Ulcerative Colitis

Ulcerative colitis (UC) is the most common form of inflammatory bowel disease, the other major type being Crohn’s disease (CD)

It is most prevalent among the Caucasian population, with the age at presentation following a bimodal distribution between 15-25yrs for most cases and a smaller peak of incidence between 55-65yrs. Prevalence in the UK is approximately 0.2%, with males and females affected equally.

The disease typically follows a remitting and relapsing course. A severe fulminant exacerbation may be life-threatening, resulting in severe systemic upset, toxic megacolon, colonic perforation and even death.

Fig. 1 – Histology of Bowel Segment in UC, showing non-granulomatous inflammation with crypt abscess (circled) formation

Fig. 1 – Histology of Bowel Segment in UC, showing non-granulomatous inflammation with crypt abscess (circled) formation

Pathophysiology

Although the exact aetiology of ulcerative colitis is unknown, current theories suggest it develops as an interaction between genetic factors and environmental triggersSmoking is protective against UC, whilst a positive family history of inflammatory bowel disease is a strong risk factor.

It is characterised by diffuse continual mucosal inflammation of the large bowel, beginning in the rectum and spreading proximally, potentially affecting the entire large bowel. A portion of the distal ileum can become affected in a small proportion of cases, termed ‘backwash ileitis’ (if the ileocaecal valve is not competent).

Histological changes include inflammation of the mucosa and submucosa, crypt abscesses, and goblet cell hypoplasia. Repeated cycles of ulceration and healing may lead to raised areas of inflamed tissue termed ‘pseudopolyps’.

Ulcerative Colitis Crohn’s Disease
Site Involvement Large bowel Entire GI tract
Inflammation Mucosa only Transmural
Microscopic Changes Crypt abscess formation Reduced goblet cells Non-granulomatous Granulomatous (non-caseating)
Macroscopic Changes Continuous inflammation (proximal from rectum) Pseudopolyps and ulcers may form Discontinuous inflammation (‘skip lesions’) Fissures and deep ulcers (‘cobblestone appearance’) Fistula formation

Table 1 – Characteristic Features of Inflammatory Bowel Disease


Clinical Features

Ulcerative colitis is typically insidious in onset. The cardinal feature is bloody diarrhoea, with visible blood in stool reported in more than 90% of cases.

The most common manifestation of ulcerative colitis is proctitis, whereby the inflammation is confined to the rectum. Patients will complain of PR bleeding and mucus discharge, increased frequency, urgency of defecation, and tenesmus.

Patients presenting with more widespread colonic involvement are more likely to experience bloody diarrhoea with clinical features of dehydration and electrolyte imbalance. Systemic symptoms also include malaise, anorexia and low-grade fever.

Unless there is a severe exacerbation, clinical examination is generally unremarkable. Fulminant colitis, toxic megacolon, or colonic perforation should be suspected if the patient complains of severe abdominal pain and on examination demonstrates systemic upset or signs of peritonism.

Disease Grading

The severity of an exacerbation can be graded using the Truelove and Witt criteria. The severity degree is based on the presence of any one of the criteria as shown in Table 2:

Criteria Mild Moderate Severe
Bowel movements (no. per day) <4 4-6 >6
Blood in stool Minimal Mild-severe Visible blood
Pyrexia No No Yes
Pulse >90 bpm No No Yes
Anaemia No No Yes
ESR (mm/hour) ≤30 30 >30

Table 2 – Truelove and Witt Criteria

Extra-Intestinal Manifestations

Ulcerative colitis, much like Crohn’s disease, is associated with extra intestinal manifestations of disease:

  • Musculoskeletal – enteropathic arthritis (typically affecting sacroiliac and other large joints) or nail clubbing
  • Skin – Erythema nodosum (Fig. 1, tender red/purple subcutaneous nodules, typically found on the patient’s shins)
  • Eyes – Episcleritis, anterior uveitis, or iritis
  • Hepatobiliary – Primary sclerosing cholangitis (chronic inflammation and fibrosis of the bile ducts)
Fig 2 - Erythema nodosum is a relatively common extra-intestinal feature of ulcerative colitis.

Fig 2 – Erythema nodosum is a relatively common extra-intestinal feature of ulcerative colitis.


Differential Diagnosis

The primary differential diagnosis for ulcerative colitis is Crohn’s disease, as this can present in a similar fashion – however patients with UC patients typically experience a more bloody diarrhoea.

Alternative forms of colitis include chronic infections (schistosomiasis, giardiasis and TB), mesenteric ischaemia, or radiation colitis. Other differentials to consider include malignancy, IBS, or coeliac disease.


Investigations

Routine bloods* (FBC, U&Es, CRP, LFTs, and clotting) are required to examine for anaemia, low albumin (secondary to malabsorption), and raised CRP and WCC.

In the UK, NICE guidelines recommend that faecal calprotectin testing is carried out in patents with recent onset lower gastrointestinal symptoms; it is raised in inflammatory bowel disease, but unchanged in irritable bowel syndrome. A stool sample should be sent for microscopy and culture.

*Liver function tests may become deranged in patients on medical treatment and clotting can become deranged in severe attacks due to the large inflammatory response affecting the coagulation cascade.

Imaging

The definitive diagnosis for ulcerative colitis is via colonoscopy with biopsy*. Characteristic macroscopic findings are of continuous inflammation with possible ulcers and pseudopolyps visible. A flexible sigmoidoscopy may be sufficient and in clinical practice full colonoscopy is only required if the diagnosis is unclear; colonoscopy should be avoided in acute severe exacerbations.

*At least two biopsies are required from five sites, including the rectum and the terminal ileum, for definitive diagnosis

In acute exacerbations, an abdominal x-ray (AXR) is used to determine if toxic megacolon and/or bowel perforation has occurred. AXR features of acute ulcerative colitis flares also include mural thickening and thumbprinting, indicating a severe inflammatory process in the bowel wall. In chronic cases of UC, a lead-pipe colon is often described – but this is usually best seen on barium studies.

Fig. 3 - (A) bowel fibrosis, secondary to chronic UC (B) active inflammation in patient with UC (C) AXR changes in active UC, showing toxic megacolon with lead-pipe colon ( seen in descending colon)

Fig. 3 – (A) bowel fibrosis, secondary to chronic UC (B) active inflammation in patient with UC (C) AXR changes in active UC, showing toxic megacolon with lead-pipe colon (seen in descending colon)


Management

Patients with suspected IBD should be referred to a gastroenterologist for confirmation of the diagnosis and initiation of treatment; those with acute severe disease should be admitted on an emergency basis.

Anti-motility drugs, such as loperamide, should be avoided in acute attacks, as these can precipitate toxic megacolon.

Inducing Remission

Any acute attacks will also warrant aggressive fluid resuscitation, nutritional support, and prophylactic heparin (due to the prothrombotic state of IBD flares).

The medical management to induce remission in Ulcerative Colitis requires use of corticosteroid therapy and immunosuppresive agents, such as mesalazine or azathioprine. Biological agents, such as infliximab, can be trialled as rescue therapy if then needed.

NICE guidelines suggest that a stepwise approach is adopted (Table 3), dependent upon the clinical severity and location of the exacerbation.

Severity Step 1  Step 2
Mild to Moderate (proctitis) Topical mesalazine or sulfasalazine Add oral prednisolone + oral tacrolimus
Mild to Moderate (extensive inflammation) High oral dose mesalazine or sulfasalazine
Severe (all spread of disease) Intravenous corticosteroids and assess the need for surgery Add infliximab if no short-term response

*Continue to step 2 if no improvement on step 1 for 4 weeks

Maintaining Remission

Once any acute event has been controlled, remission of the disease can be maintained using immunomodulators, such as mesalazine or sulfasalazine. Infliximab or alternative monoclonal antibody therapy can be used as next line therapies to maintain remission patients with recurrent symptoms.

Due to increased risk of colorectal malignancy, colonoscopic surveillance is offered to people who have had the disease for >10 years with >1 segment of bowel affected (follow-up time frame depends on risk stratification of disease following initial endoscopy).

Further Management

Patients should be referred to IBD-nurse specialists and patient support groupsEnteral nutritional support should be considered in young patients with growth concerns, with close support from a nutritional team. Antibiotics are only offered to those with obvious concurrent infection or perianal disease (typically ciprofloxacin or metronidazole).

Surgical Management

Approximately 30% of those with ulcerative colitis will at some point require surgery. Indications for acute surgical treatment include disease refractory to medical management, toxic megacolon, or bowel perforation. Surgery may also be undertaken to reduce the risk of colonic carcinoma, if dysplastic cells are detected on routine monitoring.

Total proctocolectomy is curative* (with the patient requiring an ileostomy), yet many patients for disease control will often initially undergo a sub-total colectomy with preservation of the rectum (this can excised at a later stage if symptoms persist).

*Some patients may undergo ileal pouch-anal anastomosis operation, involving the formation of a pouch from loops of ileum (act as a reservoir for intestinal contents) that is then anastamosed to the anus, aming to achieve maintain faecal continence


Complications

Patients with well-controlled UC can expect to have a similar life expectancy as those in the general population. However, the main complications of ulcerative colitis include:

  • Toxic megacolon – serious complication of ulcerative colitis, characterised by dilatation of the colon (to at least 6 cm diameter on AXR, Fig 3C)
    • Patients typically present with severe abdominal pain, abdominal distension, pyrexia, and systemic toxicity. Decompression of the bowel is required as soon as possible, due to high risk of perforation, and failure to respond to medical management is an indication for surgery.
  • Colorectal carcinoma
  • Osteoporosis – patients should be regularly assessed for fracture risk and treated as appropriate.
  • Pouchitis – inflammation of an ileal pouch (as described above). Typical symptoms include abdominal pain, bloody diarrhoea and nausea. Pouchitis should be treated with metronidazole and ciprofloxacin.

Key Points

  • Ulcerative Colitis will only affect the large bowel
  • Definitive diagnosis is made from colonoscopy with biopsy, yet this should not be done during acute attacks
  • Medical management of acute flares involves sequential escalation of treatment, from corticosteroids and immunosuppressors to biological therapies
  • Surgical input should be sort urgently in cases refractory to medical management, patients who have developed toxic megacolon, or suspected bowel perforation
  • Complications of the disease can be both intestinal and extra-intestinal manifestations

Further Reading

Ulcerative Colitis
Danese S et al., NEJM

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