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Guidelines

Guidelines Summary

In September 2019, the British Society of Gastroenterology released consensus guidelines on the management of inflammatory bowel disease.^[129] In November 2019, the European Crohn's and Colitis Organisation (ECCO) published separate guidelines on the medical and surgical management of Crohn disease.^{[130, 131]}

British Society of Gastroenterology Guidelines (BSG) (2019)

Consensus guidelines on the management of inflammatory bowel disease in adults were released in September 2019 by the British Society of Gastroenterology.^[129]

Ulcerative Colitis

In circumstances in which ulcerative colitis is diagnosed by sigmoidoscopy, the recommended procedure is a full ileocolonoscopy to delineate the extent of disease and the severity of inflammation, as well as to exclude Crohn disease.

The target of medical therapy for ulcerative colitis is symptomatic remission combined with mucosal healing.

For the initial treatment of active mild-to-moderate ulcerative colitis with 5-aminosalicylic acid (5-ASA), oral 5-ASA at 2-3 g/day is recommended; 5-ASA enemas are also recommended, rather than oral treatment alone. All patients treated with 5-ASA should undergo monitoring for nephrotoxicity, with baseline renal function testing repeated after 2-3 months, and then annually thereafter.

For corticosteroid treatment in mild-to-moderate ulcerative colitis in patients in whom 5-ASA therapy has failed or is not tolerated, oral prednisolone is recommended. Also recommended is topically acting oral corticosteroids (eg, budesonide MMX).

For corticosteroid treatment in moderate-to-severe ulcerative colitis, oral corticosteroids (eg, prednisolone at 40 mg/d with weaning over 6-8 wk) is recommended.

5-ASA is recommended as standard maintenance medical therapy. Considerations for the choice of formulation include patient preference, likelihood of adherence, and cost. Once-daily dosing is considered effective and may help improve adherence.

In cases of 5-ASA treatment failure, options to consider include thiopurine, anti–tumor necrosis factor therapy, vedolizumab, or tofacitinib. Considerations for choice of drug include clinical factors, patient choice, cost, likelihood of adherence, and local infusion capacity.

Regarding surgical management for ulcerative colitis, it is generally suggested that surgical resection of the colon and rectum should be offered to those patients with chronic active symptoms that are refractory to optimal medical therapy.

Proctitis in ulcerative colitis

The recommended treatment for mild or moderately active ulcerative proctitis is a 1-g 5-ASA suppository.

If patients do not respond to or are intolerant of 5-ASA suppositories and oral 5-ASA, they can be switched to corticosteroid suppositories.

In refractory proctitis, it is suggested that patients may require treatment with corticosteroids, immunomodulators, and/or biological therapy.

Acute severe ulcerative colitis

The recommended treatment for acute severe ulcerative colitis is high-dose intravenous corticosteroids (eg, methylprednisolone at 60 mg/day or hydrocortisone at 100 mg q6h), along with prophylactic low-molecular-weight heparin. Do not delay corticosteroid treatment for patients with suspected acute severe ulcerative colitis pending results of stool cultures and Clostridium difficile assay.

If patients do not respond by day 3, rescue therapy with intravenous infliximab or cyclosporine should be offered for patients in whom previous thiopurine therapy has failed. If patients treated with infliximab have not responded sufficiently to a 5-mg/kg dose 3-5 days after the first infusion, offer an accelerated induction regimen after a colorectal surgical consult to determine if an emergency colectomy is required.

In patients with acute severe ulcerative colitis who do not respond to rescue therapy with infliximab or cyclosporine within 7 days, or in those who deteriorate or experience complications (including severe hemorrhage, perforation, or toxic megacolon) before 7 days, subtotal colectomy and ileostomy, with preservation of the rectum, are required. Note that a delay in surgery increases the risk of surgical complications; therefore, early referral and direct involvement with specialist colorectal surgical and stoma care teams is required.

Pouches and pouchitis

The recommend first-line treatment for acute pouchitis is a 2-week course of ciprofloxacin or metronidazole. Ciprofloxacin may be better tolerated and more effective than metronidazole.

The suggested treatment for chronic pouchitis is combination antibiotic therapy (ciprofloxacin, metronidazole, tinidazole, rifaximin), oral budesonide, or oral beclomethasone.

In chronic refractory pouchitis that does not respond to antibiotics or locally acting corticosteroids, reassess the patient and consider other factors. If other factors can be excluded, the suggested next step is to offer patients biologics.

Crohn Disease

Diagnosis

Diagnostic procedures for suspected Crohn disease include ileocolonoscopy with segmental colonic and ileal biopsies, to investigate for microscopic disease, and imaging to assess the location and extent of small bowel disease.

Conventional barium fluoroscopic and nuclear medicine techniques have largely been replaced by cross-sectional imaging (ie, MRI, CT, and ultrasonography). The latter techniques have the advantage of evaluating both luminal and extraluminal disease. To avoid exposing the patient to ionizing radiation, an emphasis should be placed on magnetic resonance enterography and ultrasonography.

Capsule endoscopy may provide better sensitivity for mucosal small bowel Crohn disease compared with radiological imaging techniques, and, generally, capsule endoscopy can be performed in situations in which inflammatory small bowel disease is still suspected despite normal or equivocal cross-sectional imaging findings.

Treatment

For remission-induction treatment for mild-to-moderate ileocecal Crohn disease, the recommended therapy is ileal-release budesonide at 9 mg once daily for 8 weeks.

For remission-induction treatment for mild-to-moderate Crohn colitis, the recommended therapy is an 8-week course of systemic corticosteroids.

The suggested surgical treatment for localized ileocecal Crohn disease in patients (1) in whom initial medical therapy failed, (2) who relapsed after initial medical therapy, or (3) who prefer surgery over continued medical treatment is laparoscopic resection.

For moderate-to-severe uncomplicated luminal ileocolonic Crohn disease, the recommended treatment is systemic corticosteroids initially, but if patients have extensive disease or other poor prognostic features, consideration should be given to early introduction of biological therapy.

Avoid systemic or locally acting corticosteroids for maintenance treatment in ileocolonic Crohn disease, owing to toxicity and lack of efficacy.

For moderate-to-severe Crohn disease that is responsive to prednisolone, consider early introduction of maintenance therapy with thiopurines or methotrexate in order to minimize the risk of disease flare when prednisolone is withdrawn.

Mesalazine is not recommended for induction or maintenance of remission in Crohn disease.

Biologic therapy is recommended in patients with disease refractory to immunomodulator therapy despite dose optimization. Considerations in the drug choice (ie, anti–tumor necrosis factor therapy, ustekinumab, vedolizumab) include patient preference, cost, likelihood of adherence, safety data, and response speed to the drug.

Leucocyte apheresis should not be used for active Crohn disease, owing to lack of efficacy.

Perianal Crohn disease

The recommend procedure for assessment of perianal disease is pelvic MRI; it is an important adjunct to the clinical assessment and examination under anesthesia for evaluating the possibility of fistulizing perianal Crohn disease. Endoanal ultrasonography may also be used depending on local availability and expertise.

Setons should be placed in order to prevent reaccumulation of perianal sepsis in fistulizing Crohn disease.

Post surgery, the recommended first-line biological treatment for complex perianal fistulas is infliximab; this should be started immediately upon achieving adequate drainage of sepsis.

Owing to poor long-term results, particularly for patients with complex disease and/or ongoing disease activity, surgical options for perianal Crohn disease fistulas (eg, advancement flap, ligation of intersphincteric fistula tract, infill procedures) should only be offered to selected patients after counseling.

Postsurgical management of Crohn disease

If patients have recurrent symptoms after surgical resection for Crohn disease but no evidence of active inflammation, consider alternate diagnoses, including bacterial overgrowth, adhesions, bile salt malabsorption, functional bowel disorders, or fibrostenotic or anastomotic strictures.

Actively encourage all patients to quit smoking after intestinal resection for Crohn disease.

Mesalazine is not recommended to prevent recurrence after ileocolonic Crohn disease resection.

European Crohn's and Colitis Organisation Guidelines on Medical Treatment (ECCO) (2019)

In November 2019, the European Crohn's and Colitis Organisation (ECCO) published its guidelines on the medical management of Crohn disease (CD).^[130]

Induction of Remission

Mild-to-moderate disease

Budesonide is recommended for the induction of clinical remission in patients with active mild-to-moderate CD limited to the ileum and/or ascending colon (strong recommendation).

ECCO suggests against using 5-aminosalicylic acid (5-ASA) for induction of remission of CD (weak recommendation).

Moderate-to-severe disease

In patients with active, moderate-to-severe CD, ECCO suggests using systemic corticosteroids for the induction of clinical response and remission (weak recommendation).

The use of tumor necrosis factor (TNF) inhibitors [infliximab, adalimumab, and certolizumab pegol] is recommended to induce remission in patients with moderate-to-severe CD refractory to conventional therapy (strong recommendation).

ECCO suggests against the use of thiopurines as monotherapy for the induction of remission of moderate-to-severe luminal (weak recommendation). ECCO also suggests against the combination of adalimumab and thiopurines over adalimumab alone to achieve clinical remission and response (weak recommendation).

Combination therapy with a thiopurine is recommended when starting infliximab to induce remission in patients with moderate-to-severe CD, who have had an inadequate response to conventional therapy (strong recommendation).

Ustekinumab is recommended for induction of remission in patients with moderate-to-severe CD with inadequate response to conventional therapy and/or to anti-TNF therapy (strong recommendation).

Vedolizumab is recommended for induction of response and remission in patients with moderate-to-severe CD with inadequate response to conventional therapy and/or to anti-TNF therapy (strong recommendation).

ECCO equally suggests the use of either ustekinumab or vedolizumab for the treatment of moderate-to-severe active luminal CD in patients with previously failed anti-TNF therapy (weak recommendation).

Maintenance of Remission

ECCO recommends against the use of oral 5-ASA for maintenance of medically induced remission in patients with CD (strong recommendation).

Thiopurines are recommended for the maintenance of remission in patients with steroid-dependent CD (strong recommendation).

The early introduction of thiopurine therapy is not recommended in patients with newly diagnosed CD for maintaining remission (weak recommendation).

Parenteral methotrexate is recommended for the maintenance of remission in patients with steroid-dependent CD (weak recommendation).

Patients with CD who achieved remission with anti-TNF agents should use the same treatment for maintenance therapy (strong recommendation).

Vedolizumab is recommended for maintaining clinical remission in patients with moderate-to-severe CD who achieved remission with vedolizumab (strong recommendation).

Ustekinumab is recommended to maintain clinical remission in patients with CD who achieved remission with ustekinumab (strong recommendation).

Maintenance strategies

For CD patients in clinical remission under anti-TNF treatment, there is currently insufficient evidence to recommend for or against the use of proactive therapeutic drug monitoring to improve clinical outcomes as compared to routine care (weak recommendation).

For CD patients who have lost response to an anti-TNF agent, there is currently insufficient evidence to recommend for or against the use of reactive therapeutic drug monitoring to improve clinical outcomes (weak recommendation).

Continuation of thiopurines is suggested in CD patients in long-term remission on thiopurine maintenance therapy, as the risk of relapse is higher when the treatment is discontinued (weak recommendation).

For patients with CD who have achieved long-term remission with the combination of infliximab and immunosuppressants, ECCO suggests monotherapy with infliximab (weak recommendation).

For patients with CD who have achieved long-term remission with the combination of adalimumab and immunosuppressants, ECCO suggests monotherapy with adalimumab (weak recommendation).

There is insufficient evidence to recommend either continuation or withdrawal of anti-TNF therapy in CD patients after achieving long-term remission. Therefore, individualize the decision to continue anti-TNF therapy and always discuss potential consequences (risks/benefits) with the patient.

Perianal Fistulizing Disease

Therapeutic management of complex perianal fistulizing disease

Infliximab is recommended for the induction and maintenance of remission in complex perianal fistulae in CD (strong recommendation).

It is suggested that adalimumab may be used for induction and maintenance of remission in complex perianal fistulae in CD (weak recommendation).

In CD with complex perianal fistula, there is insufficient evidence regarding the effect of adding immunomodulators to anti-TNF on fistula healing (weak recommendation).

In CD with complex perianal fistula, there is insufficient evidence to recommend the use of either ustekinumab or vedolizumab for fistula healing (weak recommendations).

Antibiotic therapy alone is not suggested for fistula closure in patients with CD and complex perianal fistulae (weak recommendation).

Thiopurine monotherapy (azathioprine, mercaptopurine) is not suggested for fistula closure in patients with CD with complex perianal fistulae (weak recommendation).

European Crohn's and Colitis Organisation Guidelines on Surgical Management (ECCO) (2019)

In November 2019, the European Crohn's and Colitis Organisation (ECCO) published its guidelines on the surgical management of Crohn disease (CD).^[131]

Complex Perianal Fistula

Medical therapy and surgical drainage

No prospective study directly compares medical or surgical treatment of complex perianal CD fistulae either in isolation or in combination with both modalities. Observational studies support a combined medical/surgical approach to control sepsis and luminal activity.

Surgical techniques

For patients with CD and complex perianal fistulae:

Advancement flaps are a therapeutic option.
Ligation of the intersphincteric fistula tract is an option.
Fibrin glue may be a potential treatment with limited efficacy.

Do not routinely consider anal fistula plugs for closure of anoperineal fistulas in CD, as seton removal alone is equally effective.

Ano- and rectogenital fistulae related to CD are very complex and rare; thus, treatment should involve an experienced multidisciplinary team.

Stem cell therapy

Allogeneic adipose-derived stem cell (ASC) therapy could be an effective and safe treatment for complex perianal fistulae in patients with CD.

Autologous ASCs may have a positive effect for patients with CD and complex perianal fistulae, with good tolerability and safety.

Refractory Pelvic Sepsis

Pelvic sepsis and symptoms from complex perineal CD refractory to medical or surgical interventions can be controlled by a diverting stoma, but with limited rates of fistula healing and stoma closure.

Surgical Management of Abdominal CD

Approach to intra-abdominal abscess

The recommended primary approach is percutaneous image-guided drainage of well-defined accessible intra-abdominal abscesses.

Following successful image-guided drainage of an intra-abdominal abscess, medical management without surgery may be considered. A low threshold for surgery is recommended if medical management is not successful.

Preoperative Optimization

Perform preoperative nutritional assessment for all patients with CD who need surgery. Preoperative nutritional optimization with enteral or parenteral nutrition is recommended for patients with nutritional deficiencies.

Preoperative corticosteroid use is associated with an increased risk of postoperative complications. Preoperative reduction of corticosteroid doses may reduce postoperative complications but should be monitored carefully to avoid increasing the disease burden.

Current evidence suggests that preoperative treatment with anti-tumor necrosis factor (TNF) therapy, vedolizumab, or ustekinumab does not raise the risk of postoperative complications in patients with CD having abdominal surgery. Preoperative cessation of these medications is not mandatory.

Preoperative control of sepsis is recommended prior to abdominal surgery for CD.

Small-Bowel Obstruction

Deferred surgery is the preferred option in adult patients with CD who present with acute small-bowel obstruction without bowel ischemia or peritonitis.

Endoscopic balloon dilatation or surgery are both suitable treatment options for patients with short (< 5 cm) strictures of the terminal ileum in CD. Local expertise and patient preference guide the treatment selection.

Strictureplasty is a safe option to treat small bowel strictures related to CD. Strictureplasty may be preferable to resection of long segments of bowel, with a potential reduction in surgical recurrence rates.

Surgical Techniques for Abdominal CD

Laparoscopic surgery should be offered as the first-line approach in surgery for CD, depending on the presence or availability of appropriate expertise.

Consider a temporary stoma if steroids cannot be withdrawn or significantly reduced prior to surgery.

Primary anastomosis may safely be performed in the presence of anti-TNF therapy, vedolizumab, and ustekinumab, as long as other risk factors have been taken into account.

A reasonable alternative to infliximab therapy is laparoscopic resection in patients with limited, nonstricturing, ileocecal CD (diseased terminal ileum < 40 cm).

Stapled small-bowel or ileocolic side-to-side anastomoses are associated with lower rates of postoperative complications than end-to-end anastomoses in CD.

Segmental colectomy is appropriate for patients with a single involved colonic segment in CD.

A defunctioning stoma for non-acute refractory Crohn colitis may delay or avoid the need for colectomy.

Restorative proctocolectomy with ileal pouch-anal anastomosis can be considered in selected patients with refractory pancolonic CD without a history of perianal disease, taking into account the high risk of pouch failure.

American Gastroenterological Association Guidelines (AGA) (2020)

In January 2020, the American Gastroenterological Association (AGA) released their recommendations on the medical management of adult outpatients with moderate to severe ulcerative colitis (UC) and hospitalized adult patients with acute severe UC (ASUC).^[132]The focus of the guidelines is on immunomodulators, biologic agents, and small molecules for induction and maintenance of remission (for moderate to severe UC) and reducing the risk of colectomy (for ASUC).

Adult Outpatients With Moderate-Severe UC

The AGA makes a strong recommendation for using infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment.

For patients who are naïve to biologic agents, the AGA recommends that tofacitinib only be used in the setting of a clinical or registry study (no recommendation). (Updated FDA recommendations [07/26/2019] on indications for use of tofacitinib in UC recommends its use only after failure of, or intolerance to, tumor necrosis factor-alpha [TNFα] antagonists.)

Conditional recommendations

For adult outpatients with moderate-severe UC who are naïve to biologic agents, the AGA suggests using infliximab or vedolizumab, rather than adalimumab, for induction of remission.

In adult outpatients with moderate-severe UC with previous exposure to infliximab, particularly those with primary nonresponse, the AGA suggests using ustekinumab or tofacitinib, rather than vedolizumab or adalimumab, for induction of remission.

In adult outpatients with active moderate-severe UC, the AGA suggests against using thiopurine monotherapy for INDUCTION of remission. However, in adult outpatients with moderate-severe UC in remission, the AGA suggests using thiopurine monotherapy, rather than no treatment, for MAINTENANCE of remission.

In adult outpatients with moderate-severe UC, the AGA suggests against using methotrexate monotherapy, for induction or maintenance of remission.

In adult outpatients with active moderate-severe UC, the AGA conditionally suggests using biologic monotherapy (TNFα antagonists, vedolizumab, ustekinumab) rather than thiopurine monotherapy for INDUCTION of remission, whereas in those with moderate-severe UC in remission, the AGA makes no recommendation in favor of, or against, using biologic monotherapy (TNFα antagonists, vedolizumab or ustekinumab), rather than thiopurine monotherapy for MAINTENANCE of remission.

In adult outpatients with moderate-severe UC, the AGA suggests combining TNFα antagonists, vedolizumab, or ustekinumab with thiopurines or methotrexate, rather than biologic monotherapy or thiopurine monotherapy.

In adult outpatients with moderate-severe UC, the AGA suggests early use of biologic agents with or without immunomodulator therapy, rather than gradual step-up after failure of 5-aminosalicylates.

In adult outpatients with moderate-severe UC who have achieved remission with biologic agents and/or immunomodulators, or tofacitinib, the AGA suggests against continuing 5-aminosalicylates for induction and maintenance of remission.

Hospitalized Patients With ASUC

In hospitalized adult patients with ASUC refractory to intravenous (IV) corticosteroids that is being treated with infliximab, the AGA makes no recommendation on routine use of intensive versus standard infliximab dosing.

Conditional recommendations

In hospitalized adults with ASUC, the AGA suggests using an IV methylprednisolone dose equivalent of 40 to 60 mg/d rather than higher dose IV corticosteroids.

In hospitalized adults with ASUC without infections, the AGA suggests against adjunctive antibiotics.

In hospitalized adults with ASUC refractory to IV corticosteroids, the AGA suggests using infliximab or cyclosporine.

Resources

For more information, go to Crohn Disease and Ulcerative Colitis.

For more Clinical Practice Guidelines, go to Guidelines.

Medication

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Media Gallery

Inflammatory bowel disease. Severe colitis noted during colonoscopy in a patient with inflammatory bowel disease. The mucosa is grossly denuded, with active bleeding noted. The patient had her colon resected very shortly after this view was obtained.
Inflammatory bowel disease. Stricture in the terminal ileum noted during colonoscopy in a patient with inflammatory bowel disease. This image depicts a narrowed segment visible upon intubation of the terminal ileum with the colonoscope. Relatively little active inflammation is present, indicating that this is a cicatrix stricture.
Inflammatory bowel disease. Enteroenteric fistula noted on a small bowel series of x-ray films in a patient with inflammatory bowel disease. The narrow-appearing segments filled out relatively normally on subsequent films. Note that barium is just starting to enter the cecum in the right lower quadrant (viewer's left), but the barium has also started to enter the sigmoid colon toward the bottom of the picture, thus indicating the presence of a fistula from the small bowel to the sigmoid colon.
Inflammatory bowel disease. The table distinguishes features of Crohn disease (CD) and ulcerative colitis (UC).
Inflammatory bowel disease. Toxic megacolon. Courtesy of Dr. Pauline Chu.
Inflammatory bowel disease. Early pyoderma gangrenosum, before skin breakdown. Medial aspect of the right ankle in a patient with inflammatory bowel disease. Same day and same patient as in the next image.
Inflammatory bowel disease. Pyoderma gangrenosum. Courtesy of Dr. Gene Izuno.
Inflammatory bowel disease. Severe advanced pyoderma gangrenosum of the medial aspect of the left ankle in a patient with inflammatory bowel disease.
Inflammatory bowel disease. Crohn disease involving the terminal ileum. Note the "string sign" in the right lower quadrant (viewer's left).
Inflammatory bowel disease. Increased postrectal space is a known feature of ulcerative colitis.
Inflammatory bowel disease. Plain abdominal radiograph of a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumbprinting in the region of the splenic flexure of the colon.
Inflammatory bowel disease. Double-contrast barium enema study shows pseudopolyposis of the descending colon in a patient with ulcerative colitis.
Inflammatory bowel disease. Plain abdominal radiograph in a 26-year-old with a 10-year history of ulcerative colitis shows a long stricture/spasm of the ascending colon/cecum (<i>arrow</i>). Note the pseudopolyposis in the descending colon.
Inflammatory bowel disease. This single-contrast enema study in a patient with total colitis shows mucosal ulcers with a variety of shapes, including collar-button ulcers, in which undermining of the ulcers occurs, and double-tracking ulcers, in which the ulcers are longitudinally oriented.
Inflammatory bowel disease. This double-contrast barium enema study shows total colitis. Note the granular mucosa in the cecum/ascending colon and multiple strictures in the transverse and descending colon in a patient with a more than a 20-year history of ulcerative colitis.
Inflammatory bowel disease. Inflamed colonic mucosa demonstrating pseudopolyps in a patient with ulcerative colitis.
Inflammatory bowel disease. Chronic architectural changes in ulcerative colitis. Note the crypt branching and irregularity of size and shape, with an increase in chronic inflammatory cells in the lamina propria.
Inflammatory bowel disease. High-power view of a crypt abscess in ulcerative colitis shows the crypt to be dilated and filled with neutrophils and debris.
Inflammatory bowel disease. Chronic architectural changes in ulcerative colitis. Note the trifid crypt.
Inflammatory bowel disease. Basal plasmacytosis in ulcerative colitis. Plasma cells separate the crypt bases from the muscularis mucosae.
Inflammatory bowel disease. Low-power image of a colon biopsy specimen in a patient with ulcerative colitis illustrates changes limited to the mucosa. These changes include chronic alterations of the crypt architecture and an increase in chronic inflammatory cells in the lamina propria.
Inflammatory bowel disease. Bowel-wall thickening and foreshortening are apparent in this specimen from a colectomy for ulcerative colitis. In addition, the mucosa is hyperemic, with focal nodularity and ulceration.
Inflammatory bowel disease. Another gross specimen illustrating ulcerative colitis.
Inflammatory bowel disease. This is an example of low-grade glandular dysplasia in a patient with longstanding ulcerative colitis. Note the loss of mucin, nuclear hyperchromasia, and nuclear pseudostratification. See the next image.
Inflammatory bowel disease. High-grade dysplasia in the same patient as the previous image. There is significant cytologic atypia, with rounding of the nuclei and a greater degree of pseudostratification.
Inflammatory bowel disease. Histologic section from another location in the same patient as described in the previous image. This field shows glands that are suspicious for invasive carcinoma.
Inflammatory bowel disease. Computed tomography scan depicting Crohn disease in the fundus of the stomach.
Inflammatory bowel disease. Double-contrast barium enema study demonstrates marked ulceration, inflammatory changes, and narrowing of the right colon in a patient with Crohn colitis.
Inflammatory bowel disease. Cobblestoning in Crohn disease. Spot views of the terminal ileum from a small bowel follow-through study demonstrates linear longitudinal and transverse ulcerations that create a cobblestone appearance. Also, note the relatively greater involvement of the mesenteric side of the terminal ileum and the displacement of the involved loop away from the normal small bowel secondary to mesenteric inflammation and fibrofatty proliferation.
Inflammatory bowel disease. Crohn disease involving the terminal ileum. Note the "string sign" in the right lower quadrant (viewer's left).
Inflammatory bowel disease. This computed tomography scan from a patient with terminal ileal Crohn disease shows an enteroenteral fistula (arrow) between loops of diseased small intestine.
Inflammatory bowel disease. A teenage patient with Crohn disease underwent a contrast-enhanced upper gastrointestinal computed tomography study with small-bowel follow-through. Several loops of small bowel are in the pelvis. Note there is a loop of distal bowel with a thickened wall (solid arrow), which is contrasted with a less involved loop of bowel in which the intestinal wall is not thickened at all (dotted arrow).
Inflammatory bowel disease. Computed tomography scan depicting Crohn disease in the fundus of the stomach.
Inflammatory bowel disease. This colonoscopic image of a large ulcer and inflammation of the descending colon in a 12-year-old boy with Crohn disease.
Inflammatory bowel disease. This laparoscopic view depicts creeping fat along the mesentery of the terminal ileum in a patient with Crohn disease.
Inflammatory bowel disease. Cobblestone change of the mucosa of the terminal ileum in a patient with Crohn disease. Communicating fissures and crevices in the mucosa separate islands of more intact, edematous epithelium.
Inflammatory bowel disease. Fat wrapping on the serosal surface of the terminal ileum in Crohn disease. Fat wrapping often correlates directly with underlying strictures, stenosis, or areas of previous transmural inflammation.
Inflammatory bowel disease. Colonic granuloma in a patient with Crohn disease (arrow). Hematoxylin-eosin staining. Courtesy of Dr E. Ruchelli.
Inflammatory bowel disease. A deep knifelike, fissuring, transmural ulcer in Crohn disease is shown in this histologic image.
Inflammatory bowel disease. Another example of a deep, fissuring ulcer in a patient with Crohn disease. Note the increase in submucosal inflammation and scattered lymphoid aggregates.
Inflammatory bowel disease. Prominent lymphoid aggregates and granuloma in the muscularis propria and pericolic fat of patient with Crohn disease. The inflammation extends through the full thickness of the bowel wall.
Inflammatory bowel disease. A crypt abscess demonstrating active, neutrophilic inflammation in Crohn disease.
Inflammatory bowel disease. Granuloma in the mucosa in a Crohn disease patient.
Inflammatory bowel disease. Double-contrast barium enema study shows changes of ulcerative colitis disease. Note the granular mucosa.

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Table 1. Common Extraintestinal Complications of IBD in US and Europe ^[54]

Complication	Prevalence
Scleritis	18%
Anterior uveitis	17%
Gall stones (particularly in Crohn disease)	13%-34%
Inflammatory arthritis	10%-35%
Anemia	9%-74%
Aphthous stomatitis	4%-20%
Osteoporosis	2%-20%
Erythema nodosum	2%-20%
Source: Larson S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis and management. Ann Med. 2010;42:97-114.

Table 2. Extraintestinal Complications of IBD in Swiss Patients ^[55]

Complication	Crohn Disease	Ulcerative Colitis
Arthritis	33%	4%
Aphthous stomatitis	10%	4%
Uveitis	6%	3%
Erythema nodosum	6%	3%
Ankylosing spondylitis	6%	2%
Psoriasis	2%	1%
Pyoderma gangrenosum	2%	2%
Primary sclerosing cholangitis	1%	4%
Source: Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011;106:110-9.

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Author

William A Rowe, MD President, Gastroenterology Associates of Central Pennsylvania, PC; Manager, Endoscopy Center of Central Pennsylvania, LLC; Clinical Associate Professor of Surgery, Division of Colon and Rectal Surgery, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

William A Rowe, MD is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Coauthor(s)

Gary R Lichtenstein, MD Professor of Medicine, Director, Center for Inflammatory Bowel Disease, Department of Medicine, Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania

Gary R Lichtenstein, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Abbott Corp/Abbvie; Actavis; Alaven; CellCeutrix; Celgene; Ferring; Gilead; Hospira; Janssen Orthobiotech; Luitpold/American Regent; Pfizer Pharm; Prometheus Labs; Romark; Salix Pharma/Valeant; Santarus/Receptos/Celgene; Shire Pharma; Takeda; UCB<br/>Received research grant from: Salix Pharm/Valeant; Santarus/Receptos/Celgene; Shire Pharm; UCB<br/>Received author or editor honorarium or book royalty from for: Clinical Advances in Gastroenterology; Gastroenterology and Hepatology; Gastro-Hep Communications; Ironwood; Luitpold/American Regent; Merck; McMahon Publishing; Romark; SLACK Inc; Springer Science and Business Media; Up-To-Date.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American College of International Physicians, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Mechanical Engineers, American Society of Ophthalmic Plastic and Reconstructive Surgery, Biomedical Engineering Society, Canadian Medical Association,Canadian Ophthalmological Society, Contact Lens Association of Ophthalmologists, International College of Surgeons US Section, Ontario Medical Association, Quebec Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center

William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Andrew A Dahl, MD Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine

Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Eugene Hardin, MD, FAAEM, FACEP Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

Sarvotham Kini, MD Assistant Professor of Emergency Medicine, Emory University School of Medicine, Atlanta, GA

Sarvotham Kini, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Surgeons, and South Carolina Medical Association

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

William Shapiro, MD Consulting Staff, Department of Urgent Care and Emergency Medicine, Scripps Clinic and Research Foundation

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rajeev Vasudeva, MD, FACG Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association

Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.