EL TERRORISMO

27. A 36-year-old man presents to your clinic complaining of fatigue. His fatigue started 3 or 4 months ago.

His medical history is unremarkable. Review of systems is positive for occasional diarrhea, which the patient has been experiencing for several months, and for a 20-lb weight loss. Physical examination shows pallor. Occult blood is found on rectal examination. The rest of the examination is normal.

Laboratory tests reveal iron deficiency anemia, and the patient tests positive on a qualitative fecal fat test.

Results of an upper endoscopy and a colonoscopy are normal.

Which of the following tests would be most likely to provide helpful information in the workup of this patient?

❑ A. Selenium-75–labeled homocholic acid-taurine (⁷⁵SeHCAT) absorption test

❑ B. Xylose absorption test

❑ C. Bentiromide test

❑ D. Tissue transglutaminase antibody

Key Concept/Objective: To understand that gluten-sensitive enteropathy (GSE) is a cause of iron deficiency anemia

Patients with GSE may present with a variety of complaints, including weight loss, fatigue, abdominal cramps, distention, bloating, and diarrhea. Other presentations include iron deficiency anemia, osteoporosis, and easy bruising. In a patient in whom the suspicion of GSE is high, a positive tissue transglutaminase antibody test makes the diagnosis almost certain. Alternatively, the diagnosis might rest on small bowel biopsy findings. Another helpful test is the identification of an endomysial antibody. The presence of fecal fat is helpful in this patient because it confirms the suspicion of an underlying malabsorptive disorder. The xylose absorption test evaluates the absorptive surface area of the small bowel. The bentiromide test is a noninvasive test to evaluate for pancreatic exocrine insuf-ficiency. All of these tests can, however, be helpful in the evaluation of a patient with mal-absorption and diarrhea. On the basis of this patient’s clinical presentation, the tissue transglutaminase antibody test is the one most likely to be helpful with the diagnosis.

(Answer: D—Tissue transglutaminase antibody)

28. A 44-year-old woman with a history of GSE is evaluated for refractory disease. She was diagnosed with GSE 8 years ago. Her disease was initially well controlled with a gluten-free diet. Over the past few months, she has had persistent diarrhea and malabsorption that has not responded to her usual diet. Findings on phys-ical examination are consistent with chronic malnutrition. An abdominal CT scan shows no masses or anatomic abnormalities that would account for her symptoms. An endoscopy is obtained, and small bowel biopsy shows villous atrophy and a layer of collagen underneath the enterocytes.

Which of the following is the most likely explanation for this patient’s symptoms?

❑ A. Poor adherence to gluten-exclusion diet

❑ B. Collagenous sprue

❑ C. Small bowel lymphoma

❑ D. Tropical sprue

Key Concept/Objective: To know that collagenous sprue is a possible complication of gluten-sen-sitive enteropathy

Collagenous sprue is a rare, devastating disease in which there is a layer of collagen under-neath the enterocytes of the small bowel. The origin of collagenous colitis is unknown, but it develops in approximately half the patients who have refractory celiac disease. The symptoms are severe and include obvious malabsorption. The diagnosis is made on the basis of the classic histologic picture of villous atrophy and subepithelial collagen deposi-tion. Therapy for collagenous sprue is uncertain; some patients respond to steroids. Poor adherence to gluten-exclusion diet is common; however, it would not explain the histo-logic changes seen in this patient. Small bowel lymphoma can be a complication of GSE;

however, there is no evidence of this disorder on the imaging studies and biopsy. Tropical sprue is a malabsorptive disorder that appears in certain areas of the world. The diagnosis is based on the history of travel to endemic areas and a biopsy showing villous atrophy and inflammatory cells. (Answer: B—Collagenous sprue)

29. A 60-year-old man is being evaluated in your clinic for diarrhea. He started having diarrhea 6 months ago. He has undergone extensive evaluation over the past 2 months. His stool studies were consistent with steatorrhea. A stool culture for bacterial organisms was negative, as were stool studies for the pres-ence of ova and parasites. An abdominal CT scan was normal. The patient has had arthritis for 5 years.

Review of systems is positive for weight loss and occasional fever over the past 3 months. On physical examination, the patient’s temperature is 100.4° F (38° C). Skin hyperpigmentation and cervical lym-phadenopathy are noted. You order an upper endoscopy. A small bowel biopsy shows villous atrophy and macrophages with sickleform particles. A periodic acid–Schiff (PAS) stain is positive.

Which of the following therapies is indicated for this patient?

❑ A. Gluten-exclusion diet

❑ B. Steroids

❑ C. Trimethoprim-sulfamethoxazole (TMP-SMX)

❑ D. Cholestyramine

Key Concept/Objective: To be able to recognize Whipple disease

The patient has clinical and laboratory findings consistent with the diagnosis of Whipple disease. This is a rare multisystem disease caused by infection with Tropheryma whippelii.

Classically, the disease begins in a middle-aged man with a nondeforming arthritis that usually starts years before the onset of the intestinal symptoms. Arthralgias, diarrhea, abdominal pain, and weight loss are the cardinal manifestations of Whipple disease. Other complaints include fever, abdominal distention, lymphadenopathy, hyperpigmentation of the skin, and steatorrhea. The diagnosis rests on identifying the classic PAS-positive macrophages, which contain sickleform particles. The histologic lesion shows distended villi filled with the foamy, PAS-positive macrophages. Lymphatic dilatation is also present.

A flat, villous surface can be seen in extreme cases. For treatment of Whipple disease, TMP-SMX is given for 1 year. Gluten-exclusion diet is indicated in cases of GSE. Prednisone has no role in the treatment of Whipple disease. Cholestyramine is a resin that binds bile acids and can be used in cases of diarrhea related to bile acid malabsorption. (Answer: C—

Trimethoprim-sulfamethoxazole [TMP-SMX])

30. A 10-year-old boy is evaluated for edema. He developed unilateral left upper and lower extremity edema 1 year ago. On review of systems, abdominal swelling and occasional diarrhea are noted. The physical examination is remarkable for unilateral edema and abdominal shifting dullness to percussion. A com-plete blood count shows lymphopenia. The serum albumin level is low at 1 g/dl. Urinalysis shows no protein; liver function tests are within normal limits.

Which of the following would be the most likely finding on small bowel biopsy for this patient?

❑ A. Dilated lymphatics with club-shaped villi

❑ B. Intense lymphocyte infiltration of the lamina propria

❑ C. Eosinophilic invasion of the crypts on the small intestine

❑ D. Lack of plasma cells

Key Concept/Objective: To be able to recognize intestinal lymphangiectasia

This patient has classic findings of congenital intestinal lymphangiectasia. Intestinal lym-phangiectasia is often a congenital condition in which deformed lymphatics impair the transport of chylomicrons from the enterocytes to the mesenteric lymph duct. The block-age of lymphatic drainblock-age may result in chylous ascites. Protein-losing enteropathy and lymphopenia are prominent features. Modest steatorrhea is also present. In the congenital form of the disease, lymphedema of the legs or of one leg and one arm is seen. With endo-scopic examination, white villi, white nodules, and submucosal elevations may be noted.

The white appearance of the mucosa is undoubtedly caused by retained chylomicron tria-cylglycerol. Double-contrast barium x-ray examination shows smooth nodular protrusions and thick mucosal folds without ulceration. On histologic examination, dilated lymphat-ics with club-shaped villi are seen. Lymphocytic infiltration of the lamina propria can be found in other disorders, such as lymphomas and immunoproliferative disease of the small intestine. Eosinophilic invasion of the crypts on the small intestine can be found in eosinophilic gastroenteritis. Lack of plasma cells can be found in patients with hypogam-maglobulinemic sprue. (Answer: A—Dilated lymphatics with club-shaped villi)

31. A 32-year-old woman presents for evaluation of a sensitive tongue, which she has been experiencing for 2 weeks. She describes loss of appetite, weight loss of 15 lb over 3 months, and frequent (four or five times a day) loose stools. She denies having bloody stools, risk factors for HIV infection, or a personal or family history of gastrointestinal disease. She does recall briefly taking ciprofloxacin for traveler’s diar-rhea while in Indonesia 18 months ago, which resolved with therapy. Review of systems is otherwise negative. Examination reveals normal conjunctiva; a swollen, tender tongue; a normal abdomen; and trace pedal edema. Laboratory tests show a hematocrit of 27, mild hypokalemia, and hypomagnesemia.

Which of the following pairs of interventions is most likely to help with this patient’s condition?

❑ A. Folate and niacin

❑ B. Iron sulfate and tetracycline

❑ C. Gluten-free diet and prednisone

❑ D. Folate and tetracycline

❑ E. Azathioprine and prednisone

Key Concept/Objective: To be able to recognize the presentation and potential time course of tropical sprue and to understand the initial approach to therapy

Tropical sprue is a malabsorptive disease that occurs primarily in tropical locales among both residents and visitors. Its cause is unclear, but coliform bacteria have been selective-ly isolated from the jejunum of tropical sprue patients. The disease can occur while the patient is in the tropical locale, or it can present as late as 10 years after return. This patient spent time in Indonesia 18 months before presentation. Symptoms are generally much more apparent than in GSE and include prominent anorexia, weight loss, and diarrhea, as well as a high frequency of folate and vitamin B12deficiencies with accompanying mani-festations (macrocytic anemia, glossitis) and lower extremity edema. Folate should be administered as initial therapy; if the patient has had symptoms for a period longer than 4 months before the time of presentation, antibiotic therapy with tetracycline or a sul-fonamide should be administered. Other than having glossitis, this patient has no evi-dence of niacin deficiency (pellagra). The patient’s anemia could be that of iron deficien-cy, but in light of the normal conjunctiva and other physical findings, that is less likely. A gluten-free diet and, in some cases, prednisone are required for treatment of GSE.

Azathioprine and prednisone may be the initial regimen for a patient with Crohn disease.

(Answer: D—Folate and tetracycline)

32. A 64-year-old man presents to his primary care physician with a complaint of foul-smelling diarrhea, which he has had for the past 4 to 5 months. He has three or four stools a day, which he describes as oily in nature. He denies experiencing a change in the caliber of his stools, and he also denies having abdominal pain, melena, or blood per rectum. His appetite is still fairly good, but he has lost 10 lb over the past 2 months and is somewhat fatigued. His medical history is notable for hypertension,

hyperlipi-demia, type 2 diabetes with retinopathy and mild neuropathy, and gastroesophageal reflux disease. His medications include metformin, insulin, atenolol, simvastatin, aspirin, and omeprazole. The neurologic examination is notable only for mild stocking-glove neuropathy, and an S₄is heard on cardiac exami-nation. Laboratory tests reveal macrocytic anemia and mild hypoalbuminemia.

Which of the following is the most likely diagnosis for this patient?

❑ A. Crohn disease

❑ B. Intestinal lymphoma

❑ C. Bacterial overgrowth syndrome

❑ D. Hemochromatosis

❑ E. Chronic pancreatitis

Key Concept/Objective: To understand the precipitants for the bacterial overgrowth syndrome

This patient has a subacute to chronic presentation with steatorrhea and likely folate defi-ciency, vitamin B₁₂deficiency, or both. He has diabetes mellitus, which can cause stasis through autonomic neuropathy, which is not uncommon in a patient with other diabetic complications. Anything that causes intestinal stasis allows a proliferation of bacteria, which leads to changes in bile salt metabolism and impaired absorption, primarily of vita-min B12. In addition, this patient is taking a proton pump inhibitor, which can both reduce motility and change the acid milieu of the proximal small bowel, often precipitat-ing symptoms in a predisposed patient. Therapy usually entails repeated courses of antibi-otics active against anaerobes. There is no convincing evidence for the effectiveness of any of the other choices presented. (Answer: C—Bacterial overgrowth syndrome)

33. A 38-year-old man with debilitating Crohn disease who is status post a 40 cm ileal resection presents for evaluation. He recounts progressive nonbloody diarrhea since his surgery 9 months ago, which is worse in the evening. He denies having abdominal pain, nausea or vomiting, fevers, chills, or sweats. He reports no recent travel, camping, or use of antibiotics. The exam is unrevealing. Chemistries show mod-est hypokalemia and a mild non–anion gap acidosis. Fecal fat quantitative analysis reveals minimal steatorrhea.

Which therapy is most likely to help this patient?

❑ A. Cholestyramine

❑ B. Loperamide

❑ C. Tetracycline

❑ D. High-protein, low-fat diet

❑ E. Safflower oil before meals

Key Concept/Objective: To understand the effects of ileal resection on absorption, and recognize the appropriate therapy to minimize these effects

Ileal involvement is a common component of Crohn disease (regional enteritis) and may result in a poorly functioning ileum or even require resection. With moderate resections (30 to 100 cm), as in this case, malabsorption of bile salts is significant and results in bile salts entering the colon. This can lead to a secretory diarrhea known as choleretic enteropathy, the causal mechanism of which is bile salt-induced chloride secretion.

Cholestyramine reduces the distal delivery of bile salts, thus lessening the diarrhea, and would be the most appropriate therapy in this patient. With larger ileal resections (> 100 cm), steatorrhea predominates, and cholestyramine may actually exacerbate the diarrhea.

Therapy for patients undergoing larger resections is similar to that for patients with short bowel syndrome and includes antimotility agents such as loperamide and steps to increase the proportion of medium-chain fatty acids, which do not require bile salts for absorption.

Safflower oil may also be used preprandially to act via peptide YY to slow gastric empty-ing, but it would be less useful in bile salt-induced diarrhea. Tetracycline is used to treat the bacterial overgrowth syndrome. (Answer: A—Cholestyramine)

For more information, see Mansbach CM III: 4 Gastroenterology: XI Diseases Producing Malabsorption and Maldigestion. ACP Medicine Online (www.acpmedicine.com). Dale DC, Federman DD, Eds. WebMD Inc., New York, September 2003