Mild Skin Lesions Research Articles

A Comprehensive Analysis of Immunoglobulin E Levels, Allergen-Specific Sensitivities, and Clinical Manifestations in Allergic Dermatological Conditions: A Multicenter Retrospective Study in China.

To assess the correlations between Immunoglobulin E (IgE) levels, pruritus, and lesion severity in patients with eczema, atopic dermatitis, or urticaria. A retrospective study was conducted and data of 814 patients who visited the dermatology or allergy clinics of multiple hospitals, from December 2019 to December 2021, were collected. Patients were divided into children group (<18 years, 325 cases), adult group (18-60 years, 435 cases), and older population group (>60 years, 54 cases) based on the age. Baseline information, pruritus severity, severity of skin lesions, total IgE level, and specific IgE level were recorded to analyze the complex relationship between them. The prevalence of allergic conjunctivitis and allergic rhinitis in the children group was significantly higher than that in the adult and older population group (P < 0.01 or P < 0.05). The positive rate of specific IgE in children group was significantly higher than that in the adult and older population group (P < 0.01). The IgE levels in children with moderate pruritus were significantly lower than those of severe pruritus (63.39vs 114.42 IU/mL, P < 0.05). The IgE levels in children with mild and moderate skin lesions were significantly lower than those in children with severe skin lesions (58.95 vs 72.88 vs 169.15 IU/mL, P < 0.001 or P < 0.01, respectively). Relationships among age, severity of skin pruritus and lesions, and allergen-specific IgE response are complex and subtle, displaying dynamic patterns.

Therapeutic Nucleic Acids against Herpes Simplex Viruses

The Herpes simplex virus (HSV) causes a wide range of diseases, ranging from relatively mild primary skin lesions to severe and often fatal episodes of encephalitis. Currently, the most effective drugs for HSV-infected people are nucleoside analogs (e.g., acyclovir) targeting enzymes encoded by viral DNA. The effectiveness of nucleoside analogs is reduced because of poor solubility in water, rapid intracellular catabolism, high cellular toxicity, and the appearance of resistant viral strains. Antisense technology that exploits nucleic acid fragments (NA-based agents) is a promising alternative to antiviral therapy due to the high affinity of these agents to target nucleic acids, their high solubility in water, and lower cellular toxicity. In the last decade, antisense oligonucleotides have been investigated as potential drugs for various diseases associated with “harmful” nucleic acids. Oligonucleotides with different chemical modifications targeted at specific regions of the HSV genome have shown effectiveness in suppressing the virus. siRNA-based agents have demonstrated prolonged and effective (up to 99%) inhibition of HSV replication. Based on the publications reviewed in the review over the past 30 years, it can be concluded about the prospects of using NA-based agents to combat herpes viral infections.

Cefditoren pivoxil induced toxic epidermal necrolysis: a case report

Cutaneous adverse drug reactions vary in severity, from mild erythematous skin lesions to life-threatening toxic epidermal necrolysis. Antiepileptics, antipsychotics, antimicrobials, and diuretics are associated with these adverse reactions. We report a case of cefditoren pivoxil-induced toxic epidermal necrolysis in a 46-year-old Indian woman who presented initially with a maculopapular rash that eventually progressed to steroid-refractory toxic epidermal necrolysis. The patient succumbed to her illness on day 33 of the index rash following septic shock.

PS-BPR02-2: ECULIZUMAB FOR RESCUE OF THROMBOTIC MICROANGIOPATHY IN MALIGNANT HYPERTENSION ASSOCIATED WITH MCTD

Introduction: Eculizumab is effective in atypical hemolytic uremic syndrome (aHUS) caused by complement abnormalities, but its effect on secondary thrombotic microangiopathy (TMA) is obscure. We here report a case of TMA associated with malignant hypertension, who was successfully treated with an ACE inhibitor, plasma exchange and eculizumab. Case report: The patient was a 40-year-old woman presenting with severe blood pressure elevation (BP 240/140 mmHg), nausea, fatigue, headache, and visual disturbances. She had a history of systematic lupus erythematosus (SLE) and had been stable by the treatment with 5 mg/day of prednisolone and 2 mg/day of tacrolimus for a long period. This time, she exhibited Raynaud's phenomenon, mild skin lesions, and heliotrope eruption on the eyelids, together with positive anti-U1-RNP antibodies. She was diagnosed with mixed connective tissue disease (MCTD), instead of SLE. Acute kidney injury (serum creatinine, 3.24 mg/dL), anemia (hemoglobin, 8.8 g/dL) and thrombocytopenia (platelets, 137,000/μL) were observed. LDH was elevated at 780 IU/L. The haptoglobin level was decreased to less than detection sensitivity and schistocytes were observed in her peripheral blood. The plasma renin activity was beyond the highest limit. On head MRI, posterior reversible encephalopathy syndrome (PRES) was suggested. A renal biopsy was performed, and a histological diagnosis of malignant hypertensive arteriolosclerosis was obtained. Based on these findings, she was diagnosed as accelerated malignant hypertension, possibly due to TMA with a background of MCTD. She was initially treated with nicardipine, enalapril and aliskiren, but this treatment failed to ameliorate the progression of kidney injury and TMA. Therefore, plasma exchange therapy was performed three days in a row, and then hemodialysis and administration of eculizumab were introduced. After weekly induction dose (900 mg once a week) was given four times, administration of 900–1200 mg of eculizumab every 2 weeks were continued. As the treatment was continued, her renal function was improved gradually. Fifteen months after her onset of AKI and TMA, the patient was withdrawn from dialysis and eculizumab therapy. Conclusion: A body of evidence is growing that activation of the complement system may be involved in scleroderma renal crisis. However, the efficacy of eculizumab in TMA, except for aHUS, remains controversial. Our case suggest a possible efficacy of eculizumab along with plasma exchange, as the treatment of malignant hypertension due to scleroderma that was caused by MCTD.

Natural Compounds in the Battle against Microorganisms-Linalool.

The purpose of this article is to present recent studies on the antimicrobial properties of linalool, the mechanism of action on cells and detoxification processes. The current trend of employing compounds present in essential oils to support antibiotic therapy is becoming increasingly popular. Naturally occurring monoterpene constituents of essential oils are undergoing detailed studies to understand their detailed effects on the human body, both independently and in doses correlated with currently used pharmaceuticals. One such compound is linalool, which is commonly found in many herbs and is used to flavor black tea. This compound is an excellent fragrance additive for cosmetics, enhancing the preservative effect of the formulations used in them or acting as an anti-inflammatory on mild skin lesions. Previous studies have shown that it is extremely important due to its broad spectrum of biological activities, i.e., antioxidant, anti-inflammatory, anticancer, cardioprotective and antimicrobial. Among opportunistic hospital strains, it is most active against Gram-negative bacteria. The mechanism of action of linalool against microorganisms is still under intensive investigation. One of the key aspects of linalool research is biotransformation, through which its susceptibility to detoxification processes is determined.

Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis.

Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation. If both act independently, this might provide a rationale for dual or combined inhibition of both cytokines. Here, we evaluated the effect of TNF blockade in PsA patients on IL-17 levels in both skin and synovial tissue biopsies. PsA patients with mild psoriatic skin lesions were randomized to receive either adalimumab or placebo for four weeks. Synovial and skin biopsies were obtained at weeks zero and four. Skin from healthy donors (HDs) was used for comparison. Expression of IL-17A, IL-17F, IL-17RA and IL-17RC was assessed by immunohistochemistry and analyzed with digital image analysis. We found relatively low levels of IL-17 and its receptors in the skin of PsA patients compared to HD, and only IL-17F in the dermis of lesional psoriatic skin was significantly higher compared to HD skin (p = 0.0002). Histologically IL-17A, IL-17F, IL-17RA and IL-17RC in skin and synovial tissue were not downregulated by adalimumab treatment. Thus, in this cohort of PsA patients with mild psoriasis, TNF blockade did not affect the protein levels of IL-17 cytokines and its receptors in skin and synovium, despite reduced cellular inflammation and improved clinical outcome for joint involvement.

Knowledge of prevention and treatment of human papillomavirus (HPV) infections among young men

Background: Today, human papillomavirus (HPV) infection has become the most common sexually transmitted disease worldwide. Major consequences of contracting the virus include both mild skin lesions and a range of cancers, the most frequent of which are cervical cancer, penile cancer, oral cavity cancer, throat cancer, and anal cancer, undoubtedly demonstrating its high oncogenic potential. Aim of the study: The objective of this study is to determine the level of knowledge among men aged 18–26 years with regard to HPV prevention and treatment. Materials and methods: An online survey was conducted using a questionnaire developed by the authors. The questionnaire was comprised of 16 closed-ended questions and 5 questions pertaining to demographics. Chi-squared tests or Spearman’s rank correlation coefficients were used for the statistical analysis. Results: Only 27.5% of the respondents correctly answered a question regarding the number of types of the virus, and 33% correctly determined the percentage of the cases where an active infection turns into a chronic state. However, a high level of awareness of the routes of infection was demonstrated, with more than half of the respondents (63%) answering this question correctly. Additionally, more than two-thirds (67.9%) of the men indicated correctly that one of the factors facilitating infection is a young age at the time of the first contact with the virus. Nearly all respondents (90%) indicated that using condoms is an effective form of prevention. Conclusions: The results expressly indicate an insufficient level of knowledge regarding HPV among young men. Due to the high level of sexual activity in this age group, increased education with regard to the prevention of sexually transmitted diseases is needed.

The Comparative Study of Atopic Dermatitis and Chronic Hand Eczema Clinical Course in Adults after Acute Relapse Treatment

Aims: To evaluate Atopic dermatitis (AD) and Chronic hand eczema (CHE) course in adults after discontinuation of acute or sub acute relapse treatment.&#x0D; Study Design: three groups of adult patients that finished standard treatment for relapse of AD and CHE were followed up within 24 weeks of period to check disease severity, itch intensity and skin management effectiveness.&#x0D; Place and Duration of Study Sample: population of Ivano-Frankivsk region of Ukraine September 2015 – May 2021.&#x0D; Methods: 155 patients (51 females and 104 males; age between 20 and 50 years) with AD or CHE were enrolled in the study. The patients were randomized into three study groups depending on diagnosis. SCORAD index was used to assess disease severity, visual analog scale (VAS) was used to assess skin itch intensity. Frequency of disease treatment re-start with topical or systemic anti-inflammatory drugs as well as patients’sintention to ask for a treatment were calculated.&#x0D; Results: Results of our study have shown that cases of new disease worsening occured within nearest 24 weeks after AD and CHE aggravation treatment discontinuation and are quite frequent despite appropriate skin care.&#x0D; Conclusion: part of adult patients continues suffering from skin itch or mild skin lesions within nearest 24 weeks after discontinuation of intensive treatment of AD or CHE relapse. Prescription of antihistamines and/or topical anti-inflammatory treatment in addition to generally recommended skin care with emollients is crucial for patients with new worsening of the disease. Among patients with a new signs of worsening a part would unlikely ask for a new treatment immediately unless this worsening is moderate or severe.

Exantema asociado a COVID-19

A partir de marzo de 2020 se han empezado a describir lesiones cutáneas asociadas a COVID-19 que fueron agrupadas en patrones y se relacionaron con la severidad y la temporalidad de la enfermedad. Se presenta el caso de un paciente con COVID-19 leve y lesiones cutáneas que pueden atribuirse a la infección. Se realiza una revisión de las manifestaciones cutáneas asociadas a COVID-19 y la interpretación de los diagnósticos diferenciales que se pensaron en el paciente.

Infection with Nannizziopsis guarroi and Ophidiomyces ophiodiicola in reptiles in Taiwan.

Fungal infection is an emerging threat to reptiles. The main pathogens are fungi of the genera Nannizziopsis, Paranannizziopsis and Ophidiomyces. The clinical symptoms range from mild skin lesions to the dissemination of internal organs and even death. Most of the reported cases are from Europe, North America and Australia. In this study, we report the Nannizziopsis guarroi infection in one captive inland bearded dragon (Pogona vitticeps), one captive green iguana (Iguana iguana) and Ophidiomyces ophiodiicola infection in one wild red-banded snake (Dinodon rufozonatum) and one wild Chinese cobra (Naja atra) in Taiwan. The infections were confirmed by the presence of fungal elements in the tissue. The pathogens were identified based on their morphological and DNA sequence characteristics. The susceptibility profiles of the fungal strains to nine antifungal drugs were obtained using broth microdilution methods. The presence of both fungal species in Asia highlights the urgent need for surveillance and close monitoring of reptile infections to prevent them from spreading and to the possible collapse of reptile populations in the wild.

Urticária pigmentosa no adulto: tratamento bem-sucedido em associação com fototerapia

Introdução: A urticária pigmentosa em adultos é uma forma de mastocitose rara e persistente, frequentemente com manifestações sistêmicas e acometimento da medula óssea, e manifestações cutâneas menos evidentes, ao contrário do que ocorre na infância. Objetivo: Relatar um caso de início na fase adulta, com lesões cutâneas leves, que evoluiu com sintomas de liberação histamínica, porém sem acometimento sistêmico. Metodologia: As informações foram obtidas através de revisão do prontuário, entrevista com o doente, registro fotográfico e revisão da literatura. Conclusão: O diagnóstico correto e a investigação precoce do acometimento de outros órgãos são importantes, bem como o tratamento adequado e prevenção de reações anafilactoides. A fototerapia é opção interessante de tratamento nos casos refratários.

Psoriasis: the choice of optimal topical corticosteroid drug

Psoriasis is an immune-mediated skin disease that occupies one of the leading positions in the morbidity structure of the population of Ukraine. The main mechanism of triggering immunopathological processes in the skin is altered activity of CD4+, CD8+ T-lymphocytes, the synthesis of a number of pro-inflammatory cytokines (tumor necrosis factor a, interleukins-6, -8, -17, etc.) and growth factors (transforming growth factor a, vascular endothelial growth factor and others). The problem of treating psoriasis does not lose its relevance, despite the emergence of new methods of therapy and requires a personalized approach. The Ukrainian protocol for the management of patients with psoriasis (2015) determines topical glucocorticosteroids as first-choice therapy for mild or moderate psoriatic skin lesions and only in the absence of a clinical effect from monotherapy with external agents or their combinations the possibility of other types of treatment is considered. Сorticosteroids, which have a powerful effect on various parts of the pathogenesis of dermatosis, represent a unique opportunity to directly affect the lesions and, accordingly, suppress the inflammatory process in the skin, significantly reduce or eliminate subjective symptoms without resorting to systemic treatment. The effectiveness of modern topical steroids in the treatment of plaque psoriasis has level I evidence (recommendations of level A). The drug of choice in treating patients with psoriasis is the original synthetic steroid mometasone furoate 0.1 % (ointment, cream and lotion Elocom). The drug is characterized by the ability to quickly and durably block the synthesis of pro­inflammatory cytokines and reduce the severity of inflammation. Its predominantly extra­genomic mechanism of action, high lipophilicity and minimal systemic absorption reduce the risk of side effects. Topical steroid mometasone furoate 0.1 % provides quick clinical effect, ease of use due to universal dosage forms, and safety when used correctly.

Mild and severe udder cleft dermatitis—Prevalence and risk factors in Swedish dairy herds

Udder cleft dermatitis (UCD) is an inflammatory skin condition affecting the anterior parts of the udder of dairy cows. The lesions may present as mild or severe skin lesions and have been associated with mastitis and digital dermatitis. The full etiology and pathogenesis are not understood and no large-scale studies have investigated prevalence and risk factors. Therefore, the main objectives of the study were to investigate the prevalence of mild and severe UCD in Swedish dairy herds and to identify risk factors associated with such lesions. We also wanted to investigate risk factors for all cases of UCD and to determine whether UCD increases the risk for mastitis and culling. A random sample of 100 freestall dairy herds were included in the study, and each herd was visited once. Cows were registered as having no, mild, or severe UCD. Additional cow and herd data were obtained via observations, interviews, and the Swedish Official Milk Recording Scheme. The data were analyzed using logistic regression models to identify risk factors for mild and severe UCD. In total, data from 3,479 cows in 99 herds were analyzed. The prevalence of mild and severe UCD was 19 and 9%, respectively. Lesions were found in 98 of 99 herds but the within-herd prevalence of mild (0-43%) and severe (0-33%) UCD varied notably between herds. Breed (Swedish Red compared with Swedish Holstein), certain udder conformation traits, and higher parity were risk factors associated with increased risk of UCD. In addition, cows with hock lesions and cows in herds with high incidence of culling due to hoof and leg diseases had a higher risk for mild UCD. More days in milk and high milk yield were cow-related risk factors associated with severe UCD. Three housing-related factors (shorter cubicles, mattress as cubicle base, and cubicles installed before 2001 compared with 2001-2005), a high incidence of veterinary-treated clinical mastitis and culling due to udder diseases, and a low incidence of culling of first-parity cows in early lactation were herd-related risk factors associated with increased risk for severe UCD. In addition, cows in herds with a high proportion of heifers older than 17 mo that were not inseminated were associated with lower risk of all UCD. Finally, UCD was not associated with the outcomes milk somatic cell count, veterinary-treated clinical mastitis, or culling in the multivariable analyses. The etiology of UCD is most likely multifactorial, involving udder conformation traits and other cow-related risk factors as well as herd-related risk factors. The high prevalence of severe UCD lesions in Swedish dairy cows emphasizes the need for preventive measures and efficient treatments.

The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane.

ABSTRACTAll enveloped viruses, including herpesviruses, must fuse their envelope with the host membrane to deliver their genomes into target cells, making this essential step subject to interference by antibodies and drugs. Viral fusion is mediated by a viral surface protein that transits from an initial prefusion conformation to a final postfusion conformation. Strikingly, the prefusion conformation of the herpesvirus fusion protein, gB, is poorly understood. Herpes simplex virus (HSV), a model system for herpesviruses, causes diseases ranging from mild skin lesions to serious encephalitis and neonatal infections. Using cryo-electron tomography and subtomogram averaging, we have characterized the structure of the prefusion conformation and fusion intermediates of HSV-1 gB. To this end, we have set up a system that generates microvesicles displaying full-length gB on their envelope. We confirmed proper folding of gB by nondenaturing electrophoresis-Western blotting with a panel of monoclonal antibodies (MAbs) covering all gB domains. To elucidate the arrangement of gB domains, we labeled them by using (i) mutagenesis to insert fluorescent proteins at specific positions, (ii) coexpression of gB with Fabs for a neutralizing MAb with known binding sites, and (iii) incubation of gB with an antibody directed against the fusion loops. Our results show that gB starts in a compact prefusion conformation with the fusion loops pointing toward the viral membrane and suggest, for the first time, a model for gB’s conformational rearrangements during fusion. These experiments further illustrate how neutralizing antibodies can interfere with the essential gB structural transitions that mediate viral entry and therefore infectivity.

Molecular characterization of Camelpox virus isolates from Bikaner, India: Evidence of its endemicity

Camelpox is an important viral disease of camels, which may produce mild skin lesions or severe systemic infections. Camelpox virus (CMLV) isolates retrieved from an incidence of camelpox in camels at Bikaner, India were characterized on the basis of genotype and pathotype. Histopathological examination of the CMLV scab revealed intracytoplasmic-eosinophilic inclusion bodies. The phylogenetic analysis of all eight CMLV isolates for C18L gene nucleotide sequence revealed its clustering with its strains M-96 from Kazakhstan and CMS from Iran. The study will help to understand the transmission chain, pathobiology, and epidemiology of circulating CMLV strains. The full genome sequencing of some of the exemplary samples of CMLV is recommended in order to plan and implement a suitable control strategy.

Phenotypic diversity and selection maintain Leishmania amazonensis infectivity in BALB/c mouse model.

Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.

Accessory Gene Regulator Specificity Groups Among Staphylococcus aureus Isolated From Hospitalized Children

Background:: Staphylococcus aureus (S. aureus) especially those with methicillin resistance are human pathogens capable of causing a wide variety of diseases, ranging from mild skin lesions to systemic and fatal infections. Objectives:: The aim of this study was to detect the accessory gene regulator (agr) specificity groups among methicillin resistant and susceptible S. aureus isolated from children. Materials and Methods:: During July 2012 to January 2013, 22 S. aureusc linical isolates were collected from children aged between 2 to 11, in Loghman Hospital of Tehran. Antibiogram test was performed using disc diffusion method. Polymerase chain reaction (PCR) was conducted to detect mecA gene and agr specificity groups. Results:: Among 22 S. aureus clinical isolates collected from children, five isolates (22.7 %) were resistant to methicillin. fourteen isolates (63.6%) were resistant to amoxicillin and all were susceptible to vancomycin and linezolid. Agr specificity group I was detected in 12 (54.5%) isolates (in 2 MRSA and 10 MSSA isolates), agr group II in four (18%, in 3 MSSA and 1 MRSA), group III in 3 (9%, 2 in MSSA and one in MRSA), while agr specificity group IV was found in three (13.6%, 2 MSSA and 1 MRSA) isolates. Conclusions:: The agr specific group I had the highest rate of detection among pathogens isolated from hospitalized children in Tehran.

Validation of the Canine Atopic Dermatitis Extent and Severity Index (CADESI)‐4, a simplified severity scale for assessing skin lesions of atopic dermatitis in dogs

Severity scales are used to grade skin lesions in clinical trials for treatment of dogs with atopic dermatitis (AD). At this time, only two scales have been validated, namely the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-3 and the Canine Atopic Dermatitis Lesion Index (CADLI). However, the high number of assessed sites makes the CADESI-3 impractical. The aim of this study was to develop and validate a fourth version of the CADESI that is simpler and quicker to administer. Body sites, lesions and severity grades were revised by members of the International Committee on Allergic Diseases of Animals (ICADA). The newly designed CADESI-4 was tested for its validity (i.e. content, construct and criterion), reliability (i.e. inter- and intra-observer reliability and internal consistency), responsiveness (i.e. sensitivity to change) and time to administer. Disease severity benchmarks were chosen using receiver operating characteristic methodology. The CADESI-4 was simplified in comparison to its previous version to comprise 20 body sites typically affected in atopic dogs. Three lesions (erythema, lichenification and alopecia/excoriation) were scored from 0 to 3 at each site. The CADESI-4 had satisfactory validity, reliability and sensitivity to change. On average, the time to administer a CADESI-4 was one-third that of a CADESI-3. Proposed benchmarks for mild, moderate and severe AD skin lesions are 10, 35 and 60, respectively. The CADESI-4 is simpler to use and quicker to administer than its previous version. The ICADA recommends the CADESI-4 instead of the CADESI-3 to score skin lesions of AD in dogs enrolled in clinical trials.

Functional characterization of the TSC2 c.3598C&gt;T (p.R1200W) missense mutation that co‐segregates with tuberous sclerosis complex in mildly affected kindreds

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a combination of neurological symptoms and hamartomatous growths, and caused by mutations in the TSC1 and TSC2 genes. Overall, TSC2 mutations are associated with a more severe disease phenotype. We identified the c.3598C>T (R1200W) change in the TSC2 gene in seven different families. The clinical phenotypes in the families were mild, characterized by mild skin lesions, remitting epilepsy and a lack of severe mental retardation or major organ involvement. Functional analysis of the TSC2 R1200W variant, and four other TSC2 missense variants associated with a mild TSC phenotype, confirmed that the changes disrupted the TSC1-TSC2 function. Interestingly however, in each case, the TSC1-TSC2 interaction was not affected by the amino acid substitution.

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis

Although invariant natural killer T (iNKT) cells have been shown to play a critical role in the pathogenesis of asthma, the role of iNKT cells in atopic dermatitis (AD) has not been well evaluated. We investigated whether iNKT cells in patients with AD increased and whether iNKT cells were activated by thymic stromal lymphopoietin (TSLP), which is highly expressed in keratinocytes of AD. We assessed the population of iNKT cells in PBMCs of patients with AD and healthy controls (HCs) using flow cytometry. Immunohistochemistry was used to evaluate iNKT cells and TSLP expression in AD and HC skin. We also evaluated whether iNKT cells expressed the TSLP receptor, the effects of TSLP on iNKT cells, and iNKT cell-dendritic cell interactions in a TSLP-rich environment. There were more iNKT cells among PBMCs of patients with moderate to severe AD than mild AD (P < .05) and HC (P < .001). The number of iNKT cells was significantly larger in severe AD skin lesions than in mild (P < .001) or moderate AD skin lesions (P < .05). TSLP expression increased in lesional skin (P < .001) but not in the sera of patients with AD (P = .729) compared with HC. iNKT cells expressed TSLP receptor protein and mRNA. TSLP directly activated iNKT cells to secrete IL-4 and IL-13, and the concurrent addition of dendritic cells further activated IFN-gamma expression. Increased iNKT cells activated by TSLP, especially in patients with severe AD, might play an essential role in the innate allergic immune response in AD.