Ulcerative Colitis

Inflammatory bowel disease can be split into two categories – Crohn’s disease which affects any part of the gastrointestinal (GI) tract from the mouth to the anus, and Ulcerative Colitis which exclusively affects the colon. In this article, we will discuss Ulcerative colitis (UC).

Risk Factors

• Family history
• Ashkenazi Jewish ancestry
   

Smoking has been shown to be protective (but that does not mean patients should be encouraged to smoke considering the complications related to tobacco smoking!)

Pathophysiology

The understanding of the pathophysiology for ulcerative colitis is poorly understood, complex and multifactorial. Current theories suggest a combination of the following factors:

• Defective epithelial barrier
• Dysregulated immune response
• Genetic susceptibility

Defective Epithelial Barrier

A mucin layer physically separates intestinal epithelium from the bowel lumen which means luminal microbes such as those from commensal organisms are kept away from immune cells in the mucosa. In ulcerative colitis, a deficiency and disruption of this mucin barrier has been seen, which leads to increased uptake of antigens by the epithelium and immune responses against these normal commensal bacteria that form part of the gut flora. Dendritic cells in particular have been implicated as patients with UC have been found to have higher numbers of activated dendritic cells. Additionally, it has been found that patients with UC tend to have disrupted tight junctions between epithelial cells which further increases the permeability of the epithelial barrier which allows more antigens to be picked up by immune cells.

Dysregulated Immune Response

Patients with UC have been found to have a disturbed balance of T-regulatory and T-effector cells. In particular, natural killer cells have been found to produce interleukins 5 and 13 which activate an exaggerated immune response from Th2 cells leading to apoptosis of intestinal epithelial cells. Additionally, there is increased recruitment of leucocytes by means of upregulating chemoattractants such as CXCL8.

Genetic Susceptibility

Several genetic loci have been identified which increase the risk of susceptibility to UC. One example includes laminin-beta1 which is involved in the proteins that aid epithelial cell adhesion.[ii]

Clinical Features

Most frequently patients will complain of diarrhoea with blood and mucus which may be accompanied by abdominal pain. Inflammation in ulcerative colitis always begins at the rectum and may move proximally to involve other parts of the large bowel. Inflammation of the rectum (proctitis) can present with its own symptoms including tenesmus, which is the sensation that one needs to open their bowels but little/no stool is actually passed, and urgency.

Constitutional symptoms such as low-grade fever, malaise, fatigue and weight loss can also be present.

Extra-Intestinal Features

Extra-intestinal features may be present and are similar to that seen in Crohn’s i.e.

• Mouth: Oral aphthous ulcers
• Eyes: Uveitis and episcleritis
• Skin:
  • Pyoderma gangrenosum: Large ulcerations of the skin which may have pus. Usually on the legs though they can be elsewhere.
  • Erythema nodosum: Inflammation of subcutaneous tissue manifesting as tender, red nodules, usually on the shins.
• Hepatobiliary: Associated with primary sclerosing cholangitis (PSC)
• Renal: Kidney stones (calcium oxalate)
• Musculoskeletal: Spondyloarthropathy associated with Crohn’s disease

Image showing pyoderma gangrenosum

Crohnie, Public domain, via Wikimedia Commons

Investigations

Bloods

• Full blood count: Check for anaemia and raised white cells
• ESR and CRP: Can be raised
• pANCA: May be positive in patients with UC (different to Crohn’s where usually negative)[iii]
• Urea and electrolytes: Routine, particularly since patients have diarrhoea
• Liver function test: Due to associated PSC + looking for low albumin (low albumin may increase the likelihood of requiring surgery)

Stool

• Microscopy, culture and sensitivities: Check for campylobacter, shigella, E.coli etc
• C.difficile toxin assay: Rule out as patient has diarrhoea
• Faecal calprotectin: Marker of bowel inflammation

Imaging

• Abdominal X-ray: Toxic megacolon is a complication so rule this out

Colonoscopy

Colonoscopy + biopsy is the gold-standard for diagnosis. In an acute setting, a full colonoscopy is not performed as inflammation of the bowel can make it more vulnerable to perforation. To reduce this risk, a flexible sigmoidoscopy can be performed instead.

Only the colon will be involved in UC. Inflammation may be limited to the rectum (proctitis), the left side of the colon (left sided colitis) or the entire colon (pancolitis). On endoscopy, the mucosa may be friable with superficial ulceration. Other possible findings include hyperaemia, pseudopolyps, granulation tissue and bleeding.[iv]

Histopathology

The features of ulcerative colitis on histology are different to that of Crohn’s disease. Firstly, inflammation is superficial and usually does not extend past the submucosa. Crypt abscesses are usually present (inflammatory cells present in the lumen of intestinal glands) and loss of goblet cells. Lesions are also continuous rather than the skip lesions seen in Crohn’s disease.

Classification

Severity classification is important as it can help inform how the patient should be managed. One method of classification includes the Truelove and Witt’s classification (others exist).

• Mild: <4 stools per day, no/little blood, ESR <30
• Moderate: 4-6 stools per day, some blood, ESR <30
• Severe: >6 stools per day, a lot of blood, ESR >30, pyrexia, tachycardia and anaemia[v]

4 and 6 are the two numbers you need to remember for ulcerative colitis. Less than 4 stools and little blood is mild, 6 stools or more with a lot of blood is severe, and anything in between can be considered moderate.

Management

Inducing Remission

5-Aminosalicylic Acid (5-ASA) is the mainstay of treatment in ulcerative colitis – an example of this class of drugs includes mesalazine.
 

1. Proctitis:
   1. First-line: Topical (rectal) 5-ASA
   2. No remission in 4 weeks: Add oral 5-ASA
   3. If 5-ASA is contraindicated or not tolerated, or it is not inducing remission, an oral or topical corticosteroid can be used instead.
       
2. Proctosigmoiditis/Left Sided Colitis:
   1. First-line: Topical (rectal) 5-ASA
   2. No remission in 4 weeks: Add oral 5-ASA. Alternatively, you can switch to oral aminosalicylate + topical steroid.
   3. If 5-ASA is contraindicated or not tolerated, a corticosteroid can be used instead.
       
3. Extensive Disease:
   1. Topical and oral 5-ASA.
   2. No remission in 4 weeks: Stop topical 5-ASA and use oral 5-ASA + oral corticosteroid.[vi]

Managing Severe Ulcerative Colitis (i.e. >6 motions of bloody stool a day)

• Admit to hospital
• IV hydrocortisone (or IV ciclosporin if hydrocortisone is contraindicated)
• IV fluids and electrolyte replacement may be needed
• Low-molecular weight heparin for thromboembolism prophylaxis

If a patient responds to IV steroids, they can be switched to oral steroids e.g. prednisolone.

However, if they are not responding to IV steroids after 72 hours, the addition of an IV ciclosporin alongside the IV steroid can be considered (or infliximab if ciclosporin is contraindicated).

Maintaining Remission

1. Proctitis and Proctosigmoiditis: Topical 5-ASA/Oral 5-ASA/ Topical and oral 5-ASA
2. Left sided colitis/extensive disease: Oral 5-ASA at a lower maintenance dose

If remission isn’t being maintained with 5-ASA, you can consider the use of azathioprine or mercaptopurine.

Surgery

Patients with UC may require surgery either due to an acute attack leading to complications such as toxic megacolon/impending perforation or due to chronic disease which has been unresponsive to medical treatment.

Acute attacks requiring surgery are usually treated with a subtotal colectomy with an end ileostomy (subtotal as the rectum is preserved). The ileostomy may be permanent in which case the patient will undergo a completion proctectomy (to remove the rectum) at a later date, or it will be reversible. For the latter, patients undergo an ileo-anal anastomosis (J-pouch) which involves anastomosing the ileum to the anus, thus creating a reservoir for faeces. A subset of patients may experience pouchitis which is inflammation of the pouch and can present with diarrhoea, tenesmus, incontinence, leakage of stool and bleeding.iii

Pouchitis is treated with a 2-week course of either ciprofloxacin or metronidazole.[vii]

Complications

• Toxic megacolon
• Bowel perforation
• Colorectal carcinoma