Enterovirus-associated hemophagocytic syndrome in children with malignancy: report of three cases and review of the literature

Abstract

Enteroviruses can cause severe manifestations in children with malignancy. Infection-associated hemophagocytic syndrome (IAHS) due to enterovirus is a rare entity in children. Patients with malignancy and IAHS due to enterovirus were retrospectively evaluated at the University of Athens' Hematology-Oncology pediatric unit within a 6-year period (2000-2006). IAHS occurred in three cases among 56 patients with documented enteroviral infection. The diagnosis of IAHS was confirmed by bone marrow aspiration and biopsy. Nested reverse transcriptase-polymerase chain reaction (RT-PCR), sequencing of the amplified alleles, and immunohistochemistry were performed to document the presence of enterovirus. The type of enterovirus was specified by indirect immunofluorescence assay. At the early phase of the disease, patients presented mild, non-specific viral symptoms, persistent unexplained fever, and pancytopenia. At the late phase, patients had more severe manifestations, such as persistent high fever, diarrhea, weight loss, hepatosplenomegaly, and hepatic dysfunction. The therapeutic approach consisted of supportive care, administration of immunoglobulin (400 mg/kg or 2 g/kg), and pleconaril. All patients had fatal outcome; two patients succumbed to multiorgan failure (MOF), while one patient succumbed to ventricular fibrillation. IAHS usually has fulminant course and leads to severe and life-threatening complications, such as liver failure and MOF. IAHS should always be included in the differential diagnosis of viral syndrome or unexplained fever. The therapeutic approach for IAHS should be administered as early as possible, before the progression to irreversible tissue damage. Early therapeutic intervention involving high doses of immunoglobulin might be beneficial for the patient's outcome.

Infections associated with haemophagocytic syndrome

“…Enterovirus-associated haemophagocytic syndrome has been described in nine paediatric patients, 71 of whom fi ve had no underlying illness and fi ve died despite therapy. Intravenous immunoglobulin was used in seven patients with a variable success rate.…”

“…Intravenous immunoglobulin was used in seven patients with a variable success rate. 71 Other viruses found to be associated with haemophagocytic syndrome include adenovirus, measles, mumps, rubella, dengue, hantavirus, and severe acute respiratory syndrome.…”

Debate around infection-dependent hemophagocytic syndrome in paediatrics

“…An underlying disease was found in four patients who experienced a fatal outcome (lymphoid neoplasms, lymphoblastic leukemia and juvenile idiopathic arthritis). Ten patients received intravenous immunoglobulin (six in combination with corticosteroids), but only seven patients survived [72].…”

Viral infections associated with haemophagocytic syndrome

“…There are 12 cases of enterovirus-associated HPS that have been described in the English literature [143]: 5 cases occurred in infants less than 1 year of age, the oldest patient were 18 years old. Underlying diseases were found in 4 cases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia and juvenile arthritis) and was associated with a higher fatality rate (75%).…”