OVERVIEW: What every practitioner needs to know

Are you sure your patient has ulcerative colitis? What are the typical findings for this disease?

Ulcerative Colitis (UC) is an inflammatory bowel disease (IBD) that generally presents with diarrhea and rectal bleeding and little evidence for systemic disease. In general, the diagnosis is made within 6 months from the time of onset of symptoms. A small number of patients will present with symptoms suggestive of toxic megacolon, including fever, tachycardia and abdominal distension.

The most common presenting symptoms of UC include weight loss, rectal bleeding, diarrhea, and abdominal pain, whereas symptoms more characteristic of Crohn’s disease (CD) include insidious onset of abdominal pain and weight loss.

Up to 35% of pediatric patients with IBD present at least one extra-intestinal manifestation, arthritis being the most common. Although typically concurrent with exacerbation of disease in adults, extra-intestinal symptoms in children with IBD may precede the onset of gastrointestinal symptoms by years. Extra-intestinal manifestations are less common in patients with UC compared to those with Crohn’s disease, but can include joint pain and swelling, oral lesions or ulcers, nausea, vomiting, cutaneous nodules or ulcers.

Continue Reading

IBD is first characterized by disease location within the bowel and the extent of inflammation. Childhood-onset IBD may have a more aggressive or complicated clinical course than adult disease. Children typically present with moderate to severe disease activity, and up to 37% have extensive involvement (i.e., pancolitis) at presentation.

Despite obvious similarities between childhood- and adult-onset disease, a number of concerns are unique to the pediatric IBD population. A primary concern and differentiating feature of pediatric IBD is the well-established impairment in growth and skeletal development associated with the disease. More than 35% of pediatric patients with CD and up to 10% of pediatric patients with UC have impaired linear growth, which can precede the initial diagnosis by years.

What other disease/condition shares some of these symptoms?

Infectious colitis: Several bacteria are associated with severe forms of infectious colitis, including campylobacter, shigella, salmonella and Clostridium difficle. Ameobic colitis is rare in the United States.

Eosinophilic colitis: Idiopathic forms and secondary to food or environmental antigens, and parasite infestations.

Congenital immunodeficiency: Several primary immunodeficiency syndromes have been associated with an inflammatory bowel disease (IBD)-like clinical and histopathological presentation. Patients may present with clinical signs and symptoms indistinguishable from patients with IBD, including chronic abdominal pain, diarrhea and colitis like symptoms. Indeed, extra-intestinal manifestations like, failure to thrive, developmental delay and perianal diseases are common presenting complaints.

Common variable immunodeficiency is a rare disorder that is characterized by variable alterations in T and B lymphocyte cell function. Patients with a predominant humoral defect may present with nonspecific enteritis or enterocolitis that may improve with antibiotic or immunoglobulin therapy. Whereas, those patients with a predominantly cellular defect may present with an IBD like intestinal disorder that may respond to corticosteroid therapy. One such patient treated at the Johns Hopkins Children Hospital responded well to an oral 5-ASA preparation in combination with low dose corticosteroid therapy.

Leukocyte adhesion deficiency is an immune deficiency disorder where patients have a deficiency in several specific plasma membrane glycoproteins that play a role in lymphocyte adhesion and cellular toxicity. The radiological finding of the terminal ileum may be indistinguishable from those patients with Crohn’s ileocolitis. One such patient treated at our Children’s Center with Crohn’s-like enterocolitis failed medical management and ultimately required a bone marrow transplant.

Other such immunodeficiency states, including chronic granulomatous disease, glycogen storage disease type 1b and Hermansky Pudlak syndrome have unique immune defects that present with symptoms indistinguishable from Crohn’s Disease. Colonic biopsies will show multi-focal areas of chronic inflammation with multi nucleated giant cells. The precise role of any of these specific immune defects in the pathogenesis of IBD is unclear.

Rare causes: Vasculides involving the bowel, radiation enteritis, pseudo-obstruction disorders.

What caused this disease to develop at this time?

IBD is thought to be the result of an inter-play between one or more environmental factors in genetically susceptible individuals. Epidemiological studies have suggested that IBD is more common in industrialized nations, and is rare in the developing world. Although a number of dietary factors, including the increased consumption of refined sugars and polyunsaturated fats has been used as a possible explanation for these differences, no specific proof has been cited. Conversely, other environmental factors, including poor sanitation, and exposure to intestinal parasites could influence intestinal immunity, and reduce susceptibility in genetically predisposed individuals.

The diagnosis of new onset UC in families who have recently emigrated from the developing world to North America may help explain in part the influence of the environment on disease susceptibility.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

  • Stool cultures, stool for C. difficile toxins.

  • Stool for microscopy, calprotectin

  • CBC, comprehensive metabolic panel, ESR, CRP, Vitamin D.

  • Autoantibodies and other serologic testing: ANA, ANCA, ANSA.

    The presence of serum anti-neutrophil cytoplasmic antibodies (ANCA) has received much attention in the identification of patients with UC. Winter and coworkers reported ANCA to be 83% sensitive and 90% specific in identifying pediatric patients with UC. The combination of a perinuclear pattern of labeling with elevated serum ANCA titers was more specific. The presence of anti Saccharomyces cerevisiae antibodies (ASCA) has also been proposed as a sensitive and specific marker in patients with CD, especially when used in combination with ANCA.

    Over the last several years, there has been considerable debate about the clinical utility and reliability of serological testing in pediatric patients. Indeed, serological testing has shown sensitivities as low as 60% in some studies.

    Novel ELISA-based serodiagnostic assays have recently been developed to improve diagnostic accuracy. Although false-positive diagnoses were shown to be reduced by 81%, the notion that serological testing can replace a screening colonoscopy or small bowel follow-through remains highly debatable and many regard serologic testing as too unreliable to be an effective screening tool for patients with suspected IBD.

    Faced with a patient who has recurrent abdominal pain, weight loss, chornic diarrhea, etc., many gastroenterologists will depend on screening endoscopic and radiological studies before contemplating a definitive diagnosis of UC or other forms of IBD, and certainly before instituting pain management strategies and/or psychological evaluations.

    To date, there are no studies to suggest that serological testing is useful in separating CD from UC patients with indeterminant colitis. Indeed, there are no longitudinal studies that have followed patients with indeterminate colitis to establish reliable diagnostic predictive values for these tests. The diagnosis of indeterminant colitis remains a diagnostic dilemma. This is especially critical when surgical therapy is contemplated in patients with steroid refractory colitis that has been unresponsive to conventional immunomodulatory therapy.

  • Technical advances in both fiber optic colonoscopy and radiological studies have provided the gastroenterologist with several valuable tools in screening patients for IBD, and identifying clinical subtypes of UC in the pediatric population. Colonoscopy with tissue biopsy for histology is pivotal in establishing the diagnosis. Radiological studies including conventional barium studies and magnetic resonance imaging is helpful in excluding proximal gastrointestinal disease in patients where the diagnosis is uncertain.

Would imaging studies be helpful? If so, which ones?

Gadolinium Enhanced Magnetic Resonance Imaging (MRI)

CD and UC are distinguished by several clinical, pathological and radiological criteria. However, a confident distinction between CD and UC remains a taxonomic dilemma in up to 20% of cases, particularly when involvement is limited to the colon. Consequently, some patients with IBD are labeled with the diagnosis of indeterminate colitis despite the availability of improved fiberoptic colonoscopy and several novel serological and radiological tests.

In the past, the use of MRI imaging was limited due to poor resolution and motion artifact. Recent technological advances, including intravenous gadolinium, fat suppression and respiratory-suspended sequences have eliminated a phase artifact and enhanced the resolution of intestinal images. Gadolinium enhanced MRI in patients with UC shows mucosal enhancement with sparing of the submucosa, and involves the rectum with variable extension to involve the proximal colon. In contrast, gadolinium enhanced MRI in patients with CD shows transmural enhancement of the colon plus either involvement of the terminal ileum or involvement of the proximal small bowel with bowel wall thickening.

In 52 consecutive children who underwent screening MRI between 1998-2000 for suspected IBD, the histological diagnosis of either UC or CD was confirmed with a sensitivity and specificity of 96 and 90%, respectively. In total, 17 patients were diagnosed with IC by histological criteria alone. Patients with a diagnosis of IC were not considered in the statistical analysis since histology still remains the gold standard. All patients with the histological diagnosis of UC were confirmed by MRI. MRI also had a statistically lower non-classification rate when compared to histology alone, and showed an agreement of greater than 76% when compared to abdominal CT scans. Future longitudinal studies are required on those patients with a diagnosis of IC to further corroborate our MRI findings.

In comparison to UC, the standard radiological features of CD of the bowel are nonspecific and include: aphthous ulcers, thickened folds, and either distorted or effaced mucosa. In longstanding disease, standard radiological imaging may show extensive small bowel involvement with multiple and diffuse stenotic segments. Ongoing studies have shown jejunal enhancement in more than 50% of patients with CD, a figure that is much higher than that reported in either the adult (4-10%) or pediatric literature (15-20%) based on either a small bowel series or an abdominal CT scans. This improved sensitivity of MRI testing in detecting the early signs of mucosal inflammation may provide a guide for clinicians in tailoring medical and nutritional therapy (ref. 4).

Prior to the availability of MR enterography, contrast computerized tomography (CT) was the principle radiological tool used in screening patients with presumed IBD for proximal small bowel disease. CT was also proven to be useful in evaluating patients with potential complications of UC, including toxic megacolon, perforation, and malignancy. However, the increased awareness of the potential risk for radiation induced malignancy has limited its use, especially among children with IBD. Moreover, the same concern also holds true on the use of small bowel enemas.

If you are able to confirm that the patient has ulcerative colitis, what treatment should be initiated?

  • 5-aminosalicylates (5-ASA): 5-ASA remains the first-line therapy for mild-to-moderate ulcerative colitis. Both oral and topical formulations are available to deliver drug directly to the site of disease activity. In children, UC is typically under-treated because drug efficacy depends on the luminal volume. Thus, the patient’s height (which is a better predictor of length of intestinal tract), and not weight, should be a factor in deciding drug dosage. Typically, doses of 60-100 mg/kg of 5-ASA is prescribed at some institutions, including our own, and the dose is increased before therapy is considered ineffective.

    There are a number of 5-ASA compounds used in the treatment of mild-to-moderate UC. Moisture-dependent 5-ASA release preparations are better suited in pediatric patients since the capsules can be opened and ingested with food. Although these preparations release mesalamine in the proximal small bowel, bioavailability studies have shown these preparations are also effective in releasing the drug into the distal ileum and colon. Indeed, this formulation has proven efficacy in treating children with mild to moderate UC. Another mesalamine preparation, including a pH-dependent delayed and extended release granule formulation can also be administered by opening the capsule, however, physicians must be aware of differences in drug equivalency (4 capsules provide just 1.6gms of mesalamine) between these two preparations. Other pH-dependent formulations are provided in tablet form. The size of these tablets may affect their feasibility among pediatric patients with UC, especially among children less than 12 years of age.

  • Corticosteroids: Corticosteroids represent the principal acute therapy for moderate-to-severe ulcerative colitis because they are extremely effective in inducing remission and can be administered topically, orally, or parenterally. Topical or oral corticosteroid preparations are typically used in the treatment of patients with moderate disease. Oral preparations remain the mainstay of therapy for ambulatory patients with moderately severe ulcerative colitis, and intravenous preparations are used in hospitalized patients with severe disease.

  • In general, corticosteroids are dosed at 1-2mg/Kg/day up to a maximum of 60mg/day. Higher dosages are not believed to hold any potential therapeutic advantage. In comparison, topical corticosteroids (100mg/60mL) can be applied daily up to a maximum of 2 weeks. The patient should inform the pediatric gastroenterologist if there is either no perceived improvement or worsening on therapy.

  • Parenteral nutrition is a valuable source of nutritional therapy in patients with severe UC. Indeed, bowel rest can be an helpful adjunct to medical therapy in patients with severe disease. Moreover, the provision of increased calories and protein among patients with severe failure to thrive and hypoalbuminemia, respectfully can be most beneficial, especially among patients that are considered potential candidates for colectomy.

  • Cyclosporine (CSA): CSA is a peptide that blocks interieukin-2 (IL-2) production by T-helper cells. By inhibiting helper lymphocyte IL-2 production, numerous immunological effects, including lymphocyte proliferation and lymphokine production in response to antigen exposure is prevented. Oral bioavailability is variable (12-35%), and is dependent on bowel wall mucosal integrity and intestinal motility. Since cyclosporine is lipophilic, absorption is also dependent on the presence of bile. Therapeutic drug monitoring has been utilized in organ transplantation for several years, but its usefulness in the treatment of IBD has not yet been defined.

    Lichtiger and colleagues were the first clinical investigators to introduce CSA into the IBD literature. They performed a small controlled trial with IV CSA (4 mg/Kg/day) in adult patients with severe steroid unresponsive ulcerative colitis. In that study, 83% of patients treated on CSA responded favorable as compared to 0% of controls. Despite the initial clinical response, 50% of all patients ultimately required colectomy. Treem and colleagues have reached similar conclusions in a pediatric study in patients with severe UC. A correlation between clinical efficacy and blood CSA levels has yet to be determined in patients with IBD.

    Although, CSA has proven efficacy in treating patients with severe steroid refractory UC, most physicians have gravitated toward the use of biologics, including infliximab on account of its well recognized acute and chronic toxicity. Nevertheless, among physicians that feel confortable using CSA, it should be considered as a potential salvage therapy among patients with severe UC who have not shown any clinical improvement after 3-5 days of high (2mg/Kg) dose intravenous corticosteroids.

  • Infliximab: Infliximab, a chimeric human-mouse anti-tumor necrosis factor alpha monoclonal antibody, has recently been approved for the treatment of moderate-to-severe ulcerative colitis. The Active Ulcerative Colitis Trials (ACT) I and II evaluated the effectiveness of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In the 54-week ACT I (treatment failures with corticosteroids and antimetabolites) and the 30-week ACT II (treatment failure to include mesalamine) studies, clinical remission was defined as a total Mayo score of = 2 with no individual subscores > 1. An endoscopy score of = 2 was the criteria for study inclusion, and an absolute subscore of 0 or 1 was defined as mucosal healing. During the induction phase (8 weeks), a higher proportion of patients on infliximab (5 mg/kg) achieved clinical remission (ACT I, 39%; ACT II, 34%) compared with placebo (ACT I, 15%; ACT II, 6%). In both the ACT I and II studies, a mucosal healing score of 0 was achieved in > 20% of patients after 8 weeks of induction (5 mg/kg) infliximab therapy, compared with just 12% and 4% on placebo, respectively. Although mucosal healing was also shown with delayed- and sustained-release mesalamine, the ACT I and II studies were performed in patients with moderate-to-severe ulcerative colitis with a clinical history of treatment failure with either 5-ASA or antimetabolite therapy.

    In summary, infliximab is an effective induction and maintenance therapy in children with UC. It should be considered an acute therapy in lieu of CSA in patients with severe steroid refractory UC, and as maintenance therapy among those patients with steroid dependent disease refractory to anti-metabolite therapy.

  • Maintenance therapy:
    The goals of maintenance therapy include: (1) the prevention of complications associated with the disease and treatment; (2) decreasing the incidence of colonic dysplasia and cancer; and (3) reduction of the need for surgical intervention. Most important, clinicians must ensure that the patient has completed induction into remission before starting maintenance therapy. The medications used in maintenance of remission include aminosalicylates and immunomodulators.

  • 5-ASA:

    A retrospective review of the medical records of more than 400 patients who achieved and sustained a maintenance of remission with delayed-release 5-ASA revealed that maintaining the dose of 5-ASA used to induce remission during the maintenance phase increased the likelihood of individuals receiving a physician’s global assessment measurement of “normal” at 1 year post induction. This finding is clinically important in light of a recent study suggesting the suboptimal treatment of ulcerative colitis patients by community-based gastroenterologists in prescribing 5-ASA therapies. In this study, current treatment patterns did not reflect the emerging data supporting the use of effective 5-ASA doses to sustain a protracted maintenance of clinical response in patients with long-standing ulcerative colitis.

  • Corticosteroids are ineffective as maintenance therapy, and their extended use can result in steroid dependence and adverse events.

  • The immunomodulators azathioprine and 6-mercaptopurine (6-MP), given at doses of 1.5 to 2.5 and 1.0 to 1.5 mg/kg/day, respectively, are appropriate for patients who respond to steroid induction therapy but who are unable to taper steroids after induction despite adequate therapy with aminosalicylates. Azathioprine and 6-MP also have been studied for prevention of relapse in patients who achieved remission while taking these drugs. In a placebo-controlled, double-blind trial involving adult patients who achieved remission with azathioprine, continuation of azathioprine therapy reduced the 1-year relapse rate to 36% compared with a relapse rate of 59% in the placebo group. An uncontrolled retrospective review of 105 adult patients with chronic refractory ulcerative colitis showed that 87% of those subjects who discontinued 6-MP soon after successful treatment subsequently relapsed.

  • Infliximab:

    The ACT I and II studies have supported a maintenance role for infliximab therapy in patients with moderate-to-severe ulcerative colitis. The potential long-term benefit of maintenance infliximab therapy is tempered by the potential risk of toxicity, including lymphoma and opportunistic infections.

  • Combination therapy:

    It has been the practice in many institutions, including our own to initiate maintenance therapy with the anti-TNF agent Infliximab in patients that have shown clear refractoriness to either long-term 6-MP or azathioprine (AZA) therapy. Several studies, including ACCENT, CHARM and PRECISE have not shown any potential therapeutic benefit of combining anti-TNF agents with 6-MP or Azathioprine in patients with Crohn’s disease. In contrast, the SONIC study showed an improved overall clinical response in patient on combination therapy compared to those patients on monotherapy alone. That study was performed in biologically naïve patients with moderate to severe Crohn’s disease who were either naïve or had been off azathiopirne therapy for at least 3 months. A similarly designed study was recently presented in abstract form in patients with moderate to severe UC. In that 16 weeks study, 40% of patients on combination therapy achieved a steroid free remission, significantly higher than those patients on monotherapy alone (22% remission in the infliximab-only group; 24% remission in the AZA-only group). Both combination and the infliximab only treatment arms were superior to AZA in overall clinical response and mucosal healing.

What are the adverse effects associated with each treatment option?

Mesalamine preparations are very attractive therapies for children with mild to moderate UC on account of their proven efficacy, but also by the low incidence of side effects, including diarrhea, headache, nausea, abdominal pain, dyspepsia, vomiting, and rash. Although uncommon, interstitial nephritis can occur with any 5-ASA preparations. It remains the author’s opinion that routine renal functions testing be monitored accordingly with each follow-up visit.

Corticosteroids are not used for maintenance therapy in ulcerative colitis because prolonged treatment may be associated with a number of established long-term side effects, such as adrenal suppression, osteoporosis, cataracts, avascular necrosis, hypertension, and diabetes mellitus.

CSA induced cytotoxicity includes: paraesthesia (26%), hypertrichosis (13%) hypertension (11%), renal insufficiency (6%), and tremors (7%). The biggest concern with long-term CSA therapy is renal insufficiency. In general, a 20% reduction in glomerular filtration rate has been recognized with prolonged high dose CSA therapy. The risk of developing nephropathy is increased with repeated insults of high dose CSA (7.5 mg/kg/day). There have been no reported cases of lymphoma in patients treated with CSA.

The purported benefit of combination therapy in SONIC and the above referenced study in patients with moderate to severe UC is balanced with the increasing concern of hepatic T-cell lymphoma among young (<18 yrs.) patients on combination therapy. This concern has led many physicians to consider discontinuing either 6MP or AZA with the introduction of biological therapy (Infliximab) despite the potential benefit that combination therapy could reduce formation of antibodies to infliximab.

Although all anti-TNF agents are antigenic and patients can develop antibodies to anti-TNF agents, those patients on infliximab therapy are most vulnerable. Concurrent use of either AZA or 6-MP may allow for a more protracted clinical response, the precise mechanism of action is unclear. Whether this purported benefit would justify the increased risk of hepatic T-cell lymphoma is debatable, especially since adalimumab and certolizumab have proven effective in salvaging patients who had become refractory to infliximab.

What are the possible outcomes of ulcerative colitis?

Pediatric patients with IBD as well as adults with childhood-onset IBD are at increased risk for other co-morbidities, including malignancy. The risk of cancer appears to be particularly high in patients diagnosed with UC before 25 years of age and in those with a history of pancolitis. The risk of colorectal cancer in UC is directly related to disease duration, such that there is an incidence of 10% at 20 years and 40% at 35 years among children who develop ulcerative colitis before 15 years of age.

The factor with the most significant direct correlation with disease progression is severity of colitis early in the course of the illness. Patients with severe active UC are 14.8 times more likely to have disease progression compared to patients without severe colitis. Patients with left-sided colitis at diagnosis are 2.5 times more likely to progress to extensive colitis than are patients with isolated proctitis progressing to either extensive colitis or left-sided disease. Although disease progression can occur in patients of all age groups, most children will present clinically with extensive colitis at diagnosis. While those children presenting with either proctosigmoiditis or left-sided disease will rapidly progress to pancolitis within 6 years of the diagnosis.

In general, pediatricians regard ulcerative colitis as a rapidly progressive disease in children, with an associated increased likelihood of requiring procto-colectomy. The rapid induction and maintenance of disease remission remains the primary goal therapy in patients with UC. Using a Markov model, there is an 80% to 90% probability that a patient with clinically inactive disease would remain in remission for a year, with a 20% chance of relapse in the following year.

By contrast, data from patients with clinically active disease demonstrate a 70% probability of having a relapse during the year following diagnosis. The same results were shown within the posthoc analysis of the combined ACT I and ACT II data among the infliximab treated adult patients with UC. Interestingly, mucosal healing was the primary endpoint of long-term remission in those studies. The importance of tissue healing was also underscored by Froslie and coworkers. In that study, adult patients with UC that achieved tissue healing at 1 year were less likely to require colectomy in the subsequent 5 year follow-up period.

What causes this disease and how frequent is it?


Although the national incidence rates with either CD or UC vary considerably from state to state and among ethnic groups, CD is diagnosed annually at a rate of 0.2 to 8.5 per 100,000 while UC is diagnosed at a rate of 0.5 to 4.3 per 100,000. This disparity is further demonstrated by results of a large population-based North American study that found the incidence of CD to be a 4.56 per 100,000, more than double that of UC.

Genetic Factors

The lines of evidence suggesting genetic factors as a component of susceptibility have been extensively documented. Indeed, a positive family history is probably the most important risk factor for developing IBD. The lifetime risk of developing UC and CD in the first degree relatives of a proband is 1.6 and 5.2%, respectively. A high concordance for the occurrence of UC in monozygotic twins also points to the importance of genetic factors.

Other examples pointing toward the importance of genetic factors include: the higher risk of IBD in children when both parents are effects, ethnic variations, and the association with several genetically determined genetic diseases, including ankylosing spondylitis, and Turners syndrome. Family studies have also documented the occurrence of both CD and UC in the same family, thereby suggesting that these two diseases may share either one or more genes in common or that they may represent genetic pleiotropism.

Genome wide searches for susceptibility loci in CD and UC are being pursued in several countries. A linkage area on chromosome 16 has been associated with a relative risk of 1.3 in acquiring CD that is equivalent to the relative risk assigned to families with a tendency toward diabetes. This linkage on chromosome 16 has now been confirmed in at least five other study groups, three in the United States, one in Australia and one in Germany.

The strongest linkage for the IBD1 susceptibility locus on chromosome 16 was identified in affected family members with an age at disease onset before age 22. At least one family member from each of these 57 pedigrees studied had aggressive CD that required either surgical intervention or immunomodulatory therapy. This study was the first to suggest that the causative gene for CD may be linked to a specific clinical phenotype. Interestingly, there are several candidate other genes on Chromosome 16 that have also been considered in the pathogenesis of IBD, including CD19 lymphocyte genes, IL-4 and CDII integrin cluster. The linkage on chromosome 12 has been confirmed in patients with UC and in mixed CD and UC multiplex families.

Environmental Factors

IBD is thought to be the result of an inter-play between one or more environmental factors in genetically susceptible individuals. Epidemiological studies have suggested that IBD is more common in industrialized nations, and is rare in the developing world. Although a number of dietary factors, including the increased consumption of refined sugars and polyunsaturated fats has been used as a possible explanation for these differences, no specific proof has been cited. Conversely, other environmental factors, including poor sanitation, and exposure to intestinal parasites could influence intestinal immunity, and reduce susceptibility in genetically predisposed individuals.

The diagnosis of new onset UC in families who have recently emigrated from the developing world to North America may help explain in part the influence of the environment on disease susceptibility.

What complications might you expect from the disease or treatment of the disease?

Growth impairment in pediatric IBD is due to multiple factors including increased nutritional demands that normally occur during childhood in combination with increased metabolic demands and inadequate nutrition resulting from poor dietary intake, altered nutrient use, and increased fecal losses of protein and essential trace elements. Growth and sexual maturation also may be delayed by cytokines and other immunological and endocrine abnormalities. Like adults, children and adolescents with IBD may have bone demineralization with chronic corticosteroid use, decreased physical activity, and poor nutritional intake serving as contributing factors.

The serious and potential irreversible consequences of growth impairment underscore the need to ensure adequate growth and nutritional status in the management of IBD in pediatric patients. Appropriate anti-inflammatory therapy and caloric supplementation, including enteral and parenteral nutrition during acute exacerbations, can improve nutritional status and promote growth.

Iron supplementation is important in preventing iron-deficiency anemia commonly resulting from gastrointestinal blood loss and poor dietary intake. Despite these measures, however, some children with IBD may not reach their predicted height potential. Strategies for optimizing bone mineral density include periodic radiographic studies (DEXA scans); monitoring serum calcium, phosphorus, and alkaline phosphatase levels; and ensuring adequate calcium and vitamin D intake.

IBD may have profound psychosocial challenges for pediatric patients. Children and adolescents with IBD face considerable stress associated with a lifelong disease characterized by a relapsing and unpredictable disease course and potentially embarrassing symptoms. Studies in pediatric IBD patients have revealed various difficulties in psychosocial functioning, feelings of vulnerability and lack of control, lower self-esteem and energy levels, concerns about body image, and perceptions of themselves as different from their healthy peers and siblings. Not surprisingly, children and adolescents have demonstrated higher rates of anxiety and depression compared with control populations.

Although not as well studied in pediatric as in adult populations, quality of life is more compromised in children with IBD, and those with higher disease activity scores have less severe or inactive disease.

How can ulcerative colitis be prevented?

No known means of preventing disease onset.

What is the evidence?

Panccione, R, Ghosh, S, Middleton, S. “Infliximab, azathioprine or infliximab plus azathioprine for treatment of moderate to severe ulcerative colitis: The UC success trial”. Gastroenterology. 2011. pp. A385(A comparative study on the use of mono (infliximab versus azathioprinevs combination therapy in patients with UC).

Bousvaros, A, Sylvester, F, Kugathasan, S. “Challenges in pediatric inflammatorybowel disease”. Inflamm Bowel Dis. vol. 12. 2006. pp. 885-913. (Provides an excellent overview on the natural history, diagnosis and treatment of children and adolescents with ulcerative colitis.)

Reinisch, W, Sandborn, WJ, Rutgeerts, P, Feagan, BG, Rachmilewitz, D, Hanauer, SB. “Long-term infliximab maintenance therapy for ulcerative colitis: The ACT-1 and -2 extension studies”. Inflamm Bowel Dis. 2011 Apr 11. (The most pivotal study on the efficacy of infliximab in the induction and long-term maintenance of clinical response in patients with UC.)

Dubinsky, M. “Special issues in pediatric inflammatory bowel disease”. World J Gastroenterol. vol. 14. 2008. pp. 413-420.

Kugathasan, S, Judd, RH, Hoffmann, RG, Heikenen, J, Telega, G, Khan, F, Weisdorf-Schindele, S, San, PW, Perrault, J, Park, R, Yaffe, M, Brown, C, Rivera-Bennett, MT, Halabi, I, Martinez, A, Blank, E, Welin, SL, Rudolph, CD, Binion, DG. “Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study”. J Pediatr. vol. 143. 2003. pp. 525-531.

Farmer, RG, Easley, KA, Rankin, GB. “Clinical patterns, natural history, and progression of ulcerative colitis. A long-term follow-up of 1,116 patients”. Dig Dis Sci. vol. 38. 1993. pp. 1137-1146.

Darbari, A, Sena, L, Argani, P, Oliva-Hemker, JM, Thompson, R, Cuffari, C. “Gadolinium-enhanced magnetic resonance imaging: a useful radiological tool in diagnosing pediatric IBD”. Inflamm Bowel Dis. vol. 10. 2004 Mar. pp. 67-72.

Lichtiger, S, Present, DH, Kornbluth, A, Gelernt, I, Bauer, J, Galler, G, Michelassi, F, Hanauer, S. “Cyclosporine in severe ulcerative colitis refractory to steroid therapy”. N Engl J Med. vol. 330. 1994 Jun 30. pp. 1841-5.

Reinisch, W, Sandborn, WJ, Rutgeerts, P, Feagan, BG, Rachmilewitz, D, Hanauer, SB, Lichtenstein, GR, de Villiers, WJ, Blank, M, Lang, Y, Johanns, J, Colombel, JF, Present, D, Sands, BE. “Long-term infliximab maintenance therapy for ulcerative colitis: The ACT-1 and -2 extension studies”. Inflamm Bowel Dis. 2011 Apr 11.

Panccione, R, Ghosh, S, Middleton, S. “Infliximab, azathioprine or infliximab plus azathioprine for treatment of moderate to severe ulcerative colitis: The UC success trial”. Gastroenterology. 2011. pp. A385

Bousvaros, A, Sylvester, F, Kugathasan, S, Sziegethy, E, Fiocchi, C, Colleti, R, Otley, A, Amre, D, Ferry, G, Czinn, SJ, Splawski, JB, Olivia-Hemker, M, Hyams, JS, Faubion, WA, Kirschner, BS, Dubinsky, MC. “Challenges in pediatric inflammatory bowel disease”. Inflamm Bowel Dis. vol. 12. 2006. pp. 885-913.

Lichtenstein, G, Yan, S, Bala, M, Hanauer, S. “Remission in patients with Crohn’s disease associated with improvement in employment and quality of life and decrease in hospitalization and surgeries”. Am J Gastroenterol. vol. 99. 2004. pp. 91-96.

Diefenba ch, KA, Breuer, CK. “Pediatric inflammatory bowel disease”. World J Gastroenterol. vol. 12. 2006. pp. 3204-3212.

Mamula, P, Markowitz, JE, Baldassano, RN. “Inflammatory bowel disease in early childhood and adolescence: special considerations”. Gastroenterol Clin North Am. vol. 32. 2003. pp. 967-995.

Russell, RK, Drummond, HE, Nimmo, EE, Anderson, N, Smith, L, Wilson, DC, Gillett, PM, McGrogan, P, Hassan, K, Weaver, LT, Bisset, M, Mahdi, G, Satsangi, J. “Genotype-phenotype analysis in childhood-onset Crohn’s disease: NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease”. Inflamm Bowel Dis. vol. 11. 2005. pp. 955-964.

Loftus, EV. “Clincal epidemology of inflammatory bowel disease: Incidence, prevalence, and environmental influences”. Gastroenterology. vol. 126. 2004. pp. 1504-1517.

Ongoing controversies regarding etiology, diagnosis, treatment

Discussed above in treatment section.