Identification of cutaneous fungi and mites in adult atopic dermatitis: analysis by targeted 18S rRNA amplicon sequencing.

BACKGROUND: Atopic dermatitis (AD) patients have an altered skin bacterial community, with an abundance of Staphylococcus aureus associated with flares, highlighting that microbial organisms may be important for disease exacerbation. Despite strong evidence of association between bacterial skin colonisation and AD, very limited knowledge regarding the eukaryotic microbial community, including fungi and ectoparasites, in AD exists. In this study, we compared the skin and nasal eukaryotic microbial community between adult AD patients (n = 55) and non-AD healthy controls (n = 45) using targeted 18S rRNA amplicon sequencing. Analysis was based on the presence or absence of eukaryotic microorganisms. RESULTS: The cutaneous composition of the eukaryotic microbial community and the alpha-diversity differed significantly between AD patients and non-AD individuals, with increased species richness on AD skin. Alpha-diversity and beta-diversity were similar on lesional and non-lesional skin of patients. The ectoparasite Demodex folliculorum and the yeast Geotrichum candidum were significantly more prevalent on the skin of AD patients. The prevalence of D. folliculorum on lesional skin was greater among patients recently treated with topical corticosteroid. Malassezia was one of the most frequently detected genera at all sites, with M. globosa and M. restricta being the most prevalent. M. restricta was under represented in the anterior nares of AD patients as compared to the non-AD control population. CONCLUSION: Significant differences in the eukaryotic microbial communities were found between AD patients and non-AD individuals, with the most striking finding being the significantly overrepresentation of D. folliculorum on AD skin. Whether D. folliculorum can contribute to skin inflammation in AD needs further investigation.

Critically Appraised Topic on Adverse Food Reactions of Companion Animals (8): Storage Mites in Commercial Pet foods.

BACKGROUND: Dogs with year-round atopic dermatitis are often sensitized to Dermatophagoides house dust mites (HDM). Storage mites (SM) are known to grow on cereal-rich foods. Tyrophagus SM can exacerbate clinical signs of allergy in laboratory dogs sensitized to HDM. Consequently, atopic dogs with high-levels of HDM-specific IgE are likely to have a flare of signs after eating a food contaminated with SM; the development of such flares would lead to a false positive diagnosis of food allergy. Herein, we reviewed the published evidence about the growth of SM on commercial dry pet foods. RESULTS: We searched two databases on January 25, 2019 for articles providing original information on the growth of SM on commercial dog foods. We found ten articles, five reporting results of laboratory experiments and five from field studies. Storage mites, especially Tyrophagus putrescentiae, can multiply on protein- and fat-rich dog foods. The population growth is higher when the initial mite density is high and when kibbles are crushed. When storage conditions lead to the overgrowth of molds on the kibbles, the mite proliferation is higher. Storage mites do not bore holes in food packages but invade bags via defective seals. In the field, SM contamination usually is undetectable in newly-opened commercial dog foods, and, if present, their number is low. When newly-purchased bags are stored in temperate conditions indoors, little overgrowth-if any-of SM occurs. However, when kept in environmental conditions with higher temperature and humidity, Tyrophagus mites will enter and proliferate in sealed food packages. CONCLUSIONS: Commercial dry pet foods should be kept indoors and sealed to decrease the risk of contamination with SM. When performing dietary restriction (elimination) and provocation trials for the diagnosis of food allergies in dogs, it seems preferable to choose newly-purchased bags-of both original and testing diets-to reduce the probability of their contamination with SM, especially Tyrophagus putrescentiae. In case of doubt about the presence of SM in any of these foods, one should perform food challenges with single home-cooked ingredients. Storage mite contamination might lead to an erroneous diagnosis of food allergy in HDM-sensitized dogs.

Supplemental feeding of phospholipid-enriched alkyl phospholipid from krill relieves spontaneous atopic dermatitis and strengthens skin intercellular lipid barriers in NC/Nga mice.

Plasmalogen (Pls) is a glycerophospholipid derived from alkyl phospholipid (Alk) with antioxidant functions in vivo. The present study investigated the effects of ether phospholipids, such as Pls and Alk, on intercellular lipid barriers in the skin of NC/Nga mice, a model of atopic dermatitis (AD). NC/Nga mice fed Alk showed increased plasma levels of Alk and Pls. The AD-related changes in ceramide composition in the skin were abrogated by oral administration of Alk. Moreover, Alk suppressed skin inflammation in AD mice. These results indicate that Alk partially fortifies the stratum corneum lipid barrier and may be an effective treatment for AD. Abbreviations: Pls: plasmalogen; PlsCho: choline plasmalogen; PlsEtn: ethanolamine plasmalogen; Alk: alkyl phospholipid; TJ: tight junction; FA: fatty acid; AD: atopic dermatitis; SO: soybean oil; FO: fish oil; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; TG: triglyceride; PL: phospholipid; RF: retention factor; AlkCho: choline-type alkyl phospholipid; AlkEtn: ethanolamine-type alkyl phospholipid; LC-MS/MS: liquid chromatography-tandem mass spectrometry; FAR1: fatty acyl-coenzyme (Co)A reductase 1.

Total and Toxocara canis larval excretory/secretory antigen- and allergen-specific IgE in atopic and non-atopic dogs.

BACKGROUND: Total IgE concentrations are higher in dogs than in humans. Persistent Toxocara canis larval infection is prevalent in dogs and is associated with substantial specific antibody reactions. A correlation, however, between total IgE and T. canis-specific antibody levels in dogs has not been evaluated. OBJECTIVES: To determine the relationship between total IgE, T. canis-specific IgG and IgE, and allergen-specific IgE levels in atopic and non-atopic dogs, and to evaluate possible confounding factors. ANIMALS: Sera of 30 atopic and 30 non-atopic client-owned dogs. METHODS: Total IgE, T. canis-specific antibody and allergen-specific IgE levels were evaluated by ELISA. RESULTS: Total IgE, T. canis-specific antibody and allergen-specific IgE levels were significantly higher in non-atopic compared to atopic dogs. A positive correlation was demonstrated between T. canis-specific IgG and T. canis-specific IgE; T. canis-specific IgG and total IgE; T. canis-specific IgE and total IgE; and allergen-specific IgE and total IgE. No differences were detected on the basis of age, gender, vaccination status; deworming or season between atopic and non-atopic dogs. Previous immunomodulatory treatment and cause of atopy did not influence antibody levels of atopic dogs. CONCLUSIONS: Toxocara canis-specific IgE appears to be a major component of total IgE in dogs. Total and T. canis-specific IgE levels are higher in non-atopic compared to atopic dogs. It is speculated that T. canis infection may have a protective effect against the development of canine atopic dermatitis and/or that elevations in total serum IgE level are often not associated with atopic dermatitis.

Dimerized Translationally Controlled Tumor Protein-Binding Peptide Ameliorates Atopic Dermatitis in NC/Nga Mice.

Our previous study showed that dimerized translationally controlled tumor protein (dTCTP) plays a role in the pathogenesis of allergic diseases, such as asthma and allergic rhinitis. A 7-mer peptide, called dTCTP-binding peptide 2 (dTBP2), binds to dTCTP and inhibits its cytokine-like effects. We therefore examined the protective effects of dTBP2 in house dust mite-induced atopic dermatitis (AD)-like skin lesions in Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice. We found that topical administration of dTBP2 significantly reduced the AD-like skin lesions formation and mast cell infiltration in NC/Nga mice, similarly to the response seen in the Protopic (tacrolimus)-treated group. Treatment with dTBP2 also decreased the serum levels of IgE and reduced IL-17A content in skin lesions and inhibited the expression of mRNAs of interleukin IL-4, IL-5, IL-6, IL-13, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC) and thymic stromal lymphopoietin (TSLP). These findings indicate that dTBP2 not only inhibits the release of Th2 cytokine but also suppresses the production of proinflammatory cytokines in AD-like skin lesions in NC/Nga mice, by inhibiting TCTP dimer, in allergic responses. Therefore, dTCTP is a therapeutic target for AD and dTBP2 appears to have a potential role in the treatment of AD.

Atopy and Asthma in Migrants: The Function of Parasites.

Migration studies have shown that environmental factors in more developed and industrialized countries facilitate atopy and asthma in a time-dependent manner and are affected by age at immigration. Levels of immunoglobulin E are higher in immigrants than in the local population and gradually decrease to the levels of the general population. Parasitic infestation may function in the prevention and pathogenesis of atopic conditions in immigrants from developing countries. Helminths are associated with a reduced prevalence of clinically important atopic disorders, likely because of induction of a regulatory cell population mechanism. Improved understanding of the immunologic background of helminths and their protective function in humans has led to a growing interest in the possibility of reversal of allergies using parasites and the development of new therapies, such as immunomodulation for allergy using ova from parasites orally or intranasally. Strategies for primary prevention in high-risk atopic individuals and secondary prevention guidelines should be developed for populations in developing countries and for immigrants from developing countries to atopy-prevalent developed countries. Improved understanding of the function of parasitic infection in modulation of the immune response may lead to new therapeutic options for allergic conditions.

Chlorella vulgaris Attenuates Dermatophagoides Farinae-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice.

Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV) is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE). CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD.

Protease activity enhances production of thymic stromal lymphopoietin and basophil accumulation in flaky tail mice.

Epidermal barrier abnormality due to filaggrin deficiency is an important predisposing factor in the development of atopic dermatitis (AD). In addition, the expression of thymic stromal lymphopoietin (TSLP) in keratinocytes (KCs), induced by barrier disruption, can promote type 2 helper T-cell polarization. Protease activity, including protease-activated receptor-2 (PAR-2), is also known to be involved in epidermal barrier function in AD. However, to our knowledge, the relationship between protease activity and filaggrin deficiency from the perspective of AD has not been elucidated. Flaky tail (Flg(ft)) mice, known to have a mutation in the filaggrin gene, were used to assess the role of protease in KCs in the steady state and the mite-induced AD-like skin inflammation model. In the steady state, the expression and activity levels of endogenous proteases, kallikreins 5, 7, and 14, in the skin and TSLP were higher in Flg(ft) than in control mice. In addition, activation of PAR-2 by its agonist induced the production of TSLP in KCs of Flg(ft) mice, which was abrogated by a newly developed PAR-2 antagonist. Application of the PAR-2 antagonist improved symptoms and basophil accumulation in Flg(ft) mice treated with mite extracts. These results suggest that possibly through the PAR-2 activation in KCs, filaggrin deficiency induces TSLP production and basophil accumulation, which play important roles in the establishment of AD.

Late-onset onchocercal skin disease among Ethiopian immigrants.

BACKGROUND: Onchocerciasis is an infectious disease caused by the filaria Onchocerca volvulus. Very little is known regarding onchocerciasis imported from endemic to nonendemic areas. OBJECTIVES: To evaluate pruritic dermatitis simulating atopic dermatitis in Ethiopian immigrants in Israel. PATIENTS AND METHODS: A retrospective study of 27 Ethiopian immigrants to Israel was conducted. Demographics and clinical and laboratory data were collected. RESULTS: Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The average age at referral was 29 years. All of the patients emigrated from Kuwara, Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation was a combination of lichenified onchodermatitis with atrophy and depigmentation (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were treated with a single administration of oral ivermectin 200 µg mg(-1). Thirteen patients responded to the treatment. CONCLUSIONS: Immigrants from endemic regions to developed countries presenting with pruritic diseases, especially those with a clinical picture suggestive of atopic dermatitis, should be evaluated for possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost treatment, should be considered even in the absence of a proven disease. Physicians should have a high index of suspicion in patients with the corresponding residential history.

The fruits of Cudrania tricuspidata suppress development of atopic dermatitis in NC/Nga mice.

The fruits of Cudrania tricuspidata are a medicinal herb in Korea, known for its antiatherosclerotic and antiinflammatory effects. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the influx of lymphocytes into the dermis. Using an animal model of AD, we assessed whether C. tricuspidata suppresses the development of AD-like skin lesions. Cudrania tricuspidata was administered orally to NC/Nga mice with Dermatophagoides-farinae-induced AD-like lesions for 49 days. The effects of C. tricuspidata were assessed by measuring clinical symptoms, swelling of the skin on the back and ears, and plasma concentrations of mTARC (mouse thymus and activation regulated chemokine), histamine and immunoglobulin E (IgE). We found that C. tricuspidata (60 mg/kg/day) inhibited the development of AD-like skin lesions, reduced skin dermatitis scores and inhibited the histological changes induced by repeated application of D. farinae. In addition, C. tricuspidata inhibited the increases in plasma concentrations of mTARC, histamine and IgE induced by D. farinae. These findings indicate that C. tricuspidata inhibits the development of AD-like skin lesions induced by repeated applications of D. farinae in sensitized NC/Nga by suppressing plasma concentrations of mTARC, histamine and IgE.

Intradermal and serological testing for mites in healthy beagle dogs.

BACKGROUND: Intradermal testing (IDT) is widely used in veterinary medicine to select allergens for immunotherapy. The recommended concentration for mites is 250 protein nitrogen units (PNU)/mL. It is not known whether healthy dogs responding to this concentration have asymptomatic sensitization or irritation. Furthermore, interbatch and intersupplier variability of allergens has not been fully addressed. HYPOTHESIS/OBJECTIVES: The incidence of positive IDTs in healthy beagles was recorded and the value of combining these results with serology to differentiate between asymptomatic sensitization and irritancy evaluated. Additionally, the interbatch and intersupplier variability of allergens was assessed. ANIMALS: Seventeen healthy laboratory beagles with no history or clinical signs of canine atopic dermatitis were used. METHODS: Intradermal tests were performed with four mite allergens from two suppliers (varying batches). An initial IDT at 250 PNU/mL was used to determine whether decreasing or increasing test concentrations were used in the subsequent titration IDTs. Additionally, two IgE ELISA tests from different manufacturers were performed. RESULTS: Seven of 17 dogs showed IDT reactions at 250 PNU/mL. There were highly significant allergen interbatch and significant intersupplier correlations and agreement. The associations between the IDT reactions and the IgE serologies statistically identified two groups of dogs: one with positive serology and IDT reactions at 250 PNU/mL; and another with negative serology and IDT reactions. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that dogs that have IDT reactions and positive serology are asymptomatically sensitized, while dogs that react at higher allergen concentrations, but have negative serology, do so as a result of irritant reactions.

Characterization of pruritus in canine atopic dermatitis, flea bite hypersensitivity and flea infestation and its role in diagnosis.

BACKGROUND: In dogs, flea infestation (FI), flea bite hypersensitivity (FBH) and canine atopic dermatitis (CAD) have been mainly characterized by their lesions but never by their pruritus. In clinical practice, many of these dogs exhibit only pruritus. HYPOTHESIS/OBJECTIVES: The purpose of this study was to evaluate the characteristics of pruritus in these dermatoses and their potential usefulness for diagnosis. ANIMALS: Dogs included were selected from the Oniris clinical data. Cases were selected in which the dogs had only one of the three dermatoses diagnosed. The diagnosis of CAD was based on Prélaud's criteria and positive intradermal tests except flea; for FBH by compatible clinical signs and a response to an intradermal test with flea allergen; and for FI by the presence of fleas. Moreover, in each group, other primary pruritic skin diseases were excluded. METHODS: Location, behavioural manifestations, seasonality and quantification of the pruritus were evaluated. The statistical analysis used chi-squared test with a P-value <0.05. RESULTS: Three hundred and forty-six dogs were analysed, 91 with CAD, 110 FI and 145 FBH. The period (season) of onset was not statistically different either for each dermatosis or among the three dermatoses. Some locations were highly specific for one dermatosis as follows: ventral abdomen/medial surface of thigh (chewing) and radius/carpus/tibia/tarsus (chewing) in FI; back/dorsolumbar area (chewing) and tail (chewing) in FBH; and paws (chewing/licking) and face/neck (rubbing) in CAD. CONCLUSIONS AND CLINICAL IMPORTANCE: Some features of pruritus could be suggestive of the causal disease, with possible diagnostic value in pruritic dogs.

Atopy and current intestinal parasite infection: a systematic review and meta-analysis.

BACKGROUND: The rate of increase in prevalence of allergic disease in some countries implies environmental exposures may be important etiological factors. Our aim was to undertake a systematic review and meta-analysis of epidemiological studies to quantify the association between current intestinal parasite infection and the presence of atopy and to determine whether this relation is species specific. METHODS: We searched MEDLINE, EMBASE, LILIACS and CAB Abstracts (to March 2009); reviews; and reference lists from publications. No language restrictions were applied. We included studies that measured current parasite infection using direct fecal microscopy and defined atopy as allergen skin sensitization or presence of specific IgE. We estimated pooled odds ratios (OR) and 95% confidence intervals (95% CI) using data extracted from published papers using random-effects model. RESULTS: Twenty-one studies met our inclusion criteria. Current parasite infection was associated with a reduced risk of allergen skin sensitization OR 0.69 (95% CI 0.60-0.79; P < 0.01). When we restricted our analyses to current geohelminth infection, the size of effect remained similar OR 0.68 (95% CI 0.60-0.76; P < 0.01). In species-specific analysis, a consistent protective effect was found for infection with Ascaris lumbricoides, Tricuris trichuria, hookworm and Schistosomiasis. There were insufficient data to pool results for atopy defined by the presence of specific IgE. CONCLUSION: Intestinal parasite infection appears to protect against allergic sensitization. Work should continue to identify the mechanisms of this effect and means of harnessing these to reduce the global burden of allergic disease.

Presence and density of domestic mites in the microenvironment of mite-sensitive dogs with atopic dermatitis.

This study was designed to investigate the presence and density of domestic mites (DMs) in households with atopic dogs sensitive to these mites (group A; n=20), in households with clinically healthy, nonatopic dogs (group B; n=20) and in households without pets (group C; n=25). Dust samples were vacuum-collected from the owner mattress (all groups) and dog sleeping area (groups A and B) or living room couch (group C) on four consecutive occasions, reflecting the four seasons of the year. DMs were found, at least once, in 19 of 20 (95%) group A, 13 of 20 (65%) group B and 21 of 25 (84%) group C households. DM numbers per gram of dust were 0-159 (median, 8.8), 0-302 (median, 3) and 0-1473 (median, 6.9) for group A, B and C, respectively. Dermatophagoides farinae predominated in all groups, since it was identified in 60% of group A, 40% of group B and 64% of group C households. Dermatophagoides pteronyssinus was found in 45%, 35% and 48% of households, in group A, B and C, respectively. No differences were found between households with (groups A and B) or without dogs (group C). When considering both sampling sites together, frequency of DM recovery was higher in group A than in group B (P=0.044). Also, both mite frequency (P=0.011) and density (P=0.015) in dog sleeping area were higher in group A than in group B. In conclusion, presence and density of DMs is higher in the microenvironment of mite-sensitive dogs with atopic dermatitis than in that of clinically healthy nonatopic dogs.

Comparison of the presentation of atopic dermatitis induced by trinitrochlorobenzene and house dust mite in NC/Nga mice.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. To understand AD, there have been many trials establishing AD animal models. Although various trials to establish AD animal models have been existed, even the mechanisms of AD in animal models are not enough clarified. OBJECTIVES: This study assessed AD characteristics induced in Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice following trinitrochlorobenzene (TNCB) treatment for different periods and house dust mite (HDM) treatment to compare each model's immunological patterns, especially with cytokine antibody array tool. METHODS: In this study, we exposed Nc/Nga mice to TNCB or HDM extract to induce AD. Nc/Nga mice were divided into 4 groups: control, TNCB 2 weeks-treated, TNCB 8 weeks-treated, and HDM-treated groups. After AD induction, all mice were evaluated by serum immunoglobulin E (IgE) concentration and serum cytokine antibody assays, scoring of skin lesions, scoring of scratching frequency, and histological analysis. RESULTS: The results showed significant differences between groups in serum IgE concentration, skin lesion scores, and scratching frequency. The analysis results for serum cytokine antibody arrays showed that in the TNCB 8 weeks- and HDM-treated groups, but not in the TNCB 2 weeks-treated group, expressions of genes related to the immune response were enriched. Among the histological results, the skin lesions in the HDM-treated group were most similar to those of AD. CONCLUSIONS: We confirmed that immunological pattern of AD mice was markedly different between HDM and TNCB treated groups. In addition, the immunological pattern was quietly different dependent on TNCB treated duration.

Costello syndrome model mice with a HrasG12S/+ mutation are susceptible to develop house dust mite-induced atopic dermatitis.

Costello syndrome is an autosomal dominant disorder that is caused by germline HRAS mutations. Patients with Costello syndrome present craniofacial abnormalities, cardiac defects, and cancer predisposition, as well as skin abnormalities, including papillomas, keratosis pilaris, and eczematous dermatitis. However, the mechanisms underlying the dermatological abnormalities remain unclear. Here, we demonstrated that knock-in mice expressing an Hras G12S mutation (HrasG12S/+ mice) are susceptible to develop atopic dermatitis (AD)-like skin lesions, including eczema, pruritus, elevated serum IgE levels, acanthosis, and the infiltration of mast cells, basophils, and type-2 innate lymphoid cells in the dermis, after stimulation with house dust mite allergens (Dermatophagoides farinae, Dfb). Reduced skin barrier function, increased proliferation of phosphorylated ERK (p-ERK)-positive epidermal cells, and increased Th2-type cytokines as well as epithelial cell-derived cytokines, including IL-33, were observed in the skin tissue of HrasG12S/+ mice compared with Hras+/+ mice. Cultured HrasG12S/+ keratinocytes exhibited increased IL-33 expression after Dfb stimulation. PD0325901, an MEK inhibitor, ameliorated AD-like symptoms in HrasG12S/+ mice, showing decreased proliferation of p-ERK-positive epidermal cells and decreased expression of IL-33. Our findings indicate that the epidermis of HrasG12S/+ mice stimulated by Dfb strongly induced IL-33 expression and type-2 innate lymphoid cells, resulting in AD-like skin lesions. These results suggest that the epidermis of HrasG12S/+ mice are prone to development of eczematous dermatitis stimulated with house dust mite allergens.

Gastrointestinal nematode infection interferes with experimental allergic airway inflammation but not atopic dermatitis.

BACKGROUND: Some helminth infections are negatively associated with the prevalence of allergic disorders, arguing for a modulation of allergic reactions by the parasites, depending on the worm species, intensity and phase of infection and the type of disease. OBJECTIVE: The aim of this study was to analyse the influence of a chronic infection with the gastrointestinal nematode Heligmosomoides polygyrus, in a murine model of allergic airway disease and of atopic dermatitis (AD), respectively. METHODS: Mice were infected with H. polygyrus and systemically sensitized with the model allergen ovalbumin. Subsequently, the animals were challenged with the allergen either via the airways for induction of airway disease, or via skin patches for induction of dermatitis. RESULTS: Mice concomitantly infected with H. polygyrus showed diminished eosinophil and lymphocyte recruitment into the lungs and decreased allergen-specific IgE levels when compared with sensitized and airway challenged controls. In addition, animals showed a trend towards reduced airway hyper-reactivity. In contrast, no significant differences in the severity of eczematous skin lesions were observed between infected and control animals in the AD model. Although H. polygyrus infection reduced CD8+ and CD4+ T-cell infiltration into the skin and production of allergen-specific IgE, mast cell recruitment was significantly increased in worm-infected mice in the dermatitis model. The worm infection was associated with significantly elevated numbers of Foxp3+ regulatory T cells (Treg) in peribronchial lymph nodes in H. polygyrus-infected sensitized and airway challenged mice. In contrast, Treg cells were basically absent in eczematous skin and their number was not increased in skin-draining lymph nodes of mice with experimental dermatitis. CONCLUSION: Infection with the gastrointestinal nematode used in our study leads to significant inhibition of mucosa-associated but not cutaneous allergic reactions, pointing to a site specificity of the immunomodulation exerted by helminths. This finding might be an important aspect for future considerations of helminths for treatment of allergic diseases.

Unravelling the skin barrier: a new paradigm for atopic dermatitis and house dust mites.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease caused by complex interactions between genetics and environmental factors. In human beings, impairment of the skin barrier is demonstrated and thought to be responsible for enhanced penetration of allergens and increased risk for allergic sensitization. Once inflammation is triggered, further impairment of the skin barrier occurs, leading to self-perpetuating cycles of sensitizations. Canine AD appears to share many similarities with the human counterpart, clinically and immunologically. It is hypothesized that a primary defect of skin barrier function also exists in subsets of atopic dogs (e.g. in an experimental model using high IgE-producing beagles), particularly in young dogs, and in sites predisposed to the development of lesions. This impairment is present in clinically normal skin, worsens with development of lesions and can be quantified by measurement of transepidermal water loss. Therefore, the distribution of lesions in AD may be linked to a primary skin barrier defect in those sites and not simply due to contact with allergens, and increased susceptibility to penetration of allergen may exist early in life. Ultrastructurally, transmission electron microscopy reveals that clinically normal skin in atopic dogs has abnormalities in lamellar body secretion and extracellular lamellar bilayer structure when compared with normal dogs. Development of lesions worsens these changes (e.g. widening of intercellular spaces, release of lamellar bodies, and disorganization of lipid lamellae). It is proposed that the paradigm of canine AD as primarily due to immunologic aberration ('inside/outside') should be shifted to include a primary defect in barrier function ('outside/inside').

The detection of house dust mite Dermatophagoides farinae, Der f 2 and Zen-1 allergen-specific immunoglobulin E antibodies in dogs with atopic Dermatitis in Malaysia.

Canine atopic dermatitis (AD) is a chronic, inflammatory and pruritic allergic skin disease in dogs. House dust mites such as Dermatophagoides farinae are one of the known causative agents for the induction of canine AD worldwide. D. farinae protein Der f 2 is known as an important allergen involved in canine AD and recently, Zen-1 has also been identified as an allergenic protein. There is limited information on the prevalence and role of allergen sensitization to crude D. farinae extract (CDF), Der f 2 and Zen-1 among dogs diagnosed with AD in Malaysia. The aim of this study was to determine the proportion of CDF-, Der f 2- and Zen-1-specific reactive sera among dogs diagnosed with AD in Malaysia using an enzyme-linked immunosorbent assay (ELISA). Serum samples were collected from dogs diagnosed with AD from several veterinary clinics in Malaysia. The canine case records were retrieved and information on signalment, dermatological and non-dermatological histories, clinical presentation, food allergies, and exclusion of ectoparasitic, microbial and fungal skin infections were obtained through a survey form. All serum samples were evaluated to quantify the CDF-, Der f 2- and Zen-1-specific immunoglobulin E (IgE) levels. A total of 24.6%, 48.4% and 29.8% of dogs diagnosed with AD were positive for CDF-, Der f 2- and Zen-1-specific IgE, respectively. These results suggest that CDF-, Der f 2- and Zen-1 are important allergens that can contribute to AD in dogs in Malaysia, and serological testing can be performed to provide additional treatment options involving specific immunotherapies.