Cutaneous Herpes Simplex Virus Infection Research Articles

Allergic conjunctivitis: a risk factor for recurrent herpes simplex virus infections in patients with atopic dermatitis

Patients with atopic dermatitis have an increased risk of herpes simplex virus (HSV) infections. We carried out a retrospective, cross-sectional study to investigate the association of disease severity, concomitant atopic diseases and filaggrin mutations with the risk of cutaneous HSV infections in 463 patients with atopic dermatitis. The correlation between predisposing factors and HSV infections was analysed using chi-square and Mann Whitney U-tests, and the relationship was further studied with binomial logistic regression to ascertain odds ratios. Allergic conjunctivitis (aOR: 1.770; CI: 1.008-3.109; p = 0.047) and patient age (aOR: 1.022; CI: 1.007-1.036; p = 0.004) showed statistically significant associations with recurrent HSV infections and eczema herpeticum. HSV infections were not linked to severity of atopic dermatitis (p = 0.435) or filaggrin mutation status (p = 0.886). The results highlight the importance for attentiveness of HSV infections in atopic dermatitis patients with concomitant allergic conjunctivitis.

Infections in Sézary syndrome: A retrospective cohort study of 113 patients

Infections in Sézary syndrome: A retrospective cohort study of 113 patients

Comparison of the Sensitivity and Specificity of Tzanck Smear and Immunofluorescence Assay for the Diagnosis of Cutaneous Herpes Simplex Virus and Varicella Zoster Virus Infections in a Real-life Clinical Setting

Objective: This research aim to compare (1) the sensitivities and specificities of Tzanck smears and indirect immunofluorescence assays (IFA) for cutaneous HSV and VZV infections in real-life settings; and (2) the detection rates of the tests for various patient types and lesion morphologies.Materials and Methods: This retrospective study reviewed 440 and 172 samples from patients with clinically suspicious cutaneous HSV and VZV infections, respectively. All patients underwent a Tzanck smear and IFA. The gold standard for the study was agreement of pre- and post-diagnostic coding (determined by a dermatologist) for cutaneous HSV and VZV infections.Results: For HSV infections, the respective sensitivity and specificity of Tzanck smears were 32.8% and 96.6%, whereas those for IFA were 60.7% and 100%. As to VZV infections, the sensitivity and specificity of Tzanck smears were 54.3% and 97.8%, respectively, while the corresponding IFA values were 71.7% and 100%. According to disease characteristics and lesion morphologies, the detection ability of cutaneous HSV by IFA was substantially higher than Tzanck smear especially in immunosuppressed condition. Tzanck smears and IFA demonstrated no statistical difference for early-onset ( 3 days) VZV infections.Conclusion: Tzanck smears and IFA had higher sensitivities for detecting VZV than HSV infections. IFA testing in suspected cutaneous HSV patients with immunosuppressed conditions should be recommended. Despite the overall sensitivity and specificity of IFA being greater than those for Tzanck smears especially in HSV infections, the latter test is a comparable option for early-onset VZV infections.

Nasal Symptoms During Isotretinoin Therapy Can Be a Sign of Herpes Simplex Virus Infection

To the Editor: Isotretinoin (13-cis-retinoic acid)—a derivative of vitamin A—is a commonly used effective treatment for acne vulgaris that is also, but less frequently, used to treat a wide range of additional dermatological conditions, including other pilosebaceous disorders, granulomatous diseases, disorders of keratinization, scarring alopecia, cutaneous lupus erythematosus, photoaging, and nonmelanoma skin cancer prophylaxis.1 The most common adverse effects of systemic isotretinoin administration are mucocutaneous dryness, epistaxis, and cheilitis.2 Cutaneous herpes simplex virus (HSV) infection is common, chronic, and recurrent, and is caused by HSV type 1 (HSV-1) and type 2 (HSV-2). According to World Health Organization, 67% of the world's population is infected with HSV-1. Herpes simplex virus type 1 infection is usually asymptomatic; however, the virus is shed frequently and subclinically. Clinically apparent HSV-1 infection manifests in most cases as orolabial herpes lesions, which generally have a benign and self-limiting course. Reports on the relationship between vitamin A derivatives and HSV infection are inconsistent. Vitamin A derivatives are known to have virucidal activity, and isotretinoin has been used for the treatment of recurrent HSV infection with encouraging results3,4; however, in recent years, prolonged or recurrent HSV infection has been observed in patients during isotretinoin treatment.5–7 Herein, we present a patient that had recurrent nasal mucosa HSV-1 infection during isotretinoin treatment. CASE REPORT A 46-year-old woman presented with an acute painful vesicular eruption in the nasal mucosa. She reported that she had taken isotretinoin a single dose of 10 mg 7 days before the onset of the eruption. She also reported that she had experienced a similar eruption in the same area after taking another single dose of isotretinoin 3 weeks earlier. She began taking isotretinoin on an irregular basis because of keratosis pilaris approximately 1 month before presentation. The patient had a history of herpes labialis but reported not having had intranasal herpes infection before using isotretinoin. Dermatological examination showed grouped coalescing vesicles and pustules in the left nasal mucosa. The patient was not atopic, systemically ill, or immunocompromised. Polymerase chain reaction analysis was performed from the base of a fresh vesicular lesion and HSV-1 was identified. Systemic valacyclovir 500 mg twice a day was initiated, and 5 days later, the lesions were completely healed. At the 6-month follow-up, the patient reported that she had not had any HSV infections after discontinuing isotretinoin. The presented patient's frequent recurrence of HSV-1 infections after use of isotretinoin suggests that isotretinoin was a predisposing agent. The connection between isotretinoin and HSV-1 infection has been previously described.5–7 Isotretinoin-induced HSV infection is thought to be associated with mucocutaneous dryness, photosensitivity, atopy, reduced stratum corneum thickness, and a decrease in cutaneous integrity. In addition, retinoids are known to modulate immune response via their effect on T-cell differentiation and function,8 and because they decrease the number and activity of natural killer cells and cytokines.9 Although the interferon signal pathway is the most important line of host defense against HSV-1, replication or reactivation of HSV in ganglia is controlled by cells of the innate immune system.10 It is difficult to determine whether HSV reactivation is due to isotretinoin-induced mucocutaneous dryness, an immunological mechanism, or a combination of both; however, in the presented case, we think that it was most likely due to mucosal dryness, as the symptoms of infection manifested sooner than a single dose of isotretinoin is expected to affect the immune system. Intranasal HSV infection can easily be overlooked, as it mimics the symptoms of nasal dryness, a common adverse effect of isotretinoin. Dermatologists should be aware that isotretinoin can trigger intranasal HSV infection—a potentially life-threatening condition in immunosuppressed patients. Basak Yalici-Armagan, MD Department of Dermatology and Venereology Hacettepe University Faculty of Medicine Ankara, Turkey [email protected]Sibel Ersoy-Evans, MD Department of Dermatology and Venereology Hacettepe University Faculty of Medicine Ankara, Turkey

CD49a Regulates Cutaneous Resident Memory CD8+ T Cell Persistence and Response

SUMMARYCD8+ tissue-resident memory T cells (TRM) persist at sites of previous infection, where they provide rapid local protection against pathogen challenge. CD8+ TRM expressing the α1 chain (CD49a) of integrin VLA-1 have been identified within sites of resolved skin infection and in vitiligo lesions. We demonstrate that CD49a is expressed early following T cell activation in vivo, and TGF-β and IL-12 induce CD49a expression by CD8+ T cells in vitro. Despite this rapid expression, CD49a is not required for the generation of a primary CD8+ T cell response to cutaneous herpes simplex virus (HSV) infection, migration of CD8+ T cells across the epidermal basement membrane, or positioning of TRM within basal epidermis. Rather, CD49a supports CD8+ TRM persistence within skin, regulates epidermal CD8+ TRM dendritic extensions, and increases the frequency of IFN-γ+ CD8+ TRM following local antigen challenge. Our results suggest that CD49a promotes optimal cutaneous CD8+ TRM-mediated immunity.

CD49a mediates cutaneous resident memory CD8+ T cell persistence and response

Abstract Resident memory CD8+ T cells (TRM) persist at sites of previous infection where they provide rapid local protection against pathogen challenge. CD8+ TRM expressing the a1 chain (CD49a) of integrin VLA-1 have been identified within sites of resolved skin infection as well as in vitiligo lesions. This study examines the signals that regulate CD8+ T cell CD49a expression and its requirement for cutaneous TRM formation and response. We demonstrate that CD49a was expressed early following T cell activation in vivo, and that TGF-b as well as IL-12 induced CD49a expression by CD8+ T cells in vitro. Despite this rapid expression, CD49a was not required for the generation of a primary CD8+ T cell response to cutaneous herpes simplex virus (HSV) infection. Rather, CD49a mediated epidermal CD8+ TRM interaction with the extracellular matrix, supported CD8+ TRM persistence within the skin, and increased the frequency of CD8+ TRM that secrete IFN-g following local antigen challenge. Thus, our results suggest CD49a promotes optimal cutaneous CD8+ TRM-mediated immunity.

Tools for the Diagnosis of Herpes Simplex Virus 1/2: Systematic Review of Studies Published Between 2012 and 2018.

BackgroundHerpes simplex virus (HSV)-1 and HSV-2 are common infections affecting the global population, with HSV-1 estimated to affect 67% of the global population. HSV can have rare but severe manifestations, such as encephalitis and neonatal herpes, necessitating the use of reliable and accurate diagnostic tools for the detection of the viruses. Currently used HSV diagnostic tools require highly specialized skills and availability of a laboratory setting but may lack sensitivity. The numerous recently developed HSV diagnostic tools need to be identified and compared in a systematic way to make the best decision about which diagnostic tool to use. The diagnosis of HSV is essential for prompt treatment with antivirals. To select the best test for a patient, knowledge of the performance and limitations of each test is critical.ObjectiveThis systematic review has summarized recent studies evaluating HSV-1 and HSV-2 diagnostic tools.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, selection criteria, data extraction, and data analysis were determined before the commencement of the study. Studies assessing the specificity/sensitivity of HSV-1 or HSV-2 diagnostic tools published between 2012 and 2018 were included. Quality assessment of included studies was performed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool.ResultsSearches of the PubMed database yielded 264 studies; 11 studies included 11 molecular assays, and 8 studies included 19 different serological assays for the detection of HSV-1, HSV-2, or both. A greater proportion of molecular assay–based tools are being developed by commercial entities. Studies that tested molecular assays mostly focused on cutaneous and mucosal HSV infections (n=13); 2 studies focused on ocular disease, whereas only 1 study focused on the central nervous system manifestations. The Simplexa HSV 1 & 2 Direct is currently the only Food and Drug Administration–approved device for use on cerebrospinal fluid. No tools focused on prenatal screening. We also present performance metrics of tests for benchmarking of future technology. Most of the included studies had a high risk of bias rating in half of the QUADAS-2 tool risk of bias domains.ConclusionsThe use of serologic tests to diagnose genital lesions is inappropriate because positive results may be due to chronic infection, whereas negative results may overlook recent infection. The incidence of acute infections is rising. As these infections present the greatest risk to fetuses, work needs to be done to prevent vertical transfer. Prenatal screening for primary infection and subsequent medical intervention will assist in lowering the rate of neonatal herpes. In conclusion, HSV diagnosis is moving away from culture-based methods to serology-based or polymerase chain reaction–based methods. Sensitive, rapid, and efficient HSV diagnostic tools should be adopted for the prevention of acute infections and neonatal herpes.

Outpatient dermatology consultation impacts the diagnosis and management of pediatric oncology patients: A retrospective study

The impact of dermatology consultation on the care of children with oncologic conditions is unknown. To review outpatient dermatology visits and the resulting impact on diagnosis and management of pediatric oncology patients. Retrospective review of pediatric oncology patients with outpatient dermatology visits at a tertiary care center from 2008 to 2015. The most common dermatologic diagnoses in 516 patients were skin infections (21.3%) and nonmalignant skin eruptions (33.4%). A diagnosis of significant impact (ie, malignancy, adverse cutaneous drug reaction, graft-versus-host disease, varicella-zoster virus, or herpes simplex virus infection), was made at the dermatology clinic in 14.7% of visits. Consultation resulted in a change in diagnosis in 59.8% of patients, change in dermatologic management in 72.4% of patients, and change in management of noncutaneous issues in 12.4% of patients. The use of electronic medical records, the nongeneralizable study population, and the retrospective design represent potential limitations. Outpatient dermatology consultation can affect the care of pediatric oncology patients with respect to diagnosis and treatment of skin conditions and management of nondermatologic issues.

Hospital risk management of cutaneous herpes simplex virus infection.

The epidemiology of cutaneous herpes simplex infection (CHSI) has dramatically changed over the past several decades. Valaciclovir is one of a new generation of antiviral medications that has expanded treatment options for the most common cutaneous manifestations of herpes simplex virus. However, the efficacy and safety of formulations with different doses of valaciclovir remain unclear. To carry out hospital risk management by ascertaining the incidence and risk of CHSI in patients during treatment with varying doses of valaciclovir. The PubMed, MEDLINE and Web of Science electronic databases were systematically searched from database inception to date of searching. Efficacy of drug treatment was measured by average easement score (AES). Safety was characterized as the proportion of patients with drug adverse reactions (DARs) such as fever, dizziness, headache, anxiety, irritability and yellowing of the skin. Outcomes for continuous and dichotomous data were estimated by standard mean difference (SMD) and risk ratio (RR), respectively. Five randomized controlled trials involving 1753 randomized participants for efficacy assessment and 1874 randomized participants for safety assessment were identified. Valaciclovir dose increasing from 1000 mg/day improved AES only moderately, but significantly promoted the incidence of DARs. Twice-daily treatment showed no increase in therapeutic effect but greatly increased DAR incidence. The valaciclovir dose that produced a reduction in AES was 1000 mg/day: SMD = -0.73 (95% CI -0.98 to 0.48; P < 0.01) and RR = 0.95 (95% CI 0.81-1.09; P < 0.002). Increasing the daily dose of valaciclovir does not substantially improve therapeutic efficacy for CHSI but may raise DAR incidence. Drug doses of 1000 and 2000 mg/day show no significant difference in efficacy scores, but the latter exhibits a higher incidence of DARs. The dose-dependent, long-term efficacy and safety of valaciclovir remain to be explored.

Post-operative Herpes Simplex Virus Encephalitis after Surgical Resection of Meningioma: A Case Report and Review of the Literature

Background: Herpes Simplex Virus (HSV) encephalitis is a rare but life threatening complication in neurosurgical patients. Diagnosis of Herpes Simplex Encephalitis (HSVE) is based on the detection of the herpes simplex virus (HSV) DNA in patient`s CSF samples. A low threshold for both investigations with CSF PCR and empirical treatment with intravenous acyclovir is warranted. Methods and materials: In this case we discussed a 55- year-old man with HSVE after surgical resection of meningioma. We represent a rare case of HSV encephalitis. The appearance of a high grade fever (40°C) and altered consciousness and spastic quadriparesia complicated the post-operative course in a 55-year-old man who underwent surgical removal of a meningioma on the second postoperative day. Brain MRI detected brain abnormalities on the fourth day after onset of symptoms, and polymerase chain reaction (PCR) identification of HSV 1 DNA confirmed the diagnosis. Result: A positive prognosis was achieved due to the decision to start specific, high-dose antiviral therapy based on clinical suspicion, before a firm diagnosis was established. . Treatment with acyclovir was maintained for 8 weeks and patient die after severe sepsis. Conclusion: There are only few case reports of postoperative HSV1 encephalitis. These reports suggest that this rare postoperative complication is associated with a poor prognosis, with high mortality and morbidity. Neurosurgical interventions involving peripheral nerve root or ganglia have been reported to cause re-activation of cutaneous herpes simplex infection. Factors compromising the immune system may also increase susceptibility to herpes simplex infection.

Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates CD4+ and CD8+ T Cell Activation to Localized Viral Infection

The dynamics of when and where CD4(+) Tcells provide help for CD8(+) Tcell priming and which dendritic cells (DCs) activate CD4(+) Tcells invivo after localized infection are poorly understood. By using a cutaneous herpes simplex virus infection model combined with intravital 2-photon imaging of the draining lymph node (LN) to concurrently visualize pathogen-specific CD4(+) and CD8(+) Tcells, we found that early priming of CD4(+) Tcells involved clustering with migratory skin DCs. CD8(+) Tcells did not interact with migratory DCs and their activation was delayed, requiring later clustering interactions with LN-resident XCR1(+) DCs. CD4(+) Tcells interacted with these late CD8(+) Tcell clusters on resident XCR1(+) DCs. Together, these data reveal asynchronous Tcell activation by distinct DC subsets and highlight the key role of XCR1(+) DCs as the central platform for cytotoxic T lymphocyte activation and the delivery of CD4(+) Tcell help.

Disseminated cutaneous herpes simplex virus infection following UVA1 phototherapy in a patient with cutaneous T-cell lymphoma

Disseminated cutaneous herpes simplex virus infection following UVA1 phototherapy in a patient with cutaneous T-cell lymphoma

Epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection: multinucleated epithelial giant cells in the epidermis of lesional skin biopsies from patients with acantholytic dermatoses can histologically mimic a herpes virus infection.

Background:Multinucleated giant cells in the epidermis can either be epithelial or histiocytic. Epithelial multinucleated giant cells are most often associated with herpes virus infections.Purpose:To review the histologic differential diagnosis of conditions with epithelial and histiocytic multinucleated giant cells—since multinucleated giant cells in the epidermis are not always pathognomonic of a cutaneous herpes virus infection—and to summarize dermatoses in which herpes virus infection has been observed to coexist.Methods:Two individuals with acantholytic dermatoses whose initial lesional skin biopsies showed multinucleated epithelial giant cells suggestive of a herpes virus infection are reported. Using the PubMed database, an extensive literature search was performed on multinucleated giant cell (and epidermis, epithelial, and histiocytic) and herpes virus infection. Relevant papers were reviewed to discover the skin conditions with either multinucleated giant cells in the epidermis or coincident cutaneous herpes virus infection.Results:Initial skin biopsies from patients with either pemphigus vulgaris or transient acantholytic dermatosis mimicked herpes virus infection; however, laboratory studies and repeat biopsies established the correct diagnosis of their acantholytic dermatosis. Hence, epidermal multinucleated giant cells are not always a histopathologic clue to a herpes virus infection. Indeed, epithelial multinucleated giant cells in the epidermis can be observed not only in the presence of infection (herpes virus), but also acantholytic dermatoses and tumors (trichoepithelioma and pleomorphic basal cell carcinoma). Histiocytic multinucleated giant cells in the epidermis can be observed in patients with either giant cell lichenoid dermatitis or lichen nitidus of the palms.Conclusions:Epithelial and histiocytic multinucleated giant cell can occur in the epidermis. Keratinocyte-derived multinucleated giant cells are most commonly associated with herpes virus infection; yet, they can also be observed in patients with skin tumors or acantholytic dermatoses. Cutaneous herpes simplex virus infection can coexist in association with other conditions such as acantholytic dermatoses, benign skin tumors, bullous disorders, hematologic malignancies, inflammatory dermatoses, and physical therapies. However, when a herpes virus infection is suspected based upon the discovery of epithelial multinucleated giant cells in the epidermis, but either the clinic presentation or lack of response to viral therapy or absence of confirmatory laboratory studies does not support the diagnosis of a viral infection, the possibility of a primary acantholytic dermatosis should be considered and additional lesional skin biopsies performed. Also, because hematoxylin and eosin staining is not the golden standard for confirmation of autoimmune bullous dermatoses, skin biopsies for direct immunofluorescence should be performed when a primary bullous dermatosis is suspected since the histopathology observed on hematoxylin and eosin stained sections can be misleading.

Clinical utility of loop-mediated isothermal amplification assay for the diagnosis of common alpha herpesvirus skin infections

Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method with a high specificity, efficiency and speed. No reports exist regarding the usefulness of LAMP for clinically suspected skin infections caused by herpes simplex virus (HSV) or varicella zoster virus (VZV). The aim of this study was to evaluate the clinical usefulness of LAMP in the diagnosis of common cutaneous alpha herpesvirus (HSV type 1 and 2, and VZV) infections. LAMP and real-time polymerase chain reaction (PCR) were performed using swab samples collected from 106 patients with clinically suspected alpha herpesvirus skin infections. The results of LAMP performed with DNA extraction did not differ from those performed without DNA extraction. The sensitivity of LAMP tested against real-time PCR was 96% in herpes simplex, 78% in eczema herpeticum, 93% in herpes zoster and 100% in varicella. No viral DNA was detected by LAMP in all negative real-time PCR samples. Viral DNA load was significantly lower in samples with false-negative LAMP results than in the LAMP-positive samples. LAMP enables confirmation of clinically suspected cutaneous HSV and VZV infections. However, the sensitivity of LAMP is lower than real-time PCR. The accuracy of LAMP may increase if sufficient viral DNA is obtained from lesions. LAMP performed without DNA extraction remains sensitive; thus, LAMP represents a quick and economical method for the diagnosis of common alpha herpesvirus skin infections.

Disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under azathioprine and steroids: First case report and literature review

Immunosuppressive treatments used in the management of Inflammatory Bowel Disease, namely steroids, thiopurines and anti-TNF drugs, raise the risk of acquiring opportunistic infections. However, most of these infections are mild and self-limited, not requiring specific therapy or suspension of the immunosuppressors. We report a case of disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under steroids and azathioprine.

059 HSV1 Encephalitis as a postoperative complication of neurosurgical intervention

Intracranial infections following neurosurgery are most commonly caused by bacteria. Postoperative herpes simplex encephalitis has been described but rarely. A 71-year-old woman was admitted electively for resection of a recurrent...

Herpes simplex virus‐induced plasmacytic atypia

The clinical and histopathological features of cutaneous herpes simplex virus (HSV) infection have been well described. Genital herpetic infections are largely induced by HSV type 2, but 30% of cases can be caused by HSV type 1. Immunocompromised patients are known to exhibit atypical patterns of clinical presentation with variable lesion morphology and anatomic location. A subset of patients may show morphology such as nodules or verrucous lesions. Analogously, some biopsy specimens may show unusual microscopical features, such as a lack of keratinocyte cytopathology, lymphocyte infiltration or vasculopathic changes that are expected irrespective of the patient's immune status. We present the case of a patient carrying a previous diagnosis of pemphigus vulgaris, status posttreatment with methotrexate and prednisone, who developed a perineal ulcer exhibiting significant numbers of plasma cells, many of which were cytologically atypical. This morphology was suggestive of a hematopoietic malignancy. Immunoperoxidase staining for HSV decorated a focal collection of keratinocytes that lacked appreciable viral changes expected of HSV infection.

Cutaneous lumbosacral Herpes Simplex virus among patients hospitalized for an advanced disease

Cutaneous Herpes simplex virus (HSV) infections are regularly observed in lumbosacral areas, and many are refractory to appropriate initial diagnosis and management. We aimed to evaluate the incidence of lumbosacral HSV among advanced disease patients, to estimate their survival index from HSV onset, and to describe their clinical and virological characteristics. A prospective, descriptive study was conducted in a palliative and continuous care centre, collecting patients with suspected cutaneous HSV lesions in the lumbosacral area. From 2008 to 2010, 24 patients were included: 19 had HSV-2 confirmed by at least one laboratory test. Incidence of HSV-2 was 2.67% (1.73-4.33%, 95% CI). No age, gender or survival differences were observed compared to the global population in the centre. Most lesions were detected early as vesicles (14/24) or small ulcers. Sensitivity was good for all diagnostic methods (62.5% for immunofluorescence and 79.2% for culture and/or PCR). Outcome was favourable under classical antiherpetic drugs and topical antiseptic dressing. Cutaneous lumbosacral HSV remains uncommon in patients hospitalized with advanced diseases. Most of these patients suffer from pressure ulcers or other dermatitis; we advocate increased attention of this diagnosis to avoid skin complications and added pain.

Transdermal Delivery of Acyclovir Sodium Via Carbopol Gels: Role of Chemical Permeation Enhancers

The effective management of the cutaneous herpes simplex virus infections with acyclovir sodium (ACV) is limited due to reduced availability of ACV at the basal epidermis. The present research focused to improve the transcutaneous permeation of ACV from carbopol gels with different chemical permeation enhancers (dimethylsulfoxide, dlimonene, sodium taurodeoxycholate). The ex-vivo permeation was carried out using excised rat abdominal skin. The extent of ACV accumulated in the rat skin layers was also estimated and found to be higher with gel based formulations compared to reference formulation. Further, the irritancy test and histological studies were carried out to understand the mechanism of ACV permeation across stratum corneum. The improvement in the transcutaneous permeation assessed from steady state flux, permeability coefficient and enhancement ratio were significantly enhanced with gel formulations compared to reference formulation. In conclusion, research findings reveal the potential of carbopol gels for maximizing the therapeutic benefit in herpes virus infections. Keywords: Acyclovir sodium, Carbopol, Flux, Occlusivity, Permeation enhancers, Musosal, Skin Surfaces, Cutaneous Infections, Drug Vehicle, Drug Skin, Vehicle Vehicle Interaction, Permeation

Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum

Loss-of-function null mutations R501X and 2282del4 in the skin barrier gene, filaggrin (FLG), represent the most replicated genetic risk factors for atopic dermatitis (AD). Associations have not been reported in African ancestry populations. Atopic dermatitis eczema herpeticum (ADEH) is a rare but serious complication of AD resulting from disseminated cutaneous herpes simplex virus infections. We aimed to determine whether FLG polymorphisms contribute to ADEH susceptibility. Two common loss-of-function mutations plus 9 FLG single nucleotide polymorphisms were genotyped in 278 European American patients with AD, of whom 112 had ADEH, and 157 nonatopic controls. Replication was performed on 339 African American subjects. Significant associations were observed for both the R501X and 2282del4 mutations and AD among European American subjects (P = 1.46 x 10(-5), 3.87 x 10(-5), respectively), but the frequency of the R501X mutation was 3 times higher (25% vs 9%) for ADEH than for AD without eczema herpeticum (EH) (odds ratio [OR], 3.4; 1.7-6.8; P = .0002). Associations with ADEH were stronger with the combined null mutations (OR, 10.1; 4.7-22.1; P = 1.99 x 10(-11)). Associations with the R501X mutation were replicated in the African American population; the null mutation was absent among healthy African American subjects, but present among patients with AD (3.2%; P = .035) and common among patients with ADEH (9.4%; P = .0049). However, the 2282del4 mutation was absent among African American patients with ADEH and rare (<1%) among healthy individuals. The R501X mutation in the gene encoding filaggrin, one of the strongest genetic predictors of AD, confers an even greater risk for ADEH in both European and African ancestry populations, suggesting a role for defective skin barrier in this devastating condition.