Meds & Biologics
Getting a diagnosis of ulcerative colitis (UC) can feel like a long and confusing process. There is no single blood draw or quick scan that gives a definitive answer. Instead, your gastroenterologist pieces together evidence from multiple tests, each revealing a different layer of information about what is happening inside your colon. Understanding what each test measures and what the results actually mean puts you in a stronger position to have productive conversations with your care team. This guide walks through every major test used in the UC diagnostic workup and the ongoing monitoring that follows, explaining the practical meaning behind the numbers.
Blood Tests: CRP, ESR, and CBC
Blood tests are often the first step in evaluating suspected ulcerative colitis, though no single blood test can confirm the diagnosis on its own. Your doctor will typically order a complete blood count (CBC) and inflammatory markers to get a baseline picture of systemic inflammation and overall health.
C-reactive protein (CRP) is produced by the liver in response to inflammation anywhere in the body. In ulcerative colitis, CRP levels can rise during a flare, with values above 10 mg/L generally suggesting active inflammation. However, CRP correlates less reliably with disease activity in UC than in Crohn's disease because UC inflammation is confined to the mucosal surface rather than penetrating the full bowel wall. Some patients have active mucosal disease with a normal CRP, so a reassuring number does not always tell the full story.
Erythrocyte sedimentation rate (ESR) measures how quickly red blood cells settle in a test tube, with faster rates indicating more inflammation. ESR tends to change more slowly than CRP, making it better suited for tracking trends over weeks rather than capturing acute shifts. Your CBC may also reveal iron-deficiency anemia from chronic blood loss in the stool, low albumin levels suggesting poor nutritional absorption, or elevated platelet and white blood cell counts pointing toward an active inflammatory response.
Stool Tests: Fecal Calprotectin and Infection Screening
While blood tests reflect systemic inflammation, stool tests offer a more direct window into what is happening in the gut. The most important stool biomarker in ulcerative colitis is fecal calprotectin, a protein released by white blood cells when they migrate to the intestinal lining in response to inflammation. Because calprotectin is produced locally in the gut, it is far more specific to intestinal inflammation than CRP or ESR.
The American Gastroenterological Association uses a fecal calprotectin threshold of 150 micrograms per gram to help guide clinical decisions. In practical terms, results below 150 suggest that active mucosal inflammation is unlikely, values between 150 and 250 fall into a gray zone that may warrant repeat testing in a few weeks, and results above 250 strongly suggest significant intestinal inflammation. Your GI will also order stool cultures and a Clostridioides difficile toxin test before making a UC diagnosis, because bacterial infections can mimic UC symptoms almost exactly and must be ruled out first.
Colonoscopy and Sigmoidoscopy: Seeing the Inflammation
A colonoscopy with biopsy remains the gold standard for confirming an ulcerative colitis diagnosis. During this procedure, your gastroenterologist advances a flexible camera through the entire colon, examining the mucosal surface for characteristic patterns of inflammation: redness, loss of the normal vascular pattern, erosions, ulceration, and spontaneous bleeding. UC almost always begins in the rectum and extends continuously upward, which helps distinguish it from Crohn's disease, where inflammation can appear in patches throughout the digestive tract.
The severity of what your doctor sees during colonoscopy is often graded using the Mayo Endoscopic Score, which ranges from 0 to 3. A score of 0 means normal-appearing mucosa. A score of 1 indicates mild inflammation with some redness and reduced vascular pattern. A score of 2 shows more pronounced changes with absent vascular patterns and visible erosions. A score of 3 represents severe disease with deep ulceration and spontaneous bleeding.
A flexible sigmoidoscopy examines only the rectum and lower colon and is sometimes used for quicker assessments when full sedation or bowel preparation is not practical. Because UC always involves the rectum, a sigmoidoscopy can often provide useful diagnostic information, though a full colonoscopy is preferred at initial diagnosis to determine how far the disease extends.
Biopsy Results: What the Pathologist Looks For
During colonoscopy, your doctor takes small tissue samples from both inflamed and normal-appearing areas. These biopsies are sent to a pathologist who examines them under a microscope for hallmark features of chronic UC, and this microscopic evaluation is what truly confirms the diagnosis.
The pathologist looks for crypt architectural distortion, meaning the tiny glands lining the colon have become irregular, branched, or shortened rather than maintaining their normal parallel arrangement. Basal plasmacytosis, an accumulation of a specific type of immune cell at the base of the mucosa, is another strong indicator of chronic inflammatory bowel disease. Other findings include crypt abscesses where neutrophils collect inside gland lumens, goblet cell depletion, and Paneth cell metaplasia. According to research published in the Journal of Crohn's and Colitis, crypt distortion is present in 57 to 100 percent of UC cases and becomes more pronounced with longer disease duration. If your biopsy report mentions these terms, they are describing the microscopic fingerprint that distinguishes UC from other causes of colitis.
Ongoing Monitoring: How Your GI Tracks Disease Activity
Diagnosis is only the beginning. After treatment starts, many of the same tests become monitoring tools that help your gastroenterologist evaluate whether your therapy is working and whether you are reaching the goal of mucosal healing. The AGA biomarker guidelines recommend a combined strategy using symptoms plus objective biomarkers rather than relying on symptoms alone, because some patients feel well even when low-level inflammation persists.
In practice, this often means checking fecal calprotectin and CRP every few months, with the target of keeping calprotectin below 150 and CRP within the normal range. When biomarkers remain elevated despite symptom improvement, your doctor may recommend a follow-up colonoscopy to directly visualize the mucosa and confirm whether mucosal healing has been achieved. An endoscopic Mayo score of 0 or 1 is generally considered the treatment target. Over time, tracking the relationship between your lab values and your daily experience of symptoms reveals patterns that help both you and your care team make informed decisions about medication adjustments, the timing of follow-up procedures, and long-term disease management.
Track your lab results alongside your daily symptoms in Aidy. Seeing how your calprotectin, CRP, and symptom scores correlate over time gives both you and your GI a clearer picture of your disease activity.