Candace A. Sousa, DVM, Emeritus DABVP (Canine and Feline Practice), DACVD
Pruritus in dogs has many causes - sarcoptic mange, flea allergy dermatitis, atopic dermatitis, Malassezia colonization, etc. It is a hallmark of allergic skin disease. To ensure maximum success and client satisfaction, treatment approaches for allergic dermatitis in dogs must be individualized and flexible, combine several modes of therapy, and be aimed at both the primary disease and at secondary complications. The goal with each patient is to find the right combination of therapies to provide management that is effective, affordable, convenient, and produces as few adverse effects as possible.
Treatment of Acute or Short-Term Pruritus
Many allergic skin diseases are acute in onset or short term in duration. These are most commonly the diseases that can be treated, cured or prevented and include sarcoptic mange, flea allergy dermatitis, contact allergy and food allergy (also known as cutaneous adverse food reactions [CAFR]). Rapid resolution of pruritus and control of inflammation and dermatitis are the primary goals of treatment. Evidence-based reviews have shown that glucocorticoids and oclacitinib are the only 2 medications which can provide these two factors for success [See details of these below]. Treatment is usually needed for a few days up to 2 weeks while the underlying pruritic condition is treated and brought under control.
From a strictly evidence-based point of view interventions that have little or no benefit in the acute space include antihistamines, fatty acid supplements and calcineurin inhibitors.
Treating Chronic Pruritic Skin Diseases
Atopic dermatitis (AD) is the most common chronic allergic skin disease of the dog. The diagnosis is made by ruling out all other common pruritic conditions. The veterinarian and owner must focus on a management plan consisting of therapies that provide safe, effective, long-term control.
- Identification and avoidance of flare factors. If fleas have been a periodic factor, preventive measures should be instituted. Because infections are so commonly implicated in flares, consideration should be given to reducing skin colonization with frequent use of antiseptic topical products, such as shampoos, sprays or rinses.
- Improvement of skin and coat hygiene and possibly epidermal barrier function. In addition to bathing - perhaps with an antiseptic product if infections have been a problem - therapies aimed at repairing the epidermal barrier should be considered. Only limited evidence for effectiveness of such measures is available, but it appears that the evidence may be mounting. Dietary approaches may be useful; for example, supplementation with fatty acids or barrier-enhancing micronutrients. Topical approaches with spray-on or spot-on products are the subject of considerable investigation and may also be useful in certain cases.
- Long-term reduction of pruritus and lesions with drugs. Drugs that have proven effective for long-term control of pruritus and lesions of AD include oral or topical glucocorticoids; oclacitinib (Apoquel® - Zoetis); topical or oral ciclosporin A (Atopica® - Eli Lilly); and Cytopoint® (Zoetis).
- Implementation of strategies to prevent recurrence of signs. Allergen-specific immunotherapy remains a possible long-term treatment for canine AD. It is one treatment that is aimed at actually reversing an important part of the underlying pathogenesis of the disease, has an excellent safety profile, and is the only treatment that in some cases can result in a virtual cure of the disease.
Interventions that have insufficient evidence for use in controlling chronic allergic skin disease include antihistamines, pentoxifylline, misoprostol, nonsteroidal anti-inflammatory drugs, and leukotriene inhibitors. All of these therapies have received only limited study, and the evidence to date is not convincing that these medications are satisfactory long-term solutions.
Fatty acid nutritional supplements containing omega-3 fatty acids (fish oil, flax seed oil), such as eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), may help normalize the cutaneous barrier function, have anti-inflammatory effects, and may act as a steroidsparing agent or synergistically with antihistamines. It may take from 6 to 12 weeks before they are effective. The recommended dose for anti-pruritic effect is 50 mg/kg/day of combined EPA and DHA. Alternatively, a high fatty acid-containing diet may be tried. Fatty acids supplements are reported to reduce pruritus in 20 to 30% of atopic dogs. Recently, several topical lipid/fatty acid preparations have become available that claim to aid in normalizing the skin barrier. Small studies show some effectiveness in restoring the skin barrier and reducing pruritus and inflammation with these products, but larger comparative studies are needed to determine the most effective products, optimal frequency, preferred application technique, and best case selection. A 1–2-month trial is needed to judge efficacy. At the very least, these products are very safe and should result in less odor and a shinier hair coat.
In several evidence-based reviews of treatments for AD, antihistamines have not demonstrated efficacy. Veterinarians continue to try various products approved for use in humans at various doses with the belief that they are safe and inexpensive and that they may, in some cases, provide relief from pruritus in allergic dogs; but the best that can be shown is that ∼20% of dogs have benefited, which is comparable to placebo. Even the belief that they may cause sedation, which would help with pruritus, has not been shown. This is why there is no veterinary-approved antihistamine for the treatment of pruritus.
Glucocorticoids historically are the mainstay of effective treatment of pruritus and allergic skin disease. In many cases, the side effects outweigh the benefits. The goal is to use oral prednisone or prednisolone at the lowest possible dose ("comfortably itchy"). A proposed "safe annual steroid dose" has been published: 15 x weight in lb=mg prednisolone/year and can be used as a guide for dogs being managed with long-term glucocorticoid therapy. The use of long-acting injectable glucocorticoids should be avoided in the long-term management of canine allergic skin disease.
Ciclosporin is a calcineurin inhibitor that is effective as a steroid alternative for treatment of canine AD. It blocks activation of T-cells and the cytokines they produce that are involved in the allergic response reducing inflammation and pruritus. Studies have shown that the signs of canine AD can be well controlled with the use of ciclosporin, 5 mg/kg q 24 hours in approximately 50–70% of cases with increasing percentages with longer-term use. Atopica® is the veterinary form of ciclosporin and is preferred over generics. The dose is 5 mg/kg once daily. Major advantages include the lack of steroid-related side effects such as polyuria, polydipsia, weight gain, muscle weakness and personality changes. The drug is not fast acting and may take 3–6 weeks for efficacy to be seen, so is often combined with low-dose corticosteroids or oclacitinib for the first 2–3 weeks. Gastrointestinal side effects occur in approximately 15–25% of cases, but are usually self-limiting and can be minimized by slowly building up to the full dose over 10–14 days, pretreating with an antiemetic 2 hours before ciclosporin for the first 10 days, and giving medication with a small amount of food. Other less common side effects include papillomatosis, hirsutism, gingival hyperplasia, tremors/neuropathies, secondary pyoderma, and lymphoplasmacytic dermatitis. Occasional hypoalbuminemia, urinary tract infections and increased liver enzymes may be seen. Ciclosporin does not interfere with serum or intradermal allergy testing. The major disadvantage to the use of this drug is the cost, but this can be lessened with every-other-day or half-dose daily therapy, which can be attained in 40–50% of cases.
Oclacitinib (Apoquel®) has been approved for the control of pruritus associated with allergic dermatitis and for the control of atopic dermatitis in dogs 12 months of age or older. It is a novel, targeted, oral Janus kinase (JAK) enzyme inhibitor that inhibits the action of many allergic cytokines, including interleukin (IL)-31, which use the JAK STAT pathway for cell signaling. Studies have shown it is effective and safe in controlling pruritus associated with canine allergic dermatitis and atopic dermatitis. In laboratory studies, it is more rapid-acting (within 1 hour) than oral prednisolone or dexamethasone injections without steroid-related side effects. The approved dose is 0.4–0.6 mg/kg PO BID up to 14 days, then once daily for maintenance therapy. Apoquel has been safely used in conjunction with other common medications including antibiotics and parasiticides and with vaccinations. It does not interfere with serum or intradermal allergy testing.
Allergen-specific immunotherapy is the only treatment that may prevent the progression of AD or result in a cure in some cases. Immunotherapy is thought to normalize the immune response by increased production of T regulatory cells and antiinflammatory cytokines that reduce the Th2 inflammatory cascade. Once a clinical diagnosis of AD is made, the dog can be tested for the presence of allergen specific IgE antibodies to select allergens to include in the allergen-specific immunotherapy (ASIT) vaccine. The currently available tests include the intradermal test (IDT) and allergen-specific Ig E serology (ASIgES) for measurement of allergen-specific Ig E. It seems that no matter which test is performed to select allergens (serologic or intradermal), published reports show that about 60–70% of dogs with AD show at least a 50% improvement of their AD when treated with ASIT when "micromanaged" by a dermatologist. Most dermatologists recommend that injections be given once weekly, after the initial induction schedule is followed, for 1 year before a final assessment of response is made in order to maximize the chance of success. Many atopic dogs still require treatment of acute flares in pruritus with oral and/or topical anti-pruritic medications, but the frequency of medications can often be reduced. The dose and frequency of ASIT injections often needs to be adjusted during the induction period and this is where the "art of therapy" rather than using a "cookbook formula" comes in.
Recently, sublingual immunotherapy, used for years in people for the treatment of allergic rhinitis, has been tried in small groups of dogs in pilot studies with success similar to standard subcutaneous immunotherapy. Several companies, including Heska, Bio-Medical services, RESPIT and Nelco are offering sublingual formulations of their immunotherapy vaccines. Vaccines are glycerin-based and administered by the owner twice daily using a special oral applicator. Dogs may respond in 1–3 months in some cases and seem to have fewer side effects than with subcutaneous vaccines. In one study, 50% of dogs who failed the standard subcutaneous vaccine improved with the sublingual formulation. In people, the vaccine often can be discontinued after 3–5 years with long-lasting remission of clinical signs. It remains to be seen if this is the case in dogs. More studies are needed to determine the optimal dosing frequency and protocol, and how long-term efficacy compares with subcutaneous immunotherapy. This is an option for owners who cannot give injections to their pets, but requires continuous twice-daily dosing.
The most recent therapy for the treatment of canine AD is the monoclonal antibody Cytopoint. This is an injectable caninized anti-cIL-31 monoclonal antibody (mAb) specifically designed to target the cytokine IL-31, a key cytokine involved in sending the itch signal to the brain. It removes the cytokine from the circulation. It begins working within 1 day and delivers relief from itch and inflammation for 4–8 weeks. Cytopoint is safe for dogs of all ages and can be used in combination with many common medications, including parasiticides, antibiotics, antifungals, corticosteroids, vaccines, immunotherapy, antihistamines, and other antipruritics, such as oclacitinib and cyclosporine. It does not interfere with serum or intradermal allergy testing.
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