The following cases and commentary, which focus on inflammatory bowel disease, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 17).
Case 1: Flare in pregnant patient
A 22-year-old woman is evaluated for a flare of Crohn disease. A colonoscopy performed 6 months ago showed moderate, patchy, left-sided colitis extending from the descending colon to the splenic flexure. She responded to therapy with prednisone but declined maintenance therapy in advance of conceiving. She is now 12 weeks pregnant and for the past 2 weeks has experienced bloody diarrhea and left-sided abdominal pain.
On physical examination, temperature is 37.2°C (99.0°F), blood pressure is 110/66 mm Hg, and pulse rate is 76/min. Abdominal examination reveals left-sided abdominal tenderness without guarding or rebound.
Flexible sigmoidoscopy shows recurrent left-sided patchy colitis, and stool studies are negative for Clostridium difficile infection.
Which of the following is the most appropriate treatment?
B. Ciprofloxacin and metronidazole
C. Controlled ileal-release budesonide
Case 2: Pain and rectal bleeding
A 58-year-old woman is evaluated in the emergency department for a 1-day history of nausea and pain in the left lower abdomen, which was followed by the onset of several episodes of dark-red rectal bleeding. Her bowel habits were previously normal, and she has not had tenesmus, fecal urgency, constipation, diarrhea, weight change, or previous abdominal pain. She has no history of gastrointestinal bleeding, alcoholism, chronic liver disease, bleeding disorders, or cancer. Other medical problems are hypertension, hyperlipidemia, and peripheral vascular disease. Her medications are chlorthalidone, ramipril, and simvastatin. She continues to smoke 1 pack of cigarettes daily.
On physical examination, temperature is 37.0°C (98.6°F), blood pressure is 125/68 mm Hg, pulse rate is 87/min, and respiration rate is 14/min; BMI is 27. Abdominal examination reveals pain in the left lower abdomen with no guarding or rebound. No abdominal masses are noted, and the liver and spleen are not enlarged. Bowel sounds are diminished in frequency, and abdominal distention is noted. Rectal examination identifies a small amount of fresh blood and clots; no external hemorrhoids or anal fissure are noted. Femoral, popliteal, and dorsalis pedis pulses are diminished bilaterally.
Laboratory studies reveal a hemoglobin level of 10 g/dL (100 g/L), a leukocyte count of 14,000/µL (14 × 109/L), and a platelet count of 215,000/µL (215 × 109/L).
Which of the following is the most likely diagnosis?
B. Colon cancer
C. Diverticular bleeding
D. Ischemic colitis
E. Ulcerative colitis
Case 3: Skin ulcer near stoma
A 24-year-old woman is evaluated for a 1-month history of increasing pain and bleeding from a skin ulcer next to her stoma. The skin symptoms get worse each time she changes her appliance. She underwent proctocolectomy 4 years ago for medically refractory colonic Crohn disease. She has not had small-bowel involvement, and her ostomy output has been stable since surgery.
On physical examination, vital signs are normal. The skin findings are shown (Figure 1). The remainder of the skin examination is normal. The abdomen is soft with normal bowel sounds. There is no distention, tenderness, masses, or organomegaly.
Which of the following is the most likely cause of this patient's skin findings?
A. Acrodermatitis enteropathica
B. Erythema nodosum
C. Pyoderma gangrenosum
D. Squamous cell carcinoma
Case 4: Symptomatic ulcerative colitis
A 38-year-old man is evaluated in follow-up after a diagnosis of ulcerative colitis. Ten days ago he was started on prednisone, 60 mg/d, but his symptoms have not improved. He has six to nine bloody bowel movements per day and moderate abdominal pain. He has decreased his oral intake because eating exacerbates his pain and diarrhea.
On physical examination, temperature is 37.0°C (98.6°F), blood pressure is 110/56 mm Hg, and pulse rate is 96/min. He is pale but in no distress. The abdomen is diffusely tender without distention, guarding, or rebound.
Laboratory studies reveal a hemoglobin level of 9.7 g/dL (97 g/L) and a leukocyte count of 6300/µL (6.3 × 109/L).
Stool culture and Clostridium difficile assay are negative.
Which of the following is the most appropriate treatment?
A. Increase prednisone to 80 mg/d
B. Initiate adalimumab
C. Initiate ciprofloxacin and metronidazole
D. Initiate mesalamine
E. Initiate sulfasalazine
Case 5: Increasing pain and diarrhea
A 28-year-old woman is evaluated for an 8-week history of increasing lower abdominal crampy pain and diarrhea. She now has 6 to 10 bowel movements per day with one or two nocturnal stools. Stools are loose to watery with intermittent blood streaking. The pain is in the lower abdomen and has increased to 6 to 8 out of 10 in severity over the past week. She has anorexia and nausea but no vomiting or fever. She takes no medications, including NSAIDs.
On physical examination, temperature is 37.8°C (100.0°F), blood pressure is 100/54 mm Hg, and pulse rate is 96/min. She appears thin, pale, and in moderate distress. The abdomen is distended with diffuse tenderness that is most prominent in the lower quadrants. There is no rigidity, guarding, rebound tenderness, masses, or organomegaly.
Representative colonoscopy findings seen in a patchy distribution throughout the ascending, transverse, and descending colon are shown (Figure 2). The terminal ileum and rectum show no inflammation.
Which of the following is the most likely diagnosis?
A. Collagenous colitis
B. Crohn colitis
C. Ischemic colitis
D. Ulcerative colitis
Answers and commentary
Correct answer: A. Certolizumab.
The most appropriate treatment is certolizumab. The previously used treatment approach for Crohn disease (CD) was to (1) initiate therapy with 5-aminosalicylate drugs such as mesalamine at diagnosis; (2) begin thiopurine therapy with azathioprine or 6-mercaptopurine if a patient requires repeated courses of glucocorticoids; and (3) begin therapy with anti–tumor necrosis factor (anti-TNF) agents if these other therapies are unsuccessful. This paradigm has been challenged by newer studies showing that 5-aminosalicylates have only minimal, if any, efficacy in CD, and the success of treatment is significantly higher when anti-TNF therapy is begun alone or in combination with thiopurines earlier in the disease course. Many experts have abandoned the use of 5-aminosalicylates entirely for CD except perhaps for those with mild Crohn colitis. The decision to use thiopurine or anti-TNF monotherapy versus combination therapy is based on an individual patient's severity of symptoms and risk factors for developing complications of their disease balanced against the potential side effects of these treatments. This patient with new-onset CD is in her first trimester of pregnancy. Treatment with an anti-TNF agent is effective for induction and maintenance of remission in CD and is generally considered to be safe during pregnancy (FDA pregnancy category B). The three anti-TNF agents approved for CD are infliximab, adalimumab, and certolizumab. Because certolizumab is pegylated, it should have very little, if any, placental transfer and therefore is favored by some clinicians in a pregnant patient over the other two agents. Although endoscopic procedures are generally avoided in pregnant patients unless absolutely necessary, flexible sigmoidoscopy is safer than colonoscopy, and in this patient it was useful to confirm that her symptoms are due to active CD before committing her to expensive immunosuppressive medications.
Antibiotics are generally not recommended for induction of remission in CD because no particular class of drug can be endorsed based on available data. Furthermore, ciprofloxacin (pregnancy category C) should be used in pregnancy only if the potential benefits outweigh the risk to the fetus. Metronidazole is a pregnancy category B drug.
Controlled ileal-release budesonide is effective for ileocolonic CD, but it would not be effective in this patient with left-sided colitis. In addition, it is classified as category C for use during pregnancy.
Mesalamine may be used to treat ulcerative colitis, but it is not effective in most patients with CD.
Methotrexate may be effective for inducing and maintaining remission in CD, but it is contraindicated during pregnancy. Methotrexate is a classified as category X for use in pregnancy because it may cause fetal death and/or congenital abnormalities.
- Treatment with an anti–tumor necrosis factor agent is effective for induction and maintenance of remission in Crohn disease and is generally considered to be safe during pregnancy (FDA pregnancy category B).
Correct answer: D. Ischemic colitis.
The most likely diagnosis is ischemic colitis. The most common causes of acute, severe lower gastrointestinal (LGI) bleeding are colonic diverticula, angiodysplasia, colitis (due to inflammatory bowel disease, infection, ischemia, or radiation therapy), and colonic neoplasia. Other than colitis, LGI bleeding is typically painless. Ischemic colitis is due to a temporary interruption in mesenteric blood flow and typically occurs in older individuals with significant cardiac and peripheral vascular disease. Typical symptoms are the acute onset of mild, crampy abdominal pain with tenderness on examination over the affected region of the colon. Bleeding may occur early but often occurs within a few days of pain onset.
Angiodysplasia is most common among the elderly and usually presents as chronic or occult blood loss, but it can also cause acute painless, hemodynamically significant bleeding.
Colonic neoplasms may present with bleeding but it is typically of small volume and is not associated with abdominal pain.
Bleeding from a colonic diverticulum typically is acute and painless. Bleeding stops spontaneously in approximately 80% of patients but recurs in 10% to 40%.
Patients with ulcerative colitis almost always have a sense of bowel urgency due to rectal inflammation. Frequent watery bowel movements are typical, and bleeding occurs with more severe inflammation. The onset of ulcerative colitis is typically acute, and patients often remember when symptoms first started. Severe abdominal pain is an unusual manifestation of ulcerative colitis and suggests a complication such as toxic megacolon or perforation. Most patients with toxic megacolon related to ulcerative colitis have at least 1 week of bloody diarrhea symptoms.
- The presence of abdominal pain in a patient with lower gastrointestinal bleeding raises the possibility of colitis from ischemia, inflammatory bowel disease, infection, or radiation.
Correct answer: C. Pyoderma gangrenosum.
This patient's ulcerating lesion is characteristic of pyoderma gangrenosum (PG). PG is an uncommon skin disease characterized by intense neutrophilic inflammation and invasion of the skin. Lesions are classically ulcerated, but PG may also present with bullae, pustulonodules, and vegetative plaques. Typical lesions begin as painful pustules that rapidly ulcerate and expand, with an edematous, rolled, or undermined-appearing border that may have a violaceous hue.
Annular rings are sometimes noted. As with other neutrophilic dermatoses, when the process is active, approximately 25% of patients will exhibit pathergy or induction of new lesions at sites of trauma, including ostomy, phlebotomy, and intravenous sites. Peristomal PG, occurring around ostomy sites, is common and can be challenging to manage. As PG resolves, it tends to heal with atrophic scarring in a cross-like or cribriform pattern. There are no definitive diagnostic tests, and PG is a diagnosis of exclusion. Skin biopsy may be required to exclude other diseases such as cutaneous Crohn disease but may cause worsening of the PG. Treatment can be challenging, and if there is an associated underlying disease, therapy should be directed at controlling that process. Extraintestinal manifestations such as oral aphthous ulcers, arthralgia, inflammatory eye diseases, and PG are seen in approximately 10% of patients with inflammatory bowel disease.
Acrodermatitis enteropathica (AE) is an inherited or acquired metabolic disorder characterized by perioral and acral (in the extremities) erythematous and vesiculobullous dermatitis and alopecia related to zinc deficiency. AE has been associated with Crohn disease, but this patient's stomal ulcer is not consistent with AE.
Erythema nodosum is the most common cutaneous manifestation of inflammatory bowel disease, occurring in up to 20% of patients, particularly women. The lesions of EN are tender, subcutaneous nodules presenting as barely appreciable convexities on the skin surface, with a reddish hue in the acute phase. EN is frequently bilateral and symmetrical, and it usually occurs on the distal lower extremities, but it may also appear on the trunk, thighs, or upper extremities.
Squamous cell carcinoma (SCC) usually appears as a scaly, crusted, well-demarcated red papule, plaque, or nodule. SCC can develop in patients with Crohn disease, most commonly at sites of chronic, long-standing inflammation such as chronic fistulas. This patient's ulcerative skin lesion with undermined and violaceous borders is not consistent with the appearance of SCC.
- Pyoderma gangrenosum (PG) is characterized by painful pustules that rapidly ulcerate and expand, with edematous, rolled, or undermined borders that may have a violaceous hue; PG may be an extraintestinal manifestation of Crohn disease.
Correct answer: B. Initiate adalimumab.
The most appropriate treatment is to initiate an anti–tumor necrosis factor (anti-TNF) agent such as adalimumab. This patient has moderate to severe ulcerative colitis that is not responding to 60 mg/d of prednisone. Moderate to severe ulcerative colitis is often treated with oral glucocorticoids such as prednisone, 40 to 60 mg/d. Patients whose disease does not respond to oral glucocorticoids should be hospitalized and given intravenous glucocorticoids or should be treated with an anti-TNF agent. Randomized controlled clinical trials have shown three anti-TNF antibodies (infliximab, adalimumab, and golimumab) to be effective for inducing and maintaining remission in patients such as this with ulcerative colitis. Indications for hospital admission include dehydration, inability to tolerate oral intake, fever, significant abdominal tenderness, and abdominal distention.
A meta-analysis of clinical trials showed that using doses of prednisone above 60 mg/d provides little if any additional efficacy and produces more side effects.
Ciprofloxacin and metronidazole should be used in patients with severe colitis associated with high fever, significant leukocytosis, peritoneal signs, or toxic megacolon. However, antibiotics are not indicated in a patient such as this with colitis without signs of systemic toxicity.
Patients with mild to moderate ulcerative colitis respond well to 5-aminosalicylate agents. Patients with proctitis or left-sided colitis should receive topical therapy with a 5-aminosalicylate or hydrocortisone suppositories or enemas. If patients require repeated courses of glucocorticoids or become glucocorticoid dependent, thiopurines (6-mercaptopurine or azathioprine) or an anti-TNF agent should be initiated (methotrexate has not been shown to be effective in ulcerative colitis). Anti-TNF agents should be used in patients who do not maintain remission with thiopurines or patients whose disease is refractory to glucocorticoids. It is unlikely that 5-aminosalicylates would be beneficial in this patient with more severe disease that is refractory to prednisone.
- Patients with moderate to severe ulcerative colitis whose disease does not respond to oral glucocorticoids should be treated with either intravenous glucocorticoids or an anti–tumor necrosis factor agent.
Correct answer: B. Crohn colitis.
The most likely diagnosis is Crohn colitis. This patient has severe, patchy colitis with some large, deep ulcers and rectal sparing, which is consistent with Crohn colitis. In Crohn disease, endoscopic findings vary from superficial aphthous ulcers to discrete, deep ulcers that can be linear, stellate, or serpiginous and that may coalesce into a “cobblestone” appearance. Rectal sparing is typical, as are areas of inflammation separated by normal mucosa (known as skip lesions). The ileum is inspected during colonoscopy to detect ileal inflammation characteristic of Crohn disease. Histology may show patchy submucosal inflammation, but more superficial inflammation does not rule out Crohn disease.
Collagenous colitis is a form of microscopic colitis. Microscopic colitis accounts for 10% to 15% of patients with chronic, watery diarrhea. In contrast to inflammatory bowel disease, microscopic colitis is more common in older persons and does not cause endoscopically visible inflammation, as was seen in this patient.
Ischemic colitis is the most common form of intestinal ischemic injury. Approximately 90% of cases occur in patients older than 60 years. Symptoms include sudden abdominal pain and diarrhea followed by rectal bleeding. Ischemic colitis can result in segmental colitis, but it is typically not patchy and would be unusual in a 28-year-old patient.
In ulcerative colitis, inflammation typically begins in the rectum and extends proximally in a circumferential manner. Mild ulcerative colitis is characterized by mucosal edema, erythema, and loss of the normal vascular pattern. More significant disease produces granularity, friability, ulceration, and bleeding. Ulcerative colitis would typically feature rectal involvement and continuous colitis rather than patchy colitis, as was seen in this patient.
- In Crohn disease, endoscopic findings vary from superficial aphthous ulcers to discrete, deep ulcers; rectal sparing is typical, as are areas of inflammation separated by normal mucosa (known as skip lesions).