Practical glucocorticoid therapy (Sponsored by Pfizer Animal Health)

A confirmed diagnosis may not be immediately possible when a veterinarian is confronted with a pruritic dog or cat, and the list of differential diagnoses can be extensive.

1. Used appropriately, glucocorticoids can alleviate discomfort for patients with the ability to match the dose and duration of treatment to the patient's needs.

As clinicians, we are trained to consider the differential diagnoses and make a diagnosis based on the findings in the patient's history, physical examination, and diagnostic tests. While it is important to consider the possibility of scabies, demodicosis, dermatophytosis, neoplasia, and other differential diagnoses, the vast majority of pruritic patients have an allergic or flea-induced dermatitis with a secondary bacterial or yeast infection. Often, treatment of any secondary infections significantly reduces the patient's level of discomfort and pruritus. However, many patients also require additional therapy for the inflammation and pruritus associated with the underlying disease.

Acute amelioration of clinical signs can be achieved within minutes to hours, depending on the formulation and route of glucocorticoid administration. Regarding intermediate-term use of short-acting glucocorticoids, clients and patients benefit because the dose and route of administration can be changed depending on the patient's needs. This is particularly useful with atopic patients because the severity of clinical signs can vary daily and weekly.

Some common systemic glucocorticoid preparations and their inflammatory dosages for dogs are listed in Table 1.

Table 1

2. Patient-specific dosing is essential, and understanding the differences in physiologic, antipruritic, anti-inflammatory, and immunosuppressive dosages will help the practitioner safely meet the patient's and client's needs.

As clinicians, we may dismiss the idea of using glucocorticoids as a treatment in patients with a variety of clinical dermatologic signs. Our client education practices have successfully persuaded clients not to overuse this category of drugs. Consequently, we now find ourselves educating clients about the benefits of judicious and prudent glucocorticoid use for a variety of dermatoses. Explaining that animals normally produce their own glucocorticoids can help alleviate well-intentioned client aversion to therapy with glucocorticoids.

As with most medications, side effects are possible and increase in severity with higher doses and longer courses of therapy. However, glucocorticoids offer a rapid speed of efficacy, a short duration of activity, and an easily adjusted dosage regimen that is desired in the treatment of many dermatoses. Knowing that a one-time therapeutic dose of a glucocorticoid in an otherwise healthy animal can be less than the one-time diagnostic dose in a systemically ill patient ( a high-dose dexamethasone test for hyperadrenocorticism) can be liberating for clinicians who want to safely meet a patient's and client's needs. A safe annual glucocorticoid dose can allow clinicians to more comfortably manage patients and educate clients. This dose is actually less than the patient's own endogenous glucocorticoid production. (See "Guidelines for calculating glucocorticoid use.")

In veterinary dermatology, glucocorticoids have three main pharmacologic dosage ranges for dogs (Table 1). Pharmacologic dosages exceed the physiologic requirements and vary according to the desired effect. The physiologic dosage range of glucocorticoids therapy is derived from the normal daily production of endogenous cortisol. People experiencing stress have been shown to increase cortisol production to 10 times their physiologic levels. While canine dosage guidelines exist in the literature, treatment of each patient should be customized to achieve the lowest effective dosage and for the shortest period of time necessary to control the clinical signs.

3. Glucocorticoids are mainly used short-term while addressing causes of pruritus and treating complicating factors.

Many clinicians find one of the following protocols or a variation helpful when managing their allergic patients' inflammation and pruritus with glucocorticoids. They use these protocols while also addressing complicating factors and underlying or coexisting etiologies (e.g., fleas and secondary infections):

Acute canine protocol. Treat the inflammation and pruritus with two to five days of glucocorticoid therapy consisting of either a short-acting oral glucocorticoid or single injection of a short-acting glucocorticoid. I commonly use subcutaneous dexamethasone sodium phosphate (SP) at 0.5 to 1.0 mg per 10 lbs body weight. The dose is similar to the dose used for high-dose dexamethasone suppression tests. It may be administered subcutaneously or intravenously and is usually very well tolerated with minimal subsequent polyuria and polydipsia. The beneficial effects last two to five days, which is slightly longer than the other short-acting glucocorticoids.

Acute feline protocol. For short-duration oral therapy, prednisolone, methylprednisolone, or dexamethasone is more commonly utilized because cats inadequately convert prednisone to prednisolone. Cats may be difficult to administer oral medication to and they can tolerate higher doses and glucocorticoids with a longer duration. Thus, longer-acting injectable glucocorticoids such as methylprednisolone acetate are a particularly attractive alternative. Many veterinary dermatologists carefully utilize this drug successfully and safely for occasional therapy.

Intermediate-term therapy. Often, less than one week of therapy (by either a single injection or daily oral medication) is necessary to break the pruritic cycle. Administer short-acting oral preparations every 48 hours or less often to mitigate suppression of the adrenal axis. Administer intermediate-acting preparations every 72 hours or less. The safe annual steroid dose is a guideline to be considered in these patients.

You should further investigate and treat the underlying cause of the inflammation and pruritus. According to the American College of Veterinary Dermatology Task Force on Canine Atopic Dermatitis, allergen-specific immunotherapy is the only mode of therapy shown to result in partial or complete remission of canine atopic dermatitis without the further need of additional anti-inflammatory drugs.

Glucocorticoids are an integral part of our pruritic patients' comfortable existence. They have many advantages over other forms of therapy and can be safely used for therapeutic purposes. However, they are not without potential side effects. When prescribing glucocorticoids, as with so much of what we do, monitoring and client education are essential aspects of patient care.

Guidelines for calculating glucocorticoid use1

By Candace Sousa, DVM, DABVP, DACVD

As with any other class of drugs, glucocorticoids have clear value when used to treat a disorder for which they have proven therapeutic benefit and when administered at the appropriate dose, frequency, and duration of administration. The benefits of any therapy must always be weighed against the potential side effects.

The primary dosing guidelines for glucocorticoid use is to always use an appropriate induction dose to gain effective control of the clinical signs for the shortest amount of time and then taper to the lowest effective dose possible to maintain control of the condition. Furthermore, the use of alternate day therapy has been recommended to minimize adrenocortical suppression and the other side effects of the prolonged administration of glucocorticoids. For alternate-day therapy to be successful, the administration of glucocorticoids with a duration of action of 12 to 36 hours (prednisone, prednisolone, or methylprednisolone) is necessary.

When considering dose and duration, the following information may be used as a guide for the practitioner to consider when evaluating an animal needing an additional treatment course or long-term glucocorticoid therapy. These recommendations are based upon clinical experience and personal opinion. There is no evidence-based formula for what is safe, and individual variation in side effects also needs to be considered. Every animal and every disease condition differs.

The following calculations allow a practitioner to look at the total dose of exogenous (prescribed) steroid administration through the lens of what a normal patient sees naturally through the endogenous production of cortisol. This combined with using the dosing guidelines listed above may be a helpful tool for veterinarians to determine the lowest effective, safe dose possible. This "safe annual steroid dose" is a starting point and does not replace the need for monitoring with examinations and laboratory testing as indicated for animals on long-term therapy.

Calculating the "safe annual steroid dose"

A normal dog manufactures 0.2 to 1 mg/kg/day of cortisol which is necessary to survive. This is illustrated by using a 40 kg dog as an example: 40 kg X 0.4 mg X 365 days = 5840 mg of cortisol produced / year2 . Different glucocorticoids have different potencies. For example, prednisone (or prednisolone) is considered to be about 4 times as potent as hydrocortisone (cortisol), and methylprednisolone is about 5 times as potent. If you divide 5840 by 4 you get an equivalent amount of prednisone. Thus, this 40-kg dog would "see" in a normal physiologic state 5840 mg of cortisol / year, which is equivalent to approximately 1460 mg of prednisone (or prednisolone) / year.

Assuming that an animal is receiving every other day therapy for long-term glucocorticoid administration and that the practitioner is dosing for the lowest effective dose, the following calculation maybe used as a guideline to help determine a "safe annual steroid dose."

BW (kg) X 30 = mg prednisone (prednisolone) / year3

or BW (lb) X 15 = mg prednisone (prednisolone) / year

Considering the 40-kg dog:

40 X 30 = 1200 mg of prednisone to be the "safe annual steroid dose." This value is less than the range of what is considered physiologic for that dog (5840 mg cortisol / year or 1460 mg prednisone / year).

References/Notes

1. Sousa C. Glucocorticoids in veterinary dermatology. In: Bonagura, J, Twedt D, eds. Kirk's current veterinary therapy (XIV). St. Louis, Mo: Saunders/Elsevier, 2009; 400-405.

2. The lower side of the mid-range of production (0.4 mg of the 0.2 to 1 mg/kg/day range) was used for this calculation.

3. The number (30) is used as a conservative approximation for the 36.5 mg/kg/year annual dose of endogenous steroid (cortisol) produced (0.4 mg/kg/day cortisol) x 365 days / 4 (prednisone's potency factor). It was selected based on a combination of several publications reporting the side effects of glucocorticoids as related to dose as well as based upon clinical experience.