Dive Into Diagnostics

At the inaugural APP Institute Inflammatory Bowel Disease, Alexis Oonk, FNP, reviewed how to establish a diagnosis of inflammatory bowel disease, including determining phenotype, assessing the severity of disease, and using biomakers to establish benchmarks.

Alexis Oonk, FNP, is a Senior Instructor in Medicine-Gastroenterology and nurse practitioner at the University of Colorado Digestive Health Center in Aurora, Colorado.

Good afternoon. My name is Alexis Oonk, I’m a nurse practitioner at the University of Colorado. I work in the Crohn’s Colitis Center there and I have over the past decade. I am excited to talk with you today about a dive into diagnostics and mastering monitoring. And I just wanted to take a minute to thank the cochairs of the conference, Kimberly Kearns and Kim Orleck, for this opportunity.

So what are the goals of diagnosis? You know, really, we want to be evaluating symptoms that our patients present with and trying to establish a diagnosis of inflammatory bowel disease, which includes determining their phenotype, assessing the severity of their disease, as well as evaluating for any disease-related complications that would warrant specific therapy. Together, all of these things are going to help guide our therapeutic decisions.

So how is IBD diagnosed? You know, the bottom line is that there's no single test to confirm a diagnosis of IBD. It often requires a multimodal approach involving clinical history, physical exam, both noninvasive and invasive testing, that includes stool testing, serum testing, endoscopy, imaging, and then also histologic evaluation.

I just want to briefly mention that the American College of Gastroenterology proposed in 2019 guidelines for UC that they recommend against the serologic antibody testing to establish a diagnosis of UC or determine prognosis. So I won't be discussing that today,  although we will be covering other serum biomakers.

So to start with that, with regard to noninvasive testing, some of the more common serum  biomarkers include C-reactive protein, which is an acute phase reactant. It’s produced in our liver. It rises in some patients in stimulation from inflammatory cytokines. As I mentioned, it only rises in a subset of inflammatory bowel disease patients, and so there are some folks that will have active inflammation and have a normal CRP, and that's important to determine.

CRP can be affected by age, sex, and body mass index. I think the most important thing about it is that it has a short half-life of 19 hours or so, making it a useful marker to both detect inflammation, but then also monitor changes in that inflammation in response to our interventions.

The erythrocyte sedimentation rate, or ESR, is a measurement of the rate of erythrocytes migrating through the plasma, and as you can imagine, that can be affected by anemia, polycythymia, and thalcemia. It's elevated in some patients, but it can be sometimes challenging because healthy controls can sometimes have elevated levels as well as patients who may be seen in your GI clinic with irritable bowel syndrome and have active GI symptoms, but not necessarily inflammatory bowel disease.

This will peak less rapidly and take several days to decline, making it somewhat more challenging to utilize that as a marker to monitor response to immediate therapy changes and interventions.

This is just a diagram, a visual representation of C -reactive protein upregulation at a cellular level, which I think is interesting to keep in mind.

Some other noninvasive testing that I think plays a particularly important role in diagnostics of IBD are stool mark biomarkers. I’m sure many of you are familiar with fecal calprotectin. This is a calcium-binding protein derived from neutrophils and it can elevate in most patients, although again there are some instances where there is a limited extent of disease and there may be active inflammation and it may not be particularly elevated. Examples would be very limited proctitis or potentially isolated ileal inflammation. The normal for that is typically 50 to 100 or less than those values. We know that certain patients can elevate that into several thousands of times. And so it can be a useful marker to trend over time.

Lactoferrin is an older stool inflammation marker; unlike the fecal calprotectin, which gives you a quantitative level, it will give you typically a positive or negative, depending on your assay. I know that's what we have at our institution.

I think things to consider with these stool markers are that both of these biomarkers are not specific to IBD alone, and certain enteric infections can produce elevations or abnormal values in these. There are certain medications and drug therapies that can also result in abnormalities, and these can be elevated in the setting of intestinal neoplasms.

Just to point out, the AGA guidelines from February of 2023, they did highlight recommendation to use blood and stool testing for disease monitoring in our patients with ulcerative colitis. And so it's something that I think is becoming more and more commonplace, and we'll talk later on in the lecture about use of this.

Some additional laboratory studies that I think are helpful upon initial presentation include stool studies to exclude infectious ideologies or concurrent infections, particularly Clostridium difficile, which as we all know can at times be somewhat ubiquitous, but it's important to exclude that at the time of presentation. Additional hematological labs, including hemoglobin, hematocrit, and iron indices are important to assess your patient for anemia. Also, white blood cell count and platelets are both markers of inflammation and can be helpful to have initial assessment.

Albumin, conversely, can be decreased, not elevated, in the setting of folks who are having issues with their nutritional status due to their inflammatory bowel disease. Really decreased levels of albumin can also help provide information about response to therapy and prognosticate initial response.

So I think the approach to biomarkers is really that there is some challenges there. Different patients elevate different biomarkers to different degrees or at times don't elevate them at all. And there's not a single biomarker that's available that is ideal. And so it often is a compilation of several of these.

I think the best general approach is really to assess the available biomarkers in the serum and stool at the time of presentation, allowing you to be able to assess which biomarkers are going to be relevant and useful for your patient moving forward. I think it's also always really ideal to have these biomarkers benchmarked at the time or close to the time of an endoscopic or radiologic evaluation.