Diarrhea Case 6

A 45-year-old man presents to a physician because of severe chronic diarrhea accompanied by a 18 kg (40 Ib) weight loss. The diarrhea began several years ago, and has become steadily worse. It is often accompanied by excessive flatulence, and the man notes that his stools usually float. The man additionally has felt generally poorly and sometimes has experienced joint symptoms. Intestinal biopsy demonstrates

Iarge numbers of foamy macrophages distending the lamina propria. A periodic acid-Schiff (PAS) stain shows granules within the macrophages.

Q 1

Which of the following is the most likely diagnosis?

/ A. Celiac sprue

/ B. Intestinal lymphangiectasia

/ C. Lactase deficiency

/ D. Tropical sprue

/ E. Whipple disease

Q2

This patient disease has been etiologically related to infection with which of the following?

/ A. Bartonella

/ B. Borrelia

/ C. Francisella

/ D. tropheryma

/ E. Vibrio

Q3

Excessive flatulence suggests which of the following problems :

/ A. Colon obstruction

/ B. GI hypermotility

/ C. GI hypomotility

/ D. Malabsorption

/ E. Small intestinal obstruction

Q 4

BIood studies on this patient demonstrate a microcytic hypochromic anemia. The nutrient whose deficiency would most likely account for the patient's anemia is primarily absorbed in which of the following sites?

/ A. Colon

/ B. Duodenum

/ C. Esophagus

/ D. IIeum

/ E. Stomach

Q 5

This patient's illness is most effectively treated with which of the following?

/ A. Antibiotics

/ B. Chemotherapy

/ C. Radiation therapy

/ D. Steroid therapy

/ E. Surgery

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Diarrhea Case 6 Answers

A1

The correct answer is E. This patient has Whipple disease, which is a rare illness characterized by diarrhea, often severe malabsorption, and weight loss. The condition most commonly affects men aged 30 to 60. The disease may present either abruptly or insidiously. If it develops insidiously, non-gastrointestinal manifestations may bring the patient to medical attention. These may include pleuritic pain, pleural effusion, anemia, joint problems, cardiac problems, neuropsychiatric problems, eye problems, or hepatic dysfunction.

All of the other diseases listed can also cause chronic diarrhea.

Celiac sprue (choice A) shows villous atrophy on biopsy, and is related to gluten sensitivity.

Intestinal lymphangiectasia (choice B) shows dilated lymphatic channels on biopsy.

Lactase deficiency (choice C) is due to an enzymatic abnormality and is characterized by a histologically normal intestinal epithelium.

Tropical sprue (choice D) usually shows moderate broadening and shortening of villi, and an often intense inflammatory reaction.

A2

The correct answer is D. Electron microscopy of the intestinal mucosa shows that the PAS-positive granules in macrophages in Whipple disease are actually bacterial forms. The causative organism is Tropheryma whippelii, and, if necessary, its DNA can be identified with PCR technology. This is necessary because attempts to culture the organism have not, to date, been successful. At the moment, this test is available only through reference laboratories. In patients who have extraintestinal manifestations, macrophages containing the bacteria may be found in extraintestinal sites.

Bartonella(choice A) species can cause cat scratch disease, trench fever, and disseminated infections.

Borrelia(choice B) causes Lyme disease.

Francisella(choice C) causes tularemia.

Vibrio(choice E) causes cholera and other diarrheal illnesses.

A3

The correct answer is D. When a patient complains of excessive flatulence, the first step is to ask them to describe the amount and frequency of the flatulence, since some people with normal intestinal gas production have unrealistic expectations about the possibility of completely eliminating flatulence. In cases in which excessive flatulence really is present, you should think of gastrointestinal disorders that can cause malabsorption, since many cases of excessive flatulence are related to bacterial digestion of unabsorbed nutrients (notably carbohydrates) with resultant gas production as a by-product. These disorders may include a wide variety of underlying conditions including pancreatic disease, liver disease, genetic enzymatic abnormalities of the intestinal mucosa, and acquired intestinal tract disease.

Colonic obstruction (choice A), small intestinal obstruction (choice E), and GI hypomotility (choice C) can also cause gas to be retained in the bowel and be visible on abdominal x-ray films, but do not, by themselves, increase gas production.

GI hypermotility (choice B) often accompanies acute diarrheal illness, but the excessive flatulence that may also be present in that setting is secondary to malabsorption rather than the hypermotility.

A4

The correct answer is B. Microcytic, hypochromic anemia suggests iron deficiency. Patients with Whipple disease frequently develop anemia related to poor duodenal absorption of either folate (producing a macrocytic anemia) or iron. Other substances absorbed in the duodenum include water, calcium, fats, sugars, proteins, many vitamins, magnesium, and sodium.

The colon (choice A) absorbs water and electrolytes.

The esophagus (choice C) does not absorb nutrients.

The ileum (choice D) can absorb bile salts, vitamin B12, and chloride.

The stomach (choice E) can absorb water and alcohol.

A5

The correct answer is A. The symptoms of Whipple disease often dramatically improve after antibiotic therapy, although the therapy must often be continued for prolonged intervals to prevent relapse and the microscopic intestinal changes may not resolve for 2 years. Many antibiotics are effective, including chloramphenicol, tetracycline, ampicillin, penicillin, and trimethoprim-sulfamethoxazole. The other therapies listed in the choices are not usually employed with Whipple disease.

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Diarrhea Case 2

A 32-year-old woman goes to an emergency department because she has developed severe, watery diarrhea. On questioning, she reports that three days previously, she spent the weekend along the Gulf of Mexico, and ate at a raw oyster bar. About 36 hours later, she developed vomiting and an abrupt, painless, watery diarrhea. The volume of diarrhea has been copious, and she has subsequently developed intense thirst, oliguria, muscle cramps, and weakness. At the time of being seen in the emergency department, she is noted to have marked loss of tissue turgor, sunken eyes, and wrinkling of the skin of her fingers. Laboratory studies demonstrate hemoconcentration and severe metabolic acidosis with potassium depletion.

Q 1

Which of the following is the most likely cause of the woman's problems?

/ A. Amoeba infection

/ B. Bacterial infection

/ C. Food poisoning

/ D. Irritable bowel syndrome

/ E. Viral infection

Q 2

An organism cultured from the patient's stool is subsequently characterized as an oxidase-positive, gram-negative curved rod with polar

flagella that shows "shooting star" mobility and grows best on TCBS medium. Which of the following is the most likely pathogen?

/ A. Escherichia

/ B. Pseudomonas

/ C. Salmonella

/ D. Shigella

/ E. Vibiro

Q3

This organism is most likely classified as which of the following types ?

/ A. O1

/ B. O2

/ C. O5

/ D. O105

/ E. O139

Q 4

In the United States, approximately what percentage of patients who acquire this infection subsequently die?

/ A. 1% or less

/ B. 5-10%

/ C. 20-30%

/ D. 50-70%

/ E. 90% or more

Q 5

The patient responds with IV fluids, and is very much better within 24 hours. While this woman did not require antibiotic therapy, which of the

following antibiotics is used for this disease?

/ A. First generation cephalosporin

/ B. Metronidazole

/ C. Penicillin

/ D. Tetracycline

/ E. Third generation cephalosporin

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Diarrhea Case 2 Answwers

A1

The correct answer is B. This patient is severely ill and dehydrated. Severe watery diarrhea that persists is most likely to be due to a bacterial infection.

Amoeba infection (choice A) usually produces a bloody diarrhea that does not have the watery characteristic of cholera.

Food poisoning (choice C) usually begins within the first eight hours after ingestion of contaminated food, and is often over within 24 hours.

Irritable bowel syndrome (choice D) is usually a chronic, but relatively mild, problem.

Viral infection (choice E) can cause gastroenteritis, but it is not usually as debilitating as this patient's disease.

A2

The correct answer is E. The features noted are those of Vibrio cholerae, the causative organism of the severe diarrheal disease, cholera. The diarrhea is the result of the action of the cholera enterotoxin, which acts by ADP-ribosylating adenylate cyclase, leading to increased cyclic AMP with secondary increased efflux of Cl^- and H₂O. World-wide, cholera is usually spread by fecally contaminated water, but in areas such as Europe and the United States, where the general level of hygiene, sewage control, and water supply is good, the occasional cases seen are often the result of contaminated food. Some of the shellfish from the Gulf of Mexico naturally contain the organism, and ingestion of these shellfish in raw or poorly cooked form has caused cholera.

Escherichia(choice A) is oxidase-negative.

Pseudomonas(choice B) is an oxidase-positive, gram-negative rod that characteristically produces the blue pigment, pyocyanin.

Salmonella(choice C) is a motile, gram-negative rod that is a non-lactose fermenter that produces H₂S.

Shigella(choice D) are non-motile gram-negative rods.

A3

The correct answer is A. Vibrio cholera serogroup O1 is the major cause of epidemic cholera, and up until 1992 was the only cause. Since then, the O139 serogroup (choice E) has been an important pathogen in India and Bangladesh, but has not yet become important outside Asia. No other serotypes are known to cause epidemic cholera.

A4

The correct answer is A. The mortality of cholera varies markedly depending upon the general health of the individuals who become infected and the availability of adequate medical care. In extreme situations, such as in refugee camps with little sanitation, little food, and no available medical facilities, case fatality rates of 25-50% are encountered. In Europe, the Americas, and more recently Asia, case fatality rates in most situations are kept at 1% or less. A major reason for the decreased fatality rates in most parts of the world is that the World Health Organization has been encouraging endemic areas to pre-plan for epidemics and have available large numbers of previously prepared packages of oral rehydration salts.

A5

The correct answer is D. Most patients with cholera in this country who have disease severe enough to cause significant dehydration are rehydrated initially with IV fluids, and are then switched to oral fluids several hours later. In countries with more likelihood of having an epidemic and poorer medical availability, packages of oral rehydration salts to which water is added are commonly (and very effectively) used to treat cholera. Antibiotics are often not employed in milder cases. In severe cases, antibiotic therapy can reduce the volume and duration of the diarrhea experienced by the patient. The usual antibiotic of choice is tetracycline, although some resistant strains are emerging. Useful alternative drugs include ciprofloxacin, erythromycin, doxycycline, and furazolidone. No vaccine against cholera is presently available in the United States, although two vaccines (which are not completely effective) are available elsewhere in the world. The other agents listed in the choices are not used to treat cholera.

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