A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

Effect of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) in a mouse model of atopic dermatitis.

The effects of exposure to clothianidin (CLO), a neonicotinoid pesticide (NN), on the thymus and intestinal microbiota were recently revealed. Immune cells express nicotinic acetylcholine receptors (nAChRs), an NN target, suggesting CLO may disrupt the immune system. However, the relationship between CLO and atopic dermatitis (AD) is unknown. We administered a no-adverse-effect-level (NOAEL) dose of CLO to male NC/Nga mice with induced AD and measured, at three time points, key AD symptom indicators: epidermal thickening, mast cell number, total plasma IgE, and histamine levels. CLO increased total plasma IgE levels but reduced epidermal thickening, mast cell number, and plasma histamine levels in the early stages of AD. This demonstrates for the first time that CLO exposure inhibits AD's early symptoms.

Update on the role of genetic factors, environmental factors and allergens in canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic sensitisation. OBJECTIVE: This review summarises the current evidence on the role of genetic and environmental factors and allergic sensitisation in the pathogenesis of cAD since the last review by ICADA in 2015. MATERIALS AND METHODS: Online citation databases and proceedings from international meetings on genetic factors, environmental factors and allergens relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Despite intensive research efforts, the detailed genetic background predisposing to cAD and the effect of a wide range of environmental factors still need more clarification. Genome-wide association studies and investigations on genetic biomarkers, such as microRNAs, have provided some new information. Environmental factors appear to play a major role. Lifestyle, especially during puppyhood, appears to have an important impact on the developing immune system. Factors such as growing up in a rural environment, large size of family, contact with other animals, and a nonprocessed meat-based diet may reduce the risk for subsequent development of cAD. It appears that Toxocara canis infection may have a protective effect against Dermatophagoides farinae-induced cAD. House dust mites (D. farinae and D. pteronyssinus) remain the most common allergen group to which atopic dogs react. Currently, the major allergens related to D. farinae in dogs include Der f 2, Der f 15, Der f 18 and Zen 1. CONCLUSIONS AND CLINICAL RELEVANCE: Canine atopic dermatitis remains a complex, genetically heterogeneous disease that is influenced by multiple environmental factors. Further, well-designed studies are necessary to shed more light on the role of genetics, environmental factors and major allergens in the pathogenesis of cAD.

Update on the skin barrier, cutaneous microbiome and host defence peptides in canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (AD) is a complex inflammatory skin disease associated with cutaneous microbiome, immunological and skin barrier alterations. This review summarises the current evidence on skin barrier defects and on cutaneous microbiome dysfunction in canine AD. OBJECTIVE: To this aim, online citation databases, abstracts and proceedings from international meetings on skin barrier and cutaneous microbiome published between 2015 and 2023 were reviewed. RESULTS: Since the last update on the pathogenesis of canine AD, published by the International Committee on Allergic Diseases of Animals in 2015, 49 articles have been published on skin barrier function, cutaneous/aural innate immunity and the cutaneous/aural microbiome in atopic dogs. Skin barrier dysfunction and cutaneous microbial dysbiosis are essential players in the pathogenesis of canine AD. It is still unclear if such alterations are primary or secondary to cutaneous inflammation, although some evidence supports their primary involvement in the pathogenesis of canine AD. CONCLUSION AND CLINICAL RELEVANCE: Although many studies have been published since 2015, the understanding of the cutaneous host-microbe interaction is still unclear, as is the role that cutaneous dysbiosis plays in the development and/or worsening of canine AD. More studies are needed aiming to design new therapeutic approaches to restore the skin barrier, to increase and optimise the cutaneous natural defences, and to rebalance the cutaneous microbiome.

Are images worth a thousand words? A preliminary study testing a video for owner education in canine atopic dermatitis.

BACKGROUND: Successful management of canine atopic dermatitis (cAD) is challenging and effective pet owner education is crucial to successful outcomes. However, there are limited proven educational strategies in this area. Our goal was to create an effective and engaging educational tool for owners of dogs with cAD. HYPOTHESIS: Video-based education efficacy would be comparable to traditional verbal delivery. Secondary objectives included assessing client perception of the intervention, and determining if there were clinical benefits for the dogs and improved client adherence to treatment. SUBJECTS: Twenty-nine dogs with cAD and their owners were recruited from a teaching hospital of a European veterinary medicine faculty. MATERIALS AND METHODS: In this 8 week, prospective, randomised controlled study, clients in the control group (CG, n = 13) received verbal education and those in the intervention group (IG, n = 16) watched a video. Client knowledge was assessed at Day (D)0 and D56. Treatment adherence and perceived utility and appeal ratings were measured at D56. Clinical progress was assessed at D0 and D56 using CADESI-04 and PVAS10. RESULTS: The differences found in the means of cAD knowledge score, clinical outcomes, utility and appeal ratings and owners' adherence score between groups were not statistically significant. A significant association between the outcome and the intervention group concerning education success [CG, six of 13 (46.15%); IG, 15 of 16 (93.75%)] was found (p = 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Video-based instructions positively impacted owners' education and demonstrated their potential as a valuable tool. The authors believe that video-based education could be a time-efficient alternative for initial cAD education in veterinary clinics.

Update on the role of cytokines and chemokines in canine atopic dermatitis.

BACKGROUND: Cytokines and chemokines play central roles in the pathogenesis of canine atopic dermatitis (cAD). Numerous studies have been published and provide new insights into their roles in cAD. OBJECTIVES: To summarise the research updates on the role of cytokines and chemokines in the pathogenesis of cAD since the last review by the International Committee on Allergic Diseases of Animals in 2015. MATERIAL AND METHODS: Online citation databases, abstracts and proceedings from international meetings on cytokines and chemokines relevant to cAD that had been published between 2015 and 2022 were reviewed. RESULTS: Advances in technologies have allowed the simultaneous analysis of a broader range of cytokines and chemokines, which revealed an upregulation of a multipolar immunological axis (Th1, Th2, Th17 and Th22) in cAD. Most studies focused on specific cytokines, which were proposed as potential novel biomarkers and/or therapeutic targets for cAD, such as interleukin-31. Most other cytokines and chemokines had inconsistent results, perhaps as a consequence of their varied involvement in the pathogenesis of different endotypes of cAD. CONCLUSIONS AND CLINICAL RELEVANCE: Inconsistent results for many cytokines and chemokines illustrate the difficulty of studying the complex cytokine and chemokine networks in cAD, and highlight the need for more comprehensive and structured studies in the future.

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.

Open trial of recombinant Der f 2 pullulan-conjugated immunotherapy in cats.

BACKGROUND: Allermmune HDM (Zenoaq) is a recombinant Dermatophagoides farinae 2 (Der f 2) pullulan-based immunotherapy vaccine whose efficacy on house dust mite allergic dogs has been demonstrated. There is no published information on its use in cats. OBJECTIVES: The objective of the study was to evaluate the safety and short-term effects of Allermmune HDM in Dermatophagoides farinae (Df)-sensitised cats. MATERIALS AND METHODS: Eleven cats diagnosed with atopic skin syndrome received Allermmune weekly for six weeks then monthly for three months (total duration 18 weeks). On Weeks 0, 6 and 18 clinical lesions were assessed by the Feline Dermatitis Extent and Severity Index (FEDESI); owners assessed pruritus with a 10-cm Visual Analog Scale (pVAS). Concurrent medication use was recorded. The allergen-specific immunoglobulin (Ig)E were measured before study inclusion with a commercial serological assay. RESULTS: There were no evident adverse effects. FEDESI and pVAS improved significantly after six weeks (p = 0.001 and p = 0.01, respectively). The pretreatment Df-specific IgE levels were significantly higher in the cats with improved clinical scores than in the cats with no clinical score change (p = 0.009). CONCLUSIONS AND CLINICAL RELEVANCE: Allermmune HDM may be safe in cats and has the potential to alleviate signs of atopic skin syndrome. Allergen-specific IgE levels may represent an efficacy marker. Controlled studies of longer duration and larger sample size are worth pursuing.

Tumour necrosis factor-α induces C-C motif chemokine ligand 5 production in canine keratinocytes.

BACKGROUND: C-C motif chemokine ligand (CCL)5 induces skin inflammation in healthy dogs. In addition, CCL5 is overexpressed in the skin of experimental models of canine atopic dermatitis (cAD). Tumour necrosis factor (TNF)-α has been shown to be upregulated in cAD. However, it remains unclear whether TNF-α induces CCL5 production in canine keratinocytes. HYPOTHESIS/OBJECTIVES: To determine the effect of TNF-α on CCL5 production in canine keratinocyte culture and investigate possible synergy with interferon (IFN)-γ and interleukin (IL)-4. MATERIALS AND METHODS: CCL5 protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatant of a cell line of canine progenitor epidermal keratinocyte (CPEK) cells stimulated with TNF-α with or without inhibitors of the TNF receptor signalling pathway. CCL5 protein concentrations also were measured in CPEK cells stimulated with TNF-α in the absence or presence of IFN-γ, a T-helper (Th)1-type cytokine, and/or IL-4, a Th2-type cytokine. RESULTS: TNF-α increased CCL5 production in CPEK cells in time- and dose-dependent manners. Inhibitors of the TNF receptor signalling pathway diminished CCL5 production. Although neither IFN-γ nor IL-4 alone induced CCL5 production in CPEK cells, the combination of TNF-α and IFN-γ, and not IL-4, synergistically enhanced CCL5 production in these cells. CONCLUSIONS AND CLINICAL RELEVANCE: TNF-α may be involved in skin inflammation in dogs by promoting CCL5 production in keratinocytes. Furthermore, the synergistic effect of TNF-α and IFN-γ suggests that the local Th1-type milieu may aggravate skin inflammation. Further studies are required to elucidate the role of TNF-α-induced CCL5 production of keratinocytes in the pathogenesis of cAD.

Canine Models of Inflammatory Skin Diseases and Their Application in Pharmacological Research.

The purpose of this article is to provide an overview of existing pharmacological models of canine dermatitis. Canine models of dermatitis have contributed significantly to our current understanding of the pathology of dermatitis and to the development of corresponding pharmacological interventions. Specifically, canine atopic dermatitis (AD) is reviewed here, as it is one of the most common inflammatory skin diseases in dogs. Canine AD also shares clinicopathological features with human AD, making the dog a natural and optimal model for human disease. Thus, pharmacological models of canine AD may be uniquely applicable to human pharmacological research. In this article, particular attention is dedicated to relevant in vivo, in vitro, and ex vivo models of canine AD, skin barrier defect models, pruritus models, and skin immunology models. Additionally, models of superficial pyoderma and food allergy are also discussed. With understanding of findings from canine models, researchers can select the most salient features for future pharmacological drug development. © 2023 Wiley Periodicals LLC.

Interleukin-31 in serum and cerebrospinal fluid of dogs with syringomyelia.

BACKGROUND: Syringomyelia is a spinal cord cavity containing cerebrospinal fluid (CSF)-like fluid. If syringomyelia asymmetrically involves the dorsal horn grey matter of the spinal cord, affected dogs show increased signs of dysesthesia and neuropathic pain, like increased itching behaviour. In the dorsal horn, amongst others, receptors for Interleukin-31 (IL-31) can be found. IL-31 is one of the main cytokines involved in the pathogenesis of pruritus in atopic dermatitis in different species. This study investigates suspected elevated levels of IL-31 in serum and CSF of dogs showing signs of pain or increased itching behaviour related to syringomyelia. The IL-31 were measured in archived samples (52 serum and 35 CSF samples) of dogs with syringomyelia (n = 48), atopic dermatitis (n = 3) and of healthy control dogs (n = 11) using a competitive canine IL-31 ELISA. RESULTS: Mean serum IL-31 level in dogs with syringomyelia was 150.1 pg/ml (n = 39), in dogs with atopic dermatitis 228.3 pg/ml (n = 3) and in healthy dogs 80.7 pg/ml (n = 10). Mean CSF IL-31 value was 146.3 pg/ml (n = 27) in dogs with syringomyelia and 186.2 pg/ml (n = 8) in healthy dogs. Individual patients with syringomyelia (especially dogs with otitis media or otitis media and interna or intervertebral disc herniation) showed high IL-31 levels in serum and CSF samples, but the difference was not statistically significant. IL-31 serum and CSF levels did not differ significantly in dogs with syringomyelia with or without itching behaviour and with or without signs of pain. CONCLUSION: Based on this study, increased IL-31 levels seem not to be correlated with itching behaviour or signs of pain in dogs with syringomyelia, but might be caused by other underlying diseases.

A comprehensive analysis of gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs.

BACKGROUND: Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota. RESULTS: Staphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and microbial composition in the gut and skin. CONCLUSIONS: Dysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota. Video Abstract.

2023 AAHA Management of Allergic Skin Diseases in Dogs and Cats Guidelines.

These guidelines present a systematic approach to diagnosis, treatment, and management of allergic skin diseases in dogs and cats. The guidelines describe detailed diagnosis and treatment plans for flea allergy, food allergy, and atopy in dogs and for flea allergy, food allergy, and feline atopic skin syndrome in cats. Management of the allergic patient entails a multimodal approach with frequent and ongoing communication with the client. Obtaining a comprehensive history is crucial for diagnosis and treatment of allergic skin diseases, and the guidelines describe key questions to ask when presented with allergic canine and feline patients. Once a detailed history is obtained, a physical examination should be performed, a minimum dermatologic database collected, and treatment for secondary infection, ectoparasites, and pruritus (where indicated) initiated. The process of diagnosing and managing allergic skin disease can be prolonged and frustrating for clients. The guidelines offer recommendations and tips for client communication and when referral to a dermatologist should be considered, to improve client satisfaction and optimize patient outcomes.

Seroprevalence of Dermatophagoides farinae-specific IgE in dogs with atopic dermatitis in São Paulo, Brazil.

Canine atopic dermatitis (CAD) is a chronic, inflammatory, and pruritic disease of the skin resulting from the loss of the epidermal barrier, sensitization, and exacerbated production of IgE antibodies mainly directed against environmental allergens, especially to house dust mites. To select specific allergen immunotherapies with high efficacy, there are necessary studies with house dust mite allergens to improve both serological and intradermal tests. Therefore, the objective of this study was to evaluate the seroprevalence of IgE against Der f 2, Zen 1, and crude Dermatophagoides farinae allergens in dogs with AD in the State of São Paulo, Brazil. The sera of 85 dogs with clinically confirmed atopic dermatitis from the State of São Paulo (Brazil) was collected. In addition, an indirect ELISA test was conducted to detect allergen-specific serum IgE. IgE seropositivity was observed in 97.5% of the dogs for Der f 2, 95.0% for Zen 1, and 92.5% for the crude mite allergens. Due to this high prevalence of IgE specific to these allergens, we suggest that Der f 2 and Zen 1 can be considered major allergens for dogs in the State of São Paulo.

Cross-reactive carbohydrate determinants in atopic and healthy dogs and their influence on allergy test specificity.

BACKGROUND: The selection of allergens for immunotherapy in atopic dogs is often based on serum allergy testing. Cross-reactive carbohydrate determinants (CCDs) are common structures in plant and insect allergens that reportedly induce polysensitisation, reduce agreement between intradermal and serum tests and complicate allergen selection. METHODS: Thirty-four dogs with diagnosed atopic dermatitis and 10 healthy dogs were included in the study. An intradermal test was conducted in atopic dogs, and serum samples from allergic and healthy dogs were analysed for allergen-specific immunoglobulin E (IgE) before and after inhibition of detectable anti-CCD-IgE antibodies. RESULTS: Anti-CCD-IgE antibodies were not found in any of the healthy dogs and no polysensitisation to plant and insect allergens was detected. The agreement between intradermal and serum allergy test results in the atopic dogs with anti-CCD-IgE antibodies improved from slight to fair after blocking the anti-CCD-IgE antibodies. In addition, blocking clearly reduced polysensitisation to plant allergens but not to acarid allergens. LIMITATIONS: Only a limited number of healthy dogs were tested in this study. A gold standard for determining the clinical relevance of IgE sensitisation does not exist. CONCLUSION: Inhibition of anti-CCD-IgE antibodies seems to be of importance to improve serum test specificity for allergen-specific IgE in atopic dogs in relation to intradermal allergy testing.

Non-controlled, open-label trial to assess clinical and immunological parameters in atopic dogs feeding monoprotein grain free diet versus a standard grain diet.

Canine atopic dermatitis (cAD) is a common inflammatory skin disease that is treated with medicines or allergen-specific immunotherapy. An improvement diet can help treatment of cAD. The purpose of this study was compare two diets on clinical and immunological parameters in atopic dogs without food hypersensitivity. Diet A, a commercial based on rice, was offered to 22 atopic dogs during 30 days and Diet B (grain free, rich in salmon) was given to 8 atopic dogs. Clinical scores were assessed by CADESI-4 and PVAS at the beginning (T0) and at the end of the study (T30). CD4+ and CD8+ were measured in PBMCs, and serum cytokines (TNF-α, IL-10, IL-31 and IL-34) were determined. Both diets decreased CADESI-4 score and Diet A decreased PVAS score (p < 0.05). There were no statistical significant differences between diets at T30 for CD4+ and CD8+. A decrease in the IL-31 concentrations and increase in IL-10 levels (p < 0.05) was observed with Diet A at T30. There were no differences between any of the two diets when the other results at T0 and T30 were compared for any of the parameters analysed. In conclusion, the results indicate that dietary intervention had not influence on cellular component of the immune system, but a positive effect was observed on IL-31, IL-10 serum levels for Diet A. Further studies are needed to enrich dietary components of the food for atopic dogs without food hypersensibility to help improvement the management of the cAD.

A randomised, double-blinded, controlled trial to determine the efficacy of combined therapy of oclacitinib and marine oil extract PCSO-524 in dogs with atopic dermatitis.

BACKGROUND: Polyunsaturated fatty acids (PUFA) can be beneficial in the management of canine atopic dermatitis (cAD). A commercial product PCSO-524 containing PUFA has demonstrated anti-inflammatory effects in dogs. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of PCSO-524, in combination with oclacitinib in dogs with cAD. ANIMALS: Seventeen client-owned dogs with cAD. MATERIALS AND METHODS: A randomised, double-blinded, controlled trial. All dogs were treated with oclacitinib (0.4-0.6 mg/kg) twice a day for 14 days, then once a day until Day (D)42. They were randomly divided into two groups: PCSO-524 (n = 9) and sunflower oil (n = 8). Clinical status was assessed by Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and pruritus Visual Analog Scale (pVAS) at baseline (D0), D14, D28 and D42. Trans epidermal water loss (TEWL) was measured at the same time points. RESULTS: CADESI scores decreased significantly after treatment and there was a significant difference between the PCSO-524 and the control group at D28 (p = 0.04) and D42 (p = 0.03). The PCSO-524 group also demonstrated a significantly decreased pVAS on D28 and D42 (p < 0.001 and p < 0.001) compared to D0, while significant differences were observed in the control group at D14 and D28 (p < 0.01 and p = 0.04) and not at D42 (p = 0.12). The mean TEWL showed a significant decrease at D28 and D42 in the PCSO-524 group, compared to the control group (p = 0.002 and p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The combination of PCSO-524 and oclacitinib may help to alleviate the rebound effect that occurs when tapering down the dosage of oclacitinib, as compared to using oclacitinib alone for the management of cAD.

Effect of Allergen-Specific Immunotherapy on Transcriptomic Changes in Canine Atopic Dermatitis.

Canine atopic dermatitis (cAD) is a genetic, chronic, and recurrent inflammatory and pruritic skin disorder. Allergen-specific immunotherapy (ASIT) is presently recognized as the only clinically effective disease-modifying treatment for allergies. The aim of our study was to analyze the changes in gene expression observed in the peripheral blood nuclear cells of cAD patients subjected to ASIT. Blood samples designated for transcriptomic analyses were collected from AD dogs twice, before and six months after ASIT, and also from healthy dogs. Statistical analysis revealed 521 differentially expressed transcripts, among which 241 transcripts represented genes with well-described functions. Based on the available literature, we chose nine differentially expressed genes (RARRES2, DPP10, SLPI, PLSCR4, MMP9, NTSR1, CBD103, DEFB122, and IL36G) which may be important in the context of the dysregulated immune response observed in cAD patients. The expressions of five out of the nine described genes (DPP10, PLSCR4, NTSR1, DEFB122, and IL36G) changed after the application of ASIT. The expressions of three of these genes returned to the level observed in the healthy control group. The genes listed above need further investigation to determine details of their role in the molecular mechanism of immune tolerance induction in response to allergen-specific immunotherapy.