How to help owners understand atopic dermatitis and its management Wesley Power MVB CertVD MRCVS Monaleenvets.com, Monaleen Road, Castletroy, Limerick The international task force on canine atopic dermatitis (AD) defines the disease as a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical signs associated with the production of IgE antibodies, most commonly to environmental allergens. Understanding the various components of this precise definition can improve our understanding of the pathogenesis of this common disease and therefore improve our management. Because AD has a genetic basis it is seen most commonly in certain breeds. This breed predisposition tends to vary geographically, but in Ireland breeds that are most commonly affected include the West Highland white terrier, Jack Russell terriers (terriers in general), Labradors, Golden Retrievers, German Shepard’s and spaniels. The presence of abnormal genes leads to a multitude of abnormalities but their primary effect is the production of an abnormal skin barrier and a polarisation of the subsequent immune response towards the over production of allergen specific antibodies, especially allergen specific IgE. This skin barrier is composed of the outer most layers of the epidermis called the stratum corneum. This is composed of over lapping flattened a-nuclear, and therefore dead cells cemented together in a lipid emulsion called the intercellular lipid barrier. This provides both a physical and water proof barrier. In atopic patients there is a decrease in the structure and quantity of this lipid emulsion, leading to a more permeable stratum corneum. This gives allergens easier access to the epidermis and allows increased trans-epidermal water loss leading to drier skin. Dry skin has a changed microenvironment on its surface predisposing it to increased bacterial and yeast colonisation and therefore infection. Dry skin is also inherently more irritated. The increased permeability means that allergens can find their way more readily into the middle layers of the epidermis. Here they are targeted and gobbled up by resident macrophages in the epidermis called Langerhans cells. These cells transport the gobbled allergen to the local draining lymph node, and after digestion, in a process called phagocytosis, present the antigen to T helper 2 lymphocytes. These lymphocytes produce a chemical message called Interleukin 4 which tells the B lymphocytes in the lymph node to produce IgE specific to the gobbled antigen. One of the most important canine allergens is a house dust mite protein termed Der f 15. Once produced, the large amounts of IgE move in the vasculature back to the skin and attach to and arm dermal mast cells. On the surface of these mast cells IgE forms cell surface receptors and once re-exposed to the offending allergen, cross linking of these receptors by the allergen leads to mast cell degranulation, the release of preformed and newly formed inflammatory mediators and the initiation of inflammation and pruritus. Pruritus leads to self-trauma, more damage to the skin barrier and the establishment of bacterial and yeast infections, which in turn causes perpetuation of the inflammation and pruritus. A vicious cycle ensues. With chronic inflammation and infection the immune response will change to include a T helper 1 lymphocyte reaction with the subsequent chemotaxis of a broader range of leucocytes, including other macrophages and lymphocytes and there is then, less of a reliance on the allergen specific IgE response. It goes without saying, to adequately treat our atopic patients we need to intervene with a multimodal approach. No one therapy is going to control the clinical signs associated with AD. Owners need to understand from the outset that “cure” is not possible, but with a good client-vet relationship a good quality of life can be achieved. It is useful to think of treatment in a number of stages, some of which will overlap: 1. 2. 3. 4. 5. Skin barrier restoration. Flare factor avoidance. Identify and treat infections. Treat the primary inflammation (anti-pruritics). Reduce allergen exposure. 6. Allergen specific immunotherapy (ASIT). Skin barrier restoration: Diet: Improve the general plane of nutrition if the patient is on a poor quality diet in order to maximise the composition of the intercellular lipid emulsion. Try to maximise the omega 3: omega 6 fatty acid content of the diet. All the major brands carry a skin specific range, however one needs to be well informed about the actual composition of these diets before making a choice. In my opinion words like “hypoallergenic”, “allergy” and “sensitivity” are often used incorrectly and deceive and confuse owners. Shampoo therapy: If we are to use evidence based medicine in our decision making, the only shampoo therapy that has had published work on its effect is Allermyl shampoo® (Virbac). This product has been shown to decrease the level of pruritus, but showed maximal effects when used with a whirlpool bath. It utilizes Spherulite® technology, where microscopic beads formed by concentric spheres with interspersed essential oils, allow slow release of the emulsion over time providing more long term moisturising properties. It is to be presumed however that most shampoo therapy might aid atopic patients by cleansing, rehydrating and moisturising the skin. Other shampoos will also have antiseptic properties. Some however will be irritating and correct shampoo selection will vary from case to case. Spot-on essential oil preparations: Two products have emerged over the last few years. Dermosecent Essential 6® Spot-on (LDCA, France) and Douxo ®Spot-on (Sogeval, Texas). Neither product is licenced or is directly available in Ireland, however it is possible to order Dermoscent from VetDirect, a UK wholesaler. The former product is a mixture of natural essential oils and omega3 & 6 fatty acids. The latter contains phytosphingosine, which is actually a component of the lipid barrier emulsion. Both products are applied as for ectoparasiticide spot-ons, are absorbed into the sebaceous glands at that site and are then redistributed in the sebaceous secretions. I have no personal experience with these products but they do show some promise. Flare factor avoidance: Routine flea treatment: It is imperative that flea bite exposure is limited, if not completely eliminated. Flea exposure may lead the owner to believe that the AD is not under control leading to frustration. Fleas just simply muddy the water. It is important that all in contacts are also treated regularly, at least monthly. Identify any concurrent food allergy: This is an important part of the work up to allow one to confidently make an accurate diagnosis of AD in the first place. If food has been identified as a co-factor, this should be incorporated into the management. However, in the recent past there is an increasing move towards the possibility that AD and food allergy are one in the same condition, simply induced by different allergens. This seems very plausible. In the future it is possible that we will begin to treat AD and food allergy as the same condition, with different causes. Identify and treat concurrent infections: Again this is an important part of the initial work up of a pruritic patient, to allow the clinician to identify and treat separately, all the individual components that may be summating to cause the total pruritus. It will also form part of the on-going management because recurrent infections are common. Cytology should be used routinely to identify the cause of the infections and also to monitor the response to treatment. Cephalexin is commonly used at 25mg/kg twice daily, to treat bacterial infection and malassezia dermatitis can be adequately treated with miconazole/ chlorohexidine (Malaseb®,Dechra) shampoo, twice weekly for three weeks using a ten minute contact time or itraconazole 100mg (not licenced for dogs) 5-10mg/kg once daily, two days a week for three weeks (pulse therapy). These are evidenced based treatment protocols. Treat the primary inflammation (allergy): Anti-pruritics: Here we aim to treat the primary cause of the inflammation and pruritus, the allergy. This is the area that clinicians will often focus on to the detriment of other management interventions. Treating the inflammation will lead to a rapid improvement in the level of pruritus and therefore improved comfort for the patient. However, if this is the sole focus of treatment long term control will be impossible to achieve and a myriad of side effects from treatment with be the result. This is why it is important to focus on the other treatment areas first. Topical products should be used as much as possible to limit systemic effects. Hydrocortisone aceponate (Cortavance®,virbac) is very useful and safe. It is activated in the epidermis to its active form hydrocortisone 17 propionate, where it is almost completely metabolised with limited, if any systemic absorption. Chronic use does lead to skin atrophy. Betamethasone (Fusiderm®, Dechra) is also useful for localised lesions. It also contains fusidic acid and so is beneficial in concurrent bacterial infection or overgrowth. Topical tacrolimus (Protopic®,Astellas Pharma) is useful for chronic localised lesions. In acute flares it takes too long to have an effect. It is not licenced for use in animals. Systemic glucocorticoids are commonly used in the management of AD. Prednisolone at 1mg/kg divided daily and tapered is most often used in the canine patient. Our feline friends often require a higher antiinflammatory dose at 2mg/kg divided daily. Methylprednisolone is another option and seems to have fewer side effects, however it is more expensive. The use of these short acting steroids is very beneficial to control intermittent flares and also to treat seasonal cases of AD where pruritus is present for up to two months in a twelve month period. Bethemethasone and dexamethasone have longer durations of action of up to 48 hours. These drugs are rarely if ever required in the management of AD and are more likely to be necessary in immune mediated diseases rather than allergy. Ciclosporin A (Atopica®, Novartis) is licenced for the treatment of AD in both the dog and cat. It is used at 5mg/kg in dogs and 7mg/kg in cats, both once daily to every other day. It is useful for the treatment of chronic non-seasonal AD, where the owner has refused immunotherapy or where immunotherapy failed to give an adequate response. The dose used is critical. Under-dosing to reduce cost will lead to treatment failure. Reduce allergen exposure While this is a very important area to discuss with owners, it is in most cases unrealistic to expect that one can completely avoid the offending allergens. First of all there are usually a number of possible allergens involved, and secondly most allergens are air borne and unless one stops breathing are impossible to avoid. The offending allergens can be identified using serology and intradermal skin testing, or both. Shampoo therapy will remove allergens from the coat, avoidance of flea bites and possible offending food allergens have already been discussed. Because the house dust mite is one of the most common allergens owners should be encouraged to wash their pets bedding at least once weekly in a 60 degree washing machine cycle. Mattress protectors should also be encouraged. The use of HEPA vacuum cleaners should be used in the house to help avoid redistributing possible allergens indoors. Know and limit exposure of the patient to known pollen allergens. In general, flowers usually pollinate in spring, weeds late spring/summer and trees late summer/autumn. Allergen specific immunotherapy (ASIT): ASIT is the only intervention that has the potential to prevent the development of signs and alter the long term course of the disease. The offending allergens can be identified using serology and intradermal skin testing or both. It is important to take the animals history into account in order to determine which allergens are more likely to be associated with clinical signs. Remember “normal” (non-atopic animals) will also have positive results on allergy testing, which is why these tests are not used for diagnosis. Combining serology with intradermal skin testing may increase the accuracy of allergens to be included in the immunotherapy vaccine. Most immunotherapy vaccines come with a standard protocol. It is important not to rigidly stick to this protocol. Injection frequencies and amounts injected must be tailored to each patient. The mechanism of action of ASIT is not completely understood. It may result in the class switching of the allergen specific IgE to IgG. This IgG acts as a blocking antibody, preventing IgE from attaching to mast cells and therefore preventing the release of their inflammatory mediators. ASIT may also lead to an increase in Treg lymphocytes, down regulating the subsequent immune response, in a sense calming down the immune system. Bibliography: Olivry et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Veterinary Dermatology, 2010.
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