AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Ulcerative colitis (UC) is a disease characterized by remitting and relapsing inflammation of the large intestine. UC and Crohn disease (CD) account for the disorders that represent the inflammatory bowel diseases (IBDs). The hallmark symptoms of UC include abdominal cramping, diarrhea, and bloody stools. Many patterns of presentation are possible in the pediatric age group. UC is generally considered to always affect the rectum, with contiguous involvement that can include the entire large intestine.

Pathophysiology

UC is characterized by accumulations of polymorphonuclear neutrophils in the crypts of the colon (crypt abscesses) with epithelial ulceration, edema, and hemorrhage. These changes may represent the final common pathway of a heterogeneous group of diseases relating to genetic and environmental factors.

The mucosal immune system of the large intestine is continuously exposed to a wide array of antigens from ingested food products and from the billions of bacteria that live there. When activated, the cells of the mucosal immune system release cytokines that recruit inflammatory cells to the tissue and perpetuate the inflammatory response. In patients with IBD, the inflammatory response to luminal antigens may be exaggerated over that seen in healthy individuals or they may not respond normally to down-regulation. The patient's genetic background likely determines when and how the inflammatory cells of the mucosal immune system react to the environment.

Frequency

United States

About 20% of patients with UC present before age 20 years. The incidence rate for UC in North Americans aged 10-19 years is approximately 2 cases per 100,000 persons. No simple Mendelian genetic mechanism explains the transmission of IBD, yet many familial occurrences are known in 15-20% of patients. Patients in whom disease is diagnosed before age 20 years appear to have an associated family history of the disease.

Race

Early studies tended to show a higher prevalence of UC in white Americans than in black Americans. Over time, this trend seems to be decreasing, with recent incidence rates nearly the same. Asian Americans appear to have low incidences. Several studies have shown that the incidence of IBD in white Americans is up to 4 times higher in Jewish people than among other racial or ethnic groups.

Sex

No sex predilection for UC is reported.

Age

• In most studies, incidence of UC peaks between adolescence and early adulthood (ie, in people aged 15-30 y).
• A smaller peak occurs in patients aged 60-80 years.
• UC occurs less frequently in children younger than 5 years than in others.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Ulcerative colitis (UC) is a diffuse mucosal inflammation limited to the colon that affects the rectum and may extend proximally in a symmetric uninterrupted pattern to involve parts or all of the large intestine. Because UC is a mucosal disease limited to the colon, the most common presenting symptoms are rectal bleeding, diarrhea, and abdominal pain. Many patterns of presentation occur in the pediatric age group.

• Mild disease is observed in 50-60% of patients. This presentation involves insidious onset of diarrhea, later associated with hematochezia. No systemic findings of fever, weight loss, or hypoalbuminemia are observed. UC is typically confined to the distal colon and responds well to therapy.
• Moderate disease is observed in 30% of patients and is characterized by bloody diarrhea, cramps, urgency to defecate, and abdominal tenderness. Associated systemic findings, such as anorexia, weight loss, low-grade fever, and mild anemia, are present.
• Severe colitis occurs in approximately 10% of patients. This presentation involves more than 6 bloody stools per day, abdominal tenderness, fever, anemia, leukocytosis, and hypoalbuminemia. Patients with severe colitis may experience life-threatening complications, including severe hemorrhage, toxic megacolon, or intestinal perforation.
• Less than 5% of children with UC present with predominantly extraintestinal manifestations, such as growth failure, arthropathy, skin manifestations, or liver disease.
• Recently, a clinical scoring system known as the Pediatric Ulcerative Colitis Activity Index (PUCAI) has been developed and validated.¹ The PUCAI may be used more frequently to assess disease activity in clinical trials involving pediatric patients with UC.

Physical

The findings on physical examination in UC vary depending on the extent, duration, and severity of the disease. In addition to abdominal signs, many extraintestinal manifestations of UC may become evident during physical examination.

• Vital signs may indicate fever.
• • Tachycardia may represent anemia or hypovolemia.
  • Tachypnea may be present because of abdominal splinting or as a compensatory mechanism for acidosis in cases of severe dehydration.
• Comparison with growth charts may reveal delayed growth.
• • Cushingoid appearance is indicative of steroid use, usually over a long period. The patient may appear toxic in cases of fulminant disease.
  • Long-standing and severe disease may cause signs of malnutrition, such as muscle wasting.
• Abdominal examination findings are sometimes normal, but examination is likely to reveal abdominal tenderness.
• • Voluntary or involuntary guarding may be present.
  • Bowel sounds may be normal, hyperactive, or hypoactive.
  • Rushes or high-pitched tinkling may be found in cases of obstruction.
  • Rebound tenderness indicates severe disease and possible perforation.
  • A palpable mass may indicate obstruction or megacolon.
  • An enlarged spleen may be indicative of portal hypertension from associated autoimmune hepatitis or primary sclerosing cholangitis.
  • Long-standing disease can be associated with colonic stricture and evidence for bowel obstruction.
• Skin examination may reveal pallor in cases of anemia, decreased skin turgor in cases of dehydration, and jaundice, caput medusae, or spider angiomata when associated liver involvement is present. Erythema nodosum may be evident on extensor surfaces (but more common in Crohn disease [CD] than UC); pyoderma gangrenosum affects approximately 1% of patients with UC.
• Patients with episcleritis can present with a painful erythematous eye.
• • Cataracts may occur in patients with significant steroid history.
  • Scleral icterus may be indicative of liver disease.
• Joint pain (arthralgia) is a common finding in inflammatory bowel disease (IBD), although swollen or red joints (arthritis) occur less frequently. The large peripheral joints, such as the knees, ankles, wrists, and elbows, are most commonly involved, but any joint can be involved. Approximately 1% of patients with UC develop ankylosing spondylitis; most of these patients test positive for human leukocyte antigen (HLA) type B27.
• Unlike what is seen in some patients with CD, perianal examination in patients with UC should not reveal any evidence of fistulae or abscesses; however, chronic diarrhea may lead to perianal erythema, fissuring, or hemorrhoids.
• Sexual development may be delayed in patients with UC, but this finding is more common in patients with CD than in UC.

Causes

UC is thought to be a multifactorial disease.

• Data from genetic epidemiologic studies strongly support the role of genetic factors in UC. Concordance is higher among monozygotic twins than among dizygotic twins; however, the lack of perfect concordance in monozygotic twins suggests other factors in the etiology of UC as well.
• Several environmental factors have been implicated in the pathogenesis of IBD.
• • Smoking influences the course of IBD (positively in UC, negatively in CD).
  • Certain infections have been implicated in IBD (eg, measles, atypical mycobacteria infection).
  • Patients with IBD have been shown to have different colonizing bacteria than people without IBD.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Pseudomembranous (Clostridium difficile) colitis
Infectious colitis (due to Escherichia coli or Yersinia, Salmonella, or Shigella species)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC count commonly reveals a mild anemia, which can be due to chronic blood loss (ie, microcytic, hypochromic) or may represent chronic disease (ie, normocytic). In cases of fulminant colitis, severe anemia may be present.
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are frequently elevated during active disease.
• Result for antineutrophil cytoplasmic antibody with a perinuclear staining pattern (p-ANCA) are positive in up to 80% of patients with ulcerative colitis (UC) and in up to 20% of patients with Crohn disease (CD).
• Serum albumin levels may be low in fulminant colitis.
• Fecal calprotectin may be elevated during times of active inflammation.
• • Calprotectin is a calcium-binding S-100 protein found in the neutrophil cytosol that is released with cell activation or death.
  • An assay for calprotectin is now commercially available and may be useful to differentiate a disease flare from other causes of abdominal pain or diarrhea.
• Micronutrient and vitamin levels are typically low in CD but less commonly so in UC.
• Obtain stool cultures to rule out infectious colitis. Obtain an assay for E coli H7:0157 if the patient's symptoms are consistent with hemolytic uremic syndrome.
• Obtain a stool assay for C difficile toxins A and B because C difficile colitis can mimic UC or it may be responsible for a flare. Evaluation for toxin A or toxin B alone is inadequate for an accurate diagnosis of C difficile infection.
• Liver dysfunction may indicate sclerosing cholangitis or autoimmune hepatitis.

Imaging Studies

• An abdominal obstruction series (ie, supine and upright abdominal radiography) is useful to evaluate for air-fluid levels, dilated loops of bowel, evidence of obstruction, or possible toxic megacolon. No pathognomonic findings for UC on this type of study are reported.
• Barium enema study is useful to evaluate the colon for stricture and for mucosal abnormalities, especially when colonoscopy cannot be performed. Barium enema studies may also demonstrate source of bleeding other than UC, such as a polyp.
• An upper GI series with small-bowel follow-through is used to evaluate for small-bowel inflammation that would support a diagnosis of CD rather than UC.
• CT scanning of the abdomen is useful to evaluate for bowel-wall thickening and obstruction. If present, abscesses and fistulae imply a diagnosis of CD rather than UC.
• Radionuclide-tagged WBC scanning can be used to demonstrate small-bowel inflammation that differentiates CD from UC.
• MRI of the abdomen is increasingly used to evaluate the large and small bowel for inflammatory changes and to look for transmural versus mucosal inflammation.
• Wireless video capsule endoscopy, also known as the Pillcam, is an increasingly used imaging technology that may reveal small bowel involvement in inflammatory bowel disease (IBD) that differentiates CD from UC.

Procedures

• Colonoscopy with biopsy is the most valuable procedure in the evaluation of the patient with IBD.
• • Typical findings in someone with UC are inflammation first evident in the rectum that proximally extends in a contiguous fashion. The mucosa typically appears erythematous, friable, and granular, and it has lost the normally visible vascular markings.
  • Findings more consistent with CD than with UC are sparing of the rectal mucosa, aphthous ulceration, and noncontiguous or skip lesions.
• When possible, visualizing the entire colon and the last portion of the ileum (terminal ileum) is best because the terminal ileum is not actively involved in UC but is commonly involved in CD. However, patients with pancolitis occasionally have microscopic inflammation in the terminal ileum, which is thought to be secondary to reflux of colonic contents through an inflamed ileocecal valve (ie, backwash ileitis).

Histologic Findings

• Biopsy findings consistent with UC are polymorphonuclear leukocytes near the base of the crypts.
• Cryptitis describes aggregation of polys in the crypt epithelium, and the term crypt abscess is used when polys have accumulated in the lumen of the crypt.
• Lymphocytes, eosinophils, and mast cells may also be observed in the lamina propria in acute UC. However, no pathognomonic biopsy findings have been described for UC.
• Noncaseating granulomas are diagnostic of CD.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The general goals for managing inflammatory bowel disease (IBD) in children are to achieve the best possible clinical and laboratory control of the disease with the least adverse effects while permitting the patient to function as normally as possible.

Most patients with ulcerative colitis (UC) can be treated on an outpatient basis. Hospitalization is necessary when maximal outpatient therapy is unsuccessful or when patients develop severe disease.

• 5-Aminosalicylate (5-ASA)
• • The mainstay of outpatient management is anti-inflammatory therapy with 5-ASA preparations.²
  • Sulfasalazine (Azulfidine) was the first 5-ASA preparation available for the treatment of UC.
  • More recently, mesalamine (Pentasa, Asacol) was introduced. Mesalamine may have fewer adverse effects than sulfasalazine because the sulfa component has been removed. However, mesalamine is not available in a pediatric preparation.
  • Asacol tablets must be swallowed whole, which limits its use in young children.
  • Pentasa capsules may be opened so that the granules can be swallowed from a spoon (eg, mixed with applesauce), but this exposes the medicine to degradation high in the GI tract not affected in UC.
  • Balsalazide (Colazal) is another form of 5-ASA that is active in only the colon.
• Corticosteroids
• • Corticosteroids (eg, prednisone) are effective in controlling acute flares of disease but less effective at maintaining long-term remission, and numerous adverse effects make their long-term use undesirable.
  • Corticosteroids are known to cause linear growth failure, which can be a clinically significant problem in the patient with IBD. Corticosteroids cause osteoporosis, which can also be a problem, which leads to compression fractures of the spine.
  • The many undesirable cosmetic effects of corticosteroids include weight gain, acne, and cushingoid appearance.
  • Steroids may cause agitation and restlessness, as well as personality changes, such as irritability or emotional lability.
  • Despite the undesirable adverse effects, some patients depend on steroids to keep their disease under control. In other patients, the disease does not respond well to steroids. When a patient with UC demonstrates signs of steroid dependence, other treatments should be used to limit the patient's steroid exposure.
• Immunomodulatory agents
• • Immunomodulatory agents are purine analogs that inhibit purine ribonucleotide synthesis and cell proliferation. Immunosuppressive agents also inhibit the immune response of natural killer cells and cytotoxic T cells.
  • Use immunomodulatory agents, such as 6-mercaptopurine (Purinethol) and azathioprine (Imuran), in patients with IBD who are steroid dependent or whose disease is refractory to steroid treatment. These medications take approximately 3 months to have effect and, therefore, are not useful in acute exacerbations of disease.
  • Although immunomodulatory agents are usually well tolerated, they do have the potential adverse effects of pancreatitis, hepatitis, and bone-marrow suppression. The pancreatitis is usually an idiosyncratic reaction that is not dose related and that resolves on removal of the drug. The hepatitis appears to be related to the buildup of a metabolite of the medication and may resolve when the dose is adjusted. Bone-marrow suppression is dose related and may have delayed onset.
  • Monitor patients for leukopenia on a frequent basis early in the course of therapy and then less so later on.
• Intravenous corticosteroids
• • Intravenous corticosteroids (eg, methylprednisolone) may be effective in inducing remission when oral steroids are ineffective
  • Significantly increased efficacy does not appear to occur with doses above 2 mg/kg/d (not to exceed 48 mg/d).
  • High-dose intravenous steroids have the adverse effects of oral steroids and increase the likelihood of hyperglycemia and hypertension.
• Cyclosporine
• • Cyclosporine (cyclosporin A) is a potent inhibitor of the inflammatory cascade that primarily acts by inhibiting interleukin (IL)-2 production, though it also decreases the recruitment of cytotoxic T cells and blocks other inflammatory cytokines.
  • In refractory fulminant UC, cyclosporine has effectively induced remission, obviating immediate surgery. Because cyclosporine is such a potent immunosuppressive agent, the physician must be absolutely certain that an infection is not contributing to the colitis. The patient must also be considered susceptible to opportunistic infections, such as those due to cytomegalovirus (CMV) and Pneumocystis carinii.
  • Cyclosporine is nephrotoxic and may cause irreversible renal insufficiency. In addition, cyclosporine is epileptogenic and may precipitate seizures in patients, especially those with low cholesterol or magnesium levels.
  • Because of its many potential toxicities, only physicians who are experienced in its administration should use cyclosporine. In addition, for patients with UC, strongly consider surgical colectomy to treat fulminant disease because of the long-term risk of cancer and the curative nature of the surgery.
• Infliximab
• • Infliximab is a monoclonal antibody against tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine that occurs early in the inflammatory cascade.
• • Infliximab is effective in treating Crohn disease (CD) and has recently received attention and indications for use in UC.³
  • The drug is given as an intravenous infusion, typically in an induction regimen of 2 infusions over 2 weeks. In several reports, refractory UC responded to infliximab, and emergency colectomy was avoided.
  • In a retrospective series of pediatric patients with UC, 100% of patients were short-term responders, with 75% showing complete resolution of symptoms and the remaining 25% showing partial improvement after a median of 6 infusions; 67% were long-term responders after a median of 10.4 months.⁴ A better response was noted in patients who were considered steroid-dependent rather than steroid-refractory. A better response to infliximab infusions was also observed among patients concurrently taking 6-mercaptopurine; however, the concurrent use of 6-mercaptopurine and infliximab has become more controversial following reports of hepatosplenic T-cell lymphoma in patients with IBD receiving both medications.

Surgical Care

If colectomy is not performed to control symptoms, the risk of death from colon cancer is about 8% 10-25 years after colitis is diagnosed. Therefore, surgical removal of the colon is a virtual necessity for most patients with UC. Because UC is limited to the colon, colectomy is considered a curative procedure.⁵

• Approximately 5-10% of patients with UC require acute surgical intervention because of fulminant colitis refractory to medical therapy.
• In children, elective colectomy is indicated when refractory disease significantly interferes with their growth and nutrition or with their ability to maintain a normal lifestyle (ie, attend school) or when dysplasia or malignancy is detected.
• The most common procedure is the ileo-pouch anal anastomosis, in which an ileal pouch is connected to the anus to maintain continence.

Consultations

• Pediatric gastroenterologist
• Pediatric surgeon

Diet

• Patients with fulminant disease, possible obstruction, or possible toxic megacolon should ingest nothing by mouth (NPO) until their condition is stable.
• Patients should avoid poorly digested foods, such as uncooked vegetables, seeds, nuts, and high roughage, especially patients with stricture or narrowing.

Activity

The goal of therapy is to allow normal, unrestricted activity.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Anti-inflammatory agents

These drugs are used to maintain remission and to induce remission of mild flares of disease.

Drug Category: Immunosuppressive agents

These drugs are used in steroid-refractory or steroid-dependent patients.

Drug Category: Corticosteroids

These drugs are used to induce the remission of acute exacerbations.

Drug Category: TNF inhibitors

TNF is a cytokine; 2 forms with similar biologic properties have been identified. TNF-alpha, or cachectin, is produced predominantly by macrophages. TNF-beta, or lymphotoxin, is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to symptoms.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Complications

• Toxic megacolon is the most serious acute complication of ulcerative colitis (UC) and is reported to occur in up to 5% of patients; it is rare in young patients.
• • Consider toxic megacolon a medical and surgical emergency.
  • The pathogenesis of toxic megacolon is related to severe inflammation resulting in disordered intestinal motility. Disrupted mucosal integrity then may allow bacteria to enter the submucosal tissues, leading to necrosis and peritonitis. Absorptive function is also impaired, resulting in increased luminal fluid volume and electrolyte losses. Toxic megacolon usually occurs in the presence of severe pancolitis. Use of antidiarrheal agents or recent barium enema study or colonoscopy has been implicated as causes of this condition. In addition, metabolic abnormalities (eg, hypokalemia, hypomagnesemia, hypoproteinemia), impaired epithelial integrity of the colon, and altered motor function and are frequently found in patients with toxic megacolon.
  • Toxic megacolon is associated with fever, abdominal distention, and tenderness. Abdominal obstruction series reveals dilatation of the colon with loss of normal haustral markings and signs of edema. Toxic megacolon places the patient at risk for colonic perforation, gram-negative sepsis, and massive hemorrhage.
• Colonic malignancy is a clinically significant complication in patients with UC.
• • The duration of disease and pancolitis are well-recognized risk factors for malignancy, with the risk of cancer increasing over that of the general population after 10 years. Other less-characterized risk factors include sclerosing cholangitis, a bypassed and defunctionalized segment of bowel, and a low folate level.
  • Children who develop UC before age 14 years have a cumulative colorectal-cancer incidence of 5% at age 20 years and 40% at age 35 years. Patients aged 15-39 years who develop UC have a cumulative incidence of 5% at age 20 years and 30% at age 35 years. The risk for children with onset of disease in the first decade of life is unknown, but these children should undergo colonoscopic screening for dysplasia beginning in adolescence.
  • Epithelial dysplasia generally precedes carcinoma; therefore, perform yearly screening with surveillance colonoscopy and biopsy. Dysplasia can be missed on surveillance biopsy; therefore, consider prophylactic colectomy in adults who developed UC during childhood. With this in mind, psychologically prepare adolescents and young adults by discussing surgical options before the need for surgery arises.
• Extraintestinal manifestations are common in UC. Approximately 25-35% of patients with inflammatory bowel disease (IBD) have at least one extraintestinal manifestation. Extraintestinal disease may be prognostically important because the rate of pouchitis increases after colectomy in patients with UC and extraintestinal manifestations.
• • Pyoderma gangrenosum occurs in 1% of patients with UC. An indolent chronic ulcer may occur even when disease is in remission. Intralesional therapy with steroids is useful, and colectomy results in healing in approximately one half of patients.
  • Ophthalmologic manifestations most frequently occur when the disease is active. The incidence in adults is 4% but is less in children. The most common findings are episcleritis and anterior uveitis. Uveitis is usually symptomatic, causing pain or decreased vision. Patients with IBD should likely undergo routine ophthalmologic examination.
  • Arthritis is the most common extraintestinal manifestation of IBD, occurring in 10-25% of adolescents. The arthritis is usually a transient, nondeforming synovitis that involves the large joints in an asymmetric distribution. In children, arthritis may precede GI symptoms by years.
  • Hepatobiliary disease is another common extraintestinal manifestation of UC in children. Hepatobiliary complications may precede the onset of GI symptoms, they may accompany active disease, or they may develop after surgical resection. Chronic active hepatitis, granulomatous hepatitis, amyloidosis, fatty liver, and pericholangitis are some of the intrahepatic manifestations of IBD. Extrahepatic manifestations include cholelithiasis and primary sclerosing cholangitis.
  • Thromboembolic disease is considered to be the result of a hypercoagulable state that parallels disease activity and is manifested by thrombocytosis; elevated plasma fibrinogen, factor V, and factor VIII; and decreased plasma antithrombin III. The hypercoagulable state may lead to deep venous thrombosis, pulmonary emboli, and neurovascular disease.

Patient Education

• Thorough education about the pathophysiology, medications, and the short- and long-term risks of UC is an essential part of any treatment program.
• The Crohn's and Colitis Foundation of America and the Crohn's and Colitis Foundation of Canada are nonprofit organizations dedicated to the education and treatment of patients affected by Crohn disease and UC.
• The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, in concert with the Children's Digestive Health and Nutrition Foundation, have developed educational resources for children and families affected by IBD. These resources are available at Kids IBD.
• For excellent patient education resources, visit eMedicine's Crohn Disease Center and Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles, Crohn Disease in Children and Teens, Crohn Disease, and Inflammatory Bowel Disease.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize an infectious etiology (eg, enteric infection, CMV infection, C difficile infection) for colitis
• Failure to identify disease as Crohn disease (CD) before colectomy
• Failure to recognize the signs and symptoms of toxic megacolon
• Failure to recognize signs and symptoms of colonic obstruction
• Failure to adequately monitor for ophthalmologic complications of the disease or treatment of the disease
• Failure to screen for dysplasia after several years of disease
• Failure to seek other forms of treatment after the demonstration of steroid dependence

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Turner D, Otley AR, Mack D, Hyams J, de Bruijne J, Uusoue K. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. Aug 2007;133(2):423-32. [Medline].
2. Kam L. Ulcerative colitis in young adults. Complexities of diagnosis and management. Postgrad Med. Jan 1998;103(1):45-9, 53-6, 59. [Medline].
3. Mamula P, Markowitz JE, Brown KA, et al. Infliximab as a novel therapy for pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr. Mar 2002;34(3):307-11. [Medline].
4. Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. Mar 2005;11(3):213-8. [Medline].
5. Becker JM. Surgical therapy for ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am. Jun 1999;28(2):371-90, viii-ix. [Medline].
6. Andres PG, Friedman LS. Epidemiology and the natural course of inflammatory bowel disease. Gastroenterol Clin North Am. Jun 1999;28(2):255-81, vii. [Medline].
7. Baldassano RN, Piccoli DA. Inflammatory bowel disease in pediatric and adolescent patients. Gastroenterol Clin North Am. Jun 1999;28(2):445-58. [Medline].
8. Burke A, Lichtenstein GR, Rombeau JL. Nutrition and ulcerative colitis. Baillieres Clin Gastroenterol. Mar 1997;11(1):153-74. [Medline].
9. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. Jul 1998;115(1):182-205. [Medline].
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11. Lewis JD, Deren JJ, Lichtenstein GR. Cancer risk in patients with inflammatory bowel disease. Gastroenterol Clin North Am. Jun 1999;28(2):459-77, x. [Medline].
12. Mack DR, Langton C, Markowitz J, LeLeiko N, Griffiths A, Bousvaros A. Laboratory values for children with newly diagnosed inflammatory bowel disease. Pediatrics. Jun 2007;119(6):1113-9. [Medline].
13. Michetti P, Peppercorn MA. Medical therapy of specific clinical presentations. Gastroenterol Clin North Am. Jun 1999;28(2):353-70, viii. [Medline].
14. Orloski LA. Pediatric ulcerative colitis: a review of the disease and current therapy. Pediatr Nurs. Mar-Apr 1998;24(2):165-7. [Medline].
15. Papadakis KA, Targan SR. Current theories on the causes of inflammatory bowel disease. Gastroenterol Clin North Am. Jun 1999;28(2):283-96. [Medline].
16. Rajwal SR, Puntis JW, McClean P, et al. Endoscopic rectal sparing in children with untreated ulcerative colitis. J Pediatr Gastroenterol Nutr. Jan 2004;38(1):66-9. [Medline].
17. Sanders DS. The differential diagnosis of Crohn's disease and ulcerative colitis. Baillieres Clin Gastroenterol. Mar 1998;12(1):19-33. [Medline].
18. Selby W. The natural history of ulcerative colitis. Baillieres Clin Gastroenterol. Mar 1997;11(1):53-64. [Medline].
19. Stein RB, Hanauer SB. Medical therapy for inflammatory bowel disease. Gastroenterol Clin North Am. Jun 1999;28(2):297-321. [Medline].
20. Weinstein TA, Levine M, Pettei MJ, et al. Age and family history at presentation of pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. Nov 2003;37(5):609-13. [Medline].

Article Last Updated: Mar 27, 2008