INTRODUCTION — Inflammatory bowel disease (IBD) is comprised of two major disorders, ulcerative colitis (UC) and Crohn disease (CD). These disorders have distinct pathologic and clinical characteristics (table 1), but their pathogenesis remains poorly understood. (See "Definitions, epidemiology, and risk factors for inflammatory bowel disease".)
UC disease activity varies substantially among patients and over time. Among health care encounters for children with active UC, approximately 5 percent have acute severe colitis [1]. Some of these cases will be the initial manifestation of UC, while others represent exacerbations or "flares" of the chronic disease. The management of these patients is reviewed here. Other aspects of the diagnosis and management of children with UC are discussed in separate topic reviews:
●(See "Clinical presentation and diagnosis of inflammatory bowel disease in children".)
●(See "Important health maintenance issues for children and adolescents with inflammatory bowel disease".)
●(See "Management of mild to moderate ulcerative colitis in children and adolescents".)
CLINICAL ASSESSMENT
Diagnosis — The diagnosis of UC is made on the basis of clinical, laboratory, and endoscopic/histologic information. The steps in diagnosis, including the differentiation between UC and Crohn disease (CD), are described separately. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children".)
Disease severity — A pediatric UC activity index (PUCAI) has been developed to assess the activity of disease (table 2) (calculator 1) [2]. Numeric scores are given to symptoms of abdominal pain, rectal bleeding, stool consistency, stool frequency, presence of nocturnal stools, and activity level, adding to a maximum score of 85. Of these components, rectal bleeding has the most impact on the score, contributing up to 30 points. PUCAI scores are interpreted as follows [2]:
●0 to 9 – Remission
●10 to 34 – Mild disease
●35 to 64 – Moderate disease
●65 to 85 – Severe disease
The disease course of ulcerative colitis varies markedly, and is only partly predicted by disease severity at baseline. (See "Management of mild to moderate ulcerative colitis in children and adolescents", section on 'Prognosis'.)
Evaluation for infectious colitis — Infectious etiologies or superimposed infections should be excluded by stool cultures for enteric pathogens and tests for Clostridioides difficile toxins A and B [3]. Although most colitis flares are not triggered by pathogenic bacterial infection and low fevers in UC are generally caused by the colitis itself, between 5 and 25 percent of children presenting with a flare of UC have underlying C. difficile [3-6]. If concomitant C. difficile is diagnosed in a patient with a UC flare, this pathogen is usually treated, even though the clinician may not be certain whether the C. difficile is the cause of the flare or if it is bacterial colonization. The clinician must then decide whether the appropriate course of action is to treat the C. difficile, escalate immunosuppressive therapy for inflammatory bowel disease (IBD), or both [7,8]. Details of this evaluation to exclude other causes of colitis are discussed separately. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Differential diagnosis'.)
Patients with severe or steroid-refractory disease (severe colitis that does not respond promptly to intravenous [IV] glucocorticoids) should be evaluated for the possibility of cytomegalovirus (CMV) disease [3,9]. This should be done by evaluating colonic biopsies for cytomegalic inclusions and by performing immunohistochemistry tests, alone, on intestinal biopsies collected at sigmoidoscopy. Polymerase chain reaction (PCR)-based tests are not sufficiently specific to diagnose colonic CMV [3]. Full colonoscopy usually should be avoided in patients with severe colitis because of risks of perforation. Superinfection with CMV is common in adults on chronic glucocorticoid treatment and is associated with a high rate of steroid resistance (40 to 60 percent) [10]. Case series in adults suggest that treatment with antiviral agents may be effective for patients with UC and CMV superinfection [11,12]. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Pretreatment evaluation'.)
Evaluation for toxic megacolon — Patients with severe abdominal pain or distension should be evaluated with an abdominal radiograph to investigate for the potentially life-threatening complication of toxic megacolon [3]. A higher level of suspicion should be used for patients on systemic glucocorticoids because these drugs may mask the symptoms of toxic megacolon. Toxic megacolon occurs in approximately 5 percent of patients with severe UC and may be triggered by hypokalemia or opiate use.
Suggested criteria for diagnosing toxic megacolon in children with colitis are [3]:
●Acute dilation of the transverse colon, with loss of haustral folds – Diameter >4 cm on children younger than 10 years or diameter >5.6 cm in patients 10 years or older
AND
●Systemic symptoms, such as fever, tachycardia, dehydration, electrolyte disturbance, altered level of consciousness, and hypotension
Patients with toxic megacolon should be promptly evaluated and followed closely by surgeons. Emergency or urgent colectomy may be indicated, depending on the patient's condition [3]. (See "Toxic megacolon".)
Other evaluation — Blood cultures should be performed for patients with fever, radiographic evidence of toxic megacolon, or other signs suggesting bacteremia. Fecal inflammatory markers such as calprotectin are not useful for diagnosing or monitoring acute severe colitis but may be obtained at the beginning of a disease flare and then followed over time as part of clinical monitoring for recovery [3].
MEDICAL TREATMENT — Unlike Crohn disease (CD), UC is limited to the colon; as a result, surgery essentially "cures" the disease, and clinical outcomes of colectomy are generally very good. However, most patients do not desire surgery (at least initially), and medical therapy is often successful in achieving and maintaining remission. In addition, medical stabilization of an acutely ill patient may reduce surgical complications. Patients who have medically unresponsive disease, experience intolerable drug side effects, or are at high risk of developing cancer should be referred for surgery. The outcomes and potential complications of colectomy are summarized below and detailed in a separate topic review. (See 'Surgery' below and "Surgical management of ulcerative colitis".)
The following discussion outlines treatment of patients with severe colitis (as defined above) or refractory disease (ie, unresponsive to initial medical management with intravenous [IV] glucocorticoids). A consensus statement developed by an international panel of experts makes recommendations regarding medical, surgical, and nutritional management of these children [3], but there remains significant variation because of limited clinical evidence to guide treatment decisions.
Management of patients with mild or moderate disease, or with disease limited to the rectum (proctitis), is discussed separately. (See "Management of mild to moderate ulcerative colitis in children and adolescents".)
Severe disease — Children with severe disease (pediatric UC activity index [PUCAI] score 65 to 85) typically have profuse bloody diarrhea, abdominal distention or tenderness, and signs of systemic illness (fever, tachycardia, anemia, hypoalbuminemia, leukocytosis). Such patients should be treated emergently with hospitalization and surgical consultation. These patients require fluid and electrolyte management and often require replacement of blood and/or albumin.
After blood and stool cultures have been obtained, patients should be given high-dose IV glucocorticoids. Common practice is to use methylprednisolone 1 to 1.5 mg/kg per day (up to a maximum of 60 mg daily), divided in one or two daily doses [3,13]. There is some evidence that dosing above 1.5 mg/kg per day does not appear to further improve outcomes [14]. Oral 5-aminosalicylate (5-ASA) preparations should be stopped at the time of hospital admission because 5-ASA preparations are usually ineffective in acute severe exacerbations of colitis and are responsible for worsening colitis in approximately 3 percent of patients [3]. (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease", section on '5-aminosalicylic acid (5-ASA)'.)
Antibiotics are indicated in cases of suspected bacteremia, C. difficile or other enteric infection, and toxic megacolon and are continued until blood and stool cultures are negative. In children who are not suspected to have these conditions, antibiotics are not routinely recommended. However, some clinicians utilize oral, multidrug antibiotic regimens empirically and/or for colon salvage therapy in corticosteroid-refractory patients with severe colitis. Support for the latter practice comes from a randomized trial (the PRASCO trial) in which the addition of antibiotics (the combination of amoxicillin, vancomycin, metronidazole, and doxycycline/ciprofloxacin) to IV glucocorticoids may reduce disease activity after five days [15]. Another study suggested that antibiotics may also be helpful in inducing remission when utilized in conjunction with anti-tumor necrosis faction (TNF) agents [16]. Antibiotic use is still based on limited evidence, and the reduction in eventual need for colectomy has not been demonstrated [17]. (See "Management of the hospitalized adult patient with severe ulcerative colitis", section on 'Inpatient management'.)
If patients with a severe colitis flare can tolerate feeding, continuation of regular diet is appropriate; bowel rest tends to reduce stool volume but does not affect disease activity [3]. However, many patients have severe pain when they eat or cannot take in adequate calories. In these children, parenteral nutrition is required until clinical improvement allows for enteral feeding or until the patient goes to surgery. Enteral nutrition also should be stopped if toxic megacolon is suspected. (See 'Evaluation for toxic megacolon' above.)
Refractory disease — Patients who do not have a clinically meaningful response to a seven-day course of IV glucocorticoids are considered to have steroid-refractory disease, constituting approximately 30 to 40 percent of pediatric patients with severe colitis [3,18].
Patients who fail to have meaningful improvement by day 3 to 5 of IV glucocorticoids are likely to have steroid-refractory disease. These findings should prompt discussion of and preparation for second-line therapy. In such patients, a flexible sigmoidoscopy may be useful to assess disease severity, exclude cytomegalovirus (CMV), and inform treatment decisions.
The PUCAI can be a useful measure for assessing response to therapy. Patients with persistent severe colitis (PUCAI >65) after five days of IV steroids or those who are worsening despite IV steroids are good candidates for second-line therapy. Second-line therapy should also be considered for patients with persistent moderate disease (PUCAI 35 to 64) despite 7 to 10 days of IV glucocorticoids [3]. This approach is supported by a prospective study in which a PUCAI score <45 on day 3 of IV glucocorticoids was a good predictor of steroid treatment success [13]. Furthermore, a PUCAI score >70 on day 5 of IV glucocorticoids was a strong predictor of steroid treatment failure (specificity and positive predictive value 100 percent). Before initiating second-line therapy, concomitant infection should be excluded, including assessment for CMV infection via sigmoidoscopy.(See 'Evaluation for infectious colitis' above.)
Second-line treatment options include surgical colectomy or a trial of medical therapy:
●The possibility of surgery should be presented at this stage because it is an important alternative to medical therapy for steroid-refractory disease. Moreover, a substantial number of patients who choose second-line medical therapy will ultimately require surgery [3,19]. For some patients who are very ill or who have a history of difficult-to-treat disease, surgery may be considered instead of medical therapy at this stage. Surgeons with experience in inflammatory bowel disease (IBD) surgery should be consulted early in the hospital course, particularly if there is a poor initial response to IV corticosteroids. (See 'Surgery' below.)
●For patients who are reluctant to undergo colectomy and/or need more time to make the decision about surgery, medical therapy with infliximab or calcineurin inhibitors (cyclosporine or tacrolimus) can be offered (see 'Induction therapy ("rescue")' below). This second-line therapy is sometimes known as "rescue" or "salvage" therapy. Although these drugs induce remission in approximately 75 percent of children with acute severe colitis, most patients ultimately require colectomy, based on limited data [18,20,21]. The possible benefits of using cyclosporine, tacrolimus, or infliximab must be weighed against the serious risks of these drugs (infection, nephrotoxicity, and neurotoxicity for calcineurin inhibitors, and infection and infusion reactions for infliximab).
Induction therapy ("rescue") — The main options for medical therapy, including suggested dosing and monitoring, are outlined in the table (table 3), and clinical evidence is described below. Regardless of which second-line medical therapy is chosen, efforts should be made to wean the glucocorticoids so as to reduce the risk of glucocorticoid toxicity or immunosuppression from multiple medications.
Anti-tumor necrosis factor antibodies
●Infliximab – Infliximab is the most commonly utilized option as second-line therapy for patients with refractory disease [3]. This drug is a chimeric monoclonal antibody against TNF-alpha. It is effective in fistulizing, perianal, and steroid-refractory CD, but its use in pediatric UC is less defined [22]. Standard induction dosing for infliximab is 5 mg/kg, given at weeks 0, 2, and 6. However, because clearance of infliximab is accelerated in the setting of acute severe colitis, more intensive dosing may be needed (eg, doses up to 10 mg/kg per dose, given at weeks 0, 1, and 4, or even more frequently) [3]. In one retrospective study, intensified infliximab induction (defined as mean induction dose ≥7 mg/kg or interval ≤5 weeks between doses 1 and 3) was associated with increased remission and lower risk for colectomy in children with steroid-refractory UC but not steroid-dependent UC [23]. If intensive dosing is used initially and the patient responds, the dose may be gradually lowered and adjusted toward standard dosing, ideally guided by therapeutic drug monitoring. One retrospective study and meta-analysis in adults suggests that higher doses of infliximab may reduce initial colectomy rates, but long-term outcomes are similar whether standard 5 mg/kg or 10 mg/kg doses are used [24]. (See "Management of mild to moderate ulcerative colitis in children and adolescents", section on 'Infliximab'.)
A review of six pediatric case series reported a pooled short-term response rate of 75 percent and one-year response rate of 64 percent [18,20]. A multicenter study in 60 children found a similar short-term response rate (73 percent at eight weeks) but a long-term remission rate at 54 weeks of only 29 percent [25]. The authors of this study also noted, however, that "stepping up" therapy, by either increasing the dose or decreasing the time between infusions, could improve response rates in a subset of nonresponders. Infliximab appears to modestly reduce the likelihood of colectomy and overall use of glucocorticoids. In a retrospective multicenter study, 45 children treated with infliximab for UC had a cumulative risk of colectomy of 21 percent within one year and 26 percent within two years; the likelihood of requiring concomitant glucocorticoid treatment was 32 percent within one year and 48 percent within two years [26]. The efficacy and safety of infliximab and other anti-TNF antibodies for UC, including large randomized trials in adults, is discussed separately. (See "Overview of dosing and monitoring of biologic agents and small molecules for treating ulcerative colitis in adults".)
●Adalimumab – Adalimumab is also a first-line option for steroid-refractory disease. It is approved by the US Food and Drug Administration for use in children with moderate to severe pediatric UC, based on a phase 3 study that showed meaningful rates of response/remission and mucosal healing without an internal placebo comparator (compared with historical controls). Patients treated with high-dose adalimumab had higher rates of remission at week 8 compared with those on standard dosing [27]. However, the role of adalimumab in acute severe UC is not clear. In our practice, we use infliximab rather than adalimumab in this setting. Of note, higher doses of adalimumab are used for children with UC than for CD. (See "Management of mild to moderate ulcerative colitis in children and adolescents", section on 'Adalimumab'.)
●Combination therapy – Combination therapy with an anti-TNF agent and an immunomodulator (azathioprine, mercaptopurine or methotrexate) in pediatric patients is controversial. One randomized trial in adults with steroid-refractory colitis reported improved remission rates for combination treatment with azathioprine and infliximab compared with either agent alone [28]. In addition, combination therapy has been shown to decrease immunogenicity of infliximab and increase infliximab trough levels in patients with IBD. However, there is a lack of specific evidence to support this practice in children with severe and/or refractory UC. Thus, combination therapy can be entertained but only after careful discussion of the benefit:risk ratio (increased efficacy versus potential increased risk of infection and lymphoma) [3]. The potential benefits and risks of combination therapy are extrapolated from data in adults with UC [28] and children with CD, as discussed separately. (See "Medical therapies for Crohn disease in children and adolescents", section on 'Anti-TNF monotherapy versus combination therapy with an immunomodulator'.)
Calcineurin inhibitors — Calcineurin inhibitors (cyclosporine or tacrolimus) are reasonable alternatives to infliximab for patients with refractory disease [3]. These are not maintenance agents. Patients who respond to treatment should be transitioned to a maintenance drug, typically a thiopurine or vedolizumab, ideally within approximately four to six months or proceed to colectomy. Thus, an anti-TNF antibody is generally preferred for patients who have failed thiopurine therapy, unless transition to vedolizumab is planned.
●Cyclosporine – IV cyclosporine (2 to 4 mg/kg per day) has been used at some centers as an alternative to colectomy because it can achieve high rates of short-term clinical remission in adult patients with steroid-refractory colitis, although the majority of these patients ultimately require colectomy. Oral microemulsion (or "modified") cyclosporine also may be effective [29]. The conversion from IV to oral microemulsion is approximately 1:3 for the total daily dose (divided in two doses for the oral form), but drug levels should be monitored and the dose adjusted further as needed. Only a few small trials have addressed the use of cyclosporine in children with UC, with outcomes similar to those seen in adults [3]. A systematic review of eight retrospective pediatric case series reported a pooled short-term response of 81 percent, but the majority of patients (60 percent) went on to colectomy in the long term [18]. The use of this drug in adults with UC is described separately. There are no pediatric studies directly comparing the efficacy of cyclosporine to infliximab in severe UC. Adult studies show comparable short- and long-term outcomes for these therapies [30,31]. (See "Management of the hospitalized adult patient with severe ulcerative colitis", section on 'Cyclosporine'.)
●Tacrolimus – Small observational studies in children suggest that oral tacrolimus (0.2 mg/kg per day in two divided doses) may have comparable efficacy with IV cyclosporine in treating fulminant UC or Crohn colitis [32-34]. An observational study reported short-term clinical improvement in 43 of 46 children treated with oral tacrolimus (93 percent), with a marked reduction in PUCAI score [21]. However, approximately 50 percent of children treated with tacrolimus will still require colectomy within two years.
If calcineurin inhibitors (tacrolimus or cyclosporine) are used in combination or sequentially with corticosteroids and thiopurines or vedolizumab, prophylaxis against Pneumocystis jirovecii pneumonia (PCP) should be strongly considered [3,35]. In our practice, we routinely utilize PCP prophylaxis for patients on calcineurin inhibitors. (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV".)
Sequential medical therapy — Use of sequential medical "rescue" therapy (infliximab followed by cyclosporine or tacrolimus, or vice versa) remains controversial and is not recommended in a consensus guideline [3]. For patients who fail one rescue agent and are treated with another, the long-term response or remission rate is poor and there may be an increased risk of serious infection. In addition, case series in adults reported high rates of serious infection and some mortality [36,37], although somewhat lower risks were reported by a subsequent systematic review [38] (see "Management of the hospitalized adult patient with severe ulcerative colitis", section on 'Failure to respond'). Therefore, for patients with refractory disease who elect to try medical therapy but who do not have a sustained response to a single agent, we suggest that they be encouraged to proceed to colectomy rather than try an alternate rescue therapy. (See 'Surgery' below.)
Other — A few alternative medical therapies have been explored for steroid-refractory UC, but few data are available to assess their efficacy in children. Vedolizumab, a gut-selective alpha-4-beta-7 integrin antibody, has been shown to be effective in studies of adults with UC who had failed other biologic agents [39]. Retrospective studies report clinical benefit of vedolizumab in some children with UC (many of whom had milder disease). Because vedolizumab can take weeks to reach its full effect, it is considered a maintenance agent, and there is no adult or pediatric evidence supporting its efficacy in the treatment of acute severe disease [40-42]. Small retrospective studies in adults describe apparent benefit of utilizing a calcineurin inhibitor for induction and bridging to vedolizumab [43].
Use of these second- or third-line agents and/or escalation of doses beyond those approved by the US Food and Drug Administration may be appropriate and medically necessary for selected children with UC. (See "Management of mild to moderate ulcerative colitis in children and adolescents", section on 'Medical necessity of off-label use of medications in pediatrics'.)
Experimental interventions include combination oral antibiotics [17], leukocytapheresis, or rapamycin [44], but these strategies are only supported by small retrospective studies and cannot be recommended at this time.
The experience with these and other agents in adults is discussed separately. (See "Management of moderate to severe ulcerative colitis in adults".)
Maintenance phase — If the patient with severe or refractory colitis responds to rescue therapy with cyclosporine, tacrolimus, or infliximab, then the glucocorticoids can be gradually withdrawn by transitioning to oral glucocorticoids, followed by a gradual tapering of the dose. If cyclosporine or tacrolimus was used for induction, the patient should be transitioned to infliximab, adalimumab, thiopurine or vedolizumab, or, possibly, tofacitinib. While one guideline suggests weaning patients from calcineurin inhibitors within four months [3], clinicians may reasonably choose to continue treatment beyond this timeframe in special circumstances, keeping in mind the risks of prolonged therapy. Generally, for a patient with severe colitis, long-term maintenance with either an immunomodulator and/or anti-TNF agent is required. Vedolizumab may also prove to be an effective maintenance agent in children, but additional prospective pediatric evidence is needed. In addition, maintenance therapy with mesalamine or other 5-ASA can be used as an adjunct to the immunomodulator. (See "Management of mild to moderate ulcerative colitis in children and adolescents", section on 'Maintenance of remission'.)
Pain management — Abdominal pain in IBD is often due to complex etiology and does not always correlate with intestinal inflammation; thus, management may require diverse approaches. Complaints of intermittent abdominal pain are common even among patients in clinical remission, possibly due to visceral hypersensitivity, dysmotility, medication-related effects, and anxiety or depression [45]. Severe or escalating abdominal pain should prompt reevaluation for bowel perforation and toxic megacolon.
In patients with active IBD, initial strategies for management of the pain include relaxation techniques, hot packs, or oral acetaminophen [3]. Severe or escalating abdominal pain, or pain out of proportion to disease severity, may be a symptom of bowel perforation and toxic megacolon and should prompt further evaluation. When first-line steps for pain management are not effective, low-dose morphine (0.05 to 0.1 mg/kg, given infrequently) may be used sparingly and with close monitoring in the inpatient setting [3]. Such patients should be monitored closely by clinicians with experience in managing pediatric colitis because of theoretical concerns that these drugs may increase the risk for toxic megacolon. Of note, a systematic review concluded that opioids are not effective for the management of abdominal pain in children, but this review was based on limited evidence and was not focused on children with IBD [46].
Nonsteroidal antiinflammatory drugs (NSAIDs) should be avoided as they have been associated with exacerbation of disease activity [3]. This was suggested by a retrospective study in adults, which found that use of NSAIDs was associated with a 20-fold increase in the risk of IBD onset or exacerbation [47].
Venous thromboembolism — Hospitalized children and adolescents with IBD are at increased risk for thromboembolism. Though less common than in adults with IBD, thromboembolic (TE) events in children with IBD seem to occur during active disease, with risk factors including previous thromboembolism, central venous catheter, older age, parenteral nutrition, and an identified hypercoagulable condition [48]. Conservative methods of TE prevention should be used for all hospitalized patients with IBD, including hydration, mobilization, and the use of compression stockings or pneumatic devices, if appropriate [48]. Routine thromboprophylaxis (anticoagulation) for hospitalized children with IBD remains controversial but should be seriously considered for those with potential risk factors for TE [18]. (See "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents", section on 'Venous thromboembolism'.)
SURGERY — When managed with a modern protocol of medical therapies, approximately 5 to 10 percent of children with ulcerative colitis undergo colectomy within one year of diagnosis, and approximately 15 percent within three years [19,49-51]. Outcomes are only partially predicted by disease severity at baseline. (See "Management of mild to moderate ulcerative colitis in children and adolescents", section on 'Prognosis'.)
Indications
●Emergency colectomy is indicated for patients with acute severe colitis and uncontrolled hemorrhage, or complications such as toxic megacolon or bowel perforation.
●Urgent colectomy is generally indicated for those who fail to respond to aggressive medical management within two weeks or after failure of one second-line therapy, such as infliximab or a calcineurin inhibitor [3].
●Elective colectomy is indicated in patients who are unresponsive to or cannot be weaned from glucocorticoids, who experience unwanted side effects (eg, growth failure from steroids), or who have surveillance biopsies that suggest a risk for developing cancer [3,52]. Some patients may choose to undergo colectomy earlier in the disease course.
A small proportion of patients with what appears to be UC will ultimately be diagnosed with Crohn disease (CD), in which case, surgery will not be curative. Even a thorough preoperative evaluation (including review of small bowel imaging, endoscopic, histologic, and serologic data) cannot exclude this possibility. It is likely that a patient with diffuse continuous colitis, no granulomas on biopsy, and no macroscopic small bowel involvement will have UC. Nonetheless, CD may still be diagnosed in 5 to 25 percent of cases [53,54]. Some of these patients who are ultimately diagnosed with CD may need a permanent ileostomy. Patients should be made aware of this possibility.
The presence of anti-Saccharomyces cerevisiae antibodies (ASCA) is somewhat predictive of which patients with an initial diagnosis of UC or indeterminate colitis may develop evidence of CD after colectomy. In one series, the positive predictive value of ASCA immunoglobulin A (IgA) antibodies was 0.17 and the negative predictive value was 0.94; the positive predictive values are less than a family history of CD [53]. Because of these limited predictive values, these tests should not be used as an important factor in making decisions about colectomy. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Differentiation between Crohn disease and ulcerative colitis' and "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Antibody testing'.)
Technique — The most commonly performed procedure is colectomy and rectal mucosectomy with an endorectal ileoanal pull-through, creation of a distal ileal reservoir, and ileorectal anastomosis (called ileal pouch anal anastomosis [IPAA]). In the urgent surgical setting, a subtotal colectomy, terminal ileostomy, and blind rectal stump are created. After the patient recovers, the rectal mucosectomy and ileoanal pull-through with anastomosis procedure is performed.
Addressing medical and psychologic needs prior to surgery is important for the patient and to improve outcomes. Nutritional correction, treatment of infections, and psychological support are crucial. (See "Important health maintenance issues for children and adolescents with inflammatory bowel disease", section on 'Psychological screening and support'.)
Additional details on the pre- and postoperative surgical management of UC are provided in a separate topic review. (See "Surgical management of ulcerative colitis".)
Immunosuppressive therapy — Most immunosuppressive drugs can be discontinued just before surgery, with the exception of glucocorticoids, which must be tapered after surgery. If possible, efforts should be made to limit corticosteroid exposure before elective or semi-elective colectomy to optimize healing of the wounds and intestinal anastomoses.
Exposure to immunosuppressive drugs in the preoperative period probably does not have adverse effects on outcomes after surgery, although there is some uncertainty on this point. In one study, preoperative exposure to thiopurines or calcineurin inhibitors within 30 days, or infliximab within 90 days, did not significantly affect postoperative outcomes [55,56]. In another study, the use of tacrolimus prior to colectomy reduced disease severity and was not associated with complications [57]. In contrast, whether vedolizumab increases the risk of perioperative complications is controversial. Some studies suggest an increase in peristomal complications, but other meta-analyses have failed to confirm this finding [58]. (See "Surgical management of ulcerative colitis", section on 'Routine preoperative care'.)
Outcomes — Functional outcomes of IPAA for UC are generally good. Patients who undergo this surgery generally have four to eight bowel movements per day, but continence usually can be achieved [59,60]. In one series, 89 percent of patients were continent two years after undergoing IPAA with creation of a J-pouch reservoir [61]. Studies with long-term follow-up describe ongoing improvement in quality of life even many years after surgery, with some continence problems in 10 to 20 percent of patients [60,62-64]. In studies of adults undergoing the IPAA procedure, there is a reduction in fertility among females [65]. This and other surgical considerations are discussed separately. (See "Surgical management of ulcerative colitis".)
The major complication occurring after ileoanal pull-through with pouch formation is inflammation of the pouch ("pouchitis"), which occurs in 10 to 30 percent of patients [60,61]. Clinical symptoms of pouchitis include diarrhea, rectal bleeding, abdominal cramping, and malaise. Broad-spectrum antibiotics (metronidazole) or glucocorticoid enemas usually are effective therapy; in some patients, systemic steroids are required. Chronic pouchitis eventually develops in approximately 10 percent of patients [64]. Maintenance therapy may include oral bacteriotherapy (probiotics). A diagnosis of CD should be considered in patients in whom pouchitis is chronic and refractory to treatment. (See "Pouchitis: Epidemiology, pathogenesis, clinical features, and diagnosis" and "Management of acute and chronic pouchitis".)
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".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Ulcerative colitis in children (The Basics)")
●Beyond the basics topic (See "Patient education: Ulcerative colitis (Beyond the Basics)".)
SUMMARY AND RECOMMENDATIONS
●The severity of pediatric ulcerative colitis (UC) can be estimated by clinical symptoms, as quantified by the pediatric UC activity index (PUCAI) (table 2) (calculator 1). A PUCAI score of 65 to 85 indicates severe disease. Such patients typically have profuse bloody diarrhea, abdominal distention, or tenderness and often have fever, tachycardia, anemia, hypoalbuminemia, or leukocytosis. (See 'Disease severity' above.)
●For patients presenting with a flare of UC, infectious etiologies or superimposed infections should be excluded by stool cultures for enteric pathogens and tests for Clostridioides difficile toxin. For those with steroid-refractory disease, the possibility of cytomegalovirus (CMV) colitis should also be evaluated, using immunohistochemistry on intestinal biopsies taken via sigmoidoscopy. (See 'Evaluation for infectious colitis' above.)
●Patients with severe disease should be urgently admitted to a hospital. Fluids and electrolytes should be replaced and blood transfusion, albumin, and/or parenteral nutrition given if needed. Those with severe abdominal pain or distension should be evaluated with an abdominal radiograph to investigate for the potentially life-threatening complication of toxic megacolon. Antibiotics are indicated in cases of suspected bacteremia, C. difficile infection, and toxic megacolon and are continued until blood and stool cultures are negative. Some clinicians utilize broad-spectrum antibiotics more liberally, as part of induction therapy. (See 'Severe disease' above and 'Evaluation for toxic megacolon' above.)
●For patients with acute severe colitis, we recommend initiating treatment with high-dose intravenous (IV) glucocorticoids rather than infliximab or adalimumab (Grade 1B). (See 'Severe disease' above.)
●Patients who do not have a clinically meaningful response to a seven-day course of IV glucocorticoids are considered to have steroid-refractory disease. Once concomitant infection is excluded (including assessment for CMV infection via sigmoidoscopy), treatment options include surgical colectomy or a trial of second-line medical therapy. (See 'Surgery' above and 'Refractory disease' above.)
•We suggest presenting surgery as an important option at this stage. Because UC is limited to the colon, surgery essentially "cures" the disease, and clinical outcomes of colectomy are generally very good. Potential complications of colectomy include incontinence, pouchitis, and reduction in fertility among females. (See 'Outcomes' above.)
•Medical treatment options include a trial of antibody against tumor necrosis factor (anti-TNF; eg, infliximab or adalimumab), cyclosporine, or tacrolimus (table 3). A majority of children achieve short-term remission with these treatments, but less than one-third achieve long-term glucocorticoid-free remission. The possible benefits of using these drugs must be weighed against their serious risks, especially infection. (See 'Refractory disease' above.)
●Emergency colectomy is indicated for patients with acute severe colitis and uncontrolled hemorrhage or complications such as toxic megacolon or bowel perforation. We also suggest colectomy for patients with severe disease (PUCAI >65) who continue to deteriorate or do not improve during a one- to two-week period of glucocorticoid treatment (Grade 2C). Colectomy also is indicated in patients who cannot be weaned from glucocorticoids, who experience unwanted side effects (eg, growth failure from steroids), or those who fail medical "rescue" therapy. (See 'Indications' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges George H Russell, MD, MS, who contributed to an earlier version of this topic review.
