INTRODUCTION — Inflammatory bowel disease (IBD), as well as treatment-related medical or surgical interventions, can adversely affect linear growth, pubertal development, and nutritional status. Patients with IBD are also at risk for the development of complications in organs outside of the gastrointestinal tract, including the eye (iritis and uveitis), hepatobiliary tract (primary sclerosing cholangitis [PSC]), and skin (eg, erythema nodosum). Routine monitoring for these extraintestinal complications is mandatory. Finally, immunosuppressive medications used to treat patients with IBD also confer an increased risk for developing more severe infections with common pathogens and susceptibility to several less common opportunistic infections.
These risks require special health maintenance considerations, as discussed in this topic. Related issues concerning the diagnosis and management of IBD are discussed in separate topic reviews:
●(See "Clinical presentation and diagnosis of inflammatory bowel disease in children".)
●(See "Overview of the management of Crohn disease in children and adolescents".)
●(See "Management of mild to moderate ulcerative colitis in children and adolescents".)
●(See "Management of severe or refractory ulcerative colitis in children and adolescents".)
●(See "Growth failure and pubertal delay in children with inflammatory bowel disease".)
MONITORING NUTRITIONAL STATUS
Growth failure — Growth failure is a prevalent extraintestinal manifestation of IBD in children and is particularly common in patients with Crohn disease [1]. Children with exacerbations of IBD may experience an acute onset of anorexia, weight loss, and dehydration. Children with less fulminant IBD are more likely to present with indolent anorexia, poor weight gain, and decreased height velocity. If left unchecked, growth failure can result in permanent stunting. Growth failure in children with IBD can be reversed or prevented if the disease is diagnosed expediently and is subsequently well controlled through a clinical approach centered on the use of targeted antiinflammatory and immunosuppressive therapies, minimal corticosteroid exposure, and the provision of a diet sufficient to support age-appropriate gains in height and weight. (See "Growth failure and pubertal delay in children with inflammatory bowel disease".)
All children with IBD should have regular anthropometric measurements, including body weight, height, and pubertal status [2-5]. Body mass index should be calculated and tracked as well. Changes in body mass index and height percentiles should be monitored over time by plotting on a standard chart. In general, these measurements should be obtained and recorded at least every four to six months for patients with quiescent disease and more frequently for those patients with active disease or evidence of growth failure (table 1).
Radiographic determination of bone age can be a valuable component in evaluating children who present with growth failure, and results are abnormal in up to 40 percent of children with IBD [6]. Children with IBD-related growth failure typically manifest delayed bone age, and this can improve with an institution of effective medical and nutritional therapies, particularly if this is addressed in earlier pubertal stages [7]. Accurate interpretation of bone age requires the input of pediatric radiology and endocrinology staff. (See "Diagnostic approach to children and adolescents with short stature", section on 'Bone age determination'.)
Micronutrient deficiencies — Recommendations for monitoring nutritional status in children and adults with IBD vary between publications. Some authors recommend that healthy children with Crohn disease be screened annually for micronutrient deficiencies or more frequently if there is active disease or a history of surgical resection of the intestine (table 2) [4]. Low levels of vitamins A, D, and E; zinc; and selenium have been reported, especially in children with moderate or severe disease activity [8-10]. Vitamin B12 deficiency is most common in patients who have undergone ileal resection [10,11]. Folate deficiency was observed in 20 to 60 percent of adults with IBD in older case series but is much less common in studies conducted in the last decade [12,13]. Patients taking sulfasalazine or methotrexate are at increased risk for folate deficiency and may require supplementation. (See "Vitamin and mineral deficiencies in inflammatory bowel disease".)
Iron deficiency is common in patients with IBD [14]. This can result from a combination of inadequate dietary intake due to anorexia or dietary habits, increased iron loss due to gastrointestinal bleeding, and decreased iron utilization due to chronic inflammation. Patients may have difficulty tolerating oral iron supplements, especially those experiencing anorexia related to moderate or severe intestinal disease activity. As such, oral iron supplements may be most useful for treating iron deficiency in IBD patients with quiescent or mild disease. In contrast, parenteral iron repletion will likely be more effective and better tolerated than oral iron preparations for patients with significant inflammation, large iron deficit, or ongoing blood loss, as shown in a meta-analysis [15]. This issue is discussed separately. (See "Treatment of iron deficiency anemia in adults", section on 'Inflammatory bowel disease'.)
Bone mineral density — Reduced bone mineral density or osteopenia is present in approximately 30 percent of children and adolescents with IBD [16]. The osteopenia in these patients is typically associated with pubertal delay. It may result from vitamin D deficiency, insufficient calcium intake or malabsorption, disease-related inflammatory activity, or glucocorticoid therapy [17]. (See "Metabolic bone disease in inflammatory bowel disease" and "Growth failure and pubertal delay in children with inflammatory bowel disease", section on 'Clinical manifestations'.)
The prevention and treatment of bone disease in children and adolescents with IBD should focus on intensive counseling to optimize nutrition, evaluation for pubertal delay, and minimizing the use of glucocorticoids. The recommended daily intake of vitamin D and calcium for children and adolescents with IBD is identical to that for their otherwise healthy peers, including 15 micrograms (600 international units) of vitamin D for children and adolescents. The recommended calcium intake is 1000 mg daily for children 4 to 8 years of age, increasing to 1300 mg for adolescents aged 9 to 18 years. Many children cannot meet these targets by dietary intake alone and require supplements to achieve these goals. One guideline recommends a higher intake of both of these nutrients in children and adolescents with IBD, targeting a vitamin D intake of 800 to 1000 international units and a calcium intake of 1000 to 1600 mg [18]. (See "Vitamin and mineral deficiencies in inflammatory bowel disease", section on 'Calcium'.)
Monitoring serum concentrations of 25-hydroxyvitamin D (25-OHD) is recommended at least annually [4,5]. Ideally, this should be performed in the late winter or early spring, when vitamin D levels are at their annual nadir [19]. Optimal 25-OHD concentrations have not been established for children, but studies suggest that levels above 30 ng/mL will facilitate small bowel calcium absorption and blunt parathyroid hormone secretion. Further studies have suggested that 25-OHD levels in the 35 to 50 ng/mL range may be necessary to optimize this vitamin's beneficial effect(s) on the immune system [20]. Most patients will require daily supplements (delivered as vitamin D2 or D3) to maintain 25-OHD levels in this range [21].
Dual-energy x-ray absorptiometry (DXA) scanning can be used to evaluate bone density. DXA findings in children are expressed as Z-scores to reflect age-specific standards (rather than T-scores as in adults). Interpretation of DXA scanning for children remains problematic and requires adjustment for bone size. Unadjusted DXA Z-scores for age and sex may systematically underestimate bone density in shorter patients or patients with delayed growth and maturation [4,5,22,23]. It is unclear whether modest decreases in bone density predict fracture risk in children and adolescents with chronic illness [24]. (See "Overview of dual-energy x-ray absorptiometry", section on 'Children'.)
There are no widely accepted standards for monitoring bone health in children and adolescents with IBD. However, we suggest obtaining baseline densitometry (DXA) in patients with risk factors for bone disease, including those with growth failure, secondary or primary amenorrhea, pubertal delay, refractory IBD, prolonged use of glucocorticoids, or a history of clinically significant fractures [18]. Some investigators suggest repeating DXA scans annually if the bone mineral density Z-score is more than 1.0 standard deviation below the mean [18]. The availability of prospective bone density measurements should enable clinicians to stratify which of their patients are most in need of closer follow-up or nutritional supplementation.
Treatment with bisphosphonates is not recommended in children, except in unusual circumstances such as those who have experienced vertebral fractures. These agents have long half-lives and may result in the formation of bone with abnormal characteristics. As such, the long-term risks and benefits of using these agents in children have not been fully delineated [18,25]. Children with severe osteopenia or a history of recurrent fracture may benefit from referral to a specialist with expertise in endocrinology or bone health. (See "Metabolic bone disease in inflammatory bowel disease".)
INFECTION RISK — Treating children and adolescents with immunomodulators (mercaptopurine, azathioprine, or methotrexate), biologics (infliximab, adalimumab, certolizumab pegol, vedolizumab, or ustekinumab), or Janus kinase (JAK) inhibitors (tofacitinib) confers an increased risk of more severe or atypical bacterial, fungal, mycobacterial, and viral infection [26,27]. The relative increase in infectious risks conferred by immunosuppressive IBD therapies has not been fully articulated. It likely varies with choice of drug and dose, age, and other environmental and genetic risk factors specific to a particular patient. The known risks are discussed briefly below and in detail separately. (See "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections" and "Tumor necrosis factor-alpha inhibitors and mycobacterial infections".)
To minimize the risk of serious infection, we suggest that children undergo screening for latent tuberculosis (TB) before the initiation of treatment with immunosuppressive drugs, especially infliximab and other tumor necrosis factor (TNF)-inhibiting agents [28,29]. TB screening is typically performed with interferon-gamma release assays and tuberculin skin testing, sometimes supplemented with a chest radiograph [28,30]. Testing for TB in children who have been vaccinated with Bacillus Calmette-Guerin and the management of patients who are thought to be anergic are discussed separately. (See "Latent tuberculosis infection in children".)
IMMUNIZATIONS — We recommend a prompt review of a child's immunization status as soon as a diagnosis of IBD is suspected, as outlined in the table (table 3) [28]. This will enable clinicians to initiate or complete any recommended immunization series, thereby ensuring optimal protection from vaccine-preventable diseases and minimizing potential conflicts between vaccinations and the initiation of immunosuppressive medications. It is particularly important to review the patient's status for live viral vaccines, including varicella and measles, mumps, and rubella. The administration of live viral vaccines is generally contraindicated when a patient is being treated with immunosuppressive drugs. (See 'Live viral vaccines' below.)
Children with IBD should undergo routine childhood vaccines with the following special considerations:
Measurement of titers — We suggest measuring titers for measles, testing for hepatitis B surface antigen and antibody (HBsAg and HBsAb), and documentation of immunity to varicella in all children and adolescents with IBD, regardless of their immunization history. As outlined below, patients with low (nonprotective) antibody titers should be reimmunized but with special considerations for live viral vaccines.
Immunosuppressive treatment may reactivate HBV disease in patients with chronic hepatitis B virus (HBV) infection (eg, HBsAg+, HBsAb-). Treatment options for these patients are discussed separately. (See "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections", section on 'Hepatitis B' and "Clinical manifestations and diagnosis of hepatitis B virus infection in children and adolescents".)
Definition of immunosuppression — Patients are considered immunosuppressed if they are being treated with prednisone (>20 mg/day for adults if given for at least 14 days), immunomodulators (6-mercaptopurine, azathioprine, or methotrexate) or any of the growing number of biologic agents (including infliximab, adalimumab, certolizumab pegol, ustekinumab, or vedolizumab) or if they present with significant protein-calorie malnutrition [31]. Patients are considered to remain immunosuppressed for approximately three months after completing treatment with most of these agents or for one month after treatment with prednisone.
A guideline from the Infectious Disease Society of America further distinguishes between low-level and high-level immunosuppression [32]:
●Low-level immunosuppression:
•Prednisone <2 mg/kg, with a maximum of ≤20 mg per day
•Methotrexate ≤0.4 mg/kg per week
•Azathioprine ≤3 mg/kg per day
•6-mercaptopurine ≤1.5 mg/kg per day
●High-level immunosuppression:
•Treatment with doses higher than those listed for low-dose immunosuppression
•Biologic agents such as anti-tumor necrosis factor-alpha (anti-TNF-alpha) antibodies
This distinction is most relevant to decisions about immunization with the varicella vaccine. (See 'Varicella and measles' below.)
Inactivated vaccines — The administration of inactivated (killed) vaccines is safe in immunosuppressed patients. Immunization is generally effective, although immunomodulators and biologic agents may slightly attenuate the immune response to specific serotypes [33]. Therefore, any needed catch-up or reimmunization should ideally be administered at least two weeks before initiating immunosuppressive therapy [28,29].
Routine inactivated vaccines — Immunization with inactivated vaccines should be brought up to date and rigorously maintained during treatment. This includes influenza, HBV, hepatitis A virus (HAV), diphtheria/pertussis/tetanus (DTaP or Tdap), Haemophilus influenzae type B, pneumococcus, meningococcus, and human papillomavirus vaccines [4,34,35]. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups' and "Standard immunizations for children and adolescents: Overview", section on 'Infants and children'.)
Pneumococcal polysaccharide vaccine — Children with IBD should receive the standard pneumococcal conjugate vaccine series (either the 13-valent pneumococcal conjugate vaccine [PCV13] or 15-valent pneumococcal conjugate vaccine [PCV15]), which is recommended for all children in the United States. They should also receive the 23-valent pneumococcal polysaccharide vaccine (PPSV23; eg, Pneumovax 23) because they are at increased risk for invasive pneumococcal disease if they are being treated with immunosuppressive medication. PPSV23 should be administered at age ≥2 years and at least eight weeks after the last indicated dose of PCV. The PPSV should be given before initiating immunosuppressive therapy whenever possible to optimize vaccine response. Immunosuppressed patients have impaired vaccine response, particularly those receiving combination therapy (TNF-alpha inhibitors and immunomodulators) [36,37]. (See "Pneumococcal vaccination in children" and "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents'.)
Live viral vaccines — Diseases preventable with live viral vaccines include varicella, measles, rubella, and yellow fever. In general, live viral vaccines should not be given to patients with high-level immunosuppression (see 'Definition of immunosuppression' above). The immunization strategy for these diseases requires special considerations, as outlined below:
Varicella and measles — We suggest checking titers for measles and documentation of immunity to varicella (health care provider diagnosis of disease, documentation of immunization, or serologic evidence of immunity) before initiating treatment with immunomodulators or biologics [28,29]. For patients without evidence of immunity:
●If immunosuppression can be safely delayed – Immunize patients with varicella or measles vaccines at least four weeks before beginning immunosuppressive treatment.
●If patients are already immunosuppressed or if immunosuppressive treatment cannot be safely delayed – There is controversy over whether varicella immunization should be performed, and no guidelines sufficiently address this issue [31,32,34,38,39]. On the one hand, immunosuppressed children are at increased risk of developing severe, disseminated varicella if exposed to the virus. On the other hand, they may also be at risk for developing the disease due to the live-attenuated varicella vaccine. Therefore, the benefits and risks of vaccination should be weighed on a case-by-case basis. Factors contributing to the decision about whether and when to vaccinate include a child's particular disease activity, the potential for exposure to wild-type varicella in the community, and the relative risks and severity of vaccine-associated versus wild-type disease [33]. Administration of varicella vaccine can be considered for patients that are non-varicella-immune and are receiving long-term, low-level maintenance immunosuppression, as stated in guidelines from the Infectious Disease Society of America [32]. (See 'Definition of immunosuppression' above.)
Immunosuppressed children who are not immune to varicella and are exposed to the disease should be treated with varicella-zoster immune globulin, usually combined with oral or parenteral acyclovir. (See "Post-exposure prophylaxis against varicella-zoster virus infection".)
Family and household contacts of immunosuppressed patients can be safely immunized with measles and varicella vaccines [32]. Vaccine recipients who develop a vaccine-related rash should avoid contact with the immunosuppressed patient.
Rubella and yellow fever — We advise against administering these live viral vaccines to patients with IBD receiving ongoing immunosuppressive therapy, those within three months of stopping treatment, or if treatment is planned within 4 to 12 weeks [31].
Polio — Live-attenuated oral polio vaccine is still used in some low-income countries. Immunosuppressed patients and their household contacts who require poliovirus vaccination should not be given oral polio vaccine. However, they may safely be vaccinated with the inactivated poliovirus vaccine, the standard polio vaccine used in the United States and most middle- and upper-income countries. (See "Poliovirus vaccination".)
MONITORING FOR EXTRAINTESTINAL MANIFESTATIONS — Extraintestinal manifestations of IBD can involve the mouth, skin, joints, liver, eye, and (rarely) other organs (table 4). (See "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents", section on 'Extraintestinal manifestations'.)
The hepatobiliary and eye manifestations can be silent and, for this reason, warrant close monitoring for early detection and treatment, as outlined below.
Hepatobiliary disease — The most serious liver disease associated with IBD is primary sclerosing cholangitis (PSC). The chronic inflammation related to this disorder results in progressive scarring of the bile ducts, leading to complicated hepatobiliary disease, including cirrhosis and hepatobiliary cancer. Patients with IBD should undergo laboratory screening for hepatobiliary disease at diagnosis and periodically after that, through the measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGTP). Other causes of elevated serum aminotransferases include medications, cholelithiasis, and autoimmune hepatitis. PSC is characterized by GGTP and alkaline phosphatase elevation and a less pronounced elevation of ALT and AST. (See "Overview of hepatobiliary disorders in patients with inflammatory bowel disease" and "Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis" and "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents", section on 'Sclerosing cholangitis'.)
Eye examinations — Patients with Crohn disease or ulcerative colitis (UC) are at risk for developing erythema of the sclera or episcleritis, particularly in the context of active gastrointestinal symptoms. Episcleritis can be asymptomatic or associated with burning and itching. Uveitis is less common; not typically associated with increased gastrointestinal disease activity; and tends to present with eye pain, blurred vision, photophobia, and headaches. All patients with IBD should be screened for these complications as part of routine care, both by inquiring about eye symptoms and via regularly scheduled ophthalmologic examinations. (See "Dermatologic and ocular manifestations of inflammatory bowel disease", section on 'Ocular disease'.)
Referral for a full ophthalmologic examination is recommended for patients with symptoms or findings suggestive of episcleritis or uveitis and for patients on prolonged treatment with glucocorticoids [4,5]. Periodic examinations, approximately every one to two years, are also advisable for asymptomatic patients to establish a stable baseline examination and assess for early development of ocular complications.
Skin monitoring and care — The dermatologic manifestations of IBD include erythema nodosum and pyoderma gangrenosum. Rarely, other disorders, including necrotizing cutaneous vasculitis, Sweet syndrome, or epidermolysis bullosa acquisita, have been reported. (See "Dermatologic and ocular manifestations of inflammatory bowel disease", section on 'Dermatologic disease'.)
In addition to these associations, patients with IBD are at increased risk for both melanoma and nonmelanotic skin cancers [40-42]. Treatment with anti-tumor necrosis factor (anti-TNF) antibodies, such as infliximab, increases the risk for melanoma and may induce or worsen psoriasis. Immunomodulators (mercaptopurine and azathioprine) appear to increase the risk for nonmelanotic skin cancers, including basal and squamous cell carcinomas. As such, clinicians should inform patients about these risks, advise avoidance of sun exposure, and recommend formal dermatologic evaluation of any new or suspicious skin lesions as part of routine care of patients with IBD, especially for patients on anti-TNF antibody therapy [4]. (See "Dermatologic and ocular manifestations of inflammatory bowel disease", section on 'Rare dermatologic diseases' and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Cutaneous reactions'.)
PSYCHOLOGICAL SCREENING AND SUPPORT — Children and adolescents with any chronic disease, including IBD, are at risk for developing a variety of psychosocial problems. These comorbidities can interfere with their ability to participate in regular academic, social, and athletic activities and impact their ability to remain compliant with the medical management of their disease. Given these issues, psychological screening and support should be incorporated into the routine care of the patient with IBD [43].
●Screening and support – The pediatrician and gastroenterologist should be aware of, screen for, and make themselves available to address psychosocial issues honestly and openly during clinic visits. Screening for depression and other concerns is essential. Clinicians may choose to use measures such as the patient health questionnaire 9 (PHQ-9), which has been validated for use in this population for depression screening [44,45]. A depression screening toolkit has been developed for children with IBD and is designed to screen children 12 years and older [43,46]. (See "Screening tests in children and adolescents", section on 'Depression screening'.)
Patients should be referred to counseling or other appropriate supports if depression or other psychological concerns are identified. Counseling or other supports may also be useful for children or their parents to help them adapt to the challenges of dealing with a chronic illness. Unfortunately, many teenagers are either "too busy" or reluctant to attend and actively participate in such counseling. Instead, these children often get valuable psychosocial support and disease knowledge from attendance at summer camps dedicated to children with IBD [47]. Finally, many parents and children benefit from joining a support group, such as those sponsored by the Crohn's and Colitis Foundation.
●Prevalence and types of psychological problems – Case series suggest that 17 to 40 percent of pediatric patients with IBD display elements of clinical depression, anxiety, or other psychiatric diagnoses, and this is moderately increased when compared with rates reported in their siblings or from children in the general population [48-50]. Other reported problems include excessive absenteeism and reduced school functioning, teasing by peers, embarrassment during athletic activities, sleep disturbance and increased fatigue, and delayed psychosocial development [4,51-53]. Triggers for these problems may include physical differences from their peers, including short stature or pubertal delay; altered bowel patterns; increased toileting needs; or the presence of ostomies, surgical scars, or nasogastric tubes. Also, children and their families may feel burdened by the scope of requisite medical care, including frequent medication administration (up to 10 pills/day for some regimens) and office visits. Conflicts may arise between patients and their parents over appetite and eating, especially if the parents do not recognize that the underlying disease can cause anorexia. Finally, children and their parents may develop a fear of the future, particularly for patients with severe disease.
Depression in children with IBD is correlated with disease activity, psychosocial factors, and socioeconomic stressors [48,49]. While underlying emotional vulnerability may be unmasked by the psychosocial stressors outlined above, it is also possible that depression may be exacerbated by the inflammatory process itself [54,55]. This was suggested by data from a study of depressed youth with IBD, which identified subgroups with a "somatic depression" profile (characterized by objective depressive symptoms including anhedonia and fatigue, with high IBD activity) versus a "cognitive despair" profile (characterized by self-reported depressive symptoms, ostomy placements, and anxiety, with relatively low IBD activity) [56].
Sleep disturbance in children and adolescents with IBD can be related to disease activity and underlying depression [57,58]. In a study of depressed youth with Crohn disease, 53 percent reported sleep disturbance [58]. Certain types of sleep disturbance, including difficulty initiating sleep, were associated with pain and anxiety in addition to disease activity, whereas sleep duration was most closely associated with disease activity.
●Consequences – Psychosocial issues can have significant effects on the quality of life for a patient and their family, as well as interfere with disease management [59]. Anxiety or depression may affect a child's perception of abdominal pain, leading to either underreporting or overreporting of their symptoms, which can interfere with clinical monitoring of the disease [60]. Moreover, the burden of medication and medical care may lead to "medication fatigue" and nonadherence to the regimen.
The effects of IBD extend beyond the child and can significantly impact the family's emotional stress and quality of life. One study of families with adolescent children with IBD found that an adolescent's depressive symptoms significantly impacted the parent's level of distress, independent of disease activity [61]. Most of the parent respondents in this study were mothers. A separate study interviewed both parents and found that the mother's distress was closely linked to the adolescent's degree of emotional adjustment [62]. In contrast, the father's distress was more closely associated with the adolescent's disease activity.
TRANSITION TO ADULT HEALTH CARE — Facilitating a healthy transition to adult care is a fundamental goal for the pediatric clinician caring for patients with IBD. The process extends throughout adolescence and includes each of the following elements:
●The pediatric gastrointestinal clinician discusses and shapes the patient's and family's expectations after transitioning to an adult center.
●Office visits should be increasingly focused on cultivating the patient's knowledge and establishing a repertoire of disease self-management skills, emphasizing adherence to the medication regimen.
●There is a deliberate transfer of care to a specific adult provider, with an organized transfer of medical information between providers when the patient is developmentally ready (and, ideally, when they are medically stable).
●The accepting provider helps to educate the transitioning patient about any differences in protocols or procedures and provides additional time and support during the transition process.
Guidelines have been developed to facilitate an organized transition process for adolescents and young adults with IBD [63,64], with an approximate timeline for each step [65]. A "Transfer Toolkit" was developed collaboratively by a group of IBD patients and clinicians in the United States [66]. It is designed to guide patients through their transfer to adult care by developing age-appropriate knowledge and skill milestones to help them gain increasing autonomy in managing their disease.
SURVEILLANCE FOR CANCER — Individuals with IBD, and especially those with primary sclerosing cholangitis (PSC), are at increased risk for some types of cancer [67-69].
●Colorectal cancer – Patients with ulcerative colitis (UC) or Crohn colitis are at an increased risk of developing colorectal cancer [67,69]. Individuals with UC or Crohn colitis should undergo surveillance colonoscopy for cancer screening beginning 8 to 10 years after the diagnosis of their IBD, based on limited data about the magnitude and timing of cancer risk. Endoscopic and histologic data from surveillance colonoscopy is most conclusive if performed when a patient is in clinical remission [4,5,70]. The frequency of the screening should be determined by the findings on the initial colonoscopy but ranges from every one to three years.
Colorectal cancer has been reported in children younger than 18 years; factors associated with increased risk include increased duration of disease, extent of colitis, and level of inflammation. Having a first-degree relative with colorectal cancer similarly places a patient with IBD at an increased risk of colon cancer [68]. The approximate cumulative incidence of colorectal cancer in patients with pancolitis is 5 to 10 percent after 20 years of disease and 12 to 20 percent after 30 years [71]. Dysplasia is generally restricted to inflamed tissue [72]. Because children are more likely than are adults to have pancolitis at disease onset, they may be more susceptible to colorectal cancer. Colon cancer in patients with UC and Crohn colitis can occur throughout the colon, and multiple synchronous tumors can be present.
Individuals with PSC and IBD are at particularly high risk for developing colorectal cancer. In a retrospective study of more than 500 pediatric patients with PSC and colitis, the probability of developing colorectal cancer was 0.8 percent at five years after initial diagnosis and 4.8 percent at 10 years; the incidence of colorectal cancer was 2.8 cases per 1000 person-years [73]. Therefore, these individuals should begin annual colonoscopic cancer screening once the PSC is diagnosed [70,72]. (See "Surveillance and management of dysplasia in patients with inflammatory bowel disease" and "Primary sclerosing cholangitis: Inflammatory bowel disease and colorectal cancer".)
●Hepatobiliary cancer – Individuals with PSC and IBD are also at high risk for developing hepatobiliary cancer [42,69,70]. We suggest that such patients undergo annual ultrasonography of the biliary tree and serum carbohydrate antigen 19-9 (CA 19-9) measurements to screen for hepatobiliary cancer [74]. (See "Primary sclerosing cholangitis in adults: Management", section on 'Gallbladder carcinoma and cholangiocarcinoma'.)
●Small bowel cancer – The incidence of small bowel cancer in Crohn disease is also higher than in the general population [69,75]. However, because of the rarity of these tumors, the number of patients with Crohn disease experiencing this complication remains small. Patients with IBD have an increased risk of nonmelanoma skin cancer, which may be most closely related to the use of thiopurines. IBD also is associated with an increased risk for melanoma, and the use of tumor necrosis factor (TNF) inhibitors also contributes to this increased risk [41,76]. Patients should be advised to avoid excessive sun exposure and use high-strength sunscreen and other sun-protective measures. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy", section on 'Skin cancer risk'.)
●Other cancers – While increases in the incidence of squamous cell carcinoma of the anus, duodenal neoplasia, and lymphoma have all been reported in patients with Crohn disease, the strength of these associations remains unclear [42]. Several population-based studies on the incidence of lymphoma in adults with IBD have found relative risks ranging from 0.4 to 2.4 [42]. Considering the data in aggregate, they do not support an increased risk of developing lymphoma in patients with IBD compared with the general population. However, treatment with azathioprine or 6-mercaptopurine may increase the risk of lymphoma two- to fourfold [4,77]. At present, no guidelines exist for monitoring the development of these complications. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inflammatory bowel disease in children".)
SUMMARY AND RECOMMENDATIONS
●Monitoring nutritional status – Growth failure is common in patients with inflammatory bowel disease (IBD), particularly those with Crohn disease. Screening and monitoring patients for growth failure and optimizing nutrition are essential components in the longitudinal care of children and adolescents with IBD (table 1). Disturbances in these parameters are also sensitive indicators of occult IBD activity and response to therapy. (See 'Monitoring nutritional status' above and "Growth failure and pubertal delay in children with inflammatory bowel disease".)
●Infection risk and immunizations – Immunization status should be assessed before initiating immunosuppressive medications (especially infliximab and other anti-tumor necrosis factor-alpha [anti-TNF-alpha] antibodies). This assessment should include the following steps:
•Tuberculosis risk – Evaluate for tuberculosis (TB) risk factors and test for latent TB infection with an interferon-gamma release assay and tuberculin skin test, sometimes supplemented with a chest radiograph. (See 'Infection risk' above.)
•Antibody titers – Measure measles titers, test for hepatitis B surface antigen and antibody (HBsAg and HBsAb), and document immunity to varicella, as outlined in the table (table 3). (See 'Measurement of titers' above.)
-If immunization for live virus vaccines including varicella or measles is indicated, this should be given at least four weeks before initiating immunosuppressive therapy. In general, live viral vaccines should not be given to patients with high-level immunosuppression. The immunization strategy for these diseases requires special considerations. (See 'Live viral vaccines' above.)
-For patients with chronic hepatitis B virus (HBV) infection (eg, HBsAg+, Ag-), immunosuppressive treatment may reactivate the HBV disease. (See 'Measurement of titers' above.)
•Inactivated vaccines – Review the immunization history and administer all routine inactivated vaccines as needed, including influenza, hepatitis B, human papillomavirus, and pneumococcus. Whenever possible, it is preferable to administer any needed catch-up or reimmunization before initiating immunosuppression. (See 'Routine inactivated vaccines' above.)
Administer the 23-valent pneumococcal polysaccharide vaccine (PPSV23), in addition to the standard PCV. This recommendation is based on a concern that immunosuppressed patients are at increased risk of developing invasive pneumococcal disease. (See 'Pneumococcal polysaccharide vaccine' above.)
•Live viral vaccines – In general, live viral vaccines (varicella, measles, rubella, and yellow fever) should not be given to patients with high-level immunosuppression. (See 'Live viral vaccines' above.)
●Eye disease – Routinely screen for episcleritis and uveitis by inquiring about eye symptoms and examining the sclerae for injection and nodules at each clinical encounter. Referral for a full ophthalmologic examination is recommended for patients with symptoms or findings suggestive of episcleritis or uveitis and for patients on prolonged treatment with glucocorticoids. Periodic ophthalmologic examinations, approximately every one to two years, are also advisable for asymptomatic patients. (See 'Eye examinations' above.)
●Psychological screening and support – As part of routine care, inquire about depressive symptoms and anxiety, including excessive absenteeism and disruption in school functioning, sleep disturbance, and family conflict. Clinicians should refer to psychological counseling and support as needed. These issues have important effects on the quality of life for the patient and family and can interfere with disease management. (See 'Psychological screening and support' above.)
●Cancer surveillance – Patients with ulcerative colitis (UC) or extensive Crohn colitis should begin surveillance colonoscopy for cancer screening approximately 8 to 10 years after IBD diagnosis, preferably during a quiescent period of the disease. Individuals who develop primary sclerosing cholangitis (PSC) should begin annual screening for colorectal cancer as soon as the PSC is diagnosed. (See 'Surveillance for cancer' above.)
