Acute zoster plasma contains elevated amyloid, correlating with Aß42 and amylin levels, and is amyloidogenic.

Herpes zoster is associated with an increased dementia and neovascular macular degeneration risk and a decline in glycemic control in diabetes mellitus. Because amyloid is present and pathogenic in these diseases, we quantified amyloid, Aß40, Aß42, and amylin in 14 zoster and 10 control plasmas. Compared with controls, zoster plasma had significantly elevated amyloid that correlated with Aß42 and amylin levels and increased amyloid aggregation with addition of exogenous Aß42 or amylin. These results suggest that zoster plasma contains factor(s) that promotes aggregation of amyloidogenic peptides, potentially contributing to the toxic amyloid burden and explaining accelerated disease progression following zoster.

Measurement of melatonin, indole-dioxygenase, IL-6, IL-18, ferritin, CRP, and total homocysteine levels during herpes zoster.

The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses. The present study aimed to assess the levels of oxidative/inflammatory stress biomarkers in HZ patients compared with the controls. This case-control study included 43 HZ patients and 47 age-matched controls. Melatonin (MLT), Indole-dioxygenase (IDO), Interleukin-18 (IL-18), Interleukin-6 (IL-6), ferritin, C-reactive protein (hsCRP), and total homocysteine (tHcy) levels were measured and compared in both groups. The significant high levels of IDO, IL-18, IL-6, ferritin, hsCRP, and tHcy, as well as low levels of MLT were found in HZ patients compared with the controls (P < 0.001); these significant differences were also associated with rash and pain severity (P < 0.001). The final logistic regression model with the area under the curve (0.99; 95% confidence interval [CI], 0.98-1.00) showed the association of HZ with decreased level of MLT (odds ratio [OR], 0.95; 95% CI, 0.92-0.98; P = 0.007) and increased levels of tHcy (OR, 1.53; 95% CI, 1.06-2.19; P = 0.02). The findings showed increased inflammation-associated oxidative stress in HZ patients. Elevated tHcy levels and reduced MLT levels may be associated with the manifestation of HZ. More investigations are required to confirm the results.

Low level of hemoglobin A1c and the increased incidence of herpes zoster: longitudinal study.

Little is known about the association between glycemic status and herpes zoster. The aim of this study was to evaluate whether glycemic status, including both high and low hemoglobin A1c(HbA1c), is associated with subsequent herpes zoster. We conducted a retrospective longitudinal study in a large teaching hospital in Tokyo, Japan, from 2005 to 2016. We included all participants who underwent voluntary health check-ups at the hospital. Our primary outcome was the incidence of herpes zoster in groups of individuals stratified by HbA1c levels, which were compared using the generalized estimating equation (GEE), adjusting for participants' demographic characteristics, social history, body mass index, and comorbidities. A total of 81,466 participants were included in this study. The mean age (standard deviation) was 46.5 (12.1), and 39,643 (48.7%) participants were male. Among them, 1751 (2.1%) were diagnosed with diabetes prior to their first visits. After a median follow-up of 1784 [interquartile range (IQR), 749-3150] days, 673 (0.8%) participants developed herpes zoster. The incidence of herpes zoster was 1.45 per 1000 person-years. Compared with the reference group (HbA1c of 5.0-6.4%), the lowest HbA1c group (HbA1c of < 5.0%) had a significantly higher adjusted odds ratio (OR) (OR 1.63; 95% confidence interval (CI), 1.07-2.48) of developing herpes zoster. The group with an HbA1c of ≥ 9.5% had a higher but nonsignificant OR than the reference group (OR 2.15; 95% CI, 0.67-6.94). Our longitudinal study demonstrated that individuals in the lowest (< 5.0%) HbA1c group had a significantly higher risk of developing herpes zoster than the reference group (HbA1c of 5.0-6.4%) after adjusting for covariates.

Influence of comorbidities on CD4+/CD8+ proportion in HIV-positive patients in Blumenau, State of Santa Catarina: a retrospective study.

INTRODUCTION: The objective was to identify comorbidities related to HIV-positive patients in Blumenau, State of Santa Catarina. METHODS: A retrospective, descriptive observational design study which analyzed data from 424 patients assisted by the sexually transmitted disease/acquired immunodeficiency syndrome (STD/AIDS) Specialized Care Service (SCS). RESULTS: Of 424 medical records analyzed, 388 patients presented CD4+/CD8+ ratios lower than 1. The most prevalent comorbidities were smoking, depression, alcoholism, and herpes zoster infection, in males and females. CONCLUSIONS: The most relevant comorbidity in both genders was herpes zoster, an important marker of immunity in patients. The lowest mean was observed among patients with neurotoxoplasmosis.

Influence of comorbidities on CD4+/CD8+ proportion in HIV-positive patients in Blumenau, State of Santa Catarina: a retrospective study

Abstract INTRODUCTION: The objective was to identify comorbidities related to HIV-positive patients in Blumenau, State of Santa Catarina. METHODS: A retrospective, descriptive observational design study which analyzed data from 424 patients assisted by the sexually transmitted disease/acquired immunodeficiency syndrome (STD/AIDS) Specialized Care Service (SCS). RESULTS: Of 424 medical records analyzed, 388 patients presented CD4+/CD8+ ratios lower than 1. The most prevalent comorbidities were smoking, depression, alcoholism, and herpes zoster infection, in males and females. CONCLUSIONS: The most relevant comorbidity in both genders was herpes zoster, an important marker of immunity in patients. The lowest mean was observed among patients with neurotoxoplasmosis.

Brincidofovir treatment of acyclovir-resistant disseminated varicella zoster virus infection in an immunocompromised host.

Brincidofovir (BCV) is a broad-spectrum antiviral agent active in vitro against double-stranded DNA viruses including herpesviruses, adenoviruses, polyomaviruses, and poxviruses. We report successful BCV use in management of disseminated acyclovir- and cidofovir-resistant varicella zoster virus in an immunocompromised hematopoietic stem cell transplant patient with chronic graft-versus-host disease who was intolerant to foscarnet.

Anti-cytokine autoantibodies in postherpetic neuralgia.

BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN.

[Impacts of electroacupuncture combined with ultraviolet therapy on cytokines of herpes zoster at the acute stage in patients].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with ultraviolet therapy on herpes zoster at the acute stage and the impacts on serum interleukin 2 (IL-2), interleukin 6 (IL-6) and interleukin 10 (IL-10) in the patients. METHODS: Thirty-four patients of herpes zoster were randomized into a medicine group and a combined therapy group, 17 cases in each one. In the medicine group, the intravenous drops with acyclovir injection, muscular injection with cobamamide and the topical with acyclovir ointment were applied. Additionally, TDP was radiated locally. In the combined therapy group, on the basis of the treatment as the medicine group, EA and ultraviolet therapy were supplemented. The duration of treatment was 10 days in the two groups. Before and after treatment, blister relief, incrustation time and the visible analogue scale (VAS) were recorded in the two groups. The clinical efficacy was assessed in the two groups and the levels of serum IL-2, IL-6 and IL-10 were determined in the two groups. RESULTS: In the combined therapy group, the time of blister relief and incrustation was earlier apparently than that in the medicine group (both P<0.05). VAS score after treatment were reduced as compared with that before treatment in the two groups (both P<0.01), and the reducing amplitude in the combined therapy group was larger than that in the medicine group (P<0.01). The total effective rate was 94. 1% (16/17) in the combined therapy group, higher than 76.4% (13/17) in the medicine group (P<0.05). After treatment, IL-2 levels were increased as compared with those before treatment in the two groups (both P<0.05), the levels of IL-6 and IL-10 were reduced obviously as compared with those before treatment in the two groups (all P<0.01). After treatment, the levels of IL-6, IL-10 were reduced much more apparently in the combined therapy group as compared with those in the medicine group (both P<0.05). CONCLUSION: EA combined with ultraviolet irradiation more rapidly and effectively relief the symptoms of herpes zoster, significantly relief pain, shorten the duration of sickness, improve the body immunity and reduce nerve injury.

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis.

BACKGROUND: Serious adverse drug reactions of disease-modifying drugs in multiple sclerosis (MS) therapy may include enhanced susceptibility to reactivation of neurotropic herpes viruses like varicella-zoster virus (VZV) and the John Cunningham (JC) polyomavirus. OBJECTIVE: Because symptomatic reactivation of these viruses are rare events, we determined the incidence of rises in anti-VZV IgG antibody levels as a potential marker for enhanced susceptibility to subclinical and symptomatic reactivation of neurotropic viruses. METHODS: Anti-VZV IgG levels were measured in paired serum samples taken 6-8 months apart from natalizumab-treated MS patients, healthy blood donors and human immunodeficiency virus (HIV) infected patients. RESULTS: The incidence of significant rises in anti-VZV IgG levels in natalizumab-treated MS patients was 4.26 per 100 person-years, which was significantly higher than in healthy blood donors. Retrospective evaluation of the available medical records of patients with rises of anti-VZV IgG levels did not reveal herpes zoster (i.e. shingles) manifestations. CONCLUSIONS: The increased incidence of significant rises of anti-VZV IgG levels in natalizumab-treated MS patients might indicate an association of natalizumab treatment of MS with an elevated risk of a subclinical VZV reactivation and/or reinfection events. Whether this is predictive of an increased risk of herpes zoster or even symptomatic reactivation of other neurotropic viruses remains to be determined in larger prospective studies.

Varicella zoster virus reactivation after autologous SCT is a frequent event and associated with favorable outcome in myeloma patients.

The occurrence of varicella zoster virus (VZV) reactivation is increased after allogeneic transplantation, whereas limited data are available for herpes zoster (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic significance of HZ and its correlation with VZV serology in 191 consecutive myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was assessed as high or rather high in 70% of the patients. By immune fluorescence and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV antibodies at ASCT. Lower specific antibody titers at transplantation were observed in patients with HZ after ASCT than in those without reactivation (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared with patients without HZ (P=0.007). Our data indicate that VZV reactivation after ASCT is a frequent event carrying a significant disease burden and it is associated with improved survival. Low levels of specific VZV antibodies at ASCT suggest increased vulnerability for VZV reactivation.

Serum vitamin D levels are positively associated with varicella zoster immunity in chronic dialysis patients.

Uremia results in a relatively immunocompromised status, and patients under chronic dialysis have an elevated risk of developing herpes zoster (HZ). We sought to investigate the relationship between vitamin D status and immunity to varicella-zoster virus (VZV). A multicenter prevalent hemodialysis cohort was assembled between 2012 and 2013. We assayed the biochemical parameters, 25-hydroxy- (25-OH-D) and 1,25-dihydroxyvitamin D, vitamin D-binding protein levels in the sera. VZV immunity was quantitated using VZV-specific glycoprotein IgG and IgM titers. Eighty-eight patients were enrolled and their sera were analyzed. Chronic hemodialysis patients with 25-OH-D < 30 ng/ml (insufficiency or deficiency) had significantly lower VZV-IgG than those with sufficient 25-OH-D (p = 0.04). This discrepancy became more prominent if active vitamin D users alone were analyzed (p = 0.01). Generalized additive modeling showed that those with 25-OH-D higher than 27.8 ng/ml or bioavailable 25-OH-D higher than 3.88 ng/ml had significantly higher VZV-IgG levels than those with lower values. Linear regression suggested that both total and bioavailable 25-OH-D were significantly associated with higher VZV-IgG levels (p = 0.003 [total] and 0.01 [bioavailable]), whereas patients with cancer had lower VZV-IgG. Vitamin D may therefore be a potentially useful choice for raising VZV immunity in chronic dialysis patients.

Local and systemic cytokine expression in patients with postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN. METHODS: Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1ß, IL-2, and IL-8). RESULTS: IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar. CONCLUSION: While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered.

Hypereosinophilia in a boy with asthma and Varicella Zoster Virus infection.

Hypereosinophilia is a rare pediatric condition that could be secondary to infections, allergens, immunologic disorders or may be expression of a clonal proliferation. We report the case of an asthmatic boy aged 9 years who presented hypereosinophilia with spontaneous resolution. He had positive serum IgM antibodies to Varicella Zoster Virus while other tests, including genetic ones, gave negative results. Our findings suggest that in children with unexplained hypereosinophilia Varicella Zoster Virus infection should be investigated.

Herpes zoster as a marker of underlying malignancy.

BACKGROUND: Both herpes zoster and malignancy are associated with immunosuppression. However, the association between herpes zoster and the subsequent diagnosis of malignancy is unclear. We undertook this study to assess whether a diagnosis of herpes zoster is a risk factor for subsequent malignancy. METHODS: For this matched retrospective cohort study, a physician billing database was used to identify individuals 18 years of age or older with a diagnosis of herpes zoster and no prior diagnosis of cancer or HIV infection. Individuals with a herpes zoster diagnosis were matched one-to-one to individuals without a herpes zoster diagnosis, and both groups were examined for up to 5 years for diagnosis of cancer. RESULTS: A total of 542,575 individuals with a diagnosis of herpes zoster were identified. Compared with matched controls, these patients were more likely (p < 0.001) to have a history of myocardial infarction, asthma, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension. The incidence of cancer was significantly greater among individuals with herpes zoster than among those without herpes zoster, for both men and women and across all time intervals studied (up to 5 years). The greatest adjusted hazard ratio was seen 180 days after a herpes zoster diagnosis (1.19, 95% confidence interval 1.12-1.25); the hazard ratio decreased as the time from herpes zoster diagnosis increased. Lymphoma was the type of cancer with the greatest relative increase in incidence following diagnosis of herpes zoster. INTERPRETATION: There is a risk of malignancy following an episode of herpes zoster in both men and women and in all age groups 18 years and over. The risk is greatest during the first 180 days following the diagnosis of herpes zoster.

Determination and clinical correlation of markers of inflammation in unvaccinated patients with varicella-zoster infection.

BACKGROUND: Chicken pox is commonly known as a benign exenthamatous disease of childhood, occasionally neurologic or hemorrhagic complications, or even death may ensue. Early predictors of severity of disease have yet to be identified. TNF-alpha and IL-6 stimulate virus-specific immunoglobulin production and it has been postulated that determination of levels of these cytokines may be useful as a prognostic factor. PATIENTS AND METHODS: Patients who were diagnosed with a varicella-zoster virus (VZV) infection in the Outpatient Clinic of the Department of Pediatric Infectious Diseases were evaluated for eligibility. Laboratory assays included an evaluation of complete blood counts, erythrocyte-sedimentation rate (ESR), c reactive protein (CRP), and the number of tumor necrosis factor-alpha/interleukin-6-(TNF-alpha/IL-6-) producing mononuclear cells as determined by flow cytometry. RESULTS: A total of 339 patients (320 with chickenpox and 19 with shingles) were enrolled. Blood samples could only be obtained from 81 of the 320 patients with chickenpox. Patients were also divided into three groups depending on the number of skin (vesicular) lesions. (group 1, ≤ 50 lesions; group 2, 51-100 lesions; group 3, >100 lesions). Correlation analyses did not reveal the presence of a statistically significant correlation between number of skin lesions with either of white blood cells (WBC) count (p = 0.231), ESR (p = 0.879) or CRP (p = 0.373). The mean percentage of TNF-alpha-producing mononuclear cells was significantly higher in group 2 compared to group 3 (p = 0.003). A similar difference was observed with regard to IL-6-producing mononuclear cells, albeit bordering on statistical significance (p = 0.058). CONCLUSIONS: Decreased expression of the cytokines TNF-alpha and IL-6 may be responsible for the development of a more severe clinical picture in patients with VZV infection, and determination of intracellular levels of these cytokines may be of benefit for early identification of patients who may have a more severe clinical course.

Allotype analysis to distinguish the origin of varicella-zoster virus immunoglobulin G after allogeneic stem cell transplantation.

Varicella-zoster virus (VZV) reactivation is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Although previous studies have revealed that cellular immunity is important for suppressing reactivation, the role of humoral immunity against VZV has been poorly evaluated. We analyzed inherited polymorphisms in the immunoglobulin G (IgG) heavy chain constant regions of 50 HSCT recipient-donor pairs to distinguish donor-derived and recipient-derived antibodies. Twelve pairs were informative regarding the origin of IgG, since either the donors (n = 3) or recipients (n = 9) were homozygous null for the IgG1m(f) allotype. In these 9 homozygous-null recipients, allotype-specific IgG against VZV were measured by enzyme-linked immunosorbent assay and compared with measles-IgG. All 9 homozygous-null recipients were monitored for more than 1 year after HSCT, with (n = 4, localized zoster) or without (n = 5) clinical VZV disease. In 3 patients with VZV disease, donor-derived IgG against VZV was elevated between 500 to 700 days after HSCT after the episode of VZV disease. In 1 patient who suffered from VZV disease just before HSCT, donor-derived VZV IgG was elevated within 3 months after HSCT. On the other hand, 2 patients who received reduced-intensity conditioning (RIC) transplantation from an IgG1m(f) null donor maintained recipient-derived IgG against VZV for more than 1 year, whereas it was decreased within 3 months in 1 recipient who received conventional conditioning. In conclusion, the production of anti-VZV IgG by recipient plasma cells persists long after RIC. In patients without symptomatic VZV reactivation, donor-derived anti-VZV IgG did not reach titers comparable to those measured in healthy virus carriers.

Serology and serum DNA detection in shingles.

AIM: To investigate the sensitivity of various laboratory approaches in the diagnosis of herpes zoster from patient serum. METHODS: Paired sera from 53 consecutive adult patients with acute herpes zoster were tested for the presence of varicella-zoster virus (VZV) antibodies. All acute sera were tested subsequently by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. In addition, convalescent sera of patients who tested initially positive for VZV DNA underwent PCR analysis. RESULTS: VZV IgM antibodies were found by enzyme immunoassay (EIA) in 5 acute (9%) and 20 convalescent (38%) zoster sera. VZV DNA was detected by PCR in 21 (40%) acute zoster sera and was no longer detectable in the convalescent samples. A seroconversion or a fourfold or greater titre increase was found by complement fixation (CF) test in 41 (77%), by IgG indirect fluorescent antibody assay (IgG IFA) in 43 (81%) and by CF and IgG IFA combined in 45 of 53 (85%) paired zoster sera. The combination of all serological methods detected 51 (96%) and PCR combined with serology identified 52 (98%) of 53 patients. CONCLUSIONS: Optimal laboratory sensitivity in the diagnosis of herpes zoster from serum can be achieved by the combination of PCR and serology of paired serum samples. Serological methods alone are of limited value for early diagnosis of zoster when therapy can be initiated, because CF and IgG IFA need convalescent serum and IgM test sensitivity is insufficient. Early diagnosis of VZV reactivation is possible from serum by PCR in the first days of illness and test sensitivity needs further improvement. The findings highlight the need for future studies into the usefulness of PCR and serology in atypical cases of VZV reactivation.

Herpes zoster infection associated with poor peripheral blood hematopoietic stem cell mobilization.

The efficacy of peripheral blood hematopoietic stem cell (PBSC) harvest is important for successful autologous transplantation. The impact of viral infection on PBSC mobilization has rarely been reported. Here, we report a patient with relapsed diffuse large B-cell lymphoma who experienced disseminated cutaneous herpes zoster infection during the neutropenic phase of PBSC mobilization. A markedly reduced number of PBSCs was initially harvested (1.72 x 10(6)/kg, 77.2% reduction), followed by a sufficient number (7.55 x 10(6)/kg) during remobilization with the same mobilization regimen when herpes zoster infection had subsided. Because of the temporal association, we suggest that herpes zoster infection is a risk factor for poor PBSC mobilization, and remobilization with the same regimen is feasible.

Clinical relevance of quantitative varicella-zoster virus (VZV) DNA detection in plasma after stem cell transplantation.

Detection of Varicella-Zoster virus (VZV) DNA in plasma can facilitate the early recognition of complicated VZV-infection in immunocompromised hosts. The correlation of VZV-DNA in plasma with clinical presentations of VZV-infection and subsequent aciclovir treatment in allogeneic stem cell transplant (allo-SCT) recipients was studied. In 81 consecutive VZV-IgG positive allo-SCT recipients, VZV-DNA was measured at regular time points (1, 2 and 4 months) following allo-SCT and patient records were screened for VZV-related symptoms and aciclovir treatment. Subsequently, possible VZV-cases were studied in detail for the course of VZV-DNA and treatment effects. During the initial screening, VZV-DNA was detectable in seven patients. The survey of VZV-related symptoms revealed five additional possible VZV-cases. In cases where suitable plasma samples were available (10 out of 12), VZV-DNA was present almost simultaneously with the first clinical manifestations. No evidence of a preceding phase detectable by VZV-DNA only could be observed. Treatment with aciclovir was associated with a prompt reduction of VZV-DNA load. Detection of VZV-DNA in plasma in allo-SCT recipients accurately reflected the clinical presentation of VZV-infection and treatment with aciclovir. VZV-DNA detection in plasma of allo-SCT recipients appears clinically relevant as this may support early recognition and therapeutic management of VZV-infections following allo-SCT.

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

Herpes zoster (HZ), a varicella-zoster virus reactivation, frequently complicates hematopoietic stem cell transplantation (HSCT). Its incidence, complications, and associated risk factors in 310 children undergoing HSCT were reviewed. In all, 61 of 201(32%) patients who had undergone allogeneic and 10 of 109 (9%) patients who had undergone autologous HSCT developed HZ. Of 90 VZV seropositive allogeneic patients, 50 (53%) developed HZ. Seven (17%) of 41 VZV seropositive autologous patients developed HZ. Although a substantial number of patients develop HZ in the early post-HSCT period, risk for HZ persists and HZ can occur up to 5 years post-HSCT. Risk factors for HZ included age >10 years (P<0.0001), allogeneic HSCT (P<0.001), and total body irradiation (TBI) (P<0.059) in allogeneic recipients. Of 37, 22 (59%) patients experienced an elevated alanine aminotransferase (ALT), unassociated with GVHD, in the month preceding HZ. Of the 48/64 patients (75%) hospitalized for treatment (median stay, 6 days; range, 2-39), length of stay was unaffected by donor type but increased by cutaneous dissemination and visceral involvement (P=0.023 and 0.034, respectively) in allogeneic patients. Consideration of HZ infection particularly in patients >10 years of age with elevated ALT after TBI-conditioned allogeneic HSCT may permit earlier diagnosis and therapeutic intervention.