Kim Isaacs, MD, on Treating Acute Severe Ulcerative Colitis

Approximately 15%-25% of patients with ulcerative colitis (UC) will develop acute severe ulcerative colitis (ASUC), Kim Issacs, MD, stated during her presentation at the April 2 Advances in Inflammatory Bowel Diseases (AIBD) Regional Meeting in Raleigh, NC. She further noted that 20% of those patients will undergo colectomy on their first admission, while 40% will have a colectomy after 2 admissions.

Dr Isaacs is the codirector of the Multidisciplinary Center for IBD Research and Treatment and a professor of medicine in the division of gastroenterology and hepatology at University of North Carolina at Chapel Hill.

According to the proposed American College of Gastroenterology (ACG) Ulcerative Colitis Activity Index, a patient with ASUC will present with 6 or more bowel movements per day and at least 1 sign of toxicity.

Dr Isaac presented the case of a 25-year-old male who has had 3 weeks of diarrhea that began nonbloody and then became bloody after 1 week. He was at 10 stools per day but the frequency seems to be slowing down. He also complains of fever, chills, cramps, and vomiting. He has had a history of bloody stools twice that resolved after 3 days. Recently, he has been on a high protein, low-carb diet.

To look at him, Dr Isaacs stated that he seems “very sick” with fulminant colitis according to the ACG index. He had a Mayo Endoscopic Score of 3, and his x-ray reveals a toxic megacolon with labs indicating anemia, low albumin, and elevated inflammatory markers.

Toxic megacolon, Dr Isaacs explained, is a complication of ASUC that presents with radiographic evidence of colonic distension and at least 3 of the following symptoms: a temperature higher than 101.5 degrees Fahrenheit, a heart rate of 120 beats per minute or higher, a leukocyte count of greater than 10,500 with a left shift, or anemia with a hematocrit of less than 60% of normal. Patients with toxic megacolon will also present with at least 1 of the following: dehydration, changes to mental status, electrolyte abnormalities, or hypotension. A number of factors can trigger toxic megacolon, includinghypokalemia, opioids, anticholinergics, loperamide, antidepressants, infection (such as C. difficile or bacterial pathogen), colonoscopy, barium enema, or discontinuation of steroids.

Dr Isaacs cautioned that clinicians should involve the surgeon early when dealing with this complication. Toxic megacolon is considered a surgical emergency because of its high mortality rate. For ASUC, surgical options should be taken into consideration even as medical therapy is being initiated.

Dr Isaacs advised that providers can predict the need for early rescue therapy in the case of ASUC with the following labs: a fecal calprotectin at admission that is greater than 800 mg/g; a C-reactive protein (CRP) of greater than 50; albumin at less than 3; and the presence of high mucosa cytomegalovirus (CMV) DNA.

In an ASUC case with no colonic dilation, the therapy options depend on what medications the patient has already been exposed to, as well as if there are any other factors to consider (such as pregnancy, a significant comorbidity, or any clotting disorders). In any case, the patient should be referred for a surgical consultation early. Dr Isaacs stated that IV steroids can achieve a response by day 3, and other therapies include infliximab, cyclosporine, tofacitinib, and hyperbaric oxygen.

For infliximab, Dr Isaac also pointed out that accelerated dosing (either a shorter induction period or a higher initial dose followed by higher or standard induction doses) may be necessary because of potential for stool loss of infliximab. However, she warned that recent studies have shown mixed results when it came to both short- and long-term outcomes of ASUC treated with accelerated infliximab induction.

Cyclosporine has similar efficacy in ASUC as infliximab, though it has been suggested—mainly based on nonrandomized trials—that infliximab may have more favorable long-term results in avoiding colectomy. There are also concerns about side effects and monitoring with long-term use of cyclosporine. Dr Issacs suggested changing to a thiopurine, vedolizumab, or tofacitinib when transitioning to maintenance therapy, or starting cyclosporine as a combination therapy with ustekinumab, and then transitioning to ustekinumab monotherapy.

Dr Isaac reviewed a retrospective case control study in which tofacitinib showed protection against colectomy at 90 days, for patients who had previously been treated with a biologic therapy. There was also a phase 2A study in which a higher percentage of patients who had been treated with steroid plus hyperbaric oxygen therapy achieved clinical remission at day 5 of the study compared to placebo. However, there was no difference in colectomy rate over time.

Dr Isaac concluded by stressing the importance of a good history to be aware of the therapies the patient has already taken, being aware of all comorbidities and potential therapeutic side effects with ASUC, testing and treating for C. difficile, an early flexible sigmoidoscopy to assess activity and check for CMV, and administering deep vein thrombosis prophylaxis to all patients who are hospitalized for ASUC.

—Allison Casey

Isaacs KL. What’s new in acute severe UC in 2022? Presented at: Advances in Inflammatory Bowel Disease Regional Meeting; April 2, 2022; Raleigh, North Carolina.