Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation

Abstract

Summary:We report a retrospective analysis of VZV infection after haematopoietic stem cell transplantation (HSCT) in children. Thirty-three (30%) of the total 109 children who were transplanted during a 7 year period developed post-transplant VZV infection. Twenty-four of these 33 (73%) children had VZV infection within 1 year following HSCT. The cumulative incidences of post-transplant VZV infection at 1 and 5 years were 26% and 45%, respectively. The positive and negative predictive values of pretransplant VZV serology in recipients on the development of HZ following HSCT were 39% and 88%, respectively. Pretransplant VZV seropositivity in recipients was the only risk factor for post-transplant herpes zoster (HZ) infection on multivariate analysis. All patients responded to acyclovir. The median duration of VZV infection was 5 days. Three (11%) and one (3%) children with HZ developed visceral dissemination and post-herpetic neuralgia, respectively. No mortality was directly attributed to VZV infection. VZV infection remains a major cause of morbidity in children after HSCT. Further studies are warranted to evaluate the potential use of VZV vaccine in these children. Bone Marrow Transplantation (2000) 25, 167-172. Keywords: haematopoietic stem cell transplantation; herpes zoster; paediatric; varicella-zoster virus Varicella-zoster virus (VZV) is a herpes virus that causes chickenpox (CP) as a primary infection and herpes zoster (HZ) when the latent virus is reactivated. It is a significant cause of morbidity and mortality in immunocompromised patients. Ten percent of children with leukaemia on maintenance chemotherapy died of VZV infection in the preacyclovir era. 1 Haematopoietic stem cell transplantation (HSCT) is now the treatment of choice for some malignant and nonmalignant conditions in children. However, these patients are at high risk of having severe VZV infection because of significant and prolonged immunosuppression in the post-transplant period. The incidence of VZV infec- tion in children following HSCT varied from 23% to 67%. [2][3][4][5][6] Herpes zoster is one of the common late infections in post-transplant patients. The median onset of HZ following HSCT occurred at the fifth month. 7 However, risk factors for post-transplant VZV infection in children are less well defined because there are few reports on this subject. In this study, we review the incidence, risk factors, treatment and clinical outcome of VZV infection in children who underwent HSCT at our centre. Patients and methods Study population and design

Herpes zoster infection in the post-hematopoietic stem cell transplant pediatric population may be preceded by transaminitis: an institutional experience

“…1 Infrequently, HZ infection is complicated by disseminated cutaneous involvement or visceral organ involvement with significantly increased morbidity and even mortality. 2,3 The incidence of HZ in children following HSCT has been reported in the range of 23-67%, [4][5][6][7][8][9] which is comparable to the incidence in adult HSCT recipients. Some studies have suggested that children develop post-HSCT HZ earlier than adults, 4,5,7 but other studies have demonstrated a later median time of onset.…”

“…The incidence of HZ in our cohort of pediatric HSCT patients is consistent with the incidence rates previously reported. [4][5][6][7][8][9] Additionally, our study demonstrates that although a substantial number of patients develop HZ in the early post-HSCT period, there is an increase in incidence over time and HZ can occur up to 5 years post-HSCT. This is particularly evident in the allogeneic cohort who, despite incidence rates of 34 and 50% at 12 months in all allogeneic patients and seropositive allogeneic patients, respectively, experiences a substantial increase over time such that 45 and 70% of these patients, respectively, have developed HZ by 60 months post-HSCT.…”

“…Cutaneous dissemination of HZ was defined as the subsequent appearance of lesions in noncontiguous dermatomes. 9 Visceral organ dissemination was defined as histological or culture evidence of organ involvement or clinical evidence of organ involvement in the absence of other identified pathogens that might have accounted for the clinical picture. 9 Post-herpetic neuralgia was defined as the need to provide ongoing pain medications to treat pain in a dermatomal distribution following the resolution of skin lesions.…”

“…Some studies have suggested that children develop post-HSCT HZ earlier than adults, 4,5,7 but other studies have demonstrated a later median time of onset. 9 HZ complications in the post-HSCT pediatric population have been reported with variable frequency.…”

“…In the literature, transaminitis prior to the development of skin rash has been described in cases where HZ involved visceral abdominal organs, and this portended a poor outcome. 2,3 Leung et al, 9 describe a child with disseminated cutaneous HZ who had an elevated alanine aminotransferase (ALT) level noted at presentation and did not develop clinical hepatitis. Similarly, we noted that several of our patients had elevations in transaminase levels prior to onset of skin manifestations, but did not go on to develop visceral organ involvement.…”