Developments in small animal veterinary dermatology

I recently received a visit from a pair of unrelated 8-year-oldhousemate West Highland White terriers referred for chronic pruritic skin disease (Figure 1). Both Westies, a spayed female and a castrated male dog, had exhibited skin and ear disease starting before they were 1 year of age. Their histories were long and convoluted but in short, both dogs suffered from seasonal atopic dermatitis, recurrent pyoderma, and recurrent otitis externa. Previous therapies had included oral corticosteroids and cyclosporine. To my surprise, while the clinical appearance of the 2 dogs was similar, the female dog had generalized demodicosis: abundant Demodex mites (predominantly D. canis with fewer D. injai) were found on all deep skin scrapings.

Figure 1.

Female (left) and male (right) West Highland White terriers at initial presentation. Notably, the female dog exhibited minimal alopecia or skin lesions despite having high numbers of Demodex mites in skin scrapings.

The idea for this article came about when I thought about these dogs, and realized how dramatically veterinary dermatology had changed in their lifetime. The treatments I considered were ones I could not have imagined when they were 1 year old and just starting to show clinical signs. Today, I could be optimistic about helping them be comfortable quickly, without disturbing the bottle of prednisone gathering dust on my pharmacy shelf. This article describes some of the key therapeutic developments in small animal veterinary dermatology in the last decade. Most have had a very favorable effect on the landscape of dermatology in Canada, but others have provided unfortunate therapeutic challenges.

The most recent advances in veterinary dermatology have affected the way we treat our most common patients: allergic dogs. The spring of 2016 marked the arrival of a much- anticipated product in the Canadian veterinary market. Apoquel (oclacitinib; Zoetis Canada, Kirkland, Quebec) was approved in Canada for the control of pruritus associated with allergic dermatitis and the control of atopic dermatitis in dogs at least 12 months of age. Apoquel inhibits the activity of various pro-inflammatory and pruritogenic cytokines including Interleukin (IL)-31, one of the key mediators of itch in dogs. Since its launch, Apoquel has provided veterinarians with a novel, effective, and well-tolerated treatment for these very common ailments (1–3). A key benefit of the drug is its impressively rapid effect (1), comparable to that of oral corticosteroids. I chose Apoquel for treating the male Westie patient. I hoped that in addition to rapidly reducing his severe pruritus, it would provide an effective long-term therapy for his atopic dermatitis.

For the female Westie with atopic dermatitis and generalized demodicosis, I preferred to avoid drugs with the potential to inhibit normal immune function. This would have been difficult in the past, but with the recent availability of a novel therapy I had another option for controlling her pruritus. Cytopoint (lokivetmab; Zoetis Canada), a caninized anti-IL- 31monoclonal antibody, was launched in June 2017 to aid in the reduction of clinical signs associated with canine atopic dermatitis. It has been shown to be a safe (4) and effective (5,6) treatment for this disease. Despite the overlapping indication and activity on the same key cytokine, Cytopoint works very differently from Apoquel. Remarkably, it can be effective even in some dogs whose signs are not adequately controlled with the latter. Cytopoint differs from other treatments in a number of ways. It does not affect normal immune function, and can be given to dogs of any age (but should never be used in other species). It can be used in dogs with diseases that could preclude using Apoquel, Atopica (cyclosporine; Elanco Canada, Guelph, Ontario), or corticosteroids. These include patients with malignancies, severe infections, and — like my Westie patient — generalized demodicosis.

It would be difficult to overstate the positive impact that Atopica has made on veterinary dermatology. For a decade, Atopica was the only highly effective alternative to cortico-steroids available in Canada for the control of clinical signs of atopic dermatitis in dogs (7). It remains the most effective licensed treatment for feline allergic dermatitis. The use of Atopica for dermatologic indications was a game-changer that allowed, for the first time, relief for many allergic patients either without corticosteroids, or with a significant steroid-sparing effect. Compared to the therapies just described, Atopica has a slower onset of action (1). After several weeks of administration, however, its efficacy in reducing pruritus in dogs is similar to that of Apoquel (1) and the dosing frequency for Atopica can often be decreased. Cyclosporine has also received extensive extra-label use for various inflammatory dermatologic conditions. These include proliferative otitis externa, sebaceous adenitis, perianal fistulae, chronic pododermatitis, pemphigus foliaceus, reactive histiocytosis, and many other immune-mediated and autoimmune conditions (8).

Systemic corticosteroids are no longer the mainstay in treating allergic dogs, but one newer topical product deserves mention. A potent dermal corticosteroid spray with a low rate of percutaneous absorption, hydrocortisone aceponate (Cortavance Topical Spray Solution; Virbac Canada, Cambridge, Ontario), is licensed for use in dogs for a period of 7 consecutive days. Several studies confirm the efficacy and safely of this product for longer periods if needed, (7,9) though patients treated in this way should be carefully monitored for cutaneous atrophy (10).

The role of the skin barrier has received ample attention in human and veterinary allergy, and skin barrier defects have been demonstrated in canine atopic dermatitis (11). Several topical therapies and veterinary diets have been shown to enhance this barrier, and can be a useful part of the multi-modal treatment of allergic pets.

Even with the extraordinary advances in symptom-relieving treatments, addressing the cause of allergy remains a key part in managing the disease. Allergen-specific immunotherapy can change the course of atopic dermatitis or possibly effect a cure, rather than simply achieving symptom control. The development of sublingual immunotherapy products has made this treatment possible for clients reluctant to give injections. Early investigations of this treatment are promising (12), although larger studies are needed. The investigation of cutaneous adverse food reactions (food allergies) can still be difficult. A reliable serologic test for food allergens does not exist (13), and an elimination diet trial with subsequent provocation testing remains the diagnostic procedure of choice. Although client compliance remains a major hurdle in diet trials, the selection of veterinary diets available has greatly increased. Novel protein diets now include exotic offerings such as rabbit, kangaroo, and alligator-based foods. The hydrolyzed protein diet selection has also expanded to include extensively hydrolyzed feather protein foods for dogs and cats (Allergenic; Royal Canin, Guelph, Ontario).

Although it is overshadowed by the developments in allergy treatment, there has also been a revolution in the treatment of a typically stubborn parasitic disease. For dogs with generalized demodicosis, like my female Westie patient, slow improvement has typically meant many months of administering drugs with significant toxic potential. This all changed after the arrival of the first oral isoxazoline in Canada (fluralaner, Bravecto; Merck Animal Health, Kirkland, Quebec) in 2014. By 2015, a study showed unprecedentedly rapid efficacy after 1 dose of fluralaner in 8 dogs (14). A larger unpublished case study subsequently confirmed an overall response rate of 100%, with most (87.1%) of the 163 dogs achieving negative skin scrapings in 1 month, with the remainder by 2 months (15). Afoxolaner (NexGard; Mérial Canada, Baie D’Urfé, Quebec) and sarolaner (Simparica; Zoetis Canada) have also subsequently shown rapid efficacy (16,17). The treatment of demodicosis with isoxazolines intended for flea and tick control is extra-label use. Select isoxazolines have also been successfully used in the extra-label treatment of ectoparasites including Demodex cati (18), Otodectes cynotis (17), and Sarcoptes scabiei (19,20).

Along with these remarkable additions to our therapeutic arsenal have come some unwelcome challenges. The increase in methicillin-resistant staphylococci, particularly Staphylococcus pseudintermedius, S. schleiferi, and S. aureus, has been of particular concern in companion animals. These infections are especially troublesome in dogs because of this species’ predisposition to developing recurrent pyoderma. These bacteria are resistant not only to all of the beta-lactam drugs so commonly used to treat skin infections, but frequently to other antimicrobial drugs as well. Empirical systemic drug selection is contraindicated when one of these infections is suspected based on a treatment failure (21). Unfortunately, systemic treatment of methicillin-resistant staphylococcal infections can require the use of potentially toxic drugs such as rifampin and amikacin. Resistant staphylococci are now endemic in many areas. A Canadian study examining canine pyoderma cases found them in 12.1% of staphylococcal skin cultures in primary care practices (22). If there is any good news, it is that these resistant bacteria have made it apparent that systemic therapy is often unnecessary for pyoderma. For the very common superficial infections, topical therapy — such as chlorhexidine shampoos and sprays — can be just as effective as antibiotics, even when caused by resistant staphylococci (23). Topical therapy is now recommended as the sole treatment for surface and superficial methicillin-resistant staphylococcal infections whenever pet and owner compliance can be expected (21). Although the selection of topical products is limited in Canada compared to other markets, it is improving, with 2% to 4% chlorhexidine shampoos, sprays, wipes, and solutions now available for companion animals.

The catalog of developments is much longer, with just a few more listed here. Various new formulations of antibiotics allowing for easier compliance are available, with a once-daily cephalosporin (cefpodoxime proxetil, Simplicef; Zoetis Canada), an injectable cephalosporin with a long half-life (cefovecin sodium, Convenia; Zoetis Canada), and various palatable tablet formulations of cephalexin and amoxicillin-clavulanate now marketed. Gel preparations for otitis externa requiring infrequent application (e.g., Osurnia; Elanco Canada) are also simpler to administer. The selection of topical therapies in Canada is expanding, though the selection of products containing chlorhexidine combined with an azole antifungal for mixed bacterial and Malassezia infections remains limited (e.g., Douxo Pyo products; Ceva Animal Health, Cambridge, Ontario). Veterinary dermatology is an exceptionally active area of research and publication. Open-access clinical guidelines have been published by the World Association for Veterinary Dermatology (21,24), and by the International Committee on Allergic Diseases of Animals (25,26) to help veterinarians with several of the most common skin diseases.

It is an exciting time to be practicing veterinary dermatology, even if the expanding therapeutic arsenal can make treatment selection more complicated than before. Some of the developments mentioned in this article will be profiled in future Veterinary Dermatology columns. As for the Westies: they are reportedly doing very well, and I look forward to seeing them for follow-up examinations soon. Like most pets with chronic skin disease, they have a long road ahead of them. But thanks to the changing landscape of veterinary dermatology, I have more hope than ever that the road ahead for these dogs will be smoother than the one they have traveled for their first 8 years.