Introduction to inflammatory conditions of the small and large bowel

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CHAPTER 16 Introduction to inflammatory conditions of the small and large bowel

Introduction

Inflammatory disorders account for a significant proportion of bowel related disease. The two main inflammatory conditions – ulcerative colitis and Crohn’s disease, which are collectively referred to as inflammatory bowel disease (IBD) – affect up to 1 in 200 of the European and North American population between them (Kappelman et al., 2007). There are also a number of other inflammatory conditions that can affect the bowel, usually as part of wider systemic disease involving other organs, but these occur much less commonly (Table 16.1). This chapter will therefore largely focus on inflammatory bowel disease, although brief reference will be given to some of these other conditions.

Table 16.1 Inflammatory conditions affecting the bowel

Inflammatory bowel disease Connective tissue disease with gut involvement
Ulcerative colitis Behçet’s
Crohn’s disease Systemic lupus erythematosus
Microscopic colitis Rheumatoid arthritis
Systemic sclerosis
Polyarteritis nodosum
Wegener’s granulomatosis
Henoch-Schönlein
Sarcoid

Inflammatory bowel disease

The term inflammatory bowel disease (IBD) is the umbrella term for ulcerative colitis and Crohn’s disease, which are discrete inflammatory conditions of the gut that share many common features.

Ulcerative colitis, the slightly more common of the two conditions, causes inflammation of the colon, whereas Crohn’s disease can affect any part of the gastrointestinal tract from the mouth through to the anus. Both conditions tend to follow a chronic relapsing and remitting course and can lead to disabling symptoms and complications.

Studies have shown similar rates of IBD in Europe and North America where the estimated incidence of ulcerative colitis ranges from 8.8 to 13.4 new cases per 100 000 population per year, with slightly lower rates for Crohn’s disease of 5.6 to 8.6/100 000/year. The incidence of Crohn’s disease appears to be increasing, while that of ulcerative colitis is stable (Loftus et al., 2007). Rates of IBD in Africa and Asia are thought to be much lower, although limitations in case definition may have led to some underestimation. All age groups can be affected, although the condition is unusual in infancy, with the peak age of diagnosis occurring between the ages of 15 and 30 years, with a second peak between the ages of 50 and 80. Women and men are affected equally (Gunesh et al., 2008).

Microbial factors

As with environmental factors, most of the early work in this field focused on trying to identify ‘the’ infective cause of IBD. Potential candidates included Mycobacterium paratuberculosis, which is known to cause a Crohn’s-like illness in cattle called Johne’s disease. However, this has always been controversial and, to date, no clear cause has been identified, despite large amounts of research, although it remains possible that M. paratuberculosis may play some part in the IBD story (Freeman and Noble, 2005). Other equally controversial studies have focused on the measles virus and the potential link between measles vaccine and Crohn’s disease (Thompson et al., 1995) but, once again, this association has not been confirmed. Consequently, recent research has tended to move away from looking at specific organisms and has focused on the interaction between the gut and the microflora of bacteria it contains. This shows potential as an area for research, although, like the field of genetics, the area is hugely complex; for example, it has now been shown that IBD patients are more likely to have received antibiotics in childhood (Hildebrand et al., 2008), which is just one of the many factors that could have an impact on gut flora.

Signs and symptoms

The signs and symptoms of inflammatory bowel disease largely depend on the site affected and the nature of bowel involvement at the site. Consequently, the symptoms of ulcerative colitis, which only involves the colon, are more predictable than those of Crohn’s disease, which can occur anywhere within the gastrointestinal (GI) tract (Figure 16.1). However, a number of patterns can be recognized. In addition, both ulcerative colitis and Crohn’s disease can be associated with a number of symptoms that occur outside of the GI tract (Table 16.2), particularly when the disease involves the colon (Orchard, 2003).

Ulcerative colitis

Ulcerative colitis (UC) causes superficial inflammation of the colon, so the major symptoms are those of bowel upset in the form of diarrhea, urgency to pass stool and the passage of blood-stained stools. Unlike Crohn’s disease, fistula formation and bowel strictures are relatively uncommon and the lack of deep inflammation means that pain is not usually a significant symptom.

The relapsing and remitting nature of UC means patients experience symptoms at times when the disease is active, commonly referred to as a flare, interspersed by periods without symptoms. Symptoms tend to build up gradually and often last for several weeks at a time. The severity of symptoms is at least in part explained by the extent of colon affected. The rectum is inflamed in all patients, but the extent of proximal colonic inflammation varies, with approximately 30% of sufferers having disease confined to the rectum, 40% with disease of the left colon and 30% developing total colonic inflammation (Jess et al., 2006). Individuals tend to follow the same pattern with each flare leading to inflammation in the same part of the colon, with only around 15% of patients experiencing extent progression over time.

Most patients with proctitis and left-sided colitis present with relatively mild or moderate symptoms with little or no systemic upset and are managed as outpatients, whereas patients with pan colonic involvement (Figure 16.2) often have a more aggressive presentation with malaise, anemia, fever, tachycardia and abdominal pain. A proportion of patients presenting with severe disease will fail to settle despite treatment and, in the past, this type of presentation was associated with significant mortality. However, this is now largely avoided by ensuring that patients who fail to settle have surgery to remove the inflamed colon (colectomy) before complications such as bowel perforation develop. Factors that help predict patients at risk of not settling have been developed and most centers find that about 20–30% of patients presenting acutely with severe symptoms will require colectomy (Travis et al., 1996).

Crohn’s disease

Like ulcerative colitis, the symptoms of Crohn’s disease tend to reflect the site of affected bowel and, as Crohn’s disease can occur anywhere within the GI tract, there is a wider variety of presentations than in UC. The inflammation in Crohn’s disease involves the full thickness of the bowel wall (Figures 16.3 and 16.4) and, consequently, healing with fibrosis leading to scar tissue and narrowing of the bowel or ‘stricturing’ is common (Figure 16.5). Holes in the bowel wall can also develop and these often lead to communication between the bowel and skin or other abdominal structures, known as fistulae (Figure 16.6). Over time, it is estimated that between 30 and 50% of Crohn’s patients will develop fistula, with the majority involving communication between the bowel and the peri-anal skin (Schwartz et al., 2002). General systemic features, such as lethargy and abdominal pain, are also more common in Crohn’s disease.

Upper gastrointestinal Crohn’s disease

Crohn’s disease involving the esophagus, stomach or duodenum is relatively uncommon and collectively occurs in only 5% or so of patients (Figure 16.9). Symptoms that raise the possibility of upper GI involvement include dysphagia or painful swallowing (odynophagia), ulcer-like epigastric pain and pain occurring immediately or very soon after eating. This form of disease can be difficult to treat and warrants aggressive therapy.

Diagnosis and management

Diagnosis

The diagnosis of inflammatory bowel disease relies on a high index of clinical suspicion based on the symptoms, coupled with appropriate investigation to confirm the presence of the characteristic pathological features (Carter et al., 2004). Despite our increased understanding about inflammatory bowel disease, patients still often experience a delay before being diagnosed; for example, a study from the USA found that the average time from symptom onset to diagnosis was over 7 years for Crohn’s patients and just over a year for ulcerative colitis (Pimentel et al., 2000). This most likely reflects the rather non-specific nature and gradual onset of symptoms in some patients with Crohn’s disease and serves as a reminder that clinical vigilance is necessary to make the diagnosis.

When a patient presents with symptoms suggestive of inflammatory bowel disease, the initial step is usually to look for confirmatory features such as raised markers of inflammation in blood tests. If there remains concern about the diagnosis following this, then further investigation is targeted according to the suspected site of disease involvement. For ulcerative colitis patients, the disease can be diagnosed relatively easily by endoscopic assessment of the rectal and lower colonic mucosa. This can be achieved in the outpatient setting using a rigid sigmoidoscope to examine the rectal mucosa, but is more reliably done using a fiberoptic flexible sigmoidoscope or colonoscope. Here, detailed assessment of the mucosa can be obtained and biopsies taken for histological assessment. Ileo-colonic Crohn’s disease can be diagnosed in a similar way, although full colonoscopy after preparation of the patient’s bowel with laxative is necessary to ensure views of the proximal colon and terminal ileum are obtained.

Crohn’s disease involving the more proximal small bowel is less accessible to endoscopic diagnosis and diagnosis has tended to rely on demonstration of typical features of small bowel Crohn’s using radiological techniques. This has the limitation of not obtaining tissue for histological analysis, but a combination of typical features in a patient with symptoms suggestive of the diagnosis is usually reliable. The imaging of the small bowel is considered in more detail in earlier chapters and it seems likely that there will be an increasing trend towards using magnetic resonance imaging in this setting (Masselli et al., 2008), although emerging endoscopic tests such as wireless capsule endoscopy and balloon assisted enteroscopy may play a complementary role (Chong et al., 2005).

Management

The treatment of inflammatory bowel disease is complex and, for many patients, involves a combination of medical therapy to control the inflammatory process, emotional support to assist with the impact for the patient from their chronic disease, nutritional support and surgical treatment for resistant disease or where complications such as strictures or abscess develop. Treatment decisions depend on clear identification of the nature and extent of the bowel that is affected (Carter et al., 2004).

Crohn’s disease

Like ulcerative colitis, treatment of Crohn’s disease is dictated by the disease severity and site of bowel involved. Colonic Crohn’s disease is treated similarly to ulcerative colitis, although mesalazine treatment tends to be less effective and, consequently, more patients will end up on immunosuppressive therapy. Small bowel disease usually requires immunosuppressive therapy to control inflammation. Steroids are commonly used in the short term, but have limited efficacy in the long term due to side effects. Conventional immunosuppressive drugs, such as azathioprine and methotrexate, can be highly effective but, like steroids, can be limited by side effects. They also have a delayed onset of action, meaning that other drugs are often needed to bridge the time period until they become effective. Infliximab and Adalumimab are two relatively new drugs that were developed specifically to block tumor necrosis factor (TNF), which is one of the many chemicals (cytokines) involved in triggering and sustaining the inflammatory process in Crohn’s disease. Results have been encouraging with response in up to 70% of patients treated (Figure 16.10) and the use of these drugs is steadily increasing, despite treatment costs averaging around £10 000 per year. However, some concern remains about their long-term effectiveness and safety profile (Peyrin-Biroulet et al., 2008).

Despite the advances in medical therapy for Crohn’s disease, surgery is still required by up to 50% of Crohn’s patients within the first 10 years after diagnosis and, for many patients, close liaison between surgeon and physician is required to enable optimal management (Fichera and Michelassi, 2007). Common surgical procedures in Crohn’s disease include drainage of abscesses with correction of fistula and resection of segments of strictured bowel (Figure 16.11). Carefully planned and expertly performed surgery is essential to minimize loss of bowel, as patients frequently require several operations over their lifetime and the impact of cumulative bowel loss remains a concern for some patients.

Differential diagnoses

The conditions that need to be considered in the differential diagnosis of inflammatory bowel disease are largely dictated by the type of symptoms involved and can usually be distinguished based on the clinical history and results of initial investigation. Table 16.3 provides a reference to some of the common conditions that can mimic certain presentations of inflammatory bowel disease.

Table 16.3 Differential diagnosis of IBD

IBD symptoms Common conditions included in differential diagnosis
Acute bloody diarrhea (UC or Crohn’s) Infective enteritis, e.g. Campylobacter
Diverticular disease
Ischemic colitis
Colon cancer
NSAID-induced colitis
Chronic diarrhea (Crohn’s or UC) Giardia
Celiac disease
Bile salt malabsorption
Bacterial overgrowth
Microscopic colitis
Lactose intolerance
Irritable bowel syndrome
Severe abdominal pain (Crohn’s) Any cause of an acute abdomen, e.g. appendicitis
Chronic abdominal pain (Crohn’s) Diverticular disease
Irritable bowel syndrome
Abdominal malignancy
Pelvic inflammatory disease
Endometriosis
Chronic pancreatitis
Biliary pathology
Peptic ulceration
Connective tissue disease of gut
Adhesions
Malabsorption/weight loss Celiac disease
Jejunal diverticula
Pancreatic insufficiency
Anorexia
Addison’s disease
Abdominal tuberculosis

NSAID: non-steroidal anti-inflammatory drugs

Prognosis

Ulcerative colitis

Ulcerative colitis tends to follow a relapsing and remitting course over time, with about 50% of patients in full remission at any time. Once a patient achieves remission following an attack they have about a 70% chance of having a further flare during the next year. This risk can be reduced but not avoided by use of maintenance therapy. For all patients, the risk of having a colectomy within the first 10 years of diagnosis is in the region of 25%, although this is likely to be lower for patients with limited or left-sided disease (Langholz et al., 1994). The prognosis following a severe attack of colitis has been discussed previously but, with modern treatment, the risk of death should not exceed 1%. Overall life expectancy is thought not to be reduced, but there is a clearly documented increased risk of developing bowel cancer among UC patients, with a likelihood of developing bowel cancer in the region of 5–10% after 20 years. This risk seems to be focused on patients with extensive disease of the colon and it is conventional to offer such patients regular surveillance.

Crohn’s disease

Like ulcerative colitis, Crohn’s disease also follows a relapsing and remitting course over time but, unlike UC, the natural history tends to involve the gradual development of complications such as strictures and fistulae. These in turn lead to the need for surgical correction, with around 50% of patients requiring surgery within 10 years from diagnosis (Solberg et al., 2007). In contrast to UC, surgery is not curative and the disease frequently recurs with about 50% of patients requiring a further operation within 10 years of their first procedure. A proportion of patients have disease that appears to follow an aggressive course, characterized by frequent relapse and rapid development of complications. In the past, these patients were at risk of developing intestinal failure over time but, fortunately, aggressive modern management of Crohn’s disease appears to be reducing this rate. However, most studies still show that average life expectancy is slightly reduced among patients with Crohn’s disease.

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