Inflammatory Bowel Disease: 10 Cases to Test Your Dx/Rx Skills

Inflammatory bowel disease (IBD) comprises 2 major disorders: ulcerative colitis (UC) and Crohn disease (CD). UC affects the colon and is characterized by diffuse mucosal inflammation; CD can involve any part of the gastrointestinal (GI) tract, from oral cavity to anus, and is characterized by transmural inflammation. UC involves the rectum in about 95% of cases and may extend proximally in a symmetrical, circumferential, and uninterrupted pattern to involve parts or all of the large intestine.

The differential for IBD symptoms can include irritable bowel syndrome (IBS) and celiac disease (also known as celiac sprue or gluten-sensitive enteropathy). IBS is a GI syndrome characterized by chronic abdominal pain and altered bowel habits without an organic cause; it is not associated with inflammation. Celiac disease is a small-bowel disorder characterized by mucosal inflammation, villous atrophy, and crypt hyperplasia, which occur on exposure to dietary gluten.

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In North America, the reported incidence of UC is 2.2-19.2 cases per 100,000 person-years, and that for CD is 3.1-20.2 cases per 100,000 person-years.^[1,2] In a 2007 study, the prevalence of UC in adults in the United States was 238 per 100,000 population, and that of CD was 201 per 100,000 population.^[3] IBS is very common; its estimated prevalence in North America is in the range of 10-15%.^[4] In a 2012 study, the prevalence of celiac disease in United States was reported to be 0.71% (1:141); the condition is rare in minority groups and is found in 1% of non-Hispanic whites.^[5]

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An 18-year-old woman with no significant past medical history comes to the gastroenterology clinic for evaluation of watery diarrhea, abdominal pain, and rectal bleeding of 6 weeks’ duration. She has lost ~20 lb over the preceding 6 weeks. Stool studies are negative for infection. Colonoscopy shows moderate UC involving the entire colon. The patient is admitted to the hospital and started on intravenous (IV) methylprednisolone 15 mg q6hr. After 72 hours, she continues to have diarrhea (10 bowel movements/day), abdominal pain, and rectal bleeding. Flexible sigmoidoscopy is performed, revealing moderate colitis without improvement from the previous endoscopy.

What is the next step in management?

1. Continue IV methylprednisolone 15 mg q6hr
2. Start infliximab at 5 mg/kg
3. Start mesalamine at 4 g/day
4. Start azathioprine at 2.5 mg/kg

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Answer: B. Start infliximab at 5 mg/kg.

The clinical hallmark of UC is bloody diarrhea, often with prominent rectal urgency and tenesmus.^[6] In severe UC, loose bloody stools are frequent (≥6/day), with severe cramps and evidence of systemic toxicity (temperature ≥37.5°C, heart rate ≥90 beats/min, hemoglobin [Hb] <10.5 g/dL, erythrocyte sedimentation rate ≥30 mm/hr). Such patients should receive IV steroids. Those who do not respond to steroids in 72 hours should receive cyclosporine or infliximab; those who do not respond to cyclosporine or infliximab should undergo colectomy.^[7] Infliximab binds to tumor necrosis factor alpha (TNF-α), interfering with endogenous TNF-α activity. Induction is with 5 mg/kg IV at 0, 2, and 6 weeks; maintenance is with 5 mg/kg IV q8wk, which can be increased to 10 mg/kg IV q6wk. Testing for tuberculosis and hepatitis B is indicated before infliximab is started. Azathioprine can be used for moderate-to-severe UC but requires ~4-6 weeks to start taking effect; it is not appropriate for inpatients. Aminosalicylates are not indicated for steroid-refractory UC.

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A 32-year-old woman with a history of mild-to-moderate UC diagnosed 5 years ago presents to the hospital with a lower-extremity ulcer. Since her diagnosis, she has been taking mesalamine for her UC. Her last colonoscopy was done about 3 years ago and showed normal colon mucosa. About 3 weeks before the current presentation, the patient bumped her leg. A pustule was noted, which gradually turned into a deep ulcer (shown). She states that she has not had fever or chills. Recently, she has been having 3-4 watery bowel movements daily, with rectal bleeding.

What is the next step in management?

1. Start IV ciprofloxacin and metronidazole
2. Consult surgery for debridement
3. Start prednisone 40 mg/day
4. No treatment

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Answer: C. Start prednisone 40 mg/day.

Pyoderma gangrenosum (PG) is a rare, chronic, and often destructive inflammatory skin disease in which a painful nodule or pustule breaks down to form a progressively enlarging ulcer with a raised, tender, undermined border.^[8] Its incidence is uncertain but is estimated to be 3-10 patients per million annually. It can occur at any age but is most common between 20 and 50 years, with a possible slight female predominance. About 50% of cases are associated with an underlying systemic disease (most often IBD, arthritis, or lymphoproliferative disorders).^[9] The etiology is unknown and the pathogenesis poorly understood. Although PG is idiopathic in 25-50% of patients, an underlying immunologic abnormality may exist.^[9] Because histopathologic findings are nonspecific, the diagnosis of PG rests primarily on clinical features. The primary objective of biopsy is to rule out other causes of ulceration (eg, infection, vasculitis, or malignancy).^[8]

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A topical steroid or topical tacrolimus is the treatment of choice for mild, localized PG. Patients who do not respond to topical treatment or who have moderate-to-severe PG should be treated with systemic steroids, dapsone, or minocycline. In many instances, specifically in those associated with IBD, infliximab helps treat both PG and the underlying disorder. Although dapsone and minocycline can be used to treat PG, they are not first-line treatment. Ciprofloxacin with metronidazole is not the treatment for PG. The role of surgery is controversial in PG because of possible induction of pathergy. Surgical procedures should be avoided in most cases.

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A 60-year-old woman with a past medical history of diabetes comes to the clinic for evaluation of chronic diarrhea. She reports having had watery diarrhea for the past 6 weeks, but without any rectal bleeding. She has had no recent antibiotics, travel, or medication changes, and she has taken metformin for 10 years. The patient is experiencing nocturnal bowel movements and abdominal cramps and has lost 5 lb over the preceding 6 weeks. There is no family history of UC or CD. At age 50 years, she underwent colonoscopy for colorectal screening, which yielded normal findings. Stool studies are negative for Clostridium difficile and other infectious pathogens. She undergoes colonoscopy, which again appears normal. Random colon biopsies are obtained (shown).

What is the diagnosis?

1. Microscopic colitis
2. IBS
3. UC
4. Medication-induced diarrhea (from metformin)

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Answer: A. Microscopic colitis.

Microscopic colitis is a chronic, inflammatory colon disease characterized by chronic watery diarrhea. It has 2 subtypes, collagenous and lymphocytic,^[10,11] with estimated annual incidences of 1.1-5.2 and 3.1-5.5 per 100,000, respectively.^[12] Mean age at diagnosis of microscopic colitis is ~65 years. There is a female preponderance, apparently more pronounced in lymphocytic than in collagenous colitis. In addition to the chronic watery diarrhea,^[10] microscopic colitis is associated with fecal urgency, incontinence, nocturnal episodes and abdominal pain. There may be weight loss from fluid loss or decreased oral intake. Colonoscopy usually shows normal mucosa. The diagnosis is established by means of histology. Collagenous colitis is characterized by a colonic subepithelial collagen band greater than 10 µm in diameter (shown). Lymphocytic colitis is characterized by ≥20 intraepithelial lymphocytes (IELs) per 100 surface epithelial cells.^[10] Crypt architecture is usually not distorted, but focal cryptitis may be present.

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Antidiarrheals may be used alone in patients with mild diarrhea. Budesonide 9 mg/day is the treatment of choice for patients with microscopic colitis who have active disease. In patients who do not respond to budesonide, concomitant therapy with cholestyramine or bismuth subsalicylate alone can be administered. Anti-TNF agents are indicated for refractory disease.^[13] Surgery is reserved for patients with microscopic colitis that is refractory to medical therapy.

IBS is unlikely in this patient, in view of the alarm symptoms of nocturnal bowel movements and weight loss. UC is also unlikely, given the normal colonoscopy and the absence of rectal bleeding. Metformin is a common cause of diarrhea, but given that the patient has been on medication for 10 years, it is a less likely cause in this case.

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A 31-year-old man who has been taking mesalamine since being diagnosed with UC 10 years ago comes to the office with a yellowish discoloration of the eyes. He reports no history of alcohol abuse or injection drug use, and there is no family history of liver disease. He has not used acetaminophen or other over-the-counter (OTC) medications and has not recently taken antibiotics or traveled. There is no history of blood transfusions. He has had only one sexual partner. Laboratory test results are as follows: aspartate aminotransferase (AST), 146 IU/L; alanine aminotransferase (ALT), 122 IU/L; total bilirubin, 4 mg/dL; direct bilirubin, 2.3 mg/dL; and alkaline phosphatase (ALP), 524 IU/L. Ultrasonography of the abdomen shows no cholelithiasis or biliary dilation. Endoscopic retrograde cholangiopancreatography (ERCP) is performed (shown).

What is the most likely diagnosis?

1. Primary sclerosing cholangitis (PSC)
2. Primary biliary cirrhosis (PBC)
3. Autoimmune hepatitis
4. Viral hepatitis

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Answer: A. Primary sclerosing cholangitis (PSC).

PSC is a chronic cholestatic disease of the liver and bile ducts that is often progressive and can lead to end-stage liver disease. It is characterized by ongoing inflammation, destruction, and fibrosis of intrahepatic and extrahepatic bile ducts.^[14] Prevalence is 1-6 cases per 100,000; 70% of patients are men, and mean age at diagnosis is 39 years.^[15] About 75% of PSC patients have IBD; of these, 87% have UC and 13% have CD.^[16] The cause of PSC is unknown, and multiple mechanisms may contribute. Immunologically mediated bile duct injury is likely to be a major factor. Laboratory tests usually show a cholestatic pattern, but biochemical abnormalities alone are never diagnostic. Current diagnostic criteria for PSC are based on characteristic changes in the biliary tree seen on ERCP or transhepatic cholangiography. Such changes include multifocal strictures and dilatations, usually involving both the intrahepatic and the extrahepatic biliary tree (shown).

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Percutaneous liver biopsy may support the diagnosis but is rarely diagnostic. When characteristic findings are noted on cholangiography, liver biopsy is typically not required. The most specific histologic finding is fibrous obliteration of small bile ducts, with concentric replacement by connective tissue in an "onionskin" pattern.

Various immunosuppressive (glucocorticoids, cyclosporine, methotrexate, azathioprine, 6-mercaptopurine [6-MP]), anti-inflammatory (ursodeoxycholic acid), and antifibrotic agents have been used to treat PSC, but none has been shown to improve the natural history of the disease. Liver transplantation is now the treatment of choice for patients with advanced liver disease secondary to PSC.

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PBC patients present with pruritus, hyperpigmentation of the skin, and hepatomegaly with a cholestatic pattern of liver function tests; 95% are women. PBC does not cause biliary stricture noted on ERCP. Autoimmune hepatitis usually causes elevations of AST and ALT more than bilirubin and ALP. Autoimmune hepatitis can occur at any age, though it is often diagnosed in patients in their 40s or 50s and is more common in women than in men (female-to-male ratio, 3.6:1); it does not cause biliary stricture noted on ERCP. Viral hepatitis is not likely to be the cause in this patient, because no risk factors are present.

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A 29-year-old man has a history of dermatitis herpetiformis and loose bowel movements 4-6 times daily for 12 months. This is accompanied by abdominal cramps, a 5-lb weight loss, and an Hb concentration of 10.5 g/dL. On the advice of a friend, the patient removed gluten from his diet 3 months ago and subsequently noticed that his symptoms all improved. He would now like to be tested for celiac disease.

What is the most appropriate next step?

1. Observation for return of clinical symptoms and monitoring of Hb
2. Serologic testing for antigliadin antibody and antiendomysial antibody
3. Serologic testing for anti-tissue transglutaminase (TTG) antibody and immunoglobulin A (IgA) level
4. Referral to gastroenterology for esophagogastroduodenoscopy (EGD) with duodenal biopsies
5. Counseling on the role of genetic testing and analysis for HLA DQ2/DQ8

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Answer: C. Serologic testing for anti-tissue transglutaminase (TTG) antibody and IgA level.

The anti-TTG is highly sensitive and specific, reliable in patients without IgA deficiency, inexpensive, and widely available.^[18] The antigliadin antibody test is less sensitive and specific. The antiendomysial antibody test has similar sensitivity and specificity to the anti-TTG but is more expensive. In a patient on a gluten-free diet, these tests can all yield false-negative results.^[17] Some patients may still have a weakly positive anti-TTG result; accordingly, this test should be considered a first-line measure even with a gluten-free diet. EGD with biopsies is the gold standard for diagnosing celiac disease but can also yield false-negative results in a patient on a gluten-free diet. If serology is normal with a gluten-free diet, genetic testing should be offered. Counseling is needed to explain that a negative result excludes celiac disease, whereas a positive result suggests the diagnosis but cannot establish it.^[18] If genetic testing is declined, observation is appropriate.

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A 55-year-old woman has been bothered by constipation for years. She reports having one Bristol 1 bowel movement (hard, pellets) every 3-5 days; this is preceded by bloating, straining, and abdominal discomfort, and improvement occurs after the bowel movement. She has no bleeding, weight loss, or nocturnal bowel movements. Thyroid-stimulating hormone (TSH), calcium, and Hb levels are all normal. The patient underwent colonoscopy to screen for colorectal cancer 2 years ago, with normal findings. An abdominal plain film was normal. She has tried increasing fiber and water intake and has used senna, docusate, enemas, and polyethylene glycol (PEG) laxative, without much improvement.

What would be the most appropriate next step?

1. Repeat colonoscopy
2. Switch the PEG laxative to lactulose
3. Dicyclomine 20 mg q6hr as needed for abdominal discomfort
4. Lubiprostone 8 µg q12hr
5. Lubiprostone 24 µg q12hr

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Answer: D. Lubiprostone 8 µg q12hr.

The patient meets Rome III criteria for IBS with constipation (IBS-C; eg, symptom duration >3 months, altered bowel habits, and abdominal discomfort improving with defecation). Features that support the diagnosis but are not part of the Rome III criteria include hard stool, lumpy stool, straining, and the frequency of bowel movements. The Bristol stool scale is a reliable communication tool for discussing bowel movements. Equally important is to recognize symptoms that should lead to further investigation (eg, weight loss, blood in the stool, nocturnal bowel movements, and nocturnal pain). Lubiprostone is effective in IBS-C. The appropriate dosage is 8 µg q12hr; a dosage of 24 µg q12hr is appropriate for chronic idiopathic constipation.^[19] Colonoscopy rarely finds a cause of constipation, and since it was done only 2 years ago, repeat testing is unlikely to yield much. A high-fiber diet, an osmotic laxative, and common OTC regimens have been tried, with little success. Dicyclomine can help with symptoms but does not treat the underlying cause.

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A 51-year-old woman with a history of Crohn colitis comes to the office with watery diarrhea and rectal bleeding. She was previously treated with sulfasalazine but has not been taking her medication for the past 2 years. She has been requiring intermittent prednisone for worsening symptoms. The patient reports blood and stool coming out of her vagina. She underwent computed tomography (CT) of the pelvis with IV contrast and barium enema, which did not show any fistula, and then underwent colonoscopy, which showed an anal canal-vaginal fistula.

What is the best next step in managing the fistula?

1. Continue aminosalicylate therapy
2. Start prednisone 40 mg/day, and continue aminosalicylate therapy
3. Start infliximab 5 mg/kg IV
4. Refer the patient for surgery

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Answer: C. Start infliximab 5 mg/kg IV.

Major perianal complications of CD include fissures, fistulas, abscesses, and stenosis, alone or in combinations. Risk factors (eg, age <40 years, race [non-Caucasians or Sephardic Jews], and colonic disease) may play a role in their development. Anorectal fistulas develop in ~20-30% of CD patients and can be classified according to their anatomic extensions. The fistulous openings most often involve the perianal skin but can also be in the groin, vulva, or scrotum. Treatment of fistulas is determined by their anatomic complexity and the symptoms noted. For severe or refractory perianal CD, an anti-TNF-α agent (eg, infliximab or adalimumab) is the treatment of choice.^[20,21,22] If the patient is unable or unwilling to start such an agent, azathioprine and 6-MP are alternatives, but they are less effective. Surgery should be considered in patients who have simple low intersphincteric fistulas, whose fistulas are refractory to medical therapy, or who have severe or disabling symptoms.^[23]

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A 28-year-old man with UC diagnosed 1 year previously comes to the office for evaluation of painful red nodules on his lower extremities. He has been taking mesalamine and azathioprine since his diagnosis. He is still having 5-6 watery bowel movements a day with rectal bleeding. Colonoscopy shows moderately active UC in the rectum.

What is the next step in managing the skin lesion?

1. Perform biopsy of the lesion
2. Start amoxicillin 50 mg PO q6hr
3. Apply topical hydrocortisone cream
4. Initiate treatment with infliximab 5 mg/kg IV

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Answer: D. Initiate treatment with infliximab 5 mg/kg IV.

Erythema nodosum (EN) is characterized by red or violet subcutaneous nodules that usually develop in a pretibial location. Its pathogenesis is largely unclear. EN is the most frequent cutaneous finding in patients with IBD.^[24,25] It occurs more commonly with CD than with UC.^[26] Treatment directed at the underlying IBD usually eliminates EN. Systemic glucocorticoids may be necessary in the presence of refractory lesions that either precede bowel symptoms or occur during quiescent phases of IBD.

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A 44-year-old woman with Crohn ileocolitis who is taking azathioprine and sulfasalazine comes to the clinic for evaluation of redness, pain, and decreased vision in her left eye.

What is the next step in management?

1. Topical moxifloxacin eyedrops
2. Topical acyclovir eyedrops
3. Discontinuance of azathioprine because symptoms are likely to be a side effect of the drug
4. Immediate referral to ophthalmology

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Answer: D. Immediate referral to ophthalmology.

Uveitis is an inflammation of the uvea that occurs in ~1-3% of IBD patients.^[27] It presents with redness of the eye, pain, photophobia, and altered vision. Slit-lamp examination reveals inflammation in the anterior chamber with perilimbic edema, cells, and protein; corneal clouding and conjunctival injection may also be seen. An acute episode may be followed by iris atrophy, lens deposits, and synechiae. The course of the uveitis may not parallel IBD activity. Prompt diagnosis and therapy with topical or systemic steroids are required. Infliximab can be effective in patients with refractory disease.^[28] Secondary glaucoma and rarely blindness may occur if correct management is delayed. Accordingly, immediate referral to ophthalmology is indicated.

Topical antiviral or antibiotic drops are not the treatment for uveitis. Azathioprine does not cause uveitis.

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A 20-year-old man with a history of mild pancolonic UC diagnosed 3 years ago comes to the clinic for follow-up. The patient was on mesalamine when originally diagnosed with UC but has not been taking his medications for the past 1 year. He is having watery diarrhea 3-4 times daily with a small amount of rectal bleeding and urgency. Stool studies are negative for infection. Colonoscopy shows active pancolitis with decreased vascular markings.

What is the first-line treatment in this scenario?

1. Prednisone 40 mg/day PO
2. Infliximab 5 mg/kg IV
3. Oral mesalamine 4.8 g/day and mesalamine enemas 4 g/night
4. Azathioprine 2.5 mg/kg/day PO
5. Oral mesalamine 4.8 g/day

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Answer: C. Oral mesalamine 4.8 g/day and mesalamine enemas 4 g/night.

This patient has mild pancolonic UC. A systemic review and meta-analysis of 3061 citations and 12 randomized controlled trials showed that a combination of oral and topical aminosalicylates is superior to an oral aminosalicylate alone for mild-to-moderate UC.^[29] Prednisone is the treatment of choice for patients with mild UC who do not respond to combination therapy with oral and topical aminosalicylates.^[6] Azathioprine and infliximab are not treatments of choice for mild UC.

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