Biologics for the Treatment of Inflammatory Bowel Disease - Episode 2

Referral and Differential Diagnosis of IBD

Red flag symptoms that should prompt a primary care physician to refer a patient to a gastroenterologist for proper assessment for a potential inflammatory bowel disease.

Joseph Feuerstein, MD: Dr Ungaro, could you fill us in on how you make the diagnosis for ulcerative colitis and Crohn’s disease when thinking of these 2 disease processes?

Ryan Ungaro, MD: Sure. Thanks, Joe. It’s great to be here. With both diseases, there’s a broad differential diagnosis when you’re seeing a patient where they’re presenting with symptoms that can be mistaken for different etiologies. You can have a patient with diarrhea, bloody stool, and abdominal pain, which can be symptoms for multiple diseases. The first thing to consider in a patient presenting with bloody diarrhea or diarrhea and abdominal pain is infection and looking at different infectious causes of the symptoms. That’s always an IBD [inflammatory bowel disease] trigger. It’s important to rule out infection—standard stool tests are something to consider—as well as tuberculosis if you have someone coming from a developing area of the world. Considering infection in your differential is always important. Getting stool studies to understand if there’s an infectious etiology to the patient’s symptoms is very important.

Other things more in the noninfectious realm that could potentially present with similar symptoms to IBD are more systemic vasculitides or other immune-mediated diseases, like sarcoidosis. You could also have very common things like irritable bowel syndrome, presenting similarly to IBD. That’s something that needs to be teased out. Other things can lead to colonic inflammation, like NSAID [nonsteroidal anti-inflammatory drug]–induced enteritis or colitis, ischemic colitis, and other localized inflammatory conditions of the colon like microscopic colitis.

To differentiate these things, once you’ve ruled out infection with infectious stool studies, the gold standard is an endoscopy or colonoscopy to directly visualize the mucosa of the ilium and colon to get a sense of the appearance of the endoscopic lesions, and also to do biopsies during that procedure to then get a pathological examination. For both ulcerative colitis and Crohn’s disease, you’re looking for chronicity of inflammation, so chronic inflammatory infiltrates. The pathologist will tell you things that are looking at that crypt distortion of the architecture of the lining of the intestine is disrupted, and there’s chronic inflammatory cells like lymphocytes as opposed to more acute infiltrates. The gold standard in both these cases is to rule out infection and do a colonoscopy, and there’s a lot of adjunctive testing we do that we can talk about later in more detail. Ultimately these patients, when there’s not a clear diagnosis up front in the primary care setting, often wind up with a gastroenterologist to perform a procedure.

Stephen B. Hanauer, MD: From a primary care standpoint, the most common symptoms are going to be diarrhea, bleeding, and abdominal pain. When a primary care clinician is seeing a patient with diarrhea and abdominal pain, the most common diagnosis is going to be something like irritable bowel syndrome. As gastroenterologists, we try to look for red-flag conditions associated with inflammation. These would be bleeding, nocturnal bowel movements, weight loss, or extraintestinal manifestations such as arthritis or skin conditions. Those would be reasons to refer to a gastroenterologist directly to try to make a diagnosis of an inflammatory condition.

Ryan Ungaro, MD: Those are great points, Stephen. One last thing, which can be done very easily in the primary care setting, is when you have a patient with abdominal pain and diarrhea, a test that sometimes is underutilized is a stool calprotectin, which is a stool inflammatory marker. Oftentimes, people send inflammatory markers in the blood like CRP or ESR, but those can be nonspecific and from inflammation anywhere in the body. Doing a simple stool test in the primary care setting for inflammation—particularly fecal calprotectin, if that’s elevated—is telling you that there’s an inflammatory condition somewhere in the intestine most likely going on. That would be someone to refer to a GI [gastrointestinal] doctor sooner rather than later.

Joseph Feuerstein, MD: Thank you, Ryan and Steve. That was a phenomenal explanation. Bruce, is there any use of any biomarkers or noninvasive tests assisting the diagnosis of ulcerative colitis or Crohn’s disease?

Bruce E. Sands, MD: Yes. You’ve already heard about 1, fecal calprotectin, which is a marker of neutrophils. There’s a neutrophilic infiltrate that’s part of the inflammation, especially in colonic disease but also to some degree in small-bowel Crohn’s disease as well. As Ryan said, if there’s an elevation above 55 μg/mg, that would lead you to go down the pathway of trying to evaluate very closely whether the patient has IBD.

You can use CRP and sed rate. These are blood markers. But not everyone will manifest these. About 30% of the population don’t even generate CRP genetically. They don’t produce it, even if they have inflammation. It’s not a very sensitive marker, and sed rate is also not very sensitive. These blood tests are a little better for Crohn’s disease as a biomarker than they are for ulcerative colitis. You tend to not see these elevated, except in very severe presentations of ulcerative colitis. There are other tests that people will consider. Occasionally people will think of sending serologic markers to help establish a diagnosis, but I don’t recommend that. Those do not have adequate sensitivity or specificity to rule in or rule out inflammatory bowel disease. As I said earlier, genetic testing is not going to be useful either to establish a diagnosis.

Transcript edited for clarity.