Canine Health Foundation Grant #02651

Abstract: Canine atopic dermatitis (CAD) is a common allergic skin disease of dogs with a strong genetic basis. CAD can severely affect the health and well-being of dogs and current diagnosis of CAD requires time-consuming and expensive procedures for the owner. Furthermore, the molecular mechanisms underlying this condition are not well understood. Evidence from human studies suggests that several variants of atopic dermatitis (AD) exist with different mechanisms and responses to treatment. Therefore, new approaches to identify molecular markers that can help with better diagnosis and management are warranted. CAD and human AD are associated with changes in the composition of lipids in the epidermis which may precede the inflammation or result from the inflammation. The investigators will analyze the lipid composition of the epidermis and blood of healthy dogs in comparison to dogs with CAD using a novel analytical method developed by their interdisciplinary team. The results of this work could lead to new, minimally-invasive tests for the diagnosis of CAD and for the prediction and monitoring of the response of CAD patients to treatment.

Publications: Franco J, Rajwa B, Gomes P, Ferreira C, HogenEsch H (2021) Changes in the lipid composition of the epidermis and blood in dogs with atopic dermatitis identified by nontargeted lipidomics. In preparation.

Presentations: None at this time.

Year End 1 Report to Grant Sponsor from Investigator (5/26/2020): Canine atopic dermatitis (CAD) is a common allergic skin disease of dogs with a strong genetic basis. Evidence from human studies suggests that several variants of AD exist with different mechanisms and responses to treatment. Current diagnosis of CAD requires time-consuming procedures that involve a considerable cost to the owner. Therefore, new approaches to identify molecular markers that can help with better diagnosis and management of the disease are warranted. In this study, we are using our tailored methodology for lipid biomarker discovery in CAD. 30 atopic dogs and 30 healthy dogs have been recruited. Patients are males and females of several different breeds and ages with seasonal or year-round itch. CAD patients are being treated with either Apoquel®, Cytopoint® or prednisone and followed for 2 months to evaluate the lipid changes in their skin and blood. Using non-invasive sampling procedures, we have collected samples from the skin of healthy controls and from affected and non-affected areas of the skin of CAD patients, as well as blood. Preliminary statistical analysis demonstrates that lipid fingerprints of the blood and skin accurately classify samples from healthy dogs and CAD patients, whereas more overlap appears to be present in the lipid profile of lesional and nonlesional skin of CAD patients. MRM-profiling approach allows an unbiased analysis of the lipids that may result in new diagnostic biomarkers to classify disease phenotypes that will drive the development of new therapies.

Final Report to Grant Sponsor from Investigator (4/30/2021): We enrolled 30 dogs with mild to moderate atopic dermatitis and 30 healthy control animals in the study. The dogs with atopic dermatitis were treated with either Apoquel® (n=17) or Cytopoint® (n=10), whereas one dog was switched from Apoquel® to Cytopoint®, one dog was treated with prednisone followed by Apoquel®, and one dog was treated with a topical shampoo. Both Apoquel® and Cytopoint® reduced the clinical severity of the skin lesions during 8 weeks of treatment. Skin swabs and blood samples were collected from the atopic and control dogs at Day 0, and from the atopic dogs at 4 and 8 weeks after initiation of treatment. Analysis of the lipid composition of the skin and blood samples by mass spectrometry showed significant differences between atopic and control dogs. In addition, nonlesional skin of atopic dogs had a different skin lipid profile from that of control dogs. Treatment reversed the changes in lipid composition both in the skin and the blood; however, there was marked variation in the direction and extent of the changes between individual dogs. This research suggests that atopic dermatitis is associated not only with changes in lipids in the skin but also systemic changes. These lipid changes can potentially help in the diagnosis and evaluation of treatment responses in canine atopic dermatitis.