In this article, we report from Northern Iraq a cluster of GI and hepatic eosinophilic granulomatous abscesses that were not recognized in the region prior to 2009. This pathology is relatively rare, and the medical literature is vague about possible causative agents. We show that, in this region of Iraq, some eosinophilic granulomatous abscesses can be attributed to F. hepatica
and others to a fungus consistent with Basidiobolus ranarum
. Although, two of the 14 cases could not be ascribed to a specific etiologic agent, none of the patients had serological or pathological evidence for Toxocara
or Echinococcus granulosis
, the latter being the most common clinical parasitic disease of the region
The currently recommended criteria for the diagnosis of fascioliasis include peripheral eosinophilia and positive serological testing for antibodies to the organism
]. Additional symptoms of the acute hepatic stage consist of fever, malaise, right subchondral pain, and weight loss. CT may show irregular hypodense lesions within the liver
]. Stool examinations for eggs can be diagnostic but are usually negative because of a generally low concentration of adult flukes and irregular shedding of eggs
]. The immature flukes that penetrate the liver are rarely seen in histologic sections, and a tissue diagnosis of fascioliasis is usually not possible
On the basis of the serological findings, five of the 14 patients with eosinophilc abscesses were diagnosed as having F. hepatica infestations. On the basis of a borderline serological result, one additional patient was considered to be suspicious for fascioliasis. All 6 of these patients presented with right subcostal abdominal pain and eosinophilia. By CT or ultrasonography, a 3 to 6 cm in diameter cystic mass was found in the right lobe of the liver in 3 patients, and small hypodense lesions were scattered thoughout the liver in 3 other patients. The surgical pathology specimens of both the larger and the smaller lesions demonstrated eosinophilic granulomatous abscesses with no evidence of flukes or ova.
In six patients, the eosinophilic abscesses contained pauci-septate hyphae surrounded by a Splendore-Hoeppli reaction. While a definitive diagnosis requires culture, a probable diagnosis of basidiobolomycosis can be made histologically
]. The species Basidiobolus ranarum
is a Zygomycete
fungus belonging to the order Entomophthorales
]. The differential diagnosis consists of the entomophthoromycosis Conidiobolus coronatus
and Conidiobolus incongruous
that like basidiobolomycosis incites an eosinophilic granulomatous tissue reaction and the Splendore-Hoeplli phenomonon. Conidiobolus
is primarily a tropical disease that produces sinonasal infections and subcutaneous abscesses. Oropharyngeal and laryngeal disease has been reported, but Conidiobolus
is not a known cause of intestinal infections
]. Vikram et al.
] have recommended that the definition of probable GI basidiobolomycosis include the identification of disease at a site below the esophagus in the stomach, large or small intestine, anus, liver, gall bladder, or pancreas.
In this current study, patients with probable basidiobolomycosis had fever, malaise, weight loss, and mild to moderate eosinophilia, but the predominant finding was an abdominal mass with intestinal obstruction. One patient had an ulcerating oropharyngeal and glottic mass and obstructing disease of the transverse colon. This oropharyngeal disease was included as an example of GI basidiobolomycosis on the basis of the patient's colon involvement and on the basis of the definition of the GI tract by the National Library of Medicine-Medical Subject Headings including all derivatives of the embryonic entoderm from the mouth to the anus
]. As an example of probable oropharyngeal basidiobolomycosis, the case extends the reported level of GI involvement to above the stomach and overlaps with locations infected by Conidiobolus
It is suggested that GI basidiobolomycosis is acquired by the ingestion of contaminated soil or animal fecal material
]. The animal herds at the outskirts of Sulaimaniyah make dung ubiquitous, and the dry climactic conditions throughout the warm months of the year may contribute to the windborne spread of organisms
]. It is notable that five of the six patients with basidiobolomycosis were diagnosed in May, August and October, and that currently GI basidiobolomycosis is the most common deep fungal infection diagnosed in our community. It is also notable that cutaneous entomophthoromycosis, that is rare in arid climates where the great majority of GI basidiobolomycosis is reported, has not been seen in Sulaimaniyah.
In past years, sporadic cases of the biliary phase of fascioliasis have been recognized in the Sulaimaniyah governate, and in the autumn of 2007, one of the authors (TAH) conducted a study of local streams and identified F. hepatica
rediae in 4% of Lymnaeid snails
]. Rediae develop into tadpole-like cercariae that leave the snail and encyst as metacercariae on vegetation in or near streams and rivers
]. Naturally growing watercress is sold in Sulaimaniyah markets. It is a favourite vegetable for human consumption with both wild and commercial products being common sources of infection
]. Studies of hyperendemic fascioliasis in the South American Andes indicate that an increased risk of livestock infection and human transmission can be anticipated when greater numbers of cattle become concentrated around limited water sources
]. As part of our current study, we found that 27% of cattle being processed at the regional slaughter house were infected with F. hepatica
. The growth of Sulaimaniyah into areas still used for livestock may have exacerbated a generally low endemic level into one exposing increased numbers of humans to infection.
The acute phase of Fasciola hepatica
responds well to a single course of triclabendazole
]. Although triclabendazole has not been available in our pharmacies, symptoms and eosinophilia resolved with a 3 day course of 400mg of albendazole. Nevertheless, one of the patients treated with albendazole entered a chronic biliary phase of the disease two years after the initial diagnosis. Fatal fascioliasis occurs in livestock that are infected with large numbers of organisms, but this is extremely rare in humans for whom the principal manifestations are a prolonged low-grade febrile illness with some degree of anemia and hepatomegaly
The reported cases of GI basidiobolomycosis nearly all had large or small intestinal obstruction that required surgery
]. The recommended treatment is surgical removal of the infected tissues and an imidazole as anti-fungal agent with itraconozole being the most frequently recommended
]. The organism tends to be resistant to amphotericin B
]. In the review by Vikram et al.
], eight deaths occurred among four-four patients (18%) with five of the fatalities being children
]. Common features of the fatal cases were intestinal perforation and/or extensive abdominal spread of the disease
]. Of the patients who died, only one was treated with itraconozole, 4 received no anti-fungal therapy, and 3 patients an amphotericin product. In our fatal case, the patient received amphotericin B as an anti-fungal agent and died as a result of intestinal perforation before the infected tissue could be resected.
The clinicopathologic findings for the two patients in which no diagnosis could be established were similar to those diagnosed with fascioliasis. The patients had isolated hepatic abscesses, abdominal pain, and eosinophila. Both patients were treated with albendazole for presumed toxocariasis more than a year before they were tested serologically. Following eradication of organisms, the ELISA serology for Fasciola
is reported to become negative in 40% of patients at 6 months and more than 90% of patients after 12 months
]. In contrast, anti-Toxocara
IgG antibodies in patients treated for visceral toxocariasis usually remain elevated for years
]. We recognize that an organism other than F. hepatica
may have caused the two etiologically undiagnosed cases, but with the negative serology and inability to find larvae in the abscesses, we believe that a role for Toxocara
has been reasonably ruled out and that these patients may have had fascioliasis with an attenuated antibody response.
In order to reach a correct diagnosis and determine the cause of an eosinophilic granulomatous abdominal abscess, pathologists, surgeons, and physicians should be aware of the different possible etiologies. A presentation as a GI mass must be distinguished from cancer, and the granulomatous inflammation surrounding the central abscess can be mistaken for tuberculosis. We have seen the eosinophilia of fascioliasis erroneously treated as an idiopathic hypereosinophilia syndrome with imatinib mesylate.
The fungus of basidiobolomycosis is readily identified if sufficient tissue is obtained but can be missed in mucosal biopsies as it was in two of our patients. The diagnosis of fascioliasis has historically been a problem. Serological testing is often unavailable, or an ineffective method may used. Before 2003, the sensitivity of serological tests was poor, but newer ELISA kits using ES or Fas2 antigens have an estimated sensitivity of 87-93% and are currently the recommended methods for diagnosing F. hepatica
The gastrointestinal location of an eosinophilic granulomatous mass points to basidiobolomycosis, but rare examples of ectopic fascioliasis producing tumor-like colonic masses are reported
]. In addition, hepatic abscesses are found in a significant proportion of patients with basidiobolomycosis
]. It is not the location of eosinophilic granulomatous disease, but the identification of an Entomophthorales
fungus that provides for the diagnosis of basidiobolomycosis, and the absence of fungus and a positive serological test for Fasciola
that allows for the diagnosis of fascioliasis. Table
summarizes the pathological and serological findings for basidiobolomycosis, fascioliasis, and toxocariasis, the latter being included because it is considered a frequent cause of eosinophic granulomatous liver abscesses
Pathological and clinical laboratory findings in the differential diagnosis of abdominal eosinophilic granulomatous abscesses
The identification of disease at surgery uncovers only the most severely affected patients. Serological studies for F. hepatica
in the urban and rural populations of Sulaimaniyah as well as the examination of livestock are currently in progress to determine the level of the endemic situation. The clustering of basidiobolomycosis and F. hepatica
has not been previously reported. The epidemiology of F. hepatica
has been thoroughly studied but factors predisposing to basidiobolomycosis are poorly understood
]. We believe Sulaimaniyah may provide an opportunity to identify conditions that contribute to human outbreaks of both diseases.