Noncutaneous varicella‐zoster virus (VZV) infection with fatal liver failure in a child with acute lymphoblastic leukemia (ALL)

Abstract

Here, we record our experience with a 5-year-old patient who died of a rapidly progressive VZV primary infection. This young patient presented with pre-B ALL and was treated in the medium-risk branch of the ALL-BFM 95 study protocol [1]. When the boy was only 2 weeks before the end of the last intensive chemotherapeutic protocol and in complete remission, he complained about back pain and intermittent abdominal pain. Physical examination revealed no cause for the pain and laboratory values were within expected limits. Consequently, we reasoned that recent administrations of vincristine were responsible for the symptoms, and we treated him with analgesics. Thirty-six hours later, the ache had not resolved and the parents noticed petechiae where they had massaged the back of their son to soothe the pain. We asked them to bring the patient to our clinic.At the time point of admission the patient was cooperative, but seemed altered as far as behavior was concerned. He displayed signs of dehydration. Other than the petechiae mentioned earlier, the skin was normal; in particular, there was no ef¯orescence of any kind throughout the following episode. The liver was enlarged, whereas the spleen was not palpable. The remainder of the physical examination was unremarkable.We had begun intravenous rehydration, when ®rst laboratory results became available. It was noteworthy that the hemoglobin level of 17.5 g/dl was markedly elevated, whereas the total protein level of 5.0 g/dl was low. This was a sign of liver failure and was more reliable than coagulation parameters, which were still affected by recent asparaginase treatment. The laboratory values of liver enzymes and lactate dehydrogenase were indicative of an overwhelming disintegration of hepatocytes (Table I). The situation became worse, when overnight the patient needed oxygen insuf¯ation because of respiratory insuf®ciency. Simultaneously, the liver grew enormously and clinical symptoms of liver failure such as confusion, dizziness, and sleepiness were aggravated. In the morning, a complete perfusion block in the portal vein was diagnosed by ultrasound. Only a few hours later, the patient developed profound gastrointestinal bleeding. Intensive efforts to compensate the severe hypovolemia became complicated by disseminated intravasal coagulopathy, and the patient died of complications of fulminate liver failure within 24 h after admission.The pathogenetic mechanism was completely unclear, and we hypothesized that either pharmacologic toxicity or an as yet unidenti®ed infection caused the fatal liver failure. First, we analyzed the serum of the last days. There was neither elevation of asparaginase levels, nor toxic concentrations of acetaminophen or metamizole. Acetylsalicylate had not been administered. Hence, the most feasible direct pharmacologic causes were excluded. Postmortem liver biopsy was impressive, and showed that more than 80% of all hepatocytes had decomposed. Approximately one half of all vital hepatocytes were marked by macrovesicular lipid droplets ...

Fatal Visceral Varicella-Zoster Virus Infection Without Skin Involvement in a Child With Acute Lymphoblastic Leukemia

“…Rowland et al reported that 9 of 13 ALL children of visceral varicella had <5 vesicular skin lesions at the time of presentation and 1 patient never developed a skin rash [1]. There have been several case reports where visceral disseminated disease occurred in the absence of any skin involvement [1,3,6,9,10]. In the present case, an intermittent epigastric pain was the first manifestation of the visceral disease.…”

“…The patient reported here received high-dose dexamethasone (12 mg/m 2 /day for 2 courses of a 7-day administration with a 7-day interval) during the incubation period for VZV. Recently, two similar cases with fatal visceral VZV infection during chemotherapy for childhood ALL were reported [6,7]. They developed fatal hepatitis during the combination chemotherapy including dexamethasone (10 mg/m 2 /day × 21 days) just before the end of the last intensive therapy of BFM protocol.…”

Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia

“…87 This visceral dissemination may sometimes occur without skin vesicles, which makes the diagnosis difficult. 88,89 Elevated levels of liver aminotransferases may be the first sign of reactivation of VZV after SCT. 90 There are several case reports describing severe epigastric pain due to VZV gastritis, [91][92][93] and other reports of abdominal pain, hepatitis and melena, 94 paralytic ileus and ascites, 95 severe abdominal pain together with inappropriate antidiuretic hormone secretion/hyponatraemia, 96,97 HZ ophthalmicus 98 and meningo-encephalitis.…”

Risk factors for complicated varicella infection in pediatric oncology patients at a tertiary health care facility in Pakistan

“…The most frequently described complications of VZI in these patients are interstitial or necrotizing pneumonia, hepatitis with acute liver failure, bacterial super infections, and post-infectious inflammatory sequelae (e.g., cerebellar ataxia, hematological abnormalities, and glomerulonephritis encephalitis) [3][4][5][6][7][8]. The varicella-related mortality in children receiving chemotherapy was around 7%-10% before the era of antiviral therapy, with 32% having visceral dissemination [5].…”