Viral Skin Infections Research Articles

Viral infections in atopic dermatitis.

Individuals with atopic dermatitis are susceptible to frequent viral skin infections due to a compromised epidermal barrier function and immune dysregulation. The diagnosis and management of viral infections in atopic dermatitis can be challenging due to various clinical phenotypes and overlapping clinical features. The literature is reviewed for the diagnosis, aetiology, management, differential diagnoses and complications of these viral infections to provide an up-to-date clinical overview for clinicians involved in caring for patients with atopic dermatitis, including patients with skin of colour. The importance of accurate diagnosis and appropriate management in cases of uncertainty is crucial due to the risk of life-threatening complications with some viral infections. The differing presentations of these infections in patients with skin of colour is highlighted as an underrepresented area of research. Future research with greater diversity of patients is needed for patients with atopic dermatitis complicated by viral skin infections.

Hyper IgE Syndromes.

The Hyper IgE Syndromes are rare primary immunodeficiencies characterized by eczema, recurrent skin and respiratory infections and elevated serum IgE levels. Nowadays a geneticmolecular characterization is possible and allows the distinction in various monogenic pathologies, which share some clinical characteristics but also important differences. In addition to long-known STAT3 and DOCK8 gene mutations, in fact, also ZNF341, CARD11, ERBB2IP, IL6R and IL6ST genes mutations can cause the disease. The main clinical manifestations are represented by newborn rash, eczema similar to atopic dermatitis, bacterial and viral skin infections, cold abscesses, respiratory infections with possible pulmonary complications, allergies, gastrointestinal manifestations, malignancies and connective tissue abnormalities. Diagnosis is still a challenge because, especially in the early stages of life, it is difficult to distinguish from other pathologies characterized by eczema and high IgE, such as atopic dermatitis. Several scores and diagnostic pathways have been developed, but it is essential to seek a genetic diagnosis. Treatment is based on prevention and early treatment of infections, meticulous skincare, intravenous immunoglobulins and HSCT, which, in some HIES subtypes, can modify the prognosis. Prognosis is related to the affected gene, but also to early diagnosis, timely treatment of infections and early HSCT.

Comprehensive Review of Molluscum Contagiosum in Children: Prevalence, Transmission, Clinical Features, and FDA-Approved Treatments

Background: Molluscum contagiosum (MC) is a common viral skin infection affecting school-aged children, with a prevalence of 2-8%. Although self-limited, MC often requires active management to prevent spread, scarring, and to address cosmetic and social concerns. Traditional treatments have various complications, and currently, only topical berdazimer gel and cantharidin are approved by the FDA. Methods: A comprehensive literature review was conducted to assess the prevalence, transmission, clinical presentation, complications, and treatment options for MC. The review included studies from various geographic regions, focusing on both physical and chemical treatment methods, as well as newer FDA-approved therapies. Results: MC is most prevalent in children aged 2-5, with no gender-specific differences. The infection manifests as skin-colored, dome-shaped papules, primarily on exposed skin. Complications include school exclusion, social isolation, and secondary infections. Treatment options vary widely in efficacy and safety. Physical treatments like curettage and cryotherapy are effective but can cause scarring and discomfort. Chemical treatments, including potassium hydroxide and cantharidin, offer non-invasive alternatives but have side effects. Newer treatments like topical berdazimer gel and cantharidin solution are promising due to their ease of use and lower complication rates. Conclusion: MC is a significant infection in children, often necessitating treatment due to its complications. While traditional treatments have notable drawbacks, FDA-approved topical therapies, berdazimer gel, and cantharidin, provide effective and safer options. Further research is needed to optimize treatment protocols and minimize adverse effects.

A retrospective claims analysis of US pediatricians prescribing practices for the treatment of Molluscum Contagiosum

Introduction: Molluscum Contagiosum (MC), a common viral skin infection affects mostly children, is caused by Molluscipoxvirus. MC is characterized by flesh-colored, round, dome-shaped, umbilicated bumps. Pediatricians are often the first to diagnose MC. Objective: To examine US pediatrician’s MC treatment management using claims data. Methods: Syneos used the Compile Claims database to collect all medical and pharmacy claims for pediatric patients diagnosed with molluscum (ICD10 Code B081) in 2019-2020. Pediatric patients with a Molluscum (B081) claim from a pediatrician practice were calculated along with patients prescribed a prescription by the same pediatrician within 30 days of a molluscum claim. Practitioners were categorized as “wait and see,” “treater” or “referrer.” Frequency data were captured. Results: From 2019-2020, 260,788 molluscum patients ≤ 19 years were diagnosed by 56,026 healthcare providers. Pediatricians were responsible for a majority of molluscum diagnoses: 72% of patients (187,228) diagnosed by 35,017 pediatricians. Most pediatricians initially managed MC with a “wait and see” approach (91%). If a “wait and see” pediatrician initiated treatment, half managed by prescription, whereas “treaters” used in-office procedures (81%) and prescriptions (23%). Mupirocin (45%) and triamcinolone (23%) were preferred prescriptions. Conclusion: Mupirocin and triamcinolone were likely used to treat signs of inflammation indicative of MC resolution known as Beginning of the End (BOTE) sign. Neither are FDA approved for MC nor antiviral; mupirocin use without secondary bacterial infection may contribute to resistance. Newly approved MC indicated therapies should be considered and a better understanding of BOTE is essential to distinguish MC resolution from secondary infection.

How are pediatricians treating molluscum contagiosum? results from in-depth interviews

Molluscum contagiosum is a common, often persistent viral skin infection affecting children, and spread by infected individuals or objects. No molluscum management guidelines exist and only two FDA treatments have been approved in the last year, thus placing pediatricians in a clinical conundrum if molluscum treatment is warranted. When MC is particularly bothersome or persistent, parental anxiety may influence treatment. In-depth interviews with 25 pediatricians provided insight into the current MC treatment landscape and drivers of therapeutic intervention. This study reveals the important influence parental anxiety, patient characteristics, and parental involvement have on pediatrician’s molluscum management and treatment intervention practices. Professional society endorsed molluscum management guidelines and the use of safe and efficacious FDA-approved therapies would fill therapeutic gaps.

Analysis of the effects of pulsed microcurrent on pain, depression, and anxiety in patients with herpes zoster

Background: Herpes zoster is a common viral skin infection and has a high incidence rate in China. At present, conventional drugs combined with adjuvant measures are used for treatment. To improve the efficiency and shorten the time of treatment, we propose the use of pulsed microcurrent as a new adjuvant therapy. Aim: This study aimed to investigate the effects of pulsed microcurrent on pain, depression, and anxiety in patients with herpes zoster. Methods: A total of 58 patients with herpes zoster who were admitted to our hospital between April and August 2022 were selected as study participants and divided into two groups. The control group (n = 29) received conventional drug therapy, while the experimental group (n = 29) received pulsed microcurrent electrical therapy in combination with conventional drug therapy. Results: After 14 days of treatment, the scores from the visual analog scale, patient health questionnaire (PHQ) (i.e., PHQ-9), and generalized anxiety disorder (GAD) assessment (i.e., GAD-7) of the experimental group were reportedly significantly lower than those the control group (P < 0.05). Conclusion: These findings suggested that pulsed microcurrent electrical therapy combined with conventional drug therapy could effectively alleviate the pain, depression, and anxiety symptoms in patients with herpes zoster, highlighting its potential to be widely used in clinical practice. Relevance for Patients: Patients suffering from herpes zoster may opt for pulsed microcurrent electrical therapy to effectively alleviate the pain, depression, and anxiety symptoms.

Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology.

Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen, herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (Ifnlr1-/-), both the IFN-λ and the IFN-α/β receptors (Ifnar1-/-Ifnlr1-/-), or IFN-λ cytokines (Ifnl2/3-/-) and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions without affecting viral loads. We used RNAseq to define IFN-λ- and IFN-β-induced transcriptional responses in primary mouse keratinocytes. Using conditional knockout mice, we found that IFN-λ signaling in both keratinocytes and neutrophils was necessary to control HSV-1 skin lesion severity and that IFN-λ signaling in keratinocytes suppressed CXCL9-mediated neutrophil recruitment to the skin. Furthermore, depleting neutrophils or blocking CXCL9 protected against severe HSV-1 skin lesions in Ifnlr1-/- mice. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection and suggests potential applications for IFN-λ in treating viral skin infections.IMPORTANCEType III interferons (IFN-λ) have been shown to have antiviral and immunomodulatory effects at epithelial barriers such as the respiratory and gastrointestinal tracts, but their effects on the skin have not been extensively investigated. We used mice lacking IFN-λ signaling to investigate the skin-specific effects of IFN-λ against the herpes simplex virus (HSV), which targets epithelial tissues to cause cold sores and genital herpes. We found that IFN-λ limited the severity of HSV skin lesions without affecting viral load and that this protective effect required IFN-λ signaling in both keratinocytes and neutrophils. We found that IFN-λ signaling in keratinocytes suppressed neutrophil recruitment to the skin and that depleting neutrophils protected against severe HSV skin lesions in the absence of IFN-λ. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection and suggests potential applications for IFN-λ in treating viral skin infections.

An RNA-Seq analysis of coronavirus in the skin of the Pangolin

Protection of the Critically Endangered East Asian Pangolin species is hampered by the vulnerability of captive individuals to infection. Studies have previously shown the pangolin to have a unique pseudogenisation of many immunity genes (including IFNE, IFIH1, cGAS, STING, TLR5, and TLR11), and we suspected that these losses could account for this vulnerability. Here we used RNA-Seq data to show the effect of these gene losses on the transcriptional response to a viral skin infection in a deceased pangolin. This virus is very closely related to the one causing the current COVID-19 pandemic in the human population (SARS-CoV2), and we found the most upregulated pathway was the same one previously identified in the lungs of SARS-CoV2-infected humans. As predicted, we found that the pathways downstream of the lost genes were not upregulated. For example, the pseudogenised interferon epsilon (IFNE) is known to be particularly important in epithelial immunity, and we show that interferon-related responses were not upregulated in the infected pangolin skin. We suggest that the pangolin’s innate gene pseudogenisation is indeed likely to be responsible for the animal’s vulnerability to infection.

Atopic Dermatitis: Disease Background and Risk Factors.

Multiple risk factors have been associated with the development of atopic dermatitis (AD). Recent advances in understanding the role of genetics in this disease have been made, with discovery of the filaggrin (FLG) gene as the most notable so far. In addition to FLG gene mutations as a risk factor for AD, a positive family history of atopic or allergic disease in either parent has been shown to confer a greater risk of developing AD. Atopic dermatitis usually presents early in life and is thought to represent the initial step in the "atopic march," which is characterized by the development of other atopic diseases later in life such as asthma, allergic rhinitis, and/or rhinoconjunctivitis, food allergies, and hay fever. Other comorbid diseases that have been associated with AD include increase risk of viral and bacterial skin infections, neuropsychiatric diseases such as attention-deficit hyperactivity disorders (ADHD), and autistic spectrum disorder (ASD). Patients with AD have also been found to have worse sleep quality overall compared to patients without AD. In this chapter, we will discuss the risk factors associated with development of atopic dermatitis as well as the most commonly reported comorbidities in patients with this disease.

First Topical Drug for Common Viral Skin Infection.

First Topical Drug for Common Viral Skin Infection.

The Efficacy of Copper Nanoparticles in Treating Viral Skin Infections: A Systematic Review and Meta-Analysis

Viral skin infections pose a significant health concern worldwide, causing discomfort, pain, and potential complications. The development of effective treatments for these infections is crucial in minimizing their impact on individuals’ quality of life. In recent years, there has been growing interest in the potential use of copper nanoparticles as a novel therapeutic approach. Copper nanoparticles exhibit unique antimicrobial properties and have shown promise in combating various pathogens. This systematic review and meta-analysis aims to evaluate the efficacy of copper nanoparticles in treating viral skin infections, providing a comprehensive assessment of their potential as an alternative or complementary treatment modality. By synthesizing available evidence, this study aims to contribute to the growing body of knowledge regarding the use of copper nanoparticles in dermatology and guide future research and clinical practice in this field.

The Efficacy of Copper Nanoparticles in Treating Viral Skin Infections: A Systematic Review and Meta-Analysis

Viral skin infections pose a significant health concern worldwide, causing discomfort, pain, and potential complications. The development of effective treatments for these infections is crucial in minimizing their impact on individuals’ quality of life. In recent years, there has been growing interest in the potential use of copper nanoparticles as a novel therapeutic approach. Copper nanoparticles exhibit unique antimicrobial properties and have shown promise in combating various pathogens. This systematic review and meta-analysis aims to evaluate the efficacy of copper nanoparticles in treating viral skin infections, providing a comprehensive assessment of their potential as an alternative or complementary treatment modality. By synthesizing available evidence, this study aims to contribute to the growing body of knowledge regarding the use of copper nanoparticles in dermatology and guide future research and clinical practice in this field.

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

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). 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. 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. These findings indicate an important relationship between S. aureus skin infections and EH.

Open-Label Observational Study of a Topical Formulation of Calcium Spirulan Contained in a Defined Extract of the Microalga Spirulina platensis in the Treatment of Children with Molluscum Contagiosum.

Molluscum contagiosum (MC) is a common viral skin infection primarily affecting children which is difficult to treat using available therapeutic approaches. The sulfated polysaccharide named calcium spirulan (Ca-SP) has demonstrated antiviral effects against herpes simplex virus in keratinocytes in vitro, and a cream containing 1.5% Ca-SP and 1% of a defined microalgae extract (Spiralin®) effectively prevented herpes labialis in a trial with susceptible individuals. This observational study aimed to show antiviral effects of a similar formulation (Spirularin® VS) against MC in children. Children with active MC lesions were treated with Spirularin® VS cream twice daily on affected skin over several months and asked to return for follow-up visits after 1 to 3 months. Clinical status of MC infection was documented at baseline and follow-up visits. Of the 31 children enrolled in the study, 26 completed treatment and returned for control visits. Spirularin® VS cream was applied twice daily over a period of 1 to 9 months (mean treatment duration 3.9 months). 19/26 (73.1%) children achieved complete clearance of MC lesions with no clinical evidence of bacterial skin infection during treatment. No irritative skin reactions or unpleasant symptoms were observed or reported. This open-label observational study suggests that a cream formulation containing 1.5% Ca-SP and 1% Spiralin® may be an effective and safe treatment option for children with active MC lesions. The high rate of complete clearance of MC lesions and lack of adverse reactions warrant further investigation in larger, controlled trials.

Atypical Cutaneous Viral Infections Reveal an Inborn Error of Immunity in 8 Patients.

Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families.

Resident memory T cells in the lymph node balance localized and systemic protection

Abstract The endogenous mechanisms that protect against pathogen infection in the lymph node (LN) and LN metastasis during early tumor development remain poorly understood. Resident memory T cells (Trm), which do not circulate, provide highly localized protection to both pathogens and cancer, and correlate with better clinical outcomes. Here we track LN Trm development using models of cutaneous viral infection to determine the kinetics and requirements for their differentiation. We show that after viral skin infection, Trm form in the draining LN concurrent with their establishment at the initial site of infection in skin. LN Trm formed specifically in LNs draining infected skin expressing cognate antigen and did not form in contralateral controls. These data supported a hypothesis that T cell egress out of infected skin through lymphatic vessels was necessary for LN Trm formation. Consistent with this hypothesis, LN Trm were absent from mice lacking dermal lymphatic vessels indicating that either fluid transport or cellular transport from the skin to the LN was necessary for the establishment of LN Trm. To decouple LN priming from T cell egress we resected infected skin days 5 and 20 post infection. Ear resection at 5 days post infection impaired Trm formation but circulating memory T cell responses were unaffected. We demonstrated that LN Trm are poised for cell killing as evidenced by constitutive expression of granzymes, and were able to protect against viral rechallenge. These findings indicate that LN Trm are poised to provide rapid, localized protection specific to the draining LN. These data may suggest that LN’s harbor populations capable of controlling regional cancer metastasis and pathogenic infections. Supported by grants from NIH (R01CA238163)

Insights into the pathogenesis of allergic disease from dedicator of cytokinesis 8 deficiency.

Clinical observations and mechanistic studies in dedicator of cytokinesis 8 (DOCK8)-deficient patients and mice have revealed multiple mechanisms that could contribute to their unusually prevalent and severe allergic disease manifestations. Physical interactions of DOCK8 with STAT3 in B cells and T cells may contribute to increased IgE isotype switching or defective immune synapse formation that decreases T-cell receptor signal strength. A newly discovered TFH13 cell type promotes the development of life-threatening allergy via production of IL-13 and is increased in DOCK8 deficiency. Cytoskeletal derangements and cytothripsis, which were previously shown to account for the increased susceptibility to viral skin infection in DOCK8 deficiency, can lead to interplay between myeloid cells and T cells to ultimately increase production of IL-4, IL-5, and IL-13. Finally, theeffects on type-2 innate lymphoid cells may also contribute to allergic disease.

Combined immunodeficiency due to DOCK8 deficiency. State of the art

Combinedimmunodeficiency (CID) due to DOCK8 deficiency is an inborn error of immunity (IBD) characterized by dysfunctional T and B lymphocytes; The spectrum of manifestations includes allergy, autoimmunity, inflammation, predisposition to cancer, and recurrent infections. DOCK8 deficiency can be distinguished from other CIDs or within the spectrum of hyper-IgE syndromes by exhibiting profound susceptibility to viral skin infections, associated skin cancers, and severe food allergies. The 9p24.3 subtelomeric locus where DOCK8 is located includes numerous repetitive sequence elements that predispose to the generation of large germline deletions and recombination-mediated somatic DNA repair. Residual production DOCK8 protein contributes to the variable phenotype of the disease. Severe viral skin infections and varicella-zoster virus (VZV)-associated vasculopathy, reflect an essential role of the DOCK8 protein, which is required to maintain lymphocyte integrity as cells migrate through the tissues. Loss of DOCK8 causes immune deficiencies through other mechanisms, including a cell survival defect. In addition, there are alterations in the response of dendritic cells, which explains susceptibility to virus infection and regulatory T lymphocytes that could help explain autoimmunity in patients. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment; it improves eczema, allergies, and susceptibility to infections.

Association of Adult Atopic Dermatitis Severity With Bacterial, Viral, and Fungal Skin Infections.

Background: Little is known about the relationship of atopic dermatitis (AD) severity, phenotype, and persistence on different types of skin infections. Objective: To evaluate the relationship of AD characteristics and skin infections over time in adults. Methods: We performed a prospective dermatology practice-based study (n = 559). History of infection was assessed using questionnaires. AD severity was evaluated using Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Patient-reported Global Assessment (PtGA). Results: At baseline, 160 (21.4%) patients reported history of ≥1 skin infection, including 14.3% with bacterial infections. In multivariable repeated measures logistic regression models, ≥1 cutaneous infection was associated with moderate (adjusted odds ratio [95% confidence interval]: 2.67 [1.67-4.28]) and severe (6.35 [3.36-12.01]) versus mild SCORAD; as well as severe SCORAD-itch; moderate and severe versus clear-mild EASI; moderate and severe versus clear-mild PtGA; mild, moderate, and severe versus clear-almost clear IGA. Cutaneous infections were not associated with ichthyosis, palmar hyperlinearity, nummular eczema, cheilitis, or hand eczema. Specific infections varied by AD severity and body site. Persistent moderate-severe disease was associated with higher odds of skin infection. Conclusion: Skin infections were associated with AD severity but not phenotype, and may be mitigated by improved AD severity.

Pediatric Viral and Bacterial Skin Infection Profile

Background: Viral and bacterial skin infection is a common condition amongst children. In developing countries, it is a complex major health problem. However, epidemiological study on viral and bacterial skin infection in the pediatric population is still lacking, especially in Indonesia. Purpose: This study aimed to evaluate bacterial and viral skin infection amongst children and its association with age and sex. Methods: This study used a cross-sectional design with a retrospective approach. We retrieved medical records of pediatric patients admitted to Dr. Harjono S Ponorogo General Public Hospital between 2016 and 2020. Result: Of the 1,427 collected medical records, we found that the viral infection prevalence was 4.9% (n=70) and 7.5% (n= 107) for bacterial skin infection. Viral infection was most observed amongst subjects in the >12-year age group and 2–12-year for bacterial infection. Infection was more commonly observed amongst boys. Conclusion: The skin infection prevalence in Dr. Harjono S. Ponorogo General Hospital is lower compared to other studies. Skin infection of viral origin was most reported in children aged >12 years and bacterial infection in children aged 2–12. Both skin infections were more commonly observed in boys than girls.