[00:29]
Hello, I’m Dr. Erin Forster and welcome to IBDIQ, part of The IBD Project by Takeda, where we’re coming together to help enhance expertise in IBD care—right from the start.
Today, I will review diagnostic approaches for inflammatory bowel disease with you. This presentation will be a brief overview of the clinical presentation of ulcerative colitis and Crohn's disease, including the roles of laboratory tests and biomarkers.
We will also analyze how radiological and endoscopic procedures help us to identify inflammation and complications from inflammatory bowel disease.
Finally, we will explore the advanced interpretation of histopathology findings, with a focus on differentiating disease subtypes and assessing severity.
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To begin, what is inflammatory bowel disease, or IBD?
IBD is a relapsing and remitting condition characterized by chronic inflammation at various sites in the GI tract.1 There are two main types: Crohn's disease (CD) and ulcerative colitis (UC).1
Patients with ulcerative colitis predominantly present with bloody diarrhea,2 and inflammation that is diffuse and continuous from the distal colon.3
For Crohn’s disease, patients usually present with abdominal pain, diarrhea, weight loss, and fatigue.3
CD is characterized by a discontinuous pattern of inflammation, also called skip lesions, with a cobblestone appearance.3 Patients can have mesenteric creeping fat and eventually develop fibrosis from transmural inflammation.4
These pathologic inflammatory differences between UC and CD should be considered when trying to identify one of these conditions.
The diagnostic approaches for CD include endoscopy, imaging, and stool-based tests.5
[02:12]
The diagnostic approaches for UC include stool-based tests as well as endoscopy with histologic confirmation.6
We will begin with endoscopy. Use of endoscopy for the visualization of the colon and its associated inflammation is key for diagnosis and monitoring of IBD.7
There are several different endoscopic procedures that could be utilized.3
Ileocolonoscopy is an essential part of diagnosing CD that allows for direct visualization of characteristic lesions of IBD, monitoring the success or failure of a therapy, and screening for colorectal cancer.3,7
In addition to diagnosis, colonoscopy may be used 8-10 years after initial diagnosis to assess for dysplasia and remove polyps.8
For patients with upper gastrointestinal tract symptoms, esophagogastroduodenoscopy (EGD) may be used.2
Capsule endoscopy is another option when the small bowel needs to be assessed.3,4
Let’s also discuss chromoendoscopy.
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Chromoendoscopy uses topical application of stains or pigments like methylene blue; the contrast stain facilitates identification of dysplasia.4
With chromoendoscopy, IBD-related dysplasia is now likely visible and endoscopically identifiable.9
However, studies comparing chromoendoscopy and other enhanced imaging techniques such as narrow band imaging are limited.1,4
Crohn’s and UC present differently on endoscopy.6,10
Some endoscopic findings characteristic of Crohn’s include patchy inflammation with skip lesions (a hallmark feature of CD), longitudinal ulcers, cobblestone appearance of the intestinal lining, fistulous orifices, and stricture.10
There are also endoscopic severity scoring systems which allow for a more standardized assessment.9
The Simple Endoscopic Score for Crohn’s (SES-CD) is an example of an endoscopic classification and scoring system.9
The Rutgeerts Score could also be used to evaluate the risk of CD recurrence in patients who have undergone ileocolonic anastomosis.9
[04:16]
In contrast to Crohn’s, endoscopic findings in UC include a continuously inflamed segment involving the distal rectum extending proximally in the colon, loss of vascular markings, granularity and friability of the mucosa, and erosions, and in severe disease, deep ulcerations and spontaneous bleeding.6
An endoscopic severity scoring system often used in UC is the Mayo Endoscopic Subscore for ulcerative colitis.9
Additional diagnostic tools for visualization of IBD include cross-sectional imaging with computed tomography (or CT) and magnetic resonance imaging (MRI).6,7
These imaging techniques complement endoscopy as they provide different views of the GI tract that are inaccessible via endoscopic procedures.3
They are also less invasive and may be more acceptable than endoscopies for patients.11
CT imaging is reliable but has the downside of radiation exposure.
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MRI has no radiation exposure, but is expensive and may be difficult for patients to tolerate.3
Cross-sectional techniques can also assess the full thickness of the bowel wall and surrounding tissues.12
Bowel wall thickness is a robust indicator for disease activity, with a threshold of bowel wall thickness greater than 3 millimeters for active IBD in both the ileum and colon.12
Other activity parameters like neoangiogenesis and vascularization should also be assessed to determine whether the intestinal inflammation is acute or chronic.12
Because CD is a transmural disease, it makes sense to use MR enterography or intestinal ultrasound to assess transmural healing.12
Transmural healing, measured by intestinal ultrasound or MRE, is associated with better long-term patient outcomes than endoscopic mucosal healing and has been proposed as a desirable treatment target in the STRIDE-2 consensus.12
However, optimal criteria for quantifying transmural healing on cross-sectional imaging are not yet defined, and prospective studies are needed.12
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In Crohn’s, increased T2 signal and stranding of the mesenteric fat due to transmural edema and inflammation are generally specific signs of activity.12
On MRE specifically, increased mural T2 signal in the submucosa is a highly specific sign of disease activity suggesting severe inflammation.12
Fibrofatty proliferation, also known as fat wrapping, describes the hypertrophy and expansion of the mesenteric fat side, which can produce a mass-effect on adjacent bowel loops.12
Ulceration is another marker of disease activity.12 On MRE, it is seen as thin, high-signal intensity lines within thickened bowel wall and on IUS, as breaks in the mucosal layer.
MRI has also been shown to be valuable as a first-line examination technique. In a prospective observational study of 100 patients in Barcelona, investigators found that colonoscopy as a first examination aided in correct assessment of Crohn’s disease in 34% of cases, compared with 80% when MRI was used as the first examination.13
[07:24]
Another form of imaging is intestinal ultrasound (IUS)—a non-invasive, real-time, cross-sectional imaging tool.14
Ultrasound imaging offers an advantage over endoscopy in that it evaluates the transmural aspects of the inflammatory region, which is helpful for diagnosis and monitoring of disease activity.14
An advantage is that IUS is easy to use and evaluation of the treatment response in patients with IBD can be observed weeks after treatment initiation.12
IUS has 4 main metrics: bowel wall thickness (BWT), hyperemia, inflammatory fat (or iFat), and bowel wall stratification.14
The first metric, bowel wall thickness, is the most important measure of disease activity for both Crohn’s and UC; it correlates with endoscopic assessment of inflammation and bowel wall thickness greater than 3 millimeters signifies active endoscopic disease.
[08:19]
The next metric, hyperemia, is another important measure of disease activity assessed by color Doppler signal (CDS). Increased hyperemia is often representative of active disease when combined with increased bowel wall thickness.
Hypoechoic or hyperechoic changes in the bowel wall layers indicate a loss of bowel wall stratification.
Lastly, inflammatory mesenteric fat wrapping appears hyperechoic encasing the inflamed bowel.
There are many IUS activity scores that have been developed for adults with CD and UC.14 The most common and important parameters they assess are bowel wall thickness, followed by hyperemia and bowel wall stratification.
A few IUS scores have been validated with a standardized endoscopic score that can be used at the point-of-care for clinical decision-making.14
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Examples of validated IUS scores are the Simple ultrasound score for CD, and the Milan ultrasound criteria (MUC) for ulcerative colitis.14
IUS can be used to monitor treatment responses in Crohn’s disease and UC by assessing improvement in the IUS parameters (bowel wall thickness, hyperemia, iFat, and bowel wall stratification), which can typically be seen within 12 weeks of treatment initiation.14 However, the interpretation of these improvements and the timing of repeat IUS assessments is still being explored.
Leveraging IUS for IBD monitoring can improve shared understanding and enhance providers' capacity to make treatment decisions during regular clinic appointments.14
For example, in a study of 49 patients with Crohn’s disease in Germany, clinical decisions were changed after ultrasound assessment in nearly 60% of cases.15
Beside the use of endoscopy, why are biomarkers also recommended for the evaluation of patients with inflammatory bowel disease?
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Utilizing biomarkers to diagnose and monitor IBD is appealing because it can measure treatment response and serve as a non-invasive test in lieu of endoscopies.7
Let’s review these key biomarkers and their role in IBD.
Serum lab tests include erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and autoantibodies such as antineutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA).7
While these tests can be useful in assessing acute inflammation and disease,16 it should be noted that CRP is not elevated in every patient who shows active disease endoscopically.17
Perinuclear ANCAs are found in up to 70% of patients with ulcerative colitis and ASCAs are relatively specific for Crohn’s,7 but these tests are not recommended by guidelines for routine diagnosis as they do not reliably differentiate the two diseases.6,10
[11:17]
Stool-based markers that are used include fecal lactoferrin and fecal calprotectin.7
Fecal biomarkers may be used for differential diagnosis of IBD,7 and as a guide to determine whether endoscopies should be used or not.17,18
Fecal calprotectin is a nonspecific marker of inflammation that can be both elevated due to infection or inflammation.18 Since there is such a large difference in calprotectin concentration between healthy patients and those with inflammatory diseases like CD and UC, it has become a useful indicator for inflammation.7
This biomarker is useful to prioritize patients who may require colonoscopy or endoscopy, but it should be noted that calprotectin is not elevated in every patient who shows active disease endoscopically.17,18
Lactoferrin is a protein found in neutrophils, and is a marker of intestinal inflammation useful for differentiating IBD from irritable bowel syndrome (IBS).10,19
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A guideline by the AGA for the use of biomarkers has been completed for UC.18
The guideline recommends a conditional monitoring approach that combines biomarkers and symptoms rather than symptoms alone.18
For patients with UC, the AGA recommends the following18:
To monitor biomarkers every 6 to 12 months in patients in symptomatic remission and use these markers to determine the need for endoscopy. This has a moderate certainty in evidence.
The threshold for fecal calprotectin is less than 150 micrograms per gram. This has a low certainty in evidence.
For patients with moderate to severe symptoms that indicate a possible flare up, use of fecal biomarkers is recommended to confirm active inflammation instead of an endoscopy. This has a low to very low certainty in evidence.
For patients with mild symptoms and a fecal calprotectin greater than 150, an endoscopy is recommended to evaluate disease activity. This has a very low certainty in evidence.
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There is also an AGA guideline for the use of biomarkers in Crohn’s.17
Similar to UC, the guidelines for CD recommend a conditional monitoring approach for patients in symptomatic remission that combines biomarkers and symptoms rather than symptoms alone.17
For patients with Crohn’s, the AGA recommends the following17:
For asymptomatic patients following surgically induced remission, or who are at low risk of postoperative recurrence, use fecal calprotectin less than 50 micrograms per gram to avoid routine endoscopic assessment of disease activity. This has a moderate certainty in evidence.
For patients who are in symptomatic remission, fecal calprotectin less than 150 micrograms per gram and/or a CRP of less than 5 milligrams per liter can be used to rule out active inflammation and avoid a routine endoscopy procedure. This has a low to moderate certainty in evidence.
[14:12]
Endoscopy is recommended for patients with mild symptoms and a fecal calprotectin greater than 150 and/or a CRP of greater than 5 to evaluate disease severity rather than adjusting empiric treatment. This has a very low certainty in evidence.
It should be noted that for Crohn’s, biomarkers may not be an effective means of delineating endoscopic remission.17 While an SES-CD score of less than 3 is the targeted treatment outcome, studies have demonstrated that a more rigorous target of an SES-CD score of 0 may be associated with better outcomes. Data on the accuracy of biomarkers are limited. Moreover, there is significant heterogeneity in the extent and location of the involved segment in Crohn’s, which may influence biomarker sensitivity, specificity, and accuracy.
For small bowel Crohn’s, there is a lower prevalence of endoscopically active disease for given symptoms.17 This reduces the accuracy of biomarkers in patients with symptomatic Crohn’s.
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Additionally, there are no widely accepted validating scoring systems for assessing mucosal inflammation endoscopically in Crohn’s involving the proximal small bowel in isolation.17 This is determined to be a knowledge gap in biomarkers.
Now, how exactly are specimens collected for evaluation of IBD?
As endoscopies are being done, international consensus recommendations and guidelines specify that at least two biopsies of each bowel segment can be used to help assess histologic disease activity.20,21
Biopsy specimens are typically fixed in formalin and then stained with hematoxylin and eosin (H&E) to aid with the visualization of the specimen.22
IBD subtypes can be distinguished based on histopathology.22
Inflammation can be found anywhere in the entire gastrointestinal tract for Crohn’s, whereas UC is limited to the colon.22
Moreover, inflammation in UC may not be deep, whereas inflammation in patients with Crohn’s can be transmural.22
[16:15]
And, if there are granulomas present, this is typically associated with CD more than UC.22
Histopathological evaluation of dysplasia in endoscopic biopsies is crucial for surveillance of colorectal cancer in IBD patients.22
In the future, histological remission may be a treatment goal as part of the treat-to-target approach.22
In this module, we reviewed several diagnostic approaches to IBD.
We learned about:
How radiologic and endoscopic procedures can help us identify inflammation and complications from IBD.6,7,14
The role of key biomarkers.7
The interpretation of histopathology findings to differentiate disease subtypes.22
I hope that having these diagnostic approaches in your arsenal will help you feel more informed and provide your Crohn’s and ulcerative colitis patients with optimal care!
Thank you for your interest and for spending some time with IBDIQ today to help adapt to the evolving care needs of all IBD patients.
