Management

The caregiving client is a critical component of the management of chronic disease. Academic evidence-based reviews are a key factor in determining therapeutic options to discuss with a client.

A veterinarian's compassionate discussion of therapeutic costs and options, including OTC products, can result in reaffirmation of the importance of shared decision making with regards to the management of chronic disease. With this type of healthy relation­ship, should the OTC products not provide adequate relief; the client may then feel more comfortable scheduling a follow up with their veterinarian. In some cases, after educating a client who has chosen nonprescription therapy, I have written a proposed course of optional prescription drug therapy to be initi­ated in the very near future.

The multitude of factors contributing to pruritus in the atopic patient can be complex and a multimodal approach to therapy is common.

Table 2.3 Pruritus therapies.

Diagnosis

Chronic therapy recommendations

Flea-bite-induced pruritus

Food-induced pruritus

Atopy-induced pruritus

If the only diagnosis is flea bite pruritus, stringent flea control is the long term treatment of choice. Palliative antipruritic therapy may be necessary for a few months until flea control can be achieved or during exacerbations.

If the only diagnosis is food allergy, a strictly followed hypoallergenic diet is the long­term treatment of choice. Palliative antipruritic therapy may not always be helpful for food allergy/adverse reactions to food.

If the only diagnosis is atopic dermatitis, allergen specific immunotherapy (ASIT) is the long-term treatment of choice for patients. Palliative adjunct antipruritic therapy may be necessary either temporarily or for longer duration. For patients with symptoms present for less than 3 months out of the year and not anticipated to suffer from progression of their disease, palliative antipruritic therapy may be the only therapy necessary. Atopic dermatitis is often a progressive disease and medical therapeutic options may need to be changed periodically. For patients, particularly those of predisposed breeds in many geographic areas, allergy testing and ASIT may be considered before 18 months of age.

patient” (Olivry and Sousa 2001). More recently, the recognition of a defect in the epidermal barrier function in atopic patients has led to a renewed emphasis regarding skin, coat care, and shampoo therapy (Favrot et al.

A systematic evidenced-based review in 2010 evaluating interventions for the manage­ment of atopic dermatitis in dogs found six interventions to demonstrate some evidence of efficacy to decrease pruritus and/or skin lesions. These included topical tacrolimus, topical triamcinolone, oral ciclosporin, oral glucocorticoids, subcutaneous recombinant gamma interferon, and subcutaneous allergen specific immunotherapy. Importantly, one study showed a particular essential fatty acid supplement to reduce prednisolone use (Olivry et al. 2010). This review was published before the commercial availability of oclaci- tanib, which is effective and indicated for con­trol of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age (Apoquel prod­uct information 2016).

For a variety of reasons, many veterinarians utilize oral prednisone/prednisolone, oral oclacitanib or oral ciclosporin when faced with the reality of managing chronic pruritus due to atopic dermatitis. While all three of these med­ications have proven to be quite useful for this purpose, each has its own nuances. As previ­ously discussed, antihistamines and fatty acids should not be overlooked as potential adjunc­tive therapy. They may help reduce the use of these prescription medications while reducing costs and concerns about potential side effects. All of these may be useful while waiting for allergen specific immunotherapy to become effective or as adjunctive chronic therapy.

Prednisone has been used for many decades as a very cost-effective means of controlling pruritus (and inflammation). Most veterinary practitioners are well acquainted with their efficacy and side effects. Depending on dos­age, they may have different attributes. The prednisone/prednisolone dosages below are those generally utilized for dogs.

• Immunosuppressive: 2.2-4.0 mg∕kg∕q24h or divided BID for 4-10 days, then tapered to every 48 hours

• Anti-inflammatory: 1.1-2.2 mg∕kg∕q24h or divided BID for 2-6 days, then tapered to every 48 hours

• Antipruritic: 0.5 mg/kg/q 48 h

• Replacement: 0.2-0.3 mg/kg/q24h

Most atopic patients, without a pyoderma, respond well to a single SQ dexamethasone SP injection (see acute/rescue therapies later in this chapter), followed the next day by the initiation of oral prednisone approximating the daily replacement dosage of 0.2-0.3mg/ kg but actually administered every 48 hours. Over time, this results in a dosage that is cumulatively 50% of the physiological replacement dose. With every 48-hour administration, the effect on the hypotha­lamic-pituitary-adrenal axis should be mini­mal. This regimen is not effective in all cases, particularly those that are more sympto­matic. It is tailored to the individual patient, who should be monitored periodically. More severely affected patients may temporarily require a higher dose of oral prednisone after a dexamethasone injection. This protocol has also been utilized concurrently in the short to intermediate term with each of the other therapies discussed later. The careful use of a cost-effective medication such as prednisone is an important consideration for many clients.

Oclacitanib (Apoquel®), a synthetic Janus Kinase (JAK) inhibitor, has recently become widely available. Like steroids, it is fast act­ing. The veterinary package insert states the following indications: “Control of pruritus associated with allergic dermatitis and con­trol of atopic dermatitis in dogs at least 12 months of age.” The dosage is 0.4-0.6 mg/kg twice daily for up to 14 days and then administered once daily for maintenance therapy. The package insert precautions state that “Dogs receiving Apoquel® should be monitored for the development of infec­tions, including demodicosis and neopla­sia.” In order to help prevent long-term twice a day dosing by clients, many veteri­nary dermatologists start dosing with only a once a day schedule.

Ciclosporin Modified (Atopica* and generic equivalents in “modified” form so as be microemulsified for better absorption) is a cyclic polypeptide, immune modulating agent that has been commercially available for dogs for many years and somewhat more recently for cats. Unlike prednisone and oclacitanib, it is not fast acting and may require 3-6 weeks or more of therapy to determine its efficacy. The package insert states the following indications for dogs: “for the control of atopic dermatitis in dogs weighing at least 4 pounds body weight” and over 6 months of age. In cats, it is indicated: “for the control of feline allergic dermatitis as manifested by excoriations (including facial and neck), military dermatitis, eosinophilic plaques, and self-induced alopecia in cats at least 6 months of age and at least 3lbs (1.4 kg) in body weight.” The dosage in dogs is 3.3­6.7 mg/kg/day as a single daily dose for 30 days (Atopica product information 2016) and then it may be tapered in some patients. This is done by decreasing the frequency of dosing to every other day or 2-3 times a week. For cats, it is available in liquid form and the dose is 3.2 mg/lb/day (7 mg/kg/day) as a single daily dose for a minimum of 4 to 6 weeks or until resolution of clinical signs, and then tapered in a manner similar to the protocol for dogs. Ciclosporin should be used with caution with drugs that affect the P-450 enzyme system, such as ketoconazole. Vomiting and/or diarrhea are the most com­monly observed adverse reactions. Hypertrichosis, gingival hyperplasia, and papillomas are rare but well recognized in association with ciclosporine use. The feline product insert “Warnings” states: “Atopica for cats is a systemic immunosuppressant that may increase the susceptibility to infec­tion and the development of neoplasia.” In dogs, the label contraindications states: “Atopica is contraindicated for use in dogs with a history of neoplasia.”

Allergen-specific immunotherapy (ASIT) was subjected to a systematic review that confirmed the safety and efficacy of subcuta­neous ASIT in reducing the signs of atopic dermatitis (Favrot et al. 2010). After that publication, sublingual allergen specific immunotherapy (SLIT) has also been widely adopted. The general consensus among dermatologists who also utilize ASIT is that SLIT is effective and safe. Importantly, the 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis states that “ASIT is the only inter­vention that has the potential to prevent the development of signs and alter the long-term course of the disease.” For patients who have symptoms which do not respond to sympto­matic medical therapy or experience unac­ceptable side effects, even for relatively short periods of time, ASIT is indicated (Favrot et al. 2010).

A primary care veterinarian may refer a patient for allergy testing and ASIT or SLIT. This is common because immunotherapy is not as straight forward to utilize as pharma­cological therapy. Consequently, clients can become discouraged and unfortunately dis­continue therapy before allowing adequate time to provide observable benefit, which can take as long as 12 months. The protocol including dose, frequency, and duration of therapy is typically tailored to the patient and client's needs and a complex decision process. While waiting for the immunother­apy to become effective, judicious use of concurrent medical therapy in a gradually tapering manner can help control a patient's symptoms while serving to continually edu­cate the caregiver about short and long-term goals. In some patients, the overall degree of pruritus may not obviously change, but eventually all medical therapy can be dis­continued and an adequate level of comfort achieved without the use of drugs. Many practitioners utilize ASIT and SLIT with good results. If good results are not obtained, clients may then inappropriately believe that changes in testing modality and/or immunotherapy protocol are not indicated. This complicated situation is best discussed with a caregiver before allergy testing in conjunction with the option of referral to a veterinarian with specialty training in this complex modality.

The use of safe, cost-effective, and easily followed regimens for acute pruritus relief coupled with education allows the primary care practitioner, referral specialist, and cli­ent to work together towards a collaborative long-term plan aimed at controlling chronic pruritus and recurrent pyoderma due to atopic dermatitis.

Acute and Rescue Palliative

Therapy

Most pruritic patients are also inflamed. In situations where topical therapy is not enough, judicious systemic short-term glu­cocorticoid use can be an extremely effective tool to control an acute flare up of pruritus associated with atopic dermatitis that is not complicated by significant secondary infec­tion. For 25 years, this author has utilized a dexamethasone dosage similar to that used when performing a high dose dexamethasone suppression test in order to provide acute relief from pruritus and inflammation. This dosage is widely considered safe and appro­priate as a diagnostic tool even in a difficult to control diabetic patient in order to rule out Cushing's disease. Virtually all atopic patients without secondary infections should experience a significant reduction in pruritus lasting 1-4 days. If temporary relief is not noted, the tentative diagnosis of an acute atopic dermatitis exacerbation as the sole factor should be reevaluated and other causes of pruritus reconsidered. A similar improve­ment can also be achieved with oral gluco­corticoids but side effects such as polyuria, polydypsia and polyphagia are more likely and client compliance issues can complicate the assessment and plan. Oclacitanib can also be utilized to provide quick relief of pru­ritus. It is the author's clinical impression that the use of anti-inflammatory dosages as opposed to “antipruritic doses” of glucocorti­coids as a “crisis buster” is more likely to result in breaking the cycle of itch and inflam­mation and in decreasing the chronic need for prescription products. After the inflam- mation/itch cycle has been broken and the inciting factor(s) removed, three scenarios may occur. First, no further therapy may be necessary until the next time an inciting fac­tor leads to the pururitic threshold being reached. Second, mild concurrent atopy may then be adequately controlled by OTC products such as antihistamines and fatty acids. These products are more likely to be beneficial when used chronically to prevent flare ups than during an acute episode. Their consistent chronic used may decrease the need for long-term use of prescription products and rescue therapy. Third, pruri­tus will return and be symptomatic enough that prescription antipruritic therapy will be necessary. It is often a judgment call related to historical and physical examina­tion findings that lead the veterinary practi­tioner and caregiver to suspect that this will be the case and that intermediate term pre­scription management will be necessary. See earlier discussion regarding chronic management.

Common “Crisis Buster” drugs with a quick onset of activity for acute somewhat generalized pruritus associated with atopic dermatitis:

• Dexamethsone injection (anti-inflamma- tory/antipruritic dose)

• Oral prednisone, prednisolone or methyl­prednisolone (anti-inflammatory/antipru- ritic dose)

• Oral prednisolone/prednisone (antipru­ritic dose)

• Oral oclacitanib

Oral medications do offer patients and clients (who previously have been educated about reasons for acute exacerbations and therapeutic options) short-term “crisis buster” pruritus control without an acute care evaluation by their veterinarian. Many clients appreciate options for acute relief at the same time they are being educated about the potential side effects of long-term medical therapy. This balance of easy to follow symptom relief and client educa­tion emphasizes the need to identify and change the course of the underlying disease process.

In these situations, empathetic client com­munication, client engagement, and client education are essential for the both the short- and long-term well-being of the patient (Knesl et al. 2016).

My standard dexamethasone SP dose is 1 mg/10 pounds SQ or IV. This is equivalent to 0.75mg Dexamethsone/10 pounds. Using generally accepted steroid strength conver­sion values (5 mg pred/0.75mg dexametha­sone), this converts to prednisone at a dose of 1.1 mg Pred/kg. As stated elsewhere, the anti­inflammatory dose of pred is 1.0-1.5 mg/kg/ day, for 7 to 10 days. The anti-inflammatory dose is approximately 2 to 3 times the anti­pruritic dose. However, most pruritic patients are also inflamed. In these cases, I simply give one injection of dexamethasone SQ to “break the inflammatory cycle” and often do not need any more steroids while utilizing other medications. If more steroids are needed, I will then start oral prednisone 1 day later, at a standard antipruritic dose of 0.5 mg/ kg every 2 to 3 days and taper further over time. If the inflammation is severe, I will use a higher dose. For convenience sake, I often simply have the clients start the pred pills the day after the injection. For practical reasons, I typically administer the dexa- methsone subcutaneously, but will consider intravenously (IV) if necessary. I use the IV route if the client is uncertain regarding the response to steroids in the past. In this situa­tion, we call the client 24 hours later to docu­ment the response. Clinically, this technique works well in patients who have been well controlled with immunotherapy and/or other forms of medical therapy, but have suffered an exacerbation. Compared to dogs, cats seem to require about twice the dose of oral GC to achieve the same effects. Prednisolone should be used instead of pred­nisone in this species.

I emphasize the words simply and conveni­ence because the patient's primary caregiver (the client) is often burdened with many other tasks. I feel this approach is both medi­cally appropriate and helps prevent caregiver burnout as well as many financial concerns. Many clients may become emotionally and financially exhausted when overburdened with caring for an allergic pet. The doses dis­cussed were arrived at by comparing them to what would be necessary if prednisone were utilized, but trying to avoid the mineralocor­ticoid side effects. I justify the use of injectable dexamethasone SP by comparing the dose used in a high dose dexamethasone suppres­sion test. The same drug at a similar dose is used for a diagnostic test in a difficult to control diabetic dog who is also a Cushings suspect (high dose dexamethasone suppression test).