Management of Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disease that causes diarrhea, rectal bleeding, and abdominal pain. It is estimated to affect approximately 1.5 million Americans. The peak incidence appears between 30-40 years of age, and some report a second peak seen between 60-70 years of age. Ulcerative colitis is also associated with a number of extra-intestinal manifestations, including inflammatory arthropathies, primary sclerosing cholangitis, skin problems such as erythema nodosum or pyoderma gangrenosum, and eye problems such as episcleritis or uveitis.
Although the exact cause of ulcerative colitis is yet unknown, it is likely that a multitude of factors play a role in its pathogenesis. This includes genetic factors where over 160 gene variants are now identified and associated with inflammatory bowel disease; 23 of these have been noted to be specific to ulcerative colitis and 110 to both ulcerative colitis and Crohn’s disease. At least 10% of ulcerative colitis patients will have some degree of family history of inflammatory bowel disease. There is also some evidence that exposures to certain foods, medications, and other environmental agents can either increase the risk for or be protective of future development of inflammatory bowel disease. Finally, there appears to be a very close-knit interaction between the gut microbiome that is in continuous evolution from birth to adulthood and the immune and non-immune cells of the GI tract lining itself. These careful interactions are likely responsible for subsequent inflammation that may ensue.
Current guidelines for the medical treatment of ulcerative colitis are based upon the extent and clinical severity of the disease. There are a number of disease activity scoring systems to allow for defining disease severity or response to treatment. Classically, the Truelove and Witts’ classification system divides disease severity into mild, moderate, and severe disease, although the Mayo Clinic score has been most commonly used to describe disease activity in clinical trials. This score is based on a clinical description of both stool frequency and rectal bleeding along with an endoscopic score and physician rating of the disease activity.
For treatment of mild to moderate disease, either topical or oral 5-amino salicylate therapy is often utilized. For refractory or moderate to severe disease, steroids often become necessary for induction therapy followed by use of either thiopurine and/or anti-tumor necrosis factor (anti-TNF) therapy for maintenance. Therapeutic drug monitoring with anti-TNF trough levels as well as anti-drug antibodies are now utilized to monitor treatment. There are now three approved anti-TNF biologic therapies (infliximab, adalimumab and golimumab) available for the treatment of ulcerative colitis and one anti-adhesion molecule (vedolizumab) all shown to have efficacy for moderate to severe active colitis. Currently, the ultimate treatment goal is both to address clinical and patient reported outcomes (PRO) for disease remission, as well as endoscopic remission most commonly defined as mucosal healing. The use of other biomarkers such as fecal calprotectin or CRP may also assist as an adjunct to monitoring patient response to treatment.
Patients presenting with severe colitis in the hospitalized setting should be ruled out for superimposed infection with C. difficile and CMV. Generally, first-line treatment involves corticosteroid therapy with very close monitoring to assess response to medical therapy as well as surgical consultation. Consideration for anti-TNF therapy is possible in these cases, though urgent colectomy may be required with lack of improvement within the first 3-5 days of treatment. Any patient who develops worsening symptoms despite treatment will require urgent colectomy to avoid further toxicity or perforation.
Surgery for ulcerative colitis
Indications for surgery include:
Because there is an increased cancer risk associated with ulcerative colitis (estimated to be 2% by 10 years, 8% by 20 years, and 18% by 30 years after diagnosis) close surveillance screening is recommended. The American Gastroenterology Association guidelines for surveillance recommends colonoscopy to begin 8 years from onset of symptoms with the disease, or immediately if there is co-existing primary sclerosing cholangitis. Multiple random biopsies using high-definition white light colonoscopy along with targeted biopsies for any suspicious areas is recommended. Most recently, consensus guidelines suggest the use of chromoendoscopy at experienced centers, to better identify areas of dysplasia. These guidelines support the use of endoscopic excision for endoscopically visible and resectable polypoid type lesions with close follow up thereafter. However, when histology reveals high-grade dysplasia, surgical intervention is recommended due to the high-risk (>40%) of harboring an occult synchronous carcinoma in this setting. More controversial is the management of low-grade dysplasia when it is encountered on biopsy. Though, the reported risk of concomitant cancer is lower, it does occur and strong consideration for surgical intervention in these cases must also be considered.
The current gold standard treatment for ulcerative colitis involves total proctocolectomy with ileal pouch anal anastomosis. Most common ileal pouch constructions involve a J- or S-type configuration with studies demonstrating minimal functional difference between them and usually based on surgeon preference. Several studies have demonstrated excellent long-term pouch function and low rates of ileal pouch failure (between 5% and 10%). Reported stool frequencies remain fairly stable (range 6-8 per day) along with excellent quality of life maintenance. Most centers have evolved toward that of a minimally invasive approach to restorative proctocolectomy, and several laparoscopic series have been published revealing lower rates of complications, shorter hospital stay, and better cosmesis without affecting ileal-pouch function. The decision to perform these surgical procedures in two versus three stages is highly dependent on the current health of the patient and the extent of anti-inflammatory or immunologic medical therapy.
For more information
The Digestive Health Services group at UW Health provides a multidisciplinary approach to the diagnosis and management of complex and chronic disorders of the esophagus, stomach, small intestine, colon, anorectum, liver, pancreas, gallbladder and biliary tree. For questions about a patient or a referral, please contact one of our clinics.