Clinical FeaturesGastroenterology

Ulcerative colitis (UC) Explained

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) indicated by continuous inflammation of the colon’s mucosal lining, and often accompanied by ulcers and bleeding. The inflammation typically begins in the rectum and extends proximally. Unlike Crohn’s disease, which can affect any part of the gastrointestinal tract, UC is confined to the colon and rectum. While the exact cause remains unknown, UC is thought to arise from an abnormal immune response to intestinal microbiota in genetically predisposed people.

UC is classified based on the extent of inflammation and its location within the colon:

  • Ulcerative Proctitis: Inflammation is confined to the rectum.
  • Proctosigmoiditis: Inflammation involves the rectum and sigmoid colon.
  • Left-Sided Colitis: Inflammation extends from the rectum through the sigmoid and descending colon.
  • Pancolitis: Inflammation affects the entire colon, often leading to severe symptoms such as bloody diarrhea, abdominal cramps, pain, fatigue, and significant weight loss.

Epidemiology/Global prevalence

UC is the most common form of IBD globally, with a higher prevalence in developed countries, such as North America and Western Europe. This lifelong disorder impacts both physical and mental health, and there is no known cure. The most severe form, fulminant ulcerative colitis, is rare but can lead to life-threatening complications.

Clinical Presentation

The clinical manifestations of UC vary according to the severity and location of inflammation. The hallmark symptom is bloody diarrhoea, and is often accompanied by urgency, abdominal pain, and tenesmus. Symptoms range from mild, with intermittent rectal bleeding and minimal systemic involvement, to severe, with frequent bloody stools, intense abdominal pain, fever, and weight loss, and typically develop over time.

Approximately 25% of UC patients experience extraintestinal manifestations (EIMs), which can involve the skin, joints, eyes, and liver.

Etiology

The exact cause of ulcerative colitis remains unknown but encompasses multiple factors including genetics, environmental factors, abnormal immune responses, and microbial interactions. A person who has a first-degree family member with UC is four times more likely to develop it than the general population.

Diagnosis

Diagnosing UC involves excluding other conditions such as Crohn’s disease through blood tests, stool analysis, and imaging studies.

Management and Treatment

Treatment of UC is tailored to the severity and extent of the disease, incorporating both pharmacological and surgical approaches:

  • Aminosalicylates (5-ASA): First-line treatment for mild to moderate UC.
  • Corticosteroids: Used to induce remission in moderate to severe cases but are not suitable for long-term use due to their side effect profile.
  • Immunomodulators: Drugs like azathioprine, 6-mercaptopurine, or methotrexate are used to suppress the immune response and maintain remission.
  • Small Molecule Inhibitors: Janus Kinase (JAK) inhibitors help manage inflammation by targeting specific signalling pathways.
  • Surgery: typically 15-30% of UC patients will require surgery, with proctocolectomy and ileal pouch-anal anastomosis (IPAA) being the main curative procedure. In cases where IPAA is not feasible, a permanent ileostomy may be necessary.
  • Biologics and Biosimilars: recent studies have shown biological agents and their biosimilar equivalents to be effective in treating moderate to severe UC, with TNF inhibitors, integrin inhibitors, and IL-12/23 inhibitors targeting key proteins involved in the inflammatory process. They are particularly promising for patients who do not respond to conventional medical treatment.

Complications

UC, if unmanaged, can lead to several serious complications, including:

  • Anaemia due to significant blood loss
  • Severe dehydration
  • Toxic megacolon
  • Perforated colon
  • Thrombosis
  • Inflammation of the skin, joints, and eyes
  • Increased risk of colon cancer
  • Osteoporosis
  • Primary sclerosing cholangitis, liver scarring due to inflammation
  • Growth inhibition in affected children

Life-long management

Regular monitoring of disease activity and response to treatments is critical in UC management. Screening for complications, such as colorectal cancer, is essential, and patients living severe colitis for 8 to 10 years should undergo surveillance colonoscopy at regular intervals as per guidelines to identify high risk lesions/polyps and remove them in timely manner.

Written by Dr Rahim Khan, Consultant Gastroenterologist and Advanced Endoscopist at Mater Private Network, Dublin
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