• 20% to 30% of inflammatory bowel disease (IBD) cases are diagnosed during childhood
• Extraintestinal manifestations (EIM), particularly growth delay, may be the predominate presenting feature in childhood IBD
• Coinfection with Clostridium difficile increases morbidity
Approximately two million people worldwide are afflicted with IBD. IBD is more common in westernized societies and in the northern hemisphere. There is a higher incidence in Caucasians and those of Jewish descent. Approximately 20% to 30% of all patients with IBD present during childhood.1,2 Childhood incidence is estimated at 0.5 to 4.3/100,000 for ulcerative colitis (UC) and 0.2 to 8.5/100,000 for Crohn disease (CD).3 The incidence of UC has remained stable whereas pediatric CD has increased in incidence.4–7 UC and CD occur equally in the first 8 years of life and CD is more common in older children.8
The exact pathophysiology of IBD is not well understood. There is likely a combination of environmental, genetic, and immune factors. An environmental trigger may incite a deregulation of immune response to gut flora in a genetically susceptible host.9–11 Patients with IBD have less complex profiles of commensal bacteria and higher numbers of mucosa-associated bacteria as compared to healthy individuals.9 Increased intestinal permeability and food-borne bacterial infections trigger some IBD cases.
The cause of IBD is multifactorial, but there are many known risk factors. A family history of IBD carries an 8- to 10-fold greater risk and IBD frequency in first-degree relatives may be as high as 40%.3,12IBD is particularly severe in Jewish persons with familial Mediterranean fever.13 Pediatric IBD has a stronger genetic correlation, possibly because children have less lifetime exposure to environmental factors.14–16 Infections are also associated with IBD. C. difficile infection can be either an inciting or exacerbating factor.17 An increased risk of IBD has been shown in persons after acute gastroenteritis with Salmonella or Campylobacter.18,19 The risk is highest during the first year after the gastroenteritis episode, but remains high compared to matched controls for up to 15 years.19 Other environmental risk factors include: smoking (in CD; smoking is protective against UC), exclusive formula-feeding, a diet high in animal protein,20 occupation, education, climate, and stress.3
Pediatric patients with IBD typically present with signs and symptoms of colitis. Often, they have a subacute illness with abdominal pain and diarrhea that is often bloody. Fever, fatigue, anemia, and weight loss are also common presenting symptoms in IBD. Symptoms may be persistent (≥4 weeks) or recurrent (≥2 episodes in 6 months)20 EIM occur in 6% of children upon presentation have a total incidence of 25% to 35%.14 IBD relapse can be precipitated by bacterial, parasitic or viral superinfection. C. difficile and cytomegalovirus (CMV) are both the most common and most challenging to manage.17
Younger children (<8 years of age) with IBD are more likely to have isolated colonic disease. Often, because the diagnosis of either UC or CD is initially unclear, children are labeled as having indeterminate colitis (IC). There is no widely accepted definition of IC; thus, IC includes a heterogenous subset of patients. IC has been reported in 3% to 30% of pediatric IBD.21
UC is limited to the colon and involves the superficial mucosa. Typically there are continuous lesions that start from the rectum. The mucosa is friable and bleeding may occur spontaneously. With severe disease, ulcerations may develop and rarely, lesions penetrate the muscularis layer.22 The rectum is always involved in adults, but not in children. At presentation, 44% to 49% of children with UC have rectosigmoid disease, 36% to 41% have left-sided disease, and 14% to 27% have pancolitis.3 Childhood UC tends to be more severe as compared to adult. Approximately 80% to 90% of children either present with or progress to pancolitis (in contrast to 40%–50% of adults).23 There is a shorter time from diagnosis to first surgery in children with UC as compared to adults. One study demonstrated that at 10 years after diagnosis, 40% of childhood-onset UC had required a colectomy versus on 20% of adult-onset UC.24 In the majority of patients, the clinical course involves disease flares alternating with periods of remission. A minority of patients have continuous activity. Overall, disease activity tends to decrease over time.
CD is marked by transmural bowel wall inflammation throughout the gastrointestinal tract. Normal mucosa surrounds diseased segments (skip lesions). In both children and adults, CD most commonly affects the terminal ileum and right colon. Younger children have predominately colonic disease,23,25 though the upper gastrointestinal tract is involved in up to two-thirds of children with CD.26 The most common presenting symptoms of CD include abdominal pain, diarrhea, rectal bleeding, and weight loss. CD often has a more insidious onset and patients present with vague complaints of malaise and mild abdominal discomfort. EIM can dominate the clinical picture and may even be present prior to gastrointestinal symptoms in children.27 Growth and sexual developmental delay also may precede intestinal symptoms.20Diagnostic delays of months are common. The clinical course of pediatric CD tends to be more severe as compared to adults. The course is unpredictable with recurrent exacerbations of symptoms and, more rarely, continuous active disease. Ulcerations may become deep and develop complications such as abscess, fistulas, strictures, and obstruction from adhesions. Small bowel disease results in obstruction and colonic involvement often presents with bleeding. There is no direct correlation between symptoms and progression of anatomic damage. A small segment of ileitis can cause severe abdominal pain and fatigue whereas strictures and fistulas may be asymptomatic for years.2
The physical examination in pediatric IBD varies greatly depending on the location and severity of the involved gastrointestinal tract. Oral ulcers may be noted in CD. Abdominal tenderness may be mild, localized or diffuse in both CD and UC. The abdomen may be rigid or peritoneal in severe acute colitis, toxic megacolon, or intestinal perforation. A palpable mass may be present in CD, as well as perianal involvement such as fistulae, anal tags, abscesses, or fissure may be present. Gross or occult stool blood is often present.
EIM occur in 25% to 35% of children with IBD (see Table 75-1). Growth failure is the most common EIM in pediatric IBD. Inadequate nutrition, chronic steroid use, and decreased physical activity contribute to growth delays. Up to 46% of children will have a reduced height velocity before the onset of symptoms.28 CD with perianal involvement portends a higher risk for EIM than other IBD patients. Patients who develop one EIM are more likely to develop additional EIMs.29
Extraintestinal Manifestations (EIM) in Pediatric IBD
Normal laboratory test results do not exclude the diagnosis of IBD.20,30 Common abnormalities seen include anemia, thrombocytosis, increased ESR/CRP (particularly in CD) and mild elevation of AST and ALT. Low albumin is commonly present because of malnutrition in children with IBD31 Laboratory findings are more likely to be abnormal with severe disease. There is poor sensitivity and specificity of serology panels in screening for IBD. The most widely used diagnostic panel in the United States is the IBD Serology 7 panel®.32 Anti-saccharomyces cerevisiae antibody (ASCA) and perinuclear antineutrophil cytoplasmic antibody (pANCA) are disease-specific for CD and UC, respectively. Blood and leukocytes are commonly present in stool. In acute exacerbation, stool culture should be sent in children with bloody diarrhea to evaluate for Salmonella, Shigella, Yersinia, Campylobacter, C. difficile, Giardia, Escherichia Coli 0157:H7, Entamoeba, and tuberculosis. The incidence of C. difficile is greater in children as compared to adults and frequently correlates with severity of disease in young children.31
DIAGNOSTIC IMAGING FOR IBD
Endoscopy Frequently, there is endoscopic overlap between CD and UC. Diffuse colonic involvement is common in both pediatric UC and CD and both may have gastric ulcers.33
Crohn Disease Ileal inflammation is present in most CD. Non-necrotizing granulomas confirm the diagnosis of CD but are only present in approximately 50% to 60% of patients.34,35 Cobblestoning (mucosal ulcerations interlaced with normal segments of bowel), bowel wall edema, bowel narrowing or obstruction, and enteric fistulas may be seen. Noncontinuous areas of affected bowel (skip lesions) are often present and there is frequently relative rectal sparing.
Ulcerative Colitis Typically, diffuse and continuous inflammation starts at the rectum and extends proximally into the colon. Early in pediatric UC, atypical features may occur with patchy disease and relative rectal sparing. Nonspecific inflammation in the upper gastrointestinal tract may occur in up to 75% of children with UC.20 “Backwash ileitis” may occur in 10% of UC patients with pancolitis.34 Pseudopolyps, areas of regenerating mucosa from prior areas of ulceration are often present.
OTHER DIAGNOSTIC MODALITIES
Upper GI with small-bowel follow-through has been the traditional method of evaluating the upper gastrointestinal tract for IBD. Ultrasound is not currently used for IBD screening but may play a larger role in the future as bowel ultrasound becomes more established.36 Intestinal hypervascularity and thickened bowel loops can be seen in active IBD.37 Mesentery can be evaluated and fluid collections and abscesses may be visualized. Ultrasound identifies terminal ileal disease better than proximal small bowel and colonic lesions. Advanced US techniques are emerging using oral, rectal, and even IV contrast to improve scan quality. Ultrasound does not expose a child to radiation and is relatively inexpensive and accessible. CT with oral contrast can evaluate the bowel wall and lumen well, and may identify abscesses as well. MRI use is increasingly common in pediatric IBD despite less well-established technique, as it avoids the risk of radiation.38–41 Video capsule endoscopy is used in adults to evaluate CD severity. It is approved by the FDA for ages older than 10 years but pediatric GI doctors have found the capsule helpful in diagnosing children as small as 11.5 kg with an acceptable complication rate. The benefit is the avoidance of radiation, sedation, or general anesthesia.42–45
EMERGENCY DEPARTMENT IMAGING
An abdominal series may be used as an initial test in the emergency department (ED) to evaluate for serious complications of IBD. This may show bowel obstruction with air–fluid levels, free air suggestive of perforation, and evidence of toxic megacolon. Findings of toxic megacolon include colonic dilation with an abnormal mucosal contour which is typically most pronounced in the transverse colon. Acute dilatation of transverse colon to >5 to 6 cm with loss of haustral folds with severe exacerbation of colitis is diagnostic in older children and adults of toxic megacolon but the clinical appearance of illness is more important. In children younger than 10 years, transverse colonic diameter of >4 cm is suggestive of toxic megacolon.46 Ultrasound may be used in an acute exacerbation and can detect mesenteric inflammatory changes, lymphadenopathy, and abscesses. CT may be necessary in an emergent case to evaluate for perforation with an acute abdomen. (Fig. 75-1)
Figure 75-1 Image of toxic megacolon in a 14-year-old boy. Note the significant dilation of the transverse colon (>5–6 cm is suggestive of toxic megacolon) and loss of haustral folds. (Used with permission from Dr. Frank Sinatra.)
The overall goal in IBD management is to induce remission and minimize flares. Maintenance medications are used with additional medication interventions as needed for acute flares. The effectiveness of various therapies is difficult to assess because there is a lack of adequately powered, high-quality studies available in children. The current published data include studies with methodological problems that are frequently cohort studies.47 Exclusive enteral nutrition in which the patient receives exclusively elemental formula (via mouth, nasogastric tube, or gastrostomy tube) has been shown to effectively induce remission in children with IBD. This therapy is more common in Canada and western Europe and used less commonly in the United States. Adherence is difficult and exclusive enteral nutrition may be required for 6 to 8 weeks to induce remission.
Oral lesions may be treated with topical prednisolone syrup (5 mg/5 mL) or dexamethasone (0.5 mg/5 mL) 5 mL painted to lesions or swished and spit twice daily. Triamcinolone 0.1% may be used on lips two to four times per day. If disease is limited to the rectum, topical therapy is used. Rectal hydrocortisone enemas or foam or topical 5-aminosalicylate (5-ASA) enema/suppository may be used.
In both pediatric CD and UC, corticosteroids are used for induction but not maintenance of remission. Steroids are used for 2 to 4 weeks and then tapered off and ideally used for less than 4 months to diminish side effects and growth disturbances. Oral corticosteroids are used with mild disease (Prednisone 1–1.5 mg/kg per day, max 40–60 mg). Budesonide is less effective but has less adverse effects due to its high first-pass hepatic metabolism and decreased systemic effect. Oral corticosteroids are escalated to IV steroids (methylprednisolone 1 mg/kg per dose q12 h, max 60 mg per day) if the patient is unresponsive to oral corticosteroids in 1 to 2 weeks. IV steroids are initially started with severe disease (see ED care below).
5-ASA is used for both remission induction and maintenance in pediatric IBD though there are no randomized controlled trials published in children. Examples include sulfasalazine, mesalamine, olsalazine, and balsalazide. 5-ASA agents inhibit synthesis of proinflammatory prostaglandins and leukotrienes in the colon. Slight exacerbation of watery diarrhea is common during the first few weeks of 5-ASA preparations, but initial worsening of colitis symptoms (cramps, diarrhea, and rectal bleeding) indicates an adverse reaction and most commonly occurs with mesalamine. These patients are typically then termed “allergic” to 5-ASA preparations. 5-ASA agents are ineffective during an acute exacerbation and should be discontinued during a flare.
Immunomodulators (6-mercaptopurine, 6-MP, azathioprine, AZA, methotrexate): 6-MP and AZA show efficacy in inducing remission in UC and maintaining remission in pediatric CD. Both 6-MP and AZA have been shown to induce remission in 70% to 80% of steroid dependent CD but may take 2 to 4 months to work. Methotrexate has quicker onset of action but there are only small trials of its use in children.48
BIOLOGIC AGENTS (INFLIXIMAB, CYCLOSPORINE, AND TACROLIMUS)
Infliximab (most commonly used) is a chimeric monoclonal antibody directed against the cytokine tumor necrosis factor alpha. It is used both to induce and maintain remission in IBD resistant to steroids and Immunomodulators. Success rates are high but a patient may require repeated doses and treatment for a long period of time.14,49 Infusion reactions occur in 15% to 25% of patients. Initial symptoms appear like anaphylaxis including laryngospasm, shortness of breath, acute chest discomfort, hemodynamic instability, and mucosal irritability. Delayed symptoms occur 2 to 14 days after an infusion and include fever, arthritis/arthralgias, myalgias, malaise, urticarial rash. Premedication does not prevent initial infusion reaction but may decrease subsequent reactions.50,51 Reactions are typically managed by epinephrine, antihistamines, corticosteroids, and decreased infusion rate. Long-term side effects are also associated with infliximab use. Immunosuppression places patients at risk for sepsis, opportunistic infections, and lymphoma. Drug-induced lupus may occur.
Antibiotics are not indicated in acute colitis unless underlying infectious colitis is suspected.
EMERGENCY DEPARTMENT CARE—ACUTE PRESENTATION AND MANAGEMENT
Severe acute flares are characterized by more than six bloody stools per day, abdominal pain/distension, fever, tachycardia, and inflammatory changes on laboratory values. The inflammatory response from IBD alone may cause a low-grade fever. Toxic megacolon occurs in approximately 5% of adults with IBD but is less common in children. It is a surgical emergency and associated with an increased risk of perforation, sepsis, electrolyte abnormalities, and hemorrhage. Escalating abdominal pain should alert the clinician to the possibility of toxic megacolon and/or perforation. Symptoms may be masked by corticosteroid use. Bowel perforation is more common in UC than CD and typically associated with toxic megacolon. Acute flares require intravenous fluids and typically intravenous steroids. High-dose steroids (methylprednisolone 1 mg/kg/dose q12 for maximum of 30 mg q12) are most commonly used. Laboratory evaluation should include a complete blood count, electrolytes, C-reactive protein, erythrocyte sedimentation rate, albumin, and liver enzymes and function tests. Blood transfusion may be necessary. In severe colitis, blood and stool cultures including evaluation for C. difficile should be obtained to evaluate for concurrent infection. Five to 25% of patients with UC flare have underlying C. difficile and have a worse outcome.17,46,52 Steroid-resistant disease often requires endoscopy evaluation for CMV infection.53 Suspected infectious colitis, toxic megacolon, or perforation are indications for antibiotics. Routine use of opioids is discouraged because of its increased association with toxic megacolon. This presents a treatment dilemma for pain control. There have been reports of benzodiazepine use to manage tenesmus and low-dose ketamine use for pain control.46 Severe disease or complications may require surgical intervention. Adult trials show that in patients with a severe UC flare, 67% response to IV steroids, 29% required colectomies.54
Surgical intervention is reserved for patients with IBD that have not responded to medical therapy or for certain complications such as an abscess, fistula, or stricture. Surgery is also indicated in acute emergencies such as uncontrolled hemorrhage, bowel perforation, and toxic megacolon. Overall, three-fourths patients with IBD will require surgery for complications. Disease in UC is limited to the colon and a colectomy essentially “cures” the disease. Medical management is first maximized (see Surgery Complications). Risk factors for surgery in children include female gender, poor growth at presentation of disease, signs of malnutrition such as hypoalbuminemia, or those with complications such as abscess, fistula, or stricture formation.55 Endoscopic balloon dilation and steroid injection treatment is used as alternative to surgery. Success rates are higher in patients with simple strictures. Perforation is a complication.56
Overall, the incidence of surgical complications in children is between 13% and 55%.2,57–59 Early postsurgical complications include wound infections, dehiscence, pouch ischemia, and anastomotic leakage. Late complications include pouchitis and fistula formation. Intestinal obstruction may occur initially or years after initial surgery. Some patients (10% after operation) have CD diagnosed after the surgery (usually 5–10 years later).
Ileal pouchitis occurs in 7% to 44%. The majority of patients have a single initial attack after surgery. Symptoms include acute onset of diarrhea (may be >30 episodes per day), urgency, incontinence, rectal bleeding, abdominal cramping, and malaise in a patient after restorative proctocolectomy. Endoscopic examination of the pouch demonstrates mucosal hemorrhage, ulcers, and contact bleeding in the ileal mucosa. EIM of colitis often relapse with pouchitis. Treatment includes antibiotics (typically metronidazole) and corticosteroid enemas. Most cases resolve within 72 hours of treatment. Chronic pouchitis may less commonly occur. The etiology of pouchitis is unknown but theories include ischemia, bacterial overgrowth, immunologic abnormality, or recurrent disease in colonic metaplasia.
LONG-TERM COMPLICATIONS OF IB
In IBD, overall, there is a small increase in mortality of 0.5% overage matched controls.60 There does not appear to be a gender difference in the clinical outcome of IBD.61
Cancer The risk of colorectal cancer in patients with IBD overall has decreased in the past 30 years. Those with IBD onset prior to age 25 years, particularly males, still have increased risk.62 Children who develop UC before age 14 years have a colon cancer incidence rate of 5% at 20 years and 40% at 35 years. The risk of dying from colon cancer is 8% after 10 years from diagnosis.3 Cancer has been reported in children younger than 18 years of age. In addition, CD has a 40-fold increased risk of small bowel cancer.63 A diagnosis of UC and primary sclerosing cholangitis portends a high risk for colorectal cancer.64,65
Medication Complications IBD medication use has varying association with mortality.66 Immunocompromise from various agents increases risk of disseminated and opportunistic infections. Steroid use is associated with masking signs and symptoms of toxic megacolon and perforation which can increase both morbidity and mortality. Use of azathioprine and mercaptopurine increase the risk for nonmelanoma skin cancers67 and immunomodulators increase risk of lymphoma. A rare fatal form of lymphoma, hepatosplenic T-cell lymphoma is associated with 6-MP and AZA, but not with infliximab monotherapy.14
Thromboembolic Risks IBD is a well-established risk factor for recurrent venous thromboembolism. The pathophysiology behind this risk is not completely understood. It is likely multifactorial and frequently related to acquired risk factors such as surgery, immobilization, dehydration, and indwelling central venous lines.68
Growth Pediatric IBD has unique manifestations with respect to the growth and development of a child. Consequences of IBD include malnutrition, failure to thrive, delayed puberty, and short stature. Proinflammatory cytokines exert deleterious effects on growth in IBD via various mechanisms either systemically or at the level of the growth plate.69
Psychosocial Effects The psychosocial effects of a developing child with IBD can be significant and complex. Fear of strangers, separation anxiety, fear of loss of love and approval, fear of loss of control of bodily functions, and fear of pain and humiliation are common in children. Not surprisingly, up to 25% of adolescents with IBD are depressed.70 Social support, education, and skills to cope with stress are important in caring for a child with IBD.71
Other Premature subclinical atherosclerosis may occur in pediatric IBD. There are early reports that microvascular endothelial dysfunction occurs similar to lupus and rheumatoid arthritis (Table 75-2, Fig. 75-2).72
Differential Diagnosis of IBD
Peptic ulcer disease
Urinary tract infection
Irritable bowel syndrome
Figure 75-2 Algorithm for emergency department management.
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