PDE4D and miR-203 are promising biomarkers for canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific biomarkers available to diagnose CAD, and the current diagnosis is based on a combination of criteria including patient history, clinical signs, and exclusion of other relevant differential diagnoses. METHODS AND RESULTS: We examined the gene expression of phosphodiesterase 4D (PDE4D) in peripheral blood mononuclear cells (PBMCs), as well as miR-203 and miR-483 in plasma, in three groups: healthy dogs, CAD dogs, and other inflammatory pruritic skin diseases (OIPSD) such as pemphigus foliaceus, scabies, cutaneous lymphoma, and dermatophytosis. Our results showed that PDE4D gene expression in the CAD group is statistically higher compared to those in the healthy and OIPSD groups, suggesting PDE4D may be a specific marker for CAD. Nevertheless, no correlation was found between PDE4D gene expression levels and the lesion severity gauged by CAD severity index-4 (CADESI-4). We also showed that miR-203 is a generic marker for clinical dermatitis and differentiates both CAD and OIPSD inflammatory conditions from healthy controls. CONCLUSIONS: We show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted.

Canine Atopic Dermatitis: Prevalence, Impact, and Management Strategies.

Atopic dermatitis (AD) is a common inflammatory and pruritic allergic skin disease in humans and dogs worldwide. The pathogenesis of AD is multifactorial, immunologically complex, and may involve genetic factors, epidermal barrier dysfunction, microbiome changes, immune dysregulation, and allergic sensitization. Across species, prevalence of AD is on the rise. At present, there is no cure for canine AD (CAD). The treatment for CAD is multifaceted and aimed at controlling the pruritus, associated inflammation, and infections, repairing the skin barrier function, and dietary management. This review presents data on prevalence, impact, and complex immunological interactions in AD with a focus on subsequent management of the disease in the canine population. A multimodal approach for management of CAD to address varying clinical signs and responses to therapies is discussed.

Comparison of three canine nose guards for reduction of ultraviolet (UVA and UVB) solar radiation.

BACKGROUND: Protection from solar ultraviolet (UV) radiation is paramount for some dermatological conditions, yet there are no studies assessing UV nose guards for dogs. OBJECTIVES: Compare the ability of three nasal guards to block solar UV radiation (UVR) from the canine nose, using two commercial products and one created by the authors. ANIMALS: Four fabric model dogs were used in this prospective controlled trial. MATERIALS AND METHODS: Each model had a UV dosimeter applied to the dorsal nose and anterior nasal planum. Three models had nose protectors applied: (1) a mesh hood (OutFox Field Guard, OutFox For Dogs); (2) a fabric nose shield (Nose Protector, Dog Nose Protectors); or (3) a basket muzzle with ultraviolet protection factor (UPF) 50+ fabric developed by the authors. The control had no protective device applied. All the models were placed in direct sunlight and measurements taken over nine 2 h time periods. Total cumulative UVR was analysed for each location and type of guard or control. RESULTS: All guards provided statistically significant UV protection compared to control at all time points (p < 0.001). The basket muzzle with UPF 50+ guard was consistent in protecting the dorsal and anterior nose, blocking 94.2% and 94.3% UVR, respectively. The fabric nose protector blocked 99.2% UVR from the dorsal and 82.9% anterior. The mesh hood blocked 72.5% of UVR dorsal and 71.4% anterior. CONCLUSIONS AND CLINICAL RELEVANCE: Two guards were superior in blocking UVR; however, the choice of UV guard in a clinical setting depends on an individual's disease location and tolerance of the device.

Seroprevalence of Borrelia burgdorferi in Shelter Dogs in Los Angeles County.

The primary aim of this study was to establish the seroprevalence of Borrelia burgdorferi in dogs in Los Angeles County by testing shelter and client owned dogs with 2-tier ELISA testing. A secondary goal was to create a pilot study for evaluation of all Borrelia positive dogs for dermatologic signs of infection. This is the first study to look at the seroprevalence of Borrelia burgdorferi in dogs in Los Angeles County. We hypothesized that the prevalence is higher than previously predicted (0.5%-1%). 422 shelter and client owned dogs were tested for Borrelia burgdorferi with an ELISA cageside test. Seropositive animals were to have additional blood sent to a reference laboratory for further ELISA testing and examined for dermatologic manifestations of Borrelia burgdorferi. No dogs tested positive for Borrelia burgdorferi in this study population, however 3 dogs tested positive for Ehrlichia and 1 for Anaplasma, 2 other tick-borne pathogens uncommon in southern California. This is the first study in Los Angeles County to employ active surveillance regarding an important zoonotic disease. The findings prove that results from these types of studies may differ from those of predictions and passive surveillance. Dogs are sentinels for disease in people and focus should be placed on monitoring antibody levels in canine patients. This study carried out in an endemic area may prove more valuable in assessing cutaneous manifestations of Borrelia burgdorferi and provide a foundation for future hypothesis driven studies.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

A double-blinded placebo-controlled evaluation of adipose-derived mesenchymal stem cells in treatment of canine atopic dermatitis.

Mesenchymal stem cells (MSCs) have emerged as a new therapy for various immune-mediated inflammatory diseases. In this study we perform the first double-blinded, placebo-controlled evaluation of the efficacy of adipose-derived allogenic canine MSCs for the treatment of canine atopic dermatitis (cAD). Enrolled canine patients were randomly divided into placebo (PBS saline), low-dose (5 × 105 cells/kg), and high-dose (5 × 106 cells/kg) treatment groups. Each patient received three subcutaneous MSCs treatments or PBS saline at four-week intervals with injections at five sites. Patients were monitored by physical exams, pruritus visual analog scales (PVAS) signed by the primary caretaker, canine atopic dermatitis extent and severity index-4 (CADESI-4) scores by two veterinarians, and complete blood count and serum chemistry analysis along with laboratory analysis for potential biomarkers. Patients were kept off any immune-modulating drugs during the study period, and oral antibiotics and topicals were used for managing pruritus and secondary infections. The PVAS scores and the serum miR-483 levels were significantly lower in the high dose group compared to the placebo group at day90 post first-treatment. The CADESI-4 scores of the high dose group also showed downward trends. No severe adverse effects were observed in any patient in this study. The high dose MSC treatment is efficacious in alleviating the clinical signs of cAD until 30 days after the last subcutaneous administration of MSCs, and miRNA-483 may be a reliable prognostic biomarker for cAD. The MSCs efficacy and potential biomarkers should be further explored by a larger scale clinical trial.

Adverse events associated with venomous insect immunotherapy and clinical outcomes in 82 dogs (2002-2020).

BACKGROUND: Limited information is known on adverse events and efficacy associated with venomous insect immunotherapy (VIT) in canine patients. OBJECTIVES: To assess adverse events associated with VIT and perceived efficacy of VIT. ANIMALS: Records from 82 client-owned animals which received VIT were assessed. METHODS AND MATERIALS: A retrospective review of records from 2002 to 2020. Clinical history, adverse events during therapy and observations following field stings were collected from all records. Patients were grouped into reactors and nonreactors based on whether or not an adverse event had occurred during therapy. Records were evaluated to determine if a field sting had occurred and the severity of the reaction was compared to pretreatment reaction. RESULTS: Of 82 patients that were identified, 26 experienced a minimum of one adverse event. No deaths or severe anaphylactic reactions were reported. The most common adverse event was gastrointestinal upset. The overall reaction rate per injection was 2.8%. Only variation in sensitisation level (the minimum concentration of venom which elicited a positive intradermal reaction) was significantly different between groups (P = 0.014). Forty-one field challenges in 26 patients were documented. Therapy reduced the severity of reactions in 87.8% of challenges. No deaths were reported. CONCLUSION: Venom immunotherapy appears to be a safe and efficacious treatment for prevention of anaphylaxis due to insect stings in canine patients.

Phosphodiesterase 4D, miR-203 and selected cytokines in the peripheral blood are associated with canine atopic dermatitis.

Canine Atopic Dermatitis (AD) is a common complex and multifactorial disease involving immune dysregulation, genetic predisposition, skin barrier defects, environmental factors and allergic sensitization. To date, diagnosis of canine AD relies on a combination of patient history, clinical examination, allergy testing and response to diet trials/therapies with no reliable biomarkers available to distinguish AD from other diseases with similar clinical presentations. A handful of studies to identify potential biomarkers in the peripheral blood of AD dogs and healthy controls have been performed with some showing inconsistent and contradictory results. In this study, we, for the first time, report statistically significant increases in expression of phosphodiesterase 4D (PDE4D) gene in peripheral blood mononuclear cells (PBMCs) and miR-203 in plasma from AD dogs compared to healthy controls. In addition, we report a statistically non-significant change of the CD4+/CD8+ ratio, a dramatic decrease of three gene markers (PIAS1, RORA and SH2B1) as well as a panel of differential expression of cytokines in AD dogs in comparison to the healthy controls. Our study provides important insight into the complexities of canine AD, and further studies to verify the specificity of these findings for canine AD at a larger-scale are warranted.

Evaluation of dermoscopy in the diagnosis of naturally occurring dermatophytosis in cats.

BACKGROUND: A rapid, accurate screening test for dermatophytosis in cats is desirable in clinical and shelter medicine. In human dermatology, dermoscopy is used to identify dermatophyte-infected hairs by their characteristic comma hair appearance. Similar "comma-like" hairs have been observed in infected cats. HYPOTHESIS/OBJECTIVES: The purpose of this study was to evaluate the usefulness of dermoscopy for the diagnosis of naturally occurring dermatophytosis compared to fungal culture. ANIMALS: A total of 67 cats were enrolled. METHODS: This was a descriptive field study. All cats were evaluated by dermoscopy and fungal culture. Dermoscopy was performed with a hand held nonpolarized light dermoscope. RESULTS: Three dermatophyte pathogens were isolated via fungal cultures in 36 cats: Microsporum canis (n = 31), Microsporum gypseum (n = 3) and Trichophyton mentagrophytes (n = 2). Dermoscopy was positive in 21 of 36 cats with culture-confirmed dermatophytosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Dermoscopy may be a useful point-of care-test to identify infected hairs to sample for dermatophyte cultures, but a definitive diagnosis for dermatophytosis should be based on clinical signs and the results of multiple diagnostic tests.