Severe Acute Ulcerative Colitis (ASUC): The Importance of Multidisciplinary Management

Vol. 31, Special Issue 1 (July 2026)

Fabián Juliao-Baños, MD
Gastroenterology and Digestive Endoscopy
IBD Center of Excellence
Pablo Tobón Uribe Hospital
Medellín, Colombia

Viviana Parra Izquierdo, MD
Gastroenterologist — Rheumatologist
IBD Center of Excellence
International Hospital of Colombia
Cellular and Molecular Immunology Group (InMubo), Universidad El Bosque
Medellín, Colombia

Introduction

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract that primarily involves the rectum and extends proximally through the colon in a continuous pattern. It is thought to result from a dysregulated immune response to intraluminal antigens in genetically susceptible individuals. Clinically, bloody diarrhea is the hallmark symptom, and the disease course is typically characterized by alternating periods of remission and exacerbation.¹ Acute severe ulcerative colitis (ASUC) represents the most severe clinical presentation of UC and is defined by the presence of bloody diarrhea associated with systemic inflammation. Because it is a potentially life-threatening condition, ASUC requires prompt recognition and timely multidisciplinary management in specialized centers.² It has been estimated that approximately 25% of patients with UC will experience at least one severe flare requiring hospitalization during their lifetime, and nearly 20% of these cases may occur at the time of diagnosis. The risk of colectomy during the first hospitalization is around 20%, increasing to as much as 40% after recurrent hospitalizations.³ Furthermore, a systematic review reported mortality rates of 0.84% and 1.01% at 3 and 12 months of follow-up, respectively, with mortality increasing significantly with advancing age and the presence of comorbidities.⁴

Definition

The latest version of the European Crohn’s and Colitis Organization (ECCO) guidelines⁵ has adopted the Truelove & Witts classification,⁵ proposed more than 60 years ago, to define ASUC.⁶ This includes the presence of more than 6 bloody bowel movements per day, plus at least one of the following criteria: tachycardia (heart rate greater than 90 beats per minute), fever (temperature greater than 37.5 °C), hemoglobin less than 10.5 g/dL, and erythrocyte sedimentation rate (ESR) greater than 30 mm/h. A new classification proposed by the American College of Gastroenterology (ACG) proposes the term fulminant colitis, and in addition to the previous criteria, adds the following severity criteria: presence of continuous fecal urgency, fecal calprotectin levels > 150-200 mcg/g, endoscopic Mayo index of 3 and a wall thickening > 3 mm, along with submucosal edema and hyperperfusion on intestinal ultrasound (IUS).⁷

Initial Evaluation and Management

The initial evaluation and support of these individuals require management by a multidisciplinary team that includes a gastroenterologist, colorectal surgeon, nutritionist, nurse, and the support of an emergency physician, general surgeon, internist, and intensivist, according to the patient’s needs arising from their clinical condition. The goal of treatment in acute colitis is to achieve a clinical response, defined as a decrease (< 3) or normalization of the number of daily bowel movements, without visible bleeding. These criteria must be met when deciding on outpatient management, according to expert opinion.⁸

Upon admission, many patients are present with dehydration and hypokalemia due to their diarrhea, thus requiring adequate support with intravenous fluids and potassium supplementation. The oral route appears to be appropriate for nutrition, unless the patient presents with toxic megacolon or paralytic ileus. Parenteral nutrition has not been shown to be superior to enteral nutrition in these patients. Infectious causes of colitis must be ruled out. Avoid the use of medications that decrease colonic motility in patients at risk of toxic megacolon, including opioid derivatives, antidiarrheals, and anticholinergics, as well as nonsteroidal anti-inflammatory drugs (NSAIDs) due to the risk of exacerbation. A plain abdominal radiograph is part of the initial evaluation to rule out the presence of ileus, colonic dilation, or perforation. In cases of suspected abdominal sepsis or doubt regarding colonic perforation, an abdominal CT scan should be performed.⁹

Furthermore, a flexible rectosigmoidoscopy (RSC) without bowel preparation should be performed within the first 24–72 hours of admission, with minimal insufflation and biopsy sampling, to establish endoscopic severity, rule out the presence of pseudomembranes associated with Clostridioides difficile infection, and obtain biopsies to exclude cytomegalovirus (CMV) infection, especially in patients with pre-existing immunosuppression, according to ECCO recommendations.¹⁰ A recent retrospective study demonstrated that performing flexible RSC with biopsies within the first 72 hours of hospitalization results in a lower rate of colectomy (17% vs. 28%), fewer days of hospitalization, and less use of rescue therapy.¹¹

The routine use of antibiotics in the absence of an infectious focus in patients with ASUC is controversial. A recent meta-analysis of 13 studies and 785 patients showed that they are not effective in inducing a clinical response (OR: 0.94, 95% Confidence Interval CI: 0.51–1.74).¹² Given that ASUC is a hypercoagulable inflammatory state, thromboprophylaxis is recommended in hospitalized patients with ASUC. The presence of rectal bleeding is not a contraindication, and some suggest continuing thromboprophylaxis on an outpatient basis for up to 8–12 weeks, the duration of the hypercoagulable state.^{9, 13}

Initial Treatment

For over 50 years, Truelove & Jewell have changed the natural history of patients with ASUC with the use of intravenous (IV) steroids.¹⁴ The current recommended dose is 100 mg of hydrocortisone every six hours or 60 mg of methylprednisolone daily. A review of 32 randomized controlled trials (RCTs) and cohort studies, conducted between 1974 and 2006 in patients requiring IV steroids, found an overall response rate of 67%, with a colectomy rate of 27% and a mortality rate of 1%.¹⁵ One RCT demonstrated that patients with ASUC do not require continued mesalazine during hospitalization; there is no difference in clinical response to IV steroids with or without 5-ASA at seven days of follow-up.¹⁶

Risk Stratification

Several composite indices exist that allow the identification of patients with ASUC who may require “rescue” therapy after IV steroid use. One index, called the ACE score, is applied upon patient admission and includes CRP ≥50 mg/L, albumin ≤30 g/L, and a severe Mayo endoscopic index of 3, predicting a 78% steroid failure rate.¹⁷ A more recent index, called the ADMIT-ASC score, is also applied upon admission and assigns a score, including CRP ≥100 mg/L = 1 point, albumin ≤25 g/L = 1 point, UCEIS ≥4 = 1 point, and UCEIS ≥7 = 2 points; a score ≥3 predicts an 84% steroid failure rate.¹⁸ A study from Oxford (UK) found that having more than 8 bowel movements per day on day 3, or the combination of 3–8 bowel movements per day with a CRP greater than 45 mg/L, is associated with an 85% risk of steroid failure. This is known as the Oxford or Travis index.¹⁹

Rescue Therapy

Historically, patients with ASUC who did not respond to IV steroids ended up undergoing colectomy. The first drug used as rescue therapy after steroid failure was cyclosporine (Cys), an immunosuppressant macrolide that inhibits the activation of interleukin-2 (IL-2) by activated T lymphocytes through a calcineurin-dependent pathway. The first randomized controlled trial (RCT) with Cys was conducted by Lichtiger et al. in 20 patients with ASUC who had not responded to hydrocortisone for 7 days. Cys was used at a dose of 4 mg/kg/day, achieving a clinical response rate of 82% vs. 0% with placebo (P < 0.001), with a colectomy rate at 2 weeks of follow-up of 18% vs. 44%, compared with placebo (RR: 0.6, 95% CI: 0.18–2.06).20 Since then, Cys has been used in patients with ASUC at a dose of 2 mg/kg/day.

Infliximab (IFX), an anti-tumor necrosis factor alpha (anti-TNF α) agent, has been used for individuals with ASUC for several years. The first RCT with IFX was conducted in centers in Sweden and Denmark, using a single dose of 5 mg/kg as “rescue” therapy in 45 patients (24 IFX, 21 placebo) refractory to IV steroid treatment. It found a 3-month colectomy rate of 29% with IFX and 67% with placebo (P: 0.017; OR: 4.9; 95% CI: 1.4–17.0).²¹

It has been documented that individuals with ASUC have high circulating and tissue levels of tumor necrosis factor (TNF), which acts as a “sponge” that rapidly absorbs standard doses of anti-TNFs. Furthermore, it has been established that mononuclear cells of the reticuloendothelial system phagocytize and proteolytically degrade the complex formed by the anti-TNF-α drug with TNF. Finally, increased mucosal permeability associated with severe inflammation may act as a “sieve,” allowing fecal loss of anti-TNF.²²

Additionally, in an Italian multicenter study, multivariate analysis demonstrated that CRP levels ≥ 3 mg/dL (RR = 2.15, 95% CI 1.05–4.36, p = 0.003) and the presence of severe endoscopic lesions (RR = 5.13, 95% CI 1.55–16.96, p = 0.007) at the time of the acute attack were associated with a higher risk of colectomy.23 For all the above reasons, some authors suggest that patients with ASUC and CRP ≥ 3 mg/dL, serum albumin < 30 g/L, and severe endoscopic lesions (deep ulcers and spontaneous bleeding) require individualized management with a higher initial dose of IFX.²⁴ However, a recent RCT from
Australia (PREDICT-UC) compared IFX 5 mg/kg vs. 10 mg/kg in subjects with ASUC refractory to IV steroids and found no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs. 56 [61%] of 92, p=0.62).²⁵

The choice between IFX and Cys as “rescue” therapy in ASUC has been highly controversial. A recent systematic review (SR) with 18 RCTs and 26 cohort studies suggests that IFX is superior to Cys in reducing the risk of colectomy at 3 months (RR, 0.67; 95% CI, 0.48–0.92) and 12 months of follow-up (RR, 0.56; 95% CI, 0.42–0.75).²⁶

On the other hand, recent studies in hospitalized patients with ASUC already exposed to anti-TNFs have demonstrated the efficacy of Janus kinase inhibitors (anti-JAKs), such as tofacitinib at a dose of 10 mg every 8 hours orally and upadacitinib at a dose of 45 mg daily or 30 mg every 12 hours. A recent systematic review with 35 studies and 664 individuals, in the short term (<1 month), showed that the pooled clinical response and colectomy rate with tofacitinib was 77.9% (95% CI, 67.1%-86%) and 11.5% (95% CI, 7.1%-18.4%), whereas for upadacitinib, it was 86.5% (95% CI, 72.3%-94.1%) and 11.2% (95% CI, 7.2%-16.9%), respectively. The adverse events reported were venous thromboembolism (2.2%; 95% CI, 1.1%–4.7%), major adverse cardiovascular events (0.7%; 95% CI, 0.1%–10.3%), and herpes zoster (3.4%; 95% CI, 1.9%–6.1%).²⁷

An Indian RCT (TACOS) compared patients with ASUC, all receiving IV hydrocortisone, to a group that also received tofacitinib at a dose of 10 mg every 8 hours from day 1 and compared them to placebo. At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs. 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% CI 1.37–8.48, P 0.007).²⁸

Sequential therapy with cyclosporine induction followed by vedolizumab maintenance has emerged as a valuable rescue strategy in ASUC, particularly in patients with steroid-refractory disease who have failed or are not candidates for anti-TNF therapy. The rationale for this approach lies in the rapid onset of action of cyclosporine, which can induce short-term clinical response within days, thereby serving as a bridge to vedolizumab, a gut-selective biologic with a slower onset but favorable efficacy and safety for long-term maintenance. Available evidence suggests that this strategy can achieve high rates of remission while reducing colectomy risk and maintaining an acceptable safety profile. The most relevant prospective study supporting this approach showed that, among steroid-refractory ASUC patients treated with cyclosporine followed by vedolizumab, most patients achieved initial response, with sustained clinical, endoscopic, and even histologic remission during followup, as well as a high colectomy-free survival rate at 1 year, without serious adverse events.²⁹

In a recent review, only three studies, including a total of 13 patients (the largest study included 10 patients), were found to report the efficacy of ustekinumab (an IL-12 and IL-23 p40 subunit antagonist) in ASUC. All three studies were retrospective and used sequential treatment in all patients, starting with a calcineurin inhibitor for induction (cyclosporine or tacrolimus), followed by ustekinumab as maintenance therapy. With this sequential treatment strategy, colectomy was avoided in all patients. Furthermore, the rate of serious adverse events and the mortality rate attributable to ustekinumab were 0%.³⁰

Surgical Treatment

Although medical treatment is the first-line approach for managing patients with ASUC, there is a risk of colectomy, and a gastroenterologist or colorectal surgeon should be involved in the patient’s management from the time of admission. Indications for urgent colectomy include perforation, toxic megacolon, massive bleeding, and lack of response to medical treatment.⁵ An Oxford study of 80 patients with refractory colitis who underwent colectomy demonstrated that those who experienced more complications had a longer duration of medical treatment prior to surgery (8 vs. 5 days, P = 0.036).³¹ Additionally, a recent systematic review and meta-analysis, including 67,075 patients with colitis, found that postoperative mortality is lower in subjects undergoing elective surgery (0.7%, 95% CI 0.6%–0.9%) versus emergent surgery (5.3%, 95% CI: 3.8%–7.4%).32 Therefore, surgery should ideally always be semi-elective. A flowchart of the management of patients with ASUC is shown in Figure 1.

Figure 1.

Conclusion

In summary, ASUC remains a life-threatening condition that demands rapid recognition, close monitoring, and coordinated multidisciplinary care in specialized centers. Although intravenous corticosteroids remain the cornerstone of initial treatment, early risk stratification is essential to identify patients unlikely to respond and to expedite rescue therapy. Advances in medical management, including the preferential use of infliximab in selected cases and the emerging role of JAK inhibitors, have expanded the therapeutic options available for this challenging condition. Nevertheless, surgery remains a fundamental component of care, and early colorectal surgical consultation is crucial to optimize outcomes and avoid delays in intervention. Ultimately, successful management of ASUC depends on an evidence-based strategy that balances aggressive medical therapy with timely colectomy when indicated, always adhering to the principle

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