Post-Exposure Prophylaxis for Varicella-Zoster Virus Exposure in High-Risk Children.

BACKGROUND: Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin. METHODS: A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined. RESULTS: A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n = 195, 38.3%), followed by varicella immunoglobulin (n = 146, 28.7%), IVIG (n = 115, 22.6%), and combination therapy (n = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P < .0001). CONCLUSIONS: Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease.

Disseminated vaccine-induced varicella infection in a kidney transplant recipient.

A 33-year-old kidney transplant (KT) recipient presented with a disseminated pruritic, painful, vesicular rash and hepatitis 3 weeks after receiving a varicella vaccine (VAR). A skin lesion biopsy sent to the Centers for Disease Control and Prevention for genotyping confirmed vaccine-strain varicella-zoster virus (VZV) (Oka strain; vOka). The patient was successfully treated with intravenous acyclovir during a prolonged hospital stay. This case supports the contraindication of VAR in adult KT recipients and highlights the potential for severe illness when used in this population. Optimally, VZV-seronegative KT candidates should receive VAR before starting immunosuppressive medications. If this opportunity is missed, the recombinant varicella-zoster vaccine might be considered following transplantation as it is already recommended to prevent herpes zoster in VZV-seropositive immunocompromised adults. Further study is needed as data are limited on the safety and efficacy of recombinant varicella-zoster vaccine for primary varicella prevention in VZV-seronegative immunocompromised adults.

Visceral Varicella-Zoster Virus Infection in An Immunocompromised Patient: Uncommon Endoscopic Differential Diagnosis.

Varicella-Zoster virus (VZV) infection is well-known for its dermatological appearances, such as chickenpox and shingles. In addition to its dermal disease, we report a case of visceral dissemination of VZV in immunocompromised patients. A 38-year-old male Caucasian with a history of bone marrow transplantation due to diffuse large B-cell-lymphoma presented himself with severe abdominal pain. Immediate endoscopy revealed numerous gastric and duodenal ulcerations, while histological and molecular evaluation on tissue biopsies and blood samples confirmed VZV infection. Positive serological findings and history of chickenpox during childhood supported visceral VZV dissemination due to reactivation of VZV. The patient received Aciclovir treatment and fully recovered. This case illustrates that visceral dissemination of VZV may lead to acute abdominal pain due to severe mucosal ulcerations even in the absence of dermatological manifestations. Early endoscopic evaluation may therefore be crucial and the only means to immediately guide differential diagnosis, especially in immunocompromised patients. Characteristic histomorphological findings from mucosal ulcerations should lead to the immediate initiation of antiviral therapy and specific molecular evaluation in order to avoid detrimental spread of visceral VZV infection.

Spontaneous Partial Remission in a Child With B-Lineage Acute Lymphoblastic Leukemia and Chickenpox: A Role For Acyclovir?

A 2.5-year-old boy presented to his pediatrician with progressive pallor, asthenia, fever, splenomegaly, and hematomas. Leukemia was suspected, and a bone marrow aspirate confirmed acute lymphoblastic leukemia. Before chemotherapy induction, the child developed a vesicular rash and was diagnosed clinically with chickenpox. Acyclovir treatment was initiated immediately, whereas induction chemotherapy was postponed by 10 days. At the time of chickenpox resolution, a spontaneous partial recovery of his blood counts and a 50% decrease of blastic bone marrow infiltration were noted. After a brief nonsystematic review, we discuss the potential beneficial effect of acyclovir and chickenpox infection in children with leukemia.

Disseminated Varicella-zoster Virus Infection Causing Fatal Pneumonia in an Immunocompromised Patient with Chronic Interstitial Pneumonia.

Viral pneumonia caused by varicella-zoster virus (VZV) infection is a rare but important complication, especially regarding varicella infections. Although disseminated cutaneous herpes zoster (DCHZ) is often associated with visceral diseases, there have been few reports of DCHZ-related pneumonia. We herein report a rare case of a lethal disseminated VZV infection that caused severe pneumonia in a Japanese patient who had chronic interstitial pneumonia. Physicians should consider the possibility of VZV-related pneumonia, especially in patients with a medical history of hematopoietic stem cell transplantation and immunosuppressive therapy.

Reduction in the Number of Varicella-Zoster Virus-Specific T-Cells in Immunocompromised Children with Varicella.

Varicella zoster virus (VZV) causes a life-threatening infection in immunocompromised hosts. The immune response to VZV of healthy subjects has been rigorously assessed, but little is known about that of immunocompromised individuals. This study aimed to clarify the primary response to VZV infection in immunocompromised children. This prospective study enrolled six immunocompromised children (median age, 33 months; range, 20-62) receiving steroids or immunosuppressants, and 10 immunocompetent children (median age, 32 months; range, 15-81) with varicella. The immunocompromised children were three patients with acute lymphoblastic leukemia, two recipients with liver transplantation and one patient with juvenile idiopathic arthritis. Interferon-γ-producing CD69+T-cells produced by VZV stimulation (VZV-specific T-cells) were studied during the acute or convalescent phase. To further address the direct effect of immunosuppressants, we analyzed the number of VZV-specific T-cells after stimulating peripheral blood mononuclear cells obtained from healthy adults with live-attenuated VZV with or without prednisolone, cyclosporine-A, or tacrolimus. The circulating numbers of lymphocytes in the convalescent stage but not acute stage were lower in immunocompromised children compared with immunocompetent children. In the acute stage, immunocompromised patients showed lower VZV-specific CD8+T-cell counts than immunocompetent subjects. In contrast, in the convalescent phase, immunocompromised patients had lower VZV-specific CD4+T-cell counts than immunocompetent hosts. The in vitro culture of activated lymphocytes with prednisolone or immunosuppressants significantly decreased the proportion of VZV-specific CD4+T-cells. In conclusion, the decreased numbers of VZV-specific CD8+T-cells during the acute phase and VZV-specific CD4+T-cells during the convalescent phase of disease may account for severe varicella in immunocompromised children.

Varicella Zoster Virus Infection in Children with Autologous Hematopoietic Cell Transplantation: A Retrospective, Single-Center Study in Korea.

Although long-term antiviral prophylaxis is recommended to prevent varicella zoster virus (VZV) infection in seropositive recipients of allogeneic and autologous (auto-) hematopoietic cell transplantation (HCT), studies of VZV infections in pediatric auto-HCT recipients are rare. This study aimed to investigate the incidence and characteristics of VZV infection in pediatric auto-HCT recipients and explore the risk factors of VZV infection and its effect on survival outcomes. This study included all pediatric patients who underwent auto-HCT at Samsung Medical Center, Seoul, Korea, between January 1998 and December 2013. Before 2006, short-term acyclovir prophylaxis was provided until neutrophil engraftment; thereafter, routine prophylaxis was not provided. Patients who developed either herpes zoster or chickenpox within 2 years from transplantation were identified, and a chart review was performed. A total of 413 recipients and 698 auto-HCTs were included. Sixty-one episodes of VZV infections were identified in 54 patients. Fourteen cases of VZV infection (23%; 14 of 61) occurred within 30 days after auto-HCT. The cumulative incidence of the first episode of VZV infection at 2 years after transplantation was 14% (95% confidence interval [CI], 7.9% to 22.8%) in all recipients and 9% (95% CI, 1.0 to 26.6) in VZV-seronegative patients. Notably, the VZV infection rate increased with age and the VZV infection rate in patients age 15 to 19 years was almost three times higher than in patients age 0 to 4 years (28% versus 10%; P = .003). However, there was no difference in the VZV infection rate between recipients of single auto-HCT and recipients of tandem auto-HCT. Two patients died of disseminated VZV infection. VZV infection is a considerable risk in auto-HCT recipients with or without short-term prophylaxis. Universal antiviral prophylaxis might be considered, particularly in older children, regardless of VZV serologic results. To our knowledge, this is the largest study of VZV infection in pediatric auto-HCT recipients reported to date.

A case report of severe recurrent varicella in an ankylosing spondylitis patient treated with adalimumab - a new side effect after 15 years of usage.

BACKGROUND: Tumor necrosis factor-α (TNF-α) antagonists, most of which are monoclonal antibodies, became a widespread treatment for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis, psoriatic arthritis, hidradenitis suppurativa and uveitis. Their use is based on the blockage of TNF-α, which plays an important role in granulomas formation, development of phagosomes, activation and differentiation of macrophages, immune response against viral pathogens. The multiple adverse effects of TNF-α inhibition have been identified, including a two-to four-fold increased risk of active tuberculosis and other granulomatous conditions and an increased occurrence of some other serious bacterial, fungal and certain viral infections. CASE PRESENTATION: A 34-year-old male patient with disseminated varicella and pneumonitis was admitted to our hospital. The diagnosis of varicella was established serologically by enzyme immunoassay (EIA) and by polymerase chain reaction confirmation of the virus in vesicular fluid. The patient has been receiving adalimumab and methotrexate for the last 3 years due to ankylosing spondylitis and was seropositive to varicella zoster virus prior to the introduction of TNF-α antagonists. Acyclovir was administered for 10 days with the resolution of clinical illness and radiological signs of pneumonitis. CONCLUSION: Due to the use of biological agents, particularly TNF-α inhibitors, as a well-established therapy for some autoimmune diseases, new potential adverse events can be expected in the future and we wanted to point out one of them. To our knowledge this is the first case of recurrent disseminated varicella in a patient taking TNF-α antagonists.

Impacto clínico y epidemiológico de las infecciones por varicela en niños previo a la introducción de la vacuna al Calendario Nacional de Argentina / Clinical and epidemiological impact of varicella infection in children prior to the introduction of the varicella vaccine in the national immunization schedule of Argentina

Introducción. En Argentina, se estiman 400 000 casos anuales de varicela. Dado el subregistro de casos existentes, la carga de enfermedad real se desconoce. Objetivo. Evaluar la carga de enfermedad por varicela antes de la introducción de la vacuna al Calendario Nacional. Materiales y métodos. Estudio retrospectivo, analítico, observacional, realizado en tres centros asistenciales del país. Revisión de los registros de consultas ambulatorias a los Servicios de Urgencias y de las historias clínicas de las internaciones por varicela en pacientes < 18 años. Período: 1/2011-12/2013. Resultados. Fueron asistidas un total de 382782 consultas ambulatorias; 3367 (0,88 %) correspondieron a consultas por varicela; el 57,6 %, < 4 años. Requirieron internación 164 (4,9 %) con una tasa de hospitalización global de 65,3/10000 hospitalizados/año (IC 95 %: 55,4-76,5); tasa de hospitalización en niños sanos: 57,2/10 000 (IC 95 %: 67,7-48,0); mediana de edad: 31,5 meses. Las causas de internación más frecuentes fueron infecciones de piel y/o partes blandas (61,1 %) y respiratorias (10,1 %). El 54,3 % recibió tratamiento con aciclovir, y el 73,1 %, con antibióticos. Presentaron bacteriemia 5/67 (7,5 %), todas por cocos Gram(+) y en inmunocompetentes. De los 19 pacientes inmunocomprometidos, el 36,8 % tuvo complicaciones (5 infecciones de piel y/o partes blandas y 2 neumonías). La mediana de días de internación fue 4, significativamente más prolongada en pacientes inmunocomprometidos. Un paciente requirió cuidados intensivos. No hubo fallecidos. Conclusión. La carga de enfermedad registrada fue significativa, con impacto considerable en pacientes sin patología de base.

Introduction. In Argentina, an estimated 400 000 varicella cases occur annually. Given the under-recording of existing cases, the actual burden of disease is unknown. Objective. To assess the burden of varicella before the introduction of the varicella vaccine in the national immunization schedule. Materials and methods. Retrospective, analytical, observational study carried out in three hospitals of Argentina. Review of medical records from outpatient visits to the Emergency Department and from patients younger than 18 years hospitalized for varicella. Period: 1/2011-12/2013. Results. A total of 382 782 outpatients were seen; 3367(0.88%) corresponded to visits due to varicella; 57.6 % were < 4 years old. A total of 164 (4.9 %) patients required hospitalization, with an overall hospitalization rate of 65.3/10 000 hospitalized patients/year (95 % confidence interval -#91;CI-#93;: 55.4-76.5); hospitalization rate in healthy children: 57.2/10 000 (95 % CI: 67.7-48.0); median age: 31.5 months. The most common causes of hospitalization were skin and/or soft tissue infections (61.1 %) and respiratory infections (10.1 %). Also, 54.3 % were treated with acyclovir and 73.1 %, with antibiotics. Bacteremia developed in 5/67 patients (7.5 %), all cases were caused by Gram-positive cocci and occurred in immunocompetent patients. Out of 19 immunocompromised patients, 36.8 % had complications (5 skin and/or soft tissue infection and 2 pneumonia cases). The median length of stay was 4 days, which is significantly more prolonged in immunocompromised patients. One patient required intensive care. No patient died. Conclusion. The burden of disease was significant, with a considerable impact in patients without an underlying disease.

¿Es efectivo el aciclovir en el tratamiento de la varicela en niños y adolescentes? / Is acyclovir effective for the treatment of varicella in children and adolescents?

Resumen INTRODUCCIÓN: La varicela es una enfermedad infecciosa frecuente y altamente contagiosa, producida por el virus Varicella Zoster. Tradicionalmente se ha recomendado tratarla en forma sintomática, ya que existe controversia en relación a la utilidad del tratamiento antiviral, en especial en niños y adolescentes. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas, que en conjunto incluyen tres estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que el uso de aciclovir podría no disminuir las complicaciones asociadas, y no está claro si disminuye las lesiones o el prurito porque la certeza de la evidencia es muy baja.

Abstract INTRODUCTION: Varicella (chickenpox) is a frequent and highly contagious infectious disease, caused by the Varicella zoster virus. Traditionally, it has been recommended to focus on the management of symptoms, since there is controversy about the role of antivirals, particularly in children and adolescents. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews including three studies overall, all of them corresponding to randomized trials. We concluded the use of acyclovir might not decrease the associated complications, and it is not clear whether it reduces lesions or itching because the certainty of the evidence is very low.

[Varicella gastritis under immunosuppression : Case report of a woman after lung transplantation due to granulomatosis with polyangiitis]. / Varizella-Gastritis unter Immunsuppression : Kasuistik einer Patientin nach Lungentransplantation bei Granulomatose mit Polyangiitis.

A 35-year-old woman who had previously undergone a lung transplantation presented with severe abdominal pain and vomiting. The gastroscopy showed diffuse ulcerative gastric lesions. Tests for varicella zoster virus and Epstein-Barr virus via polymerase chain reactions (PCR) on endoscopically obtained gastric biopsies were found to be positive and confirmed varicella gastritis. Intravenous antiviral therapy with acyclovir was administered resulting in a normalization of all clinical symptoms, especially of abdominal pain and inflammation parameters.

Varicella in a Previously Immune Patient With Leukemia.

Infection with varicella-zoster virus (VZV) in oncology patients can result in severe disease with an increased risk of morbidity and mortality [1, 2]. Among patients on cancer chemotherapy, only nonimmune persons are considered to be susceptible to varicella [1]. We present a case of varicella in a child with leukemia that occurred despite immunity as defined by 2 doses of varicella vaccine and documentation of positive VZV immunoglobulin G titer before initiation of chemotherapy.

Cutaneous leukemic infiltration following varicella - a case of Wolf's isotopic response

Abstract Wolf's isotopic response designates the appearance of two subsequent unrelated dermatoses in the same anatomic location. We report the case of a 51-year-old man with a medical history of chronic lymphocytic leukemia without known extra-hematopoietic involvement. The patient developed a disseminated papulo-vesiculous eruption, diagnosed as varicella. Few days after recovering, an erythematous and violaceous papular dermatosis with histopathological examination compatible with leukemic infiltration appeared on the scars of previous herpetic lesions. Complete remission was obtained under systemic corticotherapy, without cutaneous recurrence or blastic transformation. Wolf's isotopic response is attributed to a localized immunologic imbalance following a certain stimulus. In this patient, herpetic infection acted as a local spur for inaugural cutaneous leukemic infiltration, with no impact on the prognosis for the underlying disease.

Incidence and consequences of varicella in children treated for cancer in Guatemala.

BACKGROUND: Varicella-zoster virus infection is associated with significant morbidity and mortality in immune-compromised children, despite treatment with antiviral agents. Universal varicella vaccine programs have significantly decreased this risk in many highincome countries, but in most low-income and middleincome countries, the burden of varicella in children treated for malignancy is poorly defined. METHODS: We retrospectively reviewed records of children at the National Unit of Pediatric Oncology (UNOP) in Guatemala diagnosed with varicella between January 2009 and March 2013 in order to calculate incidence of varicella and evaluate morbidity, mortality, treatment interruption, and cost. RESULTS: Fifty-nine cases of varicella were identified. Incidence was 23.4 cases per 1000 person-years (p-y). 66.1% of cases occurred in children with leukemia (median age 5.2 years; interquantile range 3.4-7 years) and 41.0% of these occurred during maintenance therapy. Source of exposure was identified for 14/59 (23.7%) children. Most were hospitalized (71.2%) and given intravenous acyclovir (64.4%). Eight (13.6%) children required critical care, and two (3.4%) died from disseminated varicella with multiorgan failure. Chemotherapy was delayed or omitted due to varicella in 50%. No significant differences in outcomes based on nutritional and immunologic status were detected. The minimum average cost of treatment per episode was 598.75 USD. CONCLUSIONS: Varicella is a significant problem in children treated for cancer in Guatemala, where effective post-exposure prophylaxis is limited. In the absence of universal varicella vaccination, strategies to improve recognition of exposure and the future use of novel inactivated vaccines currently under investigation in clinical trials could mitigate this burden.

Skin infections in pregnancy.

A wide array of infectious diseases can occur in pregnancy. Their acquisition, clinical presentation, and course during gestation may be altered due to an impairment of the maternal cellular immunity. Some infectious diseases can lead to serious consequences for the mother or the offspring, including congenital malformations. This review describes in detail the clinical presentation, course, management, and associated maternal and fetal risks of selected viral (varicella-zoster virus infections, condylomata acuminata), fungal (candida vulvovaginitis), bacterial (Lyme borreliosis), and parasitic (scabies) infections. The treatment options are critically reviewed. First-line therapies include acyclovir and varicella-zoster virus immunoglobulin for varicella-zoster virus infections, surgical modalities for genital warts, topical clotrimazole and oral fluconazole for Candida vulvovaginitis, amoxicillin and cefuroxime for Lyme borreliosis, and permethrin for scabies. A synopsis of maternal and fetal risks of other important infections is also included.

Gastric varicella: two cases in cancer patients.

Gastric involvement with the varicella-zoster virus is an uncommon clinical condition where early suspicion and diagnosis are important to prevent the consequences deriving from its high morbidity and mortality, which in immunocompromised patients oscillate between 9% and 41% according to the various series. Two cases of gastric involvement with the varicella-zoster virus (VZV) in two patients with blood cancer are reported below. Gastric lesions are usually preceded by typical papulovesicular skin lesions. When gastric involvement is the first symptom of the disease its diagnosis and management may be delayed, which may entail severe consequences for immunocompromised patients. It is therefore that we suggest its inclusion in the algorithm for immunocompromised patients with abdominal pain and ulcer-like endoscopic lesions.

Cutaneous leukemic infiltration following varicella - a case of Wolf's isotopic response.

Wolf's isotopic response designates the appearance of two subsequent unrelated dermatoses in the same anatomic location. We report the case of a 51-year-old man with a medical history of chronic lymphocytic leukemia without known extra-hematopoietic involvement. The patient developed a disseminated papulo-vesiculous eruption, diagnosed as varicella. Few days after recovering, an erythematous and violaceous papular dermatosis with histopathological examination compatible with leukemic infiltration appeared on the scars of previous herpetic lesions. Complete remission was obtained under systemic corticotherapy, without cutaneous recurrence or blastic transformation. Wolf's isotopic response is attributed to a localized immunologic imbalance following a certain stimulus. In this patient, herpetic infection acted as a local spur for inaugural cutaneous leukemic infiltration, with no impact on the prognosis for the underlying disease.