Echinococcosis is a zoonotic infection caused by tiny tapeworms of the genus Echinocococcus. Cystic Echinococcosis, also known as hydatid disease, is caused by Echinococcus granulosus and rarely by Echinococcus multilocularis.
- surgical procedures
- diagnostic imaging
- parasitic diseases
Hydatid disease is a parasitic infection that is endemic in Mediterranean countries, but it is worldwide present in consequence of the migratory phenomena. The disease is characterized by cystic lesions especially located in the liver and in the lungs. If the parasite goes beyond the pulmonary filter, it can spread to other localizations that are classified rare, very rare, or extremely rare locations .
2. Epidemiology of Echinococcosis
Hydatid disease is known since the ancient times and Hippocrates first described it as being located in the liver.
CE is globally distributed, with highly endemic areas mostly found in the eastern part of the Mediterranean region, northern Africa, southern and Eastern Europe, at the southern tip of South America, in Central Asia, Siberia, and western China. AE is confined to the northern hemisphere, in particular to regions of western and northern China, the Russian Federation, most countries of continental Europe, and northern countries of North America . CE occurs commonly in Bulgaria, Poland, Slovenia, and in Spain and elsewhere in Eastern and Central Europe, it is considered a serious public health problem in Turkey. AE has also emerged in Central and Eastern Europe in association with increases in fox populations. The infection has been reported in Germany, Lithuania, Slovakia, Slovenia, and Switzerland .
CE has a renewed importance in Europe, as reemerging cases have been documented . Furthermore, CE is reported in immigrants or persons with a history of travel to endemic areas . Several national surveillance systems for CE and AE exist in European countries based on voluntary data entry or on compulsory notification .
The recent Annual epidemiological report on food and waterborne diseases and zoonoses of the European Centre for Disease Prevention and Control (ECDC)  relates that in 2012 the case rate of
Mandatory notification of CE to the Italian Ministry of Health has been discontinued since 1991 (D. Min. San. 15.12.1991), and thus, the data on CE occurrence have only produced by the regional cases summaries. Therefore, information on CE distribution in Italy is still incomplete and insufficient and no data has been submitted for the European surveillance. However, an Italian Registry of CE was established by the Istituto Superiore della Sanità (http://www.iss.it/riec/). In Italy, the prevalence of the CE is high on the islands and medium in the central and southern regions of Italy [9–10] where farming and raising sheep are frequent activities, confirming that the disease is often an occupational one, and farming and raising sheep seem to be risk factors [11–12]. Data from the Italia registry reports that up to 75% of sheep and goats can be infected and up to 14 cases per 100,000 inhabitants (1,400 cases/year estimated) (http://www.iss.it/riec/).
As suggested, compulsory notification of
In 2013, the EchinoWorld website (www.echinoworld.org), sponsored by the International Association of Hydatidology, was developed. It provides a feasible and effective platform for professionals and scholars around world in the field of hydatid disease, with the aim to help prevention, diagnosis, and treatment especially in endemic countries and globally.
CE can be prevented by periodic deworming of dogs; improved hygiene in the slaughtering of livestock, including proper destruction of infected offal; and public education campaigns. Vaccination of livestock offers encouraging prospects for prevention and control. The World Health Organization reports that a program combining vaccination of lambs, deworming of dogs, and culling of older sheep could lead to the elimination of human cystic
3. Unusual locations of echinococcosis
About 90% of the hydatid cysts occur in the liver (65%–75%) and lungs (15%–20%), organs that can be affected simultaneously in about 5%–13% of the cases. If the cyst goes beyond the hepatic and pulmonary filters, it can spread to other organs. A possible dissemination through lymphatic channels could explain the presence of the cysts in uncommon sites .
The diameter of the parasite is about 25 microns–35 microns, and it can pass through the hepatic sinusoids (10 microns–100 microns), depending on the biophysical and structural features of the parasite, which has ameboid movements and different dimensions in the different stages of its biological cycle. It is as an emulsoid that adapts itself to the different diameters of the anatomic structures. Other factors such as pH, surface tension, and the presence of the colloids are also involved in explaining the passage of the parasite through the hepatic sinusoids. However, it is also possible that the parasite reaches the peripheral locations by passing the hepatic sinusoids through the presence of arteriovenous anastomoses or through anastomoses between the portal and hepatic veins. Furthermore, we should believe that the parasite is able to bypass the pulmonary capillary vessels in a similar way, otherwise, the incidence of the parasite in the lungs should be higher than in the liver .
In 1964, Grassi classified the peripheral locations of the hydatid disease into three groups:
rare locations: spleen, kidney, bone, muscle;
very rare locations: diaphragm, pancreas, thyroid, brain, salivary glands, subcutaneous tissue;
extremely rare locations: thymus, lymphatic nodes, adrenal gland, hypophysis, tonsils .
The percentage of site involvement varies and the exact incidence in unusual locations is about 8%–10%, but it is difficult to ascertain, as they are only reported as case reports .
Previous data reported that incidence of CE involving the spleen, kidney, peritoneal cavity, skin, and muscles was about 2-3% each and incidence of the heart, brain, vertebral column, ovaries, pancreas, gall bladder, thyroid gland, bones, and breast involvement was about 1% or less, each . Figure 1 summarizes updated data on frequencies of unusual locations of CE as reported in different scientific articles.
A recent meta-analysis conducted in Iran where
With the advent of modern DNA-based methods, the genetic variability of
4. Diagnostic serological tests
Immunodiagnosis is an important tool for diagnosis of hydatid infection. The increase in serum IgE is characteristic for helminthic disease and is stimulated by the synthesis of IL-4 from Th2 lymphocites . Different serological tests were developed and applied. Usually, they detect anti-Echinococcus IgG, but there are also methods for examination of IgE in serum such as RAST (RIA), ELISA, and Western blot. The sensitivity of the ImmunoCAP system, in some studies, is significantly lower than the sensitivity of both the ELISA and Western blot. In contrast, the ImmunoCAP system demonstrated increased specificity and decreased cross-reactivity compared with the ELISA. Western blot remains the principle method for the detection of CE because of its significantly higher sensitivity. The lower sensitivity of the ImmunoCAP system for detecting anti-Echinococcus IgE compared with the tests for specific IgG can be explained by the stronger IgG response in CE. Comparison of anti-Echinococcus IgE in hepatic and pulmonary CE showed significant differences in the immune response that were not only qualitative (more often positive in hepatic CE) but also quantitative (lower antibody levels in pulmonary CE). While there was a detectable difference in anti-Echinococcus IgG by ELISA and Western blot, the discrepancy was not significant. In rare locations of the disease, that are often peripheric locations, serological tests have shown a lower sensitivity. In conclusion, detection of anti-Echinococcus IgE could be applied as an additional confirmatory method when false-positive results are suspected from other immunological tests .
5. Imaging features
Radiological signs of
In addition to the liver and lungs, echinoccosis could be also found in different other organs; in these cases, the diagnosis could be difficult, and differential diagnosis is generally required.
Uncommon locations are briefly discussed, emphasizing imaging features.
Splenic cysts are commonly solitary and often develop secondary to systemic dissemination or intraperitoneal spread from ruptured liver hydatid cysts. Differential diagnosis includes epidermoid cyst, pseudocyts, abscess, or hematoma; also cystic neoplasms should be differentiated from hydatid splenic disease .
type 1: unilocular cysts (initial stage of parasite development)
type 2: multiple daughter cysts within the mother cyst (intermediate stage of parasitic development)
type 3: completely calcified cysts (death of the parasite)
In type 1 and type 2 cysts, the cyst wall may be thick or calcified (Figure 3), and both the wall and the internal septa may show enhancement after e.v. administration of the contrast agent. In up to 18% of cases, the cyst may rupture into the collecting system and at imaging several round filling defects may be seen due to the migration of daughter cysts within calices and renal pelvis . Differential diagnosis of renal hydatidosis includes simple or infected renal cyst, abscess, and cystic or necrotic neoplasms .
Hydatid cysts of the
Involvement of the
6. Clinical presentation
The unusual anatomic locations may cause difficulties in making the differential diagnosis, as
It is not easy, neither simple, to describe the clinical manifestations of a hydatid cyst located in a peripheric organ, very often each case presents different clinical features, as it appears from our series. In the rare localizations the hydatid disease in the beginning is almost always asymptomatic, due to the slow growth of the cyst, and frequently is incidentally diagnosed. While the clinical signs of the hepatic cysts depend on its size and location inside the liver, when it is located in the peripheric organs, after an initial period during which the cyst is asymptomatic, clinical signs appear only when the diameter of the cyst increases and determines “mechanical” clinical features, which will be different according to the organ where the cyst is located. Splenic hydatid disease is mainly produced by systemic dissemination or intraperitoneal spread from a ruptured liver cyst .
The clinical manifestations include abdominal pain, enlarged spleen, and fever . In renal hydatid disease, patients may be asymptomatic or refer non-specific clinical manifestation (flank mass, renal colic, persistent fever, hematuria, dysuria, pyuria, or hypertension) .
6.1. Personal series
In the Department of General Surgery of the University of Catania, Italy, from 1974 to 2014, 434 patients underwent surgical treatment for hydatid disease: in 319 cases (73.50%) the cyst was located in the liver, while in 79 cases (18.20%) it was located in the lungs. The remaining 36 patients (8.29%) presented a rare localization of the disease: in 3 patients (0.69%) the cyst was in the mediastinum, in 3 patients (0.69%) in the diaphragm, in one case (0.23%) in the dorsal muscle, and in 1 case (0.23%) in the subcutaneous tissue of the right lumbar region. In 28 cases (6.45%) the rare localization of the hydatid cyst was in the abdominal cavity: 11 cysts (2.53%) were in the peritoneal serosa, 9 (2.07%) in the spleen, 6 (1.38%) in the kidney, 1 (0.23%) in the adrenal gland, and 1 (0.23%) in the retroperitoneal region.
In the patients in whom the cyst was located in the peritoneal serosa, pain was present in 6 cases, a palpable mass in 4 cases, while in the other cases the cyst was incidentally diagnosed in an asymptomatic phase. Nine patients had a splenic localization and in 3 of them a hepatic cyst was also present. In 4 patients, a palpable mass in the left hypochondrium was present, 3 patients complained of a painful clinical picture, while 2 patients were asymptomatic. The patient with a cyst in the retroperitoneal space complained of a continuous pain in the right gluteal region with diffusion to the iliac bone and the omolateral thigh. A palpable mass was present in the mesogastrium. The patient with an adrenal cyst had perceived abdominal pain and dyspeptic symptoms with nausea . The patient with the localization in the dorsal muscle was a woman who had noticed a mass in the lower lateral part of the axilla, which had increased until it reached a diameter of 12 cm.
6.2. Atypical manifestations
Absolutely unexplainable was the growth pattern of the cyst located in the subcutaneous tissue of the lumbar region in a 77-year-old woman that we observed in 2007. The diameter of the mass was about 8 cm, and clinical examination revealed that the mass had a smooth surface with distinct margins (Figure 5a). Absolutely unusual, the report of CT that displayed the atypical behaviour of the cyst that seemed to originate from the liver through a little peduncle and then went into the muscle layer and reached the subcutaneous tissue of the lumbar region (Figure 5b) . These data were confirmed at surgery but a clear explanation of this atypical case has not been obtained. If a hydatid cyst develops into the liver, usually it grows inside the liver and outside it towards the peritoneal cavity, it can reach a great dimension but does not go over the abdominal wall muscles as an infiltrating tumor. A similar growth pattern may occur in cysts located in the liver cupola when, in consequence of an inflammatory process, go into the diaphragm and open to the bronchial tubes. However, in our case, infective processes were not present and so this case remains unexplainable.
6.3. Diagnostic evaluation and surgical treatment
In our experience, immunological tests have been very useful when the hydatid cyst was located in the liver, but have not showed the same diagnostic profit in patients affected by rare locations of the disease. In these cases, globally considered, echinotest has been positive in about one third of the cases. Diagnostic tools that have been essential to obtain the diagnosis were ultrasound and CT. The surgical treatment of the hydatid cysts peripherically located is not standardized, usually they are cases sporadically reported and the same great experience gained in the surgical treatment of the hepatic cysts is lacking. In hepatic cysts, a considerable reduction of the conservative surgical approaches has been reported and nowadays an increase in radical surgery is the preferred treatment.
In peripheric locations, the radical surgical removal without spreading the disease due to spillage of cystic fluid has been the treatment of choice, and this method has been applied to the cysts located in the peritoneum. In the splenic localization, splenectomy has always been performed and the patients underwent the standardized protocols to avoid the consequences of the overwhelming postsplenectomy infection . In the renal localizations it has been possible to avoid nephrectomy and realize a partial pericystectomy and no recurrences have been observed. The cyst located in the adrenal gland was treated by surrenectomy and the cysts located in the dorsal muscle and in the subcutaneous tissue of the lumbar region (Figure 5c) were easily removed.
7. Echinococcosis and allergy — Anaphylaxis
Allergic reactions and anaphylaxis are well-known features of CE. Elevated total IgE, as well as occurrence of specific IgE against Echinococcus antigens in the serum of patients with CE are also key biological features of the disease [33–34]. IgE-dependent immune reactions were long neglected in AE; obviously, anaphylactic reactions are far less frequent than in CE. However, specific IgE antibodies against
8. Medical treatment
In patients treated for liver and/or lung hydatid cysts, the possibility of secondary
Mebendazole (MBZ) and albendazole (ABZ) are the benzimidazole (BMZ) agents used for the treatment of hepatic CE. They interfere with the absorption of glucose through the wall of the parasite, causing glycogen depletion, and degenerative changes in echinococcal mitochondria and endoplasmic reticulum. BMZ may be favorably used alone for the treatment of small (<5 cm) CE liver cysts or for inoperable patients; BMZ is also usually associated with PAIR or surgery to prevent secondary CE. BMZ is not indicated for the treatment of inactive or calcified asymptomatic cysts, unless they are complicated lesions. Both ABZ and MBZ are effective, but ABZ is considered the drug of choice. The usual dose of orally administered ABZ is 10–15 mg/kg/day in two divided doses; if using MBZ, the daily dose is 40–50 mg/kg in three divided doses. Treatment with BMZ should be administered continuously for 3–6 month. Praziquantel has been used (40 mg/kg once a week) with ABZ for combined treatment of CE; this therapeutic association seems to be more effective than ABZ alone [40–41]. Usual adverse effects include nausea, hepatotoxicity, neutropenia, and occasionally alopecia . In patients treated for rare peripheric locations, in our opinion, treatment with BMZ should be especially recommended. In these patients, hepatic and pulmonary filters have been bypassed, so the disease should be considered systemic and chemotherapy should be promising in preventing further recurrences.
Although the incidence of
Part of the text of paragraph 6.2. “Atypical manifestations” and Figure 5 are used with kind permission of the publisher for World Journal of Gastroent erology. The Authors wish to thank Bench srl for the technical support. Main Authors (Antonio Di Cataldo, Giuseppe Petrillo, Claudia Trombatore, Stefano Palmucci, Antonella Agodi) did study conception, acquisition and interpretation of data, wrote the manuscript and performed the final critical revision. Other Authors cooperated in the writing the manuscript, according to their competence and specific knowledge.