Canine Atopic Dermatitis TreatmentJuly 9, 2013
By Lauren R. Pinchbeck DVM, MS, DACVD
Canine Atopic Dermatitis Overview
Canine atopic dermatitis (CAD) is a common pruritic skin disease affecting dogs worldwide. It likely affects 10-15% of dogs. In regions where fleas are not a problem, CAD is the most common canine allergic skin disease. Clinical signs are first noted between 6 months and 3 years of age. Several breeds are over represented including the Boston terrier, Boxer, Cairn terrier, West Highland White terrier, Scottish Terrier, Fox terrier, Yorkshire terrier, Chinese shar-pei, Cocker spaniel, English bulldog, English and Irish setter, Labrador and Golden retrievers, Pug, and German Shepherd, and miniature schnauzer. Successful management requires a basic understanding of the complexity of the disease, an accurate diagnosis, control of secondary problems, institution of a comprehensive management plan, and frequent reassessment.
Definition: Canine Atopic dermatitis is a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features. It is associated most commonly with IgE antibodies to environmental allergens. It is characterized by chronicity, pruritus, typical lesion distribution and a familial history. The involved allergens are dust mites, pollens, mold spores, danders, insects, and other miscellaneous allergens.
Diagnosis: The diagnosis of CAD begins with attaining a good history and recognizing the primary clinical signs, performing a dermatologic examination to characterize lesions and distribution, creating a differential list to work from, and performing some basic diagnostic tests to refine the differential list. The first step is to treat and control ectoparasites and resolve secondary infections. Food trials are also essential prior to confirming CAD in a dog with non-seasonal pruritus. Ultimately, the diagnosis of CAD is made based upon signalment, typical history, presentation of compatible clinical signs, and the systematic exclusion of all other pruritic skin diseases. There is no single test for CAD. It is a clinical diagnosis made by exclusion of other differentials.
History and Clinical signs: The most important aspect of evaluating a pruritic dog is obtaining a comprehensive history.
Dogs with CAD are pruritic (itchy), and pruritus is usually the initial and most salient feature of the presenting problem. If itch precedes the appearance of any rash, I am almost certain I am dealing with allergic skin disease (if parasites are already controlled for) as the primary problem. If rash precedes itch, I first evaluate the pet for other problems prior to working through the causes of itch/pruritus. Pruritus in CAD is typically highly glucocorticoid/steroid responsive (initially) and moderate in severity when not complicated by secondary infections. It may appear seasonally in the early years, but develops into a non-seasonal disease in most dogs.
Secondary infections: Dogs with CAD often develop superficial bacterial folliculitis and/or yeast dermatitis. The management of secondary infections is crucial when developing the management plan.
Parasites: The dermatologist will treat and control for all ectoparasites that are pruritic, and rule out demodecosis if there are compatible lesions. They will review clinical signs, lesions and treatment for demodecosis and sarcoptic mange. Initial evaluations should always involve appropriate skin scrapings. Empiric therapy for sarcoptic mange is often indicated early in the plan for pruritic dogs. Also, we prescribe very strict flea control for all pets in a household with an atopic dog. Fleas are a trigger factor for CAD, and flea bite hypersensitivity is often present in combination with CAD.
Dermatology examination: It is, or has been, widely believed that there is no primary lesion in CAD, but pinpoint macules or papules are often seen upon careful examination.. The skin in affected body sites is typically erythematous. With chronicity, widespread erythema, lichenification, and hyperpigmentation are noted. Excoriations are notable in some dogs. Alopecia in CAD is the result of pruritic behaviors of licking, biting, scratching, chewing, rubbing, etc. Light coated breeds may also have salivary staining at body sites that are licked and chewed. Some dogs will not have any lesions, and pruritus is the only problem. The distribution of lesions and pruritus in CAD is characteristic. Lesions will be present on the face, ears, paws, limbs, and ventral aspects of the body. The perineum is a commonly affected site. Not all sites are affected in all dogs with CAD.
Diagnostic tests: The tests performed on patients presented for pruritus will be dependent upon the history and lesions identified during a complete dermatology examination. One should be proficient in superficial skin scrapings, deep skin scrapings, skin surface cytology techniques, otic cytology, and dermatophyte culture specimen collection/test interpretation. Empiric treatment for sarcoptic mange can be considered a diagnostic test, and is always appropriate to prescribe. Diagnostic food trials are also a diagnostic test and very important.
Differential list: The differential list will be dependent on all information gathered after history is obtained, the exam is performed and results of some basic diagnostic tests are available. At the outset, all causes of pruritus are considered. If a dog has seasonal disease, flea allergy dermatitis and insect bite hypersensitivity are differentials. If pruritus is non-seasonal, without exacerbations, cutaneous adverse food reaction, sarcoptic mange, and contact hypersensitivity are differentials. Secondary infections with bacteria and yeast should always be treated and controlled, as they are an important contributor to the severity of pruritus in many cases.
Components of therapy used in the management of CAD: As there is no one cause or trigger for CAD, there is not one treatment approach that will satisfy the needs of all patients. The choice of treatment will depend on the nature and intensity of clinical signs, the presence of trigger factors, the patient acceptance of treatments recommended, and owner willingness/ability to maintain the plan. Most patients can be controlled.
1. Avoidance: Complete avoidance of offending allergens is typically not practical and is difficult to sustain. No evidence that avoidance alone is 100% successful, but certain avoidance measures can be helpful and make the pet feel better. Reducing time the pet spends outdoors is a reasonable avoidance effort. To avoid house dust mites, one could suggest covering mattresses with impermeable covers, clean & remove dust from the home frequently, use synthetic materials for pet bedding, vacuum frequently, wash bedding often, change air conditioner filters frequently, and keep humidity in the house < 50%. To avoid molds, spray regularly with mold preventers and removers, change air filters often, use dehumidifiers, avoid household plants and mulch. To avoid pollens, avoid outdoor environment when pollen counts are high, keep grass cut short, bathe dog frequently, use air conditioners and change filters often, and wipe the pet down with a wet cloth after outdoor activity.
2. Barrier Enhancement: The defective cutaneous barrier is an appealing area of study. Shampoos, sprays, and topically applied medications with barrier enhancement properties are available. All patients with CAD should be on some form of topical therapy. In addition to possible barrier enhancement, one benefit of topical therapy is mechanical removal of allergens from skin and hair coat. This likely decreases quantity of allergen in contact with skin and likely decreases the amount of percutaneous exposure of allergen through the defective cutaneous barrier.
3. Control of Secondary Infections: Antimicrobial therapy is used for active infections and may have a purpose in prophylactic therapy in some situations. Topical and systemic antimicrobials should be used as indicated. The dermatologist will ensure that there is adequate control of secondary infections as they proceed through diagnostic steps and design the management plan.
4. Immunotherapy: Immunotherapy, is the practice of administering increasing quantities of an allergen extract to an allergic subject to ameliorate symptoms associated with subsequent exposure to the causative allergen. Allergen specific immunotherapy (ASIT) should be recommended in all cases of CAD, unless clinical signs are very mild and controlled easily with nonsteroidal therapy. I recommend ASIT be incorporated early in the course of disease as a core component of the management plan.
The mechanism of action of ASIT is complex and not fully understood. Essentially, the pet is “desensitized” to specific allergens to which it has demonstrated hypersensitivity, and immune tolerance is induced. In dogs, the expected time to response is roughly 4-12 months. Generally, 60-75% of patients have at least a 50% improvement in clinical signs. A 50% reduction in pruritus should be considered favorable, as it may permit elimination of corticosteroids or other adjunctive medications.
In order to prescribe ASIT, allergens to which a dog is hypersensitive need to be identified through allergy testing. Both intradermal and serum tests detect allergens. A positive allergy test indicates the presence of excessive amounts of IgE, and a positive result may be associated with clinical allergy or subclinical hypersensitivity. The significance of a positive result can only be ascertained once all other causes for the dermatitis have been ruled out. Also, a positive result should be for an allergen present in high quantities at the time of year that the individual patient has exacerbations of skin disease. Thus, the dermatologist will review patient history prior to selection of allergens for immunotherapy.
When considering which type of test (intradermal or serum) should be performed, consider that neither modality is perfect. Both intradermal and serum testing have their place in dermatology practice. Also, neither type has been proven to be more accurate than the other. Intradermal tests have been regarded as the gold standard. Both tests, if performed and used appropriately, may provide good information. I prefer to perform both tests. A small percentage of dogs with CAD never have positive allergy tests, and this is considered to be equivalent to human intrinsic atopic dermatitis.
Intradermal allergy testing (IDT) detects the presence of tissue-bound IgE and the ability of the antibody to bind allergen and cause mast cell degranulation to form an erythematous wheal. Thus, it detects type I hypersensitivity reactions. All positive reactions might not be relevant. Positive IDT reactions have been identified in 60% of normal dogs. Negative IDT reactivity was demonstrated in 20% of dogs in a population of dogs with clinical signs of atopy. Efficacy of immunotherapy based solely on IDT test results is reported to be 60-70%.
Serum allergy testing is used to measure serum concentrations of specific IgE. None of the commercially available serum tests has been proven to be more accurate than another in reviewed publications. There are several tests available and each uses a slightly different method to detect the serum IgE levels. In the tests, the specificity of the IgE detection reagent is critically important to minimize false positives. One enzyme linked immunoassay (ELISA) is used to detect antigen-specific IgE using a unique recombinant fragment of the extracellular portion of the human high-affinity Ige receptor alpha subunit, and takes advantage of the strong affinity of this molecule for canine IgE and lack of reactivity with canine IgG.
5. Antihistamines: The appeal of antihistamines is that they are nonsteroidal and relatively safe, yet they are not approved by the FDA for the use in CAD. They are used in 30-50% of CAD patients, but only 10-15% of dogs have a sustained reduction in pruritus. Owners must administer antihistamines consistently and not just as needed. The main mechanism is to block H1 receptors in the skin and prevent or reduce the release of histamine. If only given after clinical signs are present, histamine is already circulating. Antihistamines may be the only required therapy for pets with seasonal or mild pruritus. There is a variable response between dogs to the different antihistamines. Variability is likely due to the uncertain role of histamine in the pathogenesis of AD. An owner may need to be patient and try several for 10- 14 day trials.
6. Essential Fatty acids: Fatty acids improve the skin and hair coat and enhance the epidermal barrier. Essential fatty acids cannot be synthesized and need to be supplied. Both omega 3 and omega 6 have been recommended; omega 3 for pruritus and omega 6 for the restoration of the cutaneous barrier. I recommended fish oils for all patients with CAD as part of the overall plan. They modulate leukotriene and prostaglandin synthesis, restore the normal composition of lipids in the skin, and modulate lymphocyte functions. They decrease pruritus and inflammation by altering the potency and quantity of mediators formed during inflammation. Common sources include cold water marine oil, evening primrose, borage, and black currant oil. For CAD, high dosages of omega-3 fish oils are required through diet and supplementation. The suggested dose of eicosapentaenoic acid (EPA) is 180 mg/10# of body weight per day.
7. Topicals: Shampoos, conditioners, sprays, rinses, and leave-on conditioners are available and may remove allergens from the skin surface. In addition, restoration or enhancement of the compromised epidermal barrier may reduce allergen penetration, microbe penetration, and irritant exposure to the skin immune system. When choosing products, consider the goal of topical therapy. If the dog gets recurrent infections, prescribe products with antimicrobial properties. If trying to reduce pruritus, antipruritics are recommended.
8. Corticosteroids: Corticosteroids are anti-inflammatory agents used in 65-80% of atopic dogs. They are appealing because of their rapid time to effect, but side effects occur with chronic usage. In the management of CAD, we aim to limit the usage of corticosteroids. All the other elements of our management plans are aimed at eliminating the need for corticosteroids all together. If corticosteroids are part of the plan initially or for flares, they are used strategically and carefully. Side effects of corticosteroids include PU/PD, polyphagia, behavioral changes, panting, diarrhea, GI ulceration, pancreatitis, myopathy, bacturia, pyoderma, demodicosis, respiratory tract infections, alopecia, thin skin, comedones, calcinosis cutis, osteoporosis, diabetes mellitus, and decreased synthesis of thyroid hormones. Monitoring for side effects must be scheduled and planned. At least q 6 months serum biochemistry, CBC, and urine culture are recommended in my practice.
9. Cyclosporine: There is strong evidence for the use of oral cyclosporine in the management of CAD. Cyclosporine is an anti-inflammatory medication when used at dosages recommended for CAD. It should be given on an empty stomach in dogs. Metabolism is inhibited in cases of liver dysfunction or when drugs that suppress the cytochrome p450 system are given. In the dog, CSA is metabolized rapidly in the liver by the cytochrome P450 enzyme system. Other medications also using this enzyme system may alter CSA concentrations. Ketoconazole, cimetidine, Phenobarbital, rifampin, diltiazam are examples.
For CAD, an oral microemulsion, modified, formulation is used. Compounded formulations are not modified and have exceptionally poor bioavailability. Neoral® and Atopica® (Novartis Animal Health) are microemulsified formulations. Sandimmune, some generic capsules, and compounded products are not modified. Atopica® is FDA approved for the management of CAD. It is contraindicated in any dog that has a history of malignant neoplasia.
In clinical practice, I expect that 70% of well characterized dogs with CAD will have a 50% reduction in pruritus. Some have 100% response and some still require additional medications. Patients still require assessment and reassessment on a regular basis. I have owners consider Atopica® as a component of the overall management plan. Reevaluation after 4 -8 weeks while the dog is still receiving treatment is essential to establish a response to therapy. Do not adjust dose or frequency without assessment. Many failures are attributed to the owner decreasing the frequency of administered when there has not yet been a response to therapy. Often 6-8 weeks is needed. Some dogs may be tapered to q 48 hr administration.
The safety of Atopica® has also been evaluated extensively in dogs. It is well tolerated by most dogs for long term therapy. The most common side effects reported include gingival hyperplasia, papillomatosis, vomiting, diarrhea, bacterial infections. I always advise that vomiting and diarrhea may occur. This typically is noted the first 2 weeks of therapy. If either occurs, I have the owner discontinue administration and call. Typically, signs resolve without intervention in 1-2 days. Then, I have them restart administration. When restarting, I have the owner administer the capsule with a small amount of food until it is tolerated for a few days. Then, food is discontinued, and it is administered on an empty stomach thereafter.