Severe Herpes Zoster Requiring Intravenous Antiviral Treatment in Allogeneic Hematopoietic Cell Transplantation Recipients on Standard Acyclovir Prophylaxis

Abstract

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out of 2163 patients who underwent allogeneic HCT, 22 (1.0%) developed severe HZ at a rate of 1 per 228 person-years, including dermatomal/multidermatomal disease (n = 5), disseminated skin disease (n = 5), HZ ophthalmicus (n = 4), meningitis/encephalitis (n = 4), pneumonia (n = 2), viremia (n = 1), and erythema multiforme (n = 1). Severe HZ infection occurred in a bimodal distribution during the early peri-HCT period and at 12 to 24 months post-HCT (median, 12.7 months). Twelve patients (54.5%) were compliant with ACV prophylaxis at the time of HZ diagnosis. Eleven patients (50%) died during the study period, only 2 of whom (9.1%) with active VZV infection. Mortality was higher in patients on immunosuppressive therapy (62.5% versus 16.7%; P = .045) and with concurrent graft-versus-host disease (75.0% versus 35.7%; P= .044). These data suggest that severe HZ remains an important consideration despite ACV prophylaxis.

Lesson of the month: Late, disseminated herpes zoster reactivation in a stem cell transplant recipient: implications for post-transplant prophylaxis and immune monitoring

“…VZV reactivation is a significant risk following haematopoietic (H) SCT. 1 Rates of 20-45% during the first year post-transplant were reported in the absence of antiviral prophylaxis, depending upon transplant conditioning and the presence or absence of GvHD. [2][3][4] The majority of reactivation occurs within 9-12 months, although cases of herpes zoster (HZ) have been reported as late as 3 years post-transplant.…”

“…15 However, as highlighted in this case, severe infection due to cutaneous and disseminated reactivation may still occur despite prophylaxis. 1 The reasons for this are unclear, and may include lack of adherence, impaired absorption and evolution of antiviral resistance. Most cases of VZV reactivation occur following discontinuation of antiviral prophylaxis, with reactivation rates of 31-33% reported within 3 months of discontinuation.…”

Infectious complications and vaccines

“…Reactivated VZV infec tion can be severe even dur ing appro pri ate anti vi ral pro phy laxis, espe cially if the patient is still receiv ing immu no sup pres sion. 7 Patients infected with hep a ti tis B virus or who have infected donors should receive pro phy laxis a least dur ing the time of ongo ing immu no sup pres sion. 8 Hepatitis E virus has emerged as a poten tial cause of liver cir rho sis in patients on chronic immu no sup pres sion, such as solid-organ and allo ge neic HCT trans plant recip i ents.…”

Herpes simplex virus infection, Acyclovir and IVIG treatment all independently cause gut dysbiosis

“…However, life threatening complications such as graft-versus-host disease (GVHD), relapse, and infections that include reactivated HSV and VZV limit its application [16]. HSV and varicella zoster (VZV) reactivation has been successfully suppressed by prophylactic ACV treatment, though ACV-resistant (ACVr) HSV is an emerging problem [17,18]. Long term ACV prophylactic treatment is now routine for HSCT patients, because it was found to correlate with reduced HSV and ACVr HSV disease in those treated for longer than 1 year [19].…”