Managing the itchy pet (Proceedings)

Skin disease is the second most common reason for a pet to be presented to a family veterinarian (Hill, 2006). The most common reason is preventive care! Pruritus is the most common dermatological presenting complaint along with "I need to stop that disgusting licking noise that my dog does at night!" Management of this most frustrating condition requires a solid knowledge of the complex nature of the condition, good diagnostic skills and, most importantly, good communication skills as appropriate treatment is time consuming and expensive. The diagnostic approach is discussed in detail elsewhere in the proceedings (See: The CSI approach to pruritic pets) and will be presented tomorrow morning. Today we will focus on the various treatments that are available in managing the itchy pet

The first goal is to manage the caregiver's expectations. I advise clients that the goal of therapy is not to stop the patient from licking, rubbing, biting or chewing altogether; rather, the goal of treatment is to create an "acceptable level of discomfort" using the gentlest means possible.

The American College of Veterinary Dermatology has created a task force on Canine Atopic Dermatitis. This task force looked critically at many of the treatment options that are available critically using evidence based medicine and was published in recently in Veterinary Dermatology.

Pathogenesis

In short, epidermal barrier defects are thought to facilitate contact of environmental (and possibly microbial) allergens with epidermal immune cells. Epidermal antigen-presenting cells capture allergens with allergen specific IgE, and then migrate to the dermis and regional lymph nodes. Microbial products and immune cell-derived inflammatory mediators activate keratinocytes, which, in turn, release more chemokines and cytokines. IgE-coated dermal mast cells release histamine, proteases, chemokines and cytokines following contact with allergens. There is an early influx of granulocytes (neutrophils and eosinophils), allergen-specific T-lymphocytes and dermal dendritic cells. Eosinophils degranulate and release proteins that induce dermal and epidermal damage.

Itchy Dog treatment

Control microbes

In my opinion, this is the most important part of treatment and the most frequently overlooked. Studies have shown that 67% of recurrent pyoderma is a result of hypersensitivity (Bensignor 2004). Microbes (bacteria and yeast) and self trauma all contribute to persistent inflammation in chronic skin lesions. Therefore, one of the most important considerations in the treatment of the allergic pet is to control microbial "flare factors". Without control of these organisms treatment is bound to fail. Antibiotics must be used judiciously, however, as multidrug resistant organisms are becoming more and more prevalent. Topical antimicrobial treatment is preferred for mild infections. I like 4% chlorhexidine scrubs for local areas of infection, especially for the paws. Yeast pododermatitis can also be treated with topical antifungal shampoos and ointments. Malassezia dermatitis/hypersensitivity may play a significant role and allergy testing for Malassezia has become routine in our practice. When systemic antibiotics are used, however, one needs to ensure that treatment is thorough; appropriate doses and duration of treatment is critical Accordingly, when skin infections do not clear with appropriate treatment, one must consider the possibility that 1) the problem is not infectious or 2)the pruritus is overwhelming the ability for the antibiotics to take hold or 3) that there is an additional competing factors such as hormonal disease, drug reactions, immune disease or tumors, and 4)bacterial resistance; bacterial culture is recommended in these cases

"T-shirt" therapy

Interestingly, this is one of my most effective treatments for atopic dermatitis. It is amazing how many patients feel better with this simple treatment. In fact, T-shirts for allergic pets are now available on internet web sites and have just become commercially available for sale in veterinary clinics in Canada

Antihistamines

As most studies looking into their use were open and not controlled, there is inconclusive evidence for or against their use, according to the task force findings. Indeed, I do not find that these products are useful in "putting out the fire". I use antihistamines as a control mechanism once the patient's pruritus has been relieved (with steroids, for example) or in an effort to reduce the steroid dose. I will also start antihistamines early in the "season" in dogs with a seasonally relapsing dermatitis or in very mildly affected individuals. A few blinded placebo controlled studies have found that antihistamines can be synergistic with fatty acid therapy. Try each antihistamine for a period of 7-14 days each to assess response. If using over the counter products, be sure to warn owners not to accidentally administer products that also contain decongestants, acetaminophen and the like. I like to try cetirizine (0.5 – 1 mg/Kg S-BID), diphenhydramine (2.2 Mg/Kg B-TID), chlorpheniramine (Dog: 0.22 – 0.4 mg/Kg B-TID - NO MORE THAN 1 Mg/Kg total per day; Cat 2-4 mg/Cat BID), cyproheptadine in the cat (2 mg per cat BID) and hydroxyzine (2.2 mg/Kg BID). These antihistamines can cause drowsiness. This may even help pets get a good night's sleep rather than scratching incessantly. There is a 2 week withdrawal period from antihistamines before allergy testing. Clemastine has been shown recently not to be bioavailable and to lack effect after oral use in dogs

Burows solution

I find this a very useful product that is often overlooked in the control of mild pedal pruritus when not complicated by a secondary microbial dermatitis (and sometimes even when it is)

Allergic conjunctivitis

Cool compresses to eyes are an easy and often very effective treatment for itchy eyes. I also have moderate success with the topical NSAID, ketorolac. I have not found topical antihistamine drops particularly effective, in general, although ketotifen is starting to gain some traction in my practice.

Parasiticide treatment trial and continued flea control

The use of a flea adulticide is recommended. There is evidence that the atopic status predisposes dogs to develop hypersensitivity to flea salivary antigens if exposed repeatedly to flea bites. Remember, the efficacy of topical flea control products may be affected by frequent shampooing. The use of oral adulticides would be especially beneficial in this situation. The use of flea products with activity against mites such as Cheyletiella or scabies will cover those bases in the event that they were missed on scrapings

Fatty acid supplementation

These products take a couple of months to take effect. Furthermore, I believe that these products are more useful as adjunctive therapy (to reduce the dose of steroids, increase the possible efficacy of antihistamines) as opposed to monotherapy. The task force on Atopic Dermatitis found no evidence of superiority of any particular EFA combination, dosage, ratio or formulation (including enriched diets) to improve skin and coat quality. I like to initially dose based on 40 – 50 mg per kg of Eicosapentanoic acid (EPA) and will often use diets as a means of administration as opposed to supplements.

Diet

It is important that the client understands the difference between a hypoallergenic diet and a diet for dogs with allergies. Food trials should always be considered in dogs with nonseasonal signs. One must also keep in mind that atopic dogs often acquire new hypersensitivities, and the development of a novel food allergy could be the cause of a flare. This can be quite frustrating to an owner if not explained properly. Choice of appropriate diets for food trials is discussed elsewhere in the proceedings (see The CSI approach to pruritic pets). In general, EFA-enriched diets provide higher amounts of EFA than their administration as oral supplements. Several nutritional supplements (e.g. pantothenate, choline, nicotinamide, histidine and inositol) have been incorporated into diets and have been shown to increase the production of ceramides (skin lipids) and decrease transepidermal water loss in healthy dogs.

Chronic otitis

Gentle ear treatments are the mainstay of allergic ear treatment. In Canada, I have great success with a drop especially formulated that contains Burows solution, 1% hydrocortisone, and Propylene Glycol. And there is only one formulating pharmacy that I know that does it right. However, products to try in the USA would be HB101, Burotic, and Malacetic HC

Shampoo therapies

People often overlook the benefit of bathing. Shampoo choices are beyond the scope of this talk, however, shampooing is an excellent way to relieve itchiness but the effect is short lived. Animals should be BATHED IN COOL WATER with an appropriate medicated shampoo to relieve itchiness. The shampoo choice varies with the individual pet's coat condition (although there are no current studies that support the use of any one shampoo for any condition). Bathing offers a direct soothing effect to the skin, the physical removal of surface allergens and microbes and an increase in skin hydration. Ingredients that help relieve pruritus include sulphur and salicylic acid, selenium sulfide, oatmeal and hydrocortisone. If a concurrent microbial dermatitis is present, the use of shampoo containing antimicrobial ingredients such as chlorhexidine, ketoconazole, miconazole or cetrimide are useful in controlling "flare factors". I like leave-on conditioners, as they increase contact time. Dry coats can be moisturized after bathing by using humectants or emollient sprays. Remember to advise the client that hypoallergenic shampoos are not made for allergic pets; they are made for those patients that cannot tolerate other products. Medicated shampoos should be used frequently, as often as twice weekly.

Allergen-specific immunotherapy (ASIT) is the term adopted by the task force for allergy injections. It is one of the few treatments that offer the possible outcome of a long term remission and is one of the best and safest long-term ways of managing allergies. Careful consideration of the allergens to be included in the extract is critical to the outcome. Allergy extract can be formulated in a number of ways.

Corticosteroids

Corticosteroids are very effective at relieving itchiness, of course, but their side effects are often unacceptable to the caregiver. Oral glucocorticoids prednisone, prednisolone or methylprednisolone are beneficial given at 0.5 mg/ kg once to twice daily until clinical remission occurs. Patients that do not respond to 1 mg/Kg prednisone likely have more than simple atopic dermatitis If clinical signs are very severe or do not improve rapidly, it might be necessary to maintain some dogs on longer courses at the lowest dose and frequency of administration that controls their clinical signs. Unfortunately, there are some patients where quality of life issues necessitate the use of chronic steroid treatment. In these patients, the goal is to use multimodal therapy to try to decrease the steroid use to the lowest possible dose and frequency. Temaril-P (Vanectyl-P in Canada) is a medication that combines prednisolone with the antihistamine, trimeprazine tartrate that I find very effective in lowering the dose of steroids. The use of oral glucocorticoids is normally contra-indicated in case of widespread concurrent superficial or deep bacterial skin infections, but I will sometimes offer a short burst of treatment to give the pet (and the client) a break. Clients should be warned that long-term use of glucocorticoids can result in calcinosis cutis, predispose to the development of demodicosis. Urine cultures should be performed at least twice yearly in patients on long term steroid treatment. Long acting injectable corticosteroids are not suitable for the treatment for allergic dogs (but are needed for some cats). An abstract presented to the ACVIM in 2010 by Dr Center supported a study presented in 2008 at the World Congress of Veterinary Dermatology. It estimated prednisone bioavailability in cats was ~26% relative to prednisolone. The conclusion was that the apparent limited oral bioavailability of prednisone cautions against its therapeutic use in cats.

Topical Steroid treatment (e.g. Dermacool HC, Genesis, Cortavance)

Topical glucocorticoids are certainly efficacious in the treatment of atopic dermatitis in dogs; however, one should be sure to warn the owner against overuse as prolonged applications could still predispose to adverse effects. The more potent corticosteroids are of particular concern and I have seen patients present with thinning of the skin (cutaneous atrophy), comedones and superficial follicular cysts and even iatrogenic Cushing's disease. The risk of skin atrophy appears low with the new diester glucocorticoids such as hydrocortisone aceponate (Cortavance). Topical glucocorticoids might be temporarily indicated to induce a thinning of lichenified chronic skin lesions.

Tacrolimus

One alternative to topical steroids is 0.1% tacrolimus, applied twice daily fort eh first week and then in reduced frequency. The slow onset of the product makes its use inappropriate for acute flares. Initially, application may lead to a burning sensation as is reported in humans

Cyclosporines

I have had very good success with this drug in the treatment of allergic dermatitis, among other diseases. I believe that I have found a better success rate in patients treated with the brand name product, Atopica®, as compared to generic cyclosporine. The most common side effects are intestinal upset, gingival hyperplasia and hypertrichosis. Papillomatosis and anorexia are also reported. Although there is no clear data to date, there is a theoretical possibility of an effect on "tumor surveillance". I would not recommend the use of cyclosporine in patients with a history of tumors and I would use it with caution in the geriatric patient. It is important that the caregiver is advised that the rapid response to therapy obtained following initiation of steroid therapy is not seen with this drug. I treat the patient for at least a month and assess response. If there is a 50% or greater response, there is a good chance that the patient will continue to improve and, in many cases, the dose can be decreased to two out of every three days, every other day or even twice weekly by 4 months. This is particularly important as the drug is quite expensive at the present time. I have used it quite successfully (off-label) in cats. Cats should be screened for FIV and FeLV prior to starting cyclosporine. Cats at risk of contracting toxoplasma (outdoor cats, cats on a raw meat diet) should not be treated with this drug. Cats that develop diarrhea while on cyclosporine should have a complete gastrointestinal workup, including fecal, screen for Giardia and Cryptosporidium. Haemoplasma infection should be considered in cats that develop clinical signs of the disease while on cyclosporines (anemia, pallor, weakness, inappetance, icterus. Owners should be made aware of the potential of activation of subclinical respiratory disease.

Spot-on products

At this time, there is insufficient evidence supporting the use of topical formulations containing EFA, essential oils, or complex lipid mixtures for improvement of coat quality, barrier function or any other clinically relevant benefit in dogs. However, a complex lipid mixture has been shown recently to help restore pre-existing ultrastructural lipid anomalies in a small number of dogs with atopy. Some lipid-based topical emollient products appear effective in human AD and I have had success in the local application of Allerderm Spot on, particularly in cases of pododermatitis

Local topical treatment can help some pets that just have an itchy spot and can be a very helpful aid in reducing systemic drug doses. One of my favorite products in this regard is a spray sold as Dermacool® HC, a combination of Witch Hazel (which cools things down) and 1% hydrocortisone. O.5% hydrocortisone creams and ointments are available as over the counter products in Canada and also have their place in local treatment, but these can "gum up" the hair. One of my favorite ear drops is formulated by a pharmacy in Guelph, and has found quite a following in Ontario. It is made of Burows solution with 1% hydrocortisone in propylene glycol. It is very effective for allergic ears either as intermittent or chronic treatment. As with many compounded products, there does seem to be variability in its efficacy that is dependent on the formulating pharmacy. Similar products available in the USA would include Burotic and HB101. More severe allergic otitis responds well to a short course of Synotic. Keep in mind that stronger steroid containing ear medicines should be saved for more severe cases and NOT used intermittently, in order to avoid side effects such as cartilage degeneration and resistance problems. I have very good success in allergic pododermatitis using aluminum acetate soaks (Buro-sol® from drugstore - 1 packet per pint of water). Products designed as local wipes are also very helpful in the hard to reach areas (vulvar and facial folds, for example)

Pentoxifylline, misoprostol

Interestingly, the task force also found good evidence to support the use of misoprostol, a PGE1 analog., There is also fait evidence to support the use of phosphodiesterase inhibitors (such as pentoxifylline), which suppresses numerous cytokines, decreases leukocyte adhesion and aggregation and inhibits B and T cell activation. I use pentoxifylline at either 25–35 mg/Kg BID or 10–15 mg/Kg TID, given on a full stomach. I find these products more helpful in reducing the need for other drugs than as a first line treatment

Environmental management is important when the source of allergies can be identified and the pet's exposure reduced such as in the case of house dust mites, moulds, storage mites in food. Here are a few suggestions from a handout we give to clients on environmental management:

House dust mites

     • Dust mites congregate in soft-surfaced places where there is an abundant food supply. Dust mites feed off shed human and animal skin and are thus found in bedding, mattresses, pillows, sofas and carpets

     • Encase pet bed (or mattress if pet sleeps on the bed) in an airtight vinyl encasing - in humans this is the most important thing to decrease dust mite exposure

     • Wash pet bed or any blankets in 130 F (55 C) water at least every 2 weeks (weekly preferred) and dry in hot dryer.

     • On very cold, dry winter days - "freeze" the mites prior to washing by placing the pet bed outside.

     • Minimize "dust collectors" like rugs, stuffed animals, upholstered furniture (if dog lies on the couch) etc.

     • Avoid humidifiers if possible- dust mites can't survive in dry environments. Humidity should be kept between 40-50%.

     • Vacuum weekly. Remove pet from area during vacuuming. Use a vacuum with a HEPA (high-efficiency particulate) filter.

     • Use a damp cloth for dusting.

     • "Acarosan" (benzyl benzoate) is an acarocide (substance which kills mites) and has been shown to significantly reduce dust mite counts in floor carpets for 3 months after treatment. Carpets should be vacuumed following treatment.

     • Concentrate on places where your pet spends most of his/her time (sleeps at night).

Indoor moulds

     • Moulds are found in damp areas like bathrooms, the basement and the kitchen.

     • Moulds may also be present in older dog mattresses

     • Keep your home dry and clean. Keep humidity level between 40-45%. Use a dehumidifier in the basement if needed.

     • Clean frequently with an anti-mould cleaner like vinegar or a chlorine- bleach solution.

     • Make sure your home is well ventilated, especially bathrooms and damp areas.

     • Reduce the number of house plants.

     • Avoid carpet in bathrooms or directly on concrete floors in the basement.