Chronic Inflammatory Disorders of the Bowel

Introduction

Substantial inflammation in any part of the small or large bowel usually presents with diarrhoea (i.e., frequent passage of loose stools). When inflammation affects the large bowel, the diarrhoea often contains blood. Chronic diarrhoea is defined as lasting for longer than 6 weeks, different from the acute diarrhoea of gastroenteritis, which is usually of viral origin or related to food poisoning and is usually self-limiting, though often fatal in infants in the developing world.

A chronic change of bowel habit to looser and more frequent stools, whether containing blood or not, raises the possibility of three categories of diagnosis: infective (bacillary or amoebic), inflammatory bowel diseases (ulcerative colitis, Crohn disease or rarer forms of noninfective colitis) and neoplasms (covered in the previous chapter).

The term inflammatory bowel disease usually means the two chronic bowel disorders, ulcerative colitis or Crohn disease . They share many pathophysiological and clinical features. However, Crohn disease can involve any part of the gastrointestinal (GI) tract, whilst ulcerative colitis is confined to the large bowel. When the large bowel alone is inflamed, it is important to differentiate between these conditions because management and the spectrum of complications differ substantially ( Table 28.1 ).

TABLE 28.1

Comparative Features of Ulcerative Colitis and Crohn Disease

	Ulcerative Colitis	Crohn Disease
Pathology
Inflammation General distribution Rectal involvement Ileal involvement Depth of wall involved Mucosal changes Granuloma formation Mesenteric adenopathy Fibrosis of wall	Recurrent acute inflammation with intervening quiescent phases Continuous involvement of affected part of colon Always Backwash ileitis only Mucosa only Widespread irregular superficial ulceration with or without pseudopolyps Absent Reactive hyperplasia only Minimal	Chronic relapsing inflammation Skip lesions in any part of gastrointestinal tract About 25% Involved in 80% of cases; exclusive to ileum in 50% of cases Transmural, including serosa Fissured ulceration causing ‘cobblestone’ appearance Characteristic but not always present Lymph nodes often enlarged; granulomas may be present Marked
Main Clinical Features
Diarrhoea Rectal bleeding Abdominal pain Abdominal mass General debility	Severe during acute attacks, often causing incontinence Very common Mild cramping ‘predefaecation’ pain with diarrhoeal attacks No Less marked	Less prominent Less common Dominant feature—persistent or grumbling pain with severe acute attacks Relatively common Characteristic
Complications
Strictures Fistulae Anal and perianal lesions Massive haemorrhage	Rare Rare Uncommon Occurs in fulminant disease	Common and often multiple Common Common Rare
Pathology
Intestinal obstruction Perforation Toxic megacolon Malignant change	Rare Complication of toxic megacolon May occur in fulminant attacks High risk with severe/longstanding disease	Incomplete obstruction is common Free perforation rare but perforation causing local abscess formation or internal fistula common Rare Low risk
Management
Local 5-aminosalicylic acid (ASA)/steroids Systemic steroids Oral 5-ASA Immunosuppressives Surgery	Left-sided active disease Severe exacerbations To treat mild attacks Long-term maintenance In severe cases, unresponsive to steroids As steroid-sparing agent Less common —in longstanding disease with evidence of dysplasia or malignancy —in fulminant colitis —in uncontrolled chronic disease	Less effective Severe exacerbations Less effective ‘Steroid sparing’ in intractable cases Commonly required

These diseases are chronic and relapsing by nature. They have variable responses to treatments, with a potential for complications after major surgery. The most effective management and best outcomes result from cooperation between medical and surgical gastroenterologists. Patients can mostly be managed on an outpatient basis but acute exacerbations or complications may require admission. Surgery is usually indicated when medical management has failed or when complications, such as fulminant colitis, obstruction, toxic dilatation of the colon or perforation occur. In addition, ulcerative colitis and Crohn disease are long-term risk factors for colorectal cancer .

In developing countries, infections that cause chronic large bowel inflammation are more common and may also be contracted by travellers. Amoebiasis , in particular, may mimic ulcerative colitis, and tuberculosis may mimic Crohn disease even in the UK.

Pseudomembranous and other forms of antibiotic-related colitis are increasingly common in hospitalised patients after antibiotic treatment; they are discussed in Chapter 12 . Whilst typical cases can be readily diagnosed and treated, severe forms may require emergency colectomy and may cause fatality in elderly patients. Symptoms may occur as long as 6 months after antibiotic use.

Infective causes must be excluded before inflammatory bowel disease is diagnosed because life-threatening complications can result from treating infective conditions with immunosuppressive drugs used for inflammatory bowel disease.

Epidemiology and Aetiology of Inflammatory Bowel Disease

Ulcerative colitis and Crohn colitis are considered to be separate entities but in 10% to 15% of cases, no clear distinction can be made—this is termed indeterminate colitis on resection specimens. It is possible that the diseases share aetiological factors or even represent different facets of the same disease.

Ulcerative colitis and Crohn disease are relatively common in developed countries but the diseases seem rare in most of Africa, Asia and South America. In the West, the incidence of Crohn disease appears to have increased over the past few decades (to 100 per 100,000 population per year), whilst ulcerative colitis (200 per 100,000) has remained static or may have even declined.

Most inflammatory bowel disease develops in the late teen years or 20s. Gender, social class and urban living seems to be irrelevant. In the United States of America, white people are three times more susceptible to ulcerative colitis than black people and five times more susceptible to Crohn disease.

The aetiology of these diseases remains obscure. There is a familial incidence: 6% to 8% of patients with ulcerative colitis and about 20% of those with Crohn disease have first-degree relatives with the same condition. It is likely that both conditions are genetically heterogeneous and polygenic. For Crohn disease, implicated genes include NOD2 / CARD15 . For ulcerative colitis, genes IBD1, IBD2 and IBD3 have been identified. It is postulated that the presence of more than one of these genetic mutations may result in Crohn disease.

Another similarity between the two diseases is the association with a range of non-GI autoimmune disorders involving eyes, joints, skin and liver. The most common for both ulcerative colitis and Crohn disease is ankylosing spondylitis , which is usually associated with the lymphocyte surface antigen human leucocyte antigen (HLA)-B27. In contrast, pericholangitis occurs often in ulcerative colitis but is rare in Crohn disease, and occasionally progresses to sclerosing cholangitis .

Infection is believed to play a part in initiating some cases of both ulcerative colitis and Crohn disease, as many cases follow an acute attack of gastroenteritis. Importantly, tobacco smoking is more common in patients with Crohn disease, and smoking increases disease recurrence. Ulcerative colitis, by contrast, is more prevalent in nonsmokers.

Ulcerative Colitis

Ulcerative colitis is an inflammatory disorder of the mucosa and submucosa of the large bowel only. It is characterised by recurrent acute exacerbations and intervening periods of quiescence or chronic low-grade activity. The symptom severity corresponds to the level of disease activity. Extracolonic features affect a small proportion of patients and include anaemia, inflammation of joints ( arthropathy ) and inflammation of eyes, skin and biliary tract. The disease always involves the rectum, but often extends proximally in continuity to involve a variable length of colon. In nearly 20% of cases (but only those with pancolitis, i.e., colitis involving the whole large bowel), the distal end of the ileum becomes secondarily affected; this is described as backwash ileitis .

Pathophysiology of Ulcerative Colitis

Initially, the colonic mucosa becomes acutely inflamed. Neutrophils accumulate in the lamina propria and within the tubular colonic glands to form small, highly characteristic crypt abscesses . Sloughing of the overlying mucosa produces small superficial ulcers. If the inflammatory process persists, the ulcers coalesce into extensive areas of irregular ulceration. Residual islands of intact but oedematous mucosa project into the bowel lumen; these inflammatory lesions are called pseudopolyps ( Fig. 28.1 ). The inflammation is usually confined to the mucosa and submucosa, only extending into the muscular wall and peritoneal surface in fulminating colitis .

Fig. 28.1, Ulcerative Colitis—Histopathology.

Acute inflammatory episodes range from several days’ to several months’ duration. After subsiding, they can recur months or even years later. During quiescent periods, the acute inflammation resolves and the mucosa regenerates. The lamina propria, however, remains swollen by a chronic inflammatory infiltrate of lymphocytes and plasma cells. The colonic glands show a marked reduction in the number of mucin-secreting goblet cells, histologically termed goblet cell depletion .

After the disease has been present for some time, dysplastic changes can appear in the epithelium. Dysplasia (Latin for ‘bad form’) involves recognisable changes indicating early transformation to neoplasia. After prolonged or repeated episodes of inflammation, dysplasia may progress to adenocarcinoma . The risk of malignancy is greatest for those with early onset and extensive disease, and is approximately 5% after 10 years of colitis. Endoscopic surveillance is necessary, with intervals determined by the duration and extent of disease. Cancer diagnosis may be delayed if symptoms are mistaken for a relapse of colitis and are not investigated. Cancers in these patients are often particularly aggressive and occur on average 20 years earlier than in the general population.

In longstanding colitis, the mucosa and submucosa undergo fibrosis, resulting in smoothing out of haustrations and a shortened colon, which has a characteristic radiological appearance, the so-called lead pipe colon ( Fig. 28.2 ).

Clinical Features of Ulcerative Colitis

Acute inflammatory attacks are marked by loose blood-stained stools streaked with mucus. This mucus results from inflammation of rectosigmoid colonic mucosa. As the extent of inflammation increases, the diarrhoea may become severe. The patient may pass 20 or more loose stools a day, each time preceded by cramping abdominal pain. In many patients, the urge to defaecate is so precipitate that incontinence occurs unless a lavatory is immediately available.

Any attack of ulcerative colitis may progress to the severe form of fulminant colitis ; the patient may become prostrated by dehydration, severe electrolyte disturbance and blood loss. Occasionally, the colon dilates massively and patchy necrosis eventually occurs. The patient is systemically ill with high fever, marked tachycardia and dehydration. This process, known as toxic megacolon , culminates in perforation and fatal peritonitis, unless emergency colectomy is performed.

Ulcerative colitis should probably be regarded as a systemic disorder. It is sometimes accompanied by extra-GI manifestations, summarised in Box 28.1 . During active phases, inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) are elevated and moderate anaemia and hypoalbuminaemia is common. Associated arthropathy, eye and skin disorders usually flare up in parallel with the colitis (although they may rarely precede the intestinal symptoms). However, the liver-related conditions—sclerosing cholangitis, chronic active hepatitis and bile duct carcinoma—are often independent of colitic activity and are therefore difficult to treat.

Case Histories

Fig. 28.2, Radiological Appearances (Lateral Decubitus) of Ulcerative Colitis.

BOX 28.1

Systemic Manifestations of Ulcerative Colitis

Weight Loss

Frequent during exacerbations

Anaemia

Typically chronic and nonspecific (normochromic, normocytic)

Arthropathy

Sacroiliitis/ankylosing spondylitis or rheumatoid-like arthritis, especially of large joints (approximately 20% of cases)

Uveitis and Iritis

Painful red eye or eyes (approximately 10%)

Skin Lesions

Erythema nodosum, that is, tender red nodules on the shins (uncommon), pyoderma gangrenosum, that is, purulent skin ulcers (rare)

Sclerosing Cholangitis

Progressive fibrosis of intrahepatic biliary system leading to cirrhosis, progressive liver failure, jaundice and eventually death (rare)

Clinical Examination and Investigation of Suspected Ulcerative Colitis

The typical patient referred for investigation of suspected ulcerative colitis is a young adult with a history of several weeks of frequent loose stools, later streaked with blood and mucus. The attack often starts with an attack of gastroenteritis or traveller’s diarrhoea, which fails to settle. There is sometimes a history of non-GI symptoms, such as arthropathy or uveitis.

General examination often reveals anaemia but abdominal examination is usually unremarkable. Rectal examination, followed by proctoscopy and flexible sigmoidoscopy, is mandatory to palpate, inspect and, if necessary, biopsy the rectal mucosa. The affected mucosa ranges in appearance from mildly hyperaemic and easily traumatised to extensive patchy ulceration.

At least three separate fresh stool samples should be analysed to exclude bacterial or parasitic causes or cytomegalovirus, as these conditions may closely simulate ulcerative colitis but require entirely different treatment.

Proctitis

Some patients with ulcerative colitis have inflammation confined to the lower rectum. The mucosa often has a granular appearance and the condition is described as proctitis or granular proctitis . Its cause is unknown and its course is self-limiting. It tends to recur at times of stress, often at protracted intervals. Proctitis usually responds to short courses of local 5-aminosalicylic acid (5-ASA) suppositories (see later), but can occasionally progress into a distal or even a total colitis.

Contrast Radiology

If the clinical picture and histological findings are consistent with inflammatory bowel disease, the extent and degree of colonic involvement can be assessed by barium enema examination. Radiological appearances are illustrated in Figs 28.2 and 28.3 . CT scanning is usually performed in acute disease.

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