Varicella gangrenosa: A rare chickenpox complication.

Varicella gangrenosa is a rare but life-threatening dermatological complication of infection with varicella-zoster virus. A healthy 37-year-old male who had been diagnosed with varicella 20 days back was admitted to our hospital with complaints of fever and painful necrotic skin lesions. Physical examination revealed multiple round to oval ulcers covered with eschar predominantly over arms, lower limbs, back of trunk and flanks. Streptococcus pyogenes and Staphylococcus aureus grew in wound culture. Biopsy revealed ulceration and necrosis of epidermis, and edema, hemorrhage and granulation tissue formation involving the dermis and subcutaneous tissue. The patient was treated with acyclovir - parenteral followed by oral, antibiotics and supportive measures. The lesions healed and he was discharged after 20 days. We report this case to draw attention to the fact that varicella gangrenosum, even though a rare complication, may occur in the lesions of chicken pox and that the survival of patient depends on early diagnosis and aggressive treatment.

Waning Effectiveness of One-dose Universal Varicella Vaccination in Korea, 2011-2018: a Propensity Score Matched National Population Cohort.

BACKGROUND: Despite high coverage (~98%) of universal varicella vaccination (UVV) in the Republic of Korea since 2005, reduction in the incidence rate of varicella is not obvious. The study aimed to evaluate the vaccine effectiveness (VE) of one-dose UVV by timeline and severity of the disease. METHODS: All children born in Korea in 2011 were included for this retrospective cohort study that analyzed insurance claims data from 2011-2018 and the varicella vaccination records in the immunization registry. Adjusted hazard ratios by Cox proportional hazard models were used to estimate the VE through propensity score matching by the month of birth, sex, healthcare utilization rate, and region. RESULTS: Of the total 421,070 newborns in the 2011 birth cohort, 13,360 were matched for age, sex, healthcare utilization rate, and region by the propensity score matching method. A total of 55,940 (13.29%) children were diagnosed with varicella, with the incidence rate 24.2 per 1000 person-year; 13.4% of vaccinated children and 10.4% of unvaccinated children. The VE of one-dose UVV against any varicella was 86.1% (95% confidence interval [CI], 81.4-89.5) during the first year after vaccination and 49.9% (95% CI, 43.3-55.7) during the 6-year follow-up period since vaccination, resulting in a 7.2% annual decrease of VE. The overall VE for severe varicella was 66.3%. The VE of two-dose compared to one-dose was 73.4% (95% CI, 72.2-74.6). CONCLUSION: We found lower long-term VE in one-dose vaccination and waning of effectiveness over time. Longer follow ups of the vaccinated children as well as appropriately designed studies are needed to establish the optimal strategy in preventing varicella in Korea.

A case of reactivation of varicella-zoster virus after BNT162b2 vaccine second dose?

We report a case of itchy papulovesicular rash consistent with varicella-zoster virus reactivation after Pfizer-BioNTech vaccine second dose administration. While there have been cases of varicella-zoster virus reactivation due to COVID-19 or COVID-19 vaccine inoculation in older individuals with pre-existing conditions, this case report describes the first case of varicella-zoster virus reactivation on a healthy, young male in the absence of pre-existing conditions. The mechanisms underlying varicella-zoster virus reactivation in patients with COVID-19 are unknown and should be further characterized.

[Herpes zoster and subunit vaccine].

Varicella-zoster virus (VZV) causes varicella (chickenpox) as primary infection, and latently infects neuronal cells in the dorsal root ganglia (DRG). Reactivation of VZV from DRG results in herpes zoster, often decades later. VZV is the only airborne human herpesvirus and the only herpesvirus whose symptoms (both varicella and herpes zoster) can be prevented by vaccination. Herpes zoster is significantly more common in patients with bone marrow transplants, hematological malignancies, oral Jak inhibitors, SLE, and the elderly. The brand new subunit vaccine, ShingrixⓇ, for preventing herpes zoster is a mixture of adjuvant and recombinant VZV glycoprotein gE, which is highly effective in preventing zoster even in elderly people. In this review, the author discuss the onset mechanism of zoster from the clinical findings and summarize the result of clinical trials of the subunit vaccine.

A Novel Human Skin Tissue Model To Study Varicella-Zoster Virus and Human Cytomegalovirus.

The herpesviruses varicella-zoster virus (VZV) and human cytomegalovirus (HCMV) are endemic to humans. VZV causes varicella (chicken pox) and herpes zoster (shingles), while HCMV causes serious disease in immunocompromised patients and neonates. More effective, less toxic antivirals are needed, necessitating better models to study these viruses and evaluate antivirals. Previously, VZV and HCMV models used fetal tissue; here, we developed an adult human skin model to study VZV and HCMV in culture and in vivo While VZV is known to grow in skin, it was unknown whether skin could support an HCMV infection. We used TB40/E HCMV and POka VZV strains to evaluate virus tropism in skin organ culture (SOC) and skin xenograft mouse models. Adult human skin from reduction mammoplasties was prepared for culture on NetWells or mouse implantation. In SOC, VZV infected the epidermis and HCMV infected the dermis. Specifically, HCMV infected fibroblasts, endothelial cells, and hematopoietic cells, with some infected cells able to transfer infection. VZV and HCMV mouse models were developed by subcutaneous transplantation of skin into SCID/beige or athymic nude mice at 2 independent sites. Viruses were inoculated directly into one xenograft, and widespread infection was observed for VZV and HCMV. Notably, we detected VZV- and HCMV-infected cells in the contralateral, uninoculated xenografts, suggesting dissemination from infected xenografts occurred. For the first time, we showed HCMV successfully grows in adult human skin, as does VZV. Thus, this novel system may provide a much-needed preclinical small-animal model for HCMV and VZV and, potentially, other human-restricted viruses.IMPORTANCE Varicella-zoster virus and human cytomegalovirus infect a majority of the global population. While they often cause mild disease, serious illness and complications can arise. Unfortunately, there are few effective drugs to treat these viruses, and many are toxic. To complicate this, these viruses are restricted to replication in human cells and tissues, making them difficult to study in traditional animal models. Current models rely heavily on fetal tissues, can be prohibitively expensive, and are often complicated to generate. While fetal tissue models provide helpful insights, it is necessary to study human viruses in human tissue systems to fully understand these viruses and adequately evaluate novel antivirals. Adult human skin is an appropriate model for these viruses because many target cells are present, including basal keratinocytes, fibroblasts, dendritic cells, and lymphocytes. Skin models, in culture and xenografts in immunodeficient mice, have potential for research on viral pathogenesis, tissue tropism, dissemination, and therapy.

Reliability of direct varicella zoster virus loop-mediated isothermal amplification method for rapid diagnosis of breakthrough varicella.

BACKGROUND: Since patients with breakthrough varicella (BV) have mild symptoms, clinical diagnosis is difficult. In high vaccine coverage area, as BV occurs sporadically, point of care test is required for controlling varicella outbreak. In this study, the reliability of varicella zoster virus (VZV)-loop mediated isothermal amplification (LAMP) was evaluated for the rapid diagnosis of BV. STUDY DESIGN: A total of 328 swab samples collected from patients with suspected varicella were analyzed. For the laboratory diagnosis of varicella, VZV real-time PCR was carried out using DNA extracted from swab samples. Swab samples without DNA extraction were used for VZV-LAMP(direct-LAMP). RESULTS: VZV infection was diagnosed by real-time PCR in 285 cases, including 105 natural varicella cases and 180 BV cases. VZV DNA was detected in 250 (87.8%) of the 285 cases by direct-LAMP. The presence and duration of fever, number of skin eruptions, and VZV DNA load were significantly lower in BV than natural varicella. The sensitivity of direct-LAMP for the diagnosis of varicella and BV was 93.3% and 84.4%, respectively. CONCLUSIONS: Direct LAMP was considered to be useful for rapid diagnosis of BV as it has several advantages such as low cost, ease and rapidity, as compared to real time PCR.

Vaccine-derived varicella zoster infection in a kidney transplant recipient after zoster vaccine live administration.

A 49-year-old kidney transplant recipient, presented with a skin rash, and interstitial infiltrates three weeks after receiving a live attenuated varicella-zoster vaccine. Varicella-zoster Oka-vaccine strain was detected in plasma by polymerase chain reaction and sequencing analysis targeting open reading frame 62 (ORF 62). She was treated successfully with intravenous acyclovir. Our case report supports the current contraindication of live attenuated varicella-zoster vaccine in the solid-organ transplant recipients. Recombinant subunit varicella-zoster vaccine may be the vaccine of choice in these patients; nevertheless, further information is required to establish its safety, efficacy, and optimal timing.

Effects of One-dose Varicella Vaccination on Disease Severity in Children during Outbreaks in Seoul, Korea.

BACKGROUND: In Korea, the incidence of varicella has increased despite the introduction of a universal one-dose vaccination for children aged 12-15 months in 2005. A previous study demonstrated that the vaccine effectiveness was insufficient to prevent against varicella. We assessed the effect of the varicella vaccination on disease severity. METHODS: Epidemiologic investigation of varicella cases in Seoul metropolitan area from 2015 to 2017 were used. Varicella-related symptoms such as rash were determined by the clinical practitioners. Disease severity of patients was assessed by the number of skin lesions and divided into mild (≤ 50) and moderate (51-249) to severe (≥ 250). Unconditional logistic regression analysis was performed and age was controlled. RESULTS: Among a total of 1,008 varicella cases reported, 869 cases were breakthrough cases and 139 were unvaccinated cases. The risk for occurrence of moderate-to-severe disease in the breakthrough group was 0.57 times less than that of the unvaccinated group. CONCLUSION: These data suggest that national varicella vaccination may have a significant effect on attenuation of disease severity in children.

Primary varicella infection in children with systemic juvenile idiopathic arthritis under tocilizumab therapy.

We report the clinical course and outcome of primary varicella infection in six children with systemic juvenile idiopathic arthritis (sJIA) receiving tocilizumab. None had disseminated or fatal varicella infection, but one patient developed macrophage activation syndrome (MAS) and another had an arthritis relapse. All patients had a significant elevation of serum IL-6 levels, and the two children who developed MAS or arthritis relapse showed high serum IL-18 levels, which could cause a sJIA flare-up.

Toll-like receptor signaling induces the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes.

BACKGROUND: Lympho-epithelial Kazal-type inhibitor (LEKTI) tightly controls the activities of serine proteases such as kallikrein-related peptidase (KLK) 5 and KLK7 in the epidermis. LEKTI is known to be an essential molecule for the epidermal skin barrier, as demonstrated by SPINK5 nonsense mutation, which results in Netherton syndrome. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns or damage-associated molecular patterns and produce inflammatory cytokines, chemokines, and antimicrobial peptides. However, the effect of TLR signaling on the expression of LEKTI is not clear. OBJECTIVE: To investigate whether TLR signaling can affect expression of LEKTI in epidermal keratinocytes. METHODS: We stimulated a panel of TLR ligands and investigated the expression of LEKTI in normal human epidermal keratinocytes (NHEKs). We further measured trypsin or chymotrypsin-like serine protease activity in NHEK cultured media under stimulation with TLR3 ligand, poly (I:C). Immunostaining for LEKTI was performed using skin samples from skin infectious diseases. RESULTS: TLR1/2, 3, 5, and 2/6 ligands induced the expression of LEKTI in NHEKs. The trypsin or chymotrypsin-like serine protease activity in NHEKs was up-regulated with the stimulation of poly (I:C). The gene expressions of KLK6, KLK10, KLK11, and KLK13 were also increased by poly (I:C). An immunohistochemical analysis demonstrated that the expression of LEKTI was up-regulated in the lesions of varicella, pyoderma, and rosacea. CONCLUSIONS: TLR signaling induces the expression of LEKTI in epidermal keratinocytes, which might contribute to the control of aberrant serine protease activities in inflammatory skin diseases.

RNA Polymerase III as a Gatekeeper to Prevent Severe VZV Infections.

In most individuals, varicella zoster virus (VZV) causes varicella upon primary infection and zoster during reactivation. However, in a subset of individuals, VZV may cause severe disease, including encephalitis. Host genetics is believed to be the main determinant of exacerbated disease manifestations. Recent studies have demonstrated that defects in the DNA sensor RNA polymerase III (POL III) confer selective increased susceptibility to VZV infection, thus providing fundamental new insight into VZV immunity. Here we describe the roles of POL III in housekeeping and immune surveillance during VZV infection. We present the latest knowledge on the role of POL III in VZV infection and discuss outstanding questions related to the role of POL III in VZV immunity, and how this insight can be translated into clinical medicine.