Echinococcosis: Cystic and Alveolar Disease

Hepatic Disease

Owing to the distensible nature of the liver, hepatic cysts may grow for years before becoming symptomatic. Solitary cysts are most common, and the right lobe is affected more often than the left lobe. The size of the cyst is variable, ranging from 1 to 15 cm. Hepatic cysts can cause pain in the upper abdominal region secondary to pressure from an enlarging cyst. Within the liver, the maturing cyst form of E. granulosus consists of an internal germinal layer surrounded by an acellular, parasite-derived laminated layer; together they form the endocyst. The endocyst is surrounded by the pericyst, or adventitial layer, and is largely derived from host tissue. By 3 weeks of development, the cyst is approximately 250 μm in size, and by 20 weeks, it is about 1 cm in size. The central cavity of an E. granulosus cyst is filled with hydatid fluid, which is similar in composition to the interstitial fluid. Intracystic pressure increases as the cyst grows and reaches maturity.

As the cyst grows, cells bud from the germinal layer. They develop stalks, becoming “brood” capsules in the central cystic cavity. From the wall of the brood capsule, a protoscolex develops. The protoscolex is able to develop into a daughter or secondary cyst if accidentally spilled or into a mature worm in the definitive host if ingested. As the primary cyst matures the brood capsule detaches from the germinal layer and ultimately will degenerate, releasing protoscolices into the hydatid cyst fluid, forming the “hydatid sand” characteristically found in older cysts. Daughter cysts, a pathognomonic feature of Echinococcus , resemble the primary cyst with the exception that the pericyst is not present (see Figs. 85.1 and 45.2).

Complications of hepatic echinococcosis can occur with devastating consequences if not recognized and managed properly by the clinician. Communication with and rupture of hepatic cysts into the biliary tree are well described and can result in cholangitis and cholestasis. With frank intrabiliary rupture, the daughter vesicle and germinative membrane pass into the main biliary ducts, resulting in obstructive jaundice in some cases. In these instances, patients experience epigastric pain and right-upper-quadrant pain. A cystobiliary fistula should be considered when there is acute or intermittent pain mimicking biliary colic, and these patients should be managed surgically. If cysts are left untreated, cholangitis can occur, with resultant bacterial superinfection of the cyst cavity and abscess formation. It is important to establish the diagnosis of a cystobiliary communication preoperatively because, owing to the risk of sclerosing the biliary tree, sclerosing agents should be avoided. Less commonly, portal hypertension can complicate hepatic CE by extrinsic compression of the liver or by obstruction of the inferior vena cava and hepatic outflow tract. Rarely, parasitic emboli may result from rupture of a cyst into the hepatic vein or inferior cava. Rupture or leakage of the cyst into the peritoneal cavity can result in acute or intermittent allergic manifestations and secondary CE. Mild to severe anaphylactoid reactions (and occasionally death) may follow the sudden massive release of cyst fluid.

Two commonly used imaging-based classification systems correlate individual hepatic cyst stage with natural progression of hepatic cysts and have therapeutic implications. They are the World Health Organization (WHO) Informal Working Group on Echinococcosis (IWGE) and the Gharbi classification systems; both are very similar, and this chapter refers to the WHO-IWGE classification system. The WHO-IWGE standard classification allows for a natural grouping of cysts: active CE1 and 2, CE3, and inactive (CE4 and CE5). Table 85.1 summarizes the stratified approach to treatment based on cyst stages. CE1 is a unilocular anechoic cystic lesion with a double sign. CE2 is a multiseptated, “rosette-like” “honeycomb” cyst. Both CE1 and CE2 are considered active, usually fertile cysts containing viable protoscolices. CE3a is a cyst with detached membranes (“water lily” sign), whereas CE3b has daughter cysts in a solid matrix. A cyst with heterogeneous hypoechoic or hyperechoic contents and no daughter cysts is the CE4 stage, and calcified cysts are considered CE5. CE types 4 and 5, which are inactive, have normally lost their fertility and are degenerative. When the physician is considering what the best modality of treatment for a patient with hepatic CE would be, he or she must take into consideration the location, size, and staging of the cyst.

TABLE 85.1

Treatment Modalities for Uncomplicated Cystic Echinococcosis Stratified by Cyst Stage

Image for CE1 courtesy Prof. P. Kern, Division of Infection Diseases and Clinical Immunology, Comprehensive Infectious Diseases Center, University Hospitals, Ulm, Germany; images for CE2 and CE3b courtesy Prof. C. Coyle, Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, New York; image for CE3a courtesy Prof. E. Brunetti, Division of Infectious and Tropical Diseases, University of Pavia, IRCCS S. Matteo Hospital Foundation, Pavia, Italy; images for CE4 and CE5 courtesy Prof. B. Gottstein, Institute of Parasitology, University of Bern, Bern, Switzerland.

World Health Organization Classification, 2001	Radiographic Image		Current Practice
			Surgery	Percutaneous Techniques	Medical Treatment	Suggested a
CE1		Hepatic unilocular anechoic cystic lesion with a double sign (ultrasound)	Practiced	Practiced	Practiced	PAIR + ABZ if >5 cm ABZ alone if <5 cm
CE2		Multiseptated, “rosette-like” or “honeycomb” cyst in the liver (ultrasound)	Practiced	Rarely practiced	Practiced	Non-PAIR PT + ABZ Surgery + ABZ
CE3a		Hepatic cyst with detached membranes (“water lily” sign) (ultrasound)	Practiced	Practiced	Practiced	PAIR + ABZ if >5 cm ABZ alone if <5 cm
CE3b		Hepatic cyst showing daughter cysts in solid matrix (CT scan)	Practiced	Rarely practiced	Practiced	Non-PAIR PT + ABZ Surgery + ABZ
CE4		Hepatic cyst showing heterogeneous hypoechoic or hyperechoic contents and no daughter cysts (ultrasound)	Regard as inactive; unless complicated, they should not be treated Watch and wait
CE5		Calcified hepatic cyst (CT scan)

ABZ, Albendazole; CE, cystic echinococcus; CT, computed tomography; PAIR, percutaneous aspiration-injection-reaspiration; PT, percutaneous treatment.

a See text for discussion.

Pulmonary Disease

Pulmonary hydatid disease has been reported in up to 30% of cases of hydatidosis in some series and can be either primary or secondary. Uncomplicated lung cysts rarely produce symptoms and are usually found incidentally at imaging. In patients who are symptomatic, chest pain with cough, dyspnea, and hemoptysis are often the presenting symptoms. Fever is less common and usually seen in cases of bacterial superinfection. The hydatid cyst can occur anywhere in the lung, but it settles more often on the right side and has a predilection for the lower lobes. It generally is a single cyst, and in up to 25% of cases there is a coexisting hepatic cyst. Pulmonary cysts may be multiple and/or bilateral in approximately 30% of cases. Typically, cysts grow at an average rate of 1 cm in diameter per year. However, growth rates of up to 5 cm/year have been noted. Because the period of initial cyst growth is frequently asymptomatic, pulmonary hydatid disease most frequently manifests in the second to third decade of life. Cysts may be entirely asymptomatic in 75% of cases at initial detection, and asymptomatic pulmonary cysts are more likely to be found in areas of the world where chest radiographs are taken for mass tuberculosis screening programs.

Pulmonary hydatid cysts have a two-layer wall; the outer layer (exocyst), white and fragile, is made up of concentric sheets of hyaline, and the inner layer is the germinal layer, or the endocyst. Unlike hepatic cysts, daughter cysts are rarely seen. The content is liquid, with some solid elements that constitute the “hydatid sand,” made up of hooklets and scolices. In “closed” cysts the fluid resembles water. It contains antigenic elements that are responsible for the anaphylactic phenomenon that may appear when the cyst ruptures.

As with hepatic lesions, the adventitia (pericyst) is the result of the inflammatory response of the organ in which the parasite settles. It consists of three layers: an inner layer, which is smooth and glossy; a middle layer, which is of a fibrous nature; and an outer layer, with active inflammation. Atelectasis is seen around the adventitia, but more extensive alterations such as bronchiectasis and interstitial sclerosis can be seen.

When pulmonary cysts rupture into neighboring bronchi with formation of cystobronchial fistulas, a typical “salty water and grape skin” expectoration may occur. Cysts may also become infected in this setting. A large pulmonary cyst can cause stenosis and occlusion of the bronchi. Pleural effusion may develop in 30% of the cases and may occur secondary to cyst rupture into the pleural space. Rupture can lead to severe complications, such as massive hemoptysis and tension pneumothorax.

In contrast to perforation into a bronchus, rupture of a hydatid cyst into the pleural cavity usually causes pneumothorax, pleural effusion, or empyema. Cyst rupture into the pleural cavity can also result in tension pneumothorax. Rupture of a cyst into the pleural cavity or into the bronchial tree may also lead to secondary larval spread or to allergic and anaphylactic reaction. Although extrapulmonary hydatid cyst rupture may cause fatal anaphylaxis, the incidence of this phenomenon is low in association with pulmonary cysts.

The typical radiographic appearance of pulmonary hydatid disease is that of one or more homogeneous round or oval masses with smooth borders surrounded by normal lung tissue ( Fig. 85.2 ). Large cysts can shift the mediastinum, induce a pleural reaction, or cause atelectasis of the surrounding parenchyma. Pulmonary cysts rarely calcify, and the contents of the cyst are usually homogeneous, with a density close to that of water. The introduction of air between the pericyst and exocyst produces the appearance on imaging of a thin layer around the exocyst, which is referred to as the crescent , or meniscus , sign . If the ruptured cyst communicates with the tracheobronchial tree, evacuation of the contents of the cyst results in an air-fluid level. The endocyst may appear to float in the remaining fluid, producing a characteristic radiographic feature known as the water-lily sign .

Bone Disease

Hydatid disease of the bone is rare and accounts for only 0.5% to 4% of echinococcal disease in humans. The spine is the most common site, accounting for 50% of cases, followed by the pelvis and hip. Other osseous sites for infection include the femur, tibia, fibula, ribs, scapula, clavicle, and tarsal bones. Patients experience pain, swelling, and occasionally pathologic fracture when the condition occurs in the long bones or neural compromise when it occurs in the spine.

In cases involving the spine, radiographs show pedicle erosion and loss of vertebral body height. Plain radiographic findings include multilocular osteolysis and reactive sclerosis of a honeycomb nature. Computed tomography (CT) demonstrates erosions of the body, pedicle, and lamina of the cancellous bone without a subperiosteal reaction. Magnetic resonance imaging (MRI) is superior to CT in evaluating the extent of disease preoperatively and can also be helpful for evaluating recurrence. Successful treatment of vertebral hydatidosis represents a challenge because of its invasive features. Surgery is the treatment of choice, but adjuvant anthelmintic chemotherapy is essential to control the disease locally, avoid systemic spread, and prevent recurrences. Wide surgical excision is particularly difficult to achieve in the spine and the pelvis, but medical therapy alone is not appropriate.