The antimicrobial protein RNase 7 directly restricts herpes simplex virus infection of human keratinocytes.

Approximately 22% of moderately to severely affected atopic dermatitis (AD) patients have a history of eczema herpeticum, a disseminated rash primarily caused by herpes simplex virus type 1 (HSV-1). Reduced activity of antimicrobial peptides may contribute to the increased susceptibility of AD patients to HSV-1. We previously demonstrated that the antimicrobial protein RNase 7 limits HSV-1 infection of human keratinocytes by promoting self-DNA sensing. Here, we addressed whether RNase 7 has any effect on HSV-1 infection when infecting keratinocytes without exogenously added costimulatory DNA, and which step(s) of the infection cycle RNase 7 interferes with. We quantified viral gene expression by RT-qPCR and flow cytometry, viral genome replication by qPCR, virucidal effects by plaque titration, and plaque formation and the subcellular localization of incoming HSV-1 particles by microscopy. Recombinant RNase 7 restricted HSV-1 gene expression, genome replication, and plaque formation in human keratinocytes. It decreased HSV-1 immediate-early transcripts independently of the induction of interferon-stimulated genes. Its main effect was on intracellular infection processes and not on extracellular virions or virus binding to cells. RNase 7 reduced the amount of cell-associated capsids and the HSV-1 envelope glycoprotein D at 3 but not at 0.5 h postinfection. Our data show that RNase 7 directly restricts HSV-1 infection of human keratinocytes, possibly by promoting the degradation of incoming HSV-1 particles. This suggests that RNase 7 may limit HSV-1 spread in the skin and that mechanisms that reduce its activity in the lesional skin of AD patients may increase their susceptibility to eczema herpeticum.

Eczema Herpeticum: Clinical Insights and Pathogenesis Hypotheses on Basolateral Adhesion Proteins.

Eczema herpeticum (EH) is a severe viral complication caused by the herpes simplex virus (HSV) that occurs in individuals with compromised skin barriers, such as those with atopic dermatitis (AD). EH is characterized by the rapid spread of HSV across skin lesions, potentially leading to systemic involvement. Although commonly observed in the context of AD, EH can also arise in various dermatological conditions, necessitating prompt recognition and management by healthcare providers. This case report details the diagnosis and treatment of EH in a five-year-old girl with a history of AD who presents with fever and painful skin lesions. Despite the absence of confirmatory tests initially, a positive IgM anti-HSV-1 serology, combined with clinical presentation, supported the diagnosis of EH. The patient received intravenous aciclovir, resulting in significant improvement within 48 hours. This case highlights the importance of early diagnosis and treatment, particularly when confirmatory tests are not available. The report discusses the clinical presentation of EH, which includes vesicular lesions, fever, and rapid progression. The differential diagnosis includes chickenpox, impetigo, eczema vaccinatum, and contact dermatitis. Understanding the epidemiology and pathogenesis of EH, especially in relation to AD, is crucial for effective management. The case also introduces a novel hypothesis linking structural protein alterations to immune dysfunction in EH, suggesting a need for further research. Acyclovir remains the gold standard for treating EH, and timely intervention is essential. This case underscores the necessity of a diagnostic algorithm in the absence of guidelines and highlights the role of IgM serology and clinical judgment in managing suspected EH cases.

Concurrent Presentation of Eczema Herpeticum and Acute Localized Exanthematous Pustulosis in a Patient With Atopic Dermatitis: A Rare Dermatological Convergence.

Eczema herpeticum (EH) is a severe and potentially life-threatening viral infection occurring in individuals with preexisting eczema or atopic dermatitis. It is primarily caused by the herpes simplex virus, presenting as painful vesicular eruptions on the skin. On the other hand, acute localized exanthematous pustulosis (ALEP) is a rare variant of acute generalized exanthematous pustulosis (AGEP), characterized by the sudden onset of localized, nonfollicular pustules on an erythematous base. It is often triggered by recent medication administration, and its clinical presentation mimics AGEP, although ALEP exhibits a confined distribution of pustules. Prompt diagnosis and identification of the offending agent are crucial for effective management. Both are distinct cutaneous manifestations that rarely occur concurrently, presenting unique diagnostic and therapeutic challenges.  We present the first documented case of coexisting ALEP and EH in a 32-year-old male with a history of atopic dermatitis. The patient was admitted with features suggestive of EH, including vesicular lesions over the face, along with a positive Methicillin-resistant Staphylococcus aureus (MRSA) swab. Treatment with ceftaroline initially initiated resulted in the development of localized pustules, indicative of ALEP. Transition to linezolid led to the complete resolution of both conditions, marking a compelling recovery. The distinctive interplay between EH, ALEP, and AGEP presents a novel challenge, emphasizing the need for nuanced clinical assessment and tailored therapeutic strategies. This case offers crucial insights into the intricate relationship between medication-induced dermatological conditions and underlying cutaneous vulnerabilities. This unprecedented case highlights the rarity and complex management nuances associated with the simultaneous occurrence of ALEP and EH. The successful resolution following medication adjustments underscores the need for flexibility and comprehensive evaluation in addressing such intricate dermatological scenarios, providing valuable insights into potential synergies between distinct cutaneous conditions.

Eczema herpeticum in an immunocompetent man.

BACKGROUND: Eczema herpeticum is a rapidly progressing skin complication related to the herpes simplex virus, particularly in individuals with compromised immune systems or atopic dermatitis. Eczema herpeticum is characterized by cutaneous pain, scaling, and the presence of vesicular lesions, often accompanied by secondary infection. Dissemination of the infection can lead to severe morbidity and mortality in patients without appropriate antiviral and antibiotic therapy. CASE REPORT: We presented a case of ankylosing spondylitis in a relatively young patient who did not receive immunosuppressive therapy and had no history of Human Immunodeficiency Virus, herpes zoster infection or atopic dermatitis. The patient's symptoms improved following a course of antiviral and antibiotic treatments. INTRODUCTION: The incidence of eczema herpeticum has been on the rise in recent decades, primarily due to an increased number of individuals with compromised immune systems. This increase can be attributed to various factors, including the higher prevalence of Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome, the more extensive use of immunosuppressive therapy, and what seems to be a growing incidence of atopic dermatitis.[1] This disease can be initially mistaken for Stevens-Johnson syndrome because of the rapid advancement of skin lesions, however, the atypical target lesions, flaccid bullae and prominent mucosal involvement found in Stevens-Johnson syndrome are absent in cases of eczema herpeticum. Other differential diagnoses include impetigo, disseminated herpes zoster, acute generalized exanthematous pustulosis, dermatitis herpetiformis.

Papulovesicular Riddle in an Atopic Individual.

Atopic dermatitis (AD) characterized by pruritus and eczematous lesions makes individuals susceptible to various viral and bacterial infections. Eczema herpeticum (EH), also known as Kaposi's varicelliform eruption, is a severe herpes simplex virus infection that can be observed in individuals with AD. EH manifests with monomorphic vesicles and "punched-out" erosions accompanied by hemorrhagic crusts, primarily affecting eczematous areas. Misdiagnosis, often as impetigo, can lead to severe complications and even death. Timely diagnosis and treatment with acyclovir are crucial to avert these outcomes. Here we present a case of a 19-year-old male with AD who presented with a monomorphic vesicular rash.

Atopic Dermatitis Disease Complications.

This chapter will describe infectious complications of atopic dermatitis, including bacterial, viral, and fungal infections and the evolving understanding of the relationship between atopic dermatitis and infectious disease. The underlying immunological dysregulation and poor skin barrier function associated with atopic dermatitis not only increase the likelihood of infectious complications but also lend atopic dermatitis skin vulnerable to flares induced by environmental triggers. Thus, this chapter will also highlight the impact of common external environmental agents on precipitating flares of disease. Lastly, this chapter will discuss complications that can arise from treatments and the association of atopic dermatitis with more serious conditions such as lymphoma.

Kaposi's Varicelliform Eruption: A Potentially Life-Threatening Complication of Atopic Dermatitis.

Introduction: Kaposi's varicelliform eruption (KVE), also known as eczema herpeticum or eczema vaccinatum, is an acute dermatosis that affects patients with chronic dermatopathies. The diagnosis is primarily clinical and is characterised by the presence of a vesicular exanthema on physical examination. The exanthema subsequently evolves into crusted lesions with typical circular ulcerations in 'punched-out' areas on the skin affected by the underlying dermatopathy. Case description: We present the case of a 6-year-old patient who presented to the Paediatric Emergency department with skin lesions consistent with eczema herpeticum. The patient's management was initially outpatient; however, due to the slow progression of the condition, hospitalisation and intravenous antiviral treatment were initiated. Discussion: KVE affects patients with chronic dermatoses, especially atopic dermatitis. It is important to know the clinical presentation for an early suspicion. KVE is a medical emergency that requires prompt diagnosis and treatment. It can progress to secondary viraemia, which can be fatal in up to 10% of immunocompetent individuals and up to 50% of immunocompromised individuals. It is important to be aware of this condition and to start early treatment with antivirals, especially given the high prevalence of atopic dermatitis in our population. This condition is one of the most serious complications that can occur in these patients. LEARNING POINTS: To facilitate early suspicion and diagnosis, disseminate information about eczema vaccinatum.Emphasise the importance of initiating antiviral treatment early to prevent potential complications of eczema herpeticum.If left untreated, Kaposi's varicelliform eruption can result in up to a 10% mortality rate in immunocompetent individuals and a 50% mortality rate in those who are immunocompromised.

Eczema Herpeticum Misdiagnosed as Facial Cellulitis in an African American Male.

Eczema herpeticum (EH) is a cutaneous manifestation of disseminated herpes simplex virus, commonly observed in patients with active eczema. The condition often presents with systemic symptoms, including fever and fatigue, alongside vesiculopustular skin lesions. This case report describes a 19-year-old male with active eczema who was misdiagnosed with facial cellulitis in the emergency and inpatient setting in a community tertiary hospital. With worsening rash and development of ocular symptoms, the diagnosis was reconsidered to be more consistent with EH with herpetic keratitis, which improved with antiviral treatment. This report shows the significance of maintaining a high index of suspicion for EH in patients with eczema and the potential consequences of misdiagnosis and delay in treatment. It aims to enhance clinician awareness of EH and promote a broader differential for unusual presentations of common dermatological and ophthalmologic conditions, especially when caring for patients with limited access to specialist evaluation.

Eczema Herpeticum Complicating Atopic Dermatitis: A Rare Presentation.

Atopic dermatitis (AD) has become a global health concern due to an increase in its frequency over the past few decades. This illness not only reduces the quality of life but also imposes a considerable financial burden due to the increased risk of skin infections. This case report explores the presentation of a four-month-old male infant with a personal history of atopic dermatitis that developed yellow scaly lesions on the scalp, which were assumed to be cradle cap. However, there was a clinical worsening of the cutaneous lesions, with the appearance of vesicles, so he was referred to the Pediatric Emergency Room after an urgent dermatology appointment. A blood test was performed, which revealed severe eosinophilia and a slightly increased total IgE. Considering the patient's past medical record of atopic dermatitis and the observable characteristics of the skin rash, there was a strong suspicion of eczema herpeticum (EH). Consequently, intravenous acyclovir treatment was initiated, along with an antibiotic, as there were concerns about a potential secondary infection. He was followed up with a pediatric and dermatology appointment, with a resolution of skin lesions after six weeks. EH is a rare clinical entity, usually caused by herpes simplex virus (HSV) types 1 and 2. It is a clinical entity that, while being uncommon, is one of the few dermatological emergencies responsible for a high morbidity rate, associated with the systemic spread of the viral infection.

Kaposi varicelliform eruption: an unusual presentation caused by varicella zoster virus in a healthy adult patient - a case report.

BACKGROUND: Kaposi Varicelliform Eruptions (KVE), also known as eczema herpeticum, is a rare and potentially life-threatening dermatological condition primarily attributed to herpes simplex virus (HSV) infection, with less frequent involvement of Coxsackie A16, vaccinia, Varicella Zoster, and smallpox viruses. Typically associated with pre-existing skin diseases, especially atopic dermatitis, KVE predominantly affects children but can manifest in healthy adults. Characterized by painful clusters of vesicles and sores on the skin and mucous membranes, it often masquerades as other dermatological disorders. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain relief and inflammation, though their potential role as KVE triggers remains uncertain. CASE REPORT: Here, we present a case of an 18-year-old female with KVE attributed to Varicella Zoster virus (VZV) and successfully treated with oral acyclovir within a week, underscoring the significance of early recognition and intervention. KVE can manifest with systemic symptoms like fever, fatigue, and lymphadenopathy and may involve multiple organ systems, necessitating possible antibiotic use for complications. CONCLUSION: This case underscores the importance of prompt KVE identification and consideration of antiviral therapy to enhance patient outcomes. Further research is warranted to elucidate predisposing factors for this rare condition.

[Eccema herpético en una paciente con dermatitis atópica].

Background: Eczema herpeticum is an infection caused by herpes simplex virus in patients with atopic dermatitis, among its complications we can find meningitis, encephalitis, acute liver failure, and Staphylococcus aureus infection. Case report: We report the case of a female patient of 5 years of age, with a history of atopic dermatitis complicated by eczema herpeticum, who was treated initially without relief. Her hospital stay was complicated with cross infections, which prolonged her course. Dermatology diagnosed eczema herpeticum. Immediately after the start of treatment, the patient showed improvement. Conclusions: Eczema herpeticum is a rare complication of atopic dermatitis, it must be suspected based on patient history and physical examination. Therefore, early recognition and diagnosis are of clinical importance. Without an appropriate approach, these patients can present shock, sepsis, and death.

Antecedentes: El eccema herpético es una infección causada por el virus del herpes simple, que afecta a pacientes con dermatitis atópica. Las principales complicaciones son meningitis, encefalitis, insuficiencia hepática aguda e infección por Staphylococcus aureus. Reporte de caso: Paciente pediátrica de 5 años, con antecedente de dermatitis atópica complicada con eccema herpético, que recibió tratamiento sin reacción satisfactoria. Durante la hospitalización tuvo infecciones nosocomiales que prolongaron su estancia. Luego de la evaluación por personal del servicio de Dermatología se estableció el diagnóstico de eccema herpético, con adecuado tratamiento, seguimiento y egreso sin complicaciones. Conclusiones: El eccema herpético es una complicación rara de la dermatitis atópica, que debe diagnosticarse con base en los antecedentes personales patológicos y la exploración física adecuada. La atención oportuna es de relevancia clínica, pues los pacientes pueden tener complicación serias (choque, sepsis, incluso la muerte). Palabras clave: Eccema herpético; dermatitis atópica; infección nosocomial; Staphylococcus aureus.

Dupilumab strengthens herpes simplex virus type 1-specific immune responses in atopic dermatitis.

BACKGROUND: Impaired virus clearance in a subgroup of atopic dermatitis (AD) patients can lead to severe herpes simplex virus (HSV) infections called eczema herpeticum (EH). We recently identified a type 2 skewed viral immune response in EH patients. Clinical data suggest a reduced incidence of EH in AD patients treated with dupilumab, although immunologic investigations of this phenomenon are still lacking. OBJECTIVE: We examined the impact of dupilumab on the HSV type 1 (HSV-1) specific immune response in AD, focusing on patients with (ADEH+) and without (ADEH-) a history of EH. METHODS: Sera and peripheral blood mononuclear cells were collected from ADEH+ and ADEH- patients, a subgroup of whom was receiving dupilumab treatment, and healthy controls. Serum samples were tested for IgE against HSV-1 glycoprotein D (n = 85). Peripheral blood mononuclear cells were stimulated with HSV peptides, and activated CD4+ and CD8+ cells were characterized by flow cytometry after magnetic enrichment via CD154 or CD137 (n = 60). Cytokine production of HSV-1-reactive T-cell lines (n = 33) and MHC-I tetramer+ (HSV-1-UL25) CD8+ T cells was investigated by bead assay and intracellular cytokine staining (n = 21). RESULTS: We confirmed that HSV-1-specific IgE is elevated in ADEH+ patients. During dupilumab treatment, the IgE levels were significantly decreased, reaching levels of healthy controls. HSV-1-specific TC1 frequencies were elevated in ADEH- patients treated with dupilumab compared to dupilumab-negative patients. There were no changes in the frequencies of HSV-1-specific TH cells while receiving dupilumab therapy. AD patients receiving dupilumab exhibited elevated IFN-γ and reduced IL-4 production in HSV-1-UL25-epitope-specific T cells compared to dupilumab-negative patients. CONCLUSION: Dupilumab may improve the HSV-1-specific immune response in AD as a result of an increased type I immune response and a reduction of HSV-1-specific IgE.

History of S. aureus Skin Infection Significantly Associates with History of Eczema Herpeticum in Patients with Atopic Dermatitis.

INTRODUCTION: Patients with atopic dermatitis (AD) are uniquely susceptible to a number of serious viral skin complications, including eczema herpeticum (EH), caused by herpes simplex virus. This study explored the associations between biomarkers of epithelial barrier dysfunction, type 2 immunity, Staphylococcus aureus infection, and S. aureus-specific immunoglobulin responses in a cohort of AD subjects with and without a history of EH (EH+ and EH-, respectively). METHODS: A total of 112 subjects with AD (56 EH+, 56 EH-), matched by age and AD severity, were selected from a registry of over 3000 AD subjects. Logistic regression was used to test the association between history of S. aureus skin infection and history of EH, while controlling for a number of confounders. RESULTS: Compared to those without a history of S. aureus skin infection, subjects with a history of S. aureus skin infection were found to have more than sixfold increased odds of having a history of EH (6.60, 95% confidence interval [CI]: 2.00-21.83), after adjusting for history of other viral skin infections (molluscum contagiosum virus, human papillomavirus), serum total IgE, and IgG against the S. aureus virulence factor SElX. CONCLUSIONS: These findings indicate an important relationship between S. aureus skin infections and EH.

Bacterial infections are common among eczema herpeticum inpatients in a cross-sectional analysis of the 2016 Kids' Inpatient Database.

Eczema herpeticum (EH) is a cutaneous infection with herpes simplex virus, typically in the context of atopic dermatitis. Pediatric hospitalizations for EH have increased over the past several decades, yet few studies have investigated comorbidities or epidemiology of pediatric EH inpatients. We searched the 2016 Kids' Inpatient Database and recorded demographics, comorbidities, and associated costs for patients with EH. We found bacterial infections were a common comorbidity which affected nearly half (47.4%) of hospitalized patients, suggesting the importance of regular monitoring of pediatric EH inpatients for bacterial coinfection.

Disseminated life-threatening viral skin rash in a child with atopic dermatitis.

We report the case of a toddler, with a history of mild atopic dermatitis (AD) since early infancy, presented to the Giannina Gaslini, a pediatric polyclinic hospital, 14 days after measles-mumps-rubella (MMR) vaccination, for the occurrence of a disseminated vesico-pustular rash, accompanied by general malaise, fever, restlessness, and anorexia. Eczema herpeticum (EH) was diagnosed clinically and confirmed by laboratory examinations. The exact pathogenesis of EH in AD is still debated and possibly involves an inter-play between altered cell-mediated and humoral immunity, failure to up-regulate antiviral proteins, and exposure of viral binding sites through the dermatitis and an epidermal barrier failure. We hypothesize that in this particular case, MMR vaccination might have played an additional important role in the alteration of innate immune response, facilitating the manifestation of herpes simplex virus type 1 in the form of EH.

Systemic herpes simplex virus infection in a child with eczema herpeticum.

Eczema herpeticum (EH) is a disseminated cutaneous infection with herpes simplex virus (HSV) that develops in patients with atopic dermatitis. The kinetics and clinical significance of HSV viremia in EH are poorly understood. Herein, we report HSV DNAemia in a child with EH 12 months after the completion of chemotherapy for Hodgkin lymphoma.

A rare case of eczema herpeticum associated with HIV: A case report.

Eczema herpeticum (EH), also known as Kaposi's varicelliform eruption, is a disseminated herpes simplex virus infection seen in patients with underlying skin conditions, most commonly atopic dermatitis. Monomorphic vesicles and "punched-out" erosions with hemorrhagic crusts over eczematous regions are the hallmarks of EH's presentation. Here, we discuss a first reported case of eczema herpeticum in a patient living with well controlled HIV with prior steroid use. A 30-year-old male patient living with HIV presented to the hospital with a generalized rash involving the face, neck, arms, hands, low back region, and both feet. Herpes simplex 1 and 2 by PCR DNA were detected from external auditory ear canal drainage. The patient was treated with intravenous acyclovir and responded well. He had long term history of eczema and required acyclovir prophylaxis later.