Towards a flexible and personalised development of veterinarians and veterinary nurses working in a companion animal referral care setting.

In the Netherlands, the demand for veterinarians and veterinary nurses (VNs) working within referral care is rapidly growing and currently exceeds the amount of available board-certified specialists. Simultaneously, a transparent structure to guide training and development and to assess quality of non-specialist veterinarians and VNs working in a referral setting is lacking. In response, we developed learning pathways guided by an entrustable professional activity (EPA) framework and programmatic assessment to support personalised development and competence of veterinarians and VNs working in referral settings. Between 4 and 35 EPAs varying per discipline (n = 11) were developed. To date, 20 trainees across five disciplines have been entrusted. Trainees from these learning pathways have proceeded to acquire new EPAs in addition to their already entrusted set of EPAs or progressed to specialist training during (n = 3) or after successfully completing (n = 1) the learning pathway. Due to their outcome-based approach, the learning pathways support flexible ways of development.

Efficacy of short-term combination of intralymphatic allergen immunotherapy and lokivetmab treatment in canine atopic dermatitis: A double-blinded, controlled, randomised study.

BACKGROUND: Allergen-specific immunotherapy (ASIT) is an effective therapy for canine atopic dermatitis (cAD). Intralymphatic immunotherapy (ILIT) is potentially beneficial in decreasing time to clinical effectiveness. OBJECTIVE: To compare clinical efficacy of six monthly ILIT injections combined with three monthly injections of lokivetmab (LVM) with monthly LVM monotherapy at Day (D)168. To monitor dogs treated with ILIT for an additional six months of subcutaneous immunotherapy (SCIT). ANIMALS: Thirty-six client-owned dogs with cAD. MATERIALS AND METHODS: In this double-blinded, randomised study, dogs received either six monthly injections of ILIT combined with three monthly LVM injections (ILIT group) or six monthly LVM injections (LVM group). Monthly evaluations with pruritus Visual Analogue Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and medication scores (MS) were undertaken. Owners completed a Quality of Life (QoL) questionnaire. Treatment success was predefined as ≥50% reduction in pVAS and CADESI-04 score ≤ 10. After D168, the ILIT group continued with SCIT until subjective assessment at 12 months. RESULTS: The treatment benchmark at D168 was achieved by 11.1% of the ILIT group and 11.8% of LVM group. A significant decrease in mean pVAS and CADESI scores was observed in both groups (p < 0.001). The ILIT group had a trend towards higher MS compared to LVM. QoL was better in LVM (p = 0.01). At 12 months subjective good-to-excellent response in 77.8% of dogs in the ILIT/SCIT group was seen. CONCLUSION AND CLINICAL RELEVANCE: The efficacy of this ILIT protocol was comparable with LVM monotherapy at six months. When ILIT was continued with SCIT, a favourable response was seen.

Evidence-base for the beneficial effect of nutraceuticals in canine dermatological immune-mediated inflammatory diseases - A literature review.

BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are associated with an abnormal immune response, resulting in a disturbed homeostasis and chronic inflammation. Most canine dermatological IMIDs (cDIMIDs), such as allergies, autoimmune and immune-mediated diseases, require long-term treatment with immunosuppressive drugs with potential adverse effects. In general, nutraceuticals are thought to be safe. As a result, there is a tendency for the more frequent use of nutraceuticals in veterinary medicine. OBJECTIVES: The aim of this review was to present evidence-based proof for the use of various nutraceuticals in the treatment of cDIMIDs and, where possible, to provide conclusions to guide their use in veterinary dermatological practice. METHODS: A comprehensive literature search on common cDIMIDs and nutraceuticals was performed. Only peer-reviewed articles published in English and related to the study topic were included. A total of 64 eligible publications were classified in five categories based on study design and substantively assessed on additional criteria such as standardisation of diets and number of included animals. For final appraisal, classification of major, minor or no evidence was used whereby efficacy was based on clinical outcome measurements. CONCLUSIONS: Minor evidence for the beneficial use of several nutraceuticals, including essential fatty acids, niacinamide and probiotics, was found for treatment of specific cDIMIDs. These nutraceuticals may improve clinical signs or reduce the required dose of concurrent medication (e.g. drug-sparing effect) in some dogs. Some nutraceuticals also may be used for long-term maintenance therapy. Despite some promising findings, major evidence for the use of nutraceuticals in cDIMIDs is lacking, warranting further research.

CD4+ and CD8+ skin-associated T lymphocytes in canine atopic dermatitis produce interleukin-13, interleukin-22 and interferon-γ and contain a CD25+ FoxP3+ subset.

BACKGROUND: T Cells play a major role in the immunopathogenesis of canine atopic dermatitis (cAD). However, the significance of cutaneous regulatory T cells (Tregs) and CD8(+) T cells is currently unclear. HYPOTHESIS/OBJECTIVES: The study aimed to evaluate the presence and distribution of Tregs in cAD and healthy skin and to determine the cytokine production of cutaneous CD4(+) and CD8(+) T cells. ANIMALS: Biopsies were taken from four dogs with cAD (lesional and nonlesional skin) and four healthy control dogs. METHODS: Distribution patterns of T-cell subtypes in cAD lesional, nonlesional and control skin were evaluated by immunohistochemistry. Phenotypic characterization of T cells from skin explant cultures and enzymatic digestions was performed using flow cytometry. Cytokine production of sorted CD4(+) and CD8(+) explant-derived T cells was measured by RT-qPCR. RESULTS: Regulatory T cells phenotypically characterized by CD25(+) FoxP3(+) were found in both CD4(+) and CD8(+) subsets of skin explant and digestion samples. The percentages of CD4(+) CD25(+) cells that were FoxP3(+) were similar in cAD and control skin. In atopic lesional and nonlesional explant samples, lower FoxP3(+) percentages of CD8(+) CD25(+) cells were seen compared with control skin. The presence of predominantly periadnexal CD25(+) FoxP3(+) cells was confirmed by immunohistochemistry in lesional, nonlesional and control skin. The CD4(+) /CD8(+) ratio was less than one in cAD skin with both skin explant and digestion methods. CD4(+) and CD8(+) T-cell subsets of lesional and nonlesional cAD skin were capable of producing interleukin-13, interleukin-22 and interferon-γ. CONCLUSIONS AND CLINICAL IMPORTANCE: Both CD4(+) and CD8(+) T cells are likely to contribute to the immunopathogenesis of cAD through the production of interleukin-13, interleukin-22 and interferon-γ. In both subsets, functional analysis of FoxP3(+) cells is essential to determine their role.

The immunostimulatory effect of CpG oligodeoxynucleotides on peripheral blood mononuclear cells of healthy dogs and dogs with atopic dermatitis.

Synthetic oligodeoxynucleotides containing cytosine phosphatidyl guanine-rich DNA sequences (CpG ODN) can promote T-helper type 1 (Th1) responses, reduce T-helper type 2 (Th2) responses and/or favour regulatory T cell (Treg) responses in vitro and in vivo in humans and animals, by acting via Toll-like receptor 9 (TLR9). Since CpG ODN can be used as immune-modulators for canine atopic dermatitis (AD), the aim of the current study was to investigate their immunostimulatory potential on peripheral blood mononuclear cells (PBMC) and their subsets, from AD and healthy dogs. Expression of TLR9 and cytokine mRNA in CpG ODN-stimulated and unstimulated cells was assessed by real-time quantitative PCR. Stimulation of PBMC with CpG class C ODN upregulated mRNA expression of interleukin (IL)-6, interferon (IFN)-γ and IL-12p40 in AD dogs (P<0.05). It also stimulated IFN-γ protein secretion by PBMC of atopic and healthy dogs as measured by ELISA. In healthy dogs only, CpG class C ODN stimulated IFN-α mRNA production by CD21(+) cells, and IL-10, IL-13 and IFN-γ mRNA production by CD3(+) cells. Increased expression of TLR9 mRNA was only observed in CD3(+) cells from AD dogs. No significantly increased gene expression was found in the CD11c(+) subset upon stimulation, for those genes evaluated. The results indicate that PBMC of healthy and atopic dogs are sensitive to stimulation with CpG ODN class C, with a resulting Th1 cytokine response in AD dogs and a mixed Th1/Th2/Treg cytokine response in healthy dogs. From this study, little evidence was found to support the use of CpG ODN class C for therapeutic purposes in dogs affected with AD.

Successful treatment of sebaceous adenitis in a rabbit with ciclosporin and triglycerides.

A 4-year-old rabbit was presented with a chronic exfoliative dermatitis and patchy alopecia. General physical examination revealed no abnormalities. Skin scrapings and fungal culture were negative. A blood sample was obtained for a complete blood cell count and biochemical profile, and yielded results that were within normal limits. Radiographic examination of the thorax excluded the presence of a thymoma. Histopathology of the skin showed orthokeratotic hyperkeratosis, absence of sebaceous glands and mural lymphocytic folliculitis, consistent with sebaceous adenitis. Oral treatment was started with ciclosporin dissolved in a medium-chain triglyceride solution (Miglyol 812), combined with essential fatty acids and topical propylene glycol sprays. Within 2 months of treatment, complete regression of skin lesions and regrowth of hair was observed. Serum chemistry values including kidney and liver function tests remained within reference range during the course of treatment. Histopathological examination of control biopsies of the skin showed presence of normal sebaceous glands and active hair follicles. Treatment was changed to a different pharmaceutical formulation of ciclosporin without Miglyol and deterioration of clinical signs was noticed. Using pure Miglyol 812, however, resulted in a gradual improvement of 60%. A nearly complete response was again observed after re-administration of the combination ciclosporin/Miglyol. It is hypothesized that sebaceous adenitis in the rabbit is most likely due to an autoimmune reaction directed at the sebaceous glands and a defect in lipid metabolism. The outcome indicates that a combination of ciclosporin and Miglyol 812 is a promising new treatment for sebaceous adenitis in rabbits.

Intradermal injection of Hsp60 induces cytokine responses in canine atopic and healthy skin.

The purpose of this study was to investigate the immunoregulatory potential of Hsp60 in the skin of dogs with atopic dermatitis. Three dogs with chronic atopic dermatitis and four healthy dogs were injected intradermally with Hsp60 and phosphate-buffered saline. Biopsies were taken before testing from non-injected control skin, lesional and non-lesional atopic skin, and 48 and 72 h after injection. Analysis of cytokine messenger RNA was performed using quantitative real-time polymerase chain reaction. Forty-eight hours after Hsp60 injection, a rise in interleukin (IL)-10 was found (P = 0.034) with the highest expression levels in non-lesional atopic and control skin. A rise of transforming growth factor beta (P = 0.015) and IL-12p40 (P = 0.017) was noticed 72 h after Hsp60 injection in control skin. No significant differences were observed for the expression of IL-4, IL-12p35, and interferon gamma. The results indicate that Hsp60 is able to induce cytokines of a regulatory and Th1 phenotype in the skin. Furthermore, this study seems to provide a first indication of deficient Hsp60 response in atopic dermatitis affected skin.