Page 1249 - Small Animal Internal Medicine, 6th Edition

CHAPTER 72 Treatment of Primary Immune-Mediated Diseases 1221

arthritis (RA); and the polyarthritis syndrome of Akitas. In first-line drug in treatment of perianal fistulas in dogs. These
most other immune-mediated diseases, the response to glu- exceptions are discussed in the sections on the individual
VetBooks.ir cocorticoids should be assessed before adding other immu- immune-mediated diseases (see Chapter 73).
nosuppressive drugs. If immune-mediated disease has an
underlying infectious cause, more caution should be used
before adding another immunosuppressive drug. If response GLUCOCORTICOIDS
to glucocorticoids is inadequate or the adverse effects of
glucocorticoids are unacceptable, adjunctive immunosup- Glucocorticoids (corticosteroids with primarily glucocorti-
pressive medications should be considered. Adjunctive coid activity) are the mainstay of treatment of most immune-
immunosuppressive medications should not be assumed to mediated diseases because they are effective, rapid acting,
provide immediate additional suppression to the immune and inexpensive. Several different glucocorticoid drugs are
response. Some confusion exists in the veterinary literature used in veterinary medicine, and they vary according to
about the length of time required for the adjunctive immu- duration, potency, and route of administration. Glucocorti-
nosuppressive medications to have a clinical effect. For coids are characterized by their biologic half-life as measured
example, in one study azathioprine inhibited blastogenic by duration of suppression of the hypothalamic pituitary
response of canine lymphocytes to mitogens after 7 days of adrenocortical axis (Table 72.1). Short-acting glucocorti-
treatment, although serum immunoglobulin concentrations coids such as hydrocortisone and cortisone have a biologic
were unchanged. The authors recommend that at least 7 days half-life of less than 12 hours. Intermediate-acting steroids
of therapy are necessary to gain clinical effect. If there is any such as prednisone, prednisolone, methylprednisolone, and
concern for lack of clinical effect, several of the adjunctive triamcinolone have a biologic half-life of 12 to 36 hours;
immunosuppressive medications have pharmacokinetic or and betamethasone, dexamethasone, and flumethasone
pharmacodynamic monitoring tests available to aid in have a biologic half-life of 48 hours or longer. The duration
guiding therapy. of effect of a glucocorticoid preparation is also influenced
Common adjunctive immunosuppressive medications by the chemical form of the steroid. Parenteral glucocorti-
include those that interfere with nucleotide synthesis such as coid preparations are either esters or free steroid alcohols.
azathioprine, mycophenolate, and leflunomide, as well as Highly soluble esters (e.g., dexamethasone sodium phos-
cytotoxic drugs like cyclosporine and chlorambucil. Histori- phate, prednisolone sodium succinate) and solutions of free
cally, azathioprine has been the most common second-line steroid alcohols in polyethylene glycol (dexamethasone, flu-
immunosuppressive medication used in dogs; the authors methasone) have a duration of action similar to the biologic
consider azathioprine, cyclosporine, and mycophenolate to half-life, but long-acting suspensions of insoluble steroid
all be acceptable second-line immunosuppressive medica- esters (e.g., methylprednisolone acetate suspension, triam-
tions in dogs, although there is a larger body of literature in cinolone acetonide suspension) are absorbed slowly from
support of azathioprine. The risks and benefits of each should the injection site, which markedly prolongs the duration of
be considered when selecting an adjunctive immunosup- effect. Long-acting suspensions of glucocorticoids do not
pressive medication. Chlorambucil or cyclosporine would be achieve high plasma concentrations and are therefore not
the most appropriate second-line immunosuppressive medi- ideal for use in management of immune-mediated diseases.
cations to consider in cats. Drugs such as cyclophosphamide Oral preparations are usually composed of the free steroid
and leflunomide are typically considered third-line drugs. alcohol; because absorption from the gastrointestinal tract
When adding a third-line drug, in most circumstances it is quite rapid, the duration of effect is similar to the biologic
should replace the second-line drug. Treatment with two or half-life. The antiinflammatory effects of corticosteroids cor-
more adjunctive immunosuppressive drugs at the same time relate with their glucocorticoid activity, whereas undesir-
(e.g., azathioprine and cyclosporine together) is likely to able adverse effects such as sodium retention and edema
cause much more severe immunosuppression and a high risk formation are due to their mineralocorticoid activity. Most
of secondary infection and should be avoided. Bacterial synthetic steroids such as prednisone and dexamethasone
infections that may develop in dogs and cats on long-term have higher glucocorticoid and lower mineralocorticoid
immunosuppressive drugs include lower urinary tract infec- activity than hydrocortisone. Prednisone has four times the
tions, pyelonephritis, cholangiohepatitis, hepatic abscesses, potency of hydrocortisone but 0.3 times the mineralocor-
and pyoderma; however, the overall prevalence of secondary ticoid activity; dexamethasone has 30 times the potency of
infections in patients properly dosed with immunosuppres- hydrocortisone (≈8 times the potency of prednisone) with
sive drugs is low. Fungal infections such as candidiasis may no mineralocorticoid activity.
also occur. These serious infections can be extremely difficult In most patients with immune-mediated disease, the ideal
to manage once established and should therefore be pre- route of glucocorticoid administration is oral; however, in
vented, if at all possible, by judicious use of immunosuppres- animals that are vomiting or that have diseases that interfere
sion and careful patient monitoring. with swallowing or gastrointestinal absorption, intravenous
Some exceptions exist in which a typically adjunctive administration of either prednisolone or dexamethasone
immunosuppressive is more appropriate as first-line or may be necessary. The use of long-acting parenteral drugs for
primary therapy. For example, cyclosporine is used as a treatment of immune-mediated disease is not recommended