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.

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.

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.

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.

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.

Probable walnut-induced anaphylactic reaction in a dog.

BACKGROUND: Anaphylaxis due to nuts is frequent in humans; to the best of the authors' knowledge, it has not been reported previously in dogs. CASE REPORT: A 5-year-old female, intact, Vizsla dog was presented with acute diarrhoea, vomiting, respiratory distress and erythematous wheals. The dog had eaten walnuts, which she had been fed in small amounts for years, hours before the onset of clinical signs. A diagnosis of generalized anaphylaxis was made. Skin testing and Western blotting revealed positive results with walnuts and hazelnuts. CONCLUSIONS AND CLINICAL IMPORTANCE: This case report illustrates the need for a thorough food history and for recognition that a dog may experience severe allergic reactions to unusual and regularly fed food items. It also shows that allergen specific tests may help to confirm the diagnosis and help in planning the dog's future dietary regime.

Triggers, risk factors and clinico-pathological features of urticaria in dogs - a prospective observational study of 24 cases.

BACKGROUND: Urticaria and anaphylaxis are frequently encountered in veterinary practice, but little is known about the causes and relative frequencies of these reactions. HYPOTHESIS/OBJECTIVES: This study was designed to improve current knowledge on the triggers, risk factors and clinico-pathological features of urticaria. ANIMALS: Twenty four dogs with signs of urticaria with or without anaphylaxis. METHODS: The study included dogs with cutaneous immediate-type hypersensitivity reactions. The cases were grouped by clinical severity into either an urticaria or an anaphylaxis group. All treatments and diagnostic tests (haematology, biochemical profile, allergy investigation) were recorded. A causality algorithm for urticaria and anaphylaxis (ALUA) was designed to determine the probability of the identified triggers and cofactors. Disease incidence, breed, age and gender predispositions were evaluated statistically. RESULTS: Sixteen of 24 urticaria cases were associated with anaphylaxis whilst 8 of 24 were confined to the skin. The annual hospital incidence was 0.12%. Females seemed to be over-represented (2.4:1) and most of the dog breeds were pure breed (22 of 24), with Rhodesian ridgeback, boxer, beagle, Jack Russell terrier, French bulldog and Vizslas over-represented. In addition to skin lesions, the most frequently and severely affected organ systems were the gastrointestinal and cardiovascular systems. The predominant blood abnormalities were elevated lipase and alanine aminotransferase values. Insects, food and drugs were the most commonly identified triggers. CONCLUSIONS: To the best of our knowledge, this is the first study describing the trigger factors and clinico-pathological features of dogs with urticaria in veterinary medicine. Insects, food and drugs were the most frequently detected triggers.