A family of three, with a 7-year-old son, takes a three-week tour of rural Mexico. They are careful about drinking only bottled beverages, but they frequently take their drinks on ice, and they use the local tap water when brushing their teeth. During the third week of their trip, they all experience mild abdominal cramps and diarrhea that persist for two days before clearing up. Two months after returning to the U. S., their son begins to experience abdominal pain. He also has a persistent fever and a dull pain in the right upper quadrant. When the symptoms fail to subside after three days, the family goes to their primary care physician to seek advice. The boy's vital signs are pretty-much normal except for a fever of 38.5ºC. Upon physical examination, the boy is found to have hepatomegaly and point tenderness over the liver. Otherwise, the examination is unremarkable. The physician asks if any other family members have been ill and learns that the father has been experiencing recurrent periods of mild fever. He has also lost about 14 pounds in the last month or so, even though he hasn't been making a special effort to diet. The father did not seek medical advice because the fever wasn't all that noticeable and he figured that he needed to lose weight anyway. The mother has no noticeable signs or symptoms of disease. On physical examination, the farther is found to have a slight fever (38ºC) and signs of hepatomegaly. There are no other remarkable findings.

Question 2.1: What is your preliminary diagnosis for the boy's illness?

The hepatomegaly and point tenderness, along with dull pain in the right upper quadrant, imply some sort of liver involvement. The symptoms and apparent incubation period (if the disease is tired to the Mexico trip) are not very suggestive of viral infectious hepatitis, and there is nothing about the family's history to suggest serum hepatitis. The diarrhea and related symptoms could be a coincidence, but if they are not, they may indicate some kind of gastrointestinal connection. A number of GI pathogens, mostly ameba and other parasites, can cause liver problems, and the family's travel history indicates that they could have been exposed to several such pathogens.

Question 2.2: What tests should you perform?

If a parasitic gastrointestinal disease is suspected, a stool sample should be examined for protozoan cysts, parasite ova, etc. Standard tests for liver function should be carried out to assess the possible liver involvement. A CT scan might help to define the nature of any problem in the GI tract or liver.

Test Results

Microscopic examination of the boy's stool fails to detect any obvious evidence of red blood cells, leukocytes, ova, or cysts. Alkaline phosphatase, bilirubin, AST, and ALT are all slightly elevated above normal levels. The CT scan reveals the presence of a large abscess in the right lobe of the liver.

Question 2.3: What is the final diagnosis? How can it be confirmed?

Despite the lack of cysts in the stool, the most likely explanation is amebic liver abscess arising as a complication of amebiasis. This finding is consistent with the symptoms (including the GI symptoms), the timing of the disease, and the family's travel history. Most of the other parasitic pathogens that are commonly or occasionally associated with liver disease can be considered unlikely, either on the basis of the boy's symptoms (e.g., Leishmania or Toxocara) or because they are not endemic to Mexico (e.g., Opisthorchis or Schistosoma).

A serological test (indirect hemagglutination) for antibodies against Entamoeba histolytica, the causative agent of amebiasis, is available and can be used to detect infection with this pathogen. In this case, the physician ordered the test to confirm the diagnosis of amebic liver abscess, and the boy's serum was found to contain a high titer of E. histolytica antibodies.

Question 2.4: Are the father's symptoms related to those of his son?

95% of the traveler's who develop an amebic liver abscess after leaving an endemic area do so within 5 months. Young patients are more likely than older patients to present with acute symptoms, which typically include fever, right-upper-quadrant pain (dull or pleuritic), and point tenderness over the liver. (Jaundice is rare.) Fewer than 1/3 of patients with an amebic abscess have diarrhea, despite the intestinal origin of the disease. Older patients (like the father in this case) are most likely to have a subacute course that lasts 6 months, with weight loss and hepatomegaly. About one third of these patients are febrile. In general, the clinical diagnosis of an amebic liver abscess can be difficult to establish because the signs and symptoms are often nonspecific. Since 10-15% of patients present only with fever, amebic liver abscesses must be considered in the differential diagnosis of fever of unknown origin.

Question 2.5: What complications are possible?

The most frequent complication of amebic liver abscess is pleuropulmonary involvement, which develops in 20-30% of patients. Manifestations include sterile effusions, contiguous spread from the liver, and rupture into the pleural space. Sterile effusions and contiguous spread generally resolve with medical therapy, but frank rupture into the pleural space requires drainage. A hepatobronchial fistula may cause cough productive of large amounts of necrotic material that may contain amebas. Abscesses that rupture into the peritoneum might present either as an indolent leak or as an acute abdomen. These abscesses require both percutaneous catheter drainage and medical therapy. Rupture into the pericardium, most often from abscesses in the left lobe of the liver, carries the gravest prognosis; it can occur during medical therapy and requires surgical drainage.

Question 2.6: How does this causative agent damage the liver?

Liver abscesses are always preceded by intestinal colonization, which can be asymptomatic. The blood vessels may be compromised early by lysis of the wall and thrombus formation. Trophozoites invade veins to reach the liver through the portal venous system. E. histolytica is resistant to complement-mediated lysis, which allows it to survive in the bloodstream. In the liver, neutrophils are lysed by contact with the amebas, and the release of neutrophil toxins may contribute to necrosis of hepatocytes. The liver parenchyma is replaced by necrotic material surrounded by a thin rim of congested liver tissue. The necrotic contents of a liver access are often described as "anchovy paste", although the fluid is variable in color. Amebas, if seen, tend to be located near the capsule of the abscess.

Question 2.7: How can this disease be treated?

The recommended approach is to use metronidazole (750 mg PO or IV for 5-10 days), tinidazole (2 g PO), or ornidazole (2 g PO), in combination with either iodoquinol (650 mg tid for 20 days) or paromomycin (500 mg tid for 10 days).