Abstract
Visceral larva migrans (VLM) is a systemic zoonotic parasitic disease caused by migration of the second stage larva through viscera of humans. Despite being a foremost public health problem in low- and middle-income countries (LMICs) such as India, larva migrans remains an untended zoonosis. Here, we report two cases of VLM who presented with fever and abdominal pain for a prolonged duration. On further investigation, marked peripheral eosinophilia with multiple confluent necrotizing eosinophilic granulomas were identified on histopathological examination of the liver.
Case reports
Case 1
A 16-year old girl presented with a history of intermittent abdominal pain for three months. This was associated with intermittent moderate grade fever for the previous 7–8 months. The pain had become continuous for the three days prior and was localized to the right hypochondrium with no aggravating or relieving factors. There was no history of jaundice, black stools, bleeding per rectum, passing worms in the stool, loss of weight or pica. She did not have a pet dog or cat but there were many stray dogs in the neighborhood.
On admission, she was febrile (38.3 °C) with mild pallor. There was mild liver tenderness. Investigations revealed a mild anemia (Hb 110 g/L), total leucocyte count raised (9.5 × 109/L) with raised eosinophils (40%), the absolute eosinophil count being 2.4 × 109/L. Liver function tests were normal. Blood culture and Widal tests were negative. A CT abdominal scan showed irregular hypoechoic hypodense lesions with peripheral enhancement in both lobes of the liver. Fine needle aspiration cytology from one such lesion was suggestive of acute inflammatory reaction, suggestive of parasitic etiology. IgG for Echinococcus was negative, though serum IgE was raised. Stool examination did not reveal any parasitic cyst
Based on clinical features and available investigations, the possibility of a parasitic liver abscess was suggested. Intraoperatively, multiple space occupying lesions containing purulent material were seen in liver segments 3,4,5 & 8. A non-anatomic central hepatectomy was performed; the specimen measured 13 × 11 × 5 cm. The capsule was intact and its outer surface showed diffuse yellowish discoloration. On serial slicing, multiple cavitatory lesions were identified throughout the hepatic parenchyma varying in sizes from 0.5–2.5 cm in diameter. The lesions were filled with necrotic, shaggy, grey tan to greenish material. Microscopic examination revealed multiple abscess cavities and granulomas lined by palisading histiocytes admixed with numerous eosinophils and multinucleated giant cells. The abscesses were also noted in the ductular lumen with ulceration of lining epithelium. Many Charcot Leyden crystals were also observed. However, no definite parasite was seen. Stains for acid fast bacilli and fungi were negative. A final diagnosis of liver abscess due to visceral larva migrans was made, which was treated with a course of albendazole (15 mg/kg/day) and mebendazole (25 mg/kg/day every 8 h) for 14 days.
The patient has been asymptomatic in a follow-up period of 8 years, with no recurrence of the disease.
Case 2
A 36-year old man presented with abdominal pain, high grade fever and chills for the previous three months. This was accompanied by generalized weakness. He was an urban resident. He had similar complaints some ten years previously, which were diagnosed as due to abscess in the left lobe of liver. He had undergone laparoscopic drainage and treatment with antibiotics and albendazole 400 mg for five consecutive days. He had remained asymptomatic for the next eight years, but in the past two years, had again developed similar symptoms and received the same medical treatment, but these symptoms persisted, for which reason he consulted our hospital.
Laboratory evaluation disclosed a leucocytosis of 11 × 109/L with marked eosinophilia (33%) and raised absolute eosinophil count of 3.69 × 109/L. Liver function tests and serum electrolytes were normal. A CT abdominal scan showed clustered hypodense cystic lesions in the left and caudate lobes with partial rupture into the perihepatic space suggestive of liver abscess, likely to be due to parasitic infection (Figure 1(a),(b)).
(a,b) triphasic CT abdominal scan showing clustered hypodense cystic lesions in left and caudate lobes; (c) hepatic parenchyma showing multiple coalescing nodules filled with grey white to yellow necrotic material; (d) multiple serpentine areas of necrosis surrounded by palisading histiocytes (H&E 40×); (e) photomicrographs showing abscess cavity lined by palisading histiocytes admixed with numerous eosinophils and multinucleated giant cells (H&E 100×); (f) inflammatory cells composed of multinucleated giant cells (black arrow), histiocytes and eosinophils (green arrows) (H&E 200×).
Intraoperatively, the left and caudate lobes appeared enlarged with a thickened capsule. A 12 × 10 cm firm mass was palpated. Extensive adhesions were present between the abdominal wall, transverse colon, omentum and left liver lobe. Some 20 ml of pus and putty like material was aspirated from the liver abscess. Microbiological examination was negative for acid fast bacilli, fungus and parasites. Gene Xpert test for tuberculosis was also negative.
Under clinical suspicion of a parasitic infection, a left hepatectomy with caudate lobe excision was conducted and sent for histopathological examination. The outer surface of the liver was covered by exudate. On serial slicing, the parenchyma was replaced by multiple nodules varying in size from 0.3–1 cm, which were filled with grey white to yellow necrotic material (Figure 1(c)). Histological examination showed multiple islands of necrosis surrounded by palisading histiocytes and multinucleated giant cells (Figure 1(d),(e)). Surrounding liver parenchyma showed moderate mixed inflammatory infiltrate, largely composed of lymphocytes, plasma cells and a few eosinophils (Figure 1(f)). No definite parasite was seen. Stains for acid fast bacilli and fungus were negative. Postoperatively, the patient was started with colistin and meropenem intravenously. He also received albendazole 400 mg bd for two weeks. During the follow-up period of seven years, he has stayed well without any evidence of peripheral eosinophilia or recurrence.
Discussion
Although many nematodal parasites have the ability to cause infection, the disease primarily occurs due to Toxocaracanis and Toxocaracati. Both ascarid helminths dwell in the upper digestive tract of their definitive hosts, which are dogs and cats, respectively. Visceral larva migrans (VLM) is an inflammaory state involving human tissues. The visceral organs affected include lungs, liver, central nervous system and eyes. Toxocarosis is relatively common in children as compared to adults, in rural areas than in cities. In adults, the infection is quite infrequent and remains latent for quite a long time. VLM is not an uncommon entity but is often underdiagnosed in tropical and LMICs.1,2 Those who are infected with Toxocara species are usually asymptomatic, but a few present with severe disease such as liver abscess. Although there are case reports of VLM, liver abscess caused by this disease is not commonly described. 3
A tropical climate in addition to poor socioeconomic background, overcrowding, bad hygiene, consumption of contaminated raw vegetables and geophagia are important risk factors. 4 Furthermore, stray dogs, open defecation by dogs and improper faecal disposal are conducive factors for persistence of this disease. In India, sporadic cases of this neglected parasitic zoonotic disease are the main implications for the paucity of diagnostic methods and under-reporting of human cases. Hence, recognition of larva migrans and its multiorgan involvement as an important public health problem, which will be a crucial step to combat this neglected disease.
The migrating larva incites an inflammatory response in the organs. Although the majority remain asymptomatic and the infection resolves spontaneously, serious complications may ensue. The hatched larvae cannot mature into adult worms in humans (dead end hosts), thus larvae migrate throughout their visceral organs causing an acute eosinophilic syndrome. The clinical picture depends on the larval location, intensity of infection, duration of disease and host immune response. 5 The gamut of toxocaral disease encompasses various forms, including generalized visceral larva migrans, covert toxocariasis, and compartmentalized toxocariasis (ocular and neurological). The involvement of the liver lies in its intense phenomenon of larval trapping
Diagnosis of VLM relies mostly on indirect methods particularly serology, since trapped larvae are not readily detected in biopsies. As the larvae do not mature into adults in humans, no ova are found on stool examination. The presumptive diagnosis rests on clinical signs and symptoms, laboratory findings including serology and imaging techniques. A history of contact with dogs and cats may help but is not always remembered, especially in LMICs. Supportive laboratory findings are extreme eosinophilia which may be associated with leucocytosis and anemia. Stool culture is important to rule out other parasitic infection. Hypergammaglobulinaemia is a frequent laboratory finding. Enzyme-linked immunosorbent assay (ELISA) is the most commonly used test with a reported sensitivity and specificity of 78% and 92% respectively. The positive ELISA results can further be confirmed by western blot techniques. However, these tests are expensive and are not easily available in LMICs. Also the usefulness of serological test as a diagnostic test in a low resource setup is not well documented and there are many treated cases showing high levels of antibodies for quite a long period. Sonography, CT and magnetic resonance imaging may reveal multiple abnormal patterns involving liver parenchyma. VLM on computed tomography shows confluent hypodense, peripherally rim enhancing lesions predominantly near the portal vein and the segmental branches as the parasite traverse liver through them. 6 A unique feature of these lesions is the presence of a hyperintense rim on T1-weighted sequences, with corresponding diffusion restriction on echo planar imaging. 7 Most cases are diagnosed by typical radiological picture and laboratory findings, though a diagnosis of toxocariasis may be confirmed by enzyme-linked immunosorbent assay (ELISA). In a few cases, liver biopsy may aid to diagnosis. Biopsies show necrotic areas surrounded by palisaded arrangement of histiocyte rich granulomas along with marked tissue eosinophilia. However, these findings are non-specific and can be seen in all parasitic infections. Larvae are rarely identified on biopsy but their absence does not rule out the diagnosis. Unusual and rare cases develop multiple abscesses destroying the liver parenchyma. Inflammation comprising of numerous eosinophils, neutrophils, lymphocytes and giant cells maybe noted, with remnant parasites destroyed in liver tissue, but not as a rule. Those repeatedly exposed to larger inocula of infective larva suffer with intense trapping of larva in the liver, leading to the formation of central necrosis surrounded by eosinophilic granulomas. Secondary pyogenic abscess may develop in association with Toxocariasis in some cases and it is difficult to determine the primary cause (especially with no parasites in specimen). Ascaris, Schistosoma, Fasciola hepatica can also produce a similar histologic picture with involvement of liver, and can be associated with pyogenic liver abscess, thus mimicking Toxocara infection. However, these infections have more specific geographic locations
Toxocariasis is a self-limiting disease; therefore, patients with mild symptoms do not necessarily require anti-parasitic medication. Therapy in patients with VLM is aimed at relieving symptoms and diminishing the host inflammatory response. Patients with moderate to severe symptoms, are generally treated with albendazole (10–15 mg/kg/day for 4–8 weeks) or diethylcarbamazine (6 mg/kg/day for 7–10 days). The use of adjunctive steroids is indicated in severe cases to accelerate symptom resolution. In cases with severe infection, excision of the affected organ maybe necessary. It is imperative to perform histopathological examination in all cases presenting as liver abscess, in order to obtain the correct diagnosis.
Conclusion
As VLM is an under-diagnosed entity, it should always be suspected as a cause of liver abscess when there are multiple confluent cavities associated with severe peripheral or tissue eosinophilia and characteristic radiological features, especially when serological tests are not available or unaffordable for the patient.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Declaration of patient consent
The authors certify that they have obtained the appropriate consent from the patient. The patient has given his consent for the images and other clinical information to be reported in the journal. The patient understands that the name and initials will not be published, and due efforts have been made to conceal the same.
