Maternal asthma during pregnancy and risks of allergy and asthma in progeny: A systematic review and meta-analysis.

BACKGROUND: Clinical and preclinical evidence indicate that in utero maternal asthma exposure increases progeny asthma risk. Whether maternal asthma also increases the risks of progeny allergy is unclear. OBJECTIVES: To synthesise the available evidence on the relationship between in utero exposure to maternal asthma and postnatal asthma, wheezing and allergic diseases (Prospero: CRD42020201538). SEARCH STRATEGY: We systematically searched MEDLINE [PubMed], Embase [Ovid], Web of Science, Informit Health, the Cochrane Library, CINAHL [EBSCOhost], MedNar [Deep Web Technologies], ProQuest Theses and Dissertations, Scopus [Elsevier] and Trove, to the end of 2023. SELECTION CRITERIA: Studies reporting asthma, wheeze and/or allergic disease in progeny of women with and without asthma or with asthma classified by control, exacerbation or severity. DATA COLLECTION AND ANALYSIS: Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring. MAIN RESULTS: Of 134 non-overlapping studies, 127 were included in ≥1 meta-analysis. Maternal asthma ever was associated with greater risks of asthma (65 studies, risk ratio [95% confidence interval] 1.76 [1.57-1.96]), wheeze (35 studies, 1.59 [1.52-1.66]), food allergy (5 studies, 1.32 [1.23-1.40]), allergic rhinitis (7 studies, 1.18 [1.06-1.31]) and allergic dermatitis (14 studies, 1.17 [1.11-1.23]) ever in progeny. Asthma during the pregnancy, more severe, and uncontrolled maternal asthma were each associated with greater risks of progeny asthma. CONCLUSIONS: Children of mothers with asthma are at increased risk for the development of allergic diseases. Whether improved maternal asthma control reduces risks of child allergy as well as asthma requires further investigation.

A randomised, double-blinded trial to assess the effect of oclacitinib and prednisolone on intradermal allergen and prick tests in dogs with atopic dermatitis.

BACKGROUND: Intradermal (IDT) and prick (PT) tests are used to select allergens for allergen-specific immunotherapy in dogs with atopic dermatitis (cAD). However, the use of antipruritic drugs before performing these tests may influence the results. OBJECTIVE: To evaluate the influence of the drugs oclacitinib and prednisolone on the immediate-phase reactions of IDT and PT. ANIMALS: Thirty client-owned dogs with cAD with positive reactions to at least one allergen extract on IDT or PT. MATERIALS AND METHODS: Dogs were randomly assigned to receive oclacitinib 0.4-0.58 mg/kg per os, every 12 h (n = 14), or prednisolone 0.37-0.65 mg/kg p.o., every 12 h (n = 16) for 14 days. IDT and PT were performed on Day (D)0 before treatment and on D14. RESULTS: At D14 there was no significant reduction in the means of the orthogonal diameters of the positive immediate-phase reactions of the IDT (p = 0.064) in the oclacitinib group; however, in the PT, the diameter of the positive reactions reduced significantly (p = 0.048). In both tests, there was no significant reduction in the total number of positive reactions (IDT, p > 0.999; PT, p = 0.735). In the prednisolone group, the means of the orthogonal diameters of positive immediate-phase reactions were significantly reduced in both tests (IDT, p = 0.001; PT, p ≤ 0.001) and there also was a reduction in the total number of positive reactions (IDT, p = 0.022; PT, p = 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The use of oclacitinib 0.4-0.58 mg/kg twice daily for 14 days does not interfere with IDT results in dogs with cAD. However, oclacitinib may reduce PT reactivity. The use of prednisolone 0.37-0.65 mg/kg twice daily results in a reduction in both IDT and PT results.

Assessment of owner perceptions of caregiver burden, veterinarian-client relationship and satisfaction with the provider in canine pruritus: An experimental vignette study.

BACKGROUND: Complicated treatments for skin disease are linked to owner-caregiver burden and poorer perception of the veterinarian-client relationship, regardless of disease severity. HYPOTHESES/OBJECTIVES: Using experimental vignettes, we explored the impact on owner perception of the interaction of treatment complexity and skin disease outcomes. We hypothesised that: (i) vignette conditions involving injection therapy would result in lower burden, better veterinary-client relationship and greater satisfaction relative to multimodal therapy conditions; (ii) the vignette condition of injection therapy with a completely effective outcome would be superior to all other conditions; (iii) ineffective vignette conditions would be inferior to all other conditions; and (iv) the vignette condition injection with a mostly effective outcome would be similar or superior to the multimodal therapy with a completely effective outcome condition. PARTICIPANTS: Three hundred and nine owners of pruritic dogs recruited from a general veterinary practice, pet-related podcast, or social media dog allergy group. MATERIALS AND METHODS: Participants were presented with six counterbalanced online vignettes representing three levels of treatment effectiveness (Completely Effective, Mostly Effective, Ineffective) and two treatment regimens (Multimodal, Injection). Measurements of participant perceptions of caregiver burden, veterinarian-client relationship and satisfaction were recorded. RESULTS: Injection with perfect outcome was superior to other conditions (p < 0.001). Conditions with poor effectiveness were inferior (p < 0.001). Comparison of Injection with a mostly effective outcome to Multimodal treatment with perfect outcome yielded small-to-medium effects of preference for the latter in veterinarian-client relationship and satisfaction (p < 0.01); no difference was observed for caregiver burden. When good effectiveness was assured, injection was preferred (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Owners preferred a Completely Effective outcome and were prepared to select the Injection regimen or Multimodal therapy to achieve this; Injection was preferred when effectiveness was assured.

A placebo-controlled, double-blind study evaluating the effect of orally administered polyunsaturated fatty acids on the oclacitinib dose for atopic dogs.

BACKGROUND: Supplementation of polyunsaturated fatty acids (PUFA) enables dose reduction of prednisolone and ciclosporin in canine atopic dermatitis (cAD). OBJECTIVE: To determine if oral administration of PUFA reduces the dose of oclacitinib in cAD. ANIMALS: Twenty-two client-owned dogs with cAD receiving oclacitinib. MATERIALS AND METHODS: Dogs received a fish oil product (PUFA) or paraffin oil (placebo) for 16 weeks. Owners adjusted the oclacitinib dose according to daily pruritus assessments. On Day (D)0, D56 and D112, Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), quality-of-life score (QoL), Global Assessment (GA), quality-of-coat (QoC) and adverse events were recorded. RESULTS: Mean daily oclacitinib dose was significantly reduced in the PUFA group from 0.51 ± 0.20 mg/kg/24 h (D0) to 0.19 ± 0.14 mg/kg/24 h (D85-112; p < 0.00001) and not in the placebo group (D0: 0.70 ± 0.33 mg/kg/24 h; D85-112: 0.53 ± 0.35 mg/kg/24 h, p = 0.5422). CADESI-04 did not change over time or differ between groups. PVAS was significantly lower in the PUFA group (2.8 ± 1.5) compared to placebo (4.2 ± 1.6) at D112 (p = 0.0375). QoL and QoC improved only in the PUFA group (QoL: D0: 20 ± 7, D112: 12 ± 5, p = 0.0057; QoC: D0: 0 ± 0.5, D112: 1 ± 0.5, p = 0.0410). GA on D112 was higher in the PUFA group (p = 0.008). No adverse events were observed. CONCLUSION: Oral supplementation of PUFA allowed dose reduction of oclacitinib and improved PVAS, QoL, QoC and GA. The use of PUFA is recommended and was safe in the atopic study dogs receiving oclacitinib.

Immune Metabolism in TH2 Responses: New Opportunities to Improve Allergy Treatment - Disease-Specific Findings (Part 1).

PURPOSE OF REVIEW: Recent high-level publications have shown an intricate connection between immune effector function and the metabolic state of the respective cells. In the last years, studies have begun analyzing the metabolic changes associated with allergies. As the first part of a two-article series, this review will briefly summarize the basics of immune metabolism and then focus on the recently published studies on metabolic changes observed in allergic patients. RECENT FINDINGS: In the last 3 years, immune-metabolic research in allergology had a clear focus on asthma with some studies also reporting findings in food allergy and atopic dermatitis. Current results suggest asthma to be associated with a shift in cellular metabolism towards increased aerobic glycolysis (Warburg metabolism), while also displaying substantial changes in fatty acid- and amino acid metabolism (depending on investigated patient collective, asthma phenotype, and disease severity). Understanding immune-metabolic changes in allergies will allow us to (I) better understand allergic disease pathology and (II) modulate immune-metabolic pathways to improve allergy treatment.

Skin Reactions Following Primary Total Knee Arthroplasty With an Adhesive Superficial Closure System: A Case Series.

BACKGROUND: We investigated a skin adhesive closure device consisting of a self-adhesive polyester mesh placed over the surgical incision, followed by a liquid adhesive that is spread over the mesh and surrounding the skin. It is intended to reduce wound closure times, scarring, and skin complications associated with traditional closure with sutures or staples. The aim of this study was to report on skin reactions in patients who underwent primary total knee arthroplasty (TKA) using the skin adhesive closure system. METHODS: A retrospective review of patients who underwent TKA using adhesive closure between 2016 to 2021 at a single institute was performed. A total of 1,719 cases were analyzed. Patient demographics were collected. The primary outcome was any postoperative skin reaction. Skin reactions were classified as allergic dermatitis, cellulitis, or other. Treatment(s), duration of symptoms, and surgical infections were also collected. RESULTS: A total of 5.0% (86) of patients were found to have any type of skin reaction following their TKA. Of these 86, 39 (2.3%) had symptoms of allergic dermatitis (AD), 23 (1.3%) had symptoms of cellulitis, and 24 (1.4%) had other symptoms. A total of 27 (69%) allergic dermatitis patients were treated with a topical corticosteroid cream only; their symptoms resolved within an average of 25 days. There was only 1 case of superficial infection (<0.001%). No prosthetic joint infections were observed. CONCLUSION: Despite skin reactions appearing in 5.0% of cases, the rate of infection was low. A patient-specific preoperative workup and effective treatment strategies can minimize complications associated with adhesive closure system and increase patient satisfaction following TKA.

Acceptance of oclacitinib maleate (Apoquel®) chewable tablets in client-owned dogs with allergic and atopic dermatitis.

BACKGROUND: The oral acceptance of oclacitinib maleate (Apoquel®) chewable tablets administered twice daily for 7 days at the labeled dose range of 0.4-0.6 mg/kg was evaluated in 121 dogs treated at ten general practice veterinary clinics in the United States. RESULTS: Dogs that were enrolled in the study were client-owned, ranged from 1 to 14 years of age, weighed 3.7 to 60.7 kg, and required twice daily treatment with Apoquel for allergic or atopic dermatitis for 7 days. One hundred and twenty-one (121) dogs with 1673 total dose administrations successfully completed the study and were included in the data summary. Out of a total number of 1673 administrations, 1533 (91.6%) were accepted voluntarily within 5 min, 134 (8%) were consumed with assistance (with food treats or by pilling) outside of the 5 min offering time and 6 (0.4%) doses were not consumed. The per dose percent acceptance rate for the 14 offered doses showed minimal variation ranging from 89.9 to 93.3%. CONCLUSIONS: Client-owned dogs from the general veterinary patient population that required treatment with oclacitinib found the chewable tablets to be very palatable and no aversion occurred with repeated dosing. Oclacitinib chewable tablets were well tolerated and are a palatable alternative to the film-coated tablet.

Systemic allergic dermatitis (systemic contact dermatitis) from pharmaceutical drugs: A review.

The literature on systemic allergic dermatitis (SAD; also known as systemic contact dermatitis) is reviewed. Both topical drugs (from absorption through mucosae or skin) and systemic drugs (oral, parenteral, rectal) may be responsible for the disorder. The topical route appears to be rare with 41 culprit topical drugs found to cause SAD in 95 patients. Most reactions are caused by budesonide (especially from inhalation), bufexamac, and dibucaine. SAD from systemic drugs is infrequent with 95 culprit drugs found to cause SAD in 240 patients. The drugs most frequently implicated are mitomycin C, methylprednisolone (salt, ester), and hydrocortisone (salt). The largest group of culprit drugs consisted of corticosteroids (19%), being responsible for >30% of the reactions, of which nearly 40% were not caused by therapeutic drugs, but by drug provocation tests. The most frequent manifestations of SAD from drugs are eczematous eruptions (scattered, widespread, generalized, worsening, reactivation), maculopapular eruptions, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE [baboon syndrome]) and widespread erythema or erythroderma. Therapeutic systemic drugs hardly ever cause reactivation of previously positive patch tests and infrequently of previous allergic contact dermatitis. The pathophysiology of SAD has received very little attention. Explanations for the rarity of SAD are suggested.

Structural racism and its pathways to asthma and atopic dermatitis.

Black, Latinx, and Indigenous people in the United States experience a disproportionate burden of asthma and atopic dermatitis. The study of these disease disparities has focused on proximal socioenvironmental exposures and on the biomechanistic (including genetic) differences between racial and ethnic groups. Although biomedical research in allergy and immunology stands to benefit from the inclusion of diverse study populations, the narrow focus on biologic mechanisms disregards the complexity of interactions across biologic and structural factors, including the effects of structural racism. Structural racism is the totality of ways in which society fosters discrimination by creating and reinforcing inequitable systems through intentional policies and practices sanctioned by government and institutions. It is embedded across multiple levels, including the economic, educational, health care, and judicial systems, which are manifested in inequity in the physical and social environment. In this review, we present a conceptual framework and pull from the literature to demonstrate how structural racism is a root cause of atopic disease disparities by way of residential segregation, socioeconomic position, and mass incarceration, which may lead to aberrations in the innate and adaptive immune response and the augmentation of physiologic stress responses, contributing to a disproportionate disease burden for racial and ethnic populations.

Pharmacokinetics of a single dose of oclacitinib maleate as a top dress in adult horses.

The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528 kg were administered a single dose of 0.5 mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15 min, 30 min, 45 min, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean Cmax was 486 ng/ml (range 423-549 ng/ml), and Tmax was estimated to be 1.7 h (range 0.3-3.1 h). The estimated T1/2 was 7.5-8 h.

VISTA-Ig ameliorates OXA-induced allergic dermatitis symptoms in mice.

BACKGROUND: Allergic dermatitis (AD) is a chronic inflammatory skin disease that a variety of immune cells are involved in the progression of AD. Among them, T cells are one of major players of AD pathogenesis. The V-domain Ig suppressor of T cell activation (VISTA) has been reported that it has a potential immunomodulatory for T cell response. OBJECTIVE: This study aimed to investigate immunomodulatory of recombinant VISTA-Ig fusion protein in AD mice model. METHODS: The model of AD was built with oxazolone (OXA) in BALB/c mice, then VISTA-Ig was used to treat AD by intraperitoneal (IP) injection. The ear thickness was measured by a digital thickness gauge. The ears tissues were collected and subjected to hematoxylin-eosin (H&E) and toluidine blue (TB) staining. The secretion levels of IL-4 and IgE in the serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of inflammatory cytokines (IL-1ß, IL-6, IL-12, and INF-γ) in ear tissues were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Treatment with VISTA-Ig successfully alleviated the symptoms of AD, such as erythema, horny substance, and swelling. The infiltration of inflammatory cells was significantly reduced following VISTA-Ig therapy. The secretion levels of IL-4 and IgE in the serum were significantly attenuated following treatment with VISTA-Ig. Additionally, VISTA-Ig observably down-regulated inflammatory cytokines expression in ear tissues. CONCLUSIONS & CLINICAL RELEVANCE: Taken together, our results showed that VISTA-Ig possessed the potential to be a novel immunomodulatory candidate drug against AD.

An accumulation of two populations of dendritic cells in skin-draining lymph nodes in response to the expression of thymic stromal lymphopoietin in the skin.

Thymic stromal lymphopoietin (TSLP) acts on dendritic cells (DCs), which prime helper T (Th) cells to become type 2 cytokine producing cells. Recently, a different set of populations of TSLP-responsive DCs has been discovered. Here, we identified two populations of CD103loEpCAMhi migratory DCs (fraction I and fraction II) that accumulated in skin-draining lymph nodes in response to TSLP expressed in the mouse skin. Fraction I DCs with CD11b+PDL2hi expression primed naïve Th cells to differentiate into cells secreting IFN-γ, IL-17A and IL-22, while fraction II DCs with CD11bloPDL2+ expression primed naïve Th cells to differentiate into cells secreting IL-4, IL-5, IL-9, IL-13 and IL-10. Fraction I DCs migrated from the skin via IL-4Rα signaling pathway, whereas fraction II DCs migrated partially via TSLPR signaling pathway. All suggest that at least two populations of CD103loEpCAMhi DCs with distinct functions and pathways could migrate in response to TSLP expression in the skin.

Early life stress from allergic dermatitis causes depressive-like behaviors in adolescent male mice through neuroinflammatory priming.

Allergic dermatitis (AD), associated with pruritus and itchiness, is one of the major stressful conditions early in life. AD also influences the incidence of neuropsychiatric disorders and developmental disorders through neuro-immune interactions. To the best of our knowledge, there is no report that assesses the effects of early childhood dermatitis on psychiatric disorders later in life using an animal model. Here, we developed an oxazolone (Ox)-induced AD model in the early life of male C57BL/6J mice whose ears were challenged by Ox repeatedly from postnatal days (PD) 2 to PD30. On PD30, the Ox-treated ears were remarkably thickened and showed epidermal hyperplasia coupled with increased expression of T helper 2 cytokines, interleukin (IL)-4, and IL-13 in the ear tissue. Additionally, serum immunoglobulin E levels and serum corticosterone levels were higher in the Ox-treated mice than those in the control mice. Although Ox-treated PD40 mice showed neither behavioral abnormalities nor increases in pro-inflammatory cytokine expression in the brain, this study revealed that they experienced downregulation of CD200R1 expression in the amygdala under basal conditions and that additional lipopolysaccharide (LPS) administration induced enhanced neuroinflammatory reaction as the priming effect was accompanied by an increase of Iba-1-positive microglia in the amygdala and hippocampus. Furthermore, the Ox-treated PD40 mice showed depressive-like behaviors 24 h after LPS administration, whereas the control mice did not. Interestingly, the expression of indoleamine 2,3-dioxygenase and kynurenine 3-monooxygenase, key rate-limiting enzymes of the kynurenine metabolism pathway, was upregulated in the hippocampus, prefrontal cortex, and amygdala of the Ox-treated mice 4 h after LPS administration. Based on these results, we suggest that early life stress from AD aggravates susceptibility to systemic inflammation in the adolescent brain, leading to depressive behaviors with abnormal kynurenine metabolism.

Acute and subacute oral administration of mycotoxin deoxynivalenol exacerbates the pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis.

Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to elucidate the effect of oral exposure to DON on pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis, which was generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type-2 helper T cells. To evaluate acute exposure to DON, the mice were orally administered vehicle alone, 0.1 mg/kg DON, or 0.3 mg/kg DON 48, 24, and 1 h before the final challenge with TDI. To study subacute exposure, the mice were fed DON-contaminated rodent diet (0.3 ppm) during the experimental period. After the itch behavior and ear-swelling response were monitored, the serum, auricular lymph node, and skin tissue were collected for analyzing immunocyte differentiation, cytokine determination, and histological changes. Acute oral administration of DON significantly enhanced pro-inflammatory responses including ear-swelling response, immunocyte infiltration, and cytokine productions. Histological evaluation supported the occurrence of pro-inflammatory responses. In contrast, acute DON exposure only slightly increased itch behavior. Subacute oral exposure to DON significantly up-regulated the inflammatory responses, but showed almost no effect on pruritic response. In vitro evaluation in dendritic cells and keratinocytes indicated that DON pre-exposure induced a dose-dependent significant increase in cytokine production. Our results imply that both acute and subacute exposures to DON are associated with pro-inflammatory responses in cutaneous allergy.

Oral provocation of patients allergic to sesquiterpene lactones with German chamomile tea to demonstrate possible systemic allergic dermatitis.

BACKGROUND: Most patients with contact allergy to Asteraceae plants are patch test positive to sesquiterpene lactone mix (SLM). There are several reports among these patients of a flare-up of hand eczema after ingestion of food and beverages originating from Asteraceae plants. AIM: To investigate whether German chamomile tea can elicit systemic allergic dermatitis. PATIENTS AND METHODS: Individuals with or without contact allergy to SLM were patch tested with an extract of German chamomile tea. Six weeks later, they were provoked with capsules containing either freeze-dried German chamomile tea or placebo capsules containing lactose, in a double-blind, randomized study. A numerical rating scale (NRS) was used to ascertain the volunteers' opinion of their hand eczema status. The study individuals were examined to detect a possible flare-up of healed patch test reactions to chamomile. RESULTS: None of the subjects had a flare-up of healed patch test reactions. According to the NRS, SLM-positive individuals experienced a significant worsening of hand eczema, independently of whether they received chamomile or lactose capsules. CONCLUSION: No evidence suggestive of systemic allergic dermatitis was found.

Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses.

BACKGROUND: Insect-bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type-I/type-IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin-5 (IL-5) is the key cytokine for eosinophils and we have previously shown that targeting IL-5 by vaccination reduces disease symptoms in horses. OBJECTIVE: Here, we analyzed the potential for long-term therapy by assessing a second follow-up year of the previously published study. METHODS: The vaccine consisted of equine IL-5 (eIL-5) covalently linked to a cucumber mosaic virus-like particle (VLP) containing a universal T cell epitope (CuMVTT ) using a semi-crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 µg of eIL-5-CuMVTT without adjuvant. RESULTS: The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti-eIL-5 auto-antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms. CONCLUSION: Yearly vaccination against IL-5 may be a long-term solution for the treatment of IBH and other eosinophil-mediated diseases in horses and other species including humans.

Open field study on the efficacy of fluralaner topical solution for long-term control of flea bite allergy dermatitis in client owned cats in Ile-de-France region.

BACKGROUND: Flea bite is considered to be the main cause of allergic dermatitis in cats. There is a need for treatments able to control clinical signs of allergic dermatitis associated with flea bite in cats. This was an open pre-treatment versus post-treatment clinical field study. All cats included in the study presented pruritus, skin lesions or other evidence compatible with flea infestation. Skin lesions were assessed (using SCORFAD) at days 0, 28, 56 and 84 whereas pruritus severity was assessed (using PVAS) at days 0, 15, 28, 56 and 84. On day 0, The fluralaner (280 mg/ml) product (Bravecto® spot-on for cats) was supplied in pipettes containing 0.4, 0.89 and 1.79 ml for cats of 1.2-2.8 kg, > 2.8-6.25 kg and > 6.25-12.5 kg body weight, respectively. The other animals living in the same household also received fluralaner. Based on cytological examination at day 0, oral amoxicillin and clavulanic acid was prescribed for 21 days if indicated. For cats presenting intense pruritus and discomfort at day 0, oral prednisolone at 0.5 mg/kg was prescribed for 3 days. RESULTS: During the study all cats, except for one (cat number 10), improved significantly. Post-treatment median SCORFAD scores at all evaluations were significantly different from the pre-treatment score on day 0 (P values < 0.002 for all three post treatment examination days) with a score reduction of 49% on day 28, 79% on day 56 and 87% on day 84. The PVAS score decreased significantly over the study period for all cats but one (cat number 10). Post-treatment median PVAS scores at all evaluations were significantly different from the pre-treatment PVAS score on day 0 (P value < 0.002 for all four post-treatment days) with a reduction of 46% on day 15, 67% on day 28, 82% on day 56 and 92% on day 84. No adverse reaction or other health issue was reported during the study. CONCLUSIONS: A single topical treatment with fluralaner results in a significant reduction of flea bite allergic dermatitis clinical signs in cats over the subsequent 12 weeks without any additional environmental treatment.

Neuromedin B Induces Acute Itch in Mice via the Activation of Peripheral Sensory Neurons.

Neuromedin B is expressed in nociceptive and itch-sensitive dorsal root ganglia neurons, but its peripheral pruritogenic potential is not well described. The potential of neuromedin B as a pruritogen and pro-inflammatory peptide in the skin was tested in vivo in an acute model in mice and monkeys as well as an allergic dermatitis model in mice. To identify the underlying mechanisms in vitro real time PCR analysis for neuromedin B and its receptor expression in murine mast cells and dorsal root ganglia as well as functional calcium imaging in the ganglia was applied. Neuromedin B induces itch when injected intradermally, and the peripheral signal is likely transmitted through the activation of dorsal root ganglia. Thus, neuromedin B could be an interesting new therapeutic target for peripheral processing of itch at the level of sensory neurons.

Direct activation of aryl hydrocarbon receptor by benzo[a]pyrene elicits T-helper 2-driven proinflammatory responses in a mouse model of allergic dermatitis.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that binds to various environmental chemicals and contributes to numerous toxicological effects. However, the direct effects of AhR on the development of allergic diseases are not fully understood. The main aim of this study was to elucidate the action of AhR in the development of cutaneous allergies. Initially, the potential for a direct relationship between AhR and the immune cells was investigated in vitro, using murine bone marrow-derived dendritic cells, human epidermal keratinocytes, and the mixed leukocyte reaction assay. Benzo[a]pyrene (BaP) and 6-formylindolo[3,2-b]carbazole were used as selective ligands for the AhR. Pretreatment with BaP and/or 6-formylindolo[3,2-b]carbazole significantly induced cytokine release by activated keratinocytes and T-cell proliferation, whereas interleukin-12 production in bone marrow-derived dendritic cells was reduced by AhR activation. To confirm the in vitro results, in vivo experiments were also performed in T-helper (Th)2-type hapten toluene-2,4-diisocyanate- and Th1-type hapten dinitrochlorobenzene-induced mouse models of allergic dermatitis. Mice were orally administered BaP at 48, 24 and 4 hours before the final allergen challenge. In the Th2 model, ear-swelling response and scratching behavior were promoted by BaP exposure, which supported the observed significant increases in local cytokine secretion. The infiltration of helper T cells, B cells and dendritic cells into the auricular lymph node was significantly enhanced by BaP administration, although Th1-type immune responses were not influenced by AhR activation. Our findings demonstrate that AhR activation directly activates keratinocytes and T cells, which leads to the exacerbation of Th2-type cutaneous allergy.