Page 1264 - Small Animal Internal Medicine, 6th Edition

1236 PART XI Immune-Mediated Disorders

count, and resolution of the inflammatory leukogram. Once medication is continued at the same dosage while the dose
the hematocrit increases above 30%, a taper of the predni- of prednisolone is tapered. The adjunctive medication can
VetBooks.ir sone dose can be initiated The dose is tapered by a maximal then be tapered once prednisolone has been discontinued. If
a relapse occurs during tapering of the drugs, lifelong pred-
rate of 20% to 30% per month over a 3- to 6-month period
depending on the hematocrit and severity of adverse effects.
mended at the lowest dose that controls hemolysis.
If after 6 months the prednisolone dose is tapered to a low nisolone, the adjunctive medication, or both are recom-
every-other-day dose and the disease is in remission, discon- Azathioprine has the most evidence for its use in canine
tinuation of medication should be attempted. A CBC and IMHA, though there is no evidence that its use improves
reticulocyte count should be performed before and 2 weeks response to treatment or survival. Azathioprine requires
after any change in immunosuppressive therapy. more regular monitoring of the CBC and hepatic enzymes
Some dogs with IMHA do not respond to glucocorticoid due to the risk of bone marrow suppression and hepatotoxic-
treatment alone, or the dose of prednisolone required for ity. Current recommendations are to reduce the frequency of
disease control results in unacceptable adverse effects. In administration of azathioprine to every other day after the
these cases, an additional immunosuppressive drug should first 2 weeks of daily administration to reduce the risk of
be added to the treatment regimen. One common clinical toxicity.
dilemma is whether all dogs with IMHA should be treated Cyclosporine is being used with greater frequency for the
with an additional immunosuppressive drug early in the treatment of canine IMHA. The cost of cyclosporine is a
course of treatment, or whether waiting and identifying major deterrent to its use, and its potent immunosuppressive
which dogs are likely to benefit is more appropriate. The effects mandate frequent monitoring of the patient for sec-
advantage of starting another immunosuppressive drug early ondary infections (bacterial, fungal, protozoal). The bio-
is that no time is lost waiting to identify which patients will availability of some cyclosporine formulations has been
respond to glucocorticoid treatment alone. Most adjunctive shown to be poor in dogs, making Atopica® the most appro-
immunosuppressive drugs take 2 to 4 weeks to have an priate formulation to use in veterinary patients. In a prospec-
appreciable effect on immune cells, so an argument could be tive study of 38 dogs with IMHA, no difference in survival
made that starting them earlier will save time. The disadvan- was found between dogs treated with prednisone alone and
tages include the risk of adverse effects, the cost of immuno- those treated with prednisone and cyclosporine; however,
suppressive drugs, the lack of evidence of benefit, and the most of the deaths occurred early, before the effects of
lack of consensus about which adjunctive agent should be cyclosporine had likely reached maximal effect. In a study to
considered “second line” after glucocorticoids. In a retro- characterize the predominant inflammatory cytokines in
spective study comparing a cohort of dogs treated with pred- canine IMHA, interleukin-2 (IL-2) was consistently increased
nisolone and azathioprine with a cohort of dogs treated with in dogs with IMHA. This might suggest that cyclosporine has
prednisolone alone, no benefit of azathioprine therapy could good potential for success, as the calcineurin inhibition leads
be identified. Despite this finding, other large IMHA retro- to a decreased transcription of cytokines, primarily IL-2.
spective studies report that the majority of IMHA cases are Cyclosporine appears to be relatively safe in dogs with
managed with glucocorticoids and adjunctive immunosup- IMHA, and clinical experience suggests that it is useful and
pressive agents. Use of more than one adjunctive immuno- effective in the treatment of dogs with IMHA that do not
suppressive drug concurrently is strongly discouraged respond to prednisolone or azathioprine. (For dosing and
because of the potential for severe immunosuppression and monitoring recommendations for cyclosporine, see Chapter
resultant susceptibility to infection. 72 and Tables 72.3 and 72.4.)
The choice for adjunctive immunosuppression varies Mycophenolate mofetil (MMF) has historically been used
among clinicians. The most common drugs used are aza- in refractory cases of IMHA and other immune-mediated
thioprine, cyclosporine, and mycophenolate. The authors diseases. The mechanism of MMF is similar to that of aza-
consider any of these to be appropriate adjunctive immu- thioprine. It was originally designed as an alternative to aza-
nosuppressive medications, especially in dogs that do not thioprine in human transplant patients, due to fewer side
respond within 5 to 7 days of initiating glucocorticoid treat- effects. A retrospective evaluation of dogs with IMHA treated
ment and in dogs that require more than two blood transfu- with prednisolone and mycophenolate reported dose-
sions. Adjunctive immunosuppressive medications should dependent gastrointestinal toxicity including severe hemor-
also be used in dogs known to have a poor tolerance of the rhagic diarrhea. However, when used at recommended
adverse effects of glucocorticoids (e.g., large-breed dogs) and doses, mycophenolate is well tolerated in dogs. Mycopheno-
in those with other poor prognostic indicators (e.g., intra- late is also available for intravenous administration, so it is a
vascular hemolysis, serum bilirubin concentration greater good option for patients unable/unwilling to take oral medi-
than 8 to 10 mg/dL, persistent autoagglutination, Evans cations in the early stages of the disease.
syndrome). There are anecdotal reports and a few retrospective case
The adjunctive immunosuppressive medication should be series reporting positive responses to treatment of canine
initiated at a recommended dose to achieve appropriate sup- IMHA with human intravenous immunoglobulin (hIVIG).
pression of immune cells, namely lymphocytes. Once the In a controlled, blinded, prospective study of 28 dogs with
anemia is controlled, the adjunctive immunosuppressive IMHA, no benefit was evident when three doses of hIVIG