Disease-a-Month 60 (2014) 306–313
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Clinical pearls in gastroenterology 2012 Conor Loftus, MD, Scott C. Litin, MD, John B. Bundrick, MD
Case 1 A 70-year-old male presents for evaluation of difficulty with swallowing solid food. He does not report problems swallowing liquids. The difficulty with swallowing has been present for approximately 3 years. Within the past 3 months, he also reports two episodes where he felt food lodged in his chest and with some difficulty was eventually able to expel the food. He does not have painful swallowing. He has not lost weight. He has a history of hiatal hernia with longstanding gastroesophageal reflux controlled with once daily PPI therapy. An upper endoscopy was performed revealing a somewhat tortuous esophagus and stomach but was otherwise grossly normal. Biopsies of the esophagus were not performed. Question What would you recommend next? A. B. C. D. E.
Esophageal manometry Endoscopic ultrasound of gastroesophageal junction CT scan of chest Repeat EGD with esophageal biopsies Barium esophagram
Discussion Gastric volvulus is an under-recognized complication of hiatal hernia. Patients with a paraesophageal hiatal hernia and those with intrathoracic stomach are at highest risk for the development of gastric volvulus. Acute gastric volvulus typically presents with sudden severe pain in the upper abdomen or lower chest, often associated with persistent unproductive retching, and the presentation may be mistaken for acute myocardial infarction. Chronic gastric volvulus is typically associated with milder non-specific symptoms such as dysphagia, epigastric discomfort, and fullness after eating. In this vignette, the clinical presentation and endoscopic findings are
http://dx.doi.org/10.1016/j.disamonth.2014.04.007 0011-5029/& 2014 Mosby, Inc. All rights reserved.
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suspicious for chronic gastric volvulus. This is best evaluated by performing a barium esophagram. Esophageal biopsies are unlikely to be helpful as eosinophilic esophagitis would be uncommon in this age group. Endoscopic ultrasound of gastroesophageal junction is helpful when malignancy is suspected but not confirmed with regular endoscopy (pseudoachalasia). Clinical pearl Gastric volvulus is an under-recognized complication of hiatal hernia. Patients with a paraesophageal hiatal hernia or with intrathoracic stomach are at highest risk. Gastric volvulus is best confirmed with barium esophagram. References 1. Rashid F, et al. A review article on gastric volvulus: a challenge to diagnosis management. Int J Surg. 2010;8(1):18–24.
Case 2 A 60-year-old female presents for further evaluation of chronic watery diarrhea. She had first presented 3 months prior, reporting an 8-week history of 8–10 watery bowel movements daily. Initial evaluation at that time had included laboratory and stool studies, which were unremarkable, prompting a colonoscopy with random colon biopsies. The colon was endoscopically normal but biopsies revealed evidence of lymphocytic colitis. Despite treatment with bismuth subsalicylate and budesonide (9 mg daily for 6 weeks), there has been no improvement in the patient’s diarrhea. The patient has also had shoulder pain and has been taking ibuprofen 400 mg three times daily. Additional evaluation is pursued with repeat stool studies and tissue transglutaminase antibody without abnormality being found. Question What would you recommend next? A. B. C. D. E.
Increase dose of budesonide to 12 mg daily Mesalamine 4.8 g daily Prednisone 40 mg daily Discontinue ibuprofen Citrucel two tablespoons daily
Discussion This patient with microscopic colitis has not responded to initial therapy with bismuth subsalicylate and subsequently budesonide. In patients with microscopic colitis, not responding to standard therapy (assuming patient compliance), the first step is to exclude co-existing celiac disease in light of the 5% overlap between these diagnoses. In this vignette, celiac serology (sensitivity approximately 95%) is negative, and therefore an overlap syndrome is unlikely. Numerous medications have been associated with exacerbating microscopic colitis especially NSAIDs, aspirin, proton pump inhibitors, selective serotonin reuptake inhibitors, and statins. The best evidence for an association between medication use and microscopic colitis exists for NSAIDs. NSAIDs should be discontinued in patients diagnosed with microscopic colitis.
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Clinical pearl NSAIDs may exacerbate microscopic colitis and should be discontinued in patients with this diagnosis. There is also an association between microscopic colitis and celiac disease. References 1. Beaugerie L, Pardi DS. Review article: drug-induced microscopic colitis—proposal for a scoring system and review of the literature. Aliment Pharmacol Ther. 2005;22:277–284.
Case 3 A 50-year-old male presents for evaluation of hematochezia and intermittent abdominal pain. He has had four episodes of hematochezia within the past 3 months. With the most recent episode, he was hospitalized, received blood transfusion, and underwent colonoscopy as well as upper endoscopy. On colonoscopy, blood appeared to be emanating from the ileocecal valve suggesting more proximal GI bleeding. Upper endoscopy to the level of ligament of Treitz was unremarkable. The bleeding ceased and no further investigations were performed during that hospitalization. The patient has not had bleeding since discharge. He has no significant past medical history. He does not take any medications. Question What would you recommend next? A. B. C. D. E.
Antegrade double-balloon enteroscopy Retrograde double-balloon enteroscopy CT enterography Small bowel capsule endoscopy Meckel’s scan
Discussion In this clinical vignette, the source of bleeding is likely in the small bowel because blood was emanating from the ileocecal valve at colonoscopy and the upper endoscopy was unremarkable. The approach to small bowel bleeding depends on patient characteristics and the volume of blood loss. In middle-aged individuals (as in this case), transfusion requiring blood loss from the small intestine is suggestive of a small bowel vascular tumor such as a gastrointestinal stromal tumor (GIST) or carcinoid. The intermittent abdominal pain experienced by the patient is suggestive of episodic partial small bowel obstruction as could occur with small bowel tumors. Studies have shown that CT enterography is more sensitive than capsule endoscopy for the detection of small bowel tumors. Meckel’s scan would be reasonable to pursue in a younger patient ( o 30 years old) with small bowel bleeding. Doubleballoon enteroscopy now allows for deeper intubation of the small bowel, but this is typically reserved for further diagnostic evaluation or therapeutic intervention following CT enterography and/or capsule endoscopy. Clinical pearl CT enterography is more sensitive than wireless capsule endoscopy for the detection of small bowel tumors.
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References 1. Huprich JE, Alexander JA, et al. Prospective blinded comparison of wireless capsule endoscopy and multiphase CT enterography in obscure gastrointestinal bleeding. Radiology. 2011;260 (3):744–751. 2. Hakim FA, Alexander JA, et al. CT-enterography may identify small bowel Tumors not detected by capsule endoscopy: eight years experience at Mayo Clinic, Rochester. Dig Dis Sci. 2011;56 (10):2914–2919.
Case 4 A 65-year-old female developed diarrhea 2 weeks after completion of antibiotics for a urinary tract infection. Stool testing was positive for Clostridium difficile infection, and the patient was treated with metronidazole 500 mg three times daily for 14 days. The diarrhea resolved during treatment but recurred 5 days after stopping the metronidazole. A 14-day course of metronidazole was repeated with similar outcome. The patient was then treated with a tapering course of vancomycin over 8 weeks. While being treated with vancomycin, the diarrhea again resolved but recurred 10 days after completing the therapy. The patient has insulin-dependent diabetes mellitus, hyperlipidemia, hypertension, and gastroesophageal reflux. Her current medications include insulin, simvastatin, metoprolol, and omeprazole.
Question What would you recommend next? A. B. C. D. E.
Repeat 8-week tapering course of vancomycin Fidaxomicin 200 mg twice daily for 10 days Stool transplantation Discontinue omeprazole Discontinue simvastatin
Discussion Recent studies have suggested that recurrence of Clostridium difficile infection is more common in patients who received proton pump inhibitors concurrent with treatment for C. difficile, when compared to patients who did not receive concurrent proton pump inhibitor therapy. This may in part be explained by the fact that while C. difficile spores are resistant to acid, the vegetative forms are susceptible to acid. In this clinical vignette, the recurrence of C. difficile infection may have been contributed to by concurrent omeprazole use. Fidaxomicin is the first in a new class of narrow-spectrum macrocyclic antibiotics. It has been shown to be as effective as vancomycin in the treatment of C. difficile infection, with fewer side effects and likely a lower C. difficile recurrence rate (use is currently limited by expense). Stool transplantation has been reported as a means for treating refractory C. difficile infection, but as yet is not widely accepted. Clinical pearl Proton pump inhibitor use during the treatment of C. difficile infection may be associated with an increased risk of recurrent C. difficile infection.
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References 1. Linsky A, et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Inren Med. 2010;170(9):772–778. 2. Louie TJ, et al. Fidaxomicin versus Vancomycin for recurrent Clostridium difficile infection. N Engl J Med. 2011;364:422–431.
Case 5 A 40-year-old female presents for evaluation of a 3-month history of diarrhea. She typically has 4–5 loose stools daily. The stools are non-bloody. She does not experience nocturnal diarrhea. The patient states that she has been told in the past that she suffered from irritable bowel syndrome. She has had intermittent mild abdominal pain with bloating for many years. Within the past year, the patient has been trying to lose weight by modifying caloric intake and exercising more frequently. She is very proud of the fact that she does not use table sugar any longer. She has succeeded in losing 20 lb weight. She had an upper respiratory tract infection 6 months prior, for which she received a 10-day course of antibiotics. Her family history is significant for the fact that two paternal cousins experienced diarrhea, which improved upon initiation of a gluten-free diet. The patient has had serologic testing for celiac disease (tissue transglutaminase antibody), which was negative, and has undergone stool testing including a normal Clostridium difficile toxin test (PCR-based test). Question What would you recommend next? A. B. C. D. E.
Repeat stool testing for Clostridium difficile Dietary/ingestion review Upper endoscopy with small bowel biopsy Initiate trial of citrucel Trial of lactose-free diet
Discussion All patients with chronic diarrhea have to be questioned carefully with respect to diet/ ingestions. Common causes of diarrhea that may be discovered through careful history taking include caffeinated beverages, gum chewing, and ingestion of artificial sweeteners. Artificial sweeteners and other sugar substitutes are found in a variety of foods and beverages marketed as “sugar-free” including chewing gum, candy, fruit juice, soft drinks, and table sugar substitutes. In this particular clinical vignette, the patient is attempting to lose weight, admits to avoiding regular table sugar, and needs to be asked specifically if she is ingesting artificial sweeteners. Her diarrhea is unlikely to be due to C. difficile given her negative PCR testing (sensitivity: 90–95%). A diagnosis of celiac disease is also unlikely given the negative celiac serology (sensitivity: 90– 95%). Review of ingestions should be pursued prior to considering initiation of a bulking agent or pursuing dietary modification. Clinical pearl Artificial sweeteners, caffeinated beverages, and gum chewing are potential causes of diarrhea that should be sought through careful history taking.
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Reference 1. Bauditz J, et al. Severe weight loss caused by chewing gum. Br Med J. 2008;336(7635):96–97.
Case 6 An asymptomatic 45-year-old man presents for an insurance physical. He underwent right inguinal hernia repair 5 years prior but has no other medical history. He travels extensively for work, especially to Asia. He consumes 1–2 glasses of red wine twice weekly. The patient’s mother has undergone colectomy for ulcerative colitis. The clinical examination is normal. Laboratory testing included normal CBC, alkaline phosphatase 512 U/L (normal: 45–115 U/L)— fraction 90% liver, total bilirubin 0.5 mg/dL (normal: 0.1–1.0 mg/dL), and alanine aminotransferase 25 U/L (normal: 7–55 U/L). Ultrasound of the liver reveals no evidence of biliary dilation. Question What would you do next? A. B. C. D. E.
Bone scan Serum protein electrophoresis Colonoscopy ACE level Hepatitis B and C serologies
Discussion If a patient is found to have an elevated serum alkaline phosphatase (hepatic), and the remaining liver tests are normal/near normal, the primary consideration should be for cholestatic liver disease such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) or infiltrative conditions of the liver such as malignancy, amyloidosis, sarcoidosis, or infection. When ulcerative colitis occurs in association with primary sclerosing cholangitis, the colonic disease may be minimally active or asymptomatic. In this clinical vignette, colonoscopy should be pursued to evaluate for ulcerative colitis. Bone scan is unlikely to be helpful given the alkaline phosphatase is of hepatic origin. Chronic hepatitis infection is unlikely in the setting of normal alanine aminotransferase. Clinical pearl Isolated elevation of alkaline phosphatase (hepatic) is typically due to either cholestatic liver disease (primary sclerosing cholangitis/primary biliary cirrhosis) or infiltrative disease of the liver (malignancy, amyloidosis, sarcoidosis, or infection). Ulcerative colitis, occurring in association with primary sclerosing cholangitis, may be clinically quiescent. Reference 1. Pratt DS, et al. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. 2000;342(17):1266–1271. 2. Loftus EV, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut. 2005;54(1):91–96.
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Case 7 A 65-year-old female presents for evaluation and management of possible Zollinger–Ellison syndrome. She does not report abdominal pain but has had intermittent diarrhea, alternating with constipation. She does not experience gastroesophageal reflux. The past history is significant for hypothyroidism and vitiligo, but she has not had peptic ulcer disease. Her only medication is Synthroid 0.125 mg daily. Physical examination reveals evidence of vitiligo but is otherwise normal. Laboratory studies had been performed by another care provider and included a serum gastrin level of 1200 pg/mL (normal: o180 pg/mL). Question What would you recommend next? A. B. C. D. E.
Gastric fluid analysis CT abdomen/pelvis EUS of pancreas Octreotide scan Secretin test
Discussion Hypergastrinemia usually occurs in association with either suppressed gastric acid production (acid-suppressive medication such as H2-antagonists and proton pump inhibitors) or absent gastric acid production (pernicious anemia). When hypergastrinemia is due to acidsuppressive medication, the rise in gastrin level is usually modest (2–5 times normal) and trends toward normal upon discontinuation of the medication. Hypergastrinemia due to pernicious anemia can lead to either modest or more significant elevations in gastrin level, which can also be seen in Zollinger–Ellison syndrome. Gastric fluid analysis is helpful in differentiating between pernicious anemia and Zollinger–Ellison syndrome, as patients with pernicious anemia have absent gastric acid production whereas those with Zollinger–Ellison have abundant acid production. CT scans, EUS, and Octreotide scans may be considered in patients with hypergastrinemia, in whom gastric acid production has been found to be elevated, making a diagnosis of Zollinger–Ellison syndrome more likely. Clinical pearl Hypergastrinemia is usually due to either decreased (acid-suppressive therapy) or absent (pernicious anemia) gastric acid production. Reference 1. Orlando RC, et al. Chronic hypergastrinemia: causes and consequences. Dig Dis Sci. 2007;52 (10):2482–2489.
Case 8 A 60-year-old man undergoes colonoscopy for average-risk screening. He is found to have a tight angulation of the sigmoid colon, which cannot be safely traversed, and he is sent for CT colonography. The CT colonography reveals dense sigmoid diverticulosis, but the colon is
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otherwise normal. Extracolonic findings include a duodenal periampullary diverticulum, a 9mm cyst in the head of pancreas, and the common bile duct is noted to be dilated at 10 mm. There is no associated intrahepatic bile duct dilation. The patient reports no abdominal symptoms. He underwent cholecystectomy 10 years before, and his gallbladder was filled with stones. He did not undergo intraoperative cholangiogram. His only medication is oxycodone for chronic low back pain. Clinical examination reveals no abdominal tenderness. Laboratory studies include normal bilirubin, alkaline phosphatase, and alanine aminotransferase. Question What is the most likely cause of the common bile duct dilation? A. B. C. D. E.
Periampullary diverticulum Cyst in head of pancreas Retained common bile duct stone Oxycodone Prior cholecystectomy
Discussion Asymptomatic dilation of the common bile duct is not uncommon in patients that have undergone prior cholecystectomy. This is due to increased biliary flow through the common bile duct in the absence of a reservoir for bile storage (gall bladder). If this is the sole cause for bile duct dilation, liver tests are typically normal, and there is no evidence of intrahepatic bile duct dilation. Narcotic pain medications may also cause dilation of the common bile duct by means of increasing sphincter of Oddi pressure. Periampullary diverticula and small cysts in the head of pancreas typically do not lead to biliary dilation. Patients with retained common bile duct stones usually have abdominal pain, elevated liver tests, or a combination of these findings. Clinical pearl Asymptomatic dilation of common bile duct may occur in patients following cholecystectomy. The intrahepatic bile ducts are typically not dilated in such patients. This usually does not require investigation. Reference 1. Wu SD, et al. Effect of narcotic analgesic drugs on human Oddi’s sphincter motility. World J Gastroenterol. 2004;10:2901–2904. 2. Chawla S, et al. Does cholecystectomy status influence the common bile duct diameter? Dig Dis Sci. 2010;55(4):1155–1160.
Answers: 1—E; 2—D; 3—C; 4—D; 5—B; 6—C; 7—A; 8—E.
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Clinical pearls in gastroenterology 2012 Conor Loftus, MD, Scott C. Litin, MD, John B. Bundrick, MD
Case 1 A 70-year-old male presents for evaluation of difficulty with swallowing solid food. He does not report problems swallowing liquids. The difficulty with swallowing has been present for approximately 3 years. Within the past 3 months, he also reports two episodes where he felt food lodged in his chest and with some difficulty was eventually able to expel the food. He does not have painful swallowing. He has not lost weight. He has a history of hiatal hernia with longstanding gastroesophageal reflux controlled with once daily PPI therapy. An upper endoscopy was performed revealing a somewhat tortuous esophagus and stomach but was otherwise grossly normal. Biopsies of the esophagus were not performed. Question What would you recommend next? A. B. C. D. E.
Esophageal manometry Endoscopic ultrasound of gastroesophageal junction CT scan of chest Repeat EGD with esophageal biopsies Barium esophagram
Discussion Gastric volvulus is an under-recognized complication of hiatal hernia. Patients with a paraesophageal hiatal hernia and those with intrathoracic stomach are at highest risk for the development of gastric volvulus. Acute gastric volvulus typically presents with sudden severe pain in the upper abdomen or lower chest, often associated with persistent unproductive retching, and the presentation may be mistaken for acute myocardial infarction. Chronic gastric volvulus is typically associated with milder non-specific symptoms such as dysphagia, epigastric discomfort, and fullness after eating. In this vignette, the clinical presentation and endoscopic findings are
http://dx.doi.org/10.1016/j.disamonth.2014.04.007 0011-5029/& 2014 Mosby, Inc. All rights reserved.
C. Loftus et al. / Disease-a-Month 60 (2014) 306–313
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suspicious for chronic gastric volvulus. This is best evaluated by performing a barium esophagram. Esophageal biopsies are unlikely to be helpful as eosinophilic esophagitis would be uncommon in this age group. Endoscopic ultrasound of gastroesophageal junction is helpful when malignancy is suspected but not confirmed with regular endoscopy (pseudoachalasia). Clinical pearl Gastric volvulus is an under-recognized complication of hiatal hernia. Patients with a paraesophageal hiatal hernia or with intrathoracic stomach are at highest risk. Gastric volvulus is best confirmed with barium esophagram. References 1. Rashid F, et al. A review article on gastric volvulus: a challenge to diagnosis management. Int J Surg. 2010;8(1):18–24.
Case 2 A 60-year-old female presents for further evaluation of chronic watery diarrhea. She had first presented 3 months prior, reporting an 8-week history of 8–10 watery bowel movements daily. Initial evaluation at that time had included laboratory and stool studies, which were unremarkable, prompting a colonoscopy with random colon biopsies. The colon was endoscopically normal but biopsies revealed evidence of lymphocytic colitis. Despite treatment with bismuth subsalicylate and budesonide (9 mg daily for 6 weeks), there has been no improvement in the patient’s diarrhea. The patient has also had shoulder pain and has been taking ibuprofen 400 mg three times daily. Additional evaluation is pursued with repeat stool studies and tissue transglutaminase antibody without abnormality being found. Question What would you recommend next? A. B. C. D. E.
Increase dose of budesonide to 12 mg daily Mesalamine 4.8 g daily Prednisone 40 mg daily Discontinue ibuprofen Citrucel two tablespoons daily
Discussion This patient with microscopic colitis has not responded to initial therapy with bismuth subsalicylate and subsequently budesonide. In patients with microscopic colitis, not responding to standard therapy (assuming patient compliance), the first step is to exclude co-existing celiac disease in light of the 5% overlap between these diagnoses. In this vignette, celiac serology (sensitivity approximately 95%) is negative, and therefore an overlap syndrome is unlikely. Numerous medications have been associated with exacerbating microscopic colitis especially NSAIDs, aspirin, proton pump inhibitors, selective serotonin reuptake inhibitors, and statins. The best evidence for an association between medication use and microscopic colitis exists for NSAIDs. NSAIDs should be discontinued in patients diagnosed with microscopic colitis.
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Clinical pearl NSAIDs may exacerbate microscopic colitis and should be discontinued in patients with this diagnosis. There is also an association between microscopic colitis and celiac disease. References 1. Beaugerie L, Pardi DS. Review article: drug-induced microscopic colitis—proposal for a scoring system and review of the literature. Aliment Pharmacol Ther. 2005;22:277–284.
Case 3 A 50-year-old male presents for evaluation of hematochezia and intermittent abdominal pain. He has had four episodes of hematochezia within the past 3 months. With the most recent episode, he was hospitalized, received blood transfusion, and underwent colonoscopy as well as upper endoscopy. On colonoscopy, blood appeared to be emanating from the ileocecal valve suggesting more proximal GI bleeding. Upper endoscopy to the level of ligament of Treitz was unremarkable. The bleeding ceased and no further investigations were performed during that hospitalization. The patient has not had bleeding since discharge. He has no significant past medical history. He does not take any medications. Question What would you recommend next? A. B. C. D. E.
Antegrade double-balloon enteroscopy Retrograde double-balloon enteroscopy CT enterography Small bowel capsule endoscopy Meckel’s scan
Discussion In this clinical vignette, the source of bleeding is likely in the small bowel because blood was emanating from the ileocecal valve at colonoscopy and the upper endoscopy was unremarkable. The approach to small bowel bleeding depends on patient characteristics and the volume of blood loss. In middle-aged individuals (as in this case), transfusion requiring blood loss from the small intestine is suggestive of a small bowel vascular tumor such as a gastrointestinal stromal tumor (GIST) or carcinoid. The intermittent abdominal pain experienced by the patient is suggestive of episodic partial small bowel obstruction as could occur with small bowel tumors. Studies have shown that CT enterography is more sensitive than capsule endoscopy for the detection of small bowel tumors. Meckel’s scan would be reasonable to pursue in a younger patient ( o 30 years old) with small bowel bleeding. Doubleballoon enteroscopy now allows for deeper intubation of the small bowel, but this is typically reserved for further diagnostic evaluation or therapeutic intervention following CT enterography and/or capsule endoscopy. Clinical pearl CT enterography is more sensitive than wireless capsule endoscopy for the detection of small bowel tumors.
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References 1. Huprich JE, Alexander JA, et al. Prospective blinded comparison of wireless capsule endoscopy and multiphase CT enterography in obscure gastrointestinal bleeding. Radiology. 2011;260 (3):744–751. 2. Hakim FA, Alexander JA, et al. CT-enterography may identify small bowel Tumors not detected by capsule endoscopy: eight years experience at Mayo Clinic, Rochester. Dig Dis Sci. 2011;56 (10):2914–2919.
Case 4 A 65-year-old female developed diarrhea 2 weeks after completion of antibiotics for a urinary tract infection. Stool testing was positive for Clostridium difficile infection, and the patient was treated with metronidazole 500 mg three times daily for 14 days. The diarrhea resolved during treatment but recurred 5 days after stopping the metronidazole. A 14-day course of metronidazole was repeated with similar outcome. The patient was then treated with a tapering course of vancomycin over 8 weeks. While being treated with vancomycin, the diarrhea again resolved but recurred 10 days after completing the therapy. The patient has insulin-dependent diabetes mellitus, hyperlipidemia, hypertension, and gastroesophageal reflux. Her current medications include insulin, simvastatin, metoprolol, and omeprazole.
Question What would you recommend next? A. B. C. D. E.
Repeat 8-week tapering course of vancomycin Fidaxomicin 200 mg twice daily for 10 days Stool transplantation Discontinue omeprazole Discontinue simvastatin
Discussion Recent studies have suggested that recurrence of Clostridium difficile infection is more common in patients who received proton pump inhibitors concurrent with treatment for C. difficile, when compared to patients who did not receive concurrent proton pump inhibitor therapy. This may in part be explained by the fact that while C. difficile spores are resistant to acid, the vegetative forms are susceptible to acid. In this clinical vignette, the recurrence of C. difficile infection may have been contributed to by concurrent omeprazole use. Fidaxomicin is the first in a new class of narrow-spectrum macrocyclic antibiotics. It has been shown to be as effective as vancomycin in the treatment of C. difficile infection, with fewer side effects and likely a lower C. difficile recurrence rate (use is currently limited by expense). Stool transplantation has been reported as a means for treating refractory C. difficile infection, but as yet is not widely accepted. Clinical pearl Proton pump inhibitor use during the treatment of C. difficile infection may be associated with an increased risk of recurrent C. difficile infection.
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References 1. Linsky A, et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Inren Med. 2010;170(9):772–778. 2. Louie TJ, et al. Fidaxomicin versus Vancomycin for recurrent Clostridium difficile infection. N Engl J Med. 2011;364:422–431.
Case 5 A 40-year-old female presents for evaluation of a 3-month history of diarrhea. She typically has 4–5 loose stools daily. The stools are non-bloody. She does not experience nocturnal diarrhea. The patient states that she has been told in the past that she suffered from irritable bowel syndrome. She has had intermittent mild abdominal pain with bloating for many years. Within the past year, the patient has been trying to lose weight by modifying caloric intake and exercising more frequently. She is very proud of the fact that she does not use table sugar any longer. She has succeeded in losing 20 lb weight. She had an upper respiratory tract infection 6 months prior, for which she received a 10-day course of antibiotics. Her family history is significant for the fact that two paternal cousins experienced diarrhea, which improved upon initiation of a gluten-free diet. The patient has had serologic testing for celiac disease (tissue transglutaminase antibody), which was negative, and has undergone stool testing including a normal Clostridium difficile toxin test (PCR-based test). Question What would you recommend next? A. B. C. D. E.
Repeat stool testing for Clostridium difficile Dietary/ingestion review Upper endoscopy with small bowel biopsy Initiate trial of citrucel Trial of lactose-free diet
Discussion All patients with chronic diarrhea have to be questioned carefully with respect to diet/ ingestions. Common causes of diarrhea that may be discovered through careful history taking include caffeinated beverages, gum chewing, and ingestion of artificial sweeteners. Artificial sweeteners and other sugar substitutes are found in a variety of foods and beverages marketed as “sugar-free” including chewing gum, candy, fruit juice, soft drinks, and table sugar substitutes. In this particular clinical vignette, the patient is attempting to lose weight, admits to avoiding regular table sugar, and needs to be asked specifically if she is ingesting artificial sweeteners. Her diarrhea is unlikely to be due to C. difficile given her negative PCR testing (sensitivity: 90–95%). A diagnosis of celiac disease is also unlikely given the negative celiac serology (sensitivity: 90– 95%). Review of ingestions should be pursued prior to considering initiation of a bulking agent or pursuing dietary modification. Clinical pearl Artificial sweeteners, caffeinated beverages, and gum chewing are potential causes of diarrhea that should be sought through careful history taking.
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Reference 1. Bauditz J, et al. Severe weight loss caused by chewing gum. Br Med J. 2008;336(7635):96–97.
Case 6 An asymptomatic 45-year-old man presents for an insurance physical. He underwent right inguinal hernia repair 5 years prior but has no other medical history. He travels extensively for work, especially to Asia. He consumes 1–2 glasses of red wine twice weekly. The patient’s mother has undergone colectomy for ulcerative colitis. The clinical examination is normal. Laboratory testing included normal CBC, alkaline phosphatase 512 U/L (normal: 45–115 U/L)— fraction 90% liver, total bilirubin 0.5 mg/dL (normal: 0.1–1.0 mg/dL), and alanine aminotransferase 25 U/L (normal: 7–55 U/L). Ultrasound of the liver reveals no evidence of biliary dilation. Question What would you do next? A. B. C. D. E.
Bone scan Serum protein electrophoresis Colonoscopy ACE level Hepatitis B and C serologies
Discussion If a patient is found to have an elevated serum alkaline phosphatase (hepatic), and the remaining liver tests are normal/near normal, the primary consideration should be for cholestatic liver disease such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) or infiltrative conditions of the liver such as malignancy, amyloidosis, sarcoidosis, or infection. When ulcerative colitis occurs in association with primary sclerosing cholangitis, the colonic disease may be minimally active or asymptomatic. In this clinical vignette, colonoscopy should be pursued to evaluate for ulcerative colitis. Bone scan is unlikely to be helpful given the alkaline phosphatase is of hepatic origin. Chronic hepatitis infection is unlikely in the setting of normal alanine aminotransferase. Clinical pearl Isolated elevation of alkaline phosphatase (hepatic) is typically due to either cholestatic liver disease (primary sclerosing cholangitis/primary biliary cirrhosis) or infiltrative disease of the liver (malignancy, amyloidosis, sarcoidosis, or infection). Ulcerative colitis, occurring in association with primary sclerosing cholangitis, may be clinically quiescent. Reference 1. Pratt DS, et al. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. 2000;342(17):1266–1271. 2. Loftus EV, et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut. 2005;54(1):91–96.
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Case 7 A 65-year-old female presents for evaluation and management of possible Zollinger–Ellison syndrome. She does not report abdominal pain but has had intermittent diarrhea, alternating with constipation. She does not experience gastroesophageal reflux. The past history is significant for hypothyroidism and vitiligo, but she has not had peptic ulcer disease. Her only medication is Synthroid 0.125 mg daily. Physical examination reveals evidence of vitiligo but is otherwise normal. Laboratory studies had been performed by another care provider and included a serum gastrin level of 1200 pg/mL (normal: o180 pg/mL). Question What would you recommend next? A. B. C. D. E.
Gastric fluid analysis CT abdomen/pelvis EUS of pancreas Octreotide scan Secretin test
Discussion Hypergastrinemia usually occurs in association with either suppressed gastric acid production (acid-suppressive medication such as H2-antagonists and proton pump inhibitors) or absent gastric acid production (pernicious anemia). When hypergastrinemia is due to acidsuppressive medication, the rise in gastrin level is usually modest (2–5 times normal) and trends toward normal upon discontinuation of the medication. Hypergastrinemia due to pernicious anemia can lead to either modest or more significant elevations in gastrin level, which can also be seen in Zollinger–Ellison syndrome. Gastric fluid analysis is helpful in differentiating between pernicious anemia and Zollinger–Ellison syndrome, as patients with pernicious anemia have absent gastric acid production whereas those with Zollinger–Ellison have abundant acid production. CT scans, EUS, and Octreotide scans may be considered in patients with hypergastrinemia, in whom gastric acid production has been found to be elevated, making a diagnosis of Zollinger–Ellison syndrome more likely. Clinical pearl Hypergastrinemia is usually due to either decreased (acid-suppressive therapy) or absent (pernicious anemia) gastric acid production. Reference 1. Orlando RC, et al. Chronic hypergastrinemia: causes and consequences. Dig Dis Sci. 2007;52 (10):2482–2489.
Case 8 A 60-year-old man undergoes colonoscopy for average-risk screening. He is found to have a tight angulation of the sigmoid colon, which cannot be safely traversed, and he is sent for CT colonography. The CT colonography reveals dense sigmoid diverticulosis, but the colon is
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otherwise normal. Extracolonic findings include a duodenal periampullary diverticulum, a 9mm cyst in the head of pancreas, and the common bile duct is noted to be dilated at 10 mm. There is no associated intrahepatic bile duct dilation. The patient reports no abdominal symptoms. He underwent cholecystectomy 10 years before, and his gallbladder was filled with stones. He did not undergo intraoperative cholangiogram. His only medication is oxycodone for chronic low back pain. Clinical examination reveals no abdominal tenderness. Laboratory studies include normal bilirubin, alkaline phosphatase, and alanine aminotransferase. Question What is the most likely cause of the common bile duct dilation? A. B. C. D. E.
Periampullary diverticulum Cyst in head of pancreas Retained common bile duct stone Oxycodone Prior cholecystectomy
Discussion Asymptomatic dilation of the common bile duct is not uncommon in patients that have undergone prior cholecystectomy. This is due to increased biliary flow through the common bile duct in the absence of a reservoir for bile storage (gall bladder). If this is the sole cause for bile duct dilation, liver tests are typically normal, and there is no evidence of intrahepatic bile duct dilation. Narcotic pain medications may also cause dilation of the common bile duct by means of increasing sphincter of Oddi pressure. Periampullary diverticula and small cysts in the head of pancreas typically do not lead to biliary dilation. Patients with retained common bile duct stones usually have abdominal pain, elevated liver tests, or a combination of these findings. Clinical pearl Asymptomatic dilation of common bile duct may occur in patients following cholecystectomy. The intrahepatic bile ducts are typically not dilated in such patients. This usually does not require investigation. Reference 1. Wu SD, et al. Effect of narcotic analgesic drugs on human Oddi’s sphincter motility. World J Gastroenterol. 2004;10:2901–2904. 2. Chawla S, et al. Does cholecystectomy status influence the common bile duct diameter? Dig Dis Sci. 2010;55(4):1155–1160.
Answers: 1—E; 2—D; 3—C; 4—D; 5—B; 6—C; 7—A; 8—E.
