Neonatal Peliosis With Maternal Ingestion of Pesticides

Peliosis is characterized by blood-filled cavities with an incomplete endothelial lining and can present with cholestasis, acute liver failure, or liver rupture. We present a case of neonatal peliosis likely secondary to maternal pesticide ingestion, causing liver failure, and requiring transplant. The patient was the product of an induced delivery at 352/7 weeks’ gestation because of severe intrauterine growth restriction and oligohydramnios. He was the fourth child of Vietnamese parents. The mother did not smoke, drink alcohol, or use illicit drugs. Standard prenatal serological tests were negative. Family history revealed absence of consanguinity and absence of liver and renal diseases. Parents had a history of positive tuberculosis skin tests, but normal chest x-rays. The patient was transferred after birth to a pediatric hospital for progressive cholestasis. Maximum bilirubin levels were 341 and 19 (total and conjugated) before transfer. He received phototherapy from day 3 to 5 of life. On physical examination, birth weight was 1.545 kg, length 42.5 cm, and head circumference 30 cm; the liver was palpable 3 cm below the costal margin; and there was absence of splenomegaly and no signs of portal hypertension. Initial investigations revealed anemia (hemoglobin 74 g/L) and thrombocytopenia (platelets 29 × 109 cells/L). The infant had 1 episode of hypoglycemia. An abdominal ultrasound displayed 3 hepatic lesions. An ophthalmology consult and bone marrow biopsy were unremarkable. A 25-day-old boy was transferred to our institution, in acute liver failure with hepatic lesions. Following his transfer, ultrasound showed multiple hypoechogenic lesions with anechogenic portions lacking internal vascularization more significant in the right lobe. Bile ducts were not dilated, and there was a moderate amount of ascites. Computed tomography confirmed 3 hepatic lesions and 1 splenic lesion. On magnetic resonance imaging, at least 9 ring-shaped, blood-filled cavities were observed, the largest measuring 2.5 × 1.8 × 1.9 cm (Fig. 1A). Further workup showed an α-fetoprotein level of 26,377 μg/L. Extensive immune, infectious, and metabolic workup was unremarkable (Table 1). On day 15 of admission, a surgical hepatic biopsy was performed and showed a large blood-filled lesion with a fibrous capsule, absence of viral inclusions, and extremely little parenchymal tissue. Cholestasis and brown pigments indicative of hemosiderin were observed. Intrahepatic iron was seen in half of the hepatocytes. A diagnosis of peliosis hepatis was made, but the underlying etiology remained unknown.FIGURE 1: A, Magnetic resonance imaging of the patient showing ring-shaped cavities in the liver. B, Histological findings showing blood-filled cavities.TABLE 1: Diagnostic evaluation at Sainte Justine University Hospital CenterHepatic function deteriorated and the patient presented signs of encephalopathy and was listed for transplant. Liver transplant was performed on day 57 of admission (day of life 82) with an O-positive, ABO-incompatible, cadaveric donor using liver segment II-III. The patient weighed only 3.5 kg at the time of transplant, and abdominal closure was not possible. Pathology report showed multiple blood-filled cysts of different sizes (Fig. 1B), severe lobular collapse, extensive intralobular and extralobular fibrosis, few hepatocytes structured in micronodules with a cytoplasm showing hydropic degeneration filled with brown pigments indicative of hemosiderosis, and many apoptotic hepatocytes. Immunohistochemistry was negative for viruses, and for membrane attack complexes at the hepatocyte membrane, thereby eliminating the possibility of neonatal hemochromatosis (1). The posttransplant course was complicated by a compartment syndrome with intestinal perforation on day 10, and a bile leak at the site of the anastomosis. The patient returned to the operating room 3 weeks posttransplant to repair a second bile leak and intestinal perforation. A liver biopsy performed at that time revealed discrete inflammation, but no signs of rejection or relapse of the initial disease. Further questioning revealed that the mother had consumed a green tea imported from China several times per day throughout her pregnancy. A specimen obtained from the importer company was sent to Health Canada Laboratories looking for pyrrolizidine alkaloids, herbicides, or pesticides. Fenvalerate was detected at 0.110 ppm. The patient is presently a healthy 4 year 9 month old and is followed up in our transplant clinic. DISCUSSION Peliosis was first described by Wagner in 1861 (2), peliosis meaning livid or purpura by extravasated blood (3). In addition to its effect on the liver, it can also occur in the lung, spleen, and lymph nodes and the etiology is often unknown. Our case is unique. First, to our knowledge, it is the only case of peliosis hepatis in the English-language and French-language literature that began in utero, and was successfully transplanted. There exists a case in the literature in which a pediatric patient with peliosis was listed for transplant as an adult because of hepatopulmonary syndrome (4), and another case of a successful liver transplant with reversal of peliosis, but details are unavailable because the article was published in German (5). Second, the culprit, green tea contaminated by pesticides, has never before been associated with peliosis; however, herbal tea has been associated with the development of veno-occlusive disease in a newborn (6). In the case of neonatal veno-occlusive disease, trace amounts of pyrrolizidine alkaloids, a known toxic agent, were isolated from the Tussilago farfara leaves of the ingested tea. Fenvalerate, a synthetic pyrethroid, is a pesticide commonly used to protect cotton plants and fruit and vegetable crops. Its toxicity to mammals and humans is reportedly low (7). Toś-Luty et al (13) found that fenvalerate caused parenchymatous degenerative changes to mouse hepatocytes. Fenvalerate has also been associated with hepatic, lymph node, and splenic granulomas in rats, mice, goats, and dogs, although not vascular damage (8–12). Interestingly, a study involving fenvalerate ingestion in pregnant rats showed hepatic sequelae in the newborns, specifically necrotic patches with round cell infiltration. Singh et al (14) described decreased intestinal absorption and increased hepatic copper levels in fenvalerate-intoxicated goats. Although it is plausible that liver injury from fenvalerate was mediated by copper overload, histologically the findings are different from peliosis. Hepatic copper toxicity shows hepatocytes with hydropic swelling and Mallory hyaline formation (15); furthermore, Wilson disease has never been associated with peliosis. We, unfortunately, did not measure hepatic copper content or serum copper or ceruloplasmin levels in this patient. The results indicating the higher-than-normal levels of fenvalerate were communicated to the medical team after transplant, and the study showing increased copper levels in fenvalerate-intoxicated goats was published years after our experience with this patient. In Canada, fenvalerate was voluntarily discontinued as of 2006; as such, any residues from this insecticide must not exceed the default maximum residue limit of 0.1 ppm set by Food and Drug Regulation (personal communication, Yadvinder Bhuller, MSc). The pathophysiology of peliosis remains unknown, but in adults it has been associated with human immunodeficiency virus, tuberculosis, Bartonella henselae infections, and cystic fibrosis (16–19). Cases have also been described with the use of 6-thioguanine, anabolic steroids, azathioprine, and oral contraceptives (20–23). The pediatric literature is limited, but the cases reported have been associated with cystic fibrosis, malnutrition, Fanconi anemia, adrenal tumors, Marfan syndrome, congenital cardiopathy, myotubular myopathy, and postrenal transplant (Table 2). Treatment is primarily supportive, the primary goal being hemostasis of intraperitoneal hemorrhage. Many of the cases reported resolve spontaneously with removal of the offending agent and transplant is rarely indicated.Table 2: Peliosis hepatis in the pediatric literatureAcknowledgments The authors thank Yadvinder Bhuller, Director of Health Effects Division 1, Health Evaluation Directorate, Pest Management Regulatory Agency, and Michèle Bouchard, Associate Professor, Head of the Chair in Toxicological Risk Assessment and Management and Head of the Biomarker Unit of the Xenobiotics and Nanoparticles Platform Department of Environmental and Occupational Health, Faculty of Medicine, University of Montreal, for their help with information related to fenvalerate.

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