Glucocorticoids are useful drugs. Their utilization has allowed for control of many diseases and conditions that otherwise would likely result in death or the ultimate euthanasia of many dogs and cats.
Glucocorticoids are useful drugs. Their utilization has allowed for control of many diseases and conditions that otherwise would likely result in death or the ultimate euthanasia of many dogs and cats. Diseases of altered immune responses are the prime benefactors of their efficacy. In the world of veterinary dermatology, diseases such as pemphigus foliaceus, lupus erythematosus, bullous pemphigoid and a host of others can often be successfully managed and long-term remission can be achieved with their usage. There are alternatives for therapy to these diseases however many alternative drug regimens or procedures to treat autoimmune diseases are costly, in the case of azathioprine, chlorambucil, cyclosporine and others, or not widely available, in the case of procedures such as plasmapharesis. Thus glucocorticoids have become the workhorse of drug therapy in managing these diseases or allowing for reduced dosages of other more potent drugs. In addition to their myriad of uses there are also many potential side effects and complications that may arise from their usage and appropriate monitoring is important. Despite their use in these diseases, the most common diseases with cutaneous manifestations that are treated with steroids are allergic skin disease.
This Golden Retriever shows ventral areas of erythema with secondary hyperpigmentation and alopecia.
The usefulness of glucocorticoids in helping to manage allergic skin disease, specifically atopy, is unquestioned, while their ability to control other allergic skin diseases (food allergy, flea allergy and contact allergy) is more controversial. However, owing to their undesirable side effects, the use and, in some cases, misuse may result in additional problems. In addition, there are many alternatives that exist for dealing with an allergic patient. Many of these can be safe and relatively inexpensive, so steroids may be best reserved for those patients that are nonresponsive to an exhaustive search for other control methods.
This is a common problem seen at the author's practice that at least a portion of dogs that are presented as chronic allergic dogs for intradermal skin testing, are in fact, noncontrolled bacterial or Malassezia pyodermas that have not been resolved effectively. The inability to resolve the pyoderma often results from the lack of administration of appropriate antibiotics for an appropriate length of time or due to the immunesuppressive effects of steroids leaving the body unable to resolve the pyoderma by its own immune response or both.
One of the most important pieces of advice that dermatologists can give to the general practitioner regarding glucocorticoid usage is to adhere to a well regimented and step wise workup of all pruritic dogs to eliminate these other pruritic diseases. This will allow the practitioner to be much more successful in managing pruritic patients in particular and dermatological patients in general. Pruritus in the absence of bacterial or Malassezia pyoderma, parasitic infestation (Sarcoptes, cheyletiella or fleas), lack of response to appropriate food trials as well as lack of response to various antihistamines, fatty acids and topical therapies may be an indication for glucocorticoids, however using glucocorticoids for the clinical signs of pruritus without addressing these other issues will often lead to chronic frustration for veterinarian and owner alike.
After a diagnosis of atopy has been made, either by intradermal skin test or by exclusion of other pruritic diseases, and a decision has been made to use glucocorticoids, the practitioner must select the appropriate steroid and route of administration. Various routes of administration include topical, oral, subcutaneous, intramuscular, intravenous or intralesional depending on individual disease and drug used. There are numerous synthetic glucocorticoids available for use in the United States and in general, these are more potent in regard to their glucocorticoid activity than naturally produced cortisol. Synthetic glucocorticoids also have a higher affinity for the steroid receptor, slower degradation and a longer duration of action.
Glucocorticoids are divided into three groups based on potency. Their potency is assessed relative to hydrocortisone which has an arbitrary rating of 1.0. They are divided into short acting, consisting of cortisone (.8), and hydrocortisone (1.0); intermediate acting, consisting of prednisone (4.0), methylprednisolone (5.0) and triamcinolone (5.0); and long acting, consisting of paramethasone (10.0), flumethasone (15.0), dexamethasone (30.0) and betamethasone (35.0).
Ventral aspect of paw with intense erythema from atopic dermatitis.
Duration of action for injectable glucocorticoids is influenced by the form of the glucocorticoid in the preparation. Since synthetic glucocorticoids are synthesized as esters, the less soluble the ester, the slower the rate of absorption. For example, highly soluble esters include products such as Solu-Delta Cortef (Pharmacia/Upjohn) and Azium SPÂ® (Schering-Plough). Moderately insoluble esters include products such as Depo-MedrolÂ® (Pharmacia/Upjohn) while poorly soluble esters include Vetalog (Solvay).
Several products available for use by the practitioner for topical therapy that range from weak, short-acting steroids such as hydrocortisone to the intermediate potency of triamcinolone to the high potency of betamethasone.
One percent hydrocortisone is available in numerous over-the-counter formulations and in several veterinary products including a leave-on conditioning rinse (Resicort-Virbac).
These products can be helpful in mild cases of allergic pruritus and can be used as frequently as necessary to control clinical signs. They are also appropriate for long-term usage. However the vast majority of the moderately to severely affected patients will not be adequately controlled with this drug or application route in the author's experience. High potency products containing betamethasone are also available in veterinary formulations. These products, while certainly more potent and more effective, are inappropriate for long-term usage due to side effects that are more commonly seen including cutaneous atrophy and other changes to the skin and hair follicles, as well as local immunesuppression allowing for pyoderma. In rare cases, calcinosis cutis may be noted with topical uses of more potent glucocorticoids. The author suggests that these products should be used carefully and only in short-term situations. If pruritus persists, additional diagnostics or alternate therapies should be employed.
Calcinosis cutis as a result of long-term oral prednisone therapy for atopy.
Another topical steroid, Genesis spray, (Virbac) containing an intermediate acting glucocorticoid (triamcinolone) has recently become available. The advantages of a higher potency steroid (than hydrocortisone) but one that is less potent than betamethasone may allow for increased efficacy with a decrease in potential undesirable side effects. Clinical trials have shown good efficacy although these trials were conducted for only 28 days, leaving the question regarding potential for long-term side effects open. However due to the relative potency of triamcinolone (5.0) to betamethasone (35.0), it stands to reason that this may be a better product for long-term usage. The author has used this product extensively and has seen positive results, even in some dogs that had been refractory to oral glucocorticoids.
The main preparations used for oral therapy are prednisone (4.0), methylprednisolone (5.) and triamcinolone (5.0). In rare instances, oral dexamethasone (30.0) may be utilized. Oral therapy with glucocorticoids is the standard route of administration for most veterinary dermatologists.
The vast majority of atopic dogs can be well managed with oral glucocorticoids with only a few exceptions. Oral administration is preferred since it can be more closely regulated (as opposed to repositol injections which will provide less consistent blood levels) and can be withdrawn in the case of systemic side effects. Optimal dosages for feline and canine dermatoses have not been determined, therefore oral glucocorticoid therapy should be used at the lowest possible effective dosage and for long-term therapy should only be used on an alternate day or pulse schedule. For example, prednisone and methylprednisolone may be initially dosed at .5 mg/kg q 12-24 hrs in the dog and 1 mg/kg in the cat for five to seven days and then tapered to an alternate day schedule. Triamcinolone can be used at .05-.1 mg/kg q 24 hours in the dog and cat and then tapered after seven days to an alternate day schedule as well. Even in cases in which alternate day low dose therapy is accomplished, systemic side effects may be numerous and include: behavioral changes (aggression, polyuria, polydipsia, polyphagia, panting); gastrointestinal (diarrhea, vomiting, anorexia); endocrine (adrenal gland suppression, diabetes mellitus and decreased thyroid synthesis); cutaneous (cutaneous atrophy, calcinosis cutis, comedones, milia-like cysts) and secondary infections (demodicosis, dermatophytosis, Malassezia dermatitis and bacterial dermatitis or cystitis).
In cases that are managed with glucocorticoids long-term annual or semiannual monitoring of blood chemistry, CBC and urinalyses are recommended. Annual urine cultures should also be done since many bladder infections that occur in steroid managed dogs may be asymptommatic due to the anti-inflammatory affect the glucocorticoid exhibits on the bladder wall. Without the inflammation the sense of urgency and straining seen in most cystitis cases may be absent. Lastly, in atopic cases that are refractory to oral glucocorticoids, a review of the original diagnosis is warranted to avoid missing other less steroid responsive diseases. In cases that are originally maintained but become refractory, a thorough search for complicating factors (i.e. - bacterial, Malassezia infections, fleas, Demodex) or a new disease (concomitant food allergy, scabies etc.) is recommended. The author sees cases daily that fall into these categories.
The most commonly used products in this category are methylprednisolone acetate (Depo-Medrol) and triamcinolone acetonide (Vetalog). Despite the widespread use of injectable glucocorticoids in treatment of atopy, no studies exhibiting the efficacy of long-acting injectable glucocorticoids has been undertaken in controlled trials. Due to their high potency and length of efficacy, these drugs have the highest potential for adverse reaction and in the practices of many veterinary dermatologists are not used. In fact, a recent task force appointed by the American College of Veterinary Dermatology to compile the current data and state of knowledge on atopy, recommends that these formulations not be used in the treatment of canine atopy.
If the practitioner chooses to use these products in the dog, they should be reserved for infrequent and judicious use to control acute inflammatory responses followed by investigation into other more suitable long term alternatives Since repositols do not maintain constant blood levels of glucocorticoid, they will be less effective in managing an allergic patient although suppression of the adrenal axis will occur. In cases of adverse reaction, the drug cannot be discontinued and the patient must endure the gradual elimination of the glucocorticoid from the system.
Injectable glucocorticoids may be more appropriate for the cat, since cats are more tolerant of side effects from these drugs. However systemic side effects can be seen in cats as well. So while injectable formulations may be used in the cat, if frequent administration is needed (more than q three to four months), alternative therapies (antihistamines, hyposensitization) should be investigated. The author sees numerous cats that have become completely refractory to steroids but can be managed with antihistamines (chlorpheneramine, cyproheptadine etc.)
So while corticosteroids remain an important tool in helping to manage atopic dogs and cats, many factors need to be addressed to find the best long-term management scheme in individual patients. Each case should be assessed on its own merits and no one corticosteroid or route of administration is applicable or will be effective for every case. In addition, given the advancement of better and safer long-term alternatives that are available and on the horizon, the use of corticosteroids used in general should be lessened in the future.