Inflammatory Bowel Disease

Introduction

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Inflammatory bowel disease (IBD) classically refers to Crohn’s disease and ulcerative colitis (UC). Both are chronic inflammatory diseases of the gastrointestinal (GI) tract of uncertain aetiology.

1.  Aetiology, Genetics, Pathogenesis and Pathology

Although aetiologies are unknown, the consensus is that IBD is a response to environmental triggers (infection, drugs or other agents) in genetically susceptible people. Whatever the initiator, an immune response against gut constituents — predominantly cell-medicated in Crohn’s disease and humoral and cell-mediated in UC — appears critical to pathogenesis, and production of inflammatory mediators such as cytokines are crucial.

Pathologically the two forms differ. Crohn’s disease is a focal intestinal inflammation characterized by aphthous ulcers, transmural lesions, granulomas, fat wrapping and skip lesions. It is associated with fistulas, abscesses, strictures and obstruction. Any part of the GI tract can be affected, ileocolonic disease being the most common.

In contrast, UC is a continuous, symmetrical, colonic mucosal inflammation, often associated with bleeding. Around 45% of UC patients have disease limited to the rectosigmoid, and only 20% have pancolitis.

2.   Epidemiology

IBD is more common in cooler latitudes and can occur at any age, but is most commonly diagnosed in late adolescence or early adulthood. Crohn’s disease is more common in women and smokers; UC more common in men and non-/ex-smokers.

3.   Clinical Features

Clinical features vary depending on the form and anatomic distribution of the disease. In acute presentations, assessing disease activity and identifying potentially serious complications of the disease and its treatments are equally important. To determine severity, the Truelove and Witts criteria for UC use tool frequency, rectal bleeding, fever, tachycardia, anaemia, and raised ESR. The Crohn’s Disease Activity Index uses abdominal pain, general wellbeing and opiate use, stool frequency, presence of complications, abdominal masses, anaemia and weight loss.

GI complications may include fulminant colitis, toxic megacolon, bleeding, obstruction, abscesses, perforation, fistulas, strictures, and neoplasia. Acute arthropathy and rashes are common extra-intestinal manifestations of IBD, but thromboembolic, ocular and hepatobiliary complications can be more serious and require specific therapy.

3.1    History

Diarrhoea is a frequent complaint, and the duration, number and type of motions per day are useful in assessing the activity and form of IBD.

In UC more than six motions per day suggests severe disease, and fewer than four mild disease. Bloody diarrhoea, mucus, tenesmus and rectal complaints are more common in UC. In Crohn’s disease abdominal pain and anal complaints including fissures, along with diarrhoea without rectal bleeding, are more common.

Abdominal pain in Crohn’s disease is commonly right-sided, and worse with eating. In UC, pain is less frequent and usually crampy, lower abdominal, and relieved by passing a motion. If pain is more severe, other GI complications should be considered. Fever is a marker of disease severity in IBD. Weight loss is more common in Crohn’s disease than in UC.

Enquiry for extraintestinal manifestations and past surgical procedures is helpful. A careful drug history is essential, as treatments such as steroids and immunosuppressants can cause complications.

3.2    Examination

Anaemia, fever >37.5^oC, pulse more than 90/min and abdominal tenderness are markers of more severe disease, particularly in UC. The presence of fever, dehydration, orthostatic hypotension, abdominal tenderness, distension and hypoactive bowel sounds suggests fulminant colitis. An abdominal mass is more common in Crohn’s disease and is associated with increased disease severity.

Abdominal distension raises the question of fulminant colitis, toxic mega-colon or obstruction. Toxic megacolon (colonic dilatation with severe colitis, fever, abdominal distension and tachycardia) is potentially lethal but uncommon. Rectal examination may show anal fissures, abscesses or fistulae (more common in Crohn’s disease). In patients taking immunosuppressants, signs of sepsis should be sought. A survey of joints, eyes, skin and vasculature can identify extraintestinal complications.

4   Clinical Investigation

4.1    Laboratory Tests

A full blood count to quantify anaemia and determine the need for transfusion is helpful. Leukocytosis may be present in acute disease, but leucopenia may be seen if the patient is on immunosuppressants. The ESR is usually > 30 mm/h in severe UC. Electrolytes and renal function may be abnormal in dehydration.

Iron, folate and vitamin B₁₂ deficiencies, and hypoalbuminaemia are common in IBD. Disturbed liver function tests suggest hepatobiliary complications or drug toxicity. Faecal cultures may be helpful to rule out infective diarrhoea as a cause of symptoms.

4.2    Radiology

On acute presentation, particularly with abdominal pain, abdominal and chest X-rays looking for free gas with perforation, dilated bowel loops and air-fluid levels with obstruction, or dilated transverse colon (>6 cm) with toxic megacolon may be helpful, depending on clinical features. If the transverse colon is dilated more than 12 cm, perforation is imminent. Computed tomography (CT) is indicated when fistulas, intra-abdominal or retroperitoneal abscesses are suspected. Barium studies will diagnose and differentiate between Crohn’s disease and UC, but are contraindicated in acutely unwell patients because of the risks of perforation or obstruction. MRI and ultrasound are used acutely in some centers.

4.3    Endoscopy

Endoscopy is useful for diagnosing IBD, for staging activity, and in screening for strictures or cancer. Cautious sigmoidoscopy is safe in the acutely unwell patient, but colonoscopy carries a risk of perforation. The role of wireless video capsule endoscopy is unclear.

5. Management

5.1    General Measures

Initial assessment should focus on the detection and treatment of life-threatening conditions such as septic or hypovolaemic shock, severe anaemia or dehydration. Thereafter, assessment focuses on disease activity/severity and the presence of complications. Intravenous fluid therapy, correction of electrolytes and/or transfusion may be necessary.

For abdominal pain, appropriate analgesia should be provided. Opiates should be used with caution in severe colitis as it has been suggested that toxic megacolon may be precipitated. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) appear to exacerbate IBD. Selective NSAIDs such as celecoxib may not exacerbate IBD but carry other risks. If toxic megacolon is suspected, nasogastric drainage, intravenous steroids and other medical therapy as discussed below should be commenced. Complications requiring surgery, such as bowel obstruction Opens in new window, intra-abdominal sepsis or perforation, should be ruled out early.

Treatment for IBD is usually a stepwise approach depending on severity and response with aminosalicylates and antibiotics first, then corticosteroids and immunomodulators, progressing to biologic agents and surgery.

5.2    Medical Therapy

Aminosalicylates (sulfasalazine, 5ASA/mesalamine) are used to treat mild to moderate IBD, but are more commonly effective in maintaining remission in UC. Metronidazole and/or ciprofloxacin is effective in treating perianal fistulas in Crohn’s disease. In UC, antibiotics are used preoperatively or to treat pouchitis, but otherwise are not of proven benefit, although some studies show that rifaximin, a poorly absorbed antibiotic, may be effective.

Corticosteroids induce remission of IBD but are not useful as maintenance therapy. Rectal steroids are used in mild to moderate distal UC, and prednisone 40–60 mg/day or equivalent is used for moderate or more proximal IBD. High-dose parenteral steroids (48–60 mg methylprednisolone/day) are reserved for fulminant disease. Budesonide, which has low bioavailability but high potency, appears effective both topically and orally in IBD, with fewer systemic side effects.

Immunomodulators such as azathioprine and 6-mercaptopurine are used as steroid-sparing agents or in steroid-resistant disease, but bone marrow suppression, pancreatitis Opens in new window and hepatotoxicity can be problems. Methotrexate may be useful in Crohn’s disease, and ciclosporin may be useful in severe UC.

Infliximab (anti-tumor necrosis factor (TNF) antibody) has been shown to be effective for severe or refractory Crohn’s disease, although active sepsis is an absolute contraindication. Infliximab also appears effective for refractory UC. Other immunosuppressants have been trialled.

Nutritional support, such as elemental diets or parental nutrition, is more helpful in Crohn’s disease than in UC. Vitamin and trace element supplements are more important in Crohn’s disease than UC, and in those on steroids. Antidiarrhoeals may be useful for symptom control in mild disease.

5.3    Surgical Therapy

Indications for surgery in IBD include fulminant colitis, toxic megacolon, perforation, severe GI haemorrhage, intractable disease, stricture with obstruction, abscesses, fistulas or cancer. In patients with fulminant colitis or toxic megacolon who do not respond to medical therapy, or deteriorate, subtotal colectomy is indicated. Intra-abdominal abscesses, more common in Crohn’s disease, can be drained percutaneously under CT or ultrasound guidance, but may require laparotomy.

In UC proctocolectomy is curative; however, subtotal procedures and anastomoses are often performed when disease is limited or when patients wish to avoid a stoma. As Crohn’s disease has a high recurrence rate after segmental resection, surgery is conservative to preserve bowel length and function.

6. Disposition

Patients with moderate or severe IBD require admission, usually for a trial of medical therapy. Surgical admission is indicated for perforation, obstruction, intra-abdominal sepsis or toxic megacolon. Patients with mild IBD and no complications can be managed as outpatients, with gastroenterology follow-up.