Expert Review of Gastroenterology & Hepatology
ISSN: 1747-4124 (Print) 1747-4132 (Online) Journal homepage: http://www.tandfonline.com/loi/ierh20
Endoscopic scoring systems for inflammatory bowel disease: pros and cons Gian Eugenio Tontini, Raf Bisschops & Helmut Neumann To cite this article: Gian Eugenio Tontini, Raf Bisschops & Helmut Neumann (2014) Endoscopic scoring systems for inflammatory bowel disease: pros and cons, Expert Review of Gastroenterology & Hepatology, 8:5, 543-554 To link to this article: http://dx.doi.org/10.1586/17474124.2014.899899
Published online: 20 Mar 2014.
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Date: 05 November 2015, At: 13:35
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Endoscopic scoring systems for inflammatory bowel disease: pros and cons Downloaded by [University of Pennsylvania] at 13:35 05 November 2015
Expert Rev. Gastroenterol. Hepatol. 8(5), 543–554 (2014)
Gian Eugenio Tontini1,2, Raf Bisschops3 and Helmut Neumann*1 1 Department of Medicine 1, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany 2 Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy 3 Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium *Author for correspondence: Tel.: +49 913 1853 5000 Fax: +49 913 1853 5209 [email protected]
informahealthcare.com
Endoscopy plays a pivotal role for diagnosis and assessment of disease activity and extent in patients with inflammatory bowel diseases. International guidelines recommend the use of endoscopic scoring systems for evaluation of the prognosis and efficacy of medical treatments. Ideal scoring systems are easy to use, reproducible, reliable, responsive to changes, and validated in different clinical settings in order to guide therapeutic strategies. However, currently available endoscopic scoring systems often appear as complex for routine endoscopy and suffer from insufficient interobserver agreement and lack of formal validation which often limit their use in clinical trials. Here, we describe the role of endoscopic scoring systems in inflammatory bowel diseases focusing on pros and cons in the era of advanced endoscopic imaging and mucosal healing. KEYWORDS: advanced endoscopic imaging • colonoscopy • Crohn’s disease • disease activity indices • endoscopic disease activity • inflammatory bowel disease • mucosal activity • mucosal healing • ulcerative colitis
Inflammatory bowel diseases (IBDs) are gastrointestinal chronic disorders that affect more than 1 million people in the USA and several million worldwide [1,2]. Major forms of IBD include Crohn’s disease (CD) and ulcerative colitis (UC). Although the pathophysiological background is not yet fully understood, IBD typically affects the intestinal mucosa [3]. Therefore, endoscopy plays a pivotal role for diagnosis and assessment of disease activity and extent [4]. Moreover, national and international guidelines recommend ileocolonoscopy for evaluating the efficacy of new treatments including biologic therapies and immunosuppressive agents in IBD [4–7]. In this context, mucosal healing (MH) is considered to be an important endpoint as recent evidence suggests that MH, as assessed by endoscopy, is predictive of reduced disease activity, decreased need for active treatment and lower risk of hospitalization and surgery [7–12]. Accordingly, reproducible and validated scoring systems for endoscopic assessment of disease activity and extent seem to be necessary to enable comparable results throughout different studies, to standardize endpoints and to guide therapeutic decisions. Within the last decades, various endoscopic scoring systems have been introduced (TABLES 1 & 2). Nevertheless, most of these scoring systems suffer 10.1586/17474124.2014.899899
from inconsistent definitions of how to define mucosal lesions as viewed by endoscopy [4,5,13]. In addition, there is no validated definition of MH or endoscopic remission in patients with IBD yet [4,5,14–16]. For instance, in CD, MH is commonly defined as the total disappearance of all mucosal ulcerations, while in UC, it is mostly defined as the absence of friability, ulcerations and the return to a normal mucosal vascular pattern. Both definitions are difficult to achieve and even dependent on the endoscopic imaging technology used to assess the mucosal vascular pattern. This review describes the role of endoscopic scoring systems in IBD focusing on pros and cons in the era of advanced endoscopic imaging and MH. Reproducibility & feasibility
In clinical research, the use of endoscopic scoring systems dates back to 1955 when Truelove and Witts first classified the appearance of the rectosigmoid mucosa as normal, near normal, improved, stable or worsened during a placebo-controlled trial of corticosteroids in active UC [17]. By that time, endoscopic scoring has gradually become a conditio sine qua non for clinical trials dealing with disease activity outcomes. However, most endoscopic scores are time-consuming and their complexity often
2014 Informa UK Ltd
ISSN 1747-4124
543
Review
Tontini, Bisschops & Neumann
Downloaded by [University of Pennsylvania] at 13:35 05 November 2015
Table 1. Comparison of different scoring systems for ulcerative colitis. Validation
Parameters
Thresholds
Strengths
Weaknesses
Ref.
Baron score
No
Vascular pattern, friability, bleeding
Remission: 0–1 (NV) Response: not defined
Easy and fast
Few parameters and no assessment of ulcers; use of subjective parameters (friability)
[51]
Modified baron score
No
Vascular pattern, granularity, hyperemia, friability, ulceration, bleeding
Remission: 0 (NV) Response: not defined
Easy and fast
No discrimination between ulcers; use of subjective parameters (friability)
[52]
Rachmilewitz endoscopic index
No
Granulation scattering reflected light, vascular pattern, vulnerability (contact or spontaneous bleeding), mucosal damage (mucus, fibrin, exudates, erosions and ulcer)
Remission: 0–4 (NV) Response: not defined
Easy to calculate
No discrimination between ulcers, use of subjective parameters and scale
[53]
Mayo endoscopic subscore
No
Erythema, vascular pattern, friability, bleeding, erosions and ulcerations
Remission: 0 or 0–1 (NV) Response: not defined
Easy and fast; adopted in several trials
No discrimination between ulcers, use of subjective parameters (friability)
[49,50]
UCCIS
Initial
Vascular pattern, granularity, ulceration, bleeding/friability
Remission: not defined Response: not defined
Accurate and based on rigorous methodology; provides a pancolonic assessment
Use of subjective parameters and scale; complex, requires post-procedure time to be scored
[24]
UCEIS
Initial
Vascular pattern, bleeding and erosions/ulcers
Remission: not defined Response: not defined
Accurate and based on rigorous methodology; thresholds level and responsiveness to change are under evaluation
Limited to the rectosigmoid; low agreement for normal appearing mucosa
[22,27]
NV: Not validated; UCCIS: Ulcerative Colitis Colonoscopic Index of Severity; UCEIS: Ulcerative Colitis Endoscopic Index of Severity.
requires a post hoc assessment. For instance, the CD Endoscopic Index of Severity (CDEIS) accounts four types of lesions (i.e., superficial ulcers, deep ulcers, ulcerated or nonulcerated stenosis) at five different ileocolonic segments (i.e., terminal ileum, right colon, transverse colon, left colon and rectum), as well as the percentage of ulcerated colonic surface and the percentage of surface affected on a 10-cm visual analog scale [18]. The Simple Endoscopic Score for CD (SES-CD) was further developed and validated to simplify both ulcer classification and percentage of surface involved by the disease [19]. Consistently, ulcer ‘depth’ was replaced by ulcer ‘size’, which has been supposed to be more accurate, while percentage of a given segment involved was scored by selection of one number from 0 to 3. Given this complexity, each scoring system has to be assessed ad hoc based on detailed endoscopic reports or full-length videorecordings [20]. Therefore, the calculation of complex endoscopic indices such as CDEIS or SES-CD is mostly not applicable a posteriori. In addition, the comparability between different scoring systems is often difficult to achieve. 544
Moreover, variation between observers in categorizing endoscopic lesions and disease severity was shown to be substantial, with remarkable impact on the results of clinical trials [21–23]. For example, in UC, converging lines of evidence have identified scoring of friability as a main limitation. This parameter evaluates mucosal fragility and is presumed to be an early feature of inflammatory ulceration, where minimal bleeding may occur spontaneously or after minor contact of the endoscope or biopsy forceps against the mucosa. Even among specialized gastroenterologists, the term friability was found to be less reliable compared with other endoscopic parameters when trying to distinguish between ‘incidental’ (i.e., before or after passage of the endoscope) and ‘contact’ friability (i.e., after light touch with closed biopsy forceps) [22–24]. Accordingly, the International Organization of IBD (IOIBD) has recently defined the term ‘minimal or slight friability’, which is used in the Mayo scoring system, to be ‘subjective’ and leading to ‘inconsistent results’ [6]. Consequently, friability was excluded from the Expert Rev. Gastroenterol. Hepatol. 8(5), (2014)
Endoscopic scoring systems for IBD
Review
Downloaded by [University of Pennsylvania] at 13:35 05 November 2015
Table 2. Comparison of different scoring systems for Crohn’s disease. Validation
Parameters
Thresholds
Applicability and strengths
Weaknesses
Ref.
CDEIS
Yes
Depth of ulcers (superficial and deep), extent of ulcerated and affected surface, stenosis (ulcerated and nonulcerated)
Remission: 0†,
ISSN: 1747-4124 (Print) 1747-4132 (Online) Journal homepage: http://www.tandfonline.com/loi/ierh20
Endoscopic scoring systems for inflammatory bowel disease: pros and cons Gian Eugenio Tontini, Raf Bisschops & Helmut Neumann To cite this article: Gian Eugenio Tontini, Raf Bisschops & Helmut Neumann (2014) Endoscopic scoring systems for inflammatory bowel disease: pros and cons, Expert Review of Gastroenterology & Hepatology, 8:5, 543-554 To link to this article: http://dx.doi.org/10.1586/17474124.2014.899899
Published online: 20 Mar 2014.
Submit your article to this journal
Article views: 63
View related articles
View Crossmark data
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ierh20 Download by: [University of Pennsylvania]
Date: 05 November 2015, At: 13:35
Review
Endoscopic scoring systems for inflammatory bowel disease: pros and cons Downloaded by [University of Pennsylvania] at 13:35 05 November 2015
Expert Rev. Gastroenterol. Hepatol. 8(5), 543–554 (2014)
Gian Eugenio Tontini1,2, Raf Bisschops3 and Helmut Neumann*1 1 Department of Medicine 1, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany 2 Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy 3 Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium *Author for correspondence: Tel.: +49 913 1853 5000 Fax: +49 913 1853 5209 [email protected]
informahealthcare.com
Endoscopy plays a pivotal role for diagnosis and assessment of disease activity and extent in patients with inflammatory bowel diseases. International guidelines recommend the use of endoscopic scoring systems for evaluation of the prognosis and efficacy of medical treatments. Ideal scoring systems are easy to use, reproducible, reliable, responsive to changes, and validated in different clinical settings in order to guide therapeutic strategies. However, currently available endoscopic scoring systems often appear as complex for routine endoscopy and suffer from insufficient interobserver agreement and lack of formal validation which often limit their use in clinical trials. Here, we describe the role of endoscopic scoring systems in inflammatory bowel diseases focusing on pros and cons in the era of advanced endoscopic imaging and mucosal healing. KEYWORDS: advanced endoscopic imaging • colonoscopy • Crohn’s disease • disease activity indices • endoscopic disease activity • inflammatory bowel disease • mucosal activity • mucosal healing • ulcerative colitis
Inflammatory bowel diseases (IBDs) are gastrointestinal chronic disorders that affect more than 1 million people in the USA and several million worldwide [1,2]. Major forms of IBD include Crohn’s disease (CD) and ulcerative colitis (UC). Although the pathophysiological background is not yet fully understood, IBD typically affects the intestinal mucosa [3]. Therefore, endoscopy plays a pivotal role for diagnosis and assessment of disease activity and extent [4]. Moreover, national and international guidelines recommend ileocolonoscopy for evaluating the efficacy of new treatments including biologic therapies and immunosuppressive agents in IBD [4–7]. In this context, mucosal healing (MH) is considered to be an important endpoint as recent evidence suggests that MH, as assessed by endoscopy, is predictive of reduced disease activity, decreased need for active treatment and lower risk of hospitalization and surgery [7–12]. Accordingly, reproducible and validated scoring systems for endoscopic assessment of disease activity and extent seem to be necessary to enable comparable results throughout different studies, to standardize endpoints and to guide therapeutic decisions. Within the last decades, various endoscopic scoring systems have been introduced (TABLES 1 & 2). Nevertheless, most of these scoring systems suffer 10.1586/17474124.2014.899899
from inconsistent definitions of how to define mucosal lesions as viewed by endoscopy [4,5,13]. In addition, there is no validated definition of MH or endoscopic remission in patients with IBD yet [4,5,14–16]. For instance, in CD, MH is commonly defined as the total disappearance of all mucosal ulcerations, while in UC, it is mostly defined as the absence of friability, ulcerations and the return to a normal mucosal vascular pattern. Both definitions are difficult to achieve and even dependent on the endoscopic imaging technology used to assess the mucosal vascular pattern. This review describes the role of endoscopic scoring systems in IBD focusing on pros and cons in the era of advanced endoscopic imaging and MH. Reproducibility & feasibility
In clinical research, the use of endoscopic scoring systems dates back to 1955 when Truelove and Witts first classified the appearance of the rectosigmoid mucosa as normal, near normal, improved, stable or worsened during a placebo-controlled trial of corticosteroids in active UC [17]. By that time, endoscopic scoring has gradually become a conditio sine qua non for clinical trials dealing with disease activity outcomes. However, most endoscopic scores are time-consuming and their complexity often
2014 Informa UK Ltd
ISSN 1747-4124
543
Review
Tontini, Bisschops & Neumann
Downloaded by [University of Pennsylvania] at 13:35 05 November 2015
Table 1. Comparison of different scoring systems for ulcerative colitis. Validation
Parameters
Thresholds
Strengths
Weaknesses
Ref.
Baron score
No
Vascular pattern, friability, bleeding
Remission: 0–1 (NV) Response: not defined
Easy and fast
Few parameters and no assessment of ulcers; use of subjective parameters (friability)
[51]
Modified baron score
No
Vascular pattern, granularity, hyperemia, friability, ulceration, bleeding
Remission: 0 (NV) Response: not defined
Easy and fast
No discrimination between ulcers; use of subjective parameters (friability)
[52]
Rachmilewitz endoscopic index
No
Granulation scattering reflected light, vascular pattern, vulnerability (contact or spontaneous bleeding), mucosal damage (mucus, fibrin, exudates, erosions and ulcer)
Remission: 0–4 (NV) Response: not defined
Easy to calculate
No discrimination between ulcers, use of subjective parameters and scale
[53]
Mayo endoscopic subscore
No
Erythema, vascular pattern, friability, bleeding, erosions and ulcerations
Remission: 0 or 0–1 (NV) Response: not defined
Easy and fast; adopted in several trials
No discrimination between ulcers, use of subjective parameters (friability)
[49,50]
UCCIS
Initial
Vascular pattern, granularity, ulceration, bleeding/friability
Remission: not defined Response: not defined
Accurate and based on rigorous methodology; provides a pancolonic assessment
Use of subjective parameters and scale; complex, requires post-procedure time to be scored
[24]
UCEIS
Initial
Vascular pattern, bleeding and erosions/ulcers
Remission: not defined Response: not defined
Accurate and based on rigorous methodology; thresholds level and responsiveness to change are under evaluation
Limited to the rectosigmoid; low agreement for normal appearing mucosa
[22,27]
NV: Not validated; UCCIS: Ulcerative Colitis Colonoscopic Index of Severity; UCEIS: Ulcerative Colitis Endoscopic Index of Severity.
requires a post hoc assessment. For instance, the CD Endoscopic Index of Severity (CDEIS) accounts four types of lesions (i.e., superficial ulcers, deep ulcers, ulcerated or nonulcerated stenosis) at five different ileocolonic segments (i.e., terminal ileum, right colon, transverse colon, left colon and rectum), as well as the percentage of ulcerated colonic surface and the percentage of surface affected on a 10-cm visual analog scale [18]. The Simple Endoscopic Score for CD (SES-CD) was further developed and validated to simplify both ulcer classification and percentage of surface involved by the disease [19]. Consistently, ulcer ‘depth’ was replaced by ulcer ‘size’, which has been supposed to be more accurate, while percentage of a given segment involved was scored by selection of one number from 0 to 3. Given this complexity, each scoring system has to be assessed ad hoc based on detailed endoscopic reports or full-length videorecordings [20]. Therefore, the calculation of complex endoscopic indices such as CDEIS or SES-CD is mostly not applicable a posteriori. In addition, the comparability between different scoring systems is often difficult to achieve. 544
Moreover, variation between observers in categorizing endoscopic lesions and disease severity was shown to be substantial, with remarkable impact on the results of clinical trials [21–23]. For example, in UC, converging lines of evidence have identified scoring of friability as a main limitation. This parameter evaluates mucosal fragility and is presumed to be an early feature of inflammatory ulceration, where minimal bleeding may occur spontaneously or after minor contact of the endoscope or biopsy forceps against the mucosa. Even among specialized gastroenterologists, the term friability was found to be less reliable compared with other endoscopic parameters when trying to distinguish between ‘incidental’ (i.e., before or after passage of the endoscope) and ‘contact’ friability (i.e., after light touch with closed biopsy forceps) [22–24]. Accordingly, the International Organization of IBD (IOIBD) has recently defined the term ‘minimal or slight friability’, which is used in the Mayo scoring system, to be ‘subjective’ and leading to ‘inconsistent results’ [6]. Consequently, friability was excluded from the Expert Rev. Gastroenterol. Hepatol. 8(5), (2014)
Endoscopic scoring systems for IBD
Review
Downloaded by [University of Pennsylvania] at 13:35 05 November 2015
Table 2. Comparison of different scoring systems for Crohn’s disease. Validation
Parameters
Thresholds
Applicability and strengths
Weaknesses
Ref.
CDEIS
Yes
Depth of ulcers (superficial and deep), extent of ulcerated and affected surface, stenosis (ulcerated and nonulcerated)
Remission: 0†,
