Renee L. Young, MD
True/False: Oral aphthous ulcerations may be seen in patients with Crohn’s disease or ulcerative colitis.
True. Oral aphthae occur in at least 10% of patients with active ulcerative colitis and typically resolve when this disease goes into remission. Aphthous ulcerations occur more commonly in Crohn’s disease.
Kidney stones develop with increased frequency in Crohn’s disease. What types of stones may be seen?
Oxalate kidney stones are seen in 5%–10% of Crohn’s disease patients. Steatorrhea promotes excess colonic absorption of oxalate, which leads to the development of oxalate kidney stones. Urate stones are seen less frequently and are often associated with the presence of an ileostomy and/or dehydration.
True/False: Crohn’s disease patients are predisposed to gallstone formation.
True. Fifteen percent to 30% of patients with small bowel Crohn’s disease develop gallstones. Ileal dysfunction or resection leads to alterations in the bile salt pool.
Which patients with Crohn’s disease are most at risk for the development of amyloidosis?
Those with long-standing suppurative or fistulous complications.
Amyloidosis is an unusual but life-threatening complication of inflammatory bowel disease (IBD). What is the most common presentation of this rare complication?
Nephrotic syndrome. Amyloid may also be diffusely deposited in bowel, spleen, liver, heart, and thyroid.
True/False: Primary sclerosing cholangitis is associated with both ulcerative colitis and Crohn’s disease.
True. Primary sclerosing cholangitis is seen less frequently in Crohn’s disease. With either disease, it can be complicated by the development of cholangiocarcinoma.
In what trimester of pregnancy are relapses most frequently seen in women with Crohn’s disease?
First trimester. Approximately 75% of women in remission remain so throughout pregnancy, while only one-third of women with active Crohn’s disease at the time of conception will achieve remission during pregnancy.
True/False: Crohn’s disease almost always flares after delivery in recently pregnant women.
False. The activity of the disease at conception generally reflects disease activity at term.
On the basis of radiologic and endoscopic findings, most patients with Crohn’s disease can be subdivided into three anatomic groups. Name those groups and the approximate percentage of each.
What percentage of Crohn’s colitis involves the entire colon, exclusive of small bowel disease?
Twenty-five percent. Crohn’s disease involving the colon alone has more frequent involvement of the distal colon than those patients with ileocolitis. Only one-fourth of patients with Crohn’s colitis exhibit skip lesions.
True/False: “Skip” areas are characteristic of Crohn’s disease. These areas appear normal grossly, radiologically, endoscopically, and histologically.
False. “Skip” areas of the intestine may have normal or abnormal histology.
True/False: Involvement of the rectum in a patient with colitis rules out Crohn’s disease.
False. Although rectal sparing is characteristic of Crohn’s disease and helps distinguish it from ulcerative colitis, the rectum can be involved.
True/False: The siblings of a Crohn’s disease patient are more likely to develop Crohn’s disease.
True. They are about 17 to 35 times more likely to develop Crohn’s disease than the general population.
True/False: The incidence of Crohn’s disease is declining.
False. Most recent studies throughout the world show a rising incidence of Crohn’s disease and a declining incidence of ulcerative colitis.
True/False: Smoking cessation has been associated with an increased relative risk of the occurrence of Crohn’s disease.
False. Smoking is associated with an increased relative risk for the occurrence of Crohn’s disease by a factor of 2 to 5. Smoking cessation has been associated with an increased relative risk of the occurrence of ulcerative colitis, however.
Granulomas are a pathognomonic feature of Crohn’s disease. Do these granulomas most resemble those seen in tuberculosis or sarcoidosis?
Sarcoidosis. The granulomas found in sarcoid and Crohn’s disease lack central caseation.
Describe the earliest endoscopic features of inflammation in Crohn’s disease.
Mild mucosal hyperemia and edema are the earliest findings followed by aphthae or discrete ulcerations in more advanced cases.
Describe how the mucosal surface acquires the “cobblestone” appearance frequently seen in Crohn’s disease.
Longitudinal and transverse serpiginous ulcerations form and the intervening edematous mucosa swells.
Crohn’s disease consists of transmural involvement of the intestinal tract. The bowel wall becomes thickened and the lumen narrows. Surgeons describe “creeping fat” in Crohn’s disease. What is “creeping fat”?
In Crohn’s disease, the mesentery becomes thickened, edematous, hypervascular, and fatty. Finger-like projections of this inflamed mucosa “creep” along the serosal surface of the intestine and encase the involved segment of the intestine.
True/False: Sulfasalazine has been proven to maintain remission in Crohn’s disease.
False. Sulfasalazine has been shown to be a remission-maintaining drug in ulcerative colitis only, not in Crohn’s disease.
The gastrointestinal presentation of Crohn’s disease in children and adolescents is similar to adults. Children, however, have prominent systemic complaints that often precede their gastrointestinal complaints by months to years. Name some systemic manifestations of Crohn’s disease in children and adolescents.
Arthralgias and arthritis are seen in approximately 15%. Weight loss, failure to thrive, growth failure, fever, and anemia are all manifestations of Crohn’s disease in children, particularly when the small bowel is involved.
Small bowel barium x-ray in Crohn’s disease may demonstrate separation of barium-filled loops of small bowel. Why does this occur?
Edema of the bowel wall, especially the deeper layers of the bowel, produces this separation.
When differentiating gastrointestinal tuberculosis from Crohn’s disease, which of the following can be seen in both: fistulae, granulomas, and/or normal chest x-ray?
All may be seen in both conditions. Fistulization occurs less frequently in tuberculosis. Granulomas can be seen in mesenteric lymph nodes in tuberculosis when there are no granulomas of the bowel. Crohn’s disease, however, only produces granulomas of the lymph nodes when they are also present in the bowel wall.
True/False: 6-Mercaptopurine (6-MP) and azathioprine are efficacious in treating Crohn’s disease and maintaining remission; however, acute pancreatitits develops in about 1%–3% of patients. Patients who develop pancreatitis while on one of these drugs could be challenged with the other drug.
False. Pancreatitis is reversible on withdrawing the drug but recurs upon rechallenge with 6-MP or azathioprine. Pancreatitis secondary to one drug is an absolute contraindication to use of either drug.
What is the phenomenon called when a child develops IBD at an earlier age than his/her parent?
True/False: Ulcerative colitis is more common in nonsmokers than smokers.
True. The relative risk of developing ulcerative colitis in nonsmokers compared with smokers is 2.6. The risk is particularly high in former smokers and especially former heavy smokers.
True/False: There is an association between ulcerative colitis and autoimmune disorders.
True. There is an increased incidence of thyroid disease, pernicious anemia, and diabetes.
What percentage of ulcerative colitis patients are perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) positive?
p-ANCA occurs in 60%–80% of ulcerative colitis patients and 20%–30% of patients with Crohn’s disease.
This antibody is of the IgG type and its titer does not change with disease activity. However, the titers have been reported to decline after colectomy for greater than 10 years or after very long-standing disease remission.
Which is more common in patients with ulcerative colitis—pancolitis or distal colitis?
Distal colitis. The disease is limited to rectosigmoid in 40%–50%, is pancolonic in 20%, and is left-sided in 30%–40%.
True/False: The rectum is always involved in ulcerative colitis.
False. There are rare exceptions when, in severe acute disease, the proximal colon is more severely involved than the rectum. Another etiology of apparent rectal sparing is in patients being treated with topical agents.
True/False: The shortening and narrowing of the colon in patients with history of recurrent attacks of ulcerative colitis is due to fibrosis.
False. Fibrosis is uncommon in ulcerative colitis unlike Crohn’s disease. The foreshortened colon is a result of abnormalities in the muscle layer.
Inflammation is predominantly confined to the mucosa in ulcerative colitis. What specific area of the epithelium do the neutrophils attack?
The crypts, giving rise to cryptitis.
True/False: Pseudopolyps spare the rectum.
True. The reason for this is unknown.
True/False: Active ulcerative colitis with diarrhea is almost always associated with macroscopic blood.
True. If blood is not present, the diagnosis should be questioned.
Why will patients with proctitis or proctosigmoiditis sometimes complain of constipation instead of bloody diarrhea?
Colonic motility is altered by inflammation. In distal proctitis, there is slowing of proximal colon transit and prolonged transit in the small bowel. Distal transit remains rapid.
A 62-year-old woman presents with diarrhea and, during her evaluation, a flexible sigmoidoscopy is performed. The mucosa is unremarkable. Biopsies show a thick subepithelial collagen band. What is the diagnosis?
Collagenous colitis usually reveals a normal appearing mucosa on endoscopic exam; however, it can cause friable and granular mucosa. It can be differentiated from ulcerative colitis and infectious colitis by the thickened subepithelial collagen band. A normal collagen layer is 3- to 6.9-µm thick. In collagenous colitis, the layer is 7- to 93-µm thick. The diagnosis of collagenous colitis is usually not made unless the collagen layer is at least 10-µm thick. Of note, the disease can be patchy and more prominent in the colon than the rectum.
A 20-year-old woman presents with rectal pain and pus coming from her rectum. Proctoscopic exam reveals granular rectal mucosa and a biopsy shows an intense neutrophil infiltration and Gram-positive cocci. What is the diagnosis?
Gonococcal proctitis, included in the differential of ulcerative colitis, rarely presents with diarrhea but instead with rectal pain. Biopsy confirms the diagnosis.
A patient with active ulcerative colitis was hospitalized and treated with intravenous steroids. All symptoms subsided and the patient was discharged on mesalamine and oral steroids. The patient returned in 3 months with no GI symptoms but erythema nodosum over her lower extremities. Flexible sigmoidoscopy showed no active colitis. What do you suspect is the etiology of her erythema nodosum?
Erythema nodosum is usually associated with active colitis and presents as multiple tender and inflamed nodules usually over the shins. It occurs in 2%–4% of cases of active colitis. Erythema nodosum can also occur as a reaction to sulfasalazine or mesalamine.
What haplotype is most often associated with primary sclerosing cholangitis?
Which of the following IBD patient-types is most often associated with primary sclerosing cholangitis: fulminant colitis requiring colectomy, proctitis, or mild pancolitis?
Mild pancolitis. In fact, the IBD may remain undiagnosed until after the diagnosis of liver disease. Colectomy is not protective against future development of primary sclerosing cholangitis.
True/False: Pseudopolyps or inflammatory polyps are a premalignant condition.
When should colonoscopic surveillance for dysplasia begin for patients with chronic IBD?
In patients with colitis, after 8–10 years of disease. Repeat surveillance, if no dysplasia is found, should be undertaken every 1 to 2 years.
True/False: The incidence of pyoderma gangrenosum is higher in ulcerative colitis compared to Crohn’s disease.
True. The incidence, while higher in ulcerative colitis, is only 1%–5%. It is most often associated with extensive disease of long-standing duration. One-half to one-third of patients with pyoderma have IBD.
True/False: Pericholangitis is the most common hepatic complication of IBD.
True, with a prevalence as high as 50%–80%. These patients usually present with asymptomatic elevations of alkaline phosphatase.
True/False: The development of calcium oxalate stones in Crohn’s disease occurs most often in patients with ileostomies.
False. The presence of an ileostomy in a Crohn’s patient predisposes to the development of urate stones resulting from decreased urine volumes related to high ostomy outputs. Calcium oxalate stones require an intact colon. With an absent or diseased ileum, fat malabsorption leads to unabsorbed fatty acids in the gut lumen. Calcium binds to the fatty acids instead of oxalate. Oxalate then binds to sodium (instead of calcium) and forms sodium oxalate, which is absorbed in the colon.
Granulomas in Crohn’s disease occur more commonly in the mucosa or submucosa?
Submucosa. This explains why granulomas are found more commonly in surgical specimens than endoscopic specimens.
True/False: Perforation of the colon occurs most often during the first acute attack of ulcerative colitis.
True. Free perforation can occur without toxic megacolon and occurs most frequently in the left colon.
A dermatologist refers you a patient with pyoderma gangrenosum. The patient has no gastrointestinal symptoms. What should you do?
Evaluate for the presence of IBD. At least one-third of patients with pyoderma have IBD.
True/False: Sacroileitis is symptomatic only when patients have active IBD.
False. Of the extraintestinal manifestations of IBD, sacroileitis is not one that follows the course of the bowel disease activity.
True/False: Patients with ulcerative colitis and p-ANCA positivity often have a more aggressive course.
True. These p-ANCA-positive patients may have a more treatment-resistant (5-ASA products) disease and are more likely to develop chronic pouchitis after ileal pouch anal anastomosis.
What effect does sulfasalazine have on fertility in males?
Sulfasalazine may reduce the total sperm count and sperm motility. These effects are reversible with discontinuation of the drug.
True/False: Fertility problems occur commonly in women with Crohn’s disease.
True. Fertility is normal in ulcerative colitis but impaired in Crohn’s disease. The exact explanation is yet unknown but contributing factors include impaired ovulation, fallopian tube blockage, dyspareunia, and avoidance of pregnancy on medical advice or fear of becoming pregnant and passing disease to children. Nevertheless, many women with IBD become pregnant without difficulty and deliver healthy babies.
Describe the clinical presentation of gastroduodenal Crohn’s disease.
Nearly all cases of gastroduodenal Crohn’s disease present with symptoms of peptic ulcer disease. Most cases are associated with more distal small bowel involvement.
True/False: All IBD medications should be stopped if a woman with the disease becomes pregnant or desires to become pregnant.
False. A flare of IBD during pregnancy is associated with higher infant mortality; thus, it is desirable to continue the medications. Patients with quiescent disease at conception tend to have well-controlled disease during pregnancy, as long as medications are continued. Many of the drugs used to treat IBD have not been extensively studied in pregnancy. The 5-ASA preparations are considered safe to use during pregnancy. There is data on azathioprine in pregnant renal transplant patients that suggests this drug is safe in pregnancy. Methotrexate is contraindicated during pregnancy. Extensive counseling should take place with each patient concerning the risks, benefits, and alternatives of medication use during and after pregnancy.
True/False: Olsalazine frequently causes watery diarrhea.
True. Sixteen percent of patients on olsalazine develop watery diarrhea. Gradual titration of the dose and the administration of olsalazine with meals may reduce the incidence of diarrhea.
In patients with ulcerative colitis requiring colectomy, which patients should not be considered for ileoanal pouch construction?
Women with multiple pregnancies, women with difficult deliveries, older patients, and patients with diminished anal sphincter tone. The most important contraindication to the ileoanal pouch anastomosis is poor anal sphincter function. The patient groups listed are all at risk for anal sphincter dysfunction.
Crohn’s disease patients that develop short fibrotic symptomatic strictures should be sent for surgical intervention and stricturoplasty. List contraindications to stricturoplasty.
Sepsis, perforation, phlegmon, fistula (enteroenteric or enterocutaneous—in the area of the stricturoplasty), multiple strictures in a short segment that might lend itself better to a single resection, gross ulceration and fragile mucosa at the site, colonic stricture, and carcinoma.
A 41-year-old man with a 15-year history of pancolonic ulcerative colitis that is currently in remission undergoes surveillance colonoscopy. A single biopsy shows definite high-grade dysplasia (confirmed by a second expert pathologist). What should you recommend to the patient?
Colectomy should be performed when high-grade dysplasia is found either in flat mucosa or a mass lesion (dysplasia-associated lesion or mass [DALM]).
True/False: Adenomatous polyps occur in patients with and without IBD. The management of adenomas in patients with ulcerative colitis differs from that in patients without colitis.
True. Colitis-associated cancer typically arises from flat mucosa or a DALM. A polyp should be presumed to represent a DALM if it occurs in involved mucosa. Pedunculated or sessile polyps that occur in uninvolved mucosa in patients who do not have pancolitis should be managed as they would in a patient without colitis. If a sessile adenoma is found within involved bowel, a colectomy may be considered. When a pedunculated adenoma arises in involved bowel, the bowel around the polyp should be sampled after performing a polypectomy. If there is no evidence of dysplasia in the surrounding mucosa or elsewhere, a colectomy is not necessary.
True/False: Prophylactic use of mesalamine or metronidazole has been proven to prevent postoperative recurrence of Crohn’s disease.
True/False: Calcium supplements will increase the risk of formation of oxalate kidney stones in the patient with Crohn’s disease who has had a terminal ileal resection.
False. Calcium supplements can actually decrease the formation of oxalate stones by binding with the oxalate to keep it in the gut and not in the kidney.
Considering the mucosal adaptive immune system, which interleukin involved in the Th17 pathway is likely involved in both ulcerative colitis and Crohn’s disease?
IL-23 in the newly recognized T helper 17 subset of T cell immune phenotypes has been shown to have a central role in inflammation of the colon.
True/False: The patient with colitis who is found to have positive markers for both IgG and IgA anti-Saccharomyces antibody (ASCA) is more likely to have ulcerative colitis than Crohn’s disease.
False. The so-called double ASCA-positive Crohn’s patient is more likely to have fibrostenosing and internal penetrating disease behavior.
In a female patient who is undergoing proctocolectomy for ulcerative colitis with planned ileal anal pouch anastomosis, what effect will this operation have on her fertility?
Any surgery in the pelvis, as in a proctocolectomy, can decrease fertility, generally as a result of scarring of the Fallopian tubes. Preoperative discussion should include this risk. Most of these patients have normal uterine function and may require in vitro fertilization for a successful pregnancy.
True/False: Jewish people of Ashkenazi descent are 2–3 times more likely to develop IBD, either Crohn’s disease or ulcerative colitis, than non-Jews.
True, especially Crohn’s disease.
What are risk factors for the development of colorectal cancer in the patient with ulcerative colitis?
Extent of disease (pancolitis higher risk than left-sided colitis), family history of colon cancer (first-degree relative), concomitant primary sclerosing cholangitis, and long duration of disease (increasing incidence of colorectal cancer [CRC] after 8–10 years of disease).
Compare the risk of proctocolectomy and ileal pouch anal anastomosis in a patient who has p-ANCA-positive ulcerative colitis to the patient who has p-ANCA-negative ulcerative colitis.
The complications of proctocolectomy and ileal pouch anal anastomosis include pouchitis, fistula, infertility, sepsis, and other surgical complications. The risk of pouchitis is much higher in the p-ANCA-positive patient.
A 34-year-old man with Crohn’s disease is admitted with acute epigastric abdominal pain. He has both small and large bowel involvement and has a history of a perianal fistula. His admission medications include mesalamine and azathioprine, and he just had his first infusion of infliximab last week. Lab studies are most remarkable for an elevated lipase. He does not drink alcohol and is on no other medications, has no family history of pancreatitis, and has never had pancreatitis. What is the only drug not associated with pancreatitis on his list of medications?
Infliximab has not been associated with pancreatitis. Pancreatitis can be secondary to azathioprine or 6-MP and is considered idiosyncratic. These medications should not be tried again, if there is a history of pancreatitis from either agent as pancreatitis will likely recur. More unusual and less well recognized is the occurrence of pancreatitis from mesalamine use.
A 50-year-old woman comes to your office with fever to 38.7°C and diffuse myalgias that started 10 days after her last infusion of infliximab. She has been treated with infliximab for fistulizing Crohn’s disease for the last 3 months. She was not treated with concomitant azathioprine as she developed pancreatitis 5 years ago when azathioprine was tried. She is on infliximab as a single agent and has had great results with healing of fistula. She had been treated approximately 10 years ago with a single infusion of infliximab in a clinical trial. She went to her primary care provider (PCP) initially and chest x-ray and blood and urine cultures are negative. What is the most likely cause of her fever and myalgias.
Delayed hypersensitivity reaction to infliximab. Fever and myalgias (and sometimes a rash) occurring 2–12 days post infliximab infusion in a patient that was previously exposed to infliximab and then a long period of time without infliximab is most often a delayed hypersensitivity reaction to infliximab.
What radiologic imaging test of the small bowel exposes the patient to the least amount of radiation?
Magnetic resonance enterography (MRE). In past years, small bowel barium studies were used to image the small intestine. More recently, computerized tomography enterography (CTE) and MRE have generally replaced the barium study to image the small bowel. MRE exposes the patient to less radiation than does CTE. Capsule endoscopy and small bowel enteroscopy are also used to examine the small bowel in certain instances.
True/False: Active uveitis predicts active IBD.
False. Although uveitis is an extraintestinal manifestation of IBD, it does not predict active bowel disease. Episcleritis parallels the disease activity, however.
Pyoderma gangrenosum can be seen as an extraintestinal manifestation of IBD and occurs in 1%–4% of IBD patients. Is it more common in ulcerative colitis or Crohn’s disease?
Pyoderma gangrenosum can be seen in either but seems to be slightly more common in ulcerative colitis. The ulcerative variant of pyoderma is the most common type and is the classic type seen in IBD patients.
True/False: Prednisone is the only etiology of osteopenia in patients with IBD.
False. Prednisone does contribute to bone loss in IBD patients but inflammatory cytokines also contribute. In particular, Crohn’s patients can have osteopenia or osteoporosis without any exposure to prednisone. Nutritional and other factors may also play a role.
Natalizumab is a humanized monoclonal antibody targeted against what cellular adhesion molecule?
Certolizumab pegol is a monoclonal antibody targeted against what?
Tumor necrosis factor alpha. Certolizumab is a PEGylated Fab’ fragment of a humanized TNF inhibitor monoclonal antibody.
Explain the most likely etiology of fecaluria occurring in a patient with fistulizing Crohn’s disease.
Fecaluria is generally a manifestation of a fistula to the bladder (ie, enterovesicular fistula). Patients present with stool (fecaluria) and/or air (pneumaturia) with urination and frequently develop polymicrobial bladder infections.
What drugs have been associated with definite increased risk of congenital malformation when used during pregnancy for treating IBD?
Methotrexate and thalidomide.
A 25-year-old woman with ulcerative colitis refractory to medical management is contemplating surgery but wants your input in selecting the type of operation. Her top priority is to have a child within the next few years. What is the surgical option with the least risk of infertility?
Subtotal colectomy with ileostomy and Hartmann’s pouch may be the best choice to optimize her chances of normal fertility. The ostomy can be taken down at a later date when she is done with conception. Pelvic dissection increases the risk of infertility. Total proctocolectomy with ileal pouch-anal anastomosis and total proctocolectomy with end ileostomy are procedures that require pelvic dissection to remove the rectum with increased risk of adhesions and subsequent infertility. Patients should be advised of the reduction of fertility when undergoing these surgeries. In the female patient who has undergone proctocolectomy and ileal pouch-anal anastomosis and is unable to conceive, in vitro fertilization may be an option.
• • • SUGGESTED READINGS • • •
Inflammatory bowel disease: an update on fundamental biology and clinical management. Gastroenterology. 2011;140(Suppl): 1701-1846.
Lichtenstein GR, Hanauer SB, Sandborn WJ; The practice parameters committee of the American College of Gastroenterology. Management of Crohn’s Disease in Adults. Am J Gastroenterol. 2009;104:465-483.
An evidence-based systematic review on medical therapies for inflammatory bowel diseases. Am J Gastroenterol. 2011;106(Suppl 1): S1-S25.