DESIGNING THE TREATMENT PLAN

Once the diagnosis of atopic dermatitis has been made, a treatment plan can be created. To formulate this plan, the clinician must evaluate the patient, owner, and disease severity. When evaluating the patient, the clinician must consider factors such as other concurrent medical conditions, temperament at home and in the hospital, environment (e.g., indoor only, outdoor only), and acceptance of medications. The veterinarian must evaluate the owner for similar factors, including concurrent medical illness (e.g., an owner with rheumatoid arthritis may not be able to administer allergy injections), previous compliance or lack thereof, attitude towards the patient, lifestyle, and potential financial constraints. Disease severity is considered separate from the patient, because this determines how quickly the patient may need relief. For example, in a cat with severe excoriations and alopecia secondary to intense pruritus, both an aggressive short-term and long-term plan for control may be necessary. In a cat with mild or more seasonal atopic dermatitis, a more conservative treatment plan may be adequate.

THERAPEUTIC OPTIONS

There are five generic categories of treatment options for atopic cats. These include ASIT, fatty acids, antihistamines, glucocorticoids, and other immunosuppressive medications (e.g., cyclosporine A).¹ Fatty acids, antihistamines, glucocorticoids, and other immunosuppressive medications focus on treating or modulating the inflammation triggered by the allergic reaction, whereas ASIT modulates the immune system to prevent the allergic reaction from developing. These categories are by no means exclusive nor are they the only potential treatment options. Instead, these categories are meant to be a starting point, and in the majority of patients either individually or in combination, these treatment options will provide relief for allergic cats. When creating the initial treatment plan, the veterinarian must take into account the benefits and disadvantages of each general category, and decide on a course of treatment in light of her or his observations about the patient, owner, and disease severity. For example, a cat with severe excoriations may benefit from the short-term use of oral glucocorticoids or antihistamines in combination with the initiation of immunotherapy. A noncompliant owner who may not administer allergy injections regularly may be best served by treating the patient with cyclosporine A in combination with rush induction of ASIT. On the other hand, ASIT may not be the best treatment choice in a feline patient with short seasonally recurrent disease. In the latter case a short course of antihistamines or oral glucocorticoids may be more appropriate. If this patient were to be treated with ASIT, the response to treatment could not be evaluated until the following year, but the owner would be required to administer allergy injections year round. Additionally, the expense of allergy testing and ASIT may be unwarranted for owners with financial constraints.

ALLERGEN-SPECIFIC IMMUNOTHERAPY

ASIT is the practice of administering gradually increasing quantities of an allergen extract to an allergic patient, the purpose of which is to reduce or eliminate the clinical signs associated with subsequent exposures to the causative allergen.² Although only well documented in human allergic patients and still considered a rare event, ASIT is the only therapeutic option for allergic diseases that may cure the patient through immunomodulation after years of therapy.³ Multiple clinical studies have shown ASIT to be a safe and effective treatment for human beings and dogs with atopic dermatitis.^2,³ In contrast, fewer studies have been performed in feline atopic patients.⁴ Those studies and anecdotal observations by veterinary dermatologists suggest that ASIT is an effective treatment option in atopic cats; however, its true success or failure rate is undocumented because no comprehensive studies have been completed.

MECHANISM OF ACTION

Atopic dermatitis in human beings and animals is characterized by the overproduction of allergen-specific immunoglobulin (Ig) E against normally innocuous environmental antigens. The inhalation of aeroallergens in sensitized human patients leads to Th2-biased immune deviation and subsequent production of cytokines that induce allergic disease.^5,⁶ In sensitized individuals allergen exposure induces cross-linking of FcERI receptor-bound IgE on effector cells. Once triggered this results in the immediate release of anaphylactic mediators and development of inflammation.

Although neither the underlying pathogenesis of atopic dermatitis nor the mechanism of action of ASIT in feline atopic patients has been fully elucidated, they are thought to be similar to that seen in human patients. Despite the fact that the use of ASIT in human beings began at the beginning of the twentieth century, the underlying mechanisms of ASIT are being elucidated to this day.^3,⁵^–⁷ ASIT is postulated to normalize the dysregulated immune response that characterizes the allergic state. Both short- and long-term modulations of the immune system are initiated by ASIT, including alterations in the quantities and types of inflammatory cells, modifications in the secretion of inflammatory mediators, changes in the types and concentrations of allergen-specific immunoglobulins, and modulations of T-cell functions and cytokine production.^3,⁵^–⁷

Such modulations are exhibited classically in human patients undergoing venom immunotherapy. During the first few months of treatment, a decrease is noted in both mast cell and basophil activity for degranulation and systemic anaphylaxis. This alteration in activity is thought to result from the piecemeal release of anaphylactic mediators (histamine and leukotrienes) triggered by ASIT.³ T regulatory (T reg) cells are a specific subclass of T lymphocytes that exhibit suppressive or regulatory functions. The generation of T reg cells and the suppression of allergen-specific Th1 and Th2 cells are noted in the early stages of ASIT.

T reg cells are generated within days of beginning ASIT, and contribute to the control of allergen-specific immune responses in five major ways. The first is the suppression of antigen-presenting cells; these cells support the development of Th1 and Th2 lymphocytes. Second, T reg cells suppress Th1 and Th2 cells directly. T reg cells also suppress allergen-specific IgE production along with mast cells, basophils, and eosinophils. Finally, T reg cells interact with local resident tissue cells and stimulate remodeling of these barriers. These actions eventually lead to a decrease in IgE/IgG4 ratios during ASIT. The levels of IgE allergen-specific antibodies decrease, and the levels of IgG4 blocking antibodies that prevent the cross-linking of the FcERI receptor increase over time (i.e., years). Therefore the entire desired effects of ASIT may take several years to achieve, making ASIT a long-term treatment option.^2,^3,^6,⁷

BENEFITS VERSUS DRAWBACKS OF ALLERGEN-SPECIFIC IMMUNOTHERAPY

ASIT offers an effective and safe treatment option for cats. Reported success rates range from 60 to 78 per cent in feline atopic patients.^8,⁹ Additionally, the reported incidence of side effects in feline atopic patients undergoing ASIT is very low. A thorough literature search failed to reveal any documented cases of systemic reactions in feline patients undergoing traditional ASIT. Anecdotally, reported reactions in cats are rare and consist primarily of increased pruritus; however, anaphylaxis has been reported in a few cases. It has been reported anecdotally that one cat developed localized pruritus, vomiting, and diarrhea after an injection of 0.3 mL of approximately 20,000 PNU/mL. The cat was taken to an emergency clinic and responded well to treatment. Respiratory distress and gastrointestinal signs have been reported anecdotally in another cat within 3 hours of an injection. Anaphylaxis appears to be a rare event, although the complication must be considered a theoretical possibility.

The risk of an adverse reaction appears to increase in cats undergoing rush induction of ASIT. A pilot study investigating the use of a rush induction protocol reported the development of a localized injection site reaction in two of the four cats involved in the study. This study was conducted in feline patients with naturally occurring atopic dermatitis.¹⁰ Separate studies evaluating the response of asthmatic cats sensitized to Bermuda grass allergen to more aggressive rush immunotherapy protocols have resulted in multiple systemic reactions during the induction.^5,¹¹ These reactions will be discussed in greater detail later in this chapter.

The primary drawback to ASIT from a client’s perspective appears to be the cost associated with initiating therapy. Allergy testing must be performed, and regardless of the method used, it can be cost-prohibitive for some owners. However, when one compares the costs of other therapeutic options and the monitoring required to maintain these therapies, ASIT typically is less expensive in the long term. The initial costs of ASIT may be substantial, but once maintenance therapy has been established, the costs are reasonable for most owners.

The primary drawback to ASIT for the veterinarian is the time commitment involved in ensuring successful completion of the ASIT protocol. Whether owners are administering the injections at home or bringing their cats to the hospital for their injections, the clinician or assistant/technician must follow up frequently with the client. In many patients a response to therapy is not seen for several months once therapy begins, and clients are tempted to stop prematurely before the treatment has had time to be effective. Additionally, some owners may notice adverse effects from the injections and fail to notify the clinician. Owners often believe that everything can be fixed quickly with minimal effort. A significant amount of hand holding is required to overcome this notion through the first few months of ASIT when no response to therapy is seen. Failure to follow through after beginning ASIT may lead to further frustration on the client’s part and cause the clinician to lose a patient. Therefore the decision to offer ASIT as a therapeutic option to a client is not to be entered into without thorough evaluation of the client’s and clinician’s long-term commitment to follow through.

In areas where referral to a veterinary dermatologist is a feasible option, ASIT should be considered sooner rather than later. Patients who undergo ASIT in earlier stages of disease may respond better than those who have become chronic sufferers. Many clients become frustrated and fail to express their frustration to their attending veterinarian. Instead these clients choose to seek a second opinion, often from a different hospital. As tertiary care clinicians, the clients who are referred for our opinion before becoming frustrated tend to be happier and plan on returning to the same family veterinarian. Those clients who seek referral on their own frequently are frustrated and refuse to return to their previous veterinarians.