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Ulcerative Colitis

Patient Monitoring

Assessment of body mass index (BMI) and nutritional status should occur at diagnosis. Monitoring of hemoglobin, iron status, serum folate and serum vitamin D is recommended. Monitoring of micronutrient levels during clinical and biochemical remission should be considered. For children, monitor the height and weight; for adults, monitor the weight. The response to treatment should be evaluated with a combination of clinical parameters, endoscopy, and laboratory markers eg CRP and fecal calprotectin. In patients with a clinical response to medical therapy, mucosal healing should be determined by endoscopy or through fecal calprotectin 3 to 6 months after initiation of treatment. In patients with persistent disease activity, new unexplained symptoms, or severe relapse, and before switching to another therapy, endoscopic reassessment is recommended.

Monitor frequency of relapse (pattern of disease), which is defined during the first 3 years as to: Continuous, if characterized by persistent symptoms without remission; frequent, if characterized by ≥2 relapses/year; and infrequent, if characterized by ≤1 relapse/year.

HOSPITAL MANAGEMENT OF SEVERE ULCERATIVE COLITIS

Monitoring the Patient

Do physical examinations daily to evaluate abdominal tenderness and rebound tenderness. A stool chart should be done to record number and character of bowel movements. A daily abdominal radiography should be performed if colonic dilatation is detected at presentation. An immediate surgical referral is requested if there is evidence of toxic megacolon. An objective re-evaluation should be done on the third day of intensive treatment with consideration of colectomy or treatment with IV Ciclosporin or Infliximab.

Crohn’s Disease

Patient Monitoring

Assessment of BMI and nutritional status should occur at diagnosis. Monitoring of hemoglobin, iron status, serum folate and serum vitamin D is recommended. Monitoring of micronutrient levels during clinical and biochemical remission should be considered. For children, monitor their height and weight; for adults, monitor their weight. Vitamin B12 status should be monitored, especially if there is ileal resection. The clinical and biochemical response to therapy should be evaluated within 12 weeks after treatment initiation. Endoscopic or transmural response (by IUS, MR enterography or SBCE) to therapy should be determined within 6 months after treatment initiation. In patients with persistent disease activity, new unexplained symptoms or relapse, and before switching to another therapy, endoscopic or cross-sectional reassessment may be considered. Extramural complications (eg fistulae and abscesses) should be monitored by cross-sectional imaging (IUS or MRI) together with clinical and laboratory parameters. Evaluation of perianal Crohn’s disease and fistula closure should be done with clinical evaluation in combination with endoscopic examination of the rectum and MRI.

Evaluation of perianal Crohn’s disease and fistula closure should be done with clinical evaluation in combination with endoscopic examination of the rectum and MRI. Therapeutic drug monitoring or evaluation of anti-TNF drug levels and antidrug antibodies should be considered in patients with active Crohn’s disease despite anti-TNF treatment to determine biologic failure. A biologic failure is classified into immune-mediated failure, mechanistic failure or non-immune-mediated drug failure. An immune-mediated drug failure is present when patients have low or undetectable trough concentrations and high titers of antidrug antibodies. The minimal therapeutic target tough levels for Adalimumab are >7.5 mcg/mL, Certolizumab pegol is >20 mcg/mL and Infliximab is >5 mcg/mL. Patients with history of anti-TNF antibodies have a higher risk of developing antidrug antibodies to the next agent within the same class. A combination therapy with immunomodulators such as thiopurines or Methotrexate should be considered in these patients. Mechanistic failure is present when patients with active mucosal ulceration have therapeutic levels but without antibodies. In these patients, a medication with another class and mechanism of action should be considered. A non-immune-mediated failure occurs when patients have subtherapeutic trough concentration and without antidrug antibodies. This is a consequence of a rapid drug clearance in the setting of a high inflammatory burden. This is managed by dose optimization either by dose escalation or shortening the dosing interval.

Monitoring of Clinically Asymptomatic Patients

Monitoring is recommended every 3 to 6 months in inflammatory bowel disease patients with clinical and biochemical remission to detect disease flares. Fecal calprotectin can detect relapses before clinical symptoms. An endoscopic evaluation or cross-sectional imaging is recommended in asymptomatic patients with abnormal biochemical parameters after infection has been ruled-out. The disease activity should be assessed using a combination of clinical and biochemical markers, and endoscopic and/or cross-sectional imaging, before de-escalation or withdrawal of maintenance therapy for inflammatory bowel disease. The evaluation of endoscopic activity in patients with quiescent Crohn’s disease is recommended before discontinuation of therapy. A meta-analysis has shown that discontinuation of immunomodulatory monotherapy after remission was associated with approximately 75% of patients having a relapse within 5 years after discontinuation.

Inflammatory Bowel Disease_Management 17

Monitoring of Clinically Symptomatic Patients

Patients with suspected new flares of inflammatory bowel disease should be investigated for infection, including exclusion of C difficile infection. C difficile infection is associated with poorer outcomes in ulcerative colitis, including increased colectomy rates and increased postoperative complications. Testing for CMV is reserved for steroid-resistant disease. A meta-analysis has shown that CMV infection in inflammatory bowel disease is associated with longer disease duration, reduced efficacy of corticosteroids, and increased colectomy rate. Stool examination for ova cysts and parasites and Strongyloides serology is recommended before therapy is escalated if travel history is suggestive. Ileocolonoscopy is the gold standard for investigating large bowel disease activity of symptomatic Crohn’s disease or ulcerative colitis. This provides direct mucosal visualization of the colon and terminal ileum and allows for histological assessment and therapeutic intervention. Cross-sectional imaging (IUS, MR enterography, and/or SBCE) may be used in patients with symptomatic small bowel disease. It is complementary to phenotype assessment and may be used as an alternative to ileocolonoscopy in assessing large bowel disease activity of symptomatic Crohn’s disease or ulcerative colitis. Flexible sigmoidoscopy should be considered if symptoms suggest an acute severe flare of ulcerative colitis.

A biomarker-based monitoring strategy, which includes monitoring of symptoms and biomarkers of inflammation, is recommended in ulcerative colitis patients with symptomatic remission and patients with symptomatically active ulcerative colitis to determine response to therapy. This has the advantage of giving a more accurate prognosis compared to symptoms alone resulting in optimal treatment determination and decreased risk of disease complications. A biomarker monitoring may be performed every 6 to 12 months in patients with ulcerative colitis in symptomatic remission. Fecal biomarkers (eg fecal calprotectin or fecal lactoferrin) may be used for monitoring especially in patients where biomarkers have been previously correlated with endoscopic disease activity. Studies have shown good correlation between fecal calprotectin and endoscopic disease activity in both Crohn’s disease and ulcerative colitis. Fecal calprotectin >150 μg/g, elevated fecal lactoferrin, or elevated CRP may be used to rule in active inflammation in patients with ulcerative colitis with moderate to severe symptoms suggestive of flares. Treatment adjustment should be done and routine endoscopic assessment of disease activity can be avoided. A fecal calprotectin value of <150 μg/g, normal fecal lactoferrin or normal CRP rules out active inflammation and does not necessitate routine performance of endoscopic assessment of disease activity. Fecal calprotectin cutoff of <50 μg/g may be used to detect endoscopic improvement in patients who achieved symptomatic remission after treatment adjustment in the last 1 to 3 months.

An endoscopic assessment of disease activity is recommended in patients with ulcerative colitis in symptomatic remission with elevated stool or serum markers of inflammation (eg fecal calprotectin >150 μg/g, elevated fecal lactoferrin, elevated CRP). A repeat biomarker measurement may be done within 3 to 6 months as an alternative to endoscopic assessment but endoscopic assessment is recommended in the presence of elevated biomarkers on repeat evaluation. An endoscopic assessment of disease activity is also recommended in patients with ulcerative colitis with mild symptoms with normal stool or serum markers of inflammation (fecal calprotectin <150 μg/g, normal fecal lactoferrin, normal CRP).

Malabsorption parameters should be evaluated at regular intervals in all patients with inflammatory bowel disease. The weight should be taken and recorded at every clinic visit. Patients should be screened for anemia. Patients with symptoms suggestive of active disease should be screened for anemia every 3 months. Vitamin B12 and folic acid measurements should be done every 3-6 months in patients with small bowel disease or previous resection. Measurement of vitamin D is recommended in symptomatic patients and re-evaluation after treatment to check if levels are back to normal.

Monitoring Post-surgery

Ileocolonoscopy is the reference standard for the diagnosis of postoperative recurrence after ileocolonic surgery and is recommended within the first 6 to 12 months after surgery. The postoperative recurrence rate after resection of ileocecal disease has been shown to be approximately 65-90% within 12 months, in the absence of treatment. Fecal calprotectin, IUS, MR enterography, and SBCE may be considered as non-invasive alternatives to evaluate for postoperative recurrence, especially after small bowel resection. Pouch-related symptoms can be assessed with endoscopy with biopsies.

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Monitoring of Acute Complications of Inflammatory Bowel Disease

Strictures

A cross-sectional imaging, preferably MRI or IUS, can be used to detect small bowel strictures. In Crohn’s disease, strictures are transmural and contain variable proportions of inflammation and fibrotic tissue. Colonic stricture should be evaluated to exclude malignancy and surgery should be considered.

Fistulae and Abscesses

Intraabdominal fistulae and abscesses can be detected with cross-sectional imaging. MRI is preferred because it can detect deep-seated fistulae and abscesses or pelvic fistulae. An examination under anesthesia (EUA) with drainage is recommended if perianal abscess is suspected. In perianal Crohn’s disease, endoscopic evaluation of the rectum is necessary to determine the most appropriate management strategy.

Pouch Complications

IPAA complications may be inflammatory and non-inflammatory and include abscesses, fistulae, sinus tracts and strictures. Cross-sectional imaging and endoscopy are complementary methods used to assess suspected structural complications after IPAA. Pouchography can be done to assess functional disorders and other complications.

Emergency Complications

A plain abdominal radiograph is an acceptable first diagnostic modality in acute severe colitis to detect toxic megacolon. Toxic megacolon is defined on plain abdominal X-ray as a transverse colonic dilatation >5.5 cm. CT is recommended when a perforation is suspected in patients with acute abdominal pain and established diagnosis of inflammatory bowel disease.

Postoperative Complications

A computed tomography is recommended to investigate acute postoperative complications such as anastomotic leaks and abscesses. An ultrasound may be used as an alternative but must be followed by immediate CT when results are negative or equivocal.

COLORECTAL CANCER (CRC) SURVEILLANCE

Inflammatory Bowel Disease_Follow Up

Patients with ulcerative colitis and Crohn’s disease have an increased risk of colorectal cancer, but there is much more known data about the risk in ulcerative colitis than in Crohn’s disease. The risk for inflammatory bowel disease is related to both the duration and extent of the disease and to the degree of histologic inflammation over time. Patients with ulcerative colitis who have family history of colorectal cancer have a five-fold risk of developing colorectal cancer. Patients with concomitant primary sclerosing cholangitis have an increased risk of 31% for developing colorectal cancer. Patients with >10 years persistent perianal fistulizing Crohn’s disease is considered to have an increased risk of developing perianal fistulizing CD-associated anorectal and fistula cancers which may be squamous cell cancer of the anus or adenocarcinoma. Assessment for perianal fistulizing CD-associated anorectal and fistula cancers should be considered in patients with progressive or refractory perianal symptoms (eg discharge, pain, stricture, swelling). A surveillance colonoscopy should start 8 to 10 years after diagnosis in patients with ulcerative colitis or Crohn’s disease regardless of extent of disease at the time of diagnosis. A colonoscopic surveillance is best performed when colonic disease is in remission. Pancolonic dye spraying with targeted biopsy of abnormal areas is recommended. Chromoendoscopy with targeted biopsies has been shown to increase the detection rate of dysplasia and is superior to white-light endoscopy. White-light endoscopy may be used but random biopsies (quadrantic biopsies every 10 cm) and targeted biopsies of any visible lesion should be performed. Some modalities used to assess for perianal fistulizing CD-associated anorectal and fistula cancers include MRI of the pelvis and examination under anesthesia with biopsy. A repeat chromoendoscopic colonoscopy with random biopsies is recommended within 3 to 6 months in patients with confirmed low-grade dysplasia in mucosa without an associated endoscopically visible lesion. If a dysplastic polyp is detected within an area of inflammation and can be removed, colectomy is not routinely recommended. Patients who underwent endoscopic resection for polypoid lesions have approximately a 10-fold risk of developing further dysplasia and monitoring with chromoendoscopy is recommended after 1 to 6 months, then yearly thereafter.

Patients with ulcerative colitis and with endoscopically unresectable non-polypoid dysplasia are recommended for immediate colectomy, regardless of the rate of dysplasia detected by biopsy. Patients with Crohn’s disease and visible dysplastic lesions should undergo complete endoscopic excision. Patients with Crohn’s disease with visible dysplasia not amenable to endoscopic excision or is multifocal, or if colorectal cancer is diagnosed, are recommended for total colectomy with IRA or total proctocolectomy. Several major societies have different recommendations on optimal surveillance strategies for colon cancer in patients with inflammatory bowel disease.

Society	Ulcerative Colitis	Crohn’s Disease
American Gastroenterological Association (AGA) 2021	Surveillance colonoscopy is recommended: At the time of diagnosis and then yearly in patients with primary sclerosing cholangitis Every 1 to 5 years after a negative examination based on risk factors for colorectal cancer, with current and prior burden of colonic inflammation, family history of colorectal cancer, primary sclerosing cholangitis, history of colorectal dysplasia and frequency and quality of prior surveillance examinations taken into consideration Annually in patients with moderate to severe inflammation, family history of colorectal cancer in first-degree relative <50 years of age, presence of pseudopolyposis, history of invisible dysplasia or higher-risk visible dysplasia <5 years ago Within 2 to 3 years in patients with mild inflammation, strong family history of colorectal cancer but without first-degree relative <50 years of age, features of prior severe colitis (eg moderate pseudopolyps, extensive mucosal scarring), history of invisible dysplasia or higher-risk visible dysplasia >5 years ago, history of lower risk visible dysplasia <5 years ago Within 5 years in patients with continuous disease remission since the last colonoscopy with mucosal healing on current exam plus either ≥2 consecutive exams without dysplasia or minimal historical colitis extent (ulcerative proctitis or <⅓ of colon in Crohn's disease)	Same guideline for ulcerative colitis also applies to Crohn's disease
American College of Gastroenterology (ACG) 2019	Patients with ulcerative colitis and primary sclerosing cholangitis should undergo a screening colonoscopy at the time of diagnosis of ulcerative colitis and surveillance yearly thereafter Surveillance colonoscopies should be performed at one- to three-year intervals based on the findings of previous colonoscopies and combined risk factors for colorectal cancer (younger age at diagnosis, duration of disease, greater extent of inflammation, first-degree relative with colorectal cancer)	Optimal surveillance interval has not been clearly defined
American Society for Gastrointestinal Endoscopy (ASGE) 2015	Surveillance colonoscopy is recommended: Yearly in patients with primary sclerosing cholangitis, active inflammation or history of dysplasia, anatomic abnormality (stricture, multiple pseudopolyps), or family history of colorectal cancer in a first-degree relative Every 1 to 3 years in patients with average risk Beyond every 3 years in patients with ≥2 surveillance colonoscopies which are endoscopically and histologically normal	Same guideline for ulcerative colitis also applies to Crohn's disease
British Society of Gastroenterology (BSG) 2019	Surveillance colonoscopy is recommended: At the time of primary sclerosing cholangitis diagnosis Yearly in patients with high-risk features (extensive colitis with moderate to severe active endoscopic or histologic inflammation, stricture or dysplasia within the past 5 years without surgery, primary sclerosing cholangitis, or family history of colorectal cancer in a first-degree relative diagnosed at <50 years old) Every 3 years in patients with intermediate-risk features (extensive colitis with mild active endoscopic or histologic inflammation, post-inflammatory polyps, or family history of colorectal cancer in a first-degree relative diagnosed at ≥50 years old) Every 5 years in patients with low-risk features (extensive colitis without active endoscopic or histologic inflammation or left-sided colitis or Crohn's colitis with <50% involvement) Colonoscopy targeted biopsies are recommended over random biopsies; two to four random biopsies every 10 cm is done if taking random biopsy Surveillance flexible sigmoidoscopy of pouch/rectal mucosa every year for postcolectomy patients at high risk; if without risk factors every 5 years	Same guideline for ulcerative colitis also applies to Crohn's disease
European Crohn's and Colitis Organisation (ECCO) 2022	Annual surveillance colonoscopy is recommended in patients with concurrent primary sclerosing cholangitis, irrespective of disease activity, extent and duration Surveillance colonoscopy is recommended: Yearly in patients with high-risk features (stricture or dysplasia detected within the past 5 years, primary sclerosing cholangitis, extensive colitis with severe active inflammation, or family history of colorectal cancer in a first-degree relative diagnosed at ≤50 years old) Every 2 to 3 years in patients with intermediate-risk features (extensive colitis with mild to moderate active inflammation, post-inflammatory polyps, or family history of colorectal cancer in a first-degree relative diagnosed at >50 years old) Every 5 years in patients with low-risk features (without intermediate or high-risk features)	Same guideline for ulcerative colitis also applies to Crohn's disease
National Comprehensive Cancer Network (NCCN) 2023	Surveillance colonoscopy is recommended 8 years after onset of symptoms Initiated at the time of primary sclerosing cholangitis diagnosis and then yearly in patients with primary sclerosing cholangitis independent from time of onset of symptoms Annually in patients with high-risk features (primary sclerosing cholangitis, active inflammation, family history of colorectal cancer diagnosed at <50 years old) Every 2 to 3 years in patients with low-risk features (no endoscopic/histologic active inflammation) High-definition white light endoscopy or dye-spray or high-definition virtual chromoendoscopy with targeted biopsies including samples from strictures or masses may be performed Standard-definition white light endoscopy may be performed but must be in conjunction with chromoendoscopy	Same guideline for ulcerative colitis also applies to Crohn's disease

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