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Inflammatory Bowel Disease
The term inflammatory bowel disease (IBD) is used to represent 2 distinctive disorders of idiopathic chronic intestinal inflammation: Crohn disease and ulcerative colitis. Their respective etiologies are poorly understood, and both disorders are characterized by unpredictable exacerbations and remissions. The most common time of onset of IBD is during the preadolescent/adolescent era and young adulthood. A bimodal distribution has been shown with an early onset at 10-20 yr of age and a second, smaller peak at 50-80 yr of age. Approximately 25% of patients present before 20 yr of age. IBD may begin as early as the 1st yr of life, and an increased incidence among young children has been observed since the turn of the 20th century. Children with early-onset IBD are more likely to have colonic involvement. In developed countries, these disorders are the major causes of chronic intestinal inflammation in children beyond the first few yr of life. A third, less-common category, indeterminate colitis , represents approximately 10% of pediatric patients.
Genetic and environmental influences are involved in the pathogenesis of IBD. The prevalence of Crohn disease in the United States is much lower for Hispanics and Asians than for whites and blacks. The risk of IBD in family members of an affected person has been reported in the range of 7–30%; a child whose parents both have IBD has a >35% chance of acquiring the disorder. Relatives of a patient with ulcerative colitis have a greater risk of acquiring ulcerative colitis than Crohn disease, whereas relatives of a patient with Crohn disease have a greater risk of acquiring this disorder; the 2 diseases can occur in the same family. The risk of occurrence of IBD among relatives of patients with Crohn disease is somewhat greater than for patients with ulcerative colitis.
The importance of genetic factors in the development of IBD is noted by a higher chance that both twins will be affected if they are monozygotic rather than dizygotic. The concordance rate in twins is higher in Crohn disease (36%) than in ulcerative colitis (16%). Genetic disorders that have been associated with IBD include Turner syndrome, the Hermansky-Pudlak syndrome, glycogen storage disease type Ib, and various immunodeficiency disorders. In 2001, the first IBD gene, NOD2, was identified through association mapping. A few months later, the IBD 5 risk haplotype was identified. These early successes were followed by a long period without notable risk factor discovery. Since 2006, the year of the first published genome-wide array study on IBD, there has been an exponential growth in the set of validated genetic risk factors for IBD ( Table 362.1 ).
Table 362.1
Selection of Most Important Genes Associated With Inflammatory Bowel Disease and the Most Commonly Associated Physiological Functions and Pathways
From Ashton JJ, Ennis S, Beattie RM: Early-onset paediatric inflammatory bowel disease, Lancet 1:147–158, 2017, Table 1, p 148.
| GENE NAME | ASSOCIATED DISEASE | GENE FUNCTION AND ASSOCIATED PATHWAYS | PHYSIOLOGICAL FUNCTION | |
|---|---|---|---|---|
| NOD2 | Nucleotide-binding oligomerization domain- containing protein 2 | Crohn disease | Bacterial recognition and response, NFκB activation and autophagy and apoptosis | Innate mucosal defense |
| IL10 | Interleukin 10 | Crohn disease | Antiinflammatory cytokine, NFκB inhibition, JAK-STAT regulation | Immune tolerance |
| IL10RA | Interleukin 10 receptor A | Crohn disease | Antiinflammatory cytokine receptor, NFκB inhibition, JAK-STAT regulation | Immune tolerance |
| IL10RB | Interleukin 10 receptor B | Crohn disease | Antiinflammatory cytokine receptor, NFκB inhibition, JAK-STAT regulation | Immune tolerance |
| IL23R | Interleukin 23 receptor | Crohn disease and ulcerative colitis | Immune regulation, proinflammatory pathways—JAK-STAT regulation | Interleukin 23/T helper 17 |
| TKY2 | Tyrosine kinase 2 | Crohn disease and ulcerative colitis | Inflammatory pathway signaling (interleukin 10 and 6 etc) through intracellular activity | Interleukin 23/T helper 17 |
| IRGM | Immunity related GTPase M | Crohn disease | Autophagy and apoptosis in cells infected with bacteria | Autophagy |
| ATG16L1 | Autophagy related 16 like 1 | Crohn disease | Autophagy and apoptotic pathways | Autophagy |
| SLC22A4 | Solute carrier family 22 member 4 | Crohn disease | Cellular antioxidant transporter | Solute transporters |
| CCL2 | C-C motif chemokine ligand 2 | Crohn disease | Cytokine involved in chemotaxis for monocytes | Immune cell recruitment |
| CARD9 | Caspase recruitment domain family member 9 | Crohn disease and ulcerative colitis | Apoptosis regulation and NFκB pathway activation | Oxidative stress |
| IL2 | Interleukin 2 | Ulcerative colitis | Cytokine involved in immune cell activation | T-cell regulation |
| MUC19 | Mucin 19 | Crohn disease and ulcerative colitis | Gel-forming mucin protein | Epithelial barrier |
JAK-STAT, Janus kinase-signal transducers and activators of transcription; NFκB, nuclear factor κ-light chain enhancer of activated B cells.
A perinuclear antineutrophil cytoplasmic antibody is found in approximately 70% of patients with ulcerative colitis compared with <20% of those with Crohn disease and is believed to represent a marker of genetically controlled immunoregulatory disturbance. Approximately 55% of those with Crohn disease are positive for anti– Saccharomyces cerevisiae antibody. Since the importance of these were first described, multiple other serologic and immune markers of Crohn disease and ulcerative colitis have been recognized.
IBD is caused by dysregulated or inappropriate immune response to environmental factors in a genetically susceptible host. An abnormality in intestinal mucosal immunoregulation may be of primary importance in the pathogenesis of IBD, involving activation of cytokines, triggering a cascade of reactions that results in bowel inflammation. These cytokines are recognized as known or potential targets for IBD therapies.
Multiple environmental factors are recognized to be involved in the pathogenesis of IBD, none more critical than the gut microbiota. The increasing incidence of IBD over time is likely in part attributable to alterations in the microbiome. Evidence includes association between IBD and residence in or immigration to industrialized nations, a Western diet , increased use of antibiotics at a younger age, high rates of vaccination, and less exposure to microbes at a young age. While gut microbes likely play an important role in the pathogenesis of IBD, the exact mechanism needs to be elucidated further. Some environmental factors are disease specific; for example, cigarette smoking is a risk factor for Crohn disease but paradoxically protects against ulcerative colitis.
It is usually possible to distinguish between ulcerative colitis and Crohn disease by the clinical presentation and radiologic, endoscopic, and histopathologic findings ( Table 362.2 ). It is not possible to make a definitive diagnosis in approximately 10% of patients with chronic colitis; this disorder is called indeterminate colitis. Occasionally, a child initially believed to have ulcerative colitis on the basis of clinical findings is subsequently found to have Crohn colitis. This is particularly true for the youngest patients, because Crohn disease in this patient population can more often manifest as exclusively colonic inflammation, mimicking ulcerative colitis. The medical treatments of Crohn disease and ulcerative colitis overlap.
Table 362.2
Comparison of Crohn Disease and Ulcerative Colitis
| FEATURE | CROHN DISEASE | ULCERATIVE COLITIS |
|---|---|---|
| Rectal bleeding | Sometimes | Common |
| Diarrhea, mucus, pus | Variable | Common |
| Abdominal pain | Common | Variable |
| Abdominal mass | Common | Not present |
| Growth failure | Common | Variable |
| Perianal disease | Common | Rare |
| Rectal involvement | Occasional | Universal |
| Pyoderma gangrenosum | Rare | Present |
| Erythema nodosum | Common | Less common |
| Mouth ulceration | Common | Rare |
| Thrombosis | Less common | Present |
| Colonic disease | 50–75% | 100% |
| Ileal disease | Common | None except backwash ileitis |
| Stomach–esophageal disease | More common | Chronic gastritis can be seen |
| Strictures | Common | Rare |
| Fissures | Common | Rare |
| Fistulas | Common | Rare |
| Toxic megacolon | None | Present |
| Sclerosing cholangitis | Less common | Present |
| Risk for intestinal cancers | Increased | Greatly increased |
| Discontinuous (skip) lesions | Common | Not present |
| Transmural involvement | Common | Unusual |
| Crypt abscesses | Less common | Common |
| Granulomas | Common | None |
| Linear ulcerations | Uncommon | Common |
| Perinuclear antineutrophil cytoplasmic antibody–positive | <20% | 70% |
Extraintestinal manifestations occur slightly more commonly with Crohn disease than with ulcerative colitis ( Table 362.3 ). Growth retardation is seen in 15–40% of children with Crohn disease at diagnosis. Decrease in height velocity occurs in nearly 90% of patients with Crohn disease diagnosed in childhood or adolescence. Of the extraintestinal manifestations that occur with IBD, joint, skin, eye, mouth, and hepatobiliary involvement tend to be associated with colitis, whether ulcerative or Crohn. The presence of some manifestations, such as peripheral arthritis, erythema nodosum, and anemia, correlates with activity of the bowel disease. Activity of pyoderma gangrenosum correlates less well with activity of the bowel disease, whereas sclerosing cholangitis, ankylosing spondylitis, and sacroiliitis do not correlate with intestinal disease. Arthritis occurs in 3 patterns: migratory peripheral arthritis involving primarily large joints, ankylosing spondylitis, and sacroiliitis. The peripheral arthritis of IBD tends to be nondestructive. Ankylosing spondylitis begins in the 3rd decade and occurs most commonly in patients with ulcerative colitis who have the human leukocyte antigen B27 phenotype. Symptoms include low back pain and morning stiffness; back, hips, shoulders, and sacroiliac joints are typically affected. Isolated sacroiliitis is usually asymptomatic but is common when a careful search is performed. Among the skin manifestations, erythema nodosum is most common. Patients with erythema nodosum or pyoderma gangrenosum have a high likelihood of having arthritis as well. Glomerulonephritis, uveitis, and a hypercoagulable state are other rare manifestations that occur in childhood. Cerebral thromboembolic disease has been described in children with IBD.
Table 362.3
Extraintestinal Complications of Inflammatory Bowel Disease
Modified from Kugathasan S: Diarrhea. In Kliegman RM, Greenbaum LA, Lye PS, editors: Practical strategies in pediatric diagnosis and therapy, ed 2, Philadelphia, 2004, WB Saunders, p 285.
| MUSCULOSKELETAL |
|
| SKIN AND MUCOUS MEMBRANES |
|
| DERMATOLOGIC |
|
| OCULAR |
|
| BRONCHOPULMONARY |
|
| CARDIAC |
|
| MALNUTRITION |
|
|
| HEMATOLOGIC/ONCOLOGIC |
|
| RENAL AND GENITOURINARY |
|
| PANCREATITIS |
|
| HEPATOBILIARY |
|
| ENDOCRINE AND METABOLIC |
|
| NEUROLOGIC |
|
Chronic Ulcerative Colitis
Keywords
-
incidence
-
extraintestinal manifestations
-
fulminant colitis
-
5-aminosalicylate
-
immunomodulator
-
biologic corticosteroid
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surgery
Ulcerative colitis, an idiopathic chronic inflammatory disorder, is localized to the colon and spares the upper gastrointestinal (GI) tract. Disease usually begins in the rectum and extends proximally for a variable distance. When it is localized to the rectum, the disease is ulcerative proctitis, whereas disease involving the entire colon is pancolitis. Approximately 50–80% of pediatric patients have extensive colitis, and adults more commonly have distal disease. Ulcerative proctitis is less likely to be associated with systemic manifestations, although it may be less responsive to treatment than more-diffuse disease. Approximately 30% of children who present with ulcerative proctitis experience proximal spread of the disease. Ulcerative colitis has rarely been noted to present in infancy. Dietary protein intolerance can easily be misdiagnosed as ulcerative colitis in this age group. Dietary protein intolerance (cow's milk protein) is a transient disorder; symptoms are directly associated with the intake of the offending antigen.
The incidence of ulcerative colitis has increased but not to the extent of the increase in Crohn disease; incidence varies with country of origin. The age-specific incidence rates of pediatric ulcerative colitis in North America is 2/100,000 population. The prevalence of ulcerative colitis in northern European countries and the United States varies from 100 to 200/100,000 population. Men are slightly more likely to acquire ulcerative colitis than are women; the reverse is true for Crohn disease.
Clinical Manifestations
Blood, mucus, and pus in the stool as well as diarrhea are the typical presentation of ulcerative colitis. Constipation may be observed in those with proctitis. Symptoms such as tenesmus, urgency, cramping abdominal pain (especially with bowel movements), and nocturnal bowel movements are common. The mode of onset ranges from insidious with gradual progression of symptoms to acute and fulminant ( Table 362.4 and Figs. 362.1 and 362.2 ). Fever, severe anemia, hypoalbuminemia, leukocytosis, and more than 5 bloody stools per day for 5 days define fulminant colitis . Chronicity is an important part of the diagnosis; it is difficult to know if a patient has a subacute, transient infectious colitis or ulcerative colitis when a child has had 1-2 wk of symptoms. Symptoms beyond this duration often prove to be secondary to IBD. Anorexia, weight loss, and growth failure may be present, although these complications are more typical of Crohn disease.
Table 362.4
Montreal Classification of Extent and Severity of Ulcerative Colitis
From Ordàs I, Eckmann L, Talamini M, et al: Ulcerative colitis, Lancet 380:1606–1616, 2012, Panel 2, p 1610.
|
E, extent; S, severity.
Extraintestinal manifestations that tend to occur more commonly with ulcerative colitis than with Crohn disease include pyoderma gangrenosum, sclerosing cholangitis, chronic active hepatitis, and ankylosing spondylitis. Iron deficiency can result from chronic blood loss as well as decreased intake. Folate deficiency is unusual but may be accentuated in children treated with sulfasalazine, which interferes with folate absorption. Chronic inflammation and the elaboration of a variety of inflammatory cytokines can interfere with erythropoiesis and result in the anemia of chronic disease. Secondary amenorrhea is common during periods of active disease.
The clinical course of ulcerative colitis is marked by remission and relapse, often without apparent explanation. After treatment of initial symptoms, approximately 5% of children with ulcerative colitis have a prolonged remission (longer than 3 yr). Approximately 25% of children presenting with severe ulcerative colitis require colectomy within 5 yr of diagnosis, compared with only 5% of those presenting with mild disease. It is important to consider the possibility of enteric infection with recurrent symptoms; these infections can mimic a flare-up or actually provoke a recurrence. The use of nonsteroidal antiinflammatory drugs is considered by some to predispose to exacerbation.
It is generally believed that the risk of colon cancer begins to increase after 8-10 yr of disease and can then increase by 0.5–1% per yr. The risk is delayed by approximately 10 yr in patients with colitis limited to the descending colon. Proctitis alone is associated with virtually no increase in risk over the general population. Because colon cancer is usually preceded by changes of mucosal dysplasia, it is recommended that patients who have had ulcerative colitis for longer than 8-10 yr be screened with colonoscopy and biopsies every 1-2 yr. Although this is the current standard of practice, it is not clear if morbidity and mortality are changed by this approach. Two competing concerns about this plan of management remain unresolved. The original studies may have overestimated the risk of colon cancer and, therefore, the need for surveillance has been overemphasized; and screening for dysplasia might not be adequate for preventing colon cancer in ulcerative colitis if some cancers are not preceded by dysplasia.
Differential Diagnosis
The major conditions to exclude are infectious colitis, allergic colitis, and Crohn colitis. Every child with a new diagnosis of ulcerative colitis should have stool cultured for enteric pathogens, stool evaluation for Clostridium difficile, ova and parasites, and perhaps serologic studies for amebae ( Table 362.5 ). Cytomegalovirus infection can mimic ulcerative colitis or be associated with an exacerbation of existing disease, usually in immunocompromised patients. The most difficult distinction is from Crohn disease because the colitis of Crohn disease can initially appear identical to that of ulcerative colitis, particularly in younger children. The gross appearance of the colitis or development of small bowel disease eventually leads to the correct diagnosis; this can occur years after the initial presentation.
Table 362.5
Infectious Agents Mimicking Inflammatory Bowel Disease
| AGENT | MANIFESTATIONS | DIAGNOSIS | COMMENTS |
|---|---|---|---|
| BACTERIAL | |||
| Campylobacter jejuni | Acute diarrhea, fever, fecal blood, and leukocytes | Culture | Common in adolescents, may relapse |
| Yersinia enterocolitica | Acute → chronic diarrhea, right lower quadrant pain, mesenteric adenitis–pseudoappendicitis, fecal blood, and leukocytes Extraintestinal manifestations, mimics Crohn disease |
Culture | Common in adolescents as fever of unknown origin, weight loss, abdominal pain |
| Clostridium difficile | Postantibiotic onset, watery → bloody diarrhea, pseudomembrane on sigmoidoscopy | Cytotoxin assay | May be nosocomial Toxic megacolon possible |
| Escherichia coli O157:H7 | Colitis, fecal blood, abdominal pain | Culture and typing | Hemolytic uremic syndrome |
| Salmonella | Watery → bloody diarrhea, foodborne, fecal leukocytes, fever, pain, cramps | Culture | Usually acute |
| Shigella | Watery → bloody diarrhea, fecal leukocytes, fever, pain, cramps | Culture | Dysentery symptoms |
| Edwardsiella tarda | Bloody diarrhea, cramps | Culture | Ulceration on endoscopy |
| Aeromonas hydrophila | Cramps, diarrhea, fecal blood | Culture | May be chronic Contaminated drinking water |
| Plesiomonas shigelloides | Diarrhea, cramps | Culture | Shellfish source |
| Tuberculosis | Rarely bovine, now Mycobacterium tuberculosis Ileocecal area, fistula formation |
Culture, purified protein derivative, biopsy | Can mimic Crohn disease |
| PARASITES | |||
| Entamoeba histolytica | Acute bloody diarrhea and liver abscess, colic | Trophozoite in stool, colonic mucosal flask ulceration, serologic tests | Travel to endemic area |
| Giardia lamblia | Foul-smelling, watery diarrhea, cramps, flatulence, weight loss; no colonic involvement | “Owl”-like trophozoite and cysts in stool; rarely duodenal intubation | May be chronic |
| AIDS-ASSOCIATED ENTEROPATHY | |||
| Cryptosporidium | Chronic diarrhea, weight loss | Stool microscopy | Mucosal findings not like inflammatory bowel disease |
| Isospora belli | As in Cryptosporidium | Tropical location | |
| Cytomegalovirus | Colonic ulceration, pain, bloody diarrhea | Culture, biopsy | More common when on immunosuppressive medications |
At the onset, the colitis of hemolytic uremic syndrome may be identical to that of early ulcerative colitis. Ultimately, signs of microangiopathic hemolysis (the presence of schistocytes on blood smear), thrombocytopenia, and subsequent renal failure should confirm the diagnosis of hemolytic-uremic syndrome. Although Henoch-Schönlein purpura can manifest as abdominal pain and bloody stools, it is not usually associated with colitis. Behçet disease can be distinguished by its typical features (see Chapter 186 ). Other considerations are radiation proctitis, viral colitis in immunocompromised patients, and ischemic colitis ( Table 362.6 ). In infancy, dietary protein intolerance can be confused with ulcerative colitis, although the former is a transient problem that resolves on removal of the offending protein, and ulcerative colitis is extremely rare in this age group. Hirschsprung disease can produce an enterocolitis before or within months after surgical correction; this is unlikely to be confused with ulcerative colitis.
Table 362.6
Chronic Inflammatory Bowel-Like Intestinal Disorders Including Monogenetic Diseases
| INFECTION (see Table 362.5 ) |
| AIDS-Associated |
| Toxin |
| Immune–Inflammatory |
|
| VASCULAR–ISCHEMIC DISORDERS |
|
| OTHER |
|
Diagnosis
The diagnosis of ulcerative colitis or ulcerative proctitis requires a typical presentation in the absence of an identifiable specific cause (see Tables 362.5 and 362.6 ) and typical endoscopic and histologic findings (see Tables 362.2 and 362.4 ). One should be hesitant to make a diagnosis of ulcerative colitis in a child who has experienced symptoms for <2-3 wk until infection has been excluded. When the diagnosis is suspected in a child with subacute symptoms, the physician should make a firm diagnosis only when there is evidence of chronicity on colonic biopsy. Laboratory studies can demonstrate evidence of anemia (either iron deficiency or the anemia of chronic disease) or hypoalbuminemia. Although the sedimentation rate and C-reactive protein are often elevated, they may be normal even with fulminant colitis. An elevated white blood cell count is usually seen only with more-severe colitis. Fecal calprotectin levels are usually elevated and are increasingly recognized to be a more sensitive and specific marker of GI inflammation than typical laboratory parameters. Barium enema is suggestive but not diagnostic of acute ( Fig. 362.3 ) or chronic burned-out disease ( Fig. 362.4 ).
The diagnosis of ulcerative colitis must be confirmed by endoscopic and histologic examination of the colon (see Fig. 362.1 ). Classically, disease starts in the rectum with a gross appearance characterized by erythema, edema, loss of vascular pattern, granularity, and friability. There may be a cutoff demarcating the margin between inflammation and normal colon, or the entire colon may be involved. There may be some variability in the intensity of inflammation even in those areas involved. Flexible sigmoidoscopy can confirm the diagnosis; colonoscopy can evaluate the extent of disease and rule out Crohn colitis. A colonoscopy should not be performed when fulminant colitis is suspected because of the risk of provoking toxic megacolon or causing a perforation during the procedure. The degree of colitis can be evaluated by the gross appearance of the mucosa. One does not generally see discrete ulcers, which would be more suggestive of Crohn colitis. The endoscopic findings of ulcerative colitis result from microulcers, which give the appearance of a diffuse abnormality. With very severe chronic colitis, pseudopolyps may be seen. Biopsy of involved bowel demonstrates evidence of acute and chronic mucosal inflammation. Typical histologic findings are cryptitis, crypt abscesses, separation of crypts by inflammatory cells, foci of acute inflammatory cells, edema, mucus depletion, and branching of crypts. The last finding is not seen in infectious colitis. Granulomas, fissures, or full-thickness involvement of the bowel wall (usually on surgical rather than endoscopic biopsy) suggest Crohn disease.
Perianal disease , except for mild local irritation or anal fissures associated with diarrhea, should make the clinician think of Crohn disease. Plain radiographs of the abdomen might demonstrate loss of haustral markings in an air-filled colon or marked dilation with toxic megacolon. With severe colitis, the colon may become dilated; a diameter of >6 cm, determined radiographically, in an adult suggests toxic megacolon. If it is necessary to examine the colon radiologically in a child with severe colitis (to evaluate the extent of involvement or to try to rule out Crohn disease), it is sometimes helpful to perform an upper GI contrast series with small bowel follow-through and then look at delayed films of the colon. A barium enema is contraindicated in the setting of a potential toxic megacolon.
Treatment
Medical
A medical cure for ulcerative colitis is not available; treatment is aimed at controlling symptoms and reducing the risk of recurrence, with a secondary goal of minimizing steroid exposure. The intensity of treatment varies with the severity of the symptoms.
The first drug class to be used with mild or mild-to-moderate colitis is an aminosalicylate. Sulfasalazine is composed of a sulfur moiety linked to the active ingredient 5-aminosalicylate (5-ASA). This linkage prevents the premature absorption of the medication in the upper GI tract, allowing it to reach the colon, where the 2 components are separated by bacterial cleavage. The dose of sulfasalazine is 30-100 mg/kg/24 hr (divided into 2-4 doses). Generally, the dose is not more than 2-4 g/24 hr. Hypersensitivity to the sulfa component is the major side effect of sulfasalazine and occurs in 10–20% of patients. Because of poor tolerance, sulfasalazine is used less commonly than other, better tolerated 5-ASA preparations (mesalamine, 50-100 mg/kg/day; balsalazide 2.25-6.75 g/day). Sulfasalazine and the 5-ASA preparations effectively treat active ulcerative colitis and prevent recurrence. It is recommended that the medication be continued even when the disorder is in remission. These medications might also modestly decrease the lifetime risk of colon cancer.
Approximately 5% of patients have an allergic reaction to 5-ASA, manifesting as rash, fever, and bloody diarrhea, which can be difficult to distinguish from symptoms of a flare of ulcerative colitis. 5-ASA can also be given in enema or suppository form and is especially useful for proctitis. Hydrocortisone enemas are used to treat proctitis as well, but they are probably not as effective. A combination of oral and rectal 5-ASA as well as monotherapy with rectal preparation has been shown to be more effective than just oral 5-ASA for distal colitis. Extended release budesonide may also induce remission in patients with mild-to-moderate ulcerative colitis.
Probiotics are effective in adults for maintenance of remission for ulcerative colitis, although they do not induce remission during an active flare. The most promising role for probiotics has been to prevent pouchitis, a common complication following colectomy and ileal–pouch anal anastomosis surgery.
Children with moderate to severe pancolitis or colitis that is unresponsive to 5-ASA therapy should be treated with corticosteroids, most commonly prednisone. The usual starting dose of prednisone is 1-2 mg/kg/24 hr (40-60 mg maximum dose). This medication can be given once daily. With severe colitis, the dose can be divided twice daily and can be given intravenously. Steroids are considered an effective medication for acute flares, but they are not appropriate maintenance medications because of loss of effect and side effects, including growth retardation, adrenal suppression, cataracts, osteopenia, aseptic necrosis of the head of the femur, glucose intolerance, risk of infection, mood disturbance, and cosmetic effects.
For a hospitalized patient with persistence of symptoms despite intravenous steroid treatment for 3-5 days, escalation of therapy or surgical options should be considered. The validated pediatric ulcerative colitis activity index can be used to help determine current disease severity based on clinical factors and help determine who is more likely to respond to steroids and those who will likely require escalation of therapy ( Table 362.7 ).
Table 362.7
Pediatric Ulcerative Colitis Activity Index
| ITEM | POINTS |
|---|---|
| (1) Abdominal Pain | |
| No pain | 0 |
| Pain can be ignored | 5 |
| Pain cannot be ignored | 10 |
| (2) Rectal Bleeding | |
| None | 0 |
| Small amount only, in <50% of stools | 10 |
| Small amount with most stools | 20 |
| Large amount (>50% of the stool content) | 30 |
| (3) Stool Consistency of Most Stools | |
| Formed | 0 |
| Partially formed | 5 |
| Completely unformed | 10 |
| (4) Number of Stools Per 24 hr | |
| 0-2 | 0 |
| 3-5 | 5 |
| 6-8 | 10 |
| >8 | 15 |
| (5) Nocturnal Stools (Any Episode Causing Wakening) | |
| No | 0 |
| Yes | 10 |
| (6) Activity Level | |
| No limitation of activity | 0 |
| Occasional limitation of activity | 5 |
| Severe restricted activity | 10 |
| Sum of Index (0-85) | |
With medical management, most children are in remission within 3 mo; however, 5–10% continue to have symptoms unresponsive to treatment beyond 6 mo. Many children with disease requiring frequent corticosteroid therapy are started on immunomodulators such as azathioprine (2.0-2.5 mg/kg/day) or 6-mercaptopurine (1-1.5 mg/kg/day). Uncontrolled data suggest a corticosteroid-sparing effect in many treated patients. This is not an appropriate choice in a steroid nonresponsive patient with acute severe colitis because of longer onset of action. Lymphoproliferative disorders are associated with thiopurine use. Cyclosporine, which is associated with improvement in some children with severe or fulminant colitis, is rarely used owing to its high side-effect profile, its inability to change the natural history of disease, and the increasing use of infliximab, a chimeric monoclonal antibody to tumor necrosis factor (TNF)-α, which is also effective in cases of fulminant colitis. Infliximab is effective for induction and maintenance therapy in children and adults with moderate to severe disease. TNF blocking agents are associated with an increased risk of infection (particularly tuberculosis) and malignancies (lymphoma, leukemia). Adalimumab is also approved for treatment of moderate to severe ulcerative colitis in adults. Vedolizumab, a humanized monoclonal antibody that inhibits adhesion and migration of leukocytes into the GI tract, is approved for the treatment of ulcerative colitis in adults. Tofacitinib, an oral Janus kinase inhibitor, is also approved for treatment of moderate to severe adult ulcerative colitis. A specific combination of 3-4 wide-spectrum oral antibiotics given over 2-3 wk may be effective in treating severe pediatric ulcerative colitis refractory to other therapies but is being further studied in children.
Surgical
Colectomy is performed for intractable disease, complications of therapy, and fulminant disease that is unresponsive to medical management. No clear benefit of the use of total parenteral nutrition or a continuous enteral elemental diet in the treatment of severe ulcerative colitis has been noted. Nevertheless, parenteral nutrition is used if oral intake is insufficient so that the patient will be nutritionally ready for surgery if medical management fails. With any medical treatment for ulcerative colitis, the clinician should always weigh the risk of the medication or therapy against the fact that colitis can be successfully treated surgically.
Surgical treatment for intractable or fulminant colitis is total colectomy. The optimal approach is to combine colectomy with an endorectal pull-through, where a segment of distal rectum is retained and the mucosa is stripped from this region. The distal ileum is pulled down and sutured at the internal anus with a J pouch created from ileum immediately above the rectal cuff. This procedure allows the child to maintain continence. Commonly, a temporary ileostomy is created to protect the delicate anastomosis between the sleeve of the pouch and the rectum. The ileostomy is usually closed within several months, restoring bowel continuity. At that time, stool frequency is often increased but may be improved with loperamide. The major complication of this operation is pouchitis, which is a chronic inflammatory reaction in the pouch, leading to bloody diarrhea, abdominal pain, and, occasionally, low-grade fever. The cause of this complication is unknown, although it is more common when the ileal pouch has been constructed for ulcerative colitis than for other indications (e.g., familial polyposis coli). Pouchitis is seen in 30–40% of patients who had ulcerative colitis. It commonly responds to treatment with oral metronidazole or ciprofloxacin. Probiotics have also been shown to decrease the rate of pouchitis as well as the recurrence of pouchitis following antibiotic therapy.
Support
Psychosocial support is an important part of therapy for this disorder. This may include adequate discussion of the disease manifestations and management between patient and physician, psychologic counseling for the child when necessary, and family support from a social worker or family counselor. Patient support groups have proved helpful for some families. Children with ulcerative colitis should be encouraged to participate fully in age-appropriate activities; however, activity may need to be reduced during periods of disease exacerbation.
Prognosis
The course of ulcerative colitis is marked by remissions and exacerbations. Most children with this disorder respond initially to medical management. Many children with mild manifestations continue to respond well to medical management and may stay in remission on a prophylactic 5-ASA preparation for long periods. An occasional child with mild onset, however, experiences intractable symptoms later. Beyond the 1st decade of disease, the risk of development of colon cancer begins to increase rapidly. The risk of colon cancer may be diminished with surveillance colonoscopies beginning after 8-10 yr of disease. Detection of significant dysplasia on biopsy would prompt colectomy.
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