Ulcerative colitis

Notes

Definition & classification

Inflammatory bowel disease (IBD) is an umbrella term for two chronic inflammatory disorders of the gastrointestinal system: ulcerative colitis (UC) and Crohn’s disease (CD).

UC is a disease of the colonic mucosa, which has a relapsing, remitting course. Unlike CD, UC only affects the colonic mucosa

UC is considered the most common form of IBD, with an estimated prevalence of 240 per 100,000 population. UC is more common in females. There is a bimodal peak in incidence between 15-25 and 55-65 years of age.

IDB

Aetiology

The precise aetiology of both UC and CD remains unknown. 

The current theory is of an abnormal immunological response and/or increased reaction to commensal bacteria within a genetically susceptible individual. This theory is based around three core aetiological factors: immunity, genetics and the environment.

UC aetiology

1. Immunity

There is suggested to be an abnormal immunological response to intestinal microflora. There also seems to be a protective role in patients who have previously had an appendicectomy. 

2. Genetics

Ulcerative colitis is a polygenic disease (multiple susceptible genetic loci increase the likelihood of developing UC, but do not directly cause it). It is more common in certain populations (e.g. Jewish) and there is often a positive family history.

3. Environmental

Smoking is protective in UC, whereas it is positively associated with CD. Numerous environmental factors are linked with UC; which include milk consumption, bacterial microflora alteration and medications (e.g. NSAIDs, OCP).

Pathophysiology

A number of pathophysiological changes occur due to inflammation of the colonic mucosa.

Overview 

UC affects the rectum (proctitis) first and then extends proximally to involve more of the colon. The extent to which UC affects the colonic mucosa is variable among patients.

Most patients (50%) suffer from proctitis only, however, 1/3rd of these patients will go on to develop more proximal disease. Approximately 30% have left-sided disease and up to 20% have pancolitis

Pancolitis refers to inflammation of the entire colon. Patients with pancolitis are at risk of developing backwash ileitis. This refers to reflux of colonic contents into the distal few centimetres of the ileum through the ileocaecal valve. Backwash ileitis can make distinction between UC and CD more difficult.

UC pathophysiology

The changes that occur in UC can be described as macroscopic, which are seen during endoscopy or microscopic that are seen on histology.

Macroscopic and microscopic changes in UC

Macroscopic

Macroscopically, there is evidence of continuous inflammation that extends proximally along the colon. The surface of the mucosa appears reddened and inflamed. The mucosa is also said to be easily friable to touch, and there may also be evidence of inflammatory polyps

Microscopic

Microscopic changes seen in UC are predominantly alterations in crypt architecture with the development of crypt abscesses and goblet cell depletion. There is also increased inflammatory infiltration into the lamina propria, which is largely neutrophilic.

Clinical features

The hallmark of UC is bloody diarrhoea / rectal bleeding.

Patients with UC may become acutely unwell with features of hypovolaemic shock, so it is important to resuscitate patients with respect to airway, breathing and circulation.

Symptoms

  • Weight loss 
  • Fatigue
  • Abdominal pain
  • Loose stools
  • Rectal bleeding
  • Tenesmus (incomplete emptying)
  • Urgency

Signs

  • Febrile
  • Pale
  • Dehydrated
  • Abdominal tenderness
  • Abdominal distension/mass
  • Tachycardic, hypotensive

Clinical features of UC

Toxic megacolon

A major complication of UC is toxic mega colon (TMC).  

TMC is a medical emergency, which refers to toxic, non-obstructive, dilatation of the colon (> 6cm). Patients with UC who present with abdominal distension and tenderness should be admitted for suspected TMC.

Other features suggestive of TMC include systemic symptoms such as fever (>38), tachycardia (>120), hypotension (<90), dehydrationaltered mental status and biochemical abnormalities including leukocytosisanaemia, and electrolyte derangements.

Extra-colonic manifestations

Approximately 25% of patients will develop extra-colonic manifestations during their lifetime.

Extra-colonic manifestations

Musculoskeletal

Arthritis is considered the most common extracolonic manifestation, which may be a simple peripheral arthritis or more complex spondyloarthropathy (e.g. ankylosing spondylitis). Other important musculoskeletal features include osteopaenia/osteoporosis and the presence of clubbing within the hands and feet. 

Eyes, mouth & skin

Uveitis is strongly associated with UC and refers to inflammation of the uvea. Uveitis may be divided into anterior, intermediate and posterior. Other ophthalmic features include episcleritis, which refers to superficial inflammation of the sclera. 

Extracolonic manifestations of the mouth commonly include aphthous ulcers. The skin is another organ widely affected by UC, leading to erythema nodosum, which is a type of panniculitis that classically results in multiple, painful, purple nodules on the anterior aspect of the shins.

Hepatobiliary

Numerous hepatobiliary pathologies are associated with UC including fatty liver disease and autoimmune liver disease.

However, the most common pathology is primary sclerosing cholangitis (PSC). PSC is thought to affect 3% of patients suffering from UC. Importantly, 70-95% of patients with PSC have UC. PSC should be suspected in any UC patient who has an isolated rise in ALP

Haematological

Two common haematological problems associated with UC include anaemia and thromboembolism. Both should be considered in any patient presenting with an acute exacerbation of UC, as they may require additional medical intervention. 

Investigations & diagnosis

Diagnosis is based on macroscopic assessment (e.g. endoscopy) and histological evidence (e.g. biopsy) of colonic inflammation.

Bedside

  • Observations
  • ECG
  • Urinalysis
  • Stool microscopy, culture & sensitivities
  • Ova, cysts and parasites
  • C. diff toxin (CDT)
  • Faecal calprotectin (marker of intestinal inflammation)

Bloods

  • Full blood count
  • Liver function tests 
  • Urea & electrolytes
  • CRP
  • Arterial/venous blood gas
  • Haematinics
  • Magnesium
  • Clotting
  • Autoantibodies (e.g. p-ANCA)

Imaging

Abdominal X-rays are useul for looking at dilatation of the bowel and perforations. The extent of diltation can be remembered using the 'Rule of 3's'.

Dilatation is present if:

  • Diameter of the small bowel is > 3cm
  • Diameter of the large bowel is > 6cm
  • Diameter of the caecum is > 9cm

Other forms of imaging can include an abdominal USS, which is useful for assessing wall thickening and free fluid. Computed tomography is reserved for the assessment of complications and planning for surgery. 

Special

Colonoscopy is considered the investigation of choice as it allows assessment of the whole colon. Biopsies can be taken for histological assessment of the mucosa. Caution should be taken during acute flares due to the increased risk of perforation. Sigmoidoscopy may be used as an alternative endoscopic test.

Truelove & Witts

The severity of UC in adult patients can be assessed using the Truelove & Witts' scoring

The Truelove and Witts' scoring categorise the severity of acute presentations of UC into mild, moderate and severe. The Paediatric Ulcerative Colitis Activity Index (PUCAI) is used in paediatric patients.

Mild

  • < 4 bowel motions per day.
  • Small amount of blood.

Moderate

  • 4-6 bowel motions per day.
  • Quantity of blood between mild and severe. 

Severe

  • > 6 bowel motions per day.
  • Visible blood
  • Systemic upset

Management

The general principle in the management of UC is to induce and then maintain remission.

1. Induce remission

The choice of pharmaceutical agent to induce remission in UC is dependent on the extent of colonic involvement, frequency of inflammatory exacerbations and severity of presentation. The mainstay of treatment is with immunosuppressive agents (e.g. aminosalicylates, corticosteroids).

Patients with a mild-to-moderate proctitis / proctosigmoiditis can be managed with topical (rectal) or oral aminosalicylates. Those with left-sided and extensive UC require high-dose oral aminosalicylates. If aminosalicylates fail in this patient group then oral corticosteroids and tacrolimus ( a calcineurin inhibitor) should be considered.

Patients with a severe first presentation or inflammatory exacerbation of UC require intravenous corticosteroids. If patients cannot receive corticosteroids, symptoms worsen, or they fail to respond within 72 hours then therapy should be upgraded to intravenous ciclosporin ( a calcineurin inhibitor). 

Aminosalicylates (e.g. sulphasalazine) are a group of drugs that contain the active compound 5-aminosalicylic acid (5-ASA). 5-ASA has immunosuppressive properties leading to a reduction in the immune response. Rare, but potentially severe side-effects of aminosalicylates include:

  • Acute pancreatitis
  • Hepatitis
  • Myocarditis
  • Pericarditis
  • Agranulocytosis
  • Aplastic anaemia
  • Skin reactions (e.g. Stevens-Johnson syndrome)

2. Maintenance

Most patients with UC are controlled with aminosalicylates (e.g. mesalazine). This includes patients with proctitis, proctosigmoiditis and extensive UC. Patients with UC limited to the rectum may be managed with topical aminosalicylates only. 

Patients who present with multiple inflammatory exacerbations of UC may require the use of stronger immunosuppressive agents (e.g. azathioprine and mercaptopurine). In general, if patients have two or more inflammatory exacerbations requiring steroids, or remission is not maintained by aminosalicylates, then these agents should be considered. 

3. Surgical intervention

Approximately 25% of patients with UC will have surgery at some stage.

There may be circumstances where patients require urgent surgical intervention. The indications for acute surgical management include toxic megacolon refractory to medical therapy, uncontrolled colonic bleeding, perforation, bowel obstruction secondary to suspected cancer or a fulminant attack refractory to medical therapy. 

Indications for elective surgical intervention include disease refractory to medical therapy, chronic steroid dependency, systemic complications from steroids or neoplasia found on screening biopsy.

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