Allergic Skin Diseases Research Articles

A study on periostin involvement in the pathophysiology of canine atopic skin.

Atopic dermatitis (AD) is a chronic, pruritic, and allergic skin disease in humans and animals, particularly dogs. Canine AD (cAD) has received attention as a spontaneous atopic animal model because domesticated dogs inhabit a human environment, and cAD shares several clinicopathological features with human AD (hAD). In hAD, periostin (PO) is suggested to play a critical role in the enhancement and chronicity of allergic skin inflammation; however, PO involvement in the pathogenesis of cAD is unknown. Here we aimed to clarify PO involvement in the pathophysiology of cAD and focused on the inducing factor and function of PO in canine atopic skin. Using double-labeled in situ hybridization (ISH), interleukin (IL)-13 mRNA-positive cells were detected near the keratinocytes and dermal fibroblasts expressing PO mRNA in atopic skin. Using an in vitro assay, IL-13 induced PO gene expression in both canine dermal fibroblasts and keratinocytes. PO enhanced in vitro growth of canine keratinocytes. Moreover, among PO-induced genes in cultured canine keratinocytes detected using a microarray, we identified IL-25 as a possible mediator in canine atopic skin. In addition, real time polymerase chain reaction (PCR) analysis revealed upregulation of IL-25 gene expression in PO-stimulated keratinocytes. These data suggest that IL-13 possibly derived from T helper 2 (Th2) cells stimulates PO production in both keratinocytes and fibroblasts, and then PO may play a critical role in the pathophysiology of cAD, particularly in the enhancement and chronicity of skin lesions via IL-25.

UK trends of allergic occupational skin disease attributed to fragrances 1996-2015.

Fragrances are well known to cause allergic contact dermatitis (ACD). Occupationally related cases occur, with certain groups being at higher risk. To investigate the incidence of occupationally related cases of cutaneous fragrance allergy and to evaluate trends. Data on incident cases of occupational ACD caused by fragrances between 1996 and 2015 (inclusive) reported to the EPIDERM surveillance scheme were analysed. Of the cases reported to EPIDERM during the study period, 5.2% had ACD attributed to fragrances. The highest annual incidence rates were observed in women. Hairdressers, beauticians and people working in related occupations had a 47-fold higher incidence rate ratio than the reference category (the average of all other occupations combined). Trends analysis suggested a non-significant increase in fragrance allergy over the study period among all occupations, and beauty and food workers, and a slight decrease in healthcare workers. Fragrance allergy is a significant problem in an occupational setting. Although there was no significant change in the incidence of fragrance-related allergic occupational contact dermatitis (OCD) during the 20-year study period, this does not mirror the trend in OCD, which is falling. Fragrance allergy continues to be a major contributor to OCD, and contributes to a greater proportion of cases.

Chrysin attenuates atopic dermatitis by suppressing inflammation of keratinocytes

We previously reported the inhibitory effect of chrysin, a natural flavonoid plentifully contained in propolis, vegetables and fruits, on the mast cell-mediated allergic reaction. In this study, we evaluated the effect of chrysin on atopic dermatitis (AD) and defined underlying mechanisms of action. We used an AD model in BALB/c mice by the repeated local exposure of 2,4-dinitrochlorobenzene (DNCB) and house dust mite (Dermatophagoides farinae extract, DFE) to the ears. Repeated alternative treatment of DNCB/DFE caused AD-like skin lesions. Oral administration of chrysin diminished AD symptoms such as ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. Chrysin decreased infiltration of mast cells, and reduced serum histamine level. Chrysin also suppressed AD by inhibiting the inflammatory responses of Th1, Th2, and Th17 cells in mouse lymph node and ear. Interestingly, chrysin significantly inhibited the production of cytokines, Th2 chemokines, CCL17 and CCL22 by the down-regulation of p38 MAPK, NF-κB, and STAT1 in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT). Chrysin also inhibited TNF-α/IFN-γ-stimulated IL-33 expression in HaCaT cells and mouse primary keratinocytes. Taken together, the results indicate that chrysin suppressed AD symptoms, suggesting that chrysin might be a candidate for the treatment of AD and skin allergic diseases.

Balneotherapeutic effects of high mineral spring water on the atopic dermatitis-like inflammation in hairless mice via immunomodulation and redox balance

BackgroundAtopic dermatitis (AD) is a chronic relapsing allergic inflammatory skin disease that currently affects millions of children and adults worldwide. Drugs used to treat these inflammatory diseases include anti-histamines, corticosteroids and calcineurin inhibitors but these drugs have their limitations such as adverse effects with their long-term usage. Thus, researcher’s interest in several alternative and complementary therapies are continually growing and balneotherapy is one of these approaches. Therefore, we investigate the bathing effect of high concentration mineral spring water (HMW) on redox balance and immune modulation in 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis like inflammation in hairless mice.MethodsWe induced AD-like inflammation by application of DNCB on the dorsal skin of female skh-1 hairless mice. The mice were treated with 100% pure HMW (PHMW) and 10% diluted HMW (DHMW) through bathing once a day for 4 weeks. Tacrolimus ointment (0.1%) was used as positive control (PC) and only DNCB treatment as negative control (NeC) group. The severity of skin lesion inflammation was assessed through clinical scoring and observing scratching behavior. Levels of immunoglobulin E (IgE) and inflammatory cytokines in serum were detected by ELISA and multiplex bead array system, and the levels of oxidative stress-related biomarkers and antioxidant enzyme were also measured.ResultsWe found that HMW significantly decreased the scratching behavior in PHMW and DHMW groups at the 2nd week and in PHMW group at 4th week compared to NeC group. Likewise, serum IgE level was significantly decreased in DHMW group as compared to NeC group. In line, the level of inflammatory cytokines in serum such as interleukin (IL)-1β, IL-13 and tumor necrosis factor-α were significantly inhibited in PHMW and DHMW groups compared to NeC group. In parallel, total reactive oxygen species (ROS) of serum level was significantly decreased in PHMW treatment groups compared to NeC group. Consistently, serum malondialdehyde (MDA) level in PHMW group was lower than in NeC group. By contrast, glutathione peroxidase (GPx) activity was significantly enhanced in PHMW than NeC.ConclusionCollectively, our study indicates a balneotherapeutic effect of HMW on DNCB-induced AD like inflammation in hairless mice via immunomodulation and redox balance.

Acupuncture and Cutaneous Medicine: Is It Effective?

Background: In China, acupuncture has been used as a form of medical therapy for more than 2500 years. It is a part of traditional medical practice and is used to treat the entire spectrum of human and veterinary disease. Although dermatologic disease has received much less attention in worldwide acupuncture research than pain and musculoskeletal conditions, there is a growing body of evidence suggesting acupuncture's usefulness in this area. Objective: The aim of this article was to review the evidence in the literature regarding the usefulness of acupuncture in managing dermatologic illness. Results: Trials and case reports of patients using acupuncture have been published in the areas of atopic dermatitis and urticaria, herpes zoster, psoriasis, acne, melasma, and hyperhidrosis, as well as in promoting wound healing. Itch modulation by acupuncture has been the focus of recent research as itch is a predominant symptom in allergic skin diseases and leads to serious impairment of quality of life. Conclusions: Although more research is needed, acupuncture's use in cutaneous medicine is promising in the area of itch modulation, in treating atopic dermatitis and herpes zoster pain, and in promoting wound healing.

T-Helper Type 2 Cells Direct Antigen-Induced Eosinophilic Skin Inflammation in Mice.

Eosinophilic inflammation in combination with immunoglobulin E (IgE) production is a characteristic feature of atopic dermatitis. Although activated T-helper type (Th) 2 cells play critical roles in the local accumulation and activation of eosinophils, whether they induce eosinophilic skin inflammation, independent of the IgE-mediated pathway has been unclear. To address the functional role of T cells in allergic skin diseases, we herein transferred Th1/Th2-differentiated or naive DO11.10 T cells into unprimed BALB/c mice. Ovalbumin-specific Th2 cells, as well as eosinophils, accumulated in the skin upon antigen challenge, despite the absence of antigen-specific IgE. Neither antigen-specific Th1 nor naive T cells induced eosinophil accumulation, although Th1 cells by themselves migrated into the skin. Interleukin (IL)-4, IL-5, and eotaxin were specifically produced in the skin of antigen-challenged, Th2 cell-transferred mice, whereas interferon (IFN)-γ and regulated on activation, normal T cell expressed and secreted (RANTES) were preferentially produced in Th1 cells-transferred mice. Production of monocyte chemoattractant protein (MCP)-1 and MCP-3 was enhanced by both Th1 and Th2 cells. The accumulation of eosinophils and Th2 cells in the skin was suppressed by both dexamethasone and FK506, indicating an essential role of Th2 cells in eosinophil recruitment. We conclude that Th2 cells can induce eosinophilic infiltration into the skin in the absence of antigen-specific IgE.

IL-33 and IgE stimulate mast cell production of IL-2 and regulatory T cell expansion in allergic dermatitis.

We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. Isolated murine bone marrow-derived MCs (BMMCs) were incubated with various stimulators, and IL-2 production was assessed by RT-PCR and ELISA. The response of signalling pathways was evaluated by MAPK inhibitors and Western blot analysis. The effect of MC-IL-2 on Tregs was studied by incubation of splenic T cells with conditioned media obtained from activated BMMCs. Dermatitis was elicited by repeated exposures of mouse ears to oxazolone. MCs in mouse and human skin samples were evaluated by immunostaining. BMMCs released IL-2 in response to IL-33, and IL-2 production was further enhanced by concomitant FcεRI activation. The effect of IL-33 was mediated by activation of the MAPK family members. IL-2 in conditioned media from IL-33 and IgE-stimulated BMMCs led to considerable expansion of Tregs invitro. IL-33 levels were elevated in oxazolone-challenged ears along with increased numbers of IL-2-expressing MCs. Human skin with chronic inflammation also contained IL-2-expressing MCs that colocalized with IL-33 staining in the dermis. IL-33, in collaboration with IgE, is critical for MC-IL-2 production in allergic skin disease, thus leading to Treg stimulation and suppression of allergic dermatitis.

Molecular characteristics and serodiagnostic potential of chitinase-like protein from Sarcoptes scabiei.

Scabies, caused by the mite Sarcoptes scabiei, is an allergic skin disease that affects millions of people and other mammals worldwide. This highly contagious parasitic disease is among the top 50 epidemic disease and is regarded as a neglected tropical disease. Diagnosis of scabies is difficult in the early stage, and the pathogenesis of scabies is not currently clear. Here, we expressed, identified and located the chitinase-like protein of S. scabiei (SsCLP), and evaluated its potential as an early-stage diagnostic antigen for rabbit scabies. Indirect ELISA using recombinant SsCLP (rSsCLP) exhibited diagnostic sensitivity of 94.4% (17/18) and specificity of 86.7% (26/30). Early diagnostic test after artificial infection of rabbits with S. scabiei for 1 week showed a positive detection rate of 96.7% (29/30). Immunolocalization assays showed that fluorescence signals were localized on the surface of mites and, in infected rabbits, were observed in keratinized skin and embedded mites. Intradermal skin tests of rabbits by injecting rSsCLP showed a wheal, flare and erythema reaction. These results suggest that S. scabiei chitinase-like protein is conducive to host invasion, participates in inducing the allergic response of the host, and is an effective antigen for the diagnosis of S. scabiei.

Large-scale survey to estimate the prevalence of disorders for 192 Kennel Club registered breeds

BackgroundPedigree or purebred dogs are often stated to have high prevalence of disorders which are commonly assumed to be a consequence of inbreeding and selection for exaggerated features. However, few studies empirically report and rank the prevalence of disorders across breeds although such data are of critical importance in the prioritisation of multiple health concerns, and to provide a baseline against which to explore changes over time. This paper reports an owner survey that gathered disorder information on Kennel Club registered pedigree dogs, regardless of whether these disorders received veterinary care. This study aimed to determine the prevalence of disorders among pedigree dogs overall and, where possible, determine any variation among breeds.ResultsThis study included morbidity data on 43,005 live dogs registered with the Kennel Club. Just under two thirds of live dogs had no reported diseases/conditions. The most prevalent diseases/conditions overall were lipoma (4.3%; 95% confidence interval 4.13-4.52%), skin (cutaneous) cyst (3.1%; 2.94-3.27%) and hypersensitivity (allergic) skin disorder (2.7%; 2.52-2.82%). For the most common disorders in the most represented breeds, 90 significant differences between the within breed prevalence and the overall prevalence are reported.ConclusionThe results from this study have added vital epidemiological data on disorders in UK dogs. It is anticipated that these results will contribute to the forthcoming Breed Health & Conservation Plans, a Kennel Club initiative aiming to assist in the identification and prioritisation of breeding selection objectives for health and provide advice to breeders/owners regarding steps that may be taken to minimise the risk of the disease/disorders. Future breed-specific studies are recommended to report more precise prevalence estimates within more breeds.

Evaluation of the correlation between Scoring Feline Allergic Dermatitis and Feline Extent and Severity Index and skin hydration in atopic cats.

Evaluation of the severity of clinical signs of cats with allergic skin diseases has used two scoring systems: Scoring Feline Allergic Dermatitis (SCORFAD) and the Feline Extent and Severity Index (FeDESI). The integrity of the cutaneous barrier can also be evaluated by measuring skin hydration. A correlation between the clinical score and skin hydration has been observed in humans and dogs with atopic dermatitis (AD). To demonstrate a correlation between the clinical score and skin hydration of cats affected with presumed AD. European short hair cats (n = 18): 11 females and seven males with a confirmed diagnosis of AD. SCORFAD and FeDESI scores were calculated and the measurements of skin hydration were assessed from seven body sites using corneometry. The correlation between the SCORFAD and FeDESI systems and skin hydration of each site, and the average skin hydration was calculated. There was a positive correlation between the SCORFAD score and skin hydration for the axilla, thorax and forelimb; for FeDESI and axilla and lumbar sites. There was a negative correlation between the FeDESI and skin hydration for the pinna (r = -0.47). Measurements of skin hydration could be a useful tool for the evaluation of allergic cats. There is limited evidence of any useful correlation between clinical scoring systems and measurements of hydration. The pinna may be a suitable region for the assessment of skin barrier function in normal and allergic cats.

Efficacy of APOQUEL® for the Control of Otitis Externa Secondary to Allergic Skin Disease in Client-Owned Dogs

Efficacy of APOQUEL® for the Control of Otitis Externa Secondary to Allergic Skin Disease in Client-Owned Dogs

Poly-ADP ribose polymerase-14 limits severity of allergic skin disease.

Poly-ADP ribose polymerase-14 (PARP14 or ARTD8) was initially identified as a transcriptional co-activator for signal transducer and activator of transcription 6 (Stat6), where the presence of interleukin-4 (IL-4) and activated Stat6 induces the enzymatic activity of PARP14 that promotes T helper type 2 differentiation and allergic airway disease. To further our understanding of PARP14 in allergic disease, we studied the function of PARP14 in allergic inflammation of skin using mice that express constitutively active Stat6 in T cells (Stat6VT) and develop spontaneous inflammation of the skin. We mated Stat6VT mice to Parp14-/- mice and observed that approximately 75% of the Stat6VT × Parp14-/- mice develop severe atopic dermatitis (AD)-like lesions, compared with about 50% of Stat6VT mice, and have increased morbidity compared with Stat6VT mice. Despite this, gene expression in the skin and the cellular infiltrates was only modestly altered by the absence of PARP14. In contrast, we saw significant changes in systemic T-cell cytokine production. Moreover, adoptive transfer experiments demonstrated that decreases in IL-4 production reflected a cell intrinsic role for PARP14 in Th2 cytokine control. Hence, our data suggest that although PARP14 has similar effects on T-cell cytokine production in several allergic disease models, the outcome of those effects is distinct, depending on the target organ of disease.

Anti-inflammatory potential of a heat-killed Lactobacillus strain isolated from Kimchi on house dust mite-induced atopic dermatitis in NC/Nga mice.

Atopic dermatitis (AD) is an allergic skin disease driven by the Th2-prone immune response. Therefore, a fundamental approach to restoring the Th1/Th2 balance is needed to treat AD. Eighteen different Lactobacillus strains isolated from Kimchi were screened to identify those that stimulated immune cells to secret Th1-type or Th2-type cytokines. Lactobacillus brevis NS1401 induced the greatest IFN-γ and IL-12 secretion and the least IL-4 production among the tested Lactobacillus strains. Furthermore, oral administration of heat-killed NS1401 ameliorated the symptoms of dust mite-induced AD in NC/Nga mice by decreasing the serum IgE level and reducing the number of mast cells and eosinophils in lesions. Also, the size and number of cells in the draining lymph nodes of NS1401-administered mice were significantly reduced. In agreement with these results, secretion of a Th1-type cytokine (IFN-γ) and allergen-specific IgG2a were increased, whereas secretion of Th2-type cytokines (IL-4, IL-5, and IL-10) and allergen-specific IgG1 were decreased upon administration of NS1401 in mice. Lactobacillus brevis NS1401 alleviates the symptoms of AD by restoring the Th1/Th2 balance through enhancing Th1-prone immunity. The immunomodulatory function of L.brevis NS1401 may provide effective new therapeutics against AD.

Pentanoic acid induces thymic stromal lymphopoietin production through Gq/11 and Rho-associated protein kinase signaling pathway in keratinocytes

Thymic stromal lymphopoietin (TSLP) plays an important role in allergic skin inflammation. Short-chain fatty acids (SCFAs), including pentanoic acid, are products of bacterial metabolism and are associated with allergic skin disorders. However, whether SCFAs induce TSLP production is still unclear. In this study, we evaluated the effect of SCFAs on TSLP production and found that pentanoic acid was the most efficacious of the tested SCFAs. The Gq/11 inhibitor YM-254890 and the Rho-associated protein kinase (ROCK) inhibitor Y-27632 inhibited pentanoic acid-induced TSLP production, as did transfection with Gq/11 siRNA. These results suggested that pentanoic acid-induced TSLP production was mediated by Gq/11 and ROCK, providing insights into a novel TSLP production pathway in keratinocytes. The novel mechanism of TSLP production is expected to support the development of TSLP-regulating approaches in allergic skin disorders.

The structure of occupational skin diseases among workers of diverse industrial sectors of the Republic of Bashkortostan

We have analysed the structure of occupational skin diseases diagnosed in workers of diverse industrial sectors of the Republic of Bashkortostan. It has been shown that allergic skin diseases rank first among occupational dermatoses which currently amount to 52 %. Average length of work employment in hazardous working conditions is 13,7 ± 12,2 years. Occupational allergic diseases are more common among medium-level healthcare workers. Occupational hyperkeratoses and skin cancer are mainly detected in continuous fiberglass workers.

Modern aspects of treatment of allergic dermatitis with the secondary fungal infections

Allergic skin disease pathology is widespread in the world and in the last decade has attracted the attention of doctors. In Ukraine, 40 % of adults and children suffer from all types of allergic dermatitis. The aim of this work is to study the current state of treatment of allergic dermatitis complicated with the secondary fungal infection, and substantiate the necessity for creating the extemporaneous ointment for the treatment of this skin pathology. The known recommendations of doctors concerning the treatment of allergic dermatitis include measures aimed at excluding or reducing a contact with a variety of triggers, skin care (permanent cleaning and moisturizing) and the treatment of pruritus and chronic inflammation with anti-inflammatory medicines depending on the severity, localization of lesions of the skin, as well as skin infections associated with allergic dermatitis. In addition to the systemic therapy, the topical treatment of affected areas of the skin is also recommended for patients with allergic dermatitis. The external therapy should be carried out taking into account the clinical form and stages of the disease. To analyze the existing extemporaneous formulations for the treatment of allergic dermatitis complicated with the secondary fungal infection prescriptions of various soft medicinal forms for treating allergic dermatitis approved by the Ministry of Public Health of Ukraine have been studied. The absence of antifungal components in their composition has been shown. The necessity of creating a new extemporaneous ointment for the treatment of allergic dermatitis complicated with the secondary fungal infection with the complex anti-allergic and antifungal action using a dry extract of licorice root, essential oil of lavender and terbinafine hydrochloride has been substantiated.

Treatment of presumed allergic skin disease in cats

Feline dermatology presents a number of challenges when it comes to diagnosing individual diseases, due to the more subtle and varied nature of skin lesions in cats compared to those...

Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats.

Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly “feline atopic syndrome” when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.

Research of glucocorticosteroid therapy influence on neutrophils phagocytarial activity in allergic contact dermatitis conditions

Topicality. The population sensitization increases and in this connection they observe allergic skin diseases, which is an actual problem in medicine. The main dermatitis treatment is a glucocorticosteroid therapy, but it leads to reducedimmunity and serious side effects in patients.Aim. Research of glucocorticosteroid therapy influence on neutrophils phagocytarial activity in allergic contact dermatitis conditions.Materials and methods. Studies were conducted on a model 2,4 Dinitrochlorobenzene dermatitis in rats. Neutrophil granulocyte phagocytic activity was assessed by phagocytic index and phagocytic number, and the immune system - by the level of circulating immune complexes (CIC).Results and discussion. It was established that cream containing mometasone and ceramides, ointment containing methylprednisolone does not affect on neutrophil phagocytic activity and, at the same time, does not affect on the neutrophil phagocytic quantity (phagocytic index) and their absorbing properties (phagocytic number), as well as normalize CIC levels.Conclusions. Obtained results indicate the normal course of phagocytosis and animals immune protection during the local glucocorticosteroid therapy in the allergic dermatitis conditions.

Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs.

BackgroundCanine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome‐wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin‐2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities.ObjectivesThe main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD‐affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location.Animals/MethodsSkin biopsies were collected from nine CAD‐affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology.ResultsWe observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding‐partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed.ConclusionPlakophilin‐2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes.