UC was initially reported in 1875 by Wilks and Moxon in the classic Lectures on Pathologic Anatomy . UC is predominantly diagnosed after the second decade of life. However, it is being seen with increasing frequency in younger patients, often with a more severe presentation. More recent reports document that the incidence of UC has now stabilized at 0.1–0.7 children per 1000. ^{, ,} Males and females are diagnosed with equal frequency. Western and Jewish societies are diagnosed with UC four times more frequently than Eastern cultures and developing countries, although this finding seems to be changing. ^,

Despite the research into the underlying mechanisms of UC, the exact etiology is unclear. ^, Many theories have been proposed, including infectious etiologies, genetic relationships, immunologic disturbances, and psychological factors. To date, none of these, either independently or in combination, has adequately explained causation. However, each of these factors may account for certain characteristics of the disease. The genetic relationship helps explain the racial and ethnic distribution of the disease. For instance, the relative risk for siblings with disease is 16%, and patients with extraintestinal manifestations have a high incidence of expression of the major antigen HLA-W27. Also, antineutrophil cytoplasmic antibodies have been associated with UC. However, evidence that these are present in unaffected family members of UC patients raises doubt about the relationship. ^, Finally, there are genetic predictors of disease severity. NOD-2insC polymorphism has been linked to worse outcomes in patients following ileoanal pull-through. Additionally, a single nucleotide polymorphism in chromosome 4q27 and mucin abnormalities have been implicated in poor outcomes in UC patients.

Genome-wide association studies have found over 240 susceptibility loci in IBD, ^, and more than 50 have been found to be related to UC. The major histocompatibility complex has been shown to have associations between extensive disease and colectomy. Specifically, variants on the 8.1 HLA haplotype have shown the strongest association with severe UC. Overall, few studies have included pediatric IBD patients, and more data are needed.

An infectious etiology for the basis of UC has become a rich area for investigation as evidence increases that the balance of microbial flora plays a key role in the regulation of the normal healthy intestine. ^, Although the balance of bacterial flora may have a critical role in UC, there does not appear to be a specific infectious agent that is responsible for causing the disease.

Since UC is primarily a disease of autoimmune dysregulation, it is logical that investigation would center on the immune function of those affected. The mucosal T cell and its regulation is the primary target of immunologic research. In addition, cytokine expression is another area of active interest. Interleukin (IL)-1, IL-6, and IL-1 receptor agonists all show imbalances in the UC population.

Very-early onset IBD is the onset of inflammatory bowel disease in children less than 6 years of age. The workup is different than in older children since genetic defects and immunodeficiencies should be investigated. Treatment options may differ and patients with IL-10 defects can be treated with stem cell transplant.

UC is a mucosal-based chronic inflammatory process that involves the rectum and extends proximally to include varying amounts of the colon, often in a contiguous fashion. The rectum is always involved, and in cases of pancolitis is usually the most severely affected. The characteristic microscopic findings include acute inflammation with crypt abscesses, mucosal bridging, and pseudopolyp formation. As the disease becomes more chronic in nature, the thin, distended colon becomes thickened, stiff, and foreshortened.

UC is most commonly diagnosed in young adults, but 4% have onset of symptoms before age 10 years, and 17% present between ages 10 and 20 years. The initial presentation is one of persistent diarrhea, progressing to hematochezia with mucus and purulence in the stool. Tenesmus, anorexia, weight loss, and growth retardation are also common ( Box 39.1 ). As the disease becomes more chronic, children may exhibit signs of depression and withdrawal from social and physical activities. Emotional stress has been identified as a precipitating factor in patients with relapsing disease. Most patients experience chronic colitis with periods of quiescence and episodic recurring exacerbations. Only a small fraction (10%) of patients have a single exacerbation followed by long-standing remission. Unfortunately, many children become refractory to medical therapy and ultimately require colectomy. Of children diagnosed with UC, 20% will require a colectomy before age 18 years.

In about 15% of children, the presentation is fulminant with profuse bloody diarrhea, severe cramping, abdominal pain, fever, and sepsis. Aggressive medical management will control these symptoms initially in most cases. However, up to 5% of patients will require urgent colectomy.

Colorectal carcinoma has been reported to occur in 3% of patients in the first 10 years after the initial diagnosis, and the incidence increases to 20% per decade after the first decade. Quiescent disease does not protect from the development of cancer. In fact, young age at initial UC diagnosis may be a risk factor for subsequent carcinoma.

The extraintestinal manifestations of UC are outlined in Box 39.1 and occur in 60% of children. Growth retardation and delayed bone growth are associated with the chronicity of inflammation in UC, and delayed sexual maturation has been shown to be related to low gonadotropin levels. ^, Because chronic inflammation has direct effects on growth and development, adequate disease control can relieve the growth complications that would otherwise develop. Arthralgias occur in about a quarter of UC patients, and the hips, knees, ankles, and wrists are the most commonly affected joints. The joint symptoms often complicate the diagnostic evaluation and may cause the child to be erroneously diagnosed with rheumatoid arthritis before the gastrointestinal (GI) symptoms become obvious.

Erythema nodosum occurs primarily on the trunk and manifests as tender, red, subcutaneous nodules. Pyoderma gangrenosum is usually seen on the lower legs and presents as chronic deep ulcerations of the skin ( Fig. 39.1 ). Although much more common in adults, both may occur in children and usually resolve with treatment of the primary disease.

The evolving stages of pyoderma granulosum in a patient with ulcerative colitis. (A) Early- erythematous raised lesion with ulceration. (B) Intermediate- open sore with raised border. (C) Ulceration with necrotic base.

Courtesy David I. Andrews, MD, Phoenix Children’s Hospital.

Liver function testing is associated with abnormalities in up to 10% of children with UC. When abnormal liver function is identified, the patient requires close observation for the possible manifestations of primary sclerosing cholangitis. Anemia is common and is usually due to blood loss in the stool but may also be related to anemia of chronic disease. Osteoporosis and osteomalacia may be related to decreased calcium absorption associated with poor absorption of fat-soluble vitamins and/or to increased urinary loss from chronic glucocorticoid therapy. Nephrolithiasis can develop and is often due to chronic oliguria related to inadequate intake and increased water loss in the stool.

The emotional and psychological ramifications of UC should not be dismissed. Those caring for these children will spend a great deal of time counseling, supporting, and encouraging them, and a multidisciplinary care team should include a mental healthcare worker.

As diarrhea is usually the initial symptom, evaluation begins with investigation for infectious causes of diarrhea, including Salmonella, Shigella, Campylobacter, Campylobacter jejuni, Clostridium difficile, and Entamoeba histolytica . Anemia from blood loss, elevated C-reactive protein, increased sedimentation rate, and hypoalbuminemia are commonly found at the initial presentation. Additionally, the prothrombin time may be prolonged.

Although work continues on many potential candidates, serum markers for IBD have not yet been proven to be reliable. Perinuclear antineutrophil cytoplasmic antibody (pANCA) has been shown to be specific for UC and absent in controls. Anti- Saccharomyces cerevisiae antibody (ASCA) also assists in the diagnosis of IBD: Children negative for ASCA with positive pANCA have a 70% sensitivity and 86% specificity for having UC, while positive ASCA with negative pANCA has an 86% sensitivity and 93% specificity for UC. However, having the markers is not predictive of disease severity or course. Pancreatic autoantibodies, such as NOD2/CARD15, have been shown to correlate with UC.

The improved visualization and characterization of disease found on computed tomography (CT) and magnetic resonance imaging (MRI) have enhanced their accuracy, and these two imaging modalities have replaced the contrast enema as a diagnostic standard. Characteristic findings have been described as a “lead pipe” appearance to the colon, loss of haustral markings, and a narrow lumen ( Fig. 39.2 ). Pseudopolyps can develop in chronic UC and may be seen on both imaging studies.

Axial (A) and coronal (B) magnetic resonance enterography images show the characteristic findings of an intensely inflamed and thickened ( lead pipe ) left colon ( arrows ) in a patient with ulcerative colitis.

Endoscopy is useful to confirm the diagnosis and for surveillance to monitor response to therapy. Typical endoscopic findings include a friable, inflamed mucosa with a fibrinous exudate covering the surface. Ulcers may also be seen. Biopsies may offer histologic proof of diagnosis. However, with severe inflammation, biopsies are sometimes nonspecific and may lead to perforation; therefore, experienced endoscopists often rely on the endoscopic appearance alone.

The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a tool used to assess disease severity and consists of scoring daily abdominal pain, rectal bleeding, number of stools, stool consistency, nocturnal stools, and activity level. The maximum score is 85. A score of <10 demonstrates remission, whereas a score ≥65 shows severe disease. This index has been shown to have a sensitivity and specificity of >90%. ^, A quarter of patients present with a PUCAI ≥65 and severe disease.

Pediatric UC is characterized as mild, moderate, or severe based on the number of stools per day and the presence of fever, anemia, nutritional depletion, and abdominal pain. These classifications are useful to characterize the disease and monitor the success of therapies. Prior to institution of any medical therapy, a thorough medication history must be obtained, including homeopathic remedies, as many of the patients and families will have sought herbal, dietary, or alternative forms of treatment prior to diagnosis.

Maintenance therapy for UC is based on immunosuppressive and antiinflammatory strategies. Treatment algorithms are based on severity of disease. Mild disease can often be controlled with aminosalicylic acid (5-ASA) preparations. Although it has not been proven beneficial, metronidazole is frequently added to this regimen. Moderate disease requires a more aggressive medical regimen to attain remission. In general, 5-ASA medications are used in conjunction with a short regimen of glucocorticoids, with or without 6-mercaptopurine or azathioprine. Steroids can be trialed at the initial presentation with clinical response, but after 1 year of this treatment, 29% of UC patients required surgery, and 14% developed steroid dependence in one study. In addition, the prolonged use of steroids has severe implications in children, such as linear growth restriction, osteopenia, and insulin resistance. Budesonide has a more favorable side effect profile because of first-pass metabolism, and Uceris (Salix Pharmaceuticals, Bridgewater, NJ), an extended-release formulation for colonic release, is also available. ^, Calcineurin inhibitors, such as cyclosporine and tacrolimus, are used for acute severe presentations that are not responsive to steroids. However, their use is limited due to side effects.

5-ASA medications include sulfasalazine, mesalamine, olsalazine, and balsalazide, and they are thought to exert their effects topically. 5-ASA medications are effective for inducing and maintaining remission in mild/moderate UC and can be delivered topically as a suppository or an enema. In a recent study, 47% of newly diagnosed pediatric UC patients treated with 5-ASA alone were in remission at 1 year without the use of steroids or further escalation in treatment. Azathioprine and 6-mercaptopurine can be used for maintaining remission as well. However, as immunosuppressives they make the patient more susceptible to infections and are generally avoided in children due to the risk of malignancies, such as lymphoma and nonmelanoma skin cancers.

At 1, 5, and 10 years after UC diagnosis, the risk of colectomy in children is 6.7%, 17.4%, and 21.6%, respectively, and 13% of hospitalizations result in the need for colectomy. The understanding that UC is limited to the colon and rectum and is “cured” by removing the colon has led to those caring for children with UC to consider earlier operation. In the past, the morbidity associated with proctocolectomy and permanent ileostomy was responsible for the delay in seeking surgical options until after the child was severely ill and undernourished, and the procedure carried significant operative risk. With the shift to laparoscopy and shorter hospitalizations with less pain, the threshold for colectomy has become more relaxed. Currently, operative alternatives are considered safe and effective, yielding a “new normal” of life with a J-pouch. Shared decision making and thorough explanation of the process of surgery and lifestyle changes postoperatively are imperative.

Proctocolectomy with J-Pouch Ileoanal Pouch Anastomosis

The most common restorative procedure for children with UC is currently a laparoscopic proctocolectomy with creation of a pouch and stapled ileoanal pouch anastomosis. This may be done in one, two, or three stages, depending on the patient’s condition and the surgeon’s experience and preference. In a three-staged approach, the first step is a laparoscopic colectomy with end ileostomy; the second step is the proctectomy and J-pouch creation with a protecting loop ileostomy, and the third step is taking down the ileostomy, often with a rigid proctoscopy to evaluate the healed J-pouch. Two-staged procedures may be done either by performing the proctocolectomy and J-pouch, then creating an ileostomy, or by performing the colectomy and ileostomy and as the second stage, creating the J-pouch, and not including a protecting ileostomy.

The patient is positioned in the lithotomy position with special attention taken to avoid pressure on the lateral portion of the upper calf where the peroneal nerve courses around the tibia. Pressure-induced injury to this nerve results in foot drop. Thromboembolism prevention is instituted with sequential compression devices (SCDs) applied to the legs and chemical prophylaxis depending on the institutional policy. Patients with IBD have an increased risk of thromboembolic disease. The abdomen and perineum are prepped into a single field, and a urinary catheter is inserted on the sterile field.

Although performed laparoscopically, the steps of the laparoscopic proctocolectomy are conducted in a fashion similar to the open operation. The number of ports used and placement is variable, largely determined by surgeon preference ( Fig. 39.3A, B ). Although not utilized by many surgeons, the single-site approach for this procedure has also been described. A typical laparoscopic approach is performed with a 10- to 12-mm cannula inserted in the umbilicus for a 10-mm camera, or a 5-mm port for a 5-mm camera. A 12-mm port or a Single Incision Laparoscopic Surgery (SILS) port is placed in the right lower quadrant at the future site of the diverting ileostomy. Usually two additional 5-mm ports, in the suprapubic and left lower quadrant, are also inserted.

(A) This 8-year-old child is undergoing a laparoscopic proctocolectomy with ileal pouch–anal anastomosis and temporary ileostomy. This view from the patient’s left side depicts placement of the ports for the operation. Note a 12-mm port is in the umbilicus through which a 10-mm, 45-degree angled telescope is inserted. In the right lower quadrant is another 12-mm cannula ( arrow ), which will become the site of the temporary ileostomy. Two 5-mm ports are in the left suprapubic area and the left midabdomen and are working ports for the surgeon and the assistant. (B) A SILS port is placed in the site of the future ileostomy. This serves as a multitrocar as well as a wound protector when removing the specimen.

The colorectal dissection can be started proximally or distally, and some surgeons choose to start with the colectomy, removing the large, devascularized specimen and creating the J-pouch prior to performing the proctectomy ( Fig. 39.4 ). This helps preserve a pristine pelvic dissection. After mobilizing the colon, which we do in a lateral-to-medial approach, the specimen can be exteriorized through the 12-mm right lower quadrant port or SILS site ( Fig. 39.5 ). At this point, permanent sutures can be placed on the distal rectum for future identification and an end ileostomy can be created. Six to 8 weeks later, once the patient has recovered from their severe illness, the second stage can be performed.

The dissection usually starts distally on the rectum and proceeds proximally. (A) The mesorectum has been divided, and the rectal wall has been skeletonized for several centimeters below the peritoneal reflection. (B) An articulating endoscopic stapler is about to be placed across the rectum to ligate and divide it. Following ligation and division of the distal rectum, the rectum is mobilized proximally and is then exteriorized out the site of the ileostomy.

After ligation and division of the distal rectum, the colon has been mobilized using the ultrasonic scalpel and has been exteriorized through the right lower quadrant 12-mm port site ( arrow ). After the colon is separated from the ileum, the J-pouch will be reconstructed extracorporeally ( Fig. 39.6 ).

For the second stage, or in a two-stage procedure, the J-pouch is created at this point ( Fig. 39.6 ). The length of the J-pouch is dependent on the age of the child. The goal to have the pouch sit entirely within the pelvis. The stoma is taken down, the distal segment is removed and sent to pathology. The ileum is externalized through the stoma site, and a site of distal ileum is identified that reaches the pubic tubercle and at this point it is turned back[Q9] on itself. The adjacent limbs are secured to one another, and the distal tip (the J limb) is opened. A linear stapling device is used to divide and secure the common wall between the two loops, thus creating the J-pouch. The anvil is then secured to the apex of the J-pouch. The pouch is then placed into the abdomen, and pneumoperitoneum is reestablished.

The creation of a J-pouch. (A) The J-pouch is created extracorporeally using the conventional stapler. (B) The J-pouch has been created and the anvil has been secured into the distal tip of the J-pouch in preparation for a stapled pouch–anal anastomosis.

In most children, the mesentery will reach easily to the pelvis if the ileal mesentery is mobilized up to the origin of the superior mesenteric artery. If necessary, the peritoneal leaflets lining the mesentery can be opened, with care taken to avoid injury to the underlying mesenteric vasculature. This allows more length on the mesentery to facilitate the pouch reaching the pelvis.

Attention is then paid to the proctectomy. If a first stage has been performed, the permanent sutures left serve as a landmark for the rectum. The mesorectal dissection is carried down to the peritoneal reflection, taking care to visualize and preserve the bilateral ureters. Once below the peritoneal reflection, the dissection should be carried out on the rectal wall to avoid injury to the vas deferens, seminal vesicles, or vaginal wall anteriorly. The dissection proceeds distally along the rectum to the pelvic floor musculature. Dissection can be further carried out by placing traction on the rectum and dissecting through the pelvic floor to the level of the sphincters. At this point, a stapler can be used to ligate and divide the rectum, leaving a short cuff for stapled anastomosis. Alternately, this can be done by everting the rectum through the anus, where it is transected with a stapling device close to the anus with great care taken not to injure the sphincter complex, or within the pelvis itself. The specimen is removed.

The pouch is positioned within the deep pelvis, taking care to maintain correct orientation and avoid twisting of the mesentery. The circular stapler is then placed carefully into the anus and through the sphincters. The handpiece of the stapler is inserted into the anus and joined to the anvil from the J-pouch ( Fig. 39.7 ). The stapler is deployed, and the anastomosis and mucosal rings are inspected to ensure a complete anastomosis. The pelvis is filled with water, and the pouch is inflated with air to evaluate for an anastomotic leak. As there is a small amount of rectal mucosa remaining, lifelong surveillance is needed. ^,

The double-stapled technique for the pouch–anal anastomosis has shown results similar to those with the hand-sewn technique. (A) The anvil has been placed into the pouch and is being brought close to the circular stapler, which has been introduced through the anus. (B) The anus and pouch have been approximated and the circled, stapled anastomosis performed (inset). There is usually about a 1–2-cm cuff of native rectal mucosa remaining that requires lifetime surveillance.

Copyrighted and used with permission of Mayo Foundation for Medical Education and Research, all rights reserved.

If a transanal mucosectomy is preferred, it is usually performed with a self-retaining, perianal retractor exposing the dentate line. The submucosa can be injected with an epinephrine solution (1:100,000 units) to help separate the mucosal and submucosal layers and assist with hemostasis. A circumferential mucosal incision approximately 1–2 cm above the anal pillars is created using the fine-point cautery. Multiple fine silk traction sutures are placed circumferentially around the mucosal flap, decreasing undue trauma, and making the specimen easier to handle during the dissection. The mucosa is separated from the submucosal layer in a circumferential manner from distal to proximal for approximately 5 cm. At this point, the dissection transitions to the full-thickness plane, moving outside the rectal wall and taking care to stay immediately adjacent to the rectum. The dissection is continued proximally until the transanal dissection meets the dissected tissues from the pelvis, and the rectum and colon are then removed from the abdomen. To attach the J-pouch, stay sutures are placed on the ileal enterotomy through which the stapler was fired. These stay sutures are delivered through the pelvis to the anus. The pouch is positioned within the rectal muscular cuff, and an end-to-end hand-sewn, single layer, interrupted pouch–anal anastomosis is completed using absorbable sutures ( Fig. 39.8 ). The hand-sewn technique is always the back-up plan if the stapler tears the pouch or the stapled anastomosis is not secure. If desired, an ileostomy can be created according to the surgeon’s preference.

In small patients, double-stapled ileoanal anastomosis using the endoscopic circular stapler may not be possible. Also, some surgeons prefer the hand-sewn ileoanal anastomosis. The rectal mucosectomy begins approximately 5 mm above the dentate line and continues proximally to the completed pelvic dissection. The J-pouch is then pulled through the muscle cuff and anastomosed to the anal mucosa, just above the dentate line with interrupted sutures.

Copyrighted and used with permission of Mayo Foundation for Medical Education and Research, all rights reserved.

A convenient loop of ileum is chosen to avoid tension on the distal anastomosis to create the loop ileostomy. Some authors prefer a completely divided end ileostomy, although one study found that a loop ileostomy was associated with lower complication rates at the time of later stomal closure. Although recent studies have shown that the procedure can be performed in a single stage without a stoma, it is our preference that this should be reserved for only the most select cases. Thus, we prefer to protect the pouch and the pouch–anal anastomosis with a stoma for 6–8 weeks. ^,

Recently, this operation has been described using robotic technology. ^, This approach may be especially applicable for the completion proctectomy following an emergency subtotal colectomy. A three-stage procedure is also commonly performed, especially for hospitalized, malnourished, and debilitated children. It can be done either open or laparoscopically and may have some improvement in long-term pouch outcomes.

Standard postoperative care includes early return to low-fiber diet without gastric decompression, SCDs, early mobilization, and stomal teaching. Patients may undergo a retrograde contrast study at 4 weeks postprocedure to evaluate for a leak, adequacy of the reservoir, and the ability to clear injected contrast. If there are no concerns, the child is scheduled for stoma closure. We perform rigid sigmoidoscopy of the pouch at the time of stoma closure, to evaluate the anastomosis for stricture and the pouch for signs of inflammation.

Children undergoing operation for UC can be expected to have a good outcome. The preoperative medical therapies are tapered or discontinued appropriately. These children initially will have high-frequency stooling in the first few weeks but will eventually taper to four to eight stools per day. This stool frequency can be managed with scheduled loperamide and/or diphenoxylate/atropine. Patients are advised to avoid caffeine, high-sugar and spicy foods to reduce diarrhea. Metamucil, or an equivalent soluble fiber, is helpful to thicken the stool to make it more controllable and to decrease perineal irritation. Additionally, patients can be started on probiotics after continuity is reestablished to decrease the risk of pouchitis, but since probiotics are not prescription items, they can be cost-prohibitive, and some providers only advocate for them after the first incidence of pouchitis. The child should be advised to use the toilet frequently to avoid soiling. The stooling frequency is expected to improve rapidly over the first 6 months but will continue to decrease over the first year. Patients are encouraged to work on holding the stool at first sensation to improve the interval between stools and to strengthen their sphincter control, which can help decrease nocturnal leakage. Most children will eventually experience approximately four to eight bowel movements per day, but some will continue to have nighttime bowel movements. Nighttime soiling is predictable early after reestablishing continuity but unfortunately persists in a small number of patients. In our experience, long-term continence rates are over 95%, and the ability to delay a bowel movement reaches 90 minutes in many cases.

The restorative proctocolectomy is associated with complications, ranging from wound infection to bowel obstruction, that occur in as many as 40% of patients. Most of these will not require operative intervention, but in one study 7% required operation for intestinal obstruction, 14% required dilation for an ileoanal stricture, and 16% developed pouchitis requiring treatment : though in other series, the incidence of pouchitis was well over 50% in the first 2 years. ^,

Infertility in females is another complication following pelvic dissection. This is thought to be due to adhesions to the adnexa. One meta-analysis from the early 2000s found a three-fold increase in infertility in patients undergoing J-pouch ileoanal pull-through, and another a decade later found similar infertility rates, despite changes in operative technique, with most operations being performed laparoscopically.

These patients require close observation and should be followed annually with physical exam, including evaluation for ventral or incisional hernias, digital rectal exams evaluating the distal cuff, and bloodwork to look for anemia, malnutrition, and inflammatory markers, especially if there is a suspicion of CD. The recommendation for surveillance pouchoscopy with biopsies is variable, from 1 to 3 years in the adult literature. ^, It is unclear what the standard pouch surveillance should be in the pediatric population, given that it is done under general anesthesia and the risk of neoplasia is low.

Pouchitis is a common problem and is reported to some degree in up to 80% of patients. ^, Pouchitis manifests as lower abdominal pain and with the increased frequency of watery, painful, foul-smelling stools and fever. It is typically a clinical diagnosis, but pouchoscopy with biopsies will be diagnostic. Treatment consists of metronidazole or ciprofloxacin and, in some cases, steroid or 5-ASA enemas or, if it is chronic and severe, biologics. Early recurrence after stopping antibiotics is an indication for suppressive therapy with daily metronidazole or ciprofloxacin. Various scoring strategies are available to help with evaluation and management of patients with pouchitis including the Pouchitis Disease Activity Index (PDAI), modified PDAI, and the Pouchitis Activity Score, but they have not gained widespread use outside of clinical trials. Treatment with an anti-TNF has an up to 50% success rate in patients with refractory pouchitis. ^, When pouchitis is severe or recurrent, anatomic causes should be considered, including technical problems that can be evaluated by endoscopy, CT, MRI, or contrast study. Biopsies may also reveal evidence of CD that has become evident only after the ileoanal reconstruction. Indeed, of pouches that are abandoned due to poor function, at least half are due to CD. ^, Although 15% of patients with a diagnosis of UC who undergo total proctocolectomy and reconstruction may end up with the subsequent diagnosis of CD, most of these patients can be managed without permanent ileostomy.

The cause of CD remains elusive and is most likely multifactorial. The chronic, relapsing nature of the disease suggests there may be an inciting or predisposing event, as well as a factor that maintains the inflammatory stimulus. The presence of an environmental factor in a susceptible host is a popular concept. ^,

Consideration of the intestinal microbiome as playing a causative role has gained popularity recently and may prove to explain the increasing disease incidence in light of the increasing use of antibiotics and antimicrobial agents. ^, The microbiome of patients with CD has been characterized as a “dysbiosis,” with higher total number of bacteria but less diversity when compared with healthy controls, along with a shift to an increase in the number of pathogenic microbes. ^,

Genetic studies have found that patients with the NOD2 gene on chromosome 16 have the highest rate of CD susceptibility. Interestingly, it has been shown that there are three areas of polymorphism that increase the susceptibility of developing CD. Further, an increase in the number of alleles enhances the risk, with one copy of the allele leading to a 2- to 4-fold increase as compared with having two copies of the allele leading to a 20- to 40-fold risk of developing CD. ^, The relationship between genetic mutations, in particular NOD2/CARD15 , seems to be related to particular manifestations such as early disease onset. The multiplicity of theories and investigative threads lends strong support to the concept that CD is a multifaceted disease.

CD differs from UC in several important aspects. As opposed to a mucosal-based disease, CD is a transmural inflammatory disorder that is characterized by granuloma formation and intestinal wall thickening. Typical findings are submucosal edema, fibrosis, and lymphatic dilation. Fissures and ulcerations are common and may be interspersed with areas of normal mucosa. The ulcers frequently penetrate deep into the muscularis and may progress to perforation with formation of sinus tracts, fistulae, and/or chronic abscesses ( Fig. 39.9 ). Granulomas are characteristic and help differentiate CD from UC ( Fig. 39.10 ). The granulomas most commonly occur in the submucosa but may extend into the muscularis and in adjacent lymph nodes. Although most patients will demonstrate either the classic pattern of CD or UC, many patients depict a combination of features implying there may be a spectrum of IBD in which these two entities are the opposing poles.

Some of the typical features of Crohn disease are exemplified in this opened ileocecectomy specimen. The proximal ileum ( black arrow ) is normal. Distally the mucosa is raised, is somewhat nodular, and shows several ulcerated areas, some of which are fistulous tracts that communicate with the serosal surface ( silver probe ). Note the markedly thickened, fibrotic appearing muscularis propria ( black star ).

This low-power hemoxylin and eosin–stained photomicrograph was taken from a colonic biopsy in a patient with Crohn disease. This section demonstrates a loss of the normal glandular architecture, marked expansion of the lamina propria by an infiltrate of lymphocytes, plasma cells, and eosinophils along with an epithelioid granuloma ( arrow ).

CD is typically diagnosed in young adulthood. However, its incidence in children is increasing, with approximately 20% of new cases diagnosed in children younger than 15 years of age. ^, In contrast to UC, in which diarrhea is the most common presenting symptom, the predominant presenting symptom in CD is weight loss (90%). Although acute pain may not be the symptom that prompts investigation due to its indolent onset, its presence may subsequently be elicited in up to 75% of patients. The pain is typically nonspecific and is persistent. A palpable mass in the right lower quadrant may be associated with ileocolic disease and is due to either fibrosis or a phlegmon. Diarrhea is present in 70% of patients and may be bloody. Hematochezia associated with CD is generally indicative of colonic disease. Growth impairment is found in a third of patients and may be multifactorial. Perirectal disease is present in 25% of patients and may manifest as deep, nonhealing fissures, abscesses, fistulae, and/or large skin tags. Fistulae are often encountered and are most commonly enterocutaneous in nature, but they may involve any site, including the bladder, vagina, psoas muscle, or an adjacent loop of small or large intestine. Typical findings and symptoms associated with CD and UC are outlined in Table 39.3 . The extraintestinal manifestations encountered in UC may also be seen in CD, including weight loss, growth retardation, delayed puberty, skin lesions, liver disease, uveitis, arthritis, anemia, and stomatitis.

The diagnosis of CD may be delayed by the nonspecific nature of the presentation. Regardless, patients with a suspicious constellation of gastrointestinal symptoms should either be evaluated by a pediatrician familiar with the diagnosis or referred to a gastroenterologist. The physical findings are typically related to growth failure and abdominal pain and tenderness, with the possibility of an associated mass in the right lower quadrant. Perianal disease is not uncommon and may be quite dramatic. A thorough search for extraintestinal manifestations should be conducted and may help direct further evaluation. Laboratory studies reveal a typical microcytic, hypochromic anemia. Hypoalbuminemia is common, as is an elevated sedimentation rate and C-reactive protein. Similar to those patients with UC, CD patients will also exhibit abnormalities in pANCA and antibodies to S. cerevisiae and Escherichia coli outer membrane porin.

The role of fecal calprotectin in the diagnosis of CD has expanded following its demonstration as the most accurate noninvasive marker of disease. The initial work by Tibble and colleagues has subsequently been developed and refined, so that fecal calprotectin is now an integral component of the diagnosis of CD. Inflammation within the intestinal tract leads to aggregation, activation and death of mucosal neutrophils, with the subsequent release of calprotectin in the lumen and feces. Fecal calprotectin remains a better indicator of the likelihood of CD than any serum inflammatory markers and should be obtained prior to endoscopy where possible.

As with all patients with IBD, endoscopy is important, and a normal rectum is more suspicious of CD than UC. Children with CD and rectal involvement will have linear ulcerations that are less friable than those in UC, and biopsies may demonstrate granuloma formation. Both upper and lower endoscopy with biopsies is needed in children suspected of CD. These endoscopic findings are often very helpful in differentiating CD from UC.

Radiographic evaluation plays an important role in the diagnosis and management of this disease. Prior to the increased usage of MR enterography, contrast-enhanced upper GI series with small bowel follow-through were effective in identifying strictures, often with associated proximal dilation ( Fig. 39.11 ). While CT with water-density contrast (CT enterography) has proven effective at evaluating CD, its associated radiation dosage has limited its utility. The most widely used modality, especially for the investigation of small bowel disease, is now MR enterography. This technique avoids radiation and is effective in detecting affected segments of the midgut that are inaccessible by endoscopy ( Fig. 39.12 ). ^, The magnetic resonance enterography index of activity was developed to assess the degree of transmural inflammation in adult CD patients and has now been modified for the pediatric population.

(A) This upper gastrointestinal and small bowel follow-through contrast study shows a significant stricture ( arrows ) in the terminal ileum in a patient with persistent and symptomatic Crohn disease despite medical therapy. (B) The laparoscopic view shows active inflammation with creeping fat ( arrows ) along the terminal ileum in this patient.

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