidisciplinary team setting to individu-
essential before starting therapy. Two prospective studies evaluated alise management.
3.4 Detection of emergency complications 1–38].404 In this study, CT was the preferred imaging modality.404 In
contrast, other studies showed that most postoperative CT features
Statement 3.4.1. ECCO-ESGAR Diagnostics GL [2018] overlap between patients with or without clinically important anas-
tomotic leaks, and that CT studies performed on patients shortly
In acute severe colitis, a plain abdominal radiograph is after abdominal surgery are not definitive. A negative CT does not
an acceptable first study to detect toxic megacolon. In exclude postoperative lower gastrointestinal tract leaks.405,406 A com-
selected cases, CT could be indicated as an initial method bination of CT, laboratory examinations, and clinical signs and
to screen for complications [EL3] symptoms will optimise diagnosis of such complications.
There is no evidence that the addition of intraluminal contrast
Diagnosis of toxic megacolon is usually made by clinical signs of sys- is more sensitive for detection of anastomotic dehiscence in IBD, as
temic toxicity supported by imaging confirmation. Detection of trans- peri-anastomotic located fluid-containing gas is the most prevalent
verse colonic dilatation >5.5 cm by means of plain abdominal X-ray sign of anastomotic insufficiency.406 Selected use of intraluminal con-
is still the most established radiological definition of toxic megaco- trast can be individualised according to physician preference.
lon.399 Some case series have shown that in patients with toxic mega-
colon, CT scan and IUS can be promising alternatives that provide 3.6. Surveillance for colorectal cancer in IBD

additional information.400,401 A CT scan is an important tool for diag- patients with colonic inflammation
nosis of associated perforation or ascending pylephlebitis. A study
observed that among 18 patients with toxic megacolon [four with Statement 3.6.1. ECCO-ESGAR Diagnostics GL [2018]
underlying UC], CT scans revealed abdominal complications in four
patients, missed clinically and on plain abdominal films.400 Larger [ECCO UC Guideline: statement 8D in Magro F et al.]
clinical studies are warranted to assess the diagnostic benefit of cross- Screening colonoscopy should be offered 8 years after
sectional radiological studies in the assessment of toxic megacolon. onset of symptoms to all patients to reassess disease
extent and exclude dysplasia [EL5]
When a perforation is suspected, CT should be performed

in all patients with acute abdominal pain and established Statement 3.6.2. ECCO-ESGAR Diagnostics GL [2018]
diagnosis of IBD [EL2]
[ECCO UC Guideline: statement 8E in Magro F et al.]
When disease activity is limited to the rectum without
Spontaneous free perforation is a rare but serious event in CD, but
evidence of previous or current endoscopic or microscopic
can be more common in acute severe colitis. Spontaneous free perfo-
inflammation [or both] proximal to the rectum, inclusion
ration may result from severe inflammation or superimposed malig-
in a regular surveillance colonoscopy programme is not
nancy. It is estimated that approximately 1% to 2% of patients with
necessary [EL2]
CD will present with a free perforation initially or at some time over
their disease course.402,403
In IBD patients, intestinal perforation frequently presents as a
peri-intestinal abscess that may be detected by cross-sectional imaging
methods such as IUS, MRI, or CT. A systematic review showed that in [ECCO UC Guideline: statement 8F in Magro F et al.]
this context the three techniques have a high accuracy for identifica- In patients with concurrent primary sclerosing cholan-
tion of fistulae, abscesses, and stenoses [sensitivities and specificities of gitis [PSC], annual surveillance colonoscopy should be
0.80], although IUS yields more false-positive results for abscesses.81 performed following the diagnosis of PSC, irrespective of
disease activity, extent, and duration [EL3]
3.5. Detection of postoperative complications
Statement 3.5.1. ECCO-ESGAR Diagnostics GL [2018] Statement 3.6.4. ECCO-ESGAR Diagnostics GL [2018]
Acute postoperative complications in IBD patients [mainly [ECCO UC Guideline: statement 8G in Magro F et al.]
anastomotic leaks and abscesses] should be initially Ongoing surveillance should be performed in all patients
investigated by CT [EL3]. Ultrasound may be an alter- apart from those with proctitis [EL3]. Patients with high-
native first-line investigation, but should be followed by risk features [e.g. stricture or dysplasia detected within
immediate CT, if negative or equivocal. [EL4] the past 5 years, PSC, extensive colitis with severe active
inflammation] should have their next surveillance colon-
oscopy scheduled for 1 year [EL4]. Patients with inter-
Anastomotic leaks after intestinal surgery may be promptly diag-
mediate risk factors should have their next surveillance
nosed clinically, due to specific clinical presentation in the postopera-
scheduled for 2 to 3 years. Intermediate risk factors
tive period. However, when anastomotic leaks are suspected in cases
include extensive colitis with mild or moderate active
of atypical clinical manifestations, correct and rapid radiological
inflammation, post-inflammatory polyps, or a family
diagnosis is necessary for successful management. Few studies have
history of colorectal cancer [CRC] in a first-degree rela-
been designed to assess detection of these complications in CD,81
tive diagnosed at age 50 years and above [EL5]. Patients
and most are derived from the surgical literature.404–406 A prospective
with neither intermediate nor high-risk features should
database populated over a 10-year period showed that anastomotic
have their next surveillance colonoscopy scheduled for
leaks are frequently diagnosed late in the postoperative period and
5 years [EL5]
often after initial hospital discharge [median time 12.7 days, range
On the basis of systematic endoscopic assessment, together with

Statement 3.6.5. ECCO-ESGAR Diagnostics GL [2018] medical and family history of the patient, surveillance colonoscopy
programmes have been developed to reduce CRC-associated mor-
Colonoscopic surveillance is best performed when ulcera-
bidity and mortality.363 At the onset of these programmes, an ini-
tive colitis [UC] is in remission, because it is otherwise dif-
tial screening colonoscopy is performed to reassess disease extent
ficult to discriminate between dysplasia and inflammation
and confirm the absence of dysplastic lesions.363 The timing of sur-
on mucosal biopsies [EL5]
veillance colonoscopies should be based on the level of risk of the
patient, as extensively discussed in the recent ECCO consensus363
Statement 3.6.6. ECCO-ESGAR Diagnostics GL [2018] [Table 2]. The suggested timeline for surveillance in Crohn’s colitis,
though scientific data are more limited, should be applied as for UC.
Surveillance colonoscopy should take into account local Good bowel preparation is essential for an efficient surveillance
expertise. Chromoendoscopy with targeted biopsies has colonoscopy, since the quality of the preparation in UC patients sig-
been shown to increase dysplasia detection rate [EL2]. nificantly affects the lesion detection rate.411
White-light endoscopy is less accurate. If white-light A recent colitis surveillance study demonstrated that high-definition
endoscopy is used, random biopsies [quadrantic biopsies colonoscopy improves dysplasia detection in comparison with standard

every 10 cm] and targeted biopsies of any visible lesion definition.363,412 Targeted biopsies have been shown to be not inferior
should be performed [EL3]. High-definition endoscopy to random biopsies for neoplasia detection rate per colonoscopy in a
should be used if available [EL2] randomized controlled trial.363,413 Spraying dyes, such as methylene blue
or indigo carmine,414–416 highlight subtle changes in the colonic mucosa
architecture and can improve the detection rate of dysplasia.417 There
Statement 3.6.7. ECCO-ESGAR Diagnostics GL [2018] is abundant evidence from clinical trials and real-life studies that chro-
Where dysplasia of any grade is found without an asso- moendoscopy is superior to white-light endoscopy for dysplasia detec-
ciated endoscopically visible lesion, urgent repeat chro- tion,418–426 independent of operator familiarity or from the availability of
moendoscopy should be performed by an experienced high-resolution endoscopy. Narrow-band imaging and endomicroscopy
endoscopist to determine whether a well-circumscribed cannot currently be recommended for dysplasia screening in IBD.363
lesion exists and to assess for synchronous dyspla-
sia [EL5]. A patient with confirmed low-grade dysplasia 3.7. Diagnostic and monitoring techniques during
detected in mucosa without an associated endoscopically pregnancy
visible lesion should undergo repeat chromoendoscopic
colonoscopy with additional random biopsies within Statement 3.7.1. ECCO-ESGAR Diagnostics GL [2018]
3 months [EL5]
IUS and abdominal MRI without intravenous gadolinium
are the safest techniques to examine pregnant women in
Statement 3.6.8. ECCO-ESGAR Diagnostics GL [2018] whom IBD is known or suspected, regardless of the tri-
mester [EL5]
[ECCO UC Guideline: statement 8K in Magro F et al.]
Presence of low-grade or high-grade dysplasia should be
confirmed by an independent gastrointestinal specialist
pathologist [EL5]
Endoscopy is generally considered to be safe in pregnancy;
Longstanding UC and CD with colonic inflammation are associated however, procedures should only be performed when
with an increased risk of CRC, with a variable estimate between stud- there is a strong indication and clear clinical benefit [EL3]
ies.363–365 However, the risk of CRC seems to decline over time.407–409
Possible reasons are the emergence of effective surveillance strategies, Data are scarce concerning the medical imaging of pregnant women
better control of inflammation with drugs, and a modified approach to in whom IBD is known or suspected. Recent guidelines by the
maintenance therapy or colectomy, as stated in previous guidelines.410 American College of Obstetricians and Gynecologists state that
Table 2. Timeline of endoscopic surveillance according to risk factors after screening colonoscopy.
Risk level Risk factors Surveillance
Lower risk Extensive colitis with mild endoscopic or histological inflammation Every 5 years
Colitis affecting <50% of the colon
Intermediate risk Extensive colitis with mild endoscopic or histological inflammation [or both] Every 2–3 years
CRC in a first-degree relative older than 50 years
Higher risk Extensive colitis with moderate-to-severe endoscopic or histological inflammation [or both] Yearly
CRC in a first-degree relative younger than 50 years
History of PSC [included post-OLT]
Stricture in past 5 years
Dysplasia in the past 5 years in a patient who declines surgery
CRC, colorectal cancer; PSC, primary sclerosing cholangitis; OLT, orthoptic liver transplantation.
ultrasound, MRI, CT, and nuclear medicine imaging techniques are to appropriate drug selection, using drugs appropriate for pregnancy
theoretically safe if used prudently.427 The main concerns regarding and using the minimum dose possible to achieve the desired effect.
these techniques are increased fetal temperature caused by appli- Sedative drugs should be administered to provide patient comfort;
cation of high-frequency ultrasound, or a magnetic field and fetal over-sedation should be avoided.
radiation exposure, either via X-ray or radio-isotopes.
Ultrasound and MRI are the best choice for pregnant women, but 3.8. Diagnostics for biliary extra-intestinal
application of either can theoretically increase the temperature of manifestations of IBD
maternal and fetal tissues.428,429 The Food and Drug Administration
limits the spatial-peak temporal average intensity of ultrasound Statement 3.8.1. ECCO-ESGAR Diagnostics GL [2018]
transducers to 720 mW/cm2.427 Ultrasound examination should be
performed according to the ‘as low as reasonably achievable’ prin- Ultrasound is the first-line non-invasive imaging proced-
ciple,430 accounting for exposure time related to the thermal index ure in the workup of elevated liver enzymes, cholestasis,
generated during the procedure [keeping this value <1].431,432 No spe- or both [EL1]. Magnetic resonance cholangiopancreatog-
cific data apply to IBD populations. raphy should be considered if ultrasound and serology
Regarding MRI, a recent retrospective survey of 1 424 105 are inconclusive [EL1]

deliveries from the province of Ontario compared those with first-
trimester MRI [n = 1737] with no MRI [n = 1 418 451]. MRI did
not confer additional risk of congenital anomalies, neoplasms, or Statement 3.8.2. ECCO-ESGAR Diagnostics GL [2018]
vision or hearing loss. No additional risk of nephrogenic systemic
[ECCO-EIM Guidelines: statement 7B in M. Harbord et al.]
fibrosis was found when gadolinium-enhanced MRI [n = 397] was
If high-quality magnetic resonance cholangiography is
compared with no MRI [n = 1 418 451]. Gadolinium-enhanced MRI
normal in a patient with IBD and suspected PSC, an ultra-
at any time during pregnancy was associated with an increased risk
sound-guided liver biopsy should be considered to diag-
of a broad set of rheumatological, inflammatory, or infiltrative skin
nose small-duct PSC [EL2]
conditions [adjusted hazard ratio 1.36; 95% CI 1.09–1.69] and for
stillbirth or neonatal death [adjusted relative risk 3.70; 95% CI
1.55–0.85].433 Another retrospective study of 751 neonates exposed
to 1.5T MRI in utero, compared with 10 042 unexposed neonates,
found no difference between groups regarding birthweight or inci-
dence of hearing impairment or deafness.434 [ECCO EIM Guidelines: statement 7H in M. Harbord et al.]
Specific data on MRI in pregnant women with IBD are limited. There is no evidence-based follow up regimen proven to
Stern et al. reported nine pregnant women [seven with established detect biliary neoplasia earlier in PSC. Annual ultrasonog-
CD] who underwent unenhanced MRI. Features typical of active CD raphy to detect gallbladder mass lesions is recommended
were identified with their protocol [mural thickening ≥3 mm, ulcers, [EL4]. Additional imaging (MRI/MRC, CT, or endoscopic
mural oedema, ‘comb sign’, phlegmon, abscesses, and fistulae]. MRI retrograde cholangiography [ERC]) should be performed
detected complications in four women and was sufficiently accurate without delay if cholangiocarcinoma is suspected [EL1]
to inform medical management.435 One case report described MR
colonography used safely to examine a pregnant woman of 20 weeks
gestational age with acute severe colitis, indicating conservative Statement 3.8.4. ECCO-ESGAR Diagnostics GL [2018]
therapy that avoided colectomy.436 Another case report described a
pregnant woman of 26 weeks gestational age who underwent unen- [ECCO EIM Guidelines: statement 7E in M. Harbord et al.]
hanced MRI to diagnose adhesions following ileo-anal pouch sur- In PSC patients with clinical or radiological suspicion of
gery, with no adverse events.437 Another case report did not reveal significant strictures or cholangiocarcinoma, ERC is rec-
any safety concerns in a pregnant woman with fistulising CD.438 ommended to diagnose strictures that may be amenable
X-ray exposure is associated with an increased risk of congeni- to endoscopic dilatation [with or without stenting] and for
tal malformation439,440 and childhood cancer,441 estimated at 6% brush cytology specimen evaluation [EL2]. Prophylactic
per Gy.440 However, exposure at ≤50 mGy is considered safe at any antibiotic therapy is recommended [EL1]
trimester.440 In the absence of data for IBD patients, Hurwitz et al.
showed that multidetector row CT to investigate suspected appendi- The statements above have been included in this ECCO diagnostic
citis conferred a dose of 1.52 to 1.68 cGy and 2 to 4 cGy at Months guideline for completion of endoscopic or cross-sectional imaging
0 and 3, respectively.442 Unless potential risks are outweighed by diagnostics of extra-intestinal biliary involvement in patients with
clinical need, current data do not support the use of CT or any other IBD. For detailed explanation and references, please refer to the
X-ray technique. Due to the absence of specific data regarding use of ECCO EIM guideline.244
radio-isotopes in pregnant women with suspected or diagnosed IBD,
radio-isotopes should be avoided in this patient population. Conflict of Interest Statement
Limited evidence exists regarding the utility and safety of endos-
ECCO and ESGAR have diligently maintained a disclosure policy of poten-
copy in pregnant women with IBD. Due to potential complications
tial conflicts of interests [CoI]. The conflict of interest declaration is based
described in the recent ECCO pregnancy and reproduction consen-
on a form used by the International Committee of Medical Journal Editors
sus,443 endoscopy in pregnancy should be reserved for strong indi-
[ICMJE]. The CoI statement is not only stored at the ECCO Office and the
cations. To avoid vena cava compression, pregnant patients should editorial office of JCC but also is open to public scrutiny on the ECCO website
be placed in the left pelvic tilt or left lateral position before, during, [https://www.ecco-ibd.eu/about-ecco/ecco-disclosures.html] providing a com-
and after the endoscopic procedure. Close attention should be paid prehensive overview of potential conflicts of interest of authors.
The ECCO-ESGAR Consensus Guidelines are based on an international • France: Arnaud Bourreille, Xavier Roblin, Jean- Pierre Tasu
consensus process. Any treatment decisions are a matter for the individual clini- • Germany: Britta Siegmund
cian and should not be based exclusively on the content of the ECCO-ESGAR • Greece: Ioannis Koutroubakis, Charikleia Triantopoulou
Consensus Guidelines. The European Crohn´s and Colitis Organisation, the • Ireland: Garret Cullen
European Society of Gastrointestinal and Abdominal Radiology, and/or any of • Israel: Matti Waterman
their staff members and/or any consensus contributor may not be held liable • Italy: Ennio Biscaldi
for any information published in good faith in the ECCO-ESGAR Consensus • Lithuania: Gediminas Kiudelis
Guidelines. • Moldova: Svetlana Turcan
• Poland: Maria Klopocka, Małgorzata Sładek
• Portugal: Paula Ministro dos Santos
• Romania: Mihai Mircea Diculescu
Acknowledgments • Russia: Alexander Potapov
Guidelines panel: Chairs: Andreas Sturm, Christian Maaser, and Jaap Stoker • Spain: Javier Gisbert, Rosa Bouzas
Consultant pathologist expert: Paula Borralho Nunes • Sweden: Ann-Sofie Backman, Michael Eberhardson
WG1 [Working group 1]: Initial diagnosis [or suspecting IBD], Imaging tech- • Switzerland: Dominik Weishaupt
niques in regard to location: Upper GI tract, Mid GI tract, Lower GI tract, • Trinidad & Tobago: Alexander Sinanan

Perianal disease • UK: Barney Hawthorne
Leader – Stephan Vavricka
Member – Pierre Ellul Additional reviewers who participated in the Second Voting Round:
Member – Fabiana Castiglione • Almer, Sven
Y-ECCO – Bram Verstockt • Biancone, Livia
ESGAR – Damian Tolan • Bonifacio, Cristiana
WG2: Imaging techniques in regard to clinical situations: Monitoring thera- • Civitelli, Fortunata
peutic success [inclusive calpro], Monitoring clinically asymptomatic patients, • Eder, Piotr
Monitoring clinically symptomatic patients, Imaging after surgery including • Fernandes, Carlos
ileoanal pouch • Lopetuso, Loris
Leader – Torsten Kucharzik • Luglio, Gaetano
Member – Patrick van Rheenen • Portela, Francisco
Member – Uri Kopylov • Rizzello, Fernando
Y-ECCO – Hannah Gordon • Sahnan, Kapil
ESGAR – Andrea Laghi • Sieczkowska, Joanna
WG3: Detecting [suspected] complications [stricture, fistula, abscess, anas- Reviewer, on behalf of GuiCom: Tim Raine
tomotic insufficiency, toxic megacolon, perforation]: Endoscopic and non-
medical, non-surgical interventions [stricture, abscess, bleeding], Cancer
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Journal of Crohn's and Colitis, 2019, 144–164K

ECCO Guideline/Consensus Paper

ECCO-ESGAR Guideline for Diagnostic

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Corresponding author: Christian Maaser, gastroenterologist, Outpatients Department of Gastroenterology, Hospital

Introduction of CD or UC is based on a combination of clinical, biochemical, stool,

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Serological markers may be used to support a diagnosis, though

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Statement 1.11. ECCO-ESGAR Diagnostics GL [2018] Chapter 2: Monitoring known IBD

recent study of 83 patients with moderate-to-severe UC, endoscopic

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As endoscopic access of the small bowel is more difficult, response to

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Faecal calprotectin C-reactive protein

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IBD susceptibility Intestinal Irreversible

Early targets: Intermediate: Late targets:

Figure 1. Targets along the disease progression pathway in IBD.

observational cohort of patients with asymptomatic or mildly active

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Table 1. Markers of disease activity for monitoring asymptomatic IBD patients.

Validity [correlation Responsiveness to changes in Signal-to-noise ratio [ability to dif- Practicality

Endoscopy Gold standard Gold standard Gold standard Low

FECAL CALPROTECTIN LEVEL

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TIME SINCE DIAGNOSIS

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Cross-sectional imaging and endoscopy are complemen-

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When a perforation is suspected, CT should be performed

On the basis of systematic endoscopic assessment, together with

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Risk level Risk factors Surveillance

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