Chapter 7: Gastroenterology

A 43-year-old woman complains of a burning pain in the retrosternal area. Her symptoms started about 2 years ago and initially responded to self-medication with antacids or histamine-2 receptor antagonists (H₂ blockers). However, within the last 4 months, she has had nearly daily problems. She frequently wakes up in the middle of the night with retrosternal, burning pain, radiating to her neck. She also frequently notices an acidic taste in her mouth. While antacids help somewhat, they only provide transient relief. She has otherwise been healthy. She currently takes up to 800 mg of cimetidine per day plus the antacids. She denies tobacco or alcohol use. Her physical examination is normal.

Question 7.1.1 Which of the following is NOT considered a "red flag" when it comes to patients with acid reflux/dyspepsia?

A) Weight loss.

B) Trouble swallowing liquids.

C) Trouble swallowing solids.

D) A craving for doughnuts.

Answer 7.1.1 The correct answer is "D." OK, we will give you this one. One of the most critical parts of patient assessment is to make sure there are no "red flag" symptoms that may indicate more than simple gastroesophageal reflux disease (GERD). Red flag symptoms include dysphagia, weight loss, anemia, aspiration, early satiety or vomiting, and cough. A craving for doughnuts is benign (although eating them is not) and may be seen among the book editors, police, college students, Vash the Stampede, and others.

Question 7.1.2 Which of the following statements is true?

A) All patients with GERD need endoscopy.

B) Routine endoscopy in patients with GERD markedly reduces the risk of esophageal cancer.

C) The diagnostic sensitivity and specificity of typical symptoms of GERD is >90%.

D) Patients over the age of 45 with new onset symptoms are considered to be at high risk.

E) C and D.

Answer 7.1.2 The correct answer is "E." Because of the high sensitivity and specificity of symptoms (>90%), most patients do not need endoscopy or any other procedure or test to make the diagnosis of GERD. Patients with refractory GERD or those with new symptoms over the age of 45 years (50 by some sources) warrant endoscopy. "B" is incorrect. Screening for the presence of Barrett esophagus in patients with GERD is low yield. Targeted, not routine, endoscopy may be beneficial. Even then, the benefit is limited (J Natl Cancer Inst. 2011;103:1049). This is still a matter of active debate and recommendations may change.

The patient denies any "red flags." Based on the history, you assume that this patient has GERD.

Question 7.1.3 You recommend:

A) Barium swallow study.

B) Esophageal manometry.

C) Esophagogastroduodenoscopy (EGD).

D) Ambulatory pH study of the esophagus.

E) Trial of omeprazole and lifestyle modifications.

Answer 7.1.3 The correct answer is "E." As noted above, the sensitivity and specificity of classical symptoms allows for the diagnosis of GERD without additional studies. Testing is actually less sensitive than symptoms for GERD with the sensitivity of tests varying between 50% and 70%. Many patients have a false-negative EGD. H₂ blockers can be used as the first-line treatment in patients with GERD, but this patient has already failed cimetidine. Starting a proton pump inhibitor (PPI), like omeprazole, is the next step and is preferred as the first-line therapy in patients with severe symptoms. Lifestyle modifications should be made including weight loss (if overweight); avoidance of carbonated beverages, caffeine, excessive alcohol, and large or late evening meals; avoidance of anti-cholinergics, calcium channel blockers, NSAIDs, and sedative drugs; smoking cessation; and elevation of the head of the bed using 6-in blocks.

Your patient is willing to try the PPI you prescribe, but she also wants to know about surgery that a friend had.

Question 7.1.4 Regarding surgery for GERD, you can tell her:

A) Bloating and inability to belch do not occur with antireflux surgery.

B) Antireflux surgery should be thought of as the first-line because it is vastly superior to medical therapy.

C) Years after antireflux surgery, many patients will require medication for GERD symptoms.

D) Laparoscopic fundoplication will ruin her fabulous bikini body by leaving a large midline scar.

Answer 7.1.4 The correct answer is "C." Surgery may be an option in select patients with reflux disease. The usual indications for antireflux surgery include failure of medical therapy to control symptoms and failure of medical therapy to prevent complications (e.g., stricture and pneumonia). The most commonly performed surgery is fundoplication, in which the lower esophageal sphincter is "wrapped" to enhance its competency. While fundoplication will alleviate symptoms in 80% to 95% of patients, there is progressive loss of effectiveness over time (only 40% are without medication after 10 years). Adverse effects of surgery include persistent dysphagia (requiring additional interventions in 3–7%), gas, bloating, and inability to belch. "D" is incorrect because a laparoscopic procedure should result in just a few small scars.

After a trial of your favorite PPI (that her insurance will cover after you play "Guess What's on Our Formulary"), your patient continues to have symptoms. You review lifestyle modifications with her, and she assures you that she has made these changes. You refer her for EGD. The esophageal biopsy is consistent with the visual report, which shows Barrett esophagus.

Question 7.1.5 All of the following are true regarding Barrett esophagus EXCEPT:

A) Males are more likely to have Barrett esophagus than females.

B) Barrett esophagus is due to a change in the esophageal mucosa from columnar to squamous.

C) Barrett esophagus occurs in 10% to 15% of patients with erosive esophagitis.

D) Barrett esophagus increases the risk of adenocarcinoma by up to 30-fold.

E) Patients with Barrett esophagus should undergo periodic screening EGD.

Answer 7.1.5 The correct answer is "B." Barrett esophagus is diagnosed histologically when esophageal mucosal metaplasia has occurred and the usual squamous epithelial cells have changed to columnar epithelium. Risk factors for Barrett include long-standing reflux, male gender (6:1 male:female preponderance), middle age, tobacco use, and white race. Barrett esophagus occurs in 10% to 15% of patients with erosive esophagitis, and it dramatically increases the risk of esophageal adenocarcinoma by up to 30-fold (N Engl J Med. 2011;365:1375). However, the absolute risk of adenocarcinoma is still small, about 0.12% to 2% annually. Surveillance for Barrett depends on the level of dysplasia found on initial examination, and guidelines exist that dictate the frequency with which repeat EGD should be performed.

Objectives: Did you learn to…

• Describe the diagnosis and management of GERD?

• Use H₂ blockers and PPIs in the management of GERD?

• Recognize complications of GERD and risk factors for Barrett esophagus?

A 53-year-old woman comes to your office complaining of chest pain and problems swallowing. She says food seems to hang up in the retrosternal area. This started several years ago, has gradually worsened, and now occurs at least twice per week. Generally, only solid foods cause problems. She has become very careful, only taking small bites and chewing them well before swallowing. Should she experience problems, she has found that drinking additional liquids alleviates her symptoms within minutes. She does not regurgitate food and has not lost weight.

Question 7.2.1 What is the symptom this patient is complaining of?

A) Dysphagia.

B) Globus sensation.

C) Odynophagia.

D) Aerophagia.

E) Phagophobia.

Answer 7.2.1 The correct answer is "A." Dysphagia, from the Greek dys (meaning "with difficulty" … as opposed to "Dis," which is a city in Dantes's Hell in addition to being a neologism) and phagia (meaning "to eat"), refers to the sensation that food is being hindered in its passage from the mouth to the stomach. Odynophagia refers to pain upon swallowing, aerophagia to swallowing of air, and globus sensation to a perception of a lump or fullness in the throat that is temporarily relieved by swallowing. Phagophobia is just what you think it is: fear of eating or swallowing.

Question 7.2.2 Given the above patient's description of symptoms and the location of her discomfort (food sticking in the retrosternal esophagus), what type of dysphagia is she most likely to suffer from?

A) Oropharyngeal dysphagia.

B) Esophageal dysphagia.

C) Functional dysphagia.

D) Aberrant dysphagia.

Answer 7.2.2 The correct answer is "B." Dysphagia can be differentiated by where the symptoms seem to occur. Oropharyngeal dysphagia, also known as "transfer dysphagia," arises from difficulty in the upper esophagus and pharynx. Patients complain of food getting stuck immediately upon swallowing, and when asked to point to the location, patients frequently identify the cervical region. Patients with oropharyngeal dysphagia often have more problems with liquids than solids and may complain that liquid comes out of their nose when they try to swallow. Esophageal dysphagia is usually described as beginning several seconds after swallowing, and patients frequently point to the suprasternal notch or retrosternally when trying to localize the area causing symptoms. Patients in whom no cause can be found after detailed investigation are often categorized as having functional dysphagia. There is no such thing as aberrant dysphagia.

A complete review of systems and physical examination is unrevealing. She is not taking pills that can cause erosive esophagitis such as doxycycline or bisphosphonates, she is not HIV positive making candidal and HSV esophagitis unlikely, and she again notes progressive dysphagia, initially to solids and now to liquids.

Question 7.2.3 Which of the following is the single best test to arrive at a diagnosis in this patient?

A) Barium swallow.

B) Esophageal manometry.

C) EGD.

D) Ambulatory pH study of the esophagus.

E) Diagnostic trial of a high-dose PPI.

Answer 7.2.3 The correct answer is "C." Visualization of the esophagus is critical in patients with dysphagia. Our patient presents with esophageal dysphagia for solids, which is most consistent with a structural problem, such as a stricture, web, or neoplasm. Endoscopy is the best diagnostic study to evaluate the esophageal mucosa as it allows one to obtain biopsies and perform endoscopic interventions such as dilations, if indicated. Barium swallows are second best and have fallen out of favor when endoscopy is available. Should the endoscopy come back negative, esophageal manometry ("B") may be useful as it will help determine if a motility disorder is the cause of symptoms. While a "diagnostic" trial with a PPI ("E") is an appropriate strategy in patients with typical GERD, the presence of an alarm symptom, such as dysphagia, requires further testing. "D," an ambulatory pH study, does not help in defining the etiology of the dysphagia.

The patient returns from her endoscopy. According to the report, she had severe esophagitis with confluent erosions in the distal esophagus. During your physical examination, you find the skin changes shown in Figure 7-1. When you ask about these, the patient reports a history of bluish fingertip discoloration with cold temperatures. She also complains that her fingers feel "tight" at times.

FIGURE 7-1.

Question 7.2.4 With this new information, which of the following diagnoses are you considering?

A) CREST syndrome.

B) Esophageal adenocarcinoma.

C) Metastatic colonic adenocarcinoma.

D) Sicca syndrome.

E) Peptic ulcer disease (PUD).

Answer 7.2.4 The correct answer is "A." Notice the telangiectasia in the picture above. CREST is an acronym for a syndrome that includes Calcinosis cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias. Figure 7-1 shows telangiectasias on the palmar digital pad. Up to 60% of patients with CREST have erosive esophagitis. Dysphagia is common and is due to esophageal stricture and/or dysmotility.

Question 7.2.5 Given her endoscopic findings and the fact that she likely has CREST syndrome, what treatment do you suggest?

A) H₂ blocker.

B) PPI.

C) High-dose corticosteroids.

D) H. pylori eradication.

E) Laparoscopic fundoplication.

Answer 7.2.5 The correct answer is "B." Severe reflux and dysphagia are hallmarks of CREST syndrome. The esophagus has poor motility with impaired function of the lower esophageal sphincter allowing reflux while poor motility reduces esophageal clearance. Chronic and potent acid suppressive medications, such as PPIs, are indicated. Fundoplication is relatively contraindicated, as the poor contractile function of the esophagus may not generate enough force to overcome the barrier created by fundoplication. H. pylori treatment has no role in the management of this illness. Steroids could certainly worsen the gastrointestinal (GI) symptoms by irritating the gastric mucosa. Other causes of esophageal dysphagia are listed in Table 7-1.

Objectives: Did you learn to…

• Differentiate dysphagia from other GI symptoms?

• Take an adequate history to evaluate the etiology of dysphagia?

• Describe different types of dysphagia and identify various causes of dysphagia?

• Recognize that CREST syndrome as a cause of dysphagia?

You see a 61-year-old woman in your office complaining of halitosis, heartburn, and regurgitation of undigested food 4 hours after eating. She also feels that the food is sticking in her throat.

What is the MOST LIKELY cause of her symptoms?

A) Schatzki ring.

B) Zenker diverticulum.

C) Achalasia.

D) Foreign body.

E) Esophageal web.

The correct answer is "B." Late regurgitation of undigested food is pathognomonic for Zenker diverticulum. A Zenker diverticulum is an acquired out-pouching of esophageal mucosa, which typically becomes symptomatic in middle age or later in life. The diagnosis is confirmed by lateral view of a barium swallow or by visual confirmation with EGD. The other diagnoses listed can cause dysphagia and regurgitation but are less likely. "A," Schatzki ring, is a lower esophageal mucosal ring that can "catch" food and cause dysphagia. "C," achalasia, results from a loss of innervation of the lower esophagus with impaired esophageal motility and generally occurs in young and middle-aged adults. Patients with achalasia typically have dysphagia with solids and liquids. "D," foreign body, should be diagnosable by history. Elderly adults, children, and patients with psychiatric disease are most at risk for foreign body in the esophagus. "E," esophageal web, is caused by a thin layer of mucosa across the esophageal lumen and presents much like a Schatzki ring.

A 32-year-old woman presents with 3 years of intermittent GI complaints after eating. She describes epigastric pressure and bloating after food intake. Her weight is stable. She denies heartburn, vomiting, diarrhea, constipation, or blood in her stools. She only takes a multivitamin and she has not tried any specific remedies. The physical examination is normal.

Question 7.3.1 What is the MOST LIKELY diagnosis given the information above?

A) Pyrosis.

B) PUD.

C) Nonulcer dyspepsia.

D) Stomach cancer.

Answer 7.3.1 The correct answer is "C." Nonulcer dyspepsia is an ill-defined condition characterized recurring intermittent epigastric discomfort and fullness in the absence of mucosal lesions or other structural abnormalities of the GI tract. Nonulcer dyspepsia is also known as "functional dyspepsia." While about 20% of the general population has nonulcer dyspepsia, only about 20% of these seek medical attention. Pyrosis ("A") means the same thing as heartburn; this patient has no complaints of heartburn. Stomach cancer of 3 years duration would usually be accompanied by other systemic symptoms (such as fatigue, weight loss or death—is that a systemic symptom?), which the patient denies. PUD should be accompanied by "heartburn," which is not present in our patient.

Question 7.3.2 Which of the following symptoms WOULD NOT be an expected symptom of nonulcer dyspepsia?

A) Fullness.

B) Early satiety.

C) Belching.

D) Intolerance to eggs.

Answer 7.3.2 The correct answer is "D." Nonulcer dyspepsia is characterized by all the other symptoms and also includes such symptoms as abdominal distention, borborygmi (i.e., grandpa's tummy gurgling heard across the room at Thanksgiving), epigastric or substernal pain, anorexia, nausea, vomiting, and abdominal tenderness. "D," intolerance to eggs, is not part of nonulcer dyspepsia. What have you got against eggs? The editors like eggs, poached if possible and served as eggs benedict. While there are several proposed pathophysiologic mechanisms by which nonulcer dyspepsia may occur, food intolerance is not one of them.

Question 7.3.3 What is the most appropriate next step in this patient?

A) Obtain H. pylori serum antibodies.

B) Obtain an abdominal ultrasound examination of liver, biliary tree, and pancreas.

C) Obtain a detailed dietary history.

D) Obtain an upper GI x-ray series.

E) Refer for gastroscopy.

Answer 7.3.3 The correct answer is "C." Does this seem to be a contradiction to the previous question? Well, we don't mean it to be so. Although food intolerance does not cause nonulcer dyspepsia, the symptoms of the two types of disorders overlap to some degree. Considering the prevalence of selective carbohydrate malabsorption syndromes, high intake of lactose and fructose-containing food and beverages may contribute to GI symptoms in a significant number of patients. Therefore, the history should always contain a detailed assessment of dietary habits and symptoms in relation to food intake. A more extensive workup is not necessary at this point in time as the patient is younger than 45 years of age and has no alarm symptoms. While infection with H. pylori causes gastritis and peptic ulcers, several controlled studies demonstrated no consistent benefit of H. pylori eradication in patients with dyspepsia without ulcers.

You obtain a detailed dietary history, suggesting a potential contribution of fructose intolerance and excessive carbonated beverage intake (it's those five Giant Gulp soft drinks a day). Her symptoms persist despite appropriate diet modifications. You choose to start the patient on a PPI. One week later, your nurse receives a call from your patient about severe abdominal pain and diarrhea. She has not noticed blood in her stool.

Question 7.3.4 What is the best next step?

A) She is having withdrawal from the five Giant Gulp sodas. Add back the fructose and the 2,000 kcal.

B) Check fasting gastrin level.

C) Add antibiotic therapy for bacterial overgrowth.

D) Discontinue the PPI.

E) Add an antidiarrheal.

Answer 7.3.4 The correct answer is "D." Diarrhea, including from Clostridium difficile, is a common adverse effect of PPIs that occurs in at least 5% to 7% of patients. Discontinuation generally leads to a rapid resolution in the majority of cases (although maybe not of C. difficile-related diarrhea). While reduced stomach acidity from PPIs or H₂ blockers may result in bacterial colonization of the proximal GI tract, the early onset and severity of symptoms described argue against bacterial overgrowth as the etiology of this patient's symptoms ("C"). While PPIs can elevate gastrin levels, the hypergastrinemia seen is not comparable to levels seen in Zollinger–Ellison syndrome, which can also cause diarrhea. Stool studies and empiric therapy with antidiarrheals may be considered if discontinuing the PPI does not improve symptoms.

Question 7.3.5 Which of the following IS TRUE of the natural history of nonulcer dyspepsia?

A) Most patients will not have symptom-free periods, instead having constant dyspepsia.

B) Most patients improve with placebo treatment.

C) Most patients will go on to develop ulcers.

D) Spontaneous resolution of symptoms is rare.

Answer 7.3.5 The correct answer is "B." Up to 60% of patients in placebo controlled trials respond to placebo, making it difficult to prove the efficacy of medications. As the above number suggests, spontaneous resolution of symptoms is common, while many patients will have a chronic, intermittent course characterized by symptom-free periods. Most patients will not develop serious pathology.

Objectives: Did you learn to…

• Diagnose and manage nonulcer dyspepsia?

• Appreciate the natural history of nonulcer dyspepsia?

• Recognize important side effects of PPIs?

A 56-year-old woman comes to the emergency department after a sudden episode of hematemesis. Yesterday, she had two bowel movements that were dark, sticky, and foul smelling. She woke up nauseated and has since twice vomited a small amount of bright red blood. She also feels dizzy. Because of knee pain related to skydiving 1 week ago, she started taking five tablets of naproxen (1,100 mg) twice daily. She takes no other medicines and denies any significant past medical history.

On physical examination, you find a pale, uncomfortable, but alert patient. She is tachycardic (pulse of 115 bpm) and has a drop in blood pressure from 116/72 mm Hg supine to 93/65 mm Hg standing. Her abdomen is flat with hyperactive bowel sounds. You note epigastric tenderness but no rebound or guarding. There is melena on rectal examination.

Question 7.4.1 Which of the following steps will be LEAST helpful at this point in time?

A) Admission to the hospital.

B) Immediate treatment with an intravenous (IV) H₂ blocker.

C) Referral for emergent endoscopy.

D) IV access and fluid resuscitation.

E) Laboratory tests including hemoglobin, coagulation studies, and blood type and cross-match.

Answer 7.4.1 The correct answer is "B." The patient has symptoms and clinical findings of a hemodynamically significant upper GI tract bleed. Although she is "walking and talking" just fine, fluid administration and hospital admission with close monitoring in an intensive care environment are indicated. A baseline hemoglobin and hematocrit (HCT) should be obtained. However, a normal hemoglobin does not exclude a significant acute bleed, as hemodilution (in the absence of IV fluids) requires several hours. Given the presentation, a blood transfusion may become necessary in the future; therefore, blood should be sent for type and cross-match. Early endoscopy should be performed to identify the cause of her bleeding, and endoscopic therapy should be undertaken if appropriate. Treatment with H₂ blockers does not affect the rate of bleeding; however, IV PPI therapy does decrease the risk of rebleeding in high-risk patients by increasing gastric pH to enhance coagulation. PPI therapy and endoscopy are standard of care for upper GI bleeding.

Question 7.4.2 What is the risk of suffering a clinically significant GI event on NSAIDs?

A) Up to 4% per year.

B) Up to 10% per year.

C) Up to 25% per year.

D) Up to 50% per year.

E) Nearly 99% per year.

Answer 7.4.2 The correct answer is "A." The risk of a clinically significant NSAID-related GI event, including GI bleeding, perforation, or obstruction, is about 1% to 4% per year.

The patient undergoes endoscopy, which shows a small duodenal ulcer in the bulb with a visible vessel in the ulcer base. Gastric biopsies show chemical gastropathy and no evidence of H. pylori. After endoscopic treatment, the patient recovers nicely. Then, 3 months later, she returns to your office for a follow-up evaluation. She is asymptomatic and continues taking a PPI. Her physical examination is normal. Laboratory tests show normal hemoglobin.

Question 7.4.3 What is the best next step?

A) Repeat endoscopy to document healing and rule out malignancy.

B) Upper GI x-ray series to document healing.

C) Switch to a H₂ blocker.

D) Discontinue acid-suppressive medication.

E) H. pylori antibody test.

Answer 7.4.3 The correct answer is "D." While nonhealing ulcers may be due to a neoplasm, the vast majority of duodenal ulcers are benign. Therefore, neither endoscopic nor radiologic documentation of healing is necessary. See Table 7-2 for more on risk factors for malignancy in gastric ulcers. "C" is incorrect. Patients with uncomplicated and small (<1 cm) duodenal or gastric ulcers who have received adequate treatment of H. pylori or NSAID-induced ulcer do not need long-term therapy directed at ulcer healing as long as they are asymptomatic following therapy. Antisecretory drugs can be discontinued after 4 to 6 weeks in these patients. "E" is incorrect. Serology for H. pylori will not be helpful in this patient. First, histology is as sensitive as other tests for H. pylori infection and the patient's biopsies were negative for H. pylori. Second, serologic testing does not tell us if the patient is currently infected, as many patients maintain antibody positivity even a year after treatment.

Question 7.4.4 If your patient had come back H. pylori positive, which of the following combinations IS NOT indicated in the treatment of H. pylori?

A) Omeprazole, clarithromycin, metronidazole.

B) Cephalexin, omeprazole, amoxicillin.

C) Metronidazole, amoxicillin, omeprazole.

D) Bismuth subsalicylate, metronidazole, tetracycline, lansoprazole.

E) Omeprazole, clarithromycin, amoxicillin.

Answer 7.4.4 The correct answer (and the regimen you would not want to use) is "B." All of the other regimens can be used to treat H. pylori infection. Of note are regimens "A" and "D." There is resistance to metronidazole, so it should only be used when the patient is penicillin allergic OR taking quadruple therapy. Triple therapy with PPI should be used where clarithromycin resistance is low. Quadruple therapy should be used in patients with recent or repeated exposure to clarithromycin or metronidazole or areas with high clarithromycin resistance (>15%).

Question 7.4.5 Which of the following IS NOT useful for testing for H. pylori eradication after treatment?

A) Serum IgG antibody titers.

B) CLO test.

C) Breath urea test.

D) Radioactive CO₂ blood test.

E) Stool antigen test.

Answer 7.4.5 The correct answer is "A." Remember the helpful tip above? Only 57% of patients are antibody negative to H. pylori a year after successful treatment. Thus, antibody titers cannot document eradication. All of the other tests mentioned are functional tests for the presence of H. pylori. The CLO test is done on biopsy specimens and documents the presence of urea splitting. The same is true for the breath urea test and the radioactive CO₂ blood test. In both of these tests, urea is ingested. If H. pylori is present, radioactive CO₂ is generated that can be measured in the blood or breath. Confirmation of eradication should be considered for all patients receiving H. pylori treatment, but definitely should be performed in the following: (1) patients with persistent symptoms of dyspepsia despite H. pylori treatment; (2) patients with H. pylori associated ulcer; (3) patients with gastric mucosa associated lymphoid tissue type lymphoma; (4) patients who had resection for early gastric cancer (N Engl J Med. 2010;362:1597–1604).

Objectives: Did you learn to…

• Appreciate the role of NSAID use in Peptic Ulcer Disease (PUD)?

• Manage an acute GI bleed?

• Identify patients at high risk for NSAID-induced GI toxicity?

• Learn about the treatment and diagnosis of H. pylori?

Which of these medications would be the LEAST likely cause of esophagitis if caught in the esophagus?

A) Potassium chloride.

B) Ferrous sulfate.

C) Alendronate.

D) Loratadine.

E) Tetracycline.

The correct answer is "D." Many medications can cause "pill esophagitis," including potassium chloride, ferrous sulfate, alendronate, tetracycline antibiotics, and ascorbic acid. Aspirin and other NSAIDs can also cause esophagitis. Smaller pills are less likely to cause problems. In addition to not being irritating, loratadine is tiny.

One of your patients presents complaining of diarrhea and epigastric pain unresponsive to H₂ blockers or PPIs. He denies smoking tobacco, taking NSAIDs, or drinking alcohol. Endoscopy reveals several ulcers. Biopsy for H. pylori is negative and there is no malignancy.

Which of the following would be the most appropriate laboratory test to obtain in order to discover an etiology for the multiple ulcers (and diarrhea)?

A) Vasoactive intestinal peptide (VIP).

B) Gastrin.

C) Glucagon.

D) Somatostatin.

The correct answer is "B." Some sort of screening test for gastrinoma is warranted in a patient who has recurrent or refractory ulcers and who is H. pylori negative and does not use NSAIDs. Zollinger–Ellison syndrome is the name given to the state in which there is acid hypersecretion secondary to increased gastrin production, usually from a gastrin-producing tumor (gastrinoma). Up to 1% of patients with PUD have a gastrinoma. Serum gastrin levels should be obtained with the patient fasting and off PPIs, as PPIs will increase gastrin levels. If the serum gastrin is elevated (>10 times upper normal limit), further investigations will need to be performed. Other reasons to consider obtaining a serum gastrin level include ulcers in unusual locations (distal duodenal and jejunum), family history of ulcers, and ulcers associated with severe esophagitis. "A" is incorrect. VIP actually works to suppress acid secretion. VIPomas do occur, but VIPomas are associated with watery diarrhea and hypokalemia—not ulcers. "C," glucagon, will not be of much help here. Glucagon over secretion results in hyperglycemia and anemia. "D," somatostatin, is a hormone that inhibits the secretion of gastrin and thus would be protective vis-à-vis ulcers. Somatostatin secreting tumors are very rare.

Isolated bright red hematemesis (e.g., no tachycardia and no fever), which occurs after several bouts of vomiting or dry heaves, is referred to as:

A) Boerhaave syndrome.

B) Mallory–Weiss tear.

C) Cameron lesion.

D) None of the above.

The correct answer is "B." A Mallory–Weiss tear occurs after repeated trauma to the lower esophageal and gastric mucosa from forceful retching. This can be differentiated from a Boerhaave tear by the (generally) self-limited nature of the bleeding and the absence of other symptoms. Boerhaave syndrome is a perforation of the esophagus resulting from a sudden increase in intraesophageal pressure, caused by vomiting, retching, less frequently by coughing, childbirth, or weight lifting. It occurs higher in the esophagus and is associated with mediastinitis, fever, shock, and death if intervention is not forthcoming. Cameron lesions are small ulcers in patients with a hiatal hernia, are usually an incidental finding, and are likely caused by rubbing of the stomach against the diaphragm as the hernia slides. They can bleed, but the history given above is classic for a Mallory–Weiss tear.

A 35-year-old female presents to your clinic complaining of onset of severe midepigastric pain, weight loss, and vomiting following meals. Between meals she is asymptomatic. This has been going on for the past 2 years ever since she purposefully lost 25 lb to attain a healthy weight for her height. Unfortunately, she has continued to lose weight because of the postprandial pain and vomiting. On her examination you notice a midepigastric bruit.

The most likely diagnosis is:

A) Aortic aneurysm.

B) Atherosclerotic disease of the celiac trunk.

C) Superior mesenteric artery (SMA) syndrome.

D) Chronic pancreatitis.

E) None of the above.

The correct answer is "C." This is a typical history and physical examination for SMA syndrome. SMA syndrome is more likely to occur in a patient who has lost significant weight, resulting in thinning of the mesenteric fat pad. Here's the pathophysiology: the SMA runs above the duodenum and becomes stretched and partially occluded in response to meals (as the stomach and duodenum expand), leading to mesenteric ischemia and food aversion. SMA syndrome can be diagnosed using Doppler ultrasound to demonstrate increased velocity of blood in the SMA or by a CT-angiogram. "A" and "B" are unlikely in a young patient, and "D" should not be associated with a bruit. Celiac artery syndrome may have a similar presentation to SMA syndrome but, obviously, involves the celiac trunk.

A 54-year-old man comes to your office for his annual physical. He is taking naproxen for a recent ankle injury. Based on your recommendation last year, he started taking one aspirin (81 mg) daily. He does not take any other medications. He exercises regularly, does not smoke, and drinks one glass of wine every day. Your examination is completely normal, except that a test for occult fecal blood is positive.

Question 7.5.1 What is the next best step?

A) Upper endoscopy.

B) CBC.

C) Colonoscopy.

D) A and B.

E) B and C.

Answer 7.5.1 The correct answer is "E." Current recommendations suggest screening for colorectal cancer in all patients over the age of 50 years. Testing for fecal occult blood is one of the accepted methods. However, it should only be performed as screening test in asymptomatic individuals. Moreover, the use of aspirin and/or NSAIDs and foods such as undercooked meat may increase the number of false-positive tests and should thus be avoided. Fecal immunochemical tests using the current generation of stool cards detects human hemoglobin by immunologic means. Thus, it circumvents many of the weaknesses of the old guaiac test (but not bleeding secondary to NSAIDs, etc. giving a false positive screen). Immunochemical testing is now the method of choice for detecting fecal occult blood when screening for colon cancer. However, once you have a heme-positive stool, you must proceed to colonoscopy in a patient over the age of 50. A CBC is also important to determine if the patient is anemic. Since the patient currently has no symptoms referable to upper GI pathology, evaluation of the upper GI tract should only be considered if the colonoscopy is negative.

Review of his records shows that he underwent a colonoscopy 3 years ago. Three small adenomatous polyps were found. He also had scattered diverticula in the sigmoid.

Question 7.5.2 Based on this new information, which strategy do you recommend?

A) Colonoscopy now.

B) Colonoscopy in 5 years.

C) Yearly tests for fecal occult blood.

D) Yearly tests for fecal occult blood and colonoscopy in 7 years.

E) Colonoscopy in 7 years.

Answer 7.5.2 The correct answer is "A." Adenomatous polyps are considered precancerous. Recommended follow-up of an adenomatous polyp is by colonoscopy every 3 to 5 years. So, he did not truly have a "negative" colonoscopy 3 years ago. Plus, we are not doing the colonoscopy in this case for screening purposes; it is diagnostic. We may find another source of his bleeding. If his previous colonoscopy was completely normal (no adenomatous polyps), you could argue for stopping the aspirin and NSAIDs and following up with serial fecal occult blood tests (FOBTs). In this alternative scenario, persistently positive guaiac tests would lead to colonoscopy as well.

You refer the patient for a colonoscopy. The report from the endoscopist shows one small tubular adenomatous polyp in the sigmoid colon that was completely removed. The patient wants to know when he needs another colonoscopy.

Question 7.5.3 Your answer is:

A) In 3 months.

B) In 1 year.

C) In 5 years.

D) In 10 years.

E) Any of the above is an equally valid recommendation.

Answer 7.5.3 The correct answer is "C." The current surveillance guidelines recommend the following:

1. No polyps or only rectal hyperplastic polyps, repeat in 10 years.

2. 1 to 2 tubular adenomas less than 1 cm in size with only low-grade dysplasia should have repeat colonoscopy in 5 years.

3. 3 to 10 tubular adenomas, or villous features or high-grade dysplasia should have surveillance in 3 years.

4. Patients with >10 adenomas should be screened more frequently and familial colon cancer syndromes should be considered.

5. If a large sessile polyp is removed in piecemeal fashion, then a repeat examination in 3 months is appropriate to assure complete removal.

6. If prep is not good, repeat colonoscopy at earliest convenience is indicated.

Question 7.5.4 Patients presenting with hereditary nonpolyposis colorectal cancer (HNPCC), or "Lynch syndrome," are more likely than patients with sporadic colon cancer to have which of the following findings?

A) Left-sided colon cancers.

B) Late age onset of colon cancer.

C) Multiple colon cancers diagnosed simultaneously.

D) An unusual desire to visit Lynchburg, Tennessee, and a dedication to all things Jack Daniels.

Answer 7.5.4 The correct answer is "C." Patients with HNPCC (Lynch syndrome) are at increased risk of developing colon cancer. About 5% of colon cancers occur in patients with Lynch syndrome. Transformation from an adenoma to cancer is faster in patients with Lynch syndrome. In addition, many of the neoplasms are located in the right colon, so "A" is incorrect. Compared to sporadic colon cancer patients, those with Lynch syndrome are younger at the time of diagnosis, more frequently present with multiple colon tumors, and are more likely to have extracolonic tumors—especially endometrial cancer. This is a genetic disorder, and the occurrence of colorectal and/or endometrial cancer in three relatives before the age of 50 should suggest HNPCC. The current recommendation is to perform surveillance colonoscopies at least every 3 years in these patients.

Objectives: Did you learn to…

• Describe the limitations of FOBT?

• Choose the appropriate tests and screening and surveillance intervals for colorectal neoplasias?

• Learn how family and personal history of colorectal neoplasia affects screening and surveillance strategy?

A 28-year-old graduate student comes to your office complaining of diarrhea. About 6 months ago, she noted a sudden onset of loose stools. While she initially attributed these symptoms to "stomach flu," her problem has persisted. She currently has about four to six loose bowel movements per day with nighttime defecations. She has not seen blood in her stool. In addition, she complains of cramps located in the left and occasionally right lower abdomen. The cramps are made worse with food intake and often are associated with a need to defecate. She has lost about 8 kg unintentionally within the last 3 to 4 months. She denies any travel or antibiotic use. On physical examination, you notice some tenderness in the right lower quadrant. You see a painless anal fissure in the anterior commissure, and by the appearance, you judge that the fissure is probably chronic in nature.

Question 7.6.1 What do you recommend as the next step in the evaluation and management of this patient?

A) Loperamide on a scheduled basis.

B) Referral to a holistic clinic for a coffee colonic cleansing regimen (using fair trade, shade grown organic coffee only, of course).

C) Check titers of atypical antineutrophil cytoplasmic antibodies (ANCA).

D) Colonoscopy.

E) Botulinum toxin injection into the area of the anal fissure.

Answer 7.6.1 The correct answer is "D." The patient's history and physical findings with a painless, anteriorly located anal fissure and diarrhea are consistent with Crohn disease. The best next step in her evaluation is colonoscopy with inspection of the terminal ileum. You may want to do some stool testing before colonoscopy; testing for Giardia, C. difficile toxin, and other pathogens would be reasonable. But of the choices presented, colonoscopy is the best option. "A" is inappropriate since this is long-standing with weight loss; symptomatic control is fine but we need to figure out what is going on with this patient. "B" is incorrect. She has diarrhea … her colon is already clean. "C," serologic testing, is a reasonable choice but not the best. Here is why: Crohn disease is associated with antibodies against saccharomyces (ASCA), while ulcerative colitis (UC) patients are more often positive for ANCA. However, the sensitivity of these tests is only about 60%. Moreover, there is about a 20% overlap (e.g., ANCA positive in Crohn disease), raising further questions about the overall usefulness of these tests. ASCA can also be positive in celiac disease. "E" is also incorrect. Fissures are one of the anal manifestations of Crohn disease and should be approached by treating the underlying disease rather than using surgical techniques, botulinum injection, etc. Botulinum injections, nitroglycerin ointment, and nifedipine have all been used for anal fissures with success, but we need to diagnose this patient and address the underlying disease.

Question 7.6.2 Which of the following is true regarding the pathophysiology and natural history of Crohn disease?

A) Crohn disease is a genetic disorder, transmitted in an autosomal-dominant fashion.

B) Crohn disease is a relapsing/remitting disease, and 30% of patients will improve spontaneously.

C) Patients with Crohn disease rarely progress to disease requiring surgery.

D) Maintenance therapy with glucocorticoids will reduce the rate of recurrence of Crohn disease.

E) GI fistulae and abscesses are rare complications of Crohn disease.

Answer 7.6.2 The correct answer is "B." Crohn disease and UC are both relapsing/remitting diseases. Up to 30% of initial exacerbations of Crohn disease will remit without any intervention. While there is a genetic component to inflammatory bowel disease (IBD) (up to a 100-fold increase in risk among first-degree relatives with IBD), no single, autosomal-dominant gene has been identified. "C" is incorrect because half or more of patients with Crohn disease will ultimately require some sort of surgery. "D" is incorrect. Unfortunately, chronic glucocorticoid administration does not lower the rate of relapse. There are many complications of IBD (see next question), and GI abscesses and fistulae occur with a relatively high frequency (20–40%) in Crohn disease.

Question 7.6.3 Extraintestinal features of IBD include all of the following EXCEPT:

A) Alopecia.

B) Arthritis.

C) Sclerosing cholangitis.

D) Uveitis.

E) Cholelithiasis.

Answer 7.6.3 The correct answer is "A." Alopecia is not an extraintestinal manifestation of IBD. Arthritis related to IBD (enteropathic arthritis) is fairly common and usually migratory in nature, involving the large joints. Spondyloarthropathy may also be seen. Sclerosing cholangitis and autoimmune hepatitis can occur and may be fatal. Eye disease may include uveitis and episcleritis. Importantly, the main treatment of extraintestinal manifestations is to treat the IBD. IBD spondyloarthropathy and pyoderma gangrenosum are important exceptions, as these do not always improve with the treatment of the underlying IBD.

Returning to your patient, you next see her in the emergency department, where she presents with fever, abdominal pain, and bloody diarrhea. She is tachycardic and slightly hypotensive but alert and oriented. You suspect a relapse of her Crohn disease.

Question 7.6.4 All of the following are important aspects of her management at this time EXCEPT:

A) Surgical consultation.

B) IV access and fluid administration.

C) Glucocorticoids.

D) Thalidomide.

E) Metronidazole.

Answer 7.6.4 The correct answer is "D." Thalidomide has been used as chronic therapy for IBD, but it is not indicated in the acute setting. The patient should be stabilized, and this includes IV access and fluid resuscitation. An exacerbation (or relapse) of IBD can be treated with glucocorticoids in the acute setting, and antibiotics are often helpful. It appears that metronidazole has beneficial effects that are not solely due to its antimicrobial properties. In this patient, who may have an abscess or obstruction, further evaluation (e.g., labs and abdominal CT) and surgical consultation are necessary.

Question 7.6.5 Which of the following is indicated in the long-term treatment of IBD?

A) Azathioprine.

B) Methotrexate.

C) 5-ASA moieties.

D) Loperamide.

E) All of the above.

Answer 7.6.5 The correct answer is "E." All the options are indicated for the treatment of IBD. Of special note are the 5-ASA drugs (e.g., Pentasa and Asacol). These have fewer side effects than sulfasalazine and are the initial drugs of choice for maintenance, once control of symptoms has been obtained. Systemic steroids (e.g., prednisone) are useful acutely to induce remission but should be tapered and stopped as soon as possible. Steroids are often indicated long-term for Crohn disease limited to the stomach and duodenum.

Additional drugs for the treatment of IBD include cyclosporine, 6-mercaptopurine (6-MP), infliximab, certolizumab, and adalimumab (just say Humira^®, it's much easier), among others. Antidiarrheal drugs such as loperamide are useful to control symptoms. However, be sure to avoid antidiarrheal drugs in patients who may have impending toxic megacolon. Probiotics and lactose avoidance may also be useful (although there is less evidence for these).

After discussions with your patient about ongoing therapy at discharge, you find that cost is a major consideration for her. Therefore, you consider discharging her on sulfasalazine.

Question 7.6.6 Which of the following is an absolute contraindication to the use of sulfasalazine?

A) Sulfa allergy.

B) Aspirin allergy.

C) Anemia.

D) A and B.

E) B and C.

Answer 7.6.6 The correct answer is "D." Sulfasalazine contains both sulfa and salicylate moieties and thus is contraindicated in patients with sulfa or aspirin allergy.

Question 7.6.7 Which of the following is LEAST likely to be a complication of anti-tumor necrosis factor (TNF)-alpha antibody therapy (e.g., infliximab [Remicade®]) for IBD?

A) Sepsis.

B) Headache.

C) Abdominal pain.

D) Diarrhea.

E) Anemia.

Answer 7.6.7 The correct answer is "E." Anemia will generally improve with the treatment of IBD. Anemia in IBD is often due to a combination of iron deficiency and anemia of chronic disease, but IBD can cause an autoimmune hemolytic anemia as well. All of the rest are common complications of infliximab. Infection deserves special mention. Patients on anti-TNF drugs are more prone to sepsis. In fact, ongoing infection is an absolute contraindication to the use of anti-TNF drugs. Take any complaints attributable to infection (e.g., fever) very seriously in patients on anti-TNF drugs (not that you don't take them seriously in all patients … just more seriously in these). Tuberculosis and active hepatitis B are contraindications to the use of anti-TNF drugs.

Question 7.6.8 All of the following characteristics differentiate ulcerative colitis (UC) from Crohn disease EXCEPT:

A) The risk of colon cancer is greater in UC than in Crohn disease.

B) Histologically, UC appears as transmural disease, whereas Crohn disease involves only the mucosal and submucosal layers.

C) UC almost always involves the rectum, whereas Crohn disease may or may not.

D) In UC, the diseased segments are continuous, while "skip" areas of healthy bowel are seen in Crohn disease.

Answer 7.6.8 The correct answer is "B." Histologically, UC involves only the mucosa and submucosal tissue, while Crohn disease is transmural. All of the other statements are true. UC involves the rectum in 95% of cases and advances proximally.

Objectives: Did you learn to…

• Diagnose IBD?

• Differentiate Crohn disease from UC?

• Manage a patient with IBD?

• Recognize extraintestinal manifestations and complications of IBD?

A 52-year-old woman complains of abdominal pain, bloating, and constipation. Her symptoms started about 5 years ago and became more bothersome within the last 6 months. She describes a dull pain in the left lower abdomen. This pain is alleviated by passing gas or having a bowel movement. The pain is generally related to eating, and she has had intermittent diarrhea and constipation with constipation predominating. Two years ago, she underwent a screening colonoscopy, which was completely normal. Her review of systems is notable for a weight gain of about 5 lb within the last 3 years. She is taking only a multivitamin daily. Her physical examination is normal.

Question 7.7.1 Which is the best next step?

A) Defecogram.

B) Barium enema.

C) Anorectal manometry.

D) TSH level.

E) Colonoscopy.

Answer 7.7.1 The correct answer is "D." The patient's presentation with pain and constipation meets criteria for constipation-predominant irritable bowel syndrome (IBS) (see Table 7-3). Of note, irritable bowel is not an uncommon complication of GI infections including E. coli, Campylobacter, viral infections, and Giardia (Gut. 2010;59:605). There is also a relationship between anxiety and the presence of irritable bowel. This patient underwent colonoscopy for screening 2 years prior to presentation, so further evaluation for colon cancer ("B" and "E") can be delayed unless there is another indication. Secondary causes of constipation, such as hypothyroidism, medication side effects or hypercalcemia, should be ruled out. Therefore, a TSH level should be obtained prior to deciding on additional diagnostic or therapeutic steps. At this point in time, anorectal manometry and defecogram are unnecessarily invasive procedures, and neither will help you to determine if this patient has IBS.

The patient is euthyroid. Hypercalcemia and other electrolyte abnormalities have been ruled out. Since she does not use medications other than the multivitamin, you decide to initiate the treatment of IBS. Based on available evidence, you suggest using fiber supplements such as psyllium.

Question 7.7.2 What do you tell your patient to expect?

A) Complete resolution of her symptoms.

B) Increase in stool frequency and stool volume with less need for straining.

C) Not much. Fiber supplementation doesn't work very well for IBS.

D) Decrease in abdominal pain and bloating.

E) Enlightenment and absolute bliss.

Answer 7.7.2 The correct (and unfortunate) answer is "C." Although it has been one of the mainstays of irritable bowel therapy, the efficacy of fiber for IBS has always been in question. A meta-analysis (Am J Gastroenterol. 2014;109:1367) suggests a NNT of 7 with psyllium to benefit one patient. Perhaps surprisingly, there are only 14 randomized trials of only 906 patients. While bowel habits can be successfully changed with bulking agents for constipation or loperamide for diarrhea-predominant IBS, pain is generally not affected by these measures. In fact, increased fiber intake may transiently worsen some symptoms due to fermentation and generation of gas, potentially resulting in flatulence or bloating. "E" requires special mention. Bliss and enlightenment can only occur with proper colon purging procedures provided at a very expensive resort!

Question 7.7.3 Which of the following has the best record in treating IBS?

A) Eliminating FODMAPs from the diet.

B) Probiotics.

C) Rifamixin.

D) St. John's wort.

E) Eliminating the use of GOOGLEMAPS.

Answer 7.7.3 The correct answer is "A." First, you need to know what FODMAPs are. FODMAP stands for "Fermentable, Oligo-, Di-, Monosaccharides, And Polyols." These are poorly absorbed carbohydrates that can cause fermentation and gas in the colon. Some FODMAPs include fructose, lactose, fructans (from wheat … think this is why everyone believes they have gluten intolerance?), and others. Eliminating FODMAPs from the diet seems to have the best NNT of any of the irritable bowel treatments. Of the others, probiotics have a NNT of 7 to 11 (Am J Gastroenterol. 2014;109:1547), rifaximin (at $1,200/month) has a NNT of 11 and a marginal benefit at best (N Engl J Med. 2011;364:22–32), and St. John's wort actually increases the symptoms of IBS and should be avoided. Use of GOOGLEMAPS has not been shown to have any effect on IBS symptoms aside from perhaps decreasing anxiety and symptoms related to it.

Objectives: Did you learn to…

• Diagnose and manage IBS?

• The role of FODMAPs in irritable bowel?

• Realize that both you and your patient will be frustrated with the treatments for IBS?

A 32-year-old male complains about fatigue and episodic abdominal pain. His pain is located in the periumbilical region and the left lower quadrant. It is cramp-like in nature and is associated with flatulence and diarrhea. Passing gas alleviates his symptoms. He notes that milk and other dairy products worsen his symptoms. His weight has remained stable. His prior medical history, family and social history, and physical examination are unremarkable. Laboratory tests reveal hemoglobin of 11.5 g/dL and a normal glucose and TSH.

Question 7.8.1 What is the most appropriate next step in your evaluation?

A) Lactose breath test.

B) Dietary trial of strict lactose avoidance.

C) Enteroclysis.

D) Colonoscopy.

E) Tissue transglutaminase antibody titer.

Answer 7.8.1 The correct answer is "B." The patient's symptoms are consistent with lactose intolerance. He may have malabsorption secondary to lactose intolerance, which may be partially responsible for his anemia. If his symptoms resolve with a trial of a lactose-free diet, you have your diagnosis. Follow-up should include re-checking his CBC and perhaps other studies, such as stool for occult blood. If these symptoms are new, he could have a secondary form of lactase deficiency (e.g., Crohn disease or bacterial overgrowth) or a coincidental problem with the absorption of this carbohydrate. Colon cancer is not common at this age but endoscopy should also be considered if anemia does not resolve.

The patient tries a lactose-free diet, but this is of no benefit and his abdominal cramping and diarrhea continue. At this point, you are considering additional diagnoses.

Question 7.8.2 Which of the following is LEAST likely in this patient?

A) Bacterial overgrowth syndrome.

B) Gluten-sensitive enteropathy.

C) Giardia lamblia.

D) C. difficile.

E) Whipple disease.

Answer 7.8.2 The correct answer is "E." It is unlikely that this patient has Whipple disease, which is a result of an infection with Tropheryma whippelii. Whipple disease is associated with nondeforming arthritis, weight loss, fever, diarrhea, etc. All of the others are possibilities in this patient. "A," bacterial overgrowth syndrome, presents with bloating, diarrhea, dyspepsia, and possible malabsorption and weight loss. It can occur as a result of bowel dysmotility, bowel redundancy or diverticula, chronic pancreatitis, etc. "B," gluten-sensitive enteropathy (nontropical or celiac sprue), presents with symptoms similar to those in our patient including malabsorption. "C," Giardia infection, can be chronic and presents with gas, diarrhea, and occasionally constipation. Finally, C. difficile infection (pseudomembranous colitis) can also be chronic in nature with chronic diarrhea and blood loss.

You continue to work up this patient's diarrhea with stool cultures, stool for C. difficile toxin, direct immunofluorescence analysis for Giardia and Cryptosporidium, and three stools for ova and parasites. All of the studies are negative. You now turn your attention to possible bacterial overgrowth syndrome.

Question 7.8.3 The best test(s) for bacterial overgrowth syndrome is (are):

A) Quantitative stool culture.

B) Stool leukocytes.

C) 72-hour fecal fat.

D) [14-C] d-xylose breath test.

E) B and D.

Answer 7.8.3 The correct answer is "D." The d-xylose breath test takes advantage of the fact that the bacteria responsible for bacterial overgrowth syndrome (Gram-negative aerobes) catabolize d-xylose. The breath test measures radioactive CO₂ that is formed as a result of bacterial breakdown of radioactive d-xylose. The glucose breath test, in which glucose is administered to the patient and breath hydrogen is measured, is also helpful and commonly used. However, it is less sensitive and specific than the d-xylose test and has a 30% to 40% false-negative rate. Work up of bacterial overgrowth syndrome should also include an upper GI endoscopy and possible small bowel biopsy. GI hypomotility, small bowel dilatation, or small bowel diverticula support the diagnosis of bacterial overgrowth syndrome. Of the others, "B," stool leukocytes are pretty useless in general and do not have a good correlation with infectious causes of diarrhea (high false-positive and false-negative rates). "C," fecal fat collection, is useful in documenting fat malabsorption syndromes, including those secondary to severe pancreatic insufficiency (e.g., cystic fibrosis with >90% pancreatic dysfunction) and short bowel syndrome.

This patient's d-xylose test is negative and you consider the possibility of gluten-sensitive enteropathy (celiac disease).

Question 7.8.4 Of the following, the one BEST test for the diagnosis of gluten-sensitive enteropathy is:

A) Antiendomysial antibodies.

B) Tissue transglutaminase antibodies.

C) Antigliadin antibodies.

D) Radiolabeled wheat flour absorption test.

E) All of the above are equally accurate for detecting celiac disease.

Answer 7.8.4 The correct answer is "B." Tissue transglutaminase antibodies are sensitive and specific for severe gluten-sensitive enteropathy but may be falsely negative in mild-to-moderate cases. Antiendomysial IgA antibodies are less sensitive than tissue transglutaminase antibodies for gluten-sensitive enteropathy but very specific for gluten-sensitive enteropathy. Antigliadin antibodies are less sensitive and specific and have fallen out of favor. The definitive test ("gold standard") is a small bowel biopsy and should be considered if your clinical suspicion is high and the patient has negative antibodies. Patients with positive antibodies should also have an endoscopy; the diagnosis should be confirmed by endoscopy and biopsy before committing the patient to a gluten-free diet for life.

The results of his tissue transglutaminase test are positive. You educate him about gluten-sensitive enteropathy (celiac disease) and have an endoscopy performed. A small bowel biopsy demonstrates blunted villi with a significant increase in intraepithelial lymphocytes, consistent with gluten-sensitive enteropathy. With a gluten-free diet, the patient experiences a significant increase in his energy level. Two years later he comes for a routine visit. He has gradually reintroduced some wheat products into his diet and tolerates this very well.

Question 7.8.5 What do you recommend?

A) Resume gluten-free diet.

B) Continue dietary challenge and repeat examination in 6 months.

C) Repeat small bowel biopsy.

D) Check tissue transglutaminase antibody titer.

E) Avoid wheat, but try barley or rye products.

Answer 7.8.5 The correct answer is "A." While there is no good data on the benefit of a long-term gluten-free diet in patients who can tolerate small amounts of gluten, several factors argue for continuing a gluten-free diet. The first is that many patients will have subclinical nutrient deficiencies if they reintroduce gluten. For this reason, patients with gluten-sensitive enteropathy should be screened for osteoporosis and take a multivitamin. This is especially true in pediatric patients where deficiencies may lead to stunted growth. The second is that there is some data that patients who reintroduce gluten may have increased mortality from GI lymphoma despite the fact that they are tolerating the gluten well (Ann Intern Med. 2013;159:169).

Question 7.8.6 All of the following are gluten-free grains EXCEPT:

A) Oats.

B) Corn.

C) Sticky rice.

D) Rice.

E) Millet.

Answer 7.8.6 The correct answer is "C." Sticky rice is also known as "glutinous rice" and contains gluten. The rest are gluten-free. Other gluten-free grains/starches include buckwheat, flax, quinoa, and tapioca.

Objectives: Did you learn to…

• Evaluate a patient with diarrhea?

• Recognize clinical manifestations of gluten-sensitive enteropathy?

• Manage a patient with gluten-sensitive enteropathy?

A 22-year-old previously healthy male reports a 3-day history of explosive and watery diarrhea. He is having up to 6 bowel movements per day. He recalls eating at a new Mexican restaurant 5 days ago. His head sinks a little low as he recalls drinking a "fish bowl"-sized margarita … or at least he thinks he remembers drinking it! He denies fever, blood in his stool, or recent travel. Multiple people ate the same food but he is the only one who is sick. His vital signs are normal (including supine and standing blood pressures), and the remainder of the physical examination is remarkable only for mild, diffuse abdominal tenderness.

Question 7.9.1 What is the most likely diagnosis?

A) Celiac sprue.

B) Viral gastroenteritis.

C) Lactose intolerance.

D) Small bowel bacterial overgrowth.

E) C. difficile colitis.

Answer 7.9.1 The correct answer is "B." This is always a dilemma. It can be difficult to differentiate acute gastroenteritis from food poisoning. What makes gastroenteritis more likely is that there is no clustering of cases among people who ate the same food. With only 3 days of symptoms, it would be premature to diagnose "A," "C," or "D." Without recent antibiotic exposure, "E" would be unlikely in an otherwise healthy male. See Table 7-4 for a differential diagnosis for diarrhea.

Question 7.9.2 What is the MOST appropriate next step in the care of this patient at this point?

A) Order a CBC.

B) Order electrolytes.

C) Order stool examination for ova and parasites.

D) Recommend oral hydration and antidiarrheals as needed.

E) Order an abdominal film.

Answer 7.9.2 The correct answer is "D." No workup is needed for a mild case of acute diarrhea, since such cases are usually self-limited. Generally, the history and physical examination should provide the diagnosis and indicate need for further workup. Further workup and treatment are indicated if the patient has severe or bloody diarrhea, dehydration, systemic toxicity, or severe pain.

You treat the patient with oral rehydration and prochlorperazine for some nausea and he does well. He returns to see you a few weeks later after a trip to Mexico. He liked that fish bowl-sized margarita so much that he decided to go for an original. He has diarrhea that began a couple of days after his arrival in Cancun and has now been present for 5 days. He has had frequent, watery diarrhea with nausea but no vomiting. He has noticed no blood in the stool. He was very careful to avoid salads and water but did have some ice in a soft drink and his margarita was "on the rocks."

Question 7.9.3 The most likely organism causing illness in this patient is:

A) Salmonella.

B) Shigella.

C) Enterotoxigenic E. coli.

D) Enterohemorrhagic E. coli.

E) Campylobacter.

Answer 7.9.3 The correct answer is "C." Enterotoxigenic E. coli is the most common cause of traveler diarrhea in patients traveling to Mexico. Enterohemorrhagic E. coli is less likely and should be associated with bloody diarrhea. The others are much less likely to be causes of traveler diarrhea.

Question 7.9.4 Which of the following is/are appropriate for the treatment of this patient's traveler diarrhea (remember, he has no vomiting)?

A) Oral rehydration.

B) Antidiarrheals.

C) Eat any food (e.g., no need for a bland diet with slow advancement).

D) All of the above.

E) None of the above.

Answer 7.9.4 The correct answer is "D." This patient has nonbloody diarrhea and no systemic signs, so it should be safe to treat him with antidiarrheal agents (e.g., loperamide) and avoid antibiotics. Oral rehydration is the rule unless a patient is too nauseated or has some other reason that he cannot take adequate fluids by mouth. Patients (including children) should eat anything they can tolerate. The concept of "gut rest" is a misnomer and actually leads to increased bowel permeability and more persistent diarrhea. Lactose deserves special mention. The American Academy of Pediatrics has changed their recommendations about lactose in diarrhea. They recommend withholding lactose only in children less than 3 months of age. This seems to be the group in which transient lactase deficiency occurs.

Objectives: Did you learn to…

• Evaluate a patient with acute diarrhea?

• Treat acute diarrhea?

• Recognize different bacterial causes of diarrhea?

A 49-year-old man comes to your office, requesting testing for hepatitis C. He recently attended his 25-year college reunion where an old friend he had "partied" with during experimentation with injectable drugs related that he has cirrhosis due to hepatitis C. The patient is otherwise healthy and denies any symptoms except for occasional fatigue after a long day at work. Physical examination of the patient is unremarkable. There are no stigmata of chronic liver disease.

Question 7.10.1 Which of the following is the most appropriate course of action?

A) Check a quantitative Hepatitis C virus (HCV) PCR ("viral load").

B) Order a recombinant immunoblot assay (RIBA).

C) Order HCV antibody test (enzyme immunoassay).

D) Order a qualitative HCV PCR.

E) Order ALT and AST.

Answer 7.10.1 The correct answer is "C." The sensitivity and specificity of the present-day HCV antibody test are excellent; thus, this is the best test to perform in this situation. Rarely, patients with immunologic impairment, such as HIV infection, have HCV viremia without detectable antibody, but this would not be a concern in this otherwise healthy patient. Quantitative HCV PCR is not a reliable means for diagnosing HCV infection because currently used methods are insensitive at low levels of viremia; thus, infection cannot be ruled out if the level of HCV viremia is below the lower limit of detection of the test. RIBA is an old test that is no longer used. Qualitative HCV PCR is the most sensitive test for the presence of HCV RNA, with a limit of detection that is lower than that of quantitative PCR. It is useful to establish the presence of viremia, but is more expensive than antibody testing and thus not a first-line test. Many patients with chronic HCV infection have normal liver enzymes and can still have progressive disease; therefore, in a high-risk patient, ALT and AST are not appropriate for screening for HCV.

The patient returns several weeks later to discuss his test results. His HCV antibody test is positive. A liver panel obtained that day shows an ALT of 48 IU/L (normal range, 0–20) and an AST of 39 IU/L (0–31). His albumin and total bilirubin are within normal limits. He is extremely anxious about his liver.

Question 7.10.2 To most accurately assess the degree of liver disease, your next step is to:

A) Obtain a liver–spleen scan to assess for evidence of cirrhosis.

B) Reassure the patient that his mild liver test abnormalities rule out cirrhosis.

C) Order a right upper quadrant ultrasound with Doppler to assess for evidence of cirrhosis.

D) Order elastography for evidence of cirrhosis.

E) Obtain an abdominal CT to assess for evidence of cirrhosis.

Answer 7.10.2 The correct answer is "D." Having established that the patient has hepatitis C with elevated liver enzymes, the next step is to determine the severity of his liver disease. Although his liver function tests are reassuring, this does not exclude the possibility of advanced fibrosis or even well-compensated cirrhosis. While biopsy has been the definitive test for liver fibrosis in the past (and you would not be wrong to order a biopsy if it were an option in this question), ultrasound elastography, a noninvasive technique of determining liver fibrosis, is being used more and more. The idea is that a fibrotic liver is a stiff liver. Don't worry about the details; just know that elastography (for example FibroScan) is a noninvasive and accurate method for determining the degree of hepatic fibrosis. The "F" score, discussed below, should allow you do make decisions about your hepatitis C patients. You would not be incorrect to order ultrasound imaging as well.

After a few phone calls, you find that elastography is not available anywhere nearby. The patient agrees to a liver biopsy to diagnosis cirrhosis and you make the referral. He is still very concerned about his situation and asks what you think the chances are that he already has cirrhosis.

Question 7.10.3 Regarding the development of progressive liver disease in hepatitis C, all of the following are true EXCEPT:

A) Approximately 20% of patients with chronic HCV infection will develop serious liver disease.

B) Heavy alcohol use is a risk factor for development of serious liver disease.

C) Acquisition of HCV infection after the age of 40 is associated with increased risk of developing serious liver disease.

D) HCV genotype affects the probability of developing end-stage liver disease.

E) Males are more likely than females to develop serious liver disease.

Answer 7.10.3 The correct answer is "D." While only a minority of persons infected with HCV develop serious liver disease (20%), the likelihood of progression is difficult to predict in an individual patient. Nonetheless, male gender, heavy alcohol use, and acquisition of HCV infection after the age of 40 are associated with increased risk of progressive liver disease, while genotype is not. In addition, Japanese ancestry, smoking (both cigarettes and marijuana), and acquiring hepatitis C from a blood transfusion, have been associated with an increased risk of progression. The genotype of the hepatitis C certainly makes a difference when it comes to treatment but not with progression to cirrhosis.

The patient is concerned that he may transmit the virus to his wife or children. They are tested and are found to be negative for HCV antibody. He is relieved but asks for advice to prevent infecting them.

Question 7.10.4 You advise all of the following EXCEPT:

A) No change in sexual practices is recommended for couples in a long-term monogamous relationship in which one partner is HCV+ and the other HCV–.

B) The use of condoms is recommended for couples in a long-term monogamous relationship in which one partner is HCV+ and the other HCV–.

C) Hepatitis C is not spread by hugging, sneezing, or sharing a drinking glass.

D) Household members of persons infected with HCV should not share items that might be contaminated with small amounts of blood such as razors or nail clippers.

E) Parenteral exposure to infected blood is a major route of transmission of HCV.

Answer 7.10.4 The correct answer is "B." HCV is spread by parenteral contact with infected blood. In contrast to hepatitis B, sexual transmission of HCV is inefficient and appears to be a minor route of spread. In addition, the efficacy of latex condoms in preventing disease is not known. The NIH and the US Public Health Service do not recommend condom use for patients in a stable, long-term, and monogamous relationship. That said, using condoms will likely reduce an already low risk even further.

The patient's liver biopsy shows mild-to-moderate inflammatory activity and portal and periportal fibrosis (stage 2). He is relieved to find out that he does not have cirrhosis, but remains very concerned about his hepatitis and wants to do everything possible to "get rid of" the hepatitis C. He asks about the treatment of his HCV.

Question 7.10.5 Which of the following is NOT an indication for the treatment of hepatitis C?

A) Elastography showing cirrhosis.

B) APRI of 0.25 (pre-cirrhosis).

C) Liver biopsy showing bridging fibrosis.

D) Ability to pay for the treatment.

Answer 7.10.5 The correct answer (and not an indication for hepatitis C treatment) is "B." The cutoff APRI for the treatment is 0.5 to 0.7, representing F2 fibrosis. F2 fibrosis diagnosed by any method, including biopsy or elastography (e.g., FibroSure), is an indication for the treatment. You may be wondering about "D." Starting in 2014, a wave of new and more tolerable hepatitis C treatments started to become commercially available. However, the cost of these new drugs—at least, in the United States—is immorally high, costing up to $100,000 for a complete 12-week treatment. Public and private insurers have been forced into outright rationing. (To become appropriately outraged, read this article: http://www.latimes.com/business/hiltzik/la-fi-hiltzik-20150621-column.html.) If the United States treated all of the approximately 3 million HCV infected persons with the new drugs, it would cost our country about $300 billion. Because of the pharmaceutical companies setting prices differently in different markets, at least one of these new HCV drugs costs about 1% of the U.S. price in Egypt. So … One option is to send your HCV patients to Egypt for the treatment and put them up in a nice hotel—it would be significantly cheaper.

Question 7.10.6 You tell him which of the following?

A) Combination therapy with interferon and ribavirin results in sustained virologic responses (SVR) in 40% to 70% of patients treated.

B) Combination therapy with interferon and ribavirin can cause numerous side effects including cytopenias, flu-like symptoms, worsening of autoimmune conditions, depression, and hemolytic anemia.

C) The HCV genotype is a strong predictor of response to the treatment.

D) Newer treatment regimens including ledipasvir/sofosbuvir are much more effective than the tradition combination of interferon/ribavirin.

E) All of the above.

Answer 7.10.6 The correct answer is "E." Combination therapy with interferon and ribavirin is the traditional treatment of HCV and it is clearly not as effective at achieving a SVR as the newer drugs. The HCV genotype is a major factor determining the likelihood of achieving SVR, although not the likelihood of progression to end-stage liver disease. Genotype 1 is responsive to the newer drugs, such as the combination of ledipasvir/sofosbuvir (Harvoni); an entirely oral regimen with response rates of 93% or better for genotype 1. A second entirely oral treatment is ombitasvir/paritaprevir/ritonavir/dasabuvir (Viekira Pak [U.S.]). However, it must be combined with ribavirin for genotypes 1a and 1b if cirrhosis is present. Stage of fibrosis is also a factor, and patients with stages 3 and 4 (bridging fibrosis and cirrhosis) are less likely to achieve SVR. Higher baseline viral levels also tend to predict poorer response to the treatment. Combination therapy is expensive and is associated with significant toxicities. The major concerns with ribavirin are hemolytic anemia and teratogenicity, while the interferons (standard or the long-acting pegylated forms) have a long list of potential side effects, of which neuropsychiatric problems, such as depression and irritability, are often the most troublesome. Almost no treatment regimen still requires interferon.

OK, now the game changers. Here is a table (Table 7-5) for you to review the new hepatitis C drugs and the genotype treated. This is pretty basic. For a more complete summary, see http://www.hepatitis.va.gov/pdf/treatment-considerations-2015–07.pdf. Side effects of the newer drugs are headache, GI upset, etc., and generally much less problematic than previous generations of hepatitis C treatment. What happened to the protease inhibitors (telaprevir and boceprevir), you ask? They have gone the way of the dodo bird and are no more … too many side effects when used for hepatitis C.

Objectives: Did you learn to…

• Evaluate a patient at risk for hepatitis C?

• Understand the natural history of the disease process in hepatitis C?

• Describe the transmission of hepatitis C?

• Discuss the treatment issues for a patient with hepatitis C?

A 24-year-old female graduate student from China comes to your office complaining of fatigue for the past month. She has also had a poor appetite and has lost about 3 lb over this period. She reports that she was told that she had "hepatitis" when she was about 10 years old but does not recall what type. She is otherwise healthy and takes no medications. She has no history or percutaneous exposures or blood transfusion. Her grandfather died of liver cancer.

Physical examination reveals a thin, tired-appearing woman. The liver edge is palpable 2 cm below the right costal margin and is slightly tender. There is no ascites, splenomegaly, or cutaneous stigmata of chronic liver disease.

Laboratory studies are remarkable for anemia (hemoglobin 9.1 g/dL). Liver tests reveal elevated aminotransferases (ALT 289 IU/L, AST 158 IU/L), albumin 3.2 g/dL, and total bilirubin 1.5 mg/dL (normal 0.2–1.0 mg/dL).

Question 7.11.1 Diagnostic possibilities at this point include:

A) Hepatitis A.

B) Hepatitis B.

C) Hepatitis C.

D) Autoimmune hepatitis.

E) All of the above.

Answer 7.11.1 The correct answer is "E." Constitutional symptoms such as fatigue and anorexia can be seen with any form of acute or chronic liver disease; thus, they are not helpful in establishing a specific diagnosis. The first priority is to rule out infectious hepatitis including hepatitis A, B, and acute hepatitis C. Autoimmune hepatitis deserves consideration, particularly in female patients. While HCV infection is a worldwide problem, HBV infection is endemic in Asia and Africa, and the possibility of chronic hepatitis B also warrants special attention in this patient.

Question 7.11.2 Appropriate laboratory studies at this point include which of the following?

A) Quantitative HCV PCR.

B) Hepatitis B surface antigen (HBsAg).

C) Anti-hepatitis A antibodies (IgG and IgM).

D) B and C.

E) All of the above.

Answer 7.11.2 The correct answer is "D." As discussed previously, the quantitative HCV PCR is not a useful test for diagnosing HCV infection. HCV antibody testing would be a better choice. Both HBsAg and anti-HAV are useful tests in this patient. HBsAg is helpful to assess for HBV infection (acute and chronic) and anti-HAV antibodies will rule out acute hepatitis A infection. A positive total anti-HAV (positive IgG) with a negative IgM would indicate past infection, while a positive IgM would suggest acute HAV infection. Interpreting the HBV antigens (Ag) and antibodies (Ab) can be confusing, and Table 7-6 may help.

The patient's results show a positive HbsAg, indicating ongoing hepatitis B infection. She is immune to hepatitis A and is hepatitis C negative.

After being out of contact for 4 months, she returns for a follow-up visit. She tells you that she took an herbal medicine her mother sent from China and has been feeling much better recently. Her HBsAg remains positive, but her liver enzymes, albumin, and total bilirubin are now completely normal.

Question 7.11.3 Appropriate actions at this time include:

A) Treatment with interferon-alpha 5 million units daily for 16 weeks.

B) Order hepatitis Be antigen, anti-HBe, and HBV DNA level.

C) Begin periodic screening for hepatocellular carcinoma (HCC) with ultrasound and alpha-fetoprotein (AFP).

D) A and C.

E) B and C.