Chapter 16 INFLAMMATORY BOWEL DISEASE

KEY POINTS

Ulcerative colitis:

• In ulcerative colitis (UC), the rectum is always involved, which may lead to urgency and bleeding.

• The main parameters of disease activity are the number of bowel motions per day, the presence of blood and associated systemic symptoms.

• Patients may present in fulminant colitis—they require urgent assessment and treatment at specialist centres.

• Extraintestinal manifestations affect the skin, joints, eyes and/or the liver.

• Assess the patient’s haemodynamic status for evidence of significant intravascular losses and their abdomen for distension, and/or signs of peritonism.

• C-reactive protein (CRP) is a more sensitive assay for inflammation than erythrocyte sedimentation rate (ESR).

• Sigmoidoscopy will show an abnormal rectal mucosa.

• The aims of therapy are to induce remission in active disease and to maintain remission/prevent relapse.

• Drugs that are effective in inducing remission are local or oral 5-aminosalicylates, local or oral corticosteroids, immunosuppressive agents including azathioprine and 6-mercaptopurine, and in special situations, cyclosporine and infliximab.

• Aminosalicylates should be continued indefinitely since they decrease the likelihood of recurrence.

• Azathioprine or 6-mercaptopurine are often useful in steroidunresponsive patients or those who require high doses of steroids to remain in remission.

• In acute severe or fulminant colitis, if there is no clear improvement within 3–7 days surgery should be considered.

Crohn’s disease:

• Crohn’s disease has a multifactorial aetiology and there is a genetic predisposition (NOD2/CARD15) in 30%–50% of patients.

• Crohn’s disease affects any part of the gastrointestinal tract.

• Diarrhoea and abdominal pain are common symptoms.

• Pain may be ‘inflammatory’ due to ulceration or inflammation or ‘obstructive’ from strictures.

• Left-sided colon involvement can present with symptoms similar to UC

• Perianal complications are common in Crohn’s disease.

• Clinical assessment, laboratory investigations (haematocrit, CRP, ESR) endoscopy and radiology (small bowel series and barium enema) are the main modalities for assessing disease activity.

• Current therapeutic modalities include lifestyle modification (including cessation of smoking if a factor), drug therapy, nutritional support and surgery.

• Corticosteroids are the cornerstone of therapy to induce remission.

• Azathioprine/6-mercaptopurine are useful in both inducing remission and as maintenance agents.

• New ‘biological’ agents such as infliximab are increasingly being used to induce remission as well as for maintenance.

• Surgery is reserved for the treatment of complications or when medical therapy is ineffective.

INFLAMMATORY BOWEL DISEASE

Crohn’s disease and ulcerative colitis are types of inflammatory bowel disease (IBD) characterised by inflammation leading to a disturbance of gut function and, to a greater or lesser degree, systemic symptoms. Therapy is empirical. Many patients require emotional support and contact with patient support groups is often very helpful. Although these conditions are sometimes hard to differentiate, there are sufficient differences between them to indicate distinct pathological processes. Some of these differences are listed in Table 16.1.

TABLE 16.1 Characteristics of Crohn’s disease and ulcerative colitis

	Crohn’s disease	Ulcerative colitis
Genetics	Identified susceptibility gene(s)	Weaker association
Distribution	Anywhere in the gut	Exclusively colonic
Perianal disease	Common	Uncommon
Pathology	• Full thickness of the intestinal wall • Macrophages (cell-mediated immunity) • Granulomata	• Superficial (epithelium) • Plasma cells (humoral immunity)

ULCERATIVE COLITIS

The diagnosis of ulcerative colitis (UC) is relatively easy since the inflammatory process almost always involves the rectum and generally causes urgency and bleeding. People generally present promptly when rectal bleeding is noted, but the onset may be insidious and the presentation delayed. The bleeding is persistent rather than intermittent as would be expected with local anal problems, such as haemorrhoids. Proctitis may also cause discomfort, increased frequency and a change in the consistency of the stools. Rarely, the presenting symptom may be constipation. As the disease extends more proximally and more of the mucosal surface area is involved, the symptoms become more severe: diarrhoea increases (with looser or more frequent stools) and pain may become more prominent. Systemic symptoms may also develop.

In a significant minority of patients, the presentation is as a fulminant colitis with features including fevers, anorexia and weight loss; such patients are at risk of developing life-threatening complications including toxic megacolon, perforation, peritonitis and haemorrhage, and require urgent assessment and treatment in specialist centres. Given the large surface area of the colon, it is not surprising that ulcerative pancolitis results in blood loss and consequent anaemia, protein loss, hypoalbuminaemia and fluid and electrolyte losses, and the associated metabolic disturbances.

The extraintestinal manifestations of UC may affect the skin, joints, eyes and/or the liver (Table 16.2). These may occur before, during or after the onset of gut symptoms and may be associated with disease activity. These are generally more common in UC than Crohn’s disease.

TABLE 16.2 Extraintestinal manifestations of ulcerative colitis

Skin	Erythema nodosum
	Pyoderma gangrenosum
	Aphthous stomatitis
Joints	Type 1 peripheral osteopathy*
	Type 2 arthritis**
	Sacroileitis
Eyes	Iritis
	Uveitis
	Episcleritis
Liver	Primary sclerosing cholangitis

* Acute self-limiting inflammation affecting <5 joints, lasting <5 weeks and associated with symptom relapse and with other extraintestinal manifestations.

** Chronic arthritis affecting five or more joints with a median duration of symptoms of 3 years, and associated with uveitis but not erythema nodosum.

When assessing patients with suspected UC, particular attention should be paid to the haemodynamic status for evidence of significant intravascular losses and the abdominal examination for distension, tenderness and/or signs of peritonism. There may also be signs of anaemia or significant weight loss. Sigmoidoscopy will show an abnormal rectal mucosa: there will be erythema, loss of the normal vascular pattern, contact bleeding and mucopus or blood in the lumen. In more severe disease there will be extensive ulceration and pseudopolyp formation.

The differential diagnosis is considered in Table 16.3.

TABLE 16.3 Differential diagnosis of ulcerative colitis and Crohn’s disease

• Infective causes: – Campylobacter – Salmonella – Shigella – Clostridium difficile (pseudomembranous colitis), especially in the hospital setting – Entamoeba histolytica – Mycobacterium tuberculosis (Crohn’s disease) – Yersinia (Crohn’s disease) • Cytomegalovirus • Others, e.g. Neisseriae, Herpes simplex, Chlamydiae, schistosomiasis, histoplasmosis • Acute self-limited colitis • Ischaemic colitis, especially in the elderly with evidence of widespread atherosclerosis or cardiac dysrhythmias, in particular atrial fibrillation • Carcinoma and lymphoma (rarely) • Appendiceal diseases including appendicitis and carcinoid tumours (Crohn’s disease) • Radiation enterocolitis • Non-steroidal antiinflammatory drug (NSAID)-induced ulceration (Crohn’s disease) • Vasculitis (rarely)

The diagnosis depends upon the exclusion of infective and other causes of colitis and the demonstration of the typical endoscopic and histological features of UC. Stool cultures and microscopy and studies for Clostridium difficile toxin should be sent. If there is a history of overseas travel, a warm stool smear should be performed to exclude amoebic dysentery. Patients suffering from UC may also have relapses secondary to gastrointestinal infections or non-steroidal antiinflammatory drug (NSAID) usage.

Ulcerative colitis can generally be differentiated from Crohn’s disease using endoscopic and pathological criteria (Table 16.1). UC affects the colon exclusively and almost always involves the rectum from which it extends proximally in continuity. Sigmoidoscopy will show evidence of proctitis although occasionally patients can have ‘rectal sparing’, particularly if there has been use of corticosteroid or 5-aminosalicylate enemas. Biopsies will show that the inflammation involves the more superficial layers of the mucosa, macrophages are less common and granulomata are not present. Sigmoidoscopic biopsies will help differentiate between UC and other causes of colitis, such as ischaemic colitis and radiation colitis.

Acute self-limited colitis

Some patients present with symptoms suggestive of UC, have no causative organisms grown on culture, resolve spontaneously and never have a subsequent attack. About one-half to two-thirds of patients with ‘self-limited’ colitis will develop recurrent symptoms characteristic of ulcerative colitis. The diagnosis of ulcerative colitis may be suspected after the initial presentation but is only confirmed after a subsequent attack.

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