Crohn Disease

CD usually has a more insidious onset (possibly due to delayed diagnosis) and can affect any part of the gut from the mouth to the anus. On histopathological examination, the inflammation is usually transmural and can be characterized by “skip” lesions. The hallmark finding of granulomas is, however, present in only a few patients. The most common region of involvement is ileocolonic, followed by colonic, small bowel, or gastroduodenal disease. The most common presenting symptoms are abdominal pain (86%), diarrhea (78%), or hematochezia (49%). In the pediatric population, the patient may be diagnosed with CD while being evaluated for malnutrition, short stature, delayed puberty, fatigue, or sometimes fistulizing disease. Fistulas are connections formed in gastrointestinal regions affected by ulceration to other parts of the organ or the surface of a nearby skin, seen in CD but not UC. Patients with CD have been misdiagnosed as having anorexia nervosa, or even sexual abuse. Other clinical manifestations include drainage, abscess (intra-abdominal or perianal), pain, or malnutrition. Patients with CD are at risk for having a stricture or obstruction in the small bowel or colon. As a result, they may present with bowel obstruction or even perforation leading to peritonitis.

Ulcerative Colitis

Symptoms of UC can include diarrhea, abdominal cramping, and hematochezia. Due to the presence of bloody stools, medical attention is sought much earlier than in CD. In contrast to CD, patients with UC have primarily colonic involvement confined to the mucosal layer without skip lesions, although patients can have gastritis or distal colitis. Children present with pancolitis more frequently than adults. Other extraintestinal manifestations such as weight loss, malnutrition, and delayed puberty are less commonly observed. Anemia and hypoalbuminemia are common in both types of IBD, but other inflammatory markers such as sedimentation rate and C-reactive protein may be relatively normal in UC whereas they may be elevated in CD.

Crohn Disease

The treatment of CD depends on the location, type of disease (inflammatory, stricturing, or perforating), and presence of fistulas or abscesses. Mesalamines are often used because they are safe; however, they are unlikely to induce disease remission on their own. At present, steroids are used as first-line therapy for induction of CD remission. If disease is confined to the terminal ileum and cecum, oral budesonide can be used instead of systemic steroids because it has the advantage of being released directly into these gastrointestinal regions. Budesonide also has the added advantage of extensive first-pass metabolism in the liver, making systemic side effects unlikely. For maintenance of remission immunomodulators, including mercaptopurine and methotrexate, can be used in those who cannot be weaned from steroids or who experience relapse of their CD after steroid withdrawal. Both agents have a similar mode of action but are used judiciously due to side effects, including an increased risk of lymphoma. Infliximab has been found to be helpful in both the induction and maintenance of disease remission. Other biologic agents approved for CD include adalimumab, certolizumab, and natalizumab. The latter agent works by preventing migration of plasma leukocytes and extracellular matrix proteins to the site of inflammation in the gut. There is a high risk of infection, as natalizumab is not specific for the gut.

In children, nutritional therapy is also a desirable first-line treatment because it is only slightly inferior to steroids in efficacy, and it has added advantages of promoting mucosal healing and optimizing growth. The more palatable newer formulas can be taken orally, but some patients may require placement of nasogastric or a gastrostomy tube. Nutritional therapy has no side effects, but adherence to a strict diet for 8 weeks on polymeric formula alone is often prohibitive, particularly during adolescence when peer imitation is an important driver of identify formation. Although the exact mechanism of action is not well understood, various possibilities include enhancement of the innate immune system as a result of better nutritional status, reduced antigenic load in the distal intestine, and altered gut flora. Surgery in patients with CD is used mainly for complications such as stricture, abscess, perforation, or fistulizing disease. Surgery is not curative for CD because of a high risk of postoperative disease recurrence.

Ulcerative Colitis

For mild to moderate disease severity, oral and rectal mesalamines are the mainstay of therapy. Most preparations are formulated to be released in both the terminal ileum and colon, or just the colon. These agents are now also available in once-daily dosing options to improve adherence. Mesalamines work by inhibition of NF-κB and leukotriene synthesis, modification of neutrophil-mediated tissue damage, and scavenging of reactive oxygen species. Patients who fail to respond to mesalamines or who have severe disease can be treated with oral or intravenous steroids. Steroids have a general anti-inflammatory effect and also inhibit cell-mediated immunity, but prolonged use can lead to unacceptable side effects including short stature, weight gain, moon facies, and skin striae. If a patient is unresponsive or becomes steroid dependent, then immunomodulators such as mercaptopurine may be used, and biologic agents such as infliximab, a cytokine antagonist targeting tumor necrosis factor α (TNF-α), have been effective in avoiding or at least delaying the need for surgery. TNF-α is a key cytokine involved in the pathogenesis of IBD. As a last resort, surgery can be curative in UC as the disease is confined to the colon, although it requires the surgical placement of an ostomy, either temporarily or permanently.

Adjustment Disorder/Depression and Anxiety

The diagnosis of a chronic illness such as IBD during childhood can involve a grieving process that begins with shock and disbelief and proceeds through feelings of anguish (sadness) and protest (anger) toward the gradual assimilation of illness information and adjustment to the implications of the disease. In both children and adolescents, the diagnosis of IBD can involve a sense of loss in any one of the following areas: independence, sense of control, privacy, body image, healthy self, peer relationships, roles inside and outside the family, self-confidence, productivity, future plans, familiar daily routines, ways of expressing sexuality, and pain-free existence. The child’s reaction to IBD, including the degree of perceived loss, is moderated by developmental factors, disease severity, and environmental/social factors (eg, family reaction). For example, adolescents with severe physical illness may have fragile self-esteem due to delays in physical growth or pubertal maturation, shame associated with fecal incontinence, or steroid-induced weight gain, and thus have a more challenging adjustment to the disease. There are, however, conflicting reports as to what extent self-esteem is affected by IBD. Some studies suggest that self-esteem in adolescents with IBD is comparable with that of healthy controls, contradicting others that found self-esteem worse in those affected with IBD. One factor that seems to negatively affect self-esteem is more severe disease activity and having separated parents.

Children with IBD may experience overwhelming psychological distress including guilt for being a burden to caretakers, threats to narcissistic integrity and self-esteem, regressive fear of strangers on whom the patient must rely, separation anxiety, fear of loss of love and approval, fear of loss of control of bodily functions, and fear of pain and humiliation. Invasive medical procedures can result in traumatization and reactions ranging from dissociation, emotional blunting, anxiety, and anger (Szigethy and Siegle, unpublished observations, 2009). Although initially most children deny that IBD interferes with their lives, with persistent questioning many admit frustration and anger about their IBD symptoms and treatment. Children with IBD also exhibit concern about fatigue, body image, and lack of control over activities (eg, school, sports, and work).

Several studies have found that adolescents with IBD are more depressed than adolescents with other diseases, with rates of depression as high as 25%. In a study by Mackner and colleagues, children with IBD and depression were at an increased risk of anxiety. Anxiety disorders have also been described in adolescents with IBD. Externalizing disorders (eg, disruptive behavioral disorders, conduct disorder) and attention deficit hyperactivity disorder (ADHD) have been less well studied in these children. Disordered eating (eg, severe restriction often secondary to abdominal pain) is commonly seen in clinic but the rate of eating disorders has not been studied. The temporal relationship between mood and anxiety disorders and IBD has also not been systematically examined. Children diagnosed at a younger age appear to adjust better than older teenagers. Whether this is due to a more flexible sense of self-identity, cognitive maturation, or differences in the grieving process or processing of illness experience has not been studied.

Influence of Physiologic Changes of IBD on Psychological Functioning

Physiologic changes associated with the disease process itself (eg, cytokine-induced inflammation, steroid treatment) may affect the brain, thereby resulting in emotional and behavioral changes that further compromise the child’s adjustment. Szigethy and colleagues found in a study of 102 youths with IBD that those who had moderate to severe IBD-related symptoms had significantly greater depressive severity than youths with inactive disease. Furthermore, depressive severity has been strongly associated with the degree of pain and diarrhea, as well low plasma albumin levels. Hypoalbuminemia may be a marker for both chronic inflammation and malnutrition. In another study, pediatric patients with inactive IBD or with mild disease for at least 1 year reported normal emotional/behavioral functioning, similar to that of healthy children. In children with IBD, exogenous steroids used to treat IBD have been associated with impairment in mood, executive function, and short-term memory.

In adults with IBD, there was a significant inverse correlation between sleep quality and IBD severity, and abnormal sleep patterns were reported even in patients with inactive IBD compared with normal controls. Because they often need more sleep, sleep disturbances could have an even greater impact on adolescents and adversely affect their quality of life (QOL), psychological functioning, and coping ability. Given that sleep is critical for disease healing, studies are needed to determine how IBD affects sleep architecture, duration, and quality, so that better treatments for insomnia and fatigue can be developed.

Functional Abdominal Pain

Even in remission, IBD patients may still experience severe gastrointestinal symptoms similar to those present in irritable bowel syndrome (IBS), including abdominal pain, bloating, abdominal distention, diarrhea, urgency, loose stools, constipation, hard stools, and incomplete bowel movements. In adults, approximately one-third of patients with UC and two-thirds of patients with CD report these symptoms, possibly from the visceral hypersensitivity or autonomic dysfunction induced by chronic inflammation. In adult patients with UC in remission, the prevalence of IBS-like symptoms is about 3 times higher than in healthy controls, and these patients had impaired health-related quality of life (HRQOL) similar to that of patients whose UC was in the active phase. In children with quiescent CD, rectal sensory threshold for pain (RSTP) was significantly decreased in comparison with that of healthy controls, and was similar to the RSTP of children with functional gastrointestinal disorders.

Medication Adherence

Because medications are critical to the management of IBD, medical adherence is particularly important for children with IBD. Although having to take daily medication can adversely affect QOL, the consequences of nonadherence can lead to more severe disease and QOL outcomes, including an increase risk for surgery. Adherence can be especially problematic during adolescence. One study found that medication adherence rates in pediatric IBD were 38% according to parents and 48% according to the children studied. Family dysfunction and poor child coping strategies were associated with worse adherence. In a sample of 44 patients 10 to 21 years old who had IBD, there was a significant relationship between age and dietary adherence, with younger children more likely to report better dietary adherence. In another study, medication adherence was assessed in 36 adolescents with IBD via interviews, pill counts, and biologic assays. Nonadherence to 6-mercaptopurine/azathioprine (6-MP/AZA) was related to poorer self-reported physical health QOL. In contrast, greater adherence to 5-aminosalicylate (5-ASA) was related to poorer psychological health QOL, especially social functioning, on the Pediatric Quality of Life Inventory. These results may be related to the child’s perceptions that taking multiple pills is related to poorer QOL, particularly in social realms. The interaction between social functioning and treatment adherence was also illustrated in a recent study showing that positive social relationships buffered the negative effects of peer victimization on treatment adherence in youth with IBD.

Disease Outcomes

In adults with IBD, depression and life stressors have been associated with a more refractory course of IBD; however, this has not been studied in children. Camara and colleagues found that 13 of 18 prospective studies conducted since 1980 reported a statistically significant association between stress and worsened IBD outcomes in adults. In another review, Singh and colleagues found strong evidence for an association between perceived stress levels and IBD flares. There is evidence that the course of IBD is worse in depressed patients, and in an animal model of colitis, induction of a depressive episode in mice reactivated the colitic inflammation.

Illness Perception

Several studies have probed illness perception in children and adolescents. In response to questions that explored the impact of IBD on their daily lives, children with IBD aged 7 to 19 years, themes of discomfort from symptoms and treatment, vulnerability, diminished control over their lives and future, and seeing themselves as different from healthy peers were commonly discussed. Additional difficulties noted were lack of energy, food restriction, medication side effects, diminished self-perception, and less social interaction.

In a study consisting of 50 depressed adolescents, qualitative illness narrative analysis of perception of IBD experience was conducted using responses to 10 questions in a structured interview to probe themes of pessimism, contingency (ie, a sense the child could control their disease), and coping with IBD. This study found that IBD severity was inversely correlated with positive contingency as well as positive feelings about IBD medications. In addition, depressive severity was associated with negative self-competence and sense of damaged self (McLafferty and Szigethy, unpublished observations, 2010). These correlations were not affected by age or gender. In another study examining how 17 adolescents (age 11–17 years) with IBD responded to their parents’ concern for them, ambivalence was the most prevalent theme described. There was an oscillation between seeking close contact with one’s parents and pushing them away. The other theme categories that emerged were ability/inability, compliance/resistance, and trust/distrust, suggesting that it is important to have an awareness of the simultaneous existence of conflicting attitudes, reactions, and emotions.

There are several reports of shame and embarrassment in the literature concerning adolescents with IBD. Nicholas and colleagues interviewed 80 children and adolescents (7–19 years old) with IBD, concerning the impact of IBD on their lives. The interviewees revealed negative body-image perceptions from the disease process (short stature, weight loss, physical weakness) and side effects from treatment (weight gain, acne, visible nasogastric tube). There is also embarrassment related to using public bathrooms. In another study of 20 adolescents with ostomies or J-pouches, embarrassment and shame were recurring themes that led to hesitance about revealing their ostomy, and fear that it would be discovered. Adolescents were able to develop acceptance of their ostomies over variable amounts of time, particularly with more education and independence in the care of the ostomy.

Psychosocial Functioning/Quality of Life

HRQOL is a concept that consists of the physical, emotional, and social aspects of health perception and health functioning. Several instruments are now available to measure IBD-related HRQOL, including generic and disease-specific types. Generic assessments are multidimensional problem lists designed to be applied to any population, and they are able to compare QOL in populations with different diseases. Generic measures have been used in HRQOL studies in both adults and children with IBD.

Disease-specific instruments focus on concerns relevant to a particular illness. Unlike generic measures, they can measure changes in HRQOL over time or with treatment. One disease-specific measure developed and validated for children is the IMPACT questionnaire, designed for use in youths 10 years or older. Its most recent form, IMPACT-III, consists of 35 questions encompassing 6 domains: IBD symptoms, body image, functional/social impairment, emotional impairment, treatment/interventions, and systemic impairment. The patient’s current health status is believed to have the greatest influence on responses to the IMPACT questionnaire. This pediatric IBD-specific measure accomplishes 3 tasks: (1) documenting the effects of health care interventions on patient outcomes; (2) providing a more complete picture of the patient than that available from pediatric IBD disease indices alone; and (3) helping to identify the needs of the child with IBD and success of medical management.

In pediatric IBD, adolescents with IBD symptom exacerbation are more likely to express greater psychosocial difficulty, but steroid exposure, hospitalizations, and time from IBD diagnosis did not significantly impact HRQOL in children with IBD. In young adult patients who were diagnosed with IBD as children or adolescents, HRQOL was significantly decreased when compared with healthy age-matched controls. Indeed, compared with healthy controls, children with IBD have decreased psychosocial health, social functioning, and school functioning.

Family Functioning/Interactions

Interviews with adolescents with CD stress the importance of achieving a balance between adequate social support and time for self-reflection. One area of the physically ill adolescent’s life in which this balance can be difficult to achieve is family functioning. Children with IBD who have good mental health reported a good family climate and open social network, and positive affect in mothers of adolescents with IBD is inversely correlated with the adolescents’ depression. Family conflict and low QOL have been positively correlated with pain, fatigue, depression, and lower QOL in children with IBD. Collectively, studies suggest that family functioning is an important component of how children cope with chronic illness. In addition, parents of children with IBD reported significantly less social support and mothers reported greater distress compared with parents of healthy children. The lack of social support, but not parental distress, was correlated with increased behavioral problems in children with IBD. If it is possible that a family’s dynamic is influencing the adolescent’s health status, therapy should be implemented to examine and potentially improve family functioning and parental affect.

Transition to Adulthood

Even without the presence of a chronic physical illness, adolescence is a challenging life phase with significant changes in both physiologic (eg, emotional regulation, cognitive processing, maturation of self-image) and physical (eg, pubertal changes, growth) realms. The transition from adolescence to adulthood may be particularly challenging for youth with a chronic disease such as IBD. In individual interviews 6 patients 19 to 24 years old with UC and a temporary ostomy identified several themes present in their experiences living with UC and an ostomy: embarrassment, feeling different, and unpredictability/sense of loss of control. In a study of 22 patients 15 to 21 years old who have a chronic illness (23% had IBD), most adolescents anticipating their transfer to adult care identified only negatives about the transition and felt unprepared at the time of their interview with Tuchman and colleagues. College students with active IBD have significantly poorer adjustment to college and students with IBD had lower physical QOL compared with healthy controls, suggesting that this transition is important to monitor. The goals of successful transition to adulthood include the acquisition of skills to manage their illness, including further education/knowledge about their illness as well as relaxation techniques to manage stress, to continue striving for autonomy and self-regulation and for identity formation by learning from trial and error.