pediatric inflammatory bowel disease
Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract. While no specific etiology has been identified, the complex nature of IBD gives evidence that its origin is likely multi-factorial and includes genetic susceptibilities and environmental factors. These factors induce an immune dysregulation, which in turn leads to mucosal injury. Although there is currently no cure, we have many available therapies with which we can treat the culprit (inflammation) and potentially avoid short- and long-term complications.
Historically, IBD has been classified into two main entities: Crohn disease and ulcerative colitis. Crohn disease is a deeper, transmural inflammation that can affect the gastrointestinal tract anywhere from the mouth to the anus. Ulcerative colitis is an erosive mucosal ulceration that primarily affects the large intestine. When a patient’s signs and symptoms overlap the patterns of Crohn’s and ulcerative colitis, we give a label of indeterminate colitis or IBD-unclassified (IBD-U).
Incidence of IBD is increasing in many parts of the world, though stabilizing in others.1 The burden of caring for children with IBD is increasing in the United States.2,3 Children and adolescents with IBD present in a myriad of ways and have presented by way of self-referral, primary care provider, emergency department, adult gastroenterology (GI), and pediatric medical and surgical subspecialties. In the Dayton, Ohio, area, around 200 families with children are affected with IBD.
Indications For Workup
There are many presenting signs and symptoms of IBD, including GI and non- GI signs and symptoms (referred to as extra-intestinal manifestations). One way to conceptualize differing presenting symptoms and signs is to divide these into upper GI and lower GI symptoms (Table 1). Some of the more concerning red flags from this list include weight loss, poor growth, perianal disease and nocturnal stooling.
Weight loss or decline of weight-for-age percentiles is a concerning red flag, especially in pediatrics. Children could be expected to lose weight during episodes of acute infectious gastroenteritis. These episodes may be expected to last at most seven to 10 days, with a recovery in weight occurring shortly afterwards. If the weight loss persists for greater than a month, further workup should be entertained. The same is true for linear or height growth; tapering of height velocity over a period of six or more months should prompt an evaluation for causes, including workup for IBD. Regardless of the time frame involved, it is always appropriate to speak with your local pediatric gastroenterologist. Perianal disease is another concerning red flag. Clinicians have an opportunity to make an early diagnosis by performing an external perianal exam. Early detection by the primary care provider or emergency department clinician can save months or years of untreated disease, which in turn could save lost growth potential, hospitalizations and surgeries. It is vital to perform a perirectal exam on a child you are worried could have IBD.
Nocturnal stooling is nearly always a red flag. If a child is waking up from sleep to pass a bowel movement, further questioning and investigations should be strongly considered. These may include inquiring about upper and lower GI symptoms (Table 1), obtaining infectious stool studies (see below for further workup), or performing a perirectal or rectal exam looking for deep fissures, anal tags or fistulous openings.
Extraintestinal manifestations (EIMs) may also be part of a child’s initial presentation. In a study of pediatric patients at one institution, six percent had at least one EIM before diagnosis of IBD and 29 percent had at least one EIM develop within 15 years of diagnosis.4 The most common EIMs after diagnosis of IBD include osteopenia/osteoporosis, peripheral arthritis, aphthous stomatitis, pancreatitis, iritis/uveitis, erythema nodosum, primary scleros5 ing cholangitis and compression fractures. Those who are younger when diagnosed have more opportunity to develop an EIM.4 Ankylosing spondylitis and pyoderma gangrenosum are less common EIMs that may also be familiar to clinicians. Disease type and severity are associated with the occurrence of EIMs.5
Screening for IBD may be done with labs (complete blood count, erythrocyte sedimentation rate, c-reactive protein, albumin) and/or with a fecal calprotectin. In patients with diarrhea, infectious stool studies (stool culture, C. difficile, giardia/ cryptosporidium antigen) should be considered. In general, current serology screens for IBD, which are very expensive, are neither specific nor sensitive enough to either rule in or out the diagnosis of either ulcerative colitis or Crohn disease, are of questionable value and should be discouraged. Consultation with a pediatric gastroenterologist can be helpful when determining who and when to screen. Diagnosis of IBD is accomplished by endoscopic and microscopic evaluation of the upper and lower intestines, in addition to imaging of the small intestines, typically done with magnetic resonance (MR) enterography or video capsule endoscopy. Fecal calprotectin results obtained at diagnosis and followed prospectively can be used as a non-invasive marker of disease activity throughout the course of treatment.
Laboratory results that support a diagnosis of IBD include microcytic or normocytic anemia, hypoalbuminemia and elevated inflammatory markers (including platelets, erythrocyte sedimentation rate and c-reactive protein). As noted above, an elevated fecal calprotectin also supports the diagnosis of IBD, in the setting of chronic symptoms. Endoscopically, the gastrointestinal tract of patients with IBD reveals mucosal edema, friability and ulcerations, and can have inflammatory pseudopolyps as well as other endoscopic findings. Histologically, granulomas are present in Crohn disease, with crypt abscess and architectural changes in colitis. Video capsule study can reveal small bowel ulcerations or other breaks in mucosa, suggestive of Crohn disease. MR enterography can identify direct signs of bowel wall thickening and enhancement, as well as secondary signs such as the ‘comb’ sign or sequelae of untreated disease (fistulas and abscesses; Figure 1). Crohn disease is described as inflammatory (i.e., non-stricturing and non-penetrating), stricturing, penetrating, or both stricturing and penetrating. Once a patient has been designated as having stricturing or penetrating disease, they will always have that phenotype. Ulcerative colitis is classified as having severe disease or not. In both Crohn disease and ulcerative colitis, extent of disease is also characterized. In addition to these characterizations, there are other important markers of disease severity that help determine appropriate treatment, including need for hospitalization, transfusion, growth or nutrition failure. A.
Treatments are tailored to target the extent, severity and phenotype of disease, as well as other severity markers. Treatment of IBD should seek to decrease the inflammation and its effects to improve quality of life. Complimentary treatments can also be considered, though these therapies have not been proven to decrease inflammation and change the natural history of IBD. Standard treatments are described below. Biologic medications (infliximab, adalimumab, vedolizumab, ustikinumab, others) have become a mainstay for pediatric IBD. They target a narrower part of the immune system as compared to steroids. These medications are indicated for patients with moderate to severe disease, fistulizing or penetrating phenotype in Crohn’s, extraintestinal manifestations, growth or nutrition failure, or extensive disease. Some biologics are infusion medications, whereas others are administered subcutaneously. As we learn more about these medications, we are able to deliver them in quicker and easier ways. There are many biologics currently undergoing study, including an oral form. Monitoring the therapeutic levels of these medications can help ensure adequate immune suppression, while avoiding excessive exposure and potential side effects.
Immune-modulating medications, such as 6–mercaptopurine and azathioprine (both oral medications), have been used for many years in the treatment of pediatric IBD. These medications work by suppressing white blood cell production. They require an enzyme test prior to initiation as well as careful monitoring of the white blood cell count and liver enzymes during therapy. Methotrexate is another medication in this class and can be given orally or injected. Folate supplementation is needed for anyone on chronic methotrexate therapy. Topical therapies such as mesalamine and 5–aminosalicylate products are typically used in mild ulcerative colitis. These also require regular monitoring with labs and urinalysis. They are thought to be helpful in superficial inflammation, but do not reach the deeper inflammation of Crohn disease. Many different forms of corticosteroids are also used in treatment of IBD. The most common, prednisone, carries with it substantial side effects if used chronically. We typically use prednisone as induction therapy and minimize its use as much as possible. Current “top down” thinking minimizes the use of prednisone with its substantial side effects. Other forms of steroids, including budesonide and rectal preparations of steroid, can target application of steroids and avoid most side effects.
Primary nutrition therapy (PNT) has gained traction in inducing remission in pediatric Crohn disease. PNT is exclusive or near-exclusive nutrition via semi-elemental formula. Although some can drink this nutrition, many need a nasogastric (NG) tube to ensure adequate intake. By the end of three months of PNT, the patient is transitioned to a maintenance therapy (which can include PNT). The NG tube and the social nature of eating remain barriers to this therapy; however, it remains an attractive therapy for those families who wish to avoid suppression of the immune system.
The Importance of Expertise And Continuous Improvement
Why is it important for children with IBD to follow at a center with pediatric expertise? Children present with more severe disease and with greater potential for short- and long-term comorbidities and complications as compared to adults who develop IBD. A child also has untapped growth potential. A fellowship- trained pediatric gastroenterologist has been trained in the use of the above medications, workup and management. They are attuned to subtle signs and symptoms with which children with new-onset IBD can present.
As our health system moves away from the fee-for-service model and toward bundled payments, more attention will be placed on quality metrics. These quality metrics not only allow for internal review and quality improvement, but also allow for external benchmarking. Quality improvement learning systems enable continuous process improvement as well as external benchmarking and sharing of best practices. This enables our local patient population to receive the same care that is given at the best centers across the country. Dayton Children’s participates in the ImproveCareNow network, an international learning system of 90+ centers.6,7 We have implemented population health management tools and thinking that have allowed us to dramatically improve our remission rates over the past two years. Additionally, our patients undergo annual health maintenance assessments, medical and psychosocial screenings, and surveillance management. Together, these interventions represent continuous improvement for children with IBD that ultimately help them achieve disease remission, improve their quality of life and enable their future success.
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