Describe the clinical features and management of ulcerative colitis.

Clinical Features of Ulcerative Colitis

Ulcerative colitis presents with a range of symptoms, varying in severity and extent of disease involvement. These can be broadly categorized into gastrointestinal and extraintestinal manifestations.

1. Gastrointestinal Manifestations

The primary symptoms are related to inflammation of the colon and rectum:

• Bloody Diarrhea: This is the hallmark symptom, often with mucus. The frequency can range from a few episodes per day in mild cases to more than ten in severe disease.
• Abdominal Pain and Cramping: Discomfort and cramping are common, particularly in the lower left abdomen. The severity can vary from mild to intense, often accompanying bowel movements.
• Tenesmus: A persistent feeling of needing to pass stools, even when the bowels are empty, often associated with straining and pain.
• Urgency to Defecate: A sudden and strong need to have a bowel movement.
• Rectal Bleeding: Varying in severity, from streaks of blood to significant blood loss.
• Weight Loss and Anorexia: Common during disease flares due to decreased appetite and malabsorption.
• Nausea and Vomiting: May occur, particularly in more severe cases.
• Fatigue and Malaise: Generalized tiredness and a feeling of discomfort are frequent.
• Fever: Often indicates moderate to severe disease activity or complications.

2. Extraintestinal Manifestations (EIMs)

Approximately 10-30% of UC patients experience symptoms outside the gastrointestinal tract. These can affect various organ systems:

• Joints: Arthritis, including peripheral arthritis (affecting large joints like knees, ankles) and sacroiliitis (inflammation of the sacroiliac joints).
• Skin: Erythema nodosum (tender, red nodules) and pyoderma gangrenosum (painful skin ulcers).
• Eyes: Uveitis/iritis (inflammation of the eye) and episcleritis.
• Liver and Bile Ducts: Primary sclerosing cholangitis (PSC) is strongly associated with UC, leading to inflammation and scarring of the bile ducts.
• Anemia: Often due to chronic blood loss from the inflamed colon and iron deficiency.
• Osteoporosis: Increased risk due to chronic inflammation, malabsorption, and long-term steroid use.

3. Severity Grading

The severity of ulcerative colitis is typically graded based on clinical symptoms and objective measures:

Severity	Clinical Features
Mild	Fewer than four bowel movements per day, with or without blood. No systemic signs of toxicity (e.g., fever, tachycardia).
Moderate	Four or more bowel movements per day, with or without blood. Minimal systemic signs of toxicity.
Severe	Six or more bloody bowel movements per day, accompanied by systemic toxicity (fever >37.8°C, tachycardia >90 bpm, anemia, ESR >30 mm/h). Hypoalbuminemia may also be present.
Fulminant	Eight or more bloody bowel movements per day, with severe systemic toxicity, rapid deterioration, and complications like toxic megacolon. Requires immediate hospitalization.

Management of Ulcerative Colitis

The management of ulcerative colitis is multifaceted, aiming to induce and maintain remission, improve quality of life, and prevent complications. It involves pharmacological therapy, dietary adjustments, and sometimes surgical intervention.

1. Pharmacological Management

The choice of medication depends on the disease's severity, extent, and response to previous treatments.

a. Induction of Remission (for active disease)

• 5-Aminosalicylates (5-ASAs): These are often first-line therapy for mild to moderate UC, especially proctitis or left-sided colitis. They reduce inflammation in the bowel. Examples include mesalazine (oral or topical via suppositories/enemas) and sulfasalazine. Topical 5-ASAs are particularly effective for rectal inflammation.
• Corticosteroids: Used for moderate to severe flares to rapidly reduce inflammation. They are highly effective for inducing remission but are not suitable for long-term maintenance due to significant side effects. Oral prednisolone or intravenous methylprednisolone are common. Budesonide is a corticosteroid with less systemic absorption, often used for milder cases.
• Immunomodulators: Thiopurines like azathioprine and 6-mercaptopurine are used for patients who don't respond to 5-ASAs or corticosteroids, or to reduce steroid dependence. They work by suppressing the immune system.
• Biologic Agents: For moderate to severe UC refractory to conventional therapies, biologics target specific inflammatory pathways.
  • Anti-TNF agents: Infliximab, adalimumab, and golimumab block tumor necrosis factor-alpha (TNF-α).
  • Anti-integrin agents: Vedolizumab prevents immune cells from migrating into the inflamed gut.
  • Interleukin-12/23 (IL-12/23) inhibitors: Ustekinumab targets these interleukins involved in inflammation. Mirikizumab, an IL-23p19 antagonist, is a newer option.
• Janus Kinase (JAK) Inhibitors: Small molecules like tofacitinib, which inhibit specific JAK enzymes involved in immune signaling, are approved for moderate to severe UC. Newer S1P receptor modulators like ozanimod and etrasimod are also available.

b. Maintenance of Remission (to prevent flares)

• 5-ASAs: Oral 5-ASAs are often continued long-term to maintain remission in mild to moderate UC.
• Immunomodulators: Azathioprine and 6-mercaptopurine are commonly used for long-term maintenance, particularly in steroid-dependent or refractory cases.
• Biologic Agents and JAK Inhibitors: Patients who achieved remission with biologics or JAK inhibitors often continue these therapies to sustain remission, as they are effective in reducing flare frequency.

2. Dietary and Nutritional Management

While diet does not cause UC, certain foods can aggravate symptoms during flares.

• Identification of Trigger Foods: Patients are encouraged to identify and avoid foods that worsen their symptoms (e.g., high-fiber foods, dairy if lactose intolerant, spicy foods).
• Nutritional Support: Ensuring adequate nutrition is vital, as UC can lead to malabsorption and increased energy needs. Supplements (iron, vitamins) may be required to address deficiencies.
• Probiotics: Some studies suggest a potential role for probiotics in maintaining remission, though more research is needed.

3. Surgical Management

Surgery is considered for patients with severe, refractory disease, or those who develop complications.

• Indications: Failure of medical therapy, toxic megacolon, perforation, severe dysplasia or colon cancer, uncontrolled bleeding.
• Procedures: The most common surgery is a total proctocolectomy (removal of the entire colon and rectum), often with ileal pouch-anal anastomosis (IPAA), which creates an internal pouch from the small intestine to store stool, allowing for normal defecation. Alternatively, a permanent ileostomy may be formed.

4. Recent Advancements and Future Directions

Recent years have seen a significant expansion in therapeutic options for UC, particularly for moderate to severe cases. Novel classes of drugs, such as IL-23p19 antagonists (e.g., mirikizumab, guselkumab) and S1P receptor modulators (e.g., ozanimod, etrasimod), have been approved, offering more targeted approaches to inflammation. Research also focuses on gut microbiota manipulation, enhancing mucosal barrier function, and exploring anti-inflammatory molecules like curcumin. The goal is to achieve not just clinical remission but also endoscopic and histological healing, improving long-term outcomes and reducing the risk of complications like colon cancer.

5. Multidisciplinary Approach

Effective management of UC often requires a multidisciplinary team, including gastroenterologists, colorectal surgeons, dietitians, nurses, and mental health professionals, to address the complex medical, nutritional, and psychological aspects of the disease. Regular monitoring with colonoscopy and fecal calprotectin levels is crucial for assessing disease activity and therapeutic response.