Ulcerative Colitis

Introduction

Ulcerative colitis (UC) is a chronic, relapsing-remitting, inflammatory disease which affects the large bowel and rectum. It is the most common form of inflammatory bowel disease (IBD), an umbrella term encompassing two chronic idiopathic inflammatory conditions; UC and Crohn’s disease (CD).¹

Although UC can be diagnosed at any age, its’ incidence is often described as being bimodal (15-30 years and 50-70 years).²

Anatomy and pathophysiology

The exact underlying aetiology of UC remains unclear, however, there is some evidence that the combination of an altered intestinal microbiota and compromised colonic epithelial integrity, results in the inappropriate exposure of non-sterile intestinal contents to the underlying immunological tissue causing inflammation. Genetic, environmental and dietary factors have all been suggested to have an important role in disease pathogenesis.³

Risk factors

Important risk factors for UC include:⁴

• Family history of IBD
• HLA-B27 positive
• Recent gastrointestinal infection
• NSAIDs
• Smoking cessation (overall benefits of smoking cessation still outweigh the risk of UC)
• Ashkenazi Jewish descent

Clinical features

History

Typical symptoms of UC include:³

• Diarrhoea ± blood ± mucus
• Urgency
• Tenesmus
• Lower abdominal pain
• Abdominal discomfort and bloating
• Fatigue
• Weight loss
• Malaise

Other symptoms may relate to extra-intestinal manifestations of UC:⁵    

• Ophthalmic symptoms: iritis, uveitis, episcleritis
• Dermatological symptoms: erythema nodosum, pyoderma gangrenosum
• Musculoskeletal symptoms: arthritis (both large and small joints may be affected), osteoporosis, ankylosing spondylitis
• Hepatobiliary symptoms: gallstones, primary sclerosing cholangitis (PSC)
• Renal symptoms: nephrolithiasis
• Haematological symptoms: anaemia, thromboembolism

Clinical examination

Typical findings on abdominal examination may include:

• Lower abdominal pain
• Lower abdominal tenderness
• Abdominal distension

A digital rectal examination (DRE) may also be necessary to screen for the presence of blood suggesting anorectal pathology. 

Other findings on general examination may include:

• Features of anaemia (e.g. pallor, fatigue)
• Joint pain
• Clubbing
• Erythema nodosum
• Pyoderma gangrenosum
• Uveitis
• Episcleritis

Classification

Different terms can be used to describe UC, determined by the location and extent of disease:⁶

• Proctitis: rectum
• Proctosigmoiditis: rectum and sigmoid colon
• Left-sided colitis: rectum, sigmoid colon and descending colon
• Extensive colitis: rectum, sigmoid colon, descending colon and transverse colon
• Pancolitis: rectum and entire colon

UC can also be classified based on clinical severity (mild, moderate or severe), according to Truelove and Witts criteria.

Differential diagnoses

Other diagnoses with similar clinical features that are important to consider include:⁴

• Infectious colitis
• Crohn’s disease
• Ischaemic colitis
• Radiation colitis
• Diverticulitis
• Vasculitis
• Irritable bowel syndrome (IBS): this is an important diagnosis of exclusion

Investigations

A diagnosis of UC is predominantly made based on features of the clinical history and endoscopic findings. However, it is important that other causes of colitis and diarrhoea, both infectious and non-infectious, are ruled out before a diagnosis of UC is made.

Laboratory investigations

Blood tests ⁷

Blood tests relevant to the investigation of UC include:

• FBC: anaemia, raised WCC
• U&Es
• CRP: elevated
• LFTs: hypoalbuminaemia (severe disease)
• pANCA (if PSC is suspected)

Stool tests

Stool tests relevant to the investigation of UC include:

• Faecal calprotectin is significantly raised in UC, as it is a marker of intestinal inflammation (useful for distinguishing between IBS and IBD)
• Microscopy and culture: important for the exclusion of infection (e.g. Salmonella, E.coli, Campylobacter)

Imaging

Endoscopy is the gold standard investigation for the diagnosis of UC.⁴

Sigmoidoscopy ± colonoscopy (and biopsy)

A flexible sigmoidoscopy is usually sufficient, due to the distal nature of UC, however, a full colonoscopy may be required if findings on sigmoidoscopy are unclear. A colonoscopy must be avoided in acute severe disease due to the increased risk of bowel perforation.

Macroscopic findings:

• Continuous, uniformly inflamed mucosa
• Erythematous, friable mucosa
• Abnormal vascular pattern
• Ulceration
• Inflammatory polyps (‘pseudopolyps’)

Microscopic findings (biopsy):

• Crypt abscesses
• Decreased goblet cell abundance

Additional imaging modalities

Additional imaging modalities such as plain abdominal X-ray (AXR) and computed tomography (CT) may be important for the exclusion of UC complications in an acute presentation (e.g. toxic megacolon, bowel perforation). 

Management

The two main aspects of management include the induction of remission and maintenance of remission.

Most patients are managed with optimal medical therapy which is escalated in a stepwise fashion, dependent on disease severity and symptom control. However, severe disease and uncontrollable flare-ups are likely to necessitate surgical intervention.

Treatment should be tailored to individuals, based on the severity and extent of disease, with the ultimate aim of improving quality of life and minimising the risk of complications.

Medical management⁸

Aminosalicylates (e.g. Mesalazine)

Mesalazine-5-aminosalicylic (5-ASA) is the current first-line treatment of choice for induction and maintenance of remission of mild-to-moderate ulcerative colitis.

There are both topical and oral preparations which can be used simultaneously if required.

Corticosteroids (e.g. Prednisolone)

Corticosteroids are typically used to induce remission in relapses of ulcerative colitis.

Unlike 5-ASA, corticosteroids are not used to maintain remission.

Thiopurines

Thiopurines (e.g. Azathioprine) are typically used as a steroid-sparing therapy (e.g. to reduce steroid-related side effects) to induce and maintain remission.

Before azathioprine treatment, patients must have thiopurine methyltransferase (TPMT) activity checked, as reduced or absent activity increases the risk of myelosuppression.

Biologics

Biological therapies are typically used when UC is refractory to other treatments.

Some examples of biologics used in the treatment of UC include:

• Anti-TNFa (e.g. Infliximab)
• Anti-IL-12/23 (e.g. Ustekinumab)
• Anti a₄b₇ (e.g. Vedolizumab)

Surgical management²

Surgery is predominantly reserved for patients in whom UC cannot be adequately controlled by optimal medical treatment or upon the occurrence of severe complications (e.g. toxic megacolon, bowel perforation).

Subtotal colectomy

Subtotal colectomy involves resection of part of the colon. Patients are likely to have a temporary de-functioning loop ileostomy, which can later be reversed, in order to protect the site of anastomosis.

Complete proctocolectomy

Complete proctocolectomy involves the resection of the entire colon and rectum. Patients do not undergo further anastomotic surgery and thus have a permanent ileostomy.

Restorative proctocolectomy

Restorative proctocolectomy involves resection of the entire colon and rectum and a temporary loop ileostomy, which is later reversed with further surgery involving the joining of the ileal pouch to the anal canal (ileal pouch-anal anastomosis, IPAA). 

Complete proctocolectomy with IPAA is the procedure of choice.

Complications

Untreated or poorly managed UC can result in various complications, including:⁴

• Severe bleeding
• Bowel perforation
• Toxic megacolon
• Malnutrition
• Venous thromboembolism
• Osteoporosis
• Colorectal cancer: Individuals with a long history of UC are offered colonoscopic surveillance due to their increased risk of malignancy. Frequency of surveillance is dependent on individual patient risk (low, intermediate, high).

Key points

• UC is the most common type of inflammatory bowel disease and has a relapsing-remitting course.
• Common symptoms of UC include episodic diarrhoea with urgency, rectal bleeding and abdominal pain.
• Extra-intestinal manifestations include; erythema nodosum, uveitis and joint pain.
• Topical and oral aminosalicylates are the mainstay therapies used in UC.
• Surgical intervention should not be delayed for urgent indications and usually involves partial or complete resection of the colon.
• UC increases the lifetime risk of colorectal cancer and thromboembolic events.

References

1. Guan Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. Journal of Immunology Research. Published in 2019. Available from: [LINK]
2. Ordás I, Eckmann L, Talamini M, Baumgart D and Sandborn W. Ulcerative colitis. Lancet. Published in 2012. Available from: [LINK]
3. Danese S and Fiocchi C. Ulcerative Colitis. New England Journal of Medicine. Published in 2011. Available from: [LINK]
4. BMJ Best Practice: Ulcerative colitis – Symptoms, diagnosis and treatment. Published in 2019. Available from: [LINK]
5. Levine J and Burakoff R. Extraintestinal Manifestations of Inflammatory Bowel Disease. Journal of Gastroenterology and Hepatology. Published in 2011. Available from: [LINK]
6. Ghosh S, Shand A, and Ferguson A. Ulcerative colitis. BMJ. Published in 2000. Available from: [LINK]
7. Adams S and Bornemann P. Ulcerative colitis. American Family Physician. Published in 2013. Available from: [LINK]
8. Chudy-Onwugaje K, Christian K, Farraye F, and Cross R. A State-of-the-Art Review of New and Emerging Therapies for the Treatment of IBD. Inflammatory Bowel Diseases. Published in 2019. Available from: [LINK]

Reviewer

Dr Elspeth Alstead

Consultant Gastroenterologist

Editor

Hannah Thomas