Inflammatory bowel disease
Ulcerative colitis occurs most commonly in temperate climates and in Caucasians. It is rare in Africa and the East. Ulcerative colitis is about two to three times more common than Crohn's disease, although the incidence of Crohn's disease is increasing. The disease is usually diagnosed between 15 and 45 years of age. The aetiology of ulcerative colitis is uncertain although familial clusters occur and some as yet unknown environmental factors may be relevant.
Ulcerative colitis is a mucosal disease that almost invariably affects the rectum and spreads proximally in a continuous manner. Inflammation is limited to the mucosa, except in fulminant cases, where transmural changes occur. The mucosa is congested and friable, with varying degrees of ulceration. Microscopy shows diffuse infiltration of acute and chronic inflammatory cells limited to the mucosa. The glandular structure is distorted, with goblet cell depletion and crypt abscesses. In chronic quiescent phases, the glands may be shortened and atrophic, although the endoscopic appearances may be relatively normal.
Differentiation between ulcerative colitis and Crohn's disease is most difficult when the disease is severe. In fulminant cases, the colitis is transmural, with deep ulceration and fissures. The histopathology can be confusingly similar to that of Crohn's disease. In some cases, diagnosis is made only after the rectum is removed or when Crohn's disease appears in the small bowel or the perianal region. Sometimes, the diagnosis remains uncertain and is labelled as ‘indeterminate colitis’.
Ulcerative colitis and dysplasia
Long-standing colitis may be associated with dysplasia of the epithelium. The absence of any dysplasia or the presence of high-grade dysplasia are generally well recognised by pathologists. The other categories of indefinite or low-grade dysplasia are much more variable and are subject to considerable inter-observer variation. Severe dysplasia is frequently associated with cancer elsewhere in the large bowel and represents a general field change. The incidence of dysplasia in longstanding total colitis is probably around 5–10%.
Risk for cancer rises significantly with the presence of a dysplasia-associated mass lesion (a plaque or large polyp) or stricture. The risk for cancer in colitis increases with the extent and duration of the disease. When carcinoma does occur, patients almost always have had the disease for at least 7 years. Carcinoma rarely occurs before 7 years. This time frame applies only to pancolitis (total colitis) and extensive colitis (from rectum to transverse colon and beyond). For total colitis, the risk for cancer is 3% at 10 years, rising by 1–2% per year thereafter. Patients with colitis cancers tend to be 10–20 years younger at presentation than those without inflammatory bowel disease. The tumours are more likely to be multiple and are more likely to occur in the right or transverse colon. Carcinoma in ulcerative colitis may occur in flat mucosa and may be missed on colonoscopy or barium enema. This fact provides a strong argument for routine colonoscopy surveillance with biopsy.
Surveillance for cancer in ulcerative colitis is controversial and there is no clear evidence that biopsy surveillance saves lives. In addition, cancer does arise in the non-dysplastic bowel. Surveillance with colonoscopy and biopsy is generally commenced after 7 years of disease in patients with extensive or total colitis at 2-year intervals. Biopsy specimens are taken either of specific lesions or from random sites of the colon, as dysplasia in one area may indicate the presence of an unsuspected cancer elsewhere in the colon. The risk of cancer in patients with left-sided colitis is much lower but rises sharply after 25–30 years of disease. Patients with a rectal stump after subtotal colectomy should be screened for dysplasia and carcinoma.
The clinical features depend on the severity and extent of colitis (Spectrum of ulcerative colitis). Extra-intestinal manifestations are listed in Extra-intestinal manifestations of ulcerative colitis.
The most common presentation is bloody diarrhoea in an otherwise fit patient. Patients with proctosigmoiditis may complain of tenesmus as well. More severe disease with extensive colonic involvement may cause severe diarrhoea with abdominal cramps and urgency at stool. Sigmoidoscopy shows a confluent proctitis with mucosal friability, contact bleeding, ulceration and granularity.
Acute toxic colitis
Toxic colitis and toxic megacolon are part of the spectrum of ulcerative colitis with severe attacks, and are more common in patients with pancolitis. While acute fulminating colitis usually occurs as an acute exacerbation of ulcerative colitis, it presents as an initial manifestation of inflammatory bowel disease in more than 60% of patients.
Acute toxic colitis is characterised by the abrupt onset of bloody diarrhoea, urgency, anorexia and abdominal cramps. Patients often are ill with severe anaemia and dehydration. A patient is toxic when, in addition to severe colitis, there is evidence of at least two of the following:
- tachycardia >100/min
- temperature >38.6°C
- leucocytosis >10.5×109/L
- hypoalbuminaemia <3.0g/100 mL.
Other features commonly present include stool frequency of more than nine per day, abdominal distension, tenderness, mental changes, electrolyte disturbances (hyponatraemia, hypokalaemia) and alkalosis.
Abdominal distension often indicates colonic dilatation, and tenderness suggests impending perforation. Toxic dilatation or megacolon is usually defined as a diameter exceeding 6 cm in the transverse colon on plain abdominal X-ray. Signs of septicaemia may be masked by the use of steroids.
Characteristic appearances include an erythematous mucosa with contact bleeding. The normal vascular pattern is lost and there may be blood and pus in the lumen. Biopsies are taken to establish the extent of the disease and the presence of dysplasia. A full colonoscopy is generally not performed in acute colitis because of the risk of perforation.
Double-contrast barium enema
Double-contrast barium enema will demonstrate the full extent of macroscopic disease, showing a tubular colon and mucosal ulceration.
General investigations include full blood examination, erythrocyte sedimentation rate and liver function test.
Therapy for chronic ulcerative colitis
Ulcerative colitis is a disease of remissions and exacerbations. Most management decisions are made on clinical grounds. Endoscopic evaluation is not essential but it may facilitate decisions on therapy. Colonoscopy and biopsy are more accurate than barium enema to define the extent of disease.
Steroids may be used orally, intravenously or topically as an enema. Although steroids are effective in inducing remission, they are not effective for maintaining remission. Side effects of corticosteroids are dose- and duration-related. Moon facies, acne, weight gain, mood swings, sleep disturbances and diabetes are common problems. Infections and perforations may be masked. Osteoporosis, aseptic necrosis and cataracts are problems that arise from long-term use. When steroids have been administered continuously for more than 1 month, adrenal suppression may ensue.
Sulphasalazine and aminosalicylates
Sulphasalazine is composed of sulphapyridine and 5- aminosalicylate (5-ASA) joined by an azo-bond. 5-ASA is the active therapeutic moiety, and sulphapyridine alone has no therapeutic effect and is responsible for most of the side effects.Asmall amount (approximately 20%) is absorbed by the small bowel and most of the sulphasalazine enters the colon, where the azo-bond is cleaved by colonic bacteria. 5-ASA is poorly absorbed from the colon and remains intraluminal, where it exerts the therapeutic effect. Sulphapyridine is absorbed and metabolised by the liver.
Sulphasalazine (4 g daily) benefits about 80% of patients with active mild or moderate colitis regardless of the extent of involvement. It is never used alone in severe colitis. Most patients respond within 2–3 weeks. Sulphasalazine is effective for maintenance therapy (2 g daily) in preventing relapses. It can be continued during pregnancy.
Side effects may occur in 20% of patients. Common dose-related problems of dyspepsia, nausea, anorexia and headache can be prevented by starting slowly with 500 mg qid daily for 3 or 4 days and then increasing the dose incrementally to 4 g daily. Enteric-coated tablets may be helpful. Allergic reactions with rash or fever, haematological side effects of haemolysis or neutropenia and sperm abnormalities are indications for cessation of sulphasalazine. Sulphasalazine interferes with dietary folate absorption. Folic acid supplementation is helpful in patients on long-term treatment with sulphasalazine.
When 5-ASA is taken alone by mouth, rapid absorption occurs in the upper small bowel. Various slowrelease preparations of 5-ASA have been developed and are effective in treating mildly or moderately active ulcerative colitis. They are the drug of choice in patients intolerant of sulphasalazine; however, they are more expensive. Common side effects of 5-ASA are diarrhoea, nausea and headache. Occasionally, there is a cross-allergic reaction between sulphasalazine and 5-ASA.
Azathioprine or its metabolite, 6-mercaptopurine (6-MP), is not effective as a single agent to treat acute colitis or to maintain remission. However, a steroidsparing effect is noted. Use is limited by a slow onset of action.
Although these agents have potentially serious side effects, adverse effects associated with the lower doses used in treating inflammatory bowel disease are infrequent. Pancreatitis and leucopenia are the most common side effects. Whenever possible, these drugs should be ceased 3 months before a patient becomes pregnant.
Cyclosporine may have a limited role in stabilising a patient with severe, steroid-resistant colitis to avoid emergency surgery. It has a rapid onset of action but has significant renal toxicity.
Antidiarrhoeal agents should be avoided in severe ulcerative colitis because of the risk of precipitating toxic megacolon. When the patient is not acutely ill, judicious use of loperamide, diphenoxylate or codeine and bulking agents is helpful to control symptoms and to retain medicated enemas.
Diet and nutrition
A balanced, nutritious diet is important. Some alteration in diet may help to minimise symptoms.
Therapy of proctitis and proctosigmoiditis
With proctitis alone, topical therapy with 5-ASA suppositories is effective. Other alternatives include steroid foam or 5-ASA enemas. This is usually prescribed for 4 weeks. If the symptoms have resolved, alternate-night therapy is continued for another 2 weeks. If remission has been achieved clinically and endoscopically, therapy can be stopped. Maintenance therapy is not routinely used unless the symptoms are difficult to control or there are frequent flares. If maintenance therapy is necessary, oral sulphasalazine 2 g daily may be preferred.
With proctosigmoiditis, steroid foam or 5-ASA enemas are more appropriate than suppositories. These preparations distribute medicine up to the splenic flexure. If there is no clinical response in 2–3 weeks, a trial of twice-daily enemas or oral sulphasalazine can be added. In refractory cases, oral prednisolone is prescribed to induce remission.
Therapy of extensive colitis
When colitis involves the colon proximal to the splenic flexure, systemic agents are usually necessary. The activity of the disease dictates which agents are used.
Patients with mild/moderate disease have diarrhoea, bleeding, flatus and abdominal cramps but they do not feel or look ill. About 80% of these patients respond to sulphasalazine alone.With repeated flares, long-term maintenance therapy with sulphasalazine is indicated. When patients have shown no clinical improvement after 4 weeks of sulphasalazine or 5-ASA alone, prednisolone may be added and then tapered. A check sigmoidoscopy or colonoscopy may be helpful to note the extent and severity of mucosal inflammation. Some patients have troublesome tenesmus and will respond to topical steroids or 5-ASA enemas.
While most patients can be withdrawn from steroids and maintained on sulphasalazine or 5-ASA until the next flare of disease, some patients require continuous steroid therapy. Immunosuppressive agents may be added for their steroid-sparing effect.
Patients with severe colitis are systemically ill and should be hospitalised. Initial investigations include a complete full blood examination and a serum biochemical profile. With severe toxic attacks, blood cultures and coagulation studies are also performed. A plain abdominal and erect chest radiograph is obtained to note whether there is any colonic dilatation and/or free intraperitoneal gas from perforation.
A limited unprepared sigmoidoscopy (preferably flexible) with minimal air insufflation is helpful, particularly in patients where a firm diagnosis has not been made. This will help to exclude pseudomembranous colitis and ischaemic colitis. Barium enema and colonoscopy are contraindicated in the presence of acute fulminating colitis. Stool cultures for enteric pathogens, Clostridium difficile, Campylobacter jejuni, Salmonella spp., Shigella spp., Escherichia coli and Amoeba are carried out.
Intravenous fluids are initiated to correct dehydration, hyponatraemia and hypokalaemia. Blood transfusion is sometimes necessary for anaemia. Total parenteral nutrition may be beneficial in severely ill patients.
Antibiotics are reserved for fulminant cases and are used to reduce the consequences of sepsis associated with microperforations from the friable bowel. Antibiotics effective against aerobes and anaerobes are used.
Therapy is initiated with 100 mg intravenous hydrocortisone given every 6 hours, or an equivalent dose of 60 mg prednisolone daily. In patients in whom a satisfactory response is obtained, the intravenous steroid dose is reduced after 5 days and changed to oral prednisolone. Immunosuppressive agents have little place in the treatment of toxic colitis, particularly if it appears that surgery may be indicated.
Narcotics are used with caution because of the potential of exacerbating toxic megacolon. Antidiarrhoeal agents are contraindicated.
Careful and regular clinical review with monitoring of heart rate, temperature, stool frequency, abdominal girth, leucocyte count and albumin level indicate clinical response to treatment. Serial plain radiographs of the abdomen will detect progressive colonic dilatation.
Therapy during pregnancy and nursing
Sulphasalazine and prednisolone do not have teratogenic effects. The neonate does not suffer adrenal suppression from the mother's steroid use. Immunosuppressives are not used in pregnancy, although there is a suggestion that azathioprine and 6-MP are safe in pregnancy.
Indications for surgery
Evidence of free perforation, generalised peritonitis and massive colonic haemorrhage indicates the need for emergency surgery. Surgery is indicated with deterioration of acute colitis (increasing toxicity or colonic dilatation) at any time after initiation of adequate medical management or if there has not been a clear improvement within 24–72 hours of admission. Development of toxic megacolon is usually an indication for early surgery. If the improvement has been minor after 5–7 days of adequate medical management, it is unlikely to sustain a long-term remission. In these cases, surgery is also indicated.
With adoption of more aggressive resuscitation, a coordinated plan of management and early operative intervention, mortality is less than 3%. In contrast, colonic dilatation complicated by perforation has a mortality of 33%. About half the patients with acute fulminating colitis respond to medical therapy, thereby avoiding emergency surgery. The majority of these patients develop repeated episodes of toxic dilatation or incapacitating chronic symptoms, ultimately requiring surgery.
The main indication for elective surgery is chronic illness that responds poorly to medical treatment or that is troubled by recurrent acute colitis. The threshold for surgery by gastroenterologists and patients is variable. With the advent of sphincter-preserving restorative proctocolectomy, surgery is now better accepted. Severe extra-intestinal manifestations are rare indications for surgery.
Dysplasia is currently the most sensitive marker of premalignancy. Its limitations have been discussed earlier. Presence of dysplasia from a villous or polypoidal lesion or from a stricture is an indication for prophylactic proctocolectomy. The presence of severe dysplasia from an area of flat mucosa at two separate sites in the colon is also an indication for surgery. The presence of low-grade dysplasia in flat mucosa is an indication for increased vigilance, and may ultimately require surgery.
The patient and the family are counselled jointly by the gastroenterologist and colorectal surgeon. The need for a stoma is discussed and the stoma site is marked pre-operatively. Steroids are continued and broadspectrum antibiotic prophylaxis is used. Mechanical bowel preparations are used for elective surgery but are contraindicated in emergency surgery. Prophylaxis for deep vein thrombosis is prescribed.
Restorative proctocolectomy entails removal of the entire colon and rectum. A close rectal dissection allows preservation of the pelvic autonomic nerves, especially the nervi erigentes. The technique is associated with sexual dysfunction in less than 1% of patients. A pouch is constructed using loops of the terminal 40–50 cm of ileum to replace the rectum and is anastomosed to the upper anal canal (A stapled ileal pouch-anal anastomosis.). Various designs of the ileal pouch have been described: two-loop J pouch, three-loop S pouch and four-loop J pouch (Different designs of an ileal pouch: (A) 2-loop J pouch, (B) 3-loop S pouch, (C) 4-loop W pouch. (With permission from Fazio VW, Tjandra JJ, Lavery IC. Techniques of pouch construction. In: Nicholls J, Bartolo D, Mortensen N, eds. Restorative Proctocolectomy. Oxford: Blackwell Science; 1993:18–33.)). The functions of various pouch designs are comparable. The two-loop J pouch is most popular because of its simplicity.
Controversies remain as to the distal level of anorectal transection: flush transection at the anorectal ring and a stapled ileal pouch-anal anastomosis, preserving a 2 cm strip of the anal transitional zone, or a handsewn anastomosis and stripping of the entire anorectal mucosa to the level of the dentate line. A stapled ileal pouch-anal anastomosis without mucosectomy is generally favoured because of technical expediency. The functional outcome with a stapled anastomosis is probably also superior.
Because of the large number of suture and staple lines involved and because many patients are on steroids, a temporary diverting loop ileostomy is generally performed. The diverting ileostomy is then reversed through a small parastomal incision about 3 months later. In selected ‘healthier’ patients, a diverting stoma may safely be omitted if the surgery proceeds smoothly.
Despite the technical complexity of restorative proctocolectomy, the procedure is safe. Specific postoperative complications include pelvic sepsis, with or without anastomotic breakdown, adhesive small bowel obstruction and ileostomy-related problems. Overall, 80% recover uneventfully and 20% experience some morbidity.
Functional results following restorative proctocolectomy continue to improve within the first 18 months after surgery. Most patients defecate five to six times daily and will be able to defer defecation without urgency. Few patients suffer severe faecal incontinence, although minor faecal spotting occurs in up to 25% during the day and 40% at night. Some 50% of patients use antidiarrhoeal or bulking agents at least intermittently.
Major failure requiring excision of the pouch occurs in only 2% of patients. The usual causes are persistent pelvic sepsis, unsuspected Crohn's disease or poor faecal continence.
Long-term sequelae of the ileal pouch are uncertain. ‘ouchitis’ is a vague syndrome associated with diarrhoea, abdominal cramps, low-grade fever, tenesmus and general ill health. It may be associated with endoscopic and histologic evidence of inflammation of the ileal pouch. Its pathogenesis is not known. Treatment of pouchitis is empirical. Most cases respond to metronidazole. Some require long-term low-dose metronidazole. In refractory cases, enemas containing steroid or 5-ASA can be used. In very severe cases, Crohn's disease must be excluded.
Complete proctocolectomy and permanent end ileostomy
With the advent of restorative surgery, complete proctocolectomy and permanent end ileostomy is currently indicated only in elderly patients with weak anal sphincters, in patients with advanced-stage rectal cancer and in those unwilling to undergo the more complicated restorative proctocolectomy.
Colectomy with ileorectal anastomosis
Colectomy with ileorectal anastomosis is rarely performed because it leaves the rectum with a continuing risk for inflammation and cancer. It might be considered in patients with coexisting severe portal hypertension where rectal dissection is hazardous or in children to allow them to pass through adolescence without a stoma or until conversion to a pouch.
Emergency surgery for severe acute colitis
The optimal operation is subtotal colectomy and end ileostomy (Abdominal colectomy for toxic megacolon. Lateral view showing the end ileostomy and the implanted rectosigmoid stump. (With permission from Tjandra JJ. Toxic colitis and perforation. In: Michelassi F, Milsom JW, eds. Operative Strategies in Inflammatory Bowel Disease. New York: Springer-Verlag; 1999:239.)) because of its simplicity and because it allows the later possibility of restorative surgery. Restorative proctocolectomy in the emergency situation is associated with a higher operative morbidity, especially in patients on high-dose steroids, and should be avoided. The diagnosis of ulcerative colitis and Crohn's disease is also often not clear in the acute situation.
The splenic flexure is usually the most dangerous area in an emergency colectomy because of inadvertent perforation. If the omentum is adherent to the colon, it should be resected together with the colon to minimise iatrogenic perforation.
The best way to manage the distal rectosigmoid stump remains undecided. Our preferred technique, in most cases, is to staple-transect the distal sigmoid colon at a level where it will lie without tension in the subcutaneous plane at the lower end of the midline incision. This technique avoids a troublesome discharging mucous fistula but allows for discharge of blood and pus through the wound should the distal stump break down. It also allows the rectum to be easily identified at a future laparotomy.
In 1932, Crohn and his colleagues described an inflammatory disease of the terminal ileum characterised by ulceration and fibrosis with frequent stenosis and fistula formation. They called it ‘regional ileitis’. It was later recognised that a similar inflammatory process could also affect the colon and perianal region. The cause of Crohn's disease remains unknown although immunological mechanisms play a role in the pathogenesis of mucosal inflammation.
Crohn's disease is a disease of young adults. The age at which Crohn's disease is first diagnosed peaks between 20 and 29 years, with a second smaller peak between the ages of 60 and 80 years.
Crohn's disease can affect any part of the gastrointestinal tract. Multiple areas may be involved with intervening areas of normal bowel, referred to as skip areas (Short strictures of the small bowel separated by normal skip areas.). The mesentery is thickened and the mesenteric fat creeps along the sides of the bowel wall toward the antimesenteric border. This is termed ‘fat wrapping’. The disease involves all layers of the bowel wall. Ulcerations range from small, shallow aphthous ulcers to deep fissuring ulcers. The fissuring of the mucosa and submucosal oedema can give the bowel a cobblestone appearance with the formation of pseudopolyps. Fistulas and abscesses result from full-thickness penetration of the ulcers. The bowel wall may become thickened with fibrosis, leading to stricture formation.
Perianal Crohn's disease includes large oedematous skin tags, deep fissures, perianal fistulas or abscesses.
The histological appearance varies depending on the severity of the disease but a lymphocytic infiltrate is usually seen in all layers of the bowel. Non-caseating granulomas are noted in about 50% of surgical specimens.
Extra-intestinal manifestations are similar to those described for ulcerative colitis (see Extra-intestinal manifestations of ulcerative colitis).
Patterns of intestinal involvement in Crohn's disease are often separated into three main categories: colonic (25%), ileocolic (40%) and small intestine alone (30%). Duodenal involvement occurs in only about 2%. The symptoms depend on the location of disease.
Small intestinal Crohn's disease
The most common symptoms of small intestinal Crohn's disease are diarrhoea (90%), abdominal pain (55%), anorexia, nausea and weight loss. Malaise, lassitude and anaemia are frequently present. Borborygmus denotes obstruction.
Most patients present with long-standing symptoms. Some patients present acutely with a complicated episode such as obstruction, inflammatory phlegmon, abscesses or fistulas. Occasionally, the initial presentation is with a more acute history of right iliac fossa pain and fever, and a misdiagnosis of acute appendicitis is made. The true diagnosis is revealed only at operation. Careful questioning often reveals a more chronic history that suggests Crohn's disease.
Complications of small intestinal Crohn's disease are given in Complications of Crohn's disease.
Barium small bowel follow-through will demonstrate the presence of strictures (Barium small bowel series showing small bowel strictures with proximal small bowel dilatations.), gross mucosal changes and internal fistulas. The length of the small bowel is also noted.
Small bowel enema (enteroclysis) allows better definition of the mucosal pattern than a conventional barium small bowel follow-through and demonstrates aphthous ulcers, fissures and mucosal oedema well.
Colonoscopy enables a full assessment of the colon. Focal inflammation and granulomas can be seen histologically even when the mucosa is macroscopically normal. Colonoscopy may also allow biopsy of the terminal ileal orifice when the radiological appearances of the terminal ileum are not conclusive.
Computed tomography (CT) scan may demonstrate internal fistulas, intra-abdominal abscesses and thickening of the bowel wall (Computed tomography scan showing thick-walled bowel loops in a patient with recurrent Crohn's disease after a prior ileocolic resection.).
Symptoms in Crohn's disease may be due to active inflammation or obstruction or result from previous surgery or bacterial overgrowth. Laboratory tests including full blood examination, albumin and erythrocyte sedimentation rate frequently help to determine the disease activity.
Labelled white cell scan (indium- or technetiumlabelled granulocytes) helps to differentiate whether the symptoms are primarily inflammatory or obstructive. It complements barium radiographs in detecting microperforation with abscess formation. This test is not widely used.
Crohn's disease cannot be cured. The principles of management include palliation of symptoms, control of inflammation and correction of nutritional deficiencies. About 80% of patients will require at least one operation during their lifetime.
For patients with mild to moderate disease, a 5-aminosalicylate, such as mesalazine, together with metronidazole can be used either alone or in combination. For patients with greater disease activity, oral prednisolone can be given. A short sharp course of corticosteroids is given. If the disease is going to respond to corticosteroids, this is usually complete after 4 weeks of therapy.
In severe Crohn's disease, the patient has symptoms of active disease such as diarrhoea, abdominal pain and weight loss, as well as being systemically unwell with fever and tachycardia. An abdominal mass may be present. These patients are hospitalised and are treated with intravenous hydrocortisone or high-dose prednisolone. Fluids and electrolytes are replaced. Blood transfusion may be necessary for anaemia. Intravenous broad-spectrum antibiotics such as second- or thirdgeneration cephalosporins and metronidazole are often given empirically. Most patients settle with this regimen of treatment. Parenteral nutrition is considered if serious complications such as fistulas are present or if surgery is likely.
In patients with chronic active disease, flare-ups of symptoms occur whenever the prednisolone dosage falls below 15 mg daily. They may benefit from immunosuppressive therapy. Either azathioprine or 6-mercaptopurine is used. These drugs take several weeks before a benefit is evident and may allow withdrawal of the prednisolone. Their mode of action and duration of treatment are not clear. In general, if a benefit has been demonstrated, the immunosuppressant is maintained for 1–2 years. Side effects include nausea and diarrhoea. Full blood examination at 2-month intervals is performed because bone marrow suppression occasionally occurs. The role of cyclosporine A is still being evaluated in clinical trials.
Maintenance of remission
In contrast to ulcerative colitis, there is no convincing evidence that any drug is useful in maintaining remission of small bowel Crohn's disease.
In a few studies, mesalazine in high doses has been shown to have some effectiveness in maintaining remission and might reduce relapse following surgical resection or strictureplasty. Low-dose prednisolone may also have a small benefit.
Treatment of diarrhoea depends on its causation; treatment of active disease has been discussed and bacterial overgrowth is treated with metronidazole. A bile salt-induced diarrhoea following ileal resection is treated with cholestyramine. Finally, antidiarrhoeal agents such as codeine phosphate, loperamide and diphenoxylate hydrochloride may have a small role.
Surgery for small bowel Crohn's disease
Crohn's disease is a diffuse intestinal problem and there is a high incidence of recrudescence of Crohn's disease at various sites. The rate of recurrence increases with the length of follow-up. The cumulative operation rate for patients with distal ileal disease is 80% at 5 years from the time of diagnosis. Crohn's disease cannot be cured by surgical excision and a group of patients will require repeated resections with time. Thus, there is a tendency towards more conservative or minimal surgery to minimise the risk of short-bowel syndrome from excessive resections of the small bowel. Surgery is mainly indicated for:
- stricture-causing obstructive symptoms
- phlegmonous disease not responding to medical therapy
- enterocutaneous or enterovesical fistulas
- intra-abdominal abscesses (most of these are now drained by percutaneous radiological techniques)
- acute or chronic blood loss (this is a rare indication).
The severely diseased segment is resected with a 2-cm margin of macroscopically normal bowel on either side. With extensive disease, minor evidence of Crohn's disease at the anastomotic site does not matter. The emphasis should be on preserving bowel length.
The cumulative re-operation rate after the first resection for distal ileal disease is 25% at 5 years after the first operation. Aphthous ulceration on the ileal side of the ileocolic anastomosis is present in almost all patients within 12 months of ileocolic resection. Although recurrent disease after surgery is common, surgery rapidly restores patients with incapacitating obstructing symptoms to good health.
In selective cases, strictures of the small bowel may be overcome by strictureplasty without resection. The stricture is incised longitudinally along the antimesenteric border and then sutured transversely as in Heineke-Mikulicz strictureplasty (Heineke-Mikulicz strictureplasty. The stricture is (A) incised longitudinally along the antimesenteric border and (B) then sutured transversely.) or in a side-to-side bypass as in Finney strictureplasty (Finney strictureplasty for a longer stricture using a side-to-side bypass. (With permission from Tjandra JJ, Fazio VW. Strictureplasty in Crohn's disease. In: Cameron JL, ed. Current Surgical Therapy, 4th ed. Philadelphia: Mosby Year Book; 1992;108–113.)). Strictureplasty can be accomplished with a surgical morbidity similar to resection. It relieves obstruction, modifies the progression of the disease and allows preservation of functional small bowel.
Fistula and abscess
Fistula and abscess often coexist. Small bowel enema or contrast follow-through is used to evaluate the extent of Crohn's disease in the small bowel and the presence of fistulas. Colonoscopy is performed to rule out severe disease in the colon, and especially the rectum. A CT scan will demonstrate any abscesses that may be appropriately treated by CT-guided percutaneous drainage. Fistulography sometimes provides useful information about the complexity of the fistulous tracks.
Internal fistulas are often asymptomatic and are identified incidentally at surgery. Ileosigmoid fistulas are usually due to ileal disease. Enterovesical fistulas will cause recurrent urinary tract infections and pneumaturia. The small bowel disease is resected and the viscera that is secondarily involved is closed locally. Following repair of an enterovesical fistula, a Foley catheter is left in the bladder for at least a week.
Enterocutaneous fistula in the early post-operative period is a challenging problem. It arises from anastomotic breakdown or from inadvertent damage to the small bowel unrecognised at the time of surgery. Principles of management are discussed in Chapter 28.
Colonic disease presents with bloody diarrhoea, urgency and frequency. Fibrosis and stricture may lead to subacute large bowel obstruction. Fistulation to adjacent viscera include colovesical or rectovaginal fistula. Perianal disease commonly accompanies Crohn's colitis: fleshy anal skin tags, anorectal strictures, relatively painless chronic anal fissures and painful anal canal ulcers with complex perirectal fistulas. The differences between ulcerative colitis and Crohn's colitis are given in Table 31, “Differentiation between ulcerative colitis and Crohn's colitis”.
|Ulcerative colitis||Crohn's colitis|
|Inflammation||Mucosal and submucosal||Transmural|
|Mucosa||Granular, ulcerated||Cobblestone, patchy inflammation|
|Small bowel involvement||No||Common|
|Complex anal lesions||No||Common|
|Internal fistula||No||May be|
|Carcinoma||Common in extensive and long-standing cases||Common in extensive and long-standing cases|
Steroids and mesalazine are the mainstay therapy for Crohn's colitis. Occasionally azathioprine is used for severe disease. Nutritional support is important.
Acute fulminant colitis with toxic dilatation and perforation may occur as in ulcerative colitis. Perforation can occur without toxic dilatation. The procedure of choice is a subtotal colectomy with formation of an end ileostomy.
Severe colonic bleeding may also necessitate urgent surgery. Subtotal colectomy and ileorectal anastomosis is appropriate if the rectum is relatively free of disease and the patient is fit.
Subtotal colectomy and ileorectal anastomosis is indicated in patients with severe diffuse colonic disease and rectal sparing, especially in younger patients. This operation is unwise if there is severe perianal or rectal disease or if the anal sphincters are functionally inadequate. Recurrent disease tends to occur in the pre-anastomotic segment of ileum or in the retained rectum. Many of these recurrences may be treated medically.
Total proctocolectomy and end ileostomy is indicated for extensive Crohn's colitis involving the rectum, with or without perianal disease. Sometimes this is performed for severe perianal Crohn's disease. There is a high incidence of delayed perianal wound healing, especially if there is severe perianal Crohn's disease. Preliminary faecal diversion prior to proctocolectomy may expedite healing of the perineal wound.
Perianal Crohn's disease
More than half the patients with Crohn's disease have anal lesions, especially those with rectal disease. The most common anal lesions are fleshy anal skin tags or anal fissure. These anal fissures are often at atypical sites and cause little pain, unless there is a cavitating ulcer or an associated abscess. Perianal fistulas and abscesses are often multiple and complex. Stricture at the anorectal ring is common as well.
Conservative medical and surgical treatment is the key. The underlying anal sphincter is preserved as much as possible. Many anal lesions are relatively asymptomatic and do not require specific treatment. Metronidazole, ciprofloxacin, steroids and azathioprine can have good therapeutic effects. Anti-tumour necrosis factor-α antibody is the latest development in the medical treatment of severe perianal Crohn's disease.
Proper assessment may demand an examination under anaesthesia, especially in the presence of anorectal stricture and undrained pus. Endorectal ultrasound facilitates assessment of complex fistulous tracts and abscesses.
Haemorrhoids are common problems but most have few symptoms. Dietary and topical management alone are adequate. In troublesome cases, elastic-band ligation may be performed. A haemorrhoidectomy should be avoided because of the risk of secondary sepsis and fistula formation. Anal surgery for fissure should be avoided whenever possible. Associated abscesses are drained but the anal sphincters must be preserved as much as possible. With more complex fistulous abscesses, a long-term seton through the fistula functions as an effective drain. A tube drain is also effective. If the disease is progressive or fails to respond to adequate local drainage procedures, consideration should be given to faecal diversion, followed by a proctectomy in severe cases.
Rectovaginal fistula poses a special problem in Crohn's disease. Asymptomatic patients need no treatment. A low anovaginal tract may be laid open with division of a minimal amount of the anal sphincters. In a more proximal fistula where there is no severe rectal disease, a mucosal-submucosal flap of the rectum may be advanced to repair the fistula, constituting the advancement rectal flap.
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