The world of skin allergies in pets

A pet’s skin reflects its health, yet nearly 30% of dogs suffer from skin allergies. Commonly referred to as allergic dermatitis, this skin disease can be persistent and recurrent throughout the pet’s life unless veterinarians step in.

Most common skin disease

Allergic dermatitis is an umbrella term for skin irritations caused by food allergies, contact with certain substances, reactions to fleas, or atopic dermatitis. Almost half of all skin allergies in dogs are diagnosed as atopic dermatitis (AD), leaving many breeds predisposed to frequent skin infections, a dysfunctional skin barrier, and abnormal immune responses to pathogens that breach the skin. Compared to allergies, AD is more complex because of genetic and environmental factors that combine and lead to an allergic response.

Some of the most popular dog breeds are predisposed to it, including the Boxer, Bulldog, Labrador Retriever, Pug, and West Highland White Terrier. In cats, pure breeds appear more at risk of developing atopy-like dermatitis. With the prevalence of AD continuing to grow, it is becoming apparent that preferential breeding isn’t necessarily the main factor.

The role of hygiene

The pet’s living environment also plays a crucial role. This is where the ‘hygiene hypothesis’ becomes relevant. This has been proven in humans, and studies suggest it is also applicable in cats and dogs.

In line with this theory, the more time a pet spends indoors, the less exposure it will have to beneficial bacteria found outdoors. The more processed food it eats, the less it will be exposed to bacteria and parasites in foraged diets. In combination, this limits the pet’s exposure to naturally occurring bacteria in its environment, sensitizes its immune system, and predisposes it to this skin condition.

3 triggers of skin allergies

Attempting to pinpoint what triggers an allergic response can be a frustrating process. Generally, there are 3 main factors to consider:

• Genetics Some breeds are predisposed to developing allergies. For example, when an allergen comes into contact with the skin, it triggers an immune-mediated response that stimulates immunoglobulin E (IgE) antibody production (also known as Type 4 hypersensitivity). When serum samples from 30 different breeds were tested for elevated IgE, the Boxer was most reactive to allergens.
• Environment The allergens that pets are exposed to depend on their environment. A study in northern Italy found that nearly 40% of atopic dogs are reactive to indoor allergens (specifically dust mites), compared to only 8% testing positive for outdoor allergens.
• Diet When 297 dogs were tested for cutaneous adverse food reactions (CARFs), the most common food allergens were found to be beef (34%), dairy (17%) and chicken (15%). The trend is similar in cats: beef (18%), fish (17%) and chicken (5%).

Maintaining the skin barrier

The skin barrier is both microbiological and physical. On the outer surface is the skin microbiome, representing the first line of defense. This microbiome consists of bacterial colonies that communicate with cells underneath the skin to initiate an immune response. In the case of AD, microbial diversity decreases as Staphylococcus begins to dominate and irritate the skin. The bacterial cell wall components and toxins released by this dysbiosis are enough to impair the skin barrier.

Next is the skin itself, which forms a physical barrier. While there is no definitive evidence suggesting that AD leads to a primary skin barrier impairment, inflammation and scratching during flare-ups cause secondary impairment. Once the integrity of the skin barrier is lost, any allergens that come into contact with the skin are more easily absorbed and trigger a dysregulated immune response. A recent study sampling peripheral blood found an increase in helper T lymphocytes (key immune mediators) in atopic dogs. In particular, disease severity was correlated with a subset of CD4+ CD25+ expressing regulatory T cells.

The importance of keratinocytes

Just beneath the skin’s surface are the keratinocytes. These cells maintain skin integrity and replenish the epidermis, and it has recently been discovered that keratinocytes also coordinate the skin’s immune response to invading allergens. In healthy animals, keratinocytes adhere tightly with neighboring cells and release cytokines that mediate inflammation. In the case of AD, these adhesions are lost due to increased interleukin 33 (IL-33) expression, leaving the skin porous and susceptible to allergens.

Additionally, Langerhans cells are located within the epidermis where they coordinate immune tolerance. These cells are not only responsible for mounting an immune response, but also for preventing excessive immune activation. Studies suggest that AD leads to decreased expression of IL-34, a cytokine involved in the maturation and proliferation of Langerhans cells. This combination of increased skin permeability and decreased immune surveillance leaves the skin vulnerable to allergens and AD.

Treating allergies

Treatment of AD should be aimed at avoiding broad- spectrum antibiotics and immunosuppressive steroids that only provide temporary relief. New research is focusing on using biologics to target cytokines that mediate AD. In particular, IL-31 has received much attention because of its role in pruritis. This cytokine is secreted from T helper 2 (Th2) cells and is capable of interacting with other immune cells, keratinocytes and nerve fibers.

While there has been some success in formulating a vaccine against IL-31, the primary approach has been to use a caninized monoclonal antibody designed to neutralize IL-31 and stop itching. The idea is that AD becomes much more manageable once the itching is under control. This treatment uses Lokivetmab (also known as Cytopoint), which is effective against allergic and atopic dermatitis. A recent study looking at 62 dogs with moderate to severe pruritus brought on by allergies (including AD) found that a single dose of Cytopoint resolved 94% of flare-ups by Day 7 and 100% by Day 56. Of these dogs, 34% were previously diagnosed with AD. Fortunately, IL-31 is also a promising target in cats.

Other treatment options include allergen-specific immunotherapy, but this takes time to desensitize the immune system and requires veterinarians to know which allergen is problematic. In most cases, more than one allergen is involved.

Growing knowledge

Skin allergies in pets are often lifelong conditions that need to be managed. While our knowledge of veterinary immunology continues to grow, it still lags behind human medicine. Fortunately, much of this information has been transferable to veterinary medicine, especially in the case of allergic dermatitis and treatment strategies.