Acute severe ulcerative colitis (ASUC) is a medical emergency that occurs in 15–25% of patients with ulcerative colitis. It is associated with significant morbidity, as approximately 15% of patients eventually require colectomy, and it carries a non-negligible mortality rate of around 1%.

Management should be prompt and closely monitored. Upon admission, disease severity is defined according to the Truelove and Witts criteria, which classify ASUC as the presence of six or more daily bowel movements accompanied by systemic toxicity (heart rate >90 bpm, temperature >37.8°C, hemoglobin <10.5 g/dL, erythrocyte sedimentation rate >30 mm/h, or C-reactive protein >3 mg/dL).

In such cases, hospital admission is mandatory, along with laboratory evaluation and an abdominal plain X-ray to exclude toxic megacolon (colonic dilatation >5.5 cm with systemic toxicity). The initial workup should include a complete blood count, inflammatory markers, Clostridioides difficile toxin, multiplex PCR, and stool parasitological examination when risk factors are present, as well as a Quantiferon test if not recently performed. In cases of diagnostic uncertainty, abdominal CT may be required to rule out complications such as perforation.

It is essential to discontinue anticholinergics, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs), as they may worsen the clinical course.

Treatment should begin with high-dose intravenous corticosteroids. Empirical antibiotics are not recommended unless there is suspicion of bacterial superinfection, such as in cases of toxic megacolon. Response to corticosteroids should be assessed on the third day, as approximately 30–40% of patients do not respond to this therapy. The Travis (or Oxford) score is the most widely used predictor of corticosteroid failure — patients with more than eight bowel movements per day, or more than three stools combined with CRP >45 mg/L on day 3, have about an 85% probability of requiring colectomy if treatment is not escalated.

In the absence of response, rescue therapy with infliximab or cyclosporine should be initiated promptly. Both are recommended and have comparable short- and long-term efficacy. Infliximab is associated with a greater reduction in colectomy risk but also carries a higher infection risk. However, overall efficacy remains modest, and the quality of available evidence is limited.

In selected cases, higher-dose infliximab (10 mg/kg) may be used due to unfavorable pharmacokinetics, including hypoalbuminemia and increased fecal drug loss. Alternative strategies include accelerated induction regimens during the first three doses.

Janus kinase (JAK) inhibitors such as tofacitinib or upadacitinib have emerged as promising alternatives. These agents have a rapid onset of action, high potency, no immunogenicity, and are less affected by hypoalbuminemia-related drug loss. A recent multicenter study by Honap et al. demonstrated that these therapies are effective in both the short and long term as rescue therapy for steroid-refractory ASUC.

If there is no response to rescue therapy, a third-line medical approach may be attempted, although it is generally ineffective and only delays colectomy without improving prognosis. Therefore, early surgical intervention should be considered when there is no improvement within 2–3 days.

Authors: Young GEDII

Tiago Leal, Francisco Vara Luiz, Maria José Temido, Raquel Oliveira

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