Update on canine atopy: Diagnosis and management (Proceedings)

Pathogenesis

Canine atopy has traditionally been defined as an inherited predisposition to the development of IgE (reaginic antibodies) to environmental allergens resulting in allergic disease. There are other important components of the immune system associated with canine atopic disease including Langerhans' cells, T cells, and eosinophils.

Two studies have shown some correlation between exposure to pollens shortly after birth and sensitization. Puppies born in the "off-pollen" season were less likely to develop atopic disease. High-IgE puppies were immunized with an allergen shortly after birth, but not after 3-4 months of age. Recent studies have shown IgE to be associated with epidermal antigen capture and subsequent attachment to Langerhans' cells.

Inhalation has been considered the route of entry of environmental allergens. There is strong evidence in both man and animals that percutaneous absorption is an important route of entry. In dogs, it is most likely the primary route with the IgE on the Langerhans' cells trapping the epidermal antigen, subsequent processing of the allergen by the Langerhans' cells and presentation to allergen-specific T lymphocytes. There may be an inherited defect of epidermal barrier function which contributes to the percutaneous absorption.

Clinical and experimental evidence supports the observation that secondary bacterial and yeast infections can both initiate and perpetuate episodes of Atopic Dermatitis and participate in promotion of pro-allergic immunologic responses.

History and clinical signs

A tentative diagnosis of canine atopic disease is based on the history and clinical findings and elimination of other differential diagnoses. Atopy usually manifests in the young adult dog with approximately 75% of the atopic dogs manifesting symptoms between 1 and 3 years of age. Atopy may be observed in any breed. The list of predisposed breeds includes most terrier breeds, beagle, Chinese sharpei, Dalmation, English bulldog, English setter, golden retriever, Lhasa apso, miniature schnauzer and pug, A history of chronic or relapsing bacterial or Malassezia dermatitis or otitis is common.

Clinical signs have substantial variation among atopic dogs. However, there are predicable distribution patterns of skin involvement. The face, feet, ears and cranial aspects of the extremities are frequently involved. Mild to moderate seborrheic changes are also common Checklists of criteria consistent with Atopic Dermatitis have been proposed (Table 1). These criteria are not pathognomomic but are highly suggestive for atopy. Since there is significant variation of the history and clinical signs among atopic dogs it is reasonable to include atopy as a primary differential diagnosis if the patient meets the criteria

Once the initial clinical criteria for atopy are fulfilled, other differential diagnoses must be ruled out. The following diagnoses are usually the most important to eliminate: flea allergy dermatitis, adverse reactions to food (ARF), Sarcoptic mange, pruritic bacterial folliculitis, Malassezia dermatitis, and pruritic keratinization disorders (seborrhea). Frequently, one or more of the other differential diagnoses are secondary complications of Atopic Disease (bacteria, Malassezia, seborrhea). The concurrent problems (ARF) or secondary problems can significantly alter the clinical presentation as well as response to medications.

Laboratory tests

Laboratory tests that identify reactions to specific aeroallergens merely provide additional evidence to strengthen the case for a definitive diagnosis of atopy. Serum (ELISA/Liquid phase) and intradermal skin tests are widely used to identify sensitivity to specific environmental allergens The most common factors affecting the outcome of these tests are seasonal incidence of allergens and drugs (corticosteroids and antihistamines . Some reference laboratories state that corticosteroids do not interfere with serum allergen test results. However, when possible it is recommended to withdraw all systemic prednisone or prednisolone for 3 weeks before testing. If residual corticosteroids have been administered, 6-8 week waiting period may be necessary. All steroids interfere with the intradermal skin test. Antihistamines do not interfere with the serum testing but do interfere with the intradermal tests. A minimum withdrawal time of 5-7 days is recommended.

Testing "off season" for seasonal allergens may result in weaker or false negative reactions. Young dogs tested at one to two years of age may have limited positive reactions and subsequently develop reactions to additional allergens. This is consistent with the finding that up to 60% of the dogs with seasonal pruritus will develop nonseasonal symptoms as they age. There is only partial correlation (concordance) between serological and intradermal test results. Concordance of reactions has been reported to be 19% to 77% for individual allergens. Both false negative and positive reactions may occur.

Cross-reactivity among various allergens may occur. For pollens, there are several common allergen components within plant families. Different insects may exhibit some cross-reactivity. Notably, dust mite and food storage mite reactions are common while food storage mite only reactions are infrequently observed. It is generally recommended to test for individual allergens rather than groups of allergens.

Interpretation of allergy tests

The most important factor to consider after either serum or intradermal skin test results are obtained is to determine if the positive reactions correlate with the history. If the pruritus is nonseasonal are there significant mold and dust mite reactions? In the Northeast, if the pruritus is primarily August-November, is there a positive reaction to ragweed? What are the predominant allergies in the dog's environment? If cat dander or feathers are positive reactions, are there birds, down comforters or cats in the house?

The standard allergen screens vary among reference laboratories, particularly with the number of molds included in the standard regional panels. It is important to select standard or special allergen screens based on the history. For example, if a dog has a predominant nonseasonal pruritus, an expanded mold screen should be considered. If insect reactions are suspected, an expanded insect screen may be requested.

Management

Management of atopic dermatitis is multifaceted with combinations of avoidance, pharmacology, antimicrobial therapy and immunotherapy required.

Avoidance: Total avoidance is seldom possible for the aeroallergens. However, the exposure to pollens may be limited by avoiding overgrown or mature vegetation (weed and grass pollens). Avoiding damp basements, use of dehumidifiers and minimizing exposure to damp leaves or wooded areas may minimize mold exposure. Maintenance of adequate preventative flea control will help avoid parasitic problems that may predispose or aggravate atopic disease.

Anti-inflammatory agents:

Glucocorticosteroids (0.5 to 1.0 mg/kg q24-48 hrs) have the most predictable response with the most potential adverse effects. Administer the minimal amount needed to control symptoms. If the pet is not showing any signs of pruritus, the dosage is too high or to frequent.

Cyclosporine (5 mg/kg q24 hours) and prednisone have been shown to elicit similar therapeutic results. The most common short-term adverse reactions are vomiting or loose stool. Most dogs that experience these problems when initiating treatment will tolerate the medication within a week. The maximum serum levels are obtained if cyclosporine is administered without food (2 hrs before or after). However, if there are any gastrointestinal problems, administering cyclosporine with food may overcome the symptoms. Several studies have reported no problems with long-term (at least 5 yrs) of cyclosporine treatment. If ketoconazole (5-10 mg/kg) is administered concurrently with cyclosporine, the cyclosporine dosage may be decreased by 50-60%. The liver function should be monitored when ketoconazole is being used.

Antihistamines result in variable responses. Overall 15-25% of the dogs with atopy will control satisfactorily with antihistamines. The frequency is usually q12 hours. The major adverse reaction is sedation if over dosing. The average dosage for diphenhydramine or hydroxyzine is 2 mg/kg q12 hrs. Other recommended doses are Clemastine (Tavist) at 0.05-0.1 mg/kg, chlorpheniramine at 0.4 mg/kg and Loratadine (Clariton) at 0.25-0.50 mg/kg q24 hrs. Amitriptyline (1 mg/kg) and doxepin (1-2 mg/kg) are tricyclic antidepressants with H1 blocking effect. Trimeprazine with prednisolone (Temaril P®, Pfizer) is frequently used for dogs requiring long term symptomatic antipruritic therapy. The synergistic effect of prednisone and antihistamines results in a lower dose of prednisone with fewer adverse reactions.

Essential fatty acids (Omega 3 and 6) result in variable responses (0-40%). They are most often used as adjunct therapy with other medications. Omega 3 (marine fish oils) have the most anti-inflammatory effect. Eicosapentanoic acid (EPA) at a dose of 180 mg/10 pounds body weight is an average recommended dose.

Other drugs with anti-inflammatory properties include pentoxifylline (Trental®), misoprostol (Cyotec®) and dextromorphan. These drugs have variable effects in masking the pruritus.

Topical antipruritic therapy:

Bathing weekly is indicated to help remove the aeroallergens that are gain entrance through percutaneous absorption. A colloidal oatmeal shampoo is most commonly used if there are no active skin lesions. The hygroscopic properties aid in the maintenance of normal skin surface resulting in less pruritus. Use of an antibacterial/antiyeast/antiseborrheic shampoo weekly is indicated if there is secondary infection or seborrheic signs. The application of a humectant or emollient after the bath will further aid in maintenance of the skin surface, especially if some of the oils have been removed with the antiseborrheic shampoos.

Immunotherapy (hyposensitization):

Immunotherapy should be considered when a diagnosis of atopic dermatitis has been made based on the historical and clinical criteria and testing has identified the specific allergens that are most likely to be contributing to the disease based on the correlation of the history and positive allergen reactions or when symptomatic therapy is ineffective or prone to side effects. Under the best of circumstances a 60-70% good to excellent response to hyposensitization may be expected.

After starting hyposensitization an initial period of six to eight months is often required to elicit the maximum response to allergen injections. The most important factors influencing the clinical response are 1) selecting the allergens to be included in the allergy vaccine based on the correlation of history and exposure, 2) adjusting the injection schedule (dose and frequency) when needed and 3) controlling concurrent or secondary problems that contribute to the clinical signs. The most common adverse reaction to allergy injections is a marked increase in pruritus within 24-48 hours after the injection. If this occurs, the dosage and/or frequency must be decreased. Approximately 50% of the protocols will need some adjustment. The client must be educated to monitor response and adverse reactions and the clinician and/or/technician must be prepared and available to provide the needed guidance. Good communications between the client and clinician often result in a higher rate of good response to hyposensitization, better compliance and fewer clients discontinuing hyposensitization. It is generally recommended to reevaluate the dog after 2-3 months of hyposensitization to assess initial response, identify any problems with the allergy injections or secondary complications and to reinforce the client/doctor communications required for the maximum success of hyposensitization.

Other concurrent therapy:

Concurrent antibiotics and antifungal medications are frequently required to treat secondary complications. If excessive foot licking, greasiness of axillae or groin regions or generalized seborrheic lesions are present, Malassezia must be considered. The administration of ketoconazole (5-10mg/kg q24hrs) is often needed to control the Malassezia dermatitis. A marked reduction of pruritus may be observed. Superficial pyoderma is often mildly to moderately pruritic. Antibiotics should be administered for at least 1 week after all of the pyodermic lesions are resolved. Bathing every 3-7 days with shampoos containing antibacterial/ antifungal shampoos is recommended.

Best results in the management of the atopic patient are obtained if an integrated approach is followed by 1) utilizing topical and systemic antipruritic drugs, 2) recognizing and treating all secondary complications and 3) using immunotherapy based on a strong correlation between pruritic history and the exposure to specific allergens that are positive on intradermal or serum tests.

Table 1: Clinical criteria for diagnosis of canine atopic dermatitis.

a Adapted from Willemse TA. Atopic dermatitis. In Comtemporary Issues in Small Animal Dermatology Vol. 8, Dermatology, Nesbitt GH (Ed). Churchill Livingstone, New York 1987:71.

b Prelaud P., Guagere E, Alhaidari Z, et al. Reevaluation of diagnostic criteria of canine atopic dermatitis. Rev. Med. Vet. 1998:149:1057-1064.