Initial side effects of glucocorticoids include polyuria, polydipsia, and polyphagia. With longer-term use, a myriad of other
side effects can develop such as gastric ulceration, hepatopathy (dogs), diabetes mellitus, calcinosis cutis, skin atrophy,
and secondary infections. In a retrospective study, the use of gastroprotectants such as sucralfate or histamine receptor
blockers (famotidine) had no effect on survival time in dogs with pemphigus foliaceus receiving glucocorticoids.51
In many dogs, glucocorticoids alone are insufficient to manage pemphigus foliaceus signs. In past studies, glucocorticoid
monotherapy resulted in acceptable management of pemphigus foliaceus signs in only 35% to 39% of dogs.5,52 Glucocorticoid monotherapy is more effective in cats. Complete remission with only glucocorticoids occurs in 62% to 100%
of cats with pemphigus foliaceus receiving prednisone and triamcinolone, respectively.15
Table 2: Systemic Medications Used with Glucocorticoids in Dogs with Pemphigus Foliaceus
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Any oral glucocorticoid should be tapered gradually once clinical remission of the pemphigus foliaceus is achieved (no new
pustules or erosions). The exact glucocorticoid tapering protocol will vary in each patient, but, in general, glucocorticoids
can be tapered by about 25% each time the dose is adjusted. Recheck the patient after each change in the oral glucocorticoid
dose. If the pemphigus foliaceus recurs when the glucocorticoid is tapered, another immunosuppressive medication should be
added. Likewise, when glucocorticoids alone cannot induce remission of pemphigus foliaceus, other immunosuppressive medications
are then used as adjunctive therapy so that the glucocorticoid dose may initially be decreased and glucocorticoid administration
can eventually be discontinued (Tables 2 & 3).
Azathioprine
Table 3: Systemic Medications Used with Glucocorticoids in Cats with Pemphigus Foliaceus
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Azathioprine is a purine analogue that interferes with cellular nucleic acid synthesis. Thus, its greatest cytotoxic effect
is on proliferating cells such as lymphocytes. Azathioprine is more effective at suppressing humoral immunity than cell-mediated
immunity.
Azathioprine is the medication most commonly used to manage canine pemphigus foliaceus when lesions do not respond to glucocorticoid
monotherapy. In these cases, lesions worsen or stay the same with glucocorticoids or signs relapse with lower dosages of glucocorticoids.
Adding azathioprine in a dog with pemphigus foliaceus can then reduce the need for systemic glucocorticoids and potentially
enable discontinuation of the glucocorticoid.
Azathioprine is commonly started at 2 to 2.5 mg/kg/day orally in dogs with pemphigus foliaceus. If azathioprine is being used
with glucocorticoids to manage pemphigus foliaceus signs, do not reduce the dose or frequency of glucocorticoids immediately
after starting azathioprine since azathioprine can take weeks to have an effect.
Side effects of azathioprine include bone marrow suppression resulting in leukopenia, anemia, and thrombocytopenia. Vomiting,
diarrhea, hepatotoxicosis, and acute pancreatitis can also occur. In our experience, hepatotoxicosis is the most common side
effect. Complete blood counts and serum chemistry profiles must be performed regularly while a patient is receiving azathioprine,
usually every two to three weeks during initial therapy. When azathioprine and glucocorticoids are used together, it can be
difficult to monitor for azathioprine-induced hepatotoxicosis because of the usual elevation of serum liver enzyme activities
caused by glucocorticoid administration.
Azathioprine is metabolized by an enzyme called thiopurine methyltransferase (TPMT). Low TPMT concentrations increase the
risk of myelosuppression. Variations in TPMT concentrations have been noted in dogs.53 Cats have lower TPMT concentrations than dogs do,54 and azathioprine is usually avoided in cats because of the high likelihood of severe myelosuppression.
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