Tag Archives: atopic dermatitis

Changes in Skin “Microbiome” During Canine Atopic Dermatitis Could Lead to Antibiotic-Free Therapies

Atopic dermatitis (AD), a chronic inflammatory skin condition and the most common form of eczema, is estimated to afflict as much as 10 percent of the U.S. population, and is much more common now than it was 50 years ago. Veterinary clinical estimates also show that approximately 10 percent of dogs have atopic dermatitis.

How AD arises isn’t yet fully understood, but a study from researchers from the Perelman School of Medicine at the University of Pennsylvania and Penn’s School of Veterinary Medicine, have uncovered important insights about the association of AD in dogs compared to humans. The study appears online in the Journal of Investigative Dermatology.

atopy

To a greater extent than mouse models, canine AD shares important features of the human version. For example, in both humans and dogs AD has been linked to abnormal blooms of Staphyloccocus bacteria on the skin – mostly Staphyloccocus aureus in humans, and Staphyloccocus pseudintermedius in dogs.

In the study, the research team, comprised of veterinary dermatologists, microbiologists, pathologists, and primary scientists, tracked the bacterial populations, or “microbiomes,” on dogs’ skin, and key properties of the skin’s barrier function during an occurrence of AD, and again after standard treatment with antibiotics. During the flare, researchers observed a sharp decrease in the diversity of the skin bacterial population as certain bacterial species proliferated, along with a decrease in the skin’s protective barrier. With antibiotic therapy, both measures returned to normal levels.

“In both canine and human atopic dermatitis we hypothesize there is a similar relationship among skin barrier function, the immune system, and microbes, even if the individual microbe species aren’t identical,” said senior author Elizabeth A. Grice, PhD, an assistant professor of Dermatology and Microbiology at the Perelman School of Medicine at the University of Pennsylvania. “The hope is that insights gained from this study and others like it will enable us one day to treat this condition by altering the skin’s microbiome without antibiotics.”

Thirty-two dogs (15 with canine AD, and 17 without) from Penn Vet’s Ryan Hospital were enrolled in the study. On three occasions – first during AD flares in the affected dogs, then after 4-6 weeks of targeted antibiotics, and finally 4-6 weeks after treatment concluded – the team took swabs from several areas of skin on the affected dogs. They surveyed the microbiomes of these samples by amplifying and sequencing copies of a key bacterial gene whose DNA sequence is distinct for different bacterial species.

Samples from the dogs with ongoing AD had almost ten times the proportion of Staphylococcus species, compared to the control dogs. Corynebacterium species also rose, as they typically do in humans with AD. A standard measure of the diversity of the dogs’ skin microbiomes also decreased sharply, indicating that the abnormal bacterial proliferation – chiefly from S. pseudintermedius – had crowded out other, harmless or potentially beneficial bacterial species.

At the second visit, immediately following completion of antibiotic therapy, the abundance of Staphyloccocus and Corynebacterium on the skin of affected dogs and the diversity of their skin microbiome had returned almost to the levels seen in the control dogs. Those measures remained largely the same in the third visit, after antibiotic therapy was finished.

Impairment in the skin’s ability to work as a “barrier” to keep moisture in and harmful bacteria out is considered a possible factor in triggering or advancing AD. Under the guidance of Elizabeth Mauldin, DVM DACVP, DACVD, an associate professor of Dermatopathology in Penn’s School of Veterinary Medicine, the researchers also tested skin barrier function in the dogs at each of their three visits. Results showed that the low-bacterial-diversity state of AD flares – corresponding to lesions of AD on the skin – correlated with impairments in the skin barrier, as indicated by a standard test of the water loss rate through the skin (TEWL).

“We don’t know if the bacterial overgrowth is weakening the skin’s barrier function or a weakening of the barrier is enabling the bacterial overgrowth, but we do know now that they’re correlated, and that’s a novel finding,” Grice said.

The research team is now conducting further studies of the microbiome in canine atopic dermatitis, in particular to determine how antimicrobial therapy promotes bacterial resistance.

“This investigation is a prime example of the One Health approach to research, a recognition that we’re dealing with the same disease processes in animals and in humans,” said lead author Charles Bradley, VMD, DACVP, a lecturer and dermatopathologist of pathobiology in Penn’s School of Veterinary Medicine. “The findings highlight the importance of dogs as a model for human dermatitis and help lay the groundwork for new therapeutic strategies, for example involving microbiome transplants to compete with the harmful bacterial overgrowth, as an alternative to antibiotic therapy.”

Source:  University of Pennsylvania media release

Researchers identify gene associated with eczema in dogs

A novel gene associated with canine atopic dermatitis has been identified by a team of researchers led by professors Kerstin Lindblad-Toh, Uppsala University and Åke Hedhammar, SLU, Sweden. The gene encodes a protein called plakophilin 2, which is crucial for the formation and proper functioning of the skin structure, suggesting an aberrant skin barrier as a potential risk factor for atopic dermatitis.

Details appear in the open-access journal PLoS Genetics.

Atopic dermatitis (or eczema) is an inflammatory, relapsing non-contagious skin disease affecting about 3-10 percent of dogs. The skin of a patient with atopic dermatitis becomes easily irritated by various allergens such as certain types of food, pollens or house mites. Such irritation causes very strong itching which leads to scratching, redness and flaky skin that becomes vulnerable to bacterial and yeast infections.

Despite many scientific efforts, little has been known about the genetics of the disease. In their study, researchers from Uppsala University, SLU and Broad Institute, compared DNA samples from a large group of German shepherd dogs affected by atopic dermatitis with DNA coming from healthy dogs to reveal the specific DNA segment associated with the disease.

“With the help of pet owners, we have managed to collect a unique set of DNA samples from sick and healthy dogs which allowed us to gain insight into atopic dermatitis genetics,” said first author Katarina Tengvall, Uppsala University.

Purebred dogs such as German shepherds have been selected for specific physical features for several generations. Selection led to an inadvertent enrichment for disease-risk genes in certain breeds. Moreover, the resulting architecture of canine DNA makes it easier to pinpoint segments that carry these disease risk-genes. This helped the researchers to reveal the genetics of atopic dermatitis. They found a region associated with the atopic dermatitis containing the gene PKP-2, which encodes Plakophilin-2, a protein involved in the formation and maintaining of the proper skin structure.

“The finding that certain variants of the PKP-2 gene may increase the risk of developing the disease opens new possibilities in understanding the disease mechanism leading to atopic dermatitis,” continues Katarina Tengvall.

These findings will not only lead to better understanding of the disease, which may lead to better treatment strategies long term. It also opens up the possibilities of development of a genetic test for the disease.

“Our study suggests that plakophilin-2 and an intact skin barrier is important to avoid atopic dermatitis”, says senior author, Kerstin Lindblad-Toh, professor at Uppsala University and Director of SciLifeLab Uppsala. “Another gene involved in the skin barrier has recently been linked to human atopic dermatitis emphasizing the similarity between canine and human atopic dermatitis” said Kerstin Lindblad-Toh.

Source:  AlphaGalileo Foundation media statement

Dogs respond to new skin allergy treatment

Dogs that would try to run the other way from allergy injections are finding a new oral drop to be much more palatable.  In fact, some dogs think they are a treat!

On 25th July,  at the World Congress of Veterinary Dermatology in Vancouver, British Columbia,  Dr Douglas DeBoer of the University of Wisconsin-Madison School of Veterinary Medicine presented his work which shows that placing allergy drops under a dog’s tongue can be as effective as allergy injections.

Dr DeBoer treated 217 dogs for skin allergies in his study using the drops.   Approximately 60 percent of the dogs improved significantly.  The drops require administering under the tongue twice each day.

copyright Dr Douglas DeBoer

In contrast,  allergy shots are injected approximately every 14 days.   The cost of the treatments are comparable.

Dogs can sometimes suffer a life-threatening anaphylactic reaction to allergy shots.  Even those dogs treated in the study that had previously had such a dangerous reaction did not have it when using the drops.   “Drops appear to be safer than shots in this respect,” said Dr DeBoer.

Atopic dermatitis (an itchy skin inflammation) is an allergic reaction from house dust, pollen, and mold.  Injections aim to introduce a small amount of the allergens to trigger an immune response.  The drops work on a different mechanism involved in the allergy.  Dogs that had failed to respond to allergy injections did respond to the drops.

Best of all, the drops have a sweet taste which attracted the dogs.  Some dogs came running when they heard the bottle of drops opened…