Persistent febrile hepatomegaly with eosinophilia due to hepatic capillariasis in Central China

Hepatic capillariasis is a serious parasitic zoonosis caused by the tissue-dwelling nematode Calodium hepaticum (Bancroft, 1893) — commonly known as Capillaria hepatica. It is a parasite found in the live of mammals, mainly rodents (Roberts et al., 2009). Adult worms parasitize and mature in mammalian livers, where the female worms lay her eggs. The adult worms are destroyed by the inflammatory process of the host, but the eggs remain viable in the hepatic parenchyma, where they have no means of egress until they are eaten by a carnivore predator or until the liver decomposes after death. These eggs merely pass through the digestive tract of the predator with feces. The eggs are disseminated to the soil, where they undergo embryonation, and become the infective mature eggs in 2–6 weeks. New infection occurs when a mammalian host ingests the infective embryonated eggs. After hatching in the small intestine, the larvae migrate via the portal system to the liver parenchyma, where they mature. Humans are an accidental host, and human infection is acquired by ingesting food or water contaminated with infective eggs.

Capillaria hepatica infection may cause clinical signs and symptoms of varying intensity ranging from mild to severe, with a possible fatal outcome. Wandering worms through the liver cause loss of liver cells and thereby loss of normal function. Large areas of parenchyma may be replaced by mass of eggs, which elicit granuloma formation and fibrosis in the liver parenchyma (Kaplan et al., 2001). There are typically numerous areas of focal liver parenchymal destruction and eosinophilic granulomas. Hepatomegaly can become severe, and eggs become encased in granulomatous tissue, with heavy infiltration of eosinophils and other leukocytes. Clinical manifestations of hepatic capillariasis are similar to some liver disorders, especially hepatitis with eosinophilia (Choe et al., 1993).

Hepatic capillariasis is scattered in the world. Up to the year 2010, about 40 cases of human infections had been reported in tropical and temperate countries, predominantly in Brazil, the USA, Canada, India, Japan, Korea, Germany, Italy and Czechoslovakia (Sawamura et al., 1996; Camargo et al., 2010). Two cases of children with hepatic capillariasis were documented in Guangdong and Fujian Provinces of southern China (Huang and Lin, 2004). One case of adult in Henan Province in central China was reported in this paper.

CASE DESCRIPTION

A 55-year-old woman from Doulou Village of Shangqiu City of Henan Province, presented to a local clinic with a 4-day history of fever, anorexia and tiredness. The patient was treated as suspected common cold, did not improve and was transferred to the First Affiliated Hospital of Zhengzhou University for further evaluation and treatment. On hospital admission, her main manifestations were chills and fever with a temperature of 39–40°C, cough, abdominal distension and pain, and generalized weakness. By inquiring, she is a farmer and previously in good health. She worked in her corn field inundated by rainwater at 3 weeks before onset of the disease, and sometimes drank the raw water from ditches during work. There were lots of rats in her house and fields. She has no travel history out of Henan. A physical examination showed that the abdomen was distended and tender. The liver was palpable 3 cm below the right costal margin. She had no lymphadenopathy, and no skin rash.

Initial laboratory testing revealed a normal white blood cell count of 8200, but with eosinophilia (41.6%, 3411 eosinophils/μl). Her total protein level was 65.1 g/l, with a decreased albumin of 25.1 g/l and increased globulins of 40 g/l. She had increased C-reactive protein (28.25 mg/l) and IgM (2.67 mg/l) levels. All of her surface and core antigens of hepatitis B or C virus and the antibodies to these antigens were negative. The chemistries, including liver function tests, were within normal limits. The specific antibodies against tissue-dwelling parasites (Paragonimus skrjabini, Clonorchis sinensis, Schistosoma japonicum, Spirometra masoni, Taenia solium, Trichinella spiralis and Toxoplasma gondii) were also assayed by enzyme-linked immunosorbant assay (ELISA) or immunofluorescence test, and negative. Further laboratory testing demonstrated negative ELISA results for HIV, and normal alpha-fetoprotein.

The contrast-enhanced computed tomography of the abdomen showed the irregular enhancements of liver parenchymal and no-enhanced nodular images observed during portal venous phase. A chest radiograph showed the patchy infiltration in both lungs and double pleural effusion.

The needle biopsy of the liver was performed. Histopathological sections of the liver tissues stained with haematoxylin and eosin showed a granulomatous process that partially distorted the parenchyma. The central region of these areas contained eggs. Epithelioid histiocytes and multinucleated giant cells encircled these areas. Mononuclear inflammatory cells and abundant eosinophils were observed at the periphery. The operculated eggs were barrel shaped, with a thick external wall exhibiting striations (Fig.).

Section of the needle biopsy specimen of the liver (haematoxylin and eosin stained). (a) Low-power view of the liver tissues, Note the granulomas with eggs (arrow, original magnification, ×100). (b) High-power view of a granuloma. Note in the centre the characteristic barrel-shaped operculated eggs showing a thick capsule with striation of the outer layer (original magnification, ×1000).

The patient was treated with albendazole (400 mg daily for 4 weeks) and methylprednisolone (40 mg daily for 2 weeks), with a gradual decrease over a period of 1 month. Two weeks after the beginning of treatment, there was general improvement with disappearance of the fever. Laboratory testing revealed a white blood cell count of 8200, with 9.7% eosinophils. By the time of hospital discharge (1 week after treatment), the patient presented a palpable liver 1 cm below the costal margin and showed normal laboratory test results.

DISCUSSION

The cases with hepatic capillariasis reported in the literatures include an age span of 14 months to 78 years. Children less than 5 years of age constitute a large proportion of infected human (Terrier et al., 1999). The higher incidence in this age range may be due to the more frequent soil–hand–mouth contact occurring at this age. The exact route of infection in this adult patient is unknown, but is most likely due to accidental ingestion of soil or water contaminated with mature eggs of Capillaria. This case also suggested that a poor environment at home and in her working fields is favourable for the development of this infestation with the presence of rats.

The patient reported herein presented with clinical symptoms and signs typical of the classical triad for hepatic capillariasis, i.e. persistent fever, hepatomegaly and eosinophilia. This patient also presented respiratory alterations during the development of infection, probably due to the passage of larvae through the lungs or to bronchopneumonia associated with the infection. Other symptoms and signs of this disease included splenomegaly, extreme weakness, constipation, abdominal distension, and sometimes ascites and malnutrition (Berger et al., 1990), but they were non-specific. Since this parasite is cosmopolitan and highly prevalent in rats, it is believed that many human cases may be undiagnosed or misdiagnosis, thus explaining the small number of cases described.

C. hepatica is a significant aetiology of eospinophilic granuloma of the liver, although Toxocara canis is the most common cause. Clinically, hepatica capillariasis requires differentiation from larva migrans (T. canis, T. catis and Paragonimus skrjabini), amebic hepatitis, ascaridiasis of the liver, infectious hepatitis, pyogenic hepatitis, and acute clonorchiosis and schistosomiosis. The diagnosis of hepatica capillariasis is quite difficult because the worms and eggs in the hepatic parenchyma cannot pass through the digestive tract of the patients. Discovery of C. hepatica eggs in human feces does not confirm the diagnosis since it only characterizes a spurious infection caused by eating an infected liver. Most cases have been determined after death. The definite diagnosis is established only by the histological findings in the liver biopsy of the characteristic eggs. The eggs of this parasite are elliptical in shape, bioperculated eggs showing a thick capsule with striation of the outer layer, but in some cases, the operculum might be observed only at one end of the egg as we saw in our patient. Additionally, in very early cases, there may be only immature worms without eggs. Advanced cases may also have both of adult worms and eggs in the liver (Klenzak et al., 2005).

With introduction of serological tests, the serodiagnosis of hepatica capillariasis became more convenient and efficient. IFA and ELISA has been applied for detection of the specific antibodies in hepatica capillariasis; with high sensitivity and specificity (Juncker–Voss et al., 2000), it will be possible to detect infections at an early stage, thus increasing the chances for a successful treatment significantly.

Our patient had a low parasite burden as shown in the section of liver biopsy, but exhibited significant peripheral eosinophilia and a diffuse granulomatous reaction of liver. This patient responded well after treatment with albendazole in combination with corticosteroids. This drug only acts on adult worms but are ineffective against the eggs, which will remain in the hepatic tissue, with maintenance of the lesion (Choe et al., 1993). Thus, it may be necessary to use corticosteroids to reduce the inflammatory response (Pereira and Franca, 1983), as was done here for our patient. However, the results of an experimental study in mice demonstrated that albendazole prevented ovipositing by C. hepatica by more than 99% (Cheetham and Markus, 1991). So, albendazole may continue to be the drug of choice for the treatment of human capillariasis. No side effects of the drug and doses used were observed in our patient in this study.

Finally, we report one case of adult with hepatica capillariasis in Central China. This patient likely acquired the infection by accidental ingestion of food or water contaminated with infective eggs. The disease presentation may be misdiagnosed for granulomatous disease or hepatitis with eosinophilia, and likely is undiagnosed.