Kevin C. Ruff, MD
A 36-year-old man presents with chronic diarrhea, glossitis, and peripheral neuropathy. He returned several months ago from a 6-month mission to Haiti. What is the most likely diagnosis?
What is the cause of tropical sprue?
Current evidence suggests that tropical sprue results from an infectious disease of the small intestine caused by several offending agents, all of which are toxigenic strains of coliform bacteria, including Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli. Travelers who acquire tropical sprue persist with bacterial contamination after return to a temperate climate until antibiotic treatment is given.
What is the treatment of tropical sprue?
Tetracycline or nonabsorbable sulfonamides given for several months. Additionally, daily oral folic acid and weekly parenteral B12 should be given when megaloblastic anemia is present.
What symptoms may precede gastrointestinal complaints in Whipple’s disease?
Arthralgias and fever. Migratory arthralgias of the large joints may precede the onset of diarrhea by several years.
What is the diagnostic procedure of choice for Whipple’s disease?
Upper endoscopy with multiple biopsies of duodenum or proximal jejunum. Biopsies show infiltration of the lamina propria with periodic acid-Schiff (PAS)-positive macrophages containing Gram-positive, acid-fast negative bacilli.
In the absence of histologic evidence of Whipple’s disease on small bowel biopsy, what further testing can be used to detect Tropheryma whippelii?
Polymerase chain reaction of biopsied tissue.
Why should rectal biopsy not be used to diagnose Whipple’s disease?
PAS-positive macrophages resembling those seen in Whipple’s disease may be found in the rectal lamina propria of healthy individuals and in patients with benign conditions such as melanosis coli and colonic histiocytosis.
What condition resembles Whipple’s disease histologically?
Intestinal infection with Mycobacterium avium intracellulare. The histologic lesions in these two conditions are similar; however, T. whippelii will not take up acid-fast stain.
What is the most serious sequela in a patient with Whipple’s disease?
Neurologic sequelae, including irreversible dementia, may occur several months or years after successful treatment. This suggests that, unless an antibiotic that readily penetrates the blood-brain barrier is used, the central nervous system may provide a safe haven for residual Whipple’s bacilli.
What is the treatment of Whipple’s disease?
Double-strength trimethoprim-sulfamethoxazole twice daily for a year. This antibiotic readily crosses the blood-brain barrier and should effectively eradicate central nervous system involvement. For patients intolerant of this drug, a third-generation cephalosporin can be used.
What is the treatment of a central nervous system relapse in Whipple’s disease?
Repeat initial therapy with double-strength trimethoprim-sulfamethoxazole. If unsuccessful, chloramphenicol, which also results in high central nervous system concentrations, is given at a dose of 250 mg four times a day.
What is the appearance of Cryptosporidium on mucosal biopsy specimens?
On light microscopy, the trophozoites appear as multiple, round, tiny basophilic bodies lying on the brush border of enterocytes.
After successful treatment of intestinal cryptosporidiosis in immunocompromised patients, what causes recurrence?
Seeding from the biliary tract, where Cryptosporidia can also reside.
How is Isospora belli detected in the stool?
Oocysts in the stool fluoresce bright yellow with auramine-rhodamine stain and appear pink with red-purple sporocysts on a modified acid-fast stain.
What segment of the intestinal tract is most commonly involved in histoplasmosis?
True/False: Histoplasmosis can occur in an immunocompetent host.
True. Histoplasmosis is a very common infection in the midwestern and south-central United States, where 80% of inhabitants are infected. However, gastrointestinal disease is seen only in immunocompromised individuals.
When should infection with microsporidiosis be considered?
When no other pathogens are identified in an immunocompromised patient with severe diarrhea, malabsorption, and weight loss.
What is the most specific diagnostic tool for detecting Microsporidia in intestinal biopsy specimens?
Electron microscopy. Under light microscopy, the organism is difficult to identify.
Why should patients with underlying liver disease be warned about eating raw seafood, especially raw oysters?
Vibrio vulnificus infection can be acquired through direct consumption of seafood, usually raw oysters. Subsequent septicemia has a 50% mortality rate. This infection can be lethal in patients with underlying liver disease.
What severe intestinal complications may occur in typhoid fever?
Perforation (3% of cases) and hemorrhage (20% in pre-antibiotic era). These events are not related to the severity of the disease and tend to occur in the same patient, with bleeding serving as a harbinger of a possible perforation.
True/False: The distal ileum and cecum are the most common sites of intestinal involvement with tuberculosis.
What small intestinal parasite, once ingested, has part of its life cycle in the lungs?
Ascaris lumbricoides. Duodenal larvae migrate through the epithelium into portal venous blood and eventually reach the lungs causing a pneumonitis. Larvae then migrate up the bronchioles to the pharynx, are swallowed, and develop into adults in the small intestine.
What tapeworm may cause vitamin B12 deficiency?
Diphyllobothrium latum. The worm ingests vitamin B12 and competes with the host for available vitamin B12.
What parasitic infestation may result in variceal bleeding?
Schistosomiasis. Granulomatous fibrosis occurs around entrapped ova in prehepatic portal venules with relative sparing of hepatic parenchyma. This results in presinusoidal portal hypertension.
True/False: Rotavirus, Norovirus, and Enterovirus are causes of enteritis that occur primarily in children.
False. Rotavirus and Enterovirus are most common in young children. Norovirus affects all ages and is responsible for outbreaks in camps, cruise ships, hospitals, and nursing homes.
What Gram-negative curved rod with a single flagella can cause 15–20 liters of stool per day?
True/False: Bloody diarrhea is a common symptom caused by Vibrio cholera due to the invasive nature of this organism.
False. “Rice water” stools are typical, not blood. V. cholera causes diarrhea by attaching to the intestinal epithelium and releasing a toxin which increases cAMP, leading to a secretory diarrhea.
True/False: Yersinia enterocolitis typically occurs in children over the age of 5 years and may be confused with acute appendicitis.
True. Radiographic imaging studies may be useful to distinguish between the two.
True/False: There is no substantial evidence that antibiotics alter the course of Yersinia gastrointestinal infection, even in immunocompromised patients.
True, although antibiotic treatment is mandatory in the latter.
Daycare centers and well water are risk factors for which protozoal infection?
Giardia lamblia (also known as G. intestinalis and G. duodenalis). Infective cysts are ingested and the flagellated trophozoites become active after excystation due to gastric acid exposure.
Which treatment for Giardia may be most appropriate for pregnant women?
Paromomycin is not absorbed and so poses less risk to the developing fetus than metronidazole or nitazoxanide.
What is the most likely route of transmission for Cyclospora cayetanensis?
Contaminated water or produce, especially during wet summer months. There is no person-to-person spread.
Charcot-Layden crystals are found in stool analysis for which protozoal infection?
Isosporidia. Individuals may also have peripheral eosinophilia.
A serpiginous, pruritic rash known as cutaneous larva migrans occurs in which nematode infection?
Hookworm. Exposure to soil contaminated with human waste allows entry through the skin, causing this characteristic rash.
True/False: Trichenella is identified primarily on stool testing.
False. Eggs are laid after invasion of the intestinal villae and larvae mature in striated muscle. Diagnosis is made by serology or muscle biopsy.
Which cestode is the largest human parasite?
Diphyllobothrium latum (fish tapeworm). It can grow up to 40 feet long.
Cysticercosis is caused by which parasitic organism and how is it treated?
Taenia solium. Albendazole is the treatment of choice with steroids as needed for inflammation that develops during treatment.
What is the most common tapeworm in humans?
Hymenolepis nana (dwarf tapeworm). It is the smallest but most common tapeworm in humans due to the ease of person-to-person transmission, self-inoculation, and internal autoinfection.
What intracellular parasitic infection is a common cause of diarrheal outbreaks in chlorinated pools?
Cryptosporidiosis. Cryptosporidium is chlorine resistant in the spore form with excystation occurring in the small intestine due to bile salt exposure.
What is the treatment of choice for cryptosporidiosis?
Nitazoxanide is the only known drug with consistent efficacy in treating Cryptosporidium.
What host mechanisms prevent against the development of small intestinal bacterial overgrowth (SIBO)?
Intestinal motility, gastric acid production, intestinal epithelial mucus layer, bile and pancreatic secretions, as well as the intestinal immune system.
True/False: An intact ileocecal valve is the most important anatomical factor predisposing to the development of SIBO.
False. Blind loops and strictures are more important anatomical factors. In fact, the role of the ileocecal valve in preventing SIBO in nonshort bowel syndrome patients remains unclear.
What are the most common presenting signs and symptoms of SIBO?
The most frequent presenting symptoms are abdominal pain, diarrhea, weight loss, bloating, excess flatulence, malabsorption, and anemia (usually macrocytic).
True/False: Elevated vitamin B12 and decreased folate levels are classic findings in SIBO.
False. The opposite is true; albeit, uncommon.
True/False: Given the limitations in diagnostic testing for SIBO, empiric antibiotic therapy is the recommended “diagnostic” tool of choice in suspected SIBO.
False. Although this approach appears to be commonly followed in clinical practice, it is not recommended due to the difficulty in determining the response and the cost and side effects of antibiotic treatment. (Note: Additional questions regarding SIBO, diagnostic testing for SIBO in particular, are in the Chapter 22 “Small Intestinal Motility Disorders.”)
Describe the major treatment modalities used in SIBO.
Treatment of the underlying disease and antibiotics represent the major treatment modalities. Although modification of the diet to include high-fat, low-carbohydrate, and low-fiber elements has been recommended, there is no evidence from controlled trials to support this approach.
True/False: Antibiotic therapy in SIBO should focus on anaerobic organisms.
False. Effective antibiotic treatment should cover both aerobic and anaerobic enteric bacteria given the usual broad-spectrum of the microbes involved. Similarly, bacterial culture and sensitivity testing is often not helpful since various bacterial species with different antibiotic sensitivities coexist.
What organisms are commonly implicated in traveler’s diarrhea?
E. coli (ETEC), Shigella, Campylobacter, and Salmonella are the most common bacterial causes. Viruses and parasites also may be responsible and include such organisms as rotavirus, Giardia, Cryptosporidia, and Cyclospora.
True/False: Parasitic causes of traveler’s diarrhea are common in traveler’s to Mexico.
False. Parasitic traveler’s diarrhea is rare.
True/False: Traveler’s diarrhea follows a benign, self-limited course in the vast majority of cases.
True. However, dehydration can occur and may be serious.
True/False: A college student on spring break to Cancun has an equal risk of contracting traveler’s diarrhea as a business executive attending an industry conference in Mexico City.
False. Traveler’s diarrhea is more common in younger adults than older adults and more common in traveling students or tourists than business professionals or people visiting relatives.
Since traveler’s diarrhea is generally self-limited, treatment is often symptomatic and initiated without documenting an etiologic agent. When should treatment be considered and what are the main treatment modalities?
If symptoms are severe and associated with toxicity or if they persist beyond 48 to 72 hours, intervention may be necessary. Fluid replacement is the mainstay of treatment. Antibiotics and antidiarrheal agents may also be needed.
True/False: Stool culture should always be done prior to antibiotic treatment in cases of suspected traveler’s diarrhea.
True/False: Antibiotic therapy reduces the duration of illness by about 1 day.
True. Antibiotics are warranted to treat diarrhea in those who develop moderate to severe diarrhea as characterized by more than four unformed stools daily, fever, blood, pus, or mucus in the stool. Common antibiotic agents used include fluoroquinolones, azithromycin, and rifaximin. Quinolones are usually given for 1 or 2 days after the onset of diarrhea, while the others are typically given for 3 days.
True/False: Bismuth subsalicylate can be an effective prophylaxis for traveler’s diarrhea.
True. Greater than 50% of cases of traveler’s diarrhea can be prevented by daily use of bismuth subsalicylate. Antibiotics may be more effective but are expensive and have a greater risk of side effects. Bismuth can also be used to treat an episode of traveler’s diarrhea; however, large doses are generally required with the potential for salicylate toxicity.
True/False: Prophylactic antibiotics are recommended for all travelers to developing countries.
False. Although prophylactic antibiotics prevent the majority of diarrheal disease in travelers, they are generally not recommended unless the complications of diarrhea or an underlying medical condition make the consequence of dehydration so severe that the benefits of using antibiotic prophylaxis outweigh the risks.
• • • SUGGESTED READINGS • • •
Hill DR, Beeching NJ. Travelers’ diarrhea. Curr Opin Infect Dis. 2010 Oct;23(5):481-487.
Quigley EM, Abu-Shanab A. Small intestinal bacterial overgrowth. Infect Dis Clin North Am. 2010 Dec;24(4):943-959.
Nath SK. Tropical sprue. Curr Gastroenterol Rep. 2005 Oct;7(5):343-349.
Afshar P, Redfield DC, Higginbottom PA. Whipple’s disease: a rare disease revisited. Curr Gastroenterol Rep. 2010 Aug;12(4):263-269.
Gianella R. Infectious Enteritis and Proctocolitis and Bacterial Food Poisoning. In: Feldman M, Friedman, L, Brandt L, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Diseases. 9th ed. Philadelphia, PA: Saunders-Elsevier; 2010:1843-1886.