Allergic Skin Diseases Research Articles

Characterization of cellular subpopulations and their gene expression by single-cell RNA sequencing in canine atopic dermatitis

Abstract Atopic Dermatitis (AD) is the most common, chronic, and inflammatory allergic skin disease worldwide, with a high prevalence both in children and adults, particularly in developed countries. There are limited effective treatments for severe allergic skin diseases available, thus, there is an unmet need of better understanding the molecular mechanisms and cellular populations involved in AD. Since AD in canines closely resembles the disease in humans, they are an attractive animal model for further studies. Leveraging single-cell RNA sequencing, we identified the cellular composition and shifts in cell populations in canine epidermis of atopic dogs compared to the epidermis from healthy controls. Fibroblasts and keratinocytes represented the largest cell populations, with fibroblasts decreasing in the atopic epidermis. Other populations such as endothelial vascular cells showed differences as well. Shifts in immune cell distribution included changes in subpopulations of dendritic cells and monocytes in the atopic skin. NK and T cells, particularly CD8 T cells were increased. Subclustering revealed specific cellular changes in AD dogs. We found signifiant changes in gene expression in most cell populations, with some genes differentially expressed across cells, while others were expressed in a cell specific manner. We also observed subtle differences between samples from animals with different disease progression, identifying gene expression markers changing with AD severity. Here we show that single-cell sequencing is a useful tool to define the cellular composition in canine atopic dermatitis, resolving changes in gene expression at the cellular level to advance our understanding of disease development and progression. Supported by intramural funds from Western University of Health Sciences

The effects of oclacitinib treatment on antimicrobial usage in allergic dogs in primary practice: an Australia wide case-control study

BackgroundCanine allergic dermatitis is a common diagnosis in veterinary practices which can lead to secondary infections requiring treatment with antimicrobials. A previous study suggested that dogs treated with oclacitinib in an Australian referral hospital required fewer courses of antimicrobial therapy compared to dogs receiving other anti-pruritic treatments. This study aimed to quantify the effect of oclacitinib treatment on the use of antimicrobials and other therapies in general practice veterinary clinics across Australia. A retrospective case-controlled review of patient records was designed to investigate the number of courses of antimicrobials and other therapies in dogs that received oclacitinib (Apoquel®), compared with those who received an anti-pruritic treatment that was not oclacitinib.ResultsThe target population included canine patients with a presumptive diagnosis of allergic dermatitis presenting between 2008 and 2018 to general practices contributing to the VetCompass Australia database. Patient records of interest were identified using search terms relating to allergic dermatitis, resulting in over 700,000 observations. Multivariable logistic regression models were developed to determine whether cases were prescribed fewer antimicrobial courses than controls, after adjusting for the presence of concurrent skin infections or infectious agents in ears. Our results indicate that fewer antimicrobial courses were prescribed in the cases compared to the controls. After adjusting for the concurrent skin infections, there was a significant reduction in the use of cefovecin [OR:0.62(0.39–0.98), P = 0.043], chlorhexidine [OR:0.57(0.42–0.77), P < 0.001], neomycin [OR:0.4(0.28–0.56), P < 0.001] and amoxycillin clavulanic acid (AMC) [OR: 0.55(0.39–0.78), P = 0.001] in cases compared to controls.ConclusionThis study demonstrates a potential sparing effect of oclacitinib on the prescription of antimicrobials for the treatment of allergic skin diseases in dogs. This information may assist in the planning of treatment for canine allergic dermatitis, with consideration for antimicrobial stewardship.

Aeroallergens in Atopic Dermatitis and Chronic Urticaria

While aeroallergens are a well-established trigger of asthma and allergic rhinitis, their role in allergic skin diseases such as atopic dermatitis and chronic urticaria remains controversial. This paper reviews the pathophysiology and clinical evidence for aeroallergens in these allergic skin diseases and summarizes current strategies for evaluation and management. Current evidence implicates aeroallergens as triggers of cutaneous reactions in atopic dermatitis. Direct skin contact is the likely route of trigger. Aeroallergens mayalso trigger chronic urticaria, though mechanistic studies are limited. These allergens may cross the skin barrier and directly trigger neurons to release substance P, resulting in mast cell degranulation and dumping of histamine and prostaglandin D2. Many studies link aeroallergen sensitization to chronic urticaria, and case reports suggest the utility of avoidance strategies. The role of aeroallergens as a trigger is clear in atopic dermatitis and becoming emergent in chronic urticaria. Skin prick testing or serum-specific immunoglobulin E testing may be used to determine sensitivities. Management at this time centers on avoidance, and further studies are necessary to evaluate the efficacy of aeroallergen immunotherapy for both conditions.

Anti-Allergic Effects of Fermented Red Ginseng Marc on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-like Mice Model

Atopic dermatitis (AD) is a chronic and allergic skin disease; however, there is no cure for the disease. Red ginseng is well known to have anti-AD potential, while red ginseng marc (RGM) remaining after ginseng extraction is regarded as useless and discarded. However, it has recently been reported that RGM, particularly fermented RGM (fRGM), still contains bioactive properties. Thus, the anti-allergic effects of fRGM were examined in a 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. Treatments of fRGM alleviated skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion; however, it increased glutathione contents, with downregulated gene expression for inflammatory mediators. Histopathological analyses demonstrated that fRGM suppressed epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved anti-inflammatory, antioxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph nodes. The beneficial effects were observed in the dexamethasone and fRGM groups; however, the antioxidant effects were evident only in the fRGM treatments. These results provide useful information for developing fRGM as a therapeutic source for AD.

Actualization of the issues of effective external therapy of microbial eczema: description of clinical cases

The present study discusses the etiopathogenetic theories of the occurrence of eczema – a chronic recurrent allergic skin disease often encountered in the practice of a dermatovenerologist, formed under the influence of exogenous and endogenous trigger factors, characterized by the appearance of polymorphic rash, inflammatory reaction, disorders of various systems and organs that contribute to the debut or examination of the pathological process. Among the causal influences, various exogenous factors are also noted: infectious agents – resident and transit symbionts – bacteria and fungi, viruses, as well as physical and chemical direct and indirect effects, food products, some medicines. a variety of immunological disorders are described, a modern classification of eczema with the isolation of clinical forms is indicated, a description of the clinical stage-by-stage course of eczema, features of efflorescence in acute and chronic eczema and their variants of evolution in various clinical cases the standard treatment regimens are considered – the appointment of general-acting drugs and local dosage forms. We have described in this publication various clinical cases of treatment of patients suffering from chronic microbial eczema, against the background of their somatic health or with comorbid burden using traditional therapy regimens with the inclusion of combined external agents containing a corticosteroid, an antibiotic and an antimycotic, in accordance with clinical recommendations. All patients at the end of the course of prescribed therapy noted a significant improvement in the form of almost complete relief of erythema, significant leveling of itching, disappearance of wetness, the presence of papular and papulovesicular rashes and manifestations of infiltration, peeling and lichenization of the affected areas of the dermis.

Approaching the future management of sweet itch

Insect bite hypersensitivity, commonly known as the ‘sweet itch’, continues to prove frustrating to manage in practice. Insect bite hypersensitivity is the most common allergic skin disease in horses, characterised as a hypersensitivity to the salivary proteins of the Culicodes genus of insects. The complex nature of this allergic disease means that no set of affected horses can be managed in the same way. Common approaches to sweet itch can be broken down into the categories of anti-inflammatories, allergen avoidance, skin conditioning and immunotherapy. Many effective management techniques focus on avoiding insect bites and regularly washing skin. Advances are currently being made towards effective immunotherapy, with varied results in clinical trials and in practice. As a result of this, a multimodal approach to the management of insect bite hypersensitivity is often recommended.

Features of external therapy of allergic skin diseases in children

The development of inflammatory process in the skin has proven to be primarily associated with the immune system defects, in particular T-lymphocytes: the Th2 response predominates during the acute phase of the disease, when Th2 cells are stimulated with the subsequent hyperproduction of IgE; during the chronic phase, the Th2- shifts to Th1-immune response. At the same time, a significant amount of pro-inflammatory cytokines IL-4, IL-5, IL-13, IL-31 and IFN-γ move into this process. In addition, it is known that skin reactions can be induced not only by food allergens, but also by other allergens (house dust mites, Staphylococcus aureus enterotoxins, mold fungi). The prevalence of atopic dermatitis among the children’s population is up to 20%, while half of the children have skin lesions characterized by a severe long-term course, which violates their quality of life. The main goal of external therapy of dermatoses is to achieve control over subjective symptoms (especially skin itching), as well as regression of inflammatory manifestations with subsequent persistent remission of the allergic process. Local therapy of manifestations of atopic dermatitis is based on the adequate use of various external forms, as well as means in accordance with the inflammatory manifestations and localization of the inflammatory process. The article describes clinical cases of treatment of atopic dermatitis with various variants of its course using methylprednisolone aceponate cream with ceramides, emollient agents. It has been shown that the combined use of topical corticosteroids and emollients contributes to a rapid reduction of inflammation, dry skin and itching. The absence of toxic and side effects on this type of therapy in children with high treatment efficiency is emphasized.

Efficacy of Intralesional Vitamin D3 Injection in Cutaneous Warts

Background: Cutaneous warts are common dermatological viral infection caused condition which causes cosmetic problems besides it primary morbidity like pain and discomfort. Intralesional vitamin D3 derivatives therapy is recent and effective modality for treatment of cutaneous warts. Objective: To determine the efficacy of intralesional vitamin D3 injection in cutaneous warts in local patients. Methods and patients: A descriptive case series study conducted from June to December 24, 2019 at Dermatology OPD, SMBBMU- Larkana.A sample of 65 patients with cutaneous warts, either gender, age 20-50 years, 3 months to 6 months history were included after taking a valid informed/ written consent. Pregnant and lactating women, patients on immunosuppersive therapy, signs of any systemic or local inflammation or infection, history of pasthma allergic skin disorders meningitis or convulsions, history of hypersensitivity to Vitamin D3 were excluded. The injections of vitamin D3 (vials containing 6,00,000 IU of cholecalciferol in 1 ml = 15 mg)were given at 2 weekly intervals for a maximum of four injections.A standard questionnaire was used to collect demographic and study related data. Data analysis was performed through SPSS Version-21. Descriptive and inferential statistics were calculated. Stratification was done and post stratification chi square test was applied. P-value ≤0.05 was considered as significant. Results: The mean age of patients was 27.9±5.1 with C.I (26.63-29.16) years. The Mean ± SD of duration was 4.4±1.9 with C.I (3.92-4.87) months. The Mean ± SD of number of warts was 14.3±4.2 with C.I (13.25-15.34). Out of 65 patients, 35 (53.8%) were malewhile 25 (38.5%) patients were belong to urban areas. Primary outcome of this study i-e; the efficacy was n=54 (83.1%). Stratified analysis revealed that younger age (20 – 30 years), male gender, urban residence, 3-5 mm size, 2-3 months duration (p value = 0.009) were associated with more efficacy of intralesional vitamin D3 injection in cutaneous warts. Conclusion:This study clearly demonstrates that recalcitrant plantar warts can be treated successfully with intralesional vitamin D3 injection. The immunotherapy of injection vitamin D3 has better patient compliance, good therapeutic response without cosmetic disfigurement and capable of preventing recurrences. Keywords: Efficacy, Intralesional Vitamin D3, Cutaneous Warts, Treatment,Immunotherapy

Atopic Dermatitis and Food Allergy: Best Practices and Knowledge Gaps—A Work Group Report from the AAAAI Allergic Skin Diseases Committee and Leadership Institute Project

Allergists are often asked to evaluate children with atopic dermatitis (AD) for allergen triggers to disease. Testing, particularly for food triggers, often leads to elimination diets in an effort to improve AD control. However, the dual exposure hypothesis suggests that oral tolerance to food antigens is promoted through high-dose oral exposure, where sensitization occurs through lower dose cutaneous exposure. This suggests that strict elimination diets may pose some risks in children with AD. In addition, emerging evidence suggests an important role of skin inflammation in further allergic disease and the importance of dietary exposure to maintain oral tolerance. This work group report reviews current guidelines-based management for children with moderate-to-severe AD, the evidence for current recommendations for the evaluation and management of these children, provides a nuanced examination of these studies, and addresses current knowledge gaps in the care of these children.

Regulation of eotaxin expression in skin allergic diseases.

IntroductionAs a key chemotactic factor during Eos recruitment on the allergic inflammation site, eotaxin is regarded as one of the important therapeutic targets.AimTo address the expression and regulation mechanism of eotaxin, which constitutes an important procedure in skin allergic disease and a target for drug therapy.Material and methodsAn allergic contact dermatitis (ACD) model of mouse was established. Immunohistochemical method (ICH) and flow cytometry method (FCM) were used to determine the amounts of CD4+ and CD8+ T cells and their ratios. The eotaxin mRNA and protein were evaluated by real-time PCR, ICH and western-blotting method. Nuclear factor-κB (NF-κB) nuclear translocation and STAT6 phosphorylation were studied by EMSA and western-blotting methods.ResultsWe confirmed that both CD4+ and CD8+ T cells in mouse blood and tissue increased during the allergic process, FBs was the main source for eotaxin under the allergic condition. Both TNF-α and IL-4 showed synergic effects on the up-regulation of eotaxin mRNA and protein in KC and FBs. Eotaxin can be expressed via NF-κB and STAT6 transcription after KC and FBs were stimulated by TNF-α and IL-4.ConclusionsThe obvious up-regulation of eotaxin expression in skin tissue of the mouse ACD model was confirmed, the exact expression site and dynamic process was determined both in vivo and in vitro. The eotaxin expression ability of FBs outperformed that of KC, and eotaxin expression can be regulated by TNF-α and IL-4 via NF-κB and STAT6. The overall findings may pave the way for discovering targets for new drugs and new therapeutic drugs for treating allergic diseases.

Aplicação dos óleos ozonizados nos sistemas do corpo humano e cavidade oral

ABSTRACT Wound healing consists of the coordinated cascade of molecular, cellular and biochemical events that interact for tissue recomposition to occur. The interruption or failure in this process can trigger the delay in closing the lesion and chronic wounds, in addition to infections. Ozonotherapy proves to be a promising alternative, capable of assisting in the tissue healing process, modulating the inflammatory response and preventing the development of infection. To present, analyze and discuss, through a literature review, the use of Ozonated Oils in the repair of the human body and oral cavity systems. SciELO, LILACS, MEDLINE and PubMed databases were consulted, using the following DeCS / MeSH descriptors: “ozonized oil”; “healing”; “ozone therapy”. After crossing, counting and analyzing, 13 studies were selected, according to the theme. Due to the complementary theoretical foundation, 44 articles were included, totaling 57 articles used for the present review. Ozonized Oil therapy has beneficial clinical effects, which include antimicrobial, immunostimulating, analgesic, antipoxic, immunoregulatory and antioxidant action. Topical management of ozone has proven effective for the treatment of foot-and-mouth disease, gingivitis, ulcers and dermatitis, contributing to pain relief and healing. Infectious skin diseases, abscesses, allergic skin diseases, scaly erythema, psoriasis and palmoplantar pustulosis are pathological conditions, the treatment of which benefits from the application of Ozonized Oils. Ozonized Oils have been shown to be effective in the treatment of local infections, when in appropriate formulations and in controlled cases, being a promising therapeutic alternative for tissue repair.

Atopik Dermatit ve Kronik Spontan Ürtikerde Hastalık Aktivite Skoru, Serum Parametreleri ve Deri Prick Testi Arasındaki İlişkinin Araştırılması: Kesitsel Çalışma

Objective: Atopic dermatitis and chronic spontaneous urticaria are allergic skin diseases with recurrent attacks. In this study, disease activity score and laboratory parameters were investigated in patients with atopic dermatitis and chronic spontaneous urticaria. Material and Methods: A total of 68 patients including 33 atopic dermatitis and 35 chronic spontaneous urticaria patients from the dermatology outpatient clinics were enrolled in this study. Serum levels of total immunoglobulin E (IgE), blood eosinophil and basophil counts; prevalence of sensitization to aeroallergens, and disease activity scores were compared between the two groups. Results: A higher eosinophil count in the peripheral blood was observed in atopic dermatitis patients compared to chronic spontaneous urticaria patients. Disease activity scores (SCORAD index) were positively correlated with the eosinophil count and total IgE levels. Furthermore, it was found that the basophil count increased while total IgE levels and SCORAD index scores decreased in the chronic period of the disease. Total IgE levels and SCORAD index scores were higher in atopic dermatitis patients with a positive skin prick test. In chronic spontaneous urticaria patients, it was observed that basophil counts and total IgE levels were correlated, but there was not a correlation between disease activity scores, skin prick test results, and levels of other laboratory parameters. Conclusion: The relationship of serum parameters, especially IgE levels, with the disease activity was found to be significant only in atopic dermatitis.

Evidence-Based Guidelines for SARS-COV-2 Vaccination of Patients of Skin Allergic Diseases and Patients on Immuno-Therapeutics.

There is a dearth of data regarding the safety and timing of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) vaccination of patients on immunosuppressive or immunomodulatory therapies. However, data from other vaccine trials may be extrapolated to get an idea regarding the recommendation of SARS-COV-2 vaccines. All the novel SARS-COV-2 vaccines are non-live, thus ensuring the safety of the vaccines. However, the vaccines may not be able to generate an equipotent immunogenic response in patients receiving immunotherapeutics, in comparison to those who are not. We have attempted to put forward certain statements, with respect to SARS-COV-2 vaccination of patients who are on treatment for different dermatological conditions. However, the risk-benefit ratio must be discussed between the patient and the physician, and the final call should be individualized.

Efficacy of Phototherapy With 308-nm Excimer Light for Skin Microbiome Dysbiosis and Skin Barrier Dysfunction in Canine Atopic Dermatitis.

The management of canine atopic dermatitis, an allergic skin disorder, is challenging. To investigate the effect of phototherapy using a 308-nm excimer light as a topical treatment for canine atopic dermatitis, 10 dogs with canine atopic dermatitis and 10 with non-allergic skin were enrolled in this study. Phototherapy was applied every 7 days for a total of 2 months. The skin microbiome, skin barrier function, and clinical outcomes were evaluated after phototherapy. Phototherapy significantly changed the composition of the skin microbiome of dogs with atopic dermatitis and significantly increased the relative abundance of the phyla Actinobacteria and Cyanobacteria. It significantly alleviated the clinical signs of canine atopic dermatitis without serious adverse effects. Transepidermal water loss, as a measure of skin barrier function, significantly decreased after phototherapy. In addition, phototherapy increased microbial diversity and decreased the relative abundance of Staphylococcus pseudintermedius associated with the severity of canine atopic dermatitis. These results suggest that the excimer light therapy is a suitable and safe therapeutic option for canine atopic dermatitis, which is also a spontaneous animal model of atopic dermatitis.

Novel pathogenesis of atopic dermatitis from the view of cytokines in mice and humans.

Type 2 immunity and inflammation underlie allergic skin disorders, such as atopic dermatitis (AD). In type 2 inflammation, IL-4, IL-13, and IL-5, which are signature type 2 cytokines, are mainly produced by type 2 helper T (Th2) cells and form the characteristic features of AD. Epithelial cell-derived cytokines such as IL-25, IL-33, and TSLP initiate type 2 inflammation by modulating various cells, including group 2 innate lymphoid cells. Moreover, IL-31, a newly identified type 2 cytokine produced mainly by Th2 cells, induces pruritus by acting on sensory neurons in the skin. Based on both basic and clinical findings, several biologics targeting Th2 cytokines have been developed and exhibited significant efficacy as therapeutic reagents for AD. We have summarized the roles of each cytokine (IL-4, 5, 13, 25, 31, and 33, and TSLP) in the development of type 2 inflammation, especially AD, from the view of basic studies in mice and clinical trials/observation in humans.

Serum-Derived Neuronal Exosomal microRNAs as Stress-Related Biomarkers in an Atopic Dermatitis Model.

Chronic allergic inflammatory skin disease—atopic dermatitis (AD)—is characterized by eczema, pruritus, xeroderma, and lichenification. Psychological stress is one cause of this disease; however, psychological stress will also result from the presence of AD symptoms. Previous studies have shown that psychological stress triggers neuroinflammation in the brain, where microRNAs (miRNAs) in the neuronal exosomes (nEVs) were analyzed to identify the composition of the miRNAs in the nEVs and how they were altered by AD. In this study, the AD model was induced by treatment with 2,4-dinitrochlorobenzene (DNCB). The expression patterns of neuroinflammation markers, such as brain-derived neurotrophic factor, cyclooxygenase-2, and glial fibrillary acidic protein, were subsequently evaluated over time. Among these groups, there was a significant difference in DNCB 14 days expression compared with the control; therefore, nEVs were isolated from serum and next-generation sequencing was performed. The results demonstrate that 9 miRNAs were upregulated and 16 were downregulated in the DNCB 14 days compared with the control. Previous studies have shown that some of these miRNAs are associated with stress and stress-induced depression, which suggests that the miRNAs in nEVs may also be stress-related biomarkers.

Complexity and multistability of a nonsmooth atopic dermatitis system

Atopic dermatitis (AD) has been known as the most common allergic inflammatory skin disease and its immunopathogenetic network is very complex. In this paper, to investigate the complexity of AD, we study a in silico AD model based on the mechanisms of AD disease pathogenesis, which is described by a nonsmooth system with three switches. We uncover a new oscillating behavior Os called Serious Oscillation, which can make a clear distinction between oscillating behaviors. It thus makes possible to classify AD attractors, which is very similar to AD clinical symptoms used in SCORAD index. A striking finding is that by investigating the existence and the stability of all found attractors on the parameter space for Barrier permeability κP and Immune responses αI, there exist many different types of bi- and multistability: four and five different types of bistability and multistability, respectively. By characterizing these different types of bi- and multistability, we finally conclude that the complexity of AD is caused by multistability detected in too much wide parameter ranges. In addition, we show a peculiar bifurcation phenomenon occurred in nonsmooth dynamical system. Our results suggest that the existence of multistability will make it possible to better understand the complexity of AD, which can be applicable in the development of new therapy strategies.

Immunological Targets of Biologic Drugs in Allergic Skin Diseases in Children.

Atopic dermatitis and urticaria are two invalidating skin disorders that are very common in children. Recent advances in the understanding of their specific intracellular molecular pathways have permitted the development of precise biological molecules, targeting inflammatory mediators and arresting the pathogenetic pathways of skin diseases. Many biologics with promising results have been studied, although few are currently approved in children. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat atopic dermatitis and chronic urticaria in children and adolescents.

Biologics for Asthma and Allergic Skin Diseases in Children.

An estimated 7 million children in the United States have asthma, which causes a significant health care burden and affects quality of life. The minority of these children have asthma that does not respond to Global Initiative for Asthma steps 4 and 5 care, and biological medications are recommended at this level in the 2019 Global Initiative for Asthma recommendations. In addition, biologics have been introduced into the care of children with allergic skin diseases. Omalizumab and mepolizumab are approved for children as young as 6 years, and benralizumab and dupilumab are approved for people aged ≥12 years. Reslizumab is approved only for people aged ≥18 years. These monoclonal antibodies may be added for appropriate patients when asthma or allergic skin diseases are not well controlled. Pediatricians and pediatric subspecialists should work together and be aware of the benefits and risks of these medications for their patients, as well as the practical implications of providing these options for their patients. This clinical report serves as an evaluation of the current literature on these types of medications in the treatment of children with asthma and allergic skin disease.

Detection and Analysis of Allergens in Allergic Skin Diseases

Detection and Analysis of Allergens in Allergic Skin Diseases