Ulcerative colitis (UC) was described almost 150 years ago. Despite significant advancements in the knowledge of inflammatory bowel disease (IBD), this disorder’s cause and treatment remain unresolved. Although classically thought of as a disorder of adults, many children are affected. The pediatric surgeon is often instrumental in caring for patients with this disabling disease.
No precise etiology for UC has been determined, although several theories have been suggested. It is likely that UC is due to a combination of genetic predisposition and environmental exposure to either environmental, infectious, or dietary factors. The identification of an IBD1 gene locus in Crohn’s disease supports the genetic association with IBD, although such a gene has not been identified in ulcerative colitis. A pproximately 15% of patients with UC are from families with members who have IBD. Studies of HLA antigens in patients with idiopathic ankylosing spondylitis, uveitis, and ulcerative colitis suggest a genetic predisposition, although no definite relationship has been determined. Psychological factors and stress may provoke relapses, contributing to the chronicity of the disease.
Ulcerative colitis is a disease of the rectal and colonic mucosa (the inner lining of the large intestine). The rectum is involved in more than 95% of patients, and inflammation extends proximally in a contiguous manner. Crypt abscesses are the most characteristic microscopic feature, leading to ulceration of the mucosa. In acute stages of UC, the colon distends and becomes thin; this may progress to a serious infection called toxic megacolon. With chronic ulcerative colitis, the colon becomes stiff and thickened, and what has been termed a “lead pipe” by contrast radiographs. In remission, the colon may revert to a near-normal appearance. Colonoscopy with mucosal biopsy helps to confirm the diagnosis and assess the activity of the disease.
Ulcerative colitis chiefly affects persons after the second decade of life, but at least 20% of all patients manifest symptoms before age 18. Males and females are equally affected; however, the condition is more prevalent in whites as well as Jews. The disease seems to be increasing in the United States and in Europe, although it remains uncommon in Asia .
Symptoms of UC typically begin with persistent diarrhea followed by the appearance of blood, mucus, and pus in the stool. Cramping lower abdominal pain and tenesmus (urgency to defecate) are common. Anorexia, weight loss, and growth retardation from chronic inflammation, poor appetite, and prolonged use of corticosteroids tend to occur when the disease is chronic. As a result, many children experience feelings of inferiority and lack a desire to participate in social and physical activities.
Most children with UC develop recurrent colitis with periodic relapses precipitated by emotional stress or intercurrent infection. After a few years, some patients may achieve permanent remission, although most experience chronic colitis with shorter and less frequent remissions. A single attack with complete remission occurs in less than 10% of children.
In approximately 15% of children, the onset of ulcerative colitis is acute and severe, with profuse bloody diarrhea, severe abdominal cramps, fever and sepsis (severe infection), requiring prompt hospitalization and treatment. Although most improve for varying periods with medical therapy, approximately 5% of patients develop toxic megacolon, requiring urgent operation. At least 60% of children with colitis eventually require surgical resection.
Cancer of the colon or rectum has been reported in 3% of patients during the first 10 years of disease, increasing by 20% in each subsequent decade. Cancer may develop even in patients with apparent remission. Cancer is more common in patients who have pancolitis, in patients whose symptoms began in childhood, and in patients who have frequent flare-ups of symptoms. Evidence of dysplasia of the colonic mucosa on the biopsy specimen indicates a high risk for development of carcinoma.
Extracolonic manifestations include growth retardation, arthralgias, skin lesions, failure of sexual maturation, anemia, liver disease, osteoporosis, and kidney stones. Arthralgias occur in approximately 20% of patients with ulcerative colitis, usually involving the knees, ankles, and wrists. Joint symptoms occasionally precede the onset of intestinal symptoms, sometimes being confused with juvenile rheumatoid arthritis. Ankylosing spondylitis may be seen in 1% to 6%, and sacroiliitis may be seen in 4% to 18% of patients.
Abnormal liver function tests are found in approximately 15% of patients, often due to a liver disorder such as pericholangitis, fatty infiltration of the liver, or a serious condition called sclerosing cholangitis. Patients with sclerosing cholangitis may have pruritus and right upper quadrant pain. Diagnosis is made by a special endoscopic exam called ERCP (endoscopic retrograde cholangiopancreatography). Anemia is common, usually the result of blood loss in the stool. Osteoporosis may occur from decreased calcium absorption and by increased urinary losses of calcium resulting from steroid therapy. Kidney stones occur in about 8% of patients, largely because of inadequate fluid intake to compensate for diarrheal losses and increased oxalate absorption in the terminal ileum. Uveitis is an inflammation of the iris found in less than 2% of patients.
Children with mild ulcerative colitis or who are in remission may manifest few if any positive findings on examination, although sigmoidoscopy may show friable and edematous mucosa with a thin purulent exudate. These children often show evidence of delayed growth, lack of sexual maturation, anemia, pallor, and cushingoid features from long-term corticosteroid therapy. With more severe disease, children may develop fever, dehydration, and symptoms of systemic toxicity. On sigmoidoscopy, the mucosa is often edematous and hemorrhagic and contains superficial ulcers. The mucosa is covered with a purulent, bloody exudate.
Although barium enema radiographs have been used for many years to establish the extent and severity of ulcerative colitis, most physicians recognize that better information can be obtained from flexible colonoscopy. When performed, the radiographic contrast enema study may reveal a shortened, narrow, and rigid colon with loss of haustral folds with chronic ulcerative colitis. In acute colitis, the bowel contour may have an irregular serrated border from mucosal ulcerations. The edematous mucosa between areas of ulceration appear as pseudopolyps. Swollen, inflamed mucosa can form symmetric defects along the borders, known as thumbprinting.
Differentiation of ulcerative colitis from other diseases is essential. An upper gastrointestinal series with small bowel follow-through can help differentiate Crohn’s disease from UC. Culturing of stool to rule out an infectious cause is essential because several organisms may mimic the symptoms of ulcerative colitis. Pathologic review of biopsy specimens from colonoscopy is essential. Nevertheless, 10% of patients may not be assigned accurately to either Crohn’s disease or ulcerative colitis, and have a diagnosis termed indeterminate colitis.
To address more accurately the differentiation between various causes of IBD, a panel of serologic tests has been developed. These include antineutrophil cytoplasmic antibody (ANCA), with a perinuclear staining pattern being observed in ulcerative colitis patients (pANCA). Conversely, antibody to Saccharomyces cerevisiae (ASCA) had been identified in nearly 50% of patients with Crohn’s disease. An additional antibody, anti–cathepsin G, has been identified in 63% of ulcerative colitis patients and is particularly prevalent in patients with active disease. Because of the relatively low predictive value of these tests, application of these measurements only allows one to confirm a clinical diagnosis.
Medical therapy for ulcerative colitis is based on measures to provide symptomatic relief. It is unlikely, however, that the ultimate course of the disease can be altered or a cure achieved by nonoperative treatment. Medical management may be stratified based on the clinical severity of the disease process. Patients with stable disease or who are in remission may benefit from the use of 5-aminosalicylate-based compounds, such as sulfasalazine (Azulfidine). These drugs are a mainstay for the treatment of patients with mild or moderate forms of the disease. The function of these drugs seems to be in the 5-aminosalicylate portion of the compound, which blocks the production of prostaglandins and leukotrienes. Use of different derivatives of these compounds may direct therapy to a targeted site. This includes the use of a suppository or enema for proctitis and oral compounds that are not broken down in the small bowel for targeting colonic tissue (mesalamine [Rowasa enema or oral Pentasa]).
For patients who have an acute exacerbation of symptoms, corticosteroid therapy is often used. Topical corticosteroids, such as hydrocortisone (Cortenema), can be used for a severe, distal inflammatory process. Oral prednisone is used for severe ulcerative colitis, and intravenous dosing is given for patients who are hospitalized. In general, patients respond to steroids within 7 to 10 days. Steroid therapy should be given only as long as there is an acute inflammatory process. Tapering should be instituted, with a transition to other medications. Side effects of corticosteroids should be anticipated, including growth failure, osteoporosis, hypertension, hyperglycemia, and cushingoid features.
Immunosuppressive therapy (azathioprine, 6-mercaptopurine, cyclosporine) has been advocated for patients with chronic or refractory ulcerative colitis. Azathioprine and mercaptopurine work on subgroups of T cells, and require a prolonged length of administration before their action takes effect. These drugs should be started while the child is tapering off of corticosteroids. Monitoring of the white blood cell count is essential. Additionally, both drugs may cause pancreatitis and drug-induced hepatitis. Cyclosporine works by preventing T-cell activation and by inhibition of IL-2 and IL-2 receptor expression. Its onset of action is much faster than azathioprine. It has equal efficacy to corticosteroids in treating patients with severe ulcerative colitis, and is useful in severe steroid-refractory disease. Cyclosporine does have shortcomings, however, in that it is highly immunosuppressive.
Still controversial is the use of anti–tumor necrosis factor therapy (infliximab). Although often used in patients with Crohn’s disease, a limited study of 17 adults showed that 16 responded within 6 days, with a sustained response in 2 to 10 months. Colectomy was required in only one patient.
Psychotherapy may help a patient with chronic ulcerative colitis adjust to the disease, its complications, and its side effects. Even more important than psychotherapy is the ready availability of a sympathetic and interested physician and an understanding family on whom the patient can rely.
During acute flare-ups of UC, most patients require hospitalization with intravenous fluid administration, bowel rest, increased doses of steroids, and parenteral nutrition. These measures correct the patient’s metabolic deficit and often reduce the clinical symptoms. Progression of the colitis or failure to respond to therapy is an indication for urgent operation. When the acute attack subsides, the patient may begin consuming a bland high-calorie diet.
Antidiarrheal medications, such as diphenoxylate hydrochloride with atropine sulfate (Lomotil) or loperamide hydrochloride (Imodium), may reduce the number of bowel movements and decrease rectal spasm, but they should be used with care because these drugs may induce toxic megacolon. Dietary modification may be useful to minimize intestinal stimulants (e.g., elimination of chocolate, vinegar, spicy foods, fresh vegetables, and nuts).
Ulcerative colitis can be cured by surgically removing the diseased colon and rectum. Historically, this was performed by creation of a permanent ileostomy, and the operation often was delayed until the patient was severely ill. However more recently, the growing popularity of a total proctocolectomy and endorectal pull-through procedure has allowed for consideration of surgery for many patients with chronic ulcerative colitis before severe disability and major complications develop.
Surgery in children with ulcerative colitis can be elective or emergent. Elective operation is performed on patients with chronic disease who experience continued symptoms despite medical therapy, growth retardation, severe limitation of activities, and an unacceptable quality of life. Emergency indications for operation include fulminant disease refractory to medical therapy, extensive rectal bleeding, and toxic megacolon. If the indication for surgery is growth failure, the diseased colon should be removed while the epiphyses (bone growth plates) are still open to allow for growth and development. Evaluation of the child’s condition should be done periodically during the course of therapy by the surgeon and the gastroenterologist to consider alternatives to long-term medical therapy.
Surgical options are discussed in detail beforehand with the patient and the parents. Preoperative discussion with an enterostomal therapist also helps to prepare the child and parents for an ileostomy. A short course of parenteral hyperalimentation may be used if the patient is severely malnourished. Corticosteroid therapy is maintained to avoid an acute flare-up preoperatively. Oral intake is restricted to clear liquids for 48 hours before surgery. Cleansing enemas are avoided because they may precipitate an acute flare-up of colitis. Oral antibiotics are given on the day before the operation, and intravenous antibiotics are given preoperatively.
In as much as ulcerative colitis is primarily a disease of the mucosa, a modification of the rectal mucosal stripping procedure described for treatment of Hirschsprung’s disease was the first pull-through procedure used for children. Removal of the entire rectal mucosa down to the dentate line generally does not interfere appreciably with sphincter function. Often a “double-stapled,” anastomosis may be recommended; one should discuss each option carefully with your surgeon prior to surgery.
Although numerous modifications of the endorectal pull-through have been made, it now is generally accepted as a highly desirable option for treatment of ulcerative colitis. Stooling frequency is typically high initially, regardless of whether a pouch is used or not. Another problem is nocturnal incontinence. This latter problem is particularly prevalent in younger children, with the process resolving as the child matures. Finally, it is common for children to be on multiple medications to control stooling frequency; however, most of these patients eventually wean off most of these medications.
The approach to the operation involves either a straight pull-through or the creation of a pouch. Choice of either depends on weighing the risks and benefits of each procedure. The pouch is associated with fewer bowel movements, particularly in the first year after the procedure. A pouch has the attendant risk of pouchitis, however, which may occur in 50% of patients after 10 years following pull-through. The straight pull-through avoids the risk of pouchitis; however, it is associated with more frequent bowel movements in the first postoperative year. Regardless of the type of procedure performed, as long as the lower 4 cm of the rectal muscle is not damaged, the anal sphincter resting pressure and the anal sphincter squeeze pressure approach normal values within 6 weeks.
Early surgical experience with pull-through operations indicated that a completely diverting, protecting ileostomy for several months is often advisable to minimize the risk of pelvic infection. Anastomotic leak has been found in approximately 10% to 15% of patients and has the attendant risk of leading to anal stricture. Nonetheless, some adult series have been reported in which protective ileostomy has not been used.
Two basic pouch reservoir types are generally used: the S-shaped reservoir, the J-shaped reservoir. Pouch stasis can occur, and an irrigating catheter may be required for adequate emptying. After several months, the reservoir tends to enlarge, and the spout elongates. The J-shaped reservoir, the most common pouch currently used, is usually constructed with a stapling instrument.
Intravenous steroids are tapered rapidly after surgery. Most children are discharged from the hospital by the seventh postoperative day. A water-soluble contrast enema is often performed within the first 2 months to ensure that the ileal reservoir has healed securely, and there are no leaks or sinus tracts. Most children resume full physical activities within 3 weeks. Several months after the first operation, the child may be recommended for ileostomy closure.
Management of patients following final intestinal reconstruction may be challenging. When oral feedings are begun, it is important to limit foods that cause excess stooling, including chocolate, vinegar salad dressings, and spicy foods. Medical management starts with a combination of pectins in the form of Kaopectate and low doses of Imodium. Small amounts of fiber (Metamucil or Fibercon) may be given to increase fecal bulk for the first few weeks, if necessary. Occasional rectal examinations are performed to maintain the patency of the rectal anastomosis. Use of oral metronidazole may be helpful in controlling episodes of frequent stooling because it leads to considerable bulking of the stool.
Regardless of the type of pull-through, stool frequency and continence are similar in large series of patients followed for many years. Complications are multiple, and children need long-term follow-up and care to attend to these problems .
Pouchitis first is as an inflammatory state resulting from stasis within the reservoir. Incidence may be 50% in patients followed for more than 10 years. The process may relate to the original disease because pouchitis is seen infrequently in patients with familial polyposis. Symptoms include fever, pelvic pain, bloody stools, diarrhea, and malaise. Treatment with antibiotics (metronidazole or ciprofloxacin) is usually successful. Occasionally, patients may benefit from steroid enemas. The use of probiotics may be beneficial in preventing recurrence of pouchitis when the patient is in remission.
Recurrent pouchitis may be a manifestation of Crohn’s disease, and biopsy specimens should be obtained. It has become apparent that pouchitis is more common in larger reservoirs, which empty only partially with each defecation. Although stenosis at the ileoanal anastomosis may seem to be a mild, annoying problem, it can cause reservoir distention, stasis, and pouchitis if not corrected early. Fistulas from the pouch to the perianal skin or vagina may be seen in 4% to 7% of patients. Pouch loss resulting from multiple procedures may be as high as 30%.
Other complications include the rare occurrence of pouch perforation, erectile dysfunction, reduced fertility, and incorrect diagnosis. Temporary ileostomy may be needed in certain patients, particularly if growth and development during adolescent years are not progressing at optimal rates. A fter the reservoir reconstruction has been completed, and the child has resumed normal growth, the ileostomy may be closed safely. Long-term follow-up must include proctoscopies every 2 to 3 years with biopsy specimens of the retained 1 to 2 cm of rectal cuff to rule out malignancy.
Coran AG: A personal experience with 100 consecutive total colectomies and straight ileoanal endorectal pull-throughs for benign disease of the colon and rectum in children and adults. Ann Surg 212:242-248, 2002.
This is the largest review of patients undergoing a straight pull-through for ulcerative colitis and familial polyposis. The frequency of stooling was no higher in these patients compared with patients with a reservoir by 1 year after the closure of the ileostomy.
Devroede GJ, Taylor WF, Sauer WG, et al: Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med 185:17, 1971.
This is one of the most authoritative and extensive reviews of the relationship between the length and severity of ulcerative colitis and the development of cancer.
Ekbom A, Helmick C, Zack M, Adami HO: Ulcerative colitis and colorectal cancer: A population-based study. N Engl J Med 323:1228-1233, 1990.
A well-controlled, population-based analysis of the risk of colorectal carcinoma in patients (including children) with ulcerative colitis is reported.
Fonkalsrud EW, Loar N: Long-term results after colectomy and experience with endorectal ileal pull-through procedure in children. Ann Surg 215:57, 1992.
This article contains the largest reported clinical experience with the endorectal ileal pull-through procedure for ulcerative colitis in childhood.
Joossens S, Reinisch W, Vermeire S, et al: The value of serologic markers in indeterminate colitis: A prospective follow-up study. Gastroenterology 122:1240-1447, 2002.
An excellent review is provided of the value of serologic markers to help clinicians determine if a patient has Crohn’s disease or ulcerative colitis.
Kock NG, Darle N, Kewenter J, et al: The quality of life after proctocolectomy and ileostomy: A study of patients with conventional ileostomies converted to continent ileostomies. Dis Colon Rectum 17:287, 1974.
This is one of the most extensive and authoritative reviews of the role of the continent ileostomy in the surgical treatment of ulcerative colitis.
Pemberton JH, Kelly KA, Beart RW Jr, et al: Ileal pouch-anal anastomosis for chronic ulcerative colitis. Ann Surg 206:504, 1987.
This article contains an extensive discussion and review of the current restorative proctocolectomy in the surgical treatment of ulcerative colitis by leading authorities in the field.
Podolsky DK: Inflammatory bowel disease. N Engl J Med 347:417-429, 2002.
This article is a good review of the medical treatments and etiology of IBD.
Article and graphics adapted from O'Neill: Principles of Pediatric Surgery. © 2003, Elsevier.