Alveolar Hydatid Disease
Echinococcus multilocularis is a cestode that differs morphologically and biologically in its larval and adult stages from E. granulosus. The usual definitive host is the fox, with dogs and cats acting as sources of human infection in endemic areas. Intermediate hosts are rodents and humans. The larval stage develops normally in rodents, but humans are unusual and poor intermediate hosts. The disease is usually found across much of the Soviet Union, central Europe, northern Japan, Alaska, and northern Canada. Human disease is rare in the Western Hemisphere, but the cestode is endemic in the north-central United States and Canada.
The infection usually occurs during childhood. A case-control study has identified the following risk factors: having a lifetime pattern of dog ownership, tethering dogs near the house, and living in a house built directly on the tundra rather than on gravel or permanent foundations, thus allowing contact with contaminated dog feces. 15 Other implicated factors are the drinking of unboiled melted snow and the skinning of foxes. The disease manifests usually between the ages of 19 and 40 years but has been seen in those as young as 5 years. The mean age at diagnosis in Alaska is 53 years. The disease favors neither sex.
The larval cestode persists in its proliferative phase because of the inability of humans to provide the conditions necessary for normal development. Instead of developing a thick, laminated layer and growing into large, single cysts, the parasite has a thin, deficient ectocyst that grows and infiltrates into the surrounding tissues. The growing cyst may have several small, fluid-filled pockets containing protoscoleces. Because of its structure, this larval form is called an alveolar or multilocular hydatid. It provokes a severe host reaction and becomes surrounded by an inflammatory or granulomatous reaction, instead of the fibrous host response seen with E. granulosus. A central area of necrosis is always seen.
The cyst is slow growing, behaves like a malignancy, and has been mistaken for carcinoma, which it can mimic clinically and microscopically. Untreated it can be just as devastating, with mortality rates as high as 80%. The primary site of infection is the liver, where a dense honeycomb of small, multilocular cysts is formed. The cyst appears as a solid cancerlike growth that may cavitate and attain massive size. Through the inferior vena cava it may metastasize to distant organs. Alveolar hydatid disease of the lung is invariably a metastatic focus.
Diagnosis is based on history of exposure, elevated serologic titers, and characteristic changes on radiographic studies. Physical signs are confusing, and subjective symptoms may be mild, vague, and ill defined. Patients present usually with asymptomatic hepatomegaly. When symptoms are present, they are commonly related to the abdomen: mild epigastric and right upper-quadrant abdominal pain or distress, intermittent fever, and jaundice.
On radiologic examination, hepatomegaly and hepatic calcification are the most common findings. Typically, the diagnosis is made with abdominal radiographs that show scattered radiolucent areas surrounded with calcification, sometimes referred to as the “Swiss cheese” liver calcification pattern. This finding is pathognomonic, but at least 5 years of illness must elapse before calcification can be demonstrated. Without the characteristic radiographic study, the diagnosis is rarely made preoperatively.
CT and ultrasonography will demonstrate an indistinct mass with a necrotic center. Serologic tests used are the same as those for E. granulosus but tend to produce more positive findings with high titers. Indirect hemagglutination titers decline markedly during the first year after radical surgical resection but not after chemotherapy. The EM2 ELISA, using a semipurified homologous antigen fraction, is more sensitive and specific than tests using heterologous E. granulosus antigen fractions. 16 Results may still be positive, however, even when the parasite is no longer viable. 17 Needle biopsy confirms the diagnosis. There is no risk for anaphylaxis or spillage of protoscoleces because the tumor is essentially solid.
Treatment is by surgery. Early diagnosis is very important to permit resection before infiltration becomes too extensive. However, many cases are undiagnosed until they are well advanced and the hepatic lesions are unresectable.
At surgery, liver invasion is often more extensive than suggested by the degree of calcification on the radiograph. Complete excision is the only hope. Cure is possible when partial hepatectomy or hepatic lobectomy can remove all multilocular cysts and still preserve enough organ function. Still, radical hepatic resection is curative in only 20% of cases. Palliative measures are designed to ensure adequate bile drainage.
If surgery is unsuccessful or impractical, mebendazole is recommended at 40 mg/kg/day in divided doses for life, which may prevent progression of the primary lesion and metastasis and prolong life. Benzimidazole compounds are parasitostatic rather than parasitocidal for E. multilocularis. Thus, treatment with these agents implies lifelong application. The overall success rate of such treatment ranges between 55% and 97%. Hepatic toxicity with the use of this drug can develop without warning, however, and does not seem to be dose related or likely due to hypersensitivity. Hepatic function should be monitored the entire time the drug is administered. Monitoring should be done weekly during the first month and monthly thereafter. Amphotericin B has shown to have some benefit as salvage treatment.
Though not fulminating, the disease is ultimately fatal unless early surgical intervention can remove the parasite cyst. Patients have survived at least 16 years after diagnosis. Death is due to liver failure; invasion of contiguous areas; and metastases to the lung, brain, and distant organs. The best means of preventing alveolar hydatid disease remains the control of the cestode in domestic animals, the primary source of human infection.
People who accidentally swallow the eggs of the Echinococcus multilocularis tapeworm are at risk for infection. People at high risk include trappers, hunters, veterinarians, or others who have contact with wild foxes, or coyotes, or their stool, or household dogs and cats that have the opportunity to eat wild rodents infected with AE. Humans can be exposed to these eggs by “hand-to-mouth” transfer or contamination.
- By directly ingesting food items contaminated with stool from foxes or coyotes. This might include grass, herbs, greens, or berries gathered from fields.
- By petting or handling household dogs or cats infected with the Echinococcus multilocularis tapeworm. These pets may shed the tapeworm eggs in their stool, and their fur may be contaminated. Some dogs “scent roll” in foreign material (such as wild animal feces) and may become contaminated this way.
Where is alveolar echinococcosis (AE) found?
AE is found worldwide, mostly in northern latitudes. Cases have been reported in central Europe, Russia, China, Central Asia, Japan, and North America. In North America Echinococcus multilocularis is found primarily in the north central region from eastern Montana to central Ohio, as well as Alaska and Canada. Rare human cases have been reported in Alaska, the province of Manitoba, and Minnesota. Prevalence among wild foxes and coyotes can be high, and may reach over 50% in some areas; however, even in these areas, transmission to humans has been low.
What are the symptoms of alveolar echinococcosis (AE)?
AE is caused by tumor-like or cyst-like tapeworm larvae growing in the body. AE usually involves the liver, but can spread to other organs of the body. Because the cysts are slow-growing, infection with AE may not produce any symptoms for many years. Pain or discomfort in the upper abdominal region, weakness, and weight loss may occur as a result of the growing cysts. Symptoms may mimic those of liver cancer and cirrhosis of the liver.
What should I do if I think I have alveolar echinococcosis (AE)?
See your health care provider if you think you may have alveolar echinococcosis (AE). Diagnosis of AE can be made by a blood test that looks for the presence of antibodies to Echinococcus multilocularis.
How is alveolar echinococcosis (AE) treated?
Surgery is the most common form of treatment for AE, although removal of the entire parasite mass is not always possible. After surgery, medication may be necessary to keep the cyst from growing back.
Can alveolar echinococcosis (AE) be prevented?
If you live in an area where Echinococcus multilocularis is found in rodents and wild canines, take the following precautions to avoid infection:
- Don’t touch a fox, coyote, or other wild canine, dead or alive, unless you are wearing gloves. Hunters and trappers should use plastic gloves to avoid exposure.
- Don’t keep wild animals, especially wild canines, as pets or encourage them to come close to your home.
- Don’t allow your dogs and cats to wander freely or to capture and eat rodents.
- If you think that your pet may have eaten rodents, consult your veterinarian about possible preventive treatments.
- Wash your hands with soap and warm water after handling dogs or cats, and before handling food.
- Teach children the importance of washing hands to prevent infection.
- Do not collect or eat wild fruits or vegetables picked directly from the ground. All wild-picked foods should be washed carefully or cooked before eating.
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This information is not meant to be used for self-diagnosis or as a substitute for consultation with a health care provider. If you have any questions about the parasites described above or think that you may have a parasitic infection, consult a health care provider.
Echinococcosis is a parasitic infection of humans caused by the larval stage of the tapeworm Echinococcus. Of the two main forms of the infection, the unilocular cystic form caused by E. granulosus is far more common than the rare multilocular alveolar form caused by E. multilocularis .
E. granulosus cysts are characterized by typical radiologic patterns that are easily diagnosed, but diagnosis of E. multilocularis lesions is more difficult. The alveolar cysts grow by exogenous proliferation and behave like a malignant neoplasm. Therefore, E. multilocularis lesions can cause physicians to generate a long list of differential diagnoses, including malignant tumors. However, making the correct diagnosis is possible if imaging findings are correlated with appropriate clinical findings.
We give an overview of the various radiologic patterns produced by E. multilocularis lesions as seen on sonography, CT, and MR imaging and discuss the involvement of various organs and tissues and common complications.
E. multilocularis is endemic in much of the upper Midwest of the United States, Alaska, Canada, Japan, central Europe, and parts of Russia . Definitive hosts are foxes and, less commonly, cats and dogs. Intermediate hosts are wild rodents. Humans are infested either by direct contact with definitive hosts or indirectly by intake of contaminated water or contaminated plants such as wild berries. E. multilocularis can affect any organ or tissue in the body, although the liver and the lungs are the most common sites of hydatid disease. Diagnosis can be established by imaging techniques, immunologic tests, or percutaneous biopsy.
E. multilocularis produces multilocular alveolar cysts (1-10 mm in diameter) that resemble alveoli and grow by exogenous proliferation with cysts progressively invading the host tissue by peripheral extension of the processes originating in the germinal layer. The larva causes invasive and destructive changes in the human host that often lead to complications.
The liver is the most common site of E. multilocularis infection with more than 90% of patients having infected livers. Splenic involvement is rare, representing less than 5% of all manifestations of the infection in humans. The lesions may be single or multiple. Seventy percent of these lesions develop in the right liver lobe and 60% in the hilar region .
The clinical course of alveolar hydatid disease resembles that of a slowly developing tumor. In the liver, the oncosphere (the first larval stage of E. multilocularis) under-goes a metamorphosis into the metacestodal stage. Small, low-attenuation cysts with diameters of less than 1 cm (Figs. 1A and 1B ) represent metacestodal vesicles . These fluid-filled vesicles of the asexually proliferating metacestodes are composed of an inner germinal layer, a syncytial tegument, and an outer acellular “laminated” layer. Growing E. multilocularis lesions show a great tendency to form central liquefactive necrosis, which may be surrounded by vital metacestodal vesicles. Necrosis is caused by vascular involvement associated with ischemia .
On sonography, these lesions usually show a “hailstorm pattern” ( Fig. 2A ). This pattern represents the histopathologically heterogeneous stroma containing microscopic metacestodal vesicles, areas of nonliquefactive necrosis, entrapped host tissue, and microcalcifications, which account for the stroma’s relatively increased echogenicity [2, 4].
CT ( Fig. 2B ) and MR imaging display multiple irregular, ill-defined lesions scattered throughout the involved liver tissue. This radiologic pattern resembles that of metastases or primary hepatic neoplasm .
Large areas of central necrosis are difficult to differentiate from abscesses. (Figs. 3A , 3B , and 4 ). However, there is poor or no enhancement after bolus administration of IV contrast medium, emphasizing poor vascularization of the parasitic lesion. Usually, no lymphadenopathy is observed .
In advanced stages, peripheral calcifications may be seen within the areas of central necrosis (Figs. 5A and 5B ). Secondary pyogenic infection may occur at any time during the course of disease, resulting in abscess formation ( Fig. 5C ). Apart from the typical peripheral irregular calcifications, large homogeneous ( Fig. 6 ), multiple punctiform ( Fig. 7A ), or scattered calcifications may be seen. Calcifications are found in 90% of all infected patients .
Hilar infiltration is observed in approximately 50% of all patients, resulting in dilatation of the intrahepatic bile ducts (Figs. 7A and 7B ) and invasion of the portal vein (Figs. 8 and 9 , the portal branches, and the hepatic veins. These conditions lead to hypoperfusion and subsequent atrophy of the affected liver segments (Figs. 7A and 10 ). This atrophy is further aggravated by marked fibroinflammatory reactions of the liver tissue .
Lung involvement is rare in E. multilocularis infections . Patients with pulmonary lesions may remain asymptomatic for a long time, and thus the lesions are often discovered incidentally. The disease spreads either by hematogenous dissemination ( Fig. 11 ) or by direct invasion of parasitic tissue from adjacent structures ( Fig. 12A ).
Multiple bilateral pulmonary lesions are difficult to distinguish from other pulmonary diseases such as pulmonary metastatic disease, E. granulosus infection, Wegener’s granulomatosis, or other granulomatous lung diseases.
Clinical symptoms include thoracolumbar pain, abscess and fistula formation, and painless palpable nodules. In most patients, bone lesions develop as a result of progressive invasion of the adjacent echinococcal tissue into the bone. Therefore, the sternum and the vertebrae ( Fig. 12C ) are the most common sites of osseous lesions. Lesions caused by hematogenous dissemination have been described in the ribs, vertebrae, and gluteal region .
Soft-tissue lesions are displayed clearly on MR imaging and CT. Multiple small, clustered cystic structures can be identified ( Fig. 13 ). Contrast enhancement is probably due to an inflammatory reaction of adjacent soft tissue .
Involvement of the peritoneum occurs because of secondary infection caused by either cyst rupture or direct invasion from adjacent structures. Patients present with abdominal distention, meteorism, and constipation.
On CT, the omentum appears thickened by multiple thin-walled hypodense cysts resembling pseudomyxoma peritonei ( Fig. 3C ). Lesions of the same morphology can be found in the minor pelvis mimicking drop-metastases or primary urogenital tumors ( Fig. 3D ). However, ascites is often missing even in cases of extensive involvement of the peritoneal cavity . Pancreas, adrenal glands ( Fig. 13 ), and kidneys ( Fig. 14 ) may be affected by direct spread of adjacent echinococcal tissue or by hematogenous metastases. Retroperitoneal lesions may infiltrate veins and enclose arteries (Figs. 12B , 12C , 12D ).
E. multilocularis lesions are difficult to diagnose. The frequent presence of clusters of microcalcifications (appearing in 90% of the patients) is of great value in establishing a positive diagnosis, especially if the patient has few clinical symptoms and no history suggesting exposure to E. multilocularis, such as residing in a rural area. In cases of extensive peritoneal or retroperitoneal involvement, contrast enhancement and ascites usually are missing.
Presented at the annual meeting of the Radiological Society of North America, Chicago, November 1999.
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