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.

Independent COL17A1 Variants in Cats with Junctional Epidermolysis Bullosa.

Epidermolysis bullosa (EB), characterized by defective adhesion of the epidermis to the dermis, is a heterogeneous disease with many subtypes in human patients and domestic animals. We investigated two unrelated cats with recurring erosions and ulcers on ear pinnae, oral mucosa, and paw pads that were suggestive of EB. Histopathology confirmed the diagnosis of EB in both cats. Case 1 was severe and had to be euthanized at 5 months of age. Case 2 had a milder course and was alive at 11 years of age at the time of writing. Whole genome sequencing of both affected cats revealed independent homozygous variants in COL17A1 encoding the collagen type XVII alpha 1 chain. Loss of function variants in COL17A1 lead to junctional epidermolysis bullosa (JEB) in human patients. The identified splice site variant in case 1, c.3019+1del, was predicted to lead to a complete deficiency in collagen type XVII. Case 2 had a splice region variant, c.769+5G>A. Assessment of the functional impact of this variant on the transcript level demonstrated partial aberrant splicing with residual expression of wildtype transcript. Thus, the molecular analyses provided a plausible explanation of the difference in clinical severity between the two cases and allowed the refinement of the diagnosis in the affected cats to JEB. This study highlights the complexity of EB in animals and contributes to a better understanding of the genotype-phenotype correlation in COL17A1-related JEB.

Hymenoptera Venom Immunotherapy in Dogs: Safety and Clinical Efficacy.

Hymenoptera allergens are the main triggers for anaphylaxis in susceptible dogs and humans. Hymenoptera venom specific immunotherapy (VIT), the only disease-modifying treatment, has the potential to prevent future life-threatening reactions in human patients. Prospective clinical data on VIT efficacy in dogs are currently lacking. Therefore, the aim of this study was to show that VIT is not only safe but also efficacious in preventing anaphylaxis in dogs allergic to Hymenoptera. This uncontrolled prospective clinical trial included 10 client-owned dogs with a history of anaphylaxis following repeated Hymenoptera stings. The sensitization to bee and wasp allergens was demonstrated by intradermal testing (IDT) and allergen-specific IgE serology. For VIT induction (induction phase), dogs received a shortened rush immunotherapy protocol with aqueous allergens, which was then followed by monthly injections of 100 µg of alum-precipitated allergen (maintenance phase). VIT efficacy was determined by observing patients' clinical reactions to re-stings. No systemic adverse events were seen during the induction and maintenance phases. From the seven re-stung dogs, only one developed a mild angioedema at the site of the sting; the remaining dogs were asymptomatic. These results show that VIT represents a safe and effective treatment option for Hymenoptera-allergic dogs.

First description of Arthroderma lilyanum in a rabbit with a focal alopecic area of the forelimb.

Dermatophytosis is an important zoonotic disease in pet rabbits. While common clinical signs of dermatophytosis can occur, rabbits can also be asymptomatically infected. This case report describes a rabbit from Switzerland, with a focal alopecic area on one forepaw. Dermatophyte culture of a hair and skin sample taken from the lesion revealed growth of a dermatophyte, that was identified as the recently described species Arthroderma (A.) lilyanum by sequencing of the internal transcribed spacer (ITS) and ß-tubulin genes. After local treatment with a disinfectant containing octenidine dihydrochloride and phenoxyethanol twice daily for two weeks, the lesion fully healed. Although it is not clear whether the dermatophyte was responsible for the lesion or if it was an incidental finding with an asymptomatic infection, the current report shows, that the host spectrum and geographical distribution of A. lilyanum are broader than previously thought.

Comparison of the Gut Microbiome between Atopic and Healthy Dogs-Preliminary Data.

Human studies show that in addition to skin barrier and immune cell dysfunction, both the cutaneous and the gut microbiota can influence the pathogenesis of atopic diseases. There is currently no data on the gut-skin axis in allergic canines. Therefore, the aim of this study was to assess the bacterial diversity and composition of the gut microbiome in dogs with atopic dermatitis (AD). Stool samples from adult beagle dogs (n = 3) with spontaneous AD and a healthy control group (n = 4) were collected at Days 0 and 30. After the first sampling, allergic dogs were orally dosed on a daily basis with oclacitinib for 30 days, and then re-sampled. Sequencing of the V3-V4 region of the 16S rRNA gene was performed on the Illumina MiSeq platform and the data were analyzed using QIIME2. The atopic dogs had a significantly lower gut microbiota alpha-diversity than healthy dogs (p = 0.033). In healthy dogs, a higher abundance of the families Lachnospiraceae (p = 0.0006), Anaerovoracaceae (p = 0.006) and Oscillospiraceae (p = 0.021) and genera Lachnospira (p = 0.022), Ruminococcustorques group (p = 0.0001), Fusobacterium (p = 0.022) and Fecalibacterium (p = 0.045) was seen, when compared to allergic dogs. The abundance of Conchiformibius (p = 0.01), Catenibacterium spp. (p = 0.007), Ruminococcus gnavus group (p = 0.0574) and Megamonas (p = 0.0102) were higher in allergic dogs. The differences in alpha-diversity and on the compositional level remained the same after 1 month, adding to the robustness of the data. Additionally, we could also show that a 4-week treatment course with oclacitinib was not associated with changes in the gut microbiota diversity and composition in atopic dogs. This study suggests that alterations in the gut microbiota diversity and composition may be associated with canine AD. Large-scale studies preferably associated to a multi-omics approach and interventions targeting the gut microbiota are needed to confirm these results.

Phaeohyphomycosis caused by Phialophora americana in a dog.

Phaeohyphomycosis was diagnosed in a 6-year-old, male castrated Dachshund on immunosuppressive treatment. The fungus was identified by culture and PCR as Phialophora americana. This is the first reported case of infection with this pathogen in a dog. The infection was successfully managed medically, without surgical intervention.

Une phaéohyphomycose a été diagnostiquée chez un teckel mâle castré de 6 ans sous traitement immunosuppresseur. Le champignon a été identifié par culture et PCR comme Phialophora americana. Il s'agit du premier cas rapporté d'infection par cet agent pathogène chez un chien. L'infection a été prise en charge médicalement avec succès, sans intervention chirurgicale.

Se diagnosticó feohifomicosis en un macho de Teckel castrado de 6 años en tratamiento inmunosupresor. El hongo fue identificado por cultivo y PCR como Phialophora americana. Este es el primer caso reportado de infección por este patógeno en un perro. La infección se manejó con éxito médicamente, sin intervención quirúrgica.

Feohifomicose foi diagnosticada em um cão da raça Dachshund, macho castrado, de seis anos de idade, em tratamento imunossupressivo. O fungo identificado por cultura e PCR foi Phialophora americana. Este é o primeiro relato de caso de infecção por este patógeno em um cão. A infecção foi bem conduzida com tratamento medicamentoso, sem intervenção cirúrgica.

Interleukin 10 and transforming growth factor-beta 1 plasma levels in atopic dogs before and during immunotherapy.

BACKGROUND: Human studies suggest that the cytokines, interleukin 10 (IL-10) and transforming growth factor-beta 1 (TGF-ß1) may play an important role in allergen-specific immunotherapy (ASIT). However, there is little known about the function of these cytokines in atopic dogs. This study compared the plasma levels of IL-10 and TGF-ß1 in atopic and control dogs and investigated their changes during different ASIT approaches. METHODS: A total of 54 atopic and 32 control dogs were included. Immunotherapy was performed in 30 atopic dogs. The dogs undergoing immunotherapy were allocated to four groups of different ASIT approaches (namely subcutaneous, intralymphatic, sublingual ASIT and subcutaneous ASIT with recombinant allergens). Blood samples were collected at four timepoints throughout the one year of ASIT. Canine atopic dermatitis extent and severity index, pruritus visual analogue scale and medication score were recorded at each timepoint. Commercially available ELISA kits were used to quantify IL-10 and TGF-ß1 in plasma. RESULTS: There was no significant difference in IL-10 and TGF-ß1 between atopic and control dogs. The IL-10 levels were significantly increased in the intralymphatic group at the end of the study. No significant differences were found in the other groups for both IL-10 and TGF-ß1. CONCLUSION: The findings of this work suggest that IL-10 and TGF-ß1 cannot be used to monitor the course of the disease during ASIT.

Independent DSG4 frameshift variants in cats with hair shaft dystrophy.

Investigations of hereditary phenotypes in spontaneous mutants may help to better understand the physiological functions of the altered genes. We investigated two unrelated domestic shorthair cats with bulbous swellings of the hair shafts. The clinical, histopathological, and ultrastructural features were similar to those in mice with lanceolate hair phenotype caused by loss-of-function variants in Dsg4 encoding desmoglein 4. We sequenced the genomes from both affected cats and compared the data of each affected cat to 61 control genomes. A search for private homozygous variants in the DSG4 candidate gene revealed independent frameshift variants in each case, c.76del or p.Ile26fsLeu*4 in case no. 1 and c.1777del or p.His593Thrfs*23 in case no. 2. DSG4 is a transmembrane glycoprotein located primarily in the extracellular part of desmosomes, a complex of adhesion molecules responsible for connecting the keratin intermediate filaments of neighbouring epithelial cells. Desmosomes are essential for normal hair shaft formation. Both identified DSG4 variants in the affected cats lead to premature stop codons and truncate major parts of the open-reading frame. We assume that this leads to a complete loss of DSG4 function, resulting in an incorrect formation of the desmosomes and causing the development of defective hair shafts. Together with the knowledge on the effects of DSG4 variants in other species, our data suggest that the identified DSG4 variants cause the hair shaft dystrophy. To the best of our knowledge, this study represents the first report of pathogenic DSG4 variants in domestic animals.

A novel therapeutic diet can significantly reduce the medication score and pruritus of dogs with atopic dermatitis during a nine-month controlled study.

BACKGROUND: Canine atopic dermatitis (cAD) is a common chronic relapsing pruritic skin disease for which management commonly relies on life-long use of immunomodulatory drugs. A number of the medications used are associated with adverse effects and the potential for complications during long-term use. HYPOTHESIS: The goal of the study was to determine if a complete and balanced diet formulated for therapeutic benefit could contribute towards management of cAD. We hypothesised that the diet would reduce pruritus while also reducing the requirement for medication during the study period. ANIMALS, MATERIALS AND METHODS: Forty privately owned dogs, having undergone a comprehensive diagnosis for cAD, were randomly allocated to two groups, each group being fed one of two diets (test or control) for up to nine months. We assessed pruritus, Canine Atopic Dermatitis Extent and Severity Index-(4th iteration) and medication score, the latter reflecting the medication required to maintain a satisfactory quality of life for the animal. RESULTS: Both diets were well-accepted and -tolerated. There was a significant improvement in the pruritus score after three months of feeding the therapeutic diet (P = 0.0001). No such improvement was observed at any time point in the group of dogs given the control diet. There was a reduced drug requirement for dogs receiving the therapeutic diet after three months (P = 0.058), and that decrease was significant at six months (P = 0.021) and nine months (P = 0.018). No improvement was seen at any time point in the control group. CONCLUSION: The results suggest that a novel therapeutic diet can assist in the management of cAD by helping to control pruritus and reducing reliance on medication.

Atopic dermatitis in West Highland white terriers - Part III: early life peripheral blood regulatory T cells are reduced in atopic dermatitis.

BACKGROUND: Regulatory T (Treg) cells are involved in homeostasis of immune regulation and suppression of inflammation and T-cell polarisation. Current knowledge regarding the role of Treg cells in the initiation of allergic disease is limited for both people and dogs. OBJECTIVES: To explore the role of circulating Treg cells and their possible influencing factors, on the development of atopic dermatitis (AD). METHODS AND MATERIALS: This study followed part of a birth cohort of West Highland white terrier dogs and classified them according to eventual clinical signs of AD (i.e. allergic versus healthy). The Treg phenotypes were assessed longitudinally by flow cytometry at 3, 3-12 and 12-36 months of age, and associated with development of AD. Different early life antigenic factors [endotoxins and allergens in house dust, Toxocara canis-specific immunoglobulin (Ig)E/IgG, allergen-specific and total IgE, skin microbiota] were measured at three months of age, and a possible association with Treg cell levels was assessed. RESULTS: The percentages of CD4+ CD25+ Foxp3+ Treg cells in healthy dogs were significantly higher at in 3-month-old (mean 4.5% healthy versus 3.3% allergic; P = 0.021) and <1-year-old (4.0% healthy versus 2.9% allergic; P = 0.028) dogs when compared to percentages of Treg cells in dogs that developed AD. There was a significantly positive correlation between the relative abundance of Lachnospiraceae on the skin and CD4+ CD25+ Foxp3+ Treg cells in puppies that became allergic (r = 0.568, P = 0.017). CONCLUSION AND CLINICAL IMPORTANCE: Further large-scale studies are needed to identify the practical value of these findings in AD diagnosis, treatment and prevention.

Sensitivity and specificity of a shortened elimination diet protocol for the diagnosis of food-induced atopic dermatitis (FIAD).

BACKGROUND: The gold standard to diagnose food allergy in dogs is an eight week elimination diet trial (EDT) followed by a re-challenge. A recent study demonstrated that a shorter EDT is possible if prednisolone is administered initially. HYPOTHESIS/OBJECTIVES: The goal was to evaluate the sensitivity and specificity of the EDT based on the number of relapses after prednisolone discontinuation. In addition, the aim was to determine whether the initial treatment length or the replacement of prednisolone with oclacitinib would influence the outcome. ANIMALS: Eighty-seven dogs with atopic dermatitis. METHODS AND MATERIALS: Dogs were fed an elimination diet and treated with either prednisolone or oclacitinib for two to three weeks. Relapsing dogs were treated a second time. In the absence of a relapse after two weeks off medication, dogs then were challenged. Dogs never achieving two weeks off treatment without relapse received the regular EDT. RESULTS: Fifty-eight of 87 dogs completed the study. Thirty-nine of 58 dogs received prednisolone; 21 of these were diagnosed with FIAD and had no relapse (n = 14), one relapse (n = 6) or two relapses (n = 1). Nineteen of 58 dogs received oclacitinib; 11 of these were deemed food-allergic and had no relapse (n = 7) or two relapses (n = 4). The initial treatment duration did not influence the outcome. The threshold of one relapse or less for the diagnosis of FIAD was associated with a sensitivity of 95% for prednisolone and 63% for oclacitinib. The specificity was 100% for both drugs. CONCLUSION AND CLINICAL IMPORTANCE: Initial prednisolone or oclacitinib use in EDT shortens the time to diagnosis of FIAD.

Hair follicle dystrophy in a litter of domestic cats resembling lanceolate hair mutant mice.

BACKGROUND: A new congenital hair-shaft abnormality resembling the lanceolate hair phenotype of rodents is described in a litter of four domestic short hair (DSH) cats. Data relating to hair shaft and follicle disorders remain scarce in veterinary medicine. OBJECTIVES: To describe and compare structural abnormalities in these cats with other hair dystrophies in cats and other mammals. ANIMALS: A DSH cat litter with progressive noninflammatory alopecia. METHODS AND MATERIALS: Histopathological evaluation, scanning and transmission electron microscopy, and X-ray based element analysis defined the hair and skin changes in cats born with alopecia. Findings were compared to archival data from normal cats and lanceolate hair (Dsg4lahJ ) and Keratin 75 (Krt75tm1Der ) mutant mice. RESULTS: Light and scanning electron microscopy of the hairs revealed lance- or spear-head shaped defects of the hair tip. Histological findings were swollen hair shafts, initially above the hair bulb matrix and later found in the distal parts of the telogen hair follicles, similar to those observed in Dsg4lahJ Krt75tm1Der mutant mice. Transmission electron microscopy of the hair shaft and hair follicles showed a loss in the normal structure of the guard hairs in the alopecic cats. There was a statistically significant decrease in sulfur content just below the defects in the hair shafts (trichothiodystrophy). CONCLUSION AND CLINICAL IMPORTANCE: A rare form of congenital alopecia resulting in follicular dystrophy is described in cats which is similar to hair follicle and hair-shaft changes reported in several mutant mouse strains with single gene mutations in adhesion molecules or keratin genes.

Venom immunotherapy for Hymenoptera allergy in a dog.

A 1.5-year-old male castrated dog was presented in anaphylactic shock after suffering an apparent bee sting. Immunotherapy with bee venom was initiated based upon history, skin testing and serological testing for allergen-specific immunoglobulin (Ig)E. The dog was maintained on venom immunotherapy for five years and showed no signs of adverse effects from therapy or from repeated bee stings.

Un chien castré de 1,5 ans a été présenté pour choc anaphylactique après avoir été piqué par une abeille. L'immunothérapie avec le venin d'abeille a été initié en fonction des commémoratifs, des tests cutanés et des tests sérologiques pour les immunoglobulines (Ig)E spécifiques d'allergènes. Le chien a été maintenu sous immunothérapie au venin pendant cinq ans et n'a montré aucun effet indésirable du traitement ou a la suite d'autres piqures d'abeilles.

Un perro macho castrado de 1,5 años se presentó en shock anafiláctico luego de sufrir una aparente picadura de abeja. La inmunoterapia con veneno de abeja se inició basándose en el historial, las pruebas cutáneas y las pruebas serológicas para la inmunoglobulina (Ig)E específica de alérgenos. El perro se mantuvo con inmunoterapia con veneno durante cinco años y no experimentó efectos adversos con la terapia o con repetidas picaduras de abeja.

Um cão macho castrado de 1 ano e meio de idade foi apresentado em choque anafilático após aparentemente ter sido picado por abelha. Iniciou-se a imunoterapia com veneno de abelha baseado na história clínica, testes alérgicos cutâneos e sorológicos para imunoglobulina (Ig)E alérgeno-específica. O cão foi mantido em imunoterapia com veneno por cinco anos e não apresentou nenhum efeito adverso do tratamento ou de novas picadas de abelha.

A comparative study of subcutaneous, intralymphatic and sublingual immunotherapy for the long-term control of dogs with nonseasonal atopic dermatitis.

BACKGROUND: Allergen-specific immunotherapy (ASIT) is the only causative treatment of canine atopic dermatitis (cAD). Different routes for administration of ASIT have been used; however, comparative studies are lacking. HYPOTHESIS/OBJECTIVES: The present study compared the efficacy and safety of subcutaneous (SCIT), intralymphatic (ILIT) and sublingual (SLIT) immunotherapy. ANIMALS: 30 atopic dogs were included and allocation to three groups (SCIT, n = 8; ILIT, n = 12; SLIT, n = 10) was determined by the owners. METHODS AND MATERIALS: ASIT was administered using routine protocols. The pruritus Visual Analog Scale (PVAS), canine atopic dermatitis extent and severity index (CADESI), concurrent medications and adverse events were recorded initially and one, three, six and 12 months later. The main outcome measure was return to a normal status, which included CADESI <12, PVAS <2.5 and medication score <10. RESULTS: Drop-outs were distributed evenly and 23 dogs finished the study (SCIT, n = 6; ILIT, n = 10; SLIT, n = 7). Adverse reactions to treatment were rare. At the start of the study, the three groups were homogeneous with respect to clinical signs and concurrent medications. After 12 months of ASIT, the CADESI and PVAS had decreased with a stable medication score in the ILIT and SCIT groups (P < 0.05), while all three scores had increased in the SLIT group. Return to normal state was achieved in one of six (17%) dogs receiving SCIT, in six of 10 (60%) dogs receiving ILIT and in one of seven (14%) dogs receiving SLIT. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that SCIT and ILIT improved clinical signs of cAD, whereas ILIT had a much higher return to normal rate.

Atopic dermatitis in a cohort of West Highland white terriers in Switzerland. Part II: estimates of early life factors and heritability.

BACKGROUND: There is accumulating evidence in studies of allergic diseases in humans and dogs that environmental experiences during the first months of life can influence the development of allergic disease. No prospective study has evaluated this in veterinary medicine. HYPOTHESIS/OBJECTIVES: To assess early-life risk factors for canine atopic dermatitis (cAD) and estimate its heritability. ANIMALS: A West Highland white terrier birth cohort (n = 107) followed up to three years of age recording the development of cAD. METHODS AND MATERIALS: The effect of environmental factors [house dust mites (HDM), hygiene, feeding, lifestyle] and early-life determinants [breeder, mode of delivery, birth season, sex, litter size, early-life immunoglobulin E (IgE) levels] were assessed, using Stata SE 15.1 statistical analysis. Heritabilities were estimated using the R program packages MCMCglmm and QGglmm. RESULTS: Maternal allergic status [P = 0.013, odds ratio (OR 3.3)], male sex (P = 0.06), mode of delivery (P = 0.12), breeder (P = 0.06), presence of HDM (P = 0.11) and environmental hygiene level (P = 0.15) were identified as possible influence factors by bivariate analyses. In the multivariate analysis the male sex was significantly associated with the development of cAD in the offspring (P = 0.03, OR 2.4). The heritabilities on the observed scale were 0.31 (direct), 0.04 (maternal genetic effects) and 0.03 (maternal permanent environmental effects). CONCLUSION AND CLINICAL IMPORTANCE: These results suggest that several environmental factors could influence the development of cAD but clearly demonstrate the genetic influence of the individual and the dam. Further studies are needed to identify specific environmental factors, which could be potential targets for primary disease intervention.

Atopic dermatitis in West Highland white terriers - part I: natural history of atopic dermatitis in the first three years of life.

BACKGROUND: Canine atopic dermatitis (cAD) is a common allergic skin disease that is known to affect individuals early in life; the natural history of its initial development has not been documented. Some breeds such as West Highland white terriers (WHWTs) are highly predisposed to cAD. OBJECTIVES: To follow 100 WHWT puppies during their first three years and to record the onset of clinical signs of cAD. ANIMALS: One hundred and eight puppies from 29 litters were included and 90 were followed for three years. METHODS AND MATERIALS: Puppies were examined initially while with their breeders. After adoption, the owners were contacted twice each year and dogs were examined by veterinarians if signs compatible with cAD were detected; diagnosis of cAD was by two different definitions. The onset, location of the clinical signs and severity of cAD, as well as co-morbidities were recorded. RESULTS: The prevalence of cAD in the cohort was 52%. Most affected dogs (60%) developed signs of cAD during their first year of life and males were over-represented. The location of clinical signs mirrored those of previous descriptions. The severity of cAD was mild in 36% and severe in 13% of affected WHWTs. Dogs with cAD often exhibited other atopic diseases, but only gastro-intestinal signs were significantly different between WHWTs with and without cAD. Adverse reaction to foods was diagnosed in 24% of dogs. CONCLUSION AND CLINICAL IMPORTANCE: This longitudinal study of puppies from a predisposed breed sheds new light on the early development of cAD in WHWTs.

The usefulness of short-course prednisolone during the initial phase of an elimination diet trial in dogs with food-induced atopic dermatitis.

BACKGROUND: Food allergy is a possible cause of atopic dermatitis (AD) in dogs; it is typically diagnosed following an eight-week elimination diet trial (EDT) and a provocation with the original diet. This lengthy procedure is difficult for owners and its interpretation may be unclear. HYPOTHESIS/OBJECTIVES: To test the effect of prednisolone used in the first weeks of an EDT in order to reduce the total time period for diagnosis. The goal was to perform food challenges earlier than after the traditionally recommended eight weeks. ANIMALS: Fifty-three dogs with AD were included in the study. METHODS AND MATERIALS: All dogs were fed a commercially available extensively hydrolyzed protein-based commercial pet food and treated with prednisolone for at least two weeks to control pruritus and inflammation. Dogs were challenged two weeks after prednisolone finished, provided that no flare had occurred. Dogs with relapsing signs were fed the hydrolyzate for at least eight weeks with or without further prednisolone treatment. RESULTS: Ten of 53 dogs (19%) had no relapse after two weeks off prednisolone: they were subsequently challenged with their regular food, had a relapse of signs and were diagnosed with a food-induced AD within four to six weeks of starting the EDT. In the other dogs, signs remained uncontrolled without prednisolone or relapsed rapidly after its discontinuation: they were considered nonfood-allergic after an eight week EDT. CONCLUSION AND CLINICAL IMPORTANCE: This study demonstrates that a shorter EDT is possible if the allergic pruritus and inflammation are initially controlled with a short course of glucocorticoids. This shortened trial is likely to improve owner adherence and facilitate the diagnosis of food allergy.

Circulating CD4(+)CD25(+)Foxp3(+) T regulatory cell levels in an experimental model of canine atopic dermatitis.

BACKGROUND: The pathogenesis of canine atopic dermatitis (cAD) is characterized immunologically by an imbalanced T-cell response. Mechanisms of immune regulation in cAD have not yet been completely elucidated. OBJECTIVES: To investigate peripheral blood T regulatory (Treg) cells and their associated cytokines (TGF-ß and IL-10) in an experimental model of cAD. ANIMALS: Eight beagle dogs that were initially naïve and subsequently sensitized to house dust mites (HDM). METHODS AND MATERIALS: T regulatory cell phenotyping was performed by flow-cytometric analysis on peripheral blood; serum cytokine levels were measured by ELISA, before sensitization and after challenge with HDM allergens. Additionally, clinical scores and allergen-specific IgE were determined. RESULTS: After challenge of sensitized dogs to HDM allergen, a significant increase of Treg cells and simultaneous decrease in the serum TGF-ß were observed. However, in most dogs, serum IL-10 values were below the detection limit. Treg cell proportions before sensitization were significantly negatively correlated with the HDM-specific IgE levels and clinical scores after induction of AD signs. CONCLUSION AND CLINICAL IMPORTANCE: The results confirm that Treg responses are involved in the pathogenesis of an experimental model cAD. Further investigations are required to clarify the precise immune modulating function of canine Treg cells and their interplay with other immune cell types.

Itch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors.

Chronic itch is a highly debilitating condition affecting about 10% of the general population. The relay of itch signals is under tight control by inhibitory circuits of the spinal dorsal horn, which may offer a hitherto unexploited therapeutic opportunity. Here, we found that specific pharmacological targeting of inhibitory α2 and α3GABAA receptors reduces acute histaminergic and non-histaminergic itch in mice. Systemic treatment with an α2/α3GABAA receptor selective modulator alleviates also chronic itch in a mouse model of atopic dermatitis and in dogs sensitized to house dust mites, without inducing sedation, motor dysfunction, or loss of antipruritic activity after prolonged treatment. Transsynaptic circuit tracing, immunofluorescence, and electrophysiological experiments identify spinal α2 and α3GABAA receptors as likely molecular targets underlying the antipruritic effect. Our results indicate that drugs targeting α2 and α3GABAA receptors are well-suited to alleviate itch, including non-histaminergic chronic itch for which currently no approved treatment exists.

An open study on the efficacy of a recombinant Der f 2 (Dermatophagoides farinae) immunotherapy in atopic dogs in Hungary and Switzerland.

BACKGROUND: Previously published studies evaluating a recombinant Der f 2-based immunotherapy have demonstrated efficacy in the treatment of dogs experimentally and naturally sensitized to house dust mites (HDM). Der f 2 sensitization is thought to play a minor role in European atopic dogs sensitized to HDM. OBJECTIVE: The study evaluated the short-term efficacy of a recombinant Der f 2 product in the treatment of naturally sensitized atopic dogs in Switzerland and Hungary. ANIMALS: Fifteen atopic dogs with positive test reactions to Dermatophagoides farinae (Df). MATERIAL AND METHODS: Recombinant Der f 2 allergens were injected subcutaneously at increasing doses once weekly for 6 weeks. Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), pruritus Visual Analog Scale (pVAS) and medication scores were assessed at days 0 and 42. Efficacy was recorded as excellent, good, fair or poor, depending on the number of scores decreasing by more than 50%. RESULTS: Mean CADESI, pVAS and medication scores at inclusion were 35, 6 and 15 (SD = 30, 2, 7), respectively. At Day 42 the scores decreased to 8, 3 and 5, respectively (Wilcoxon matched pairs signed rank tests P = 0.0002, 0.002 and 0.001). Four dogs were classified as excellent responders with a reduction of >50% in all three scores. Nine dogs were classified as good (five) or fair (four) responders and scores deteriorated in two dogs. CONCLUSION: These data suggest that recombinant Der f2 allergens may be as effective and show benefit faster than traditional allergen immunotherapy in European dogs sensitized to Df.