Chlorambucil is an alkylating agent that causes cross-linking of cellular DNA. Doses range from 0.1 to 0.2 mg/kg orally every
24 to 48 hours. Side effects include vomiting, diarrhea, anorexia, and myelosuppression.52 Chlorambucil is especially used in cats with pemphigus foliaceus that fail to respond to glucocorticoids since azathioprine
is not a treatment option for cats. Complete blood counts and serum chemistry profiles must be performed regularly while a
patient is receiving chlorambucil, usually every two to three weeks during initial therapy.
Cyclosporine is a calcineurin inhibitor that blocks the transcription of cytokine genes in activated T cells.55 Cyclosporine is an approved treatment for canine atopic dermatitis (Atopica—Novartis Animal Health) and is used extralabel
for a variety of other immune-mediated conditions in dogs and cats.56 Cyclosporine's side effects in dogs and cats include inappetence, vomiting, diarrhea, gingival hyperplasia, hirsutism, papillomas,
psoriasiform lichenoid-like dermatosis, and disseminated toxoplasmosis.57,58 The microemulsion form of cyclosporine (Atopica; Neoral—Novartis) is more readily absorbed in dogs and cats and should be
used instead of other forms of cyclosporine such as Sandimmune (Novartis). Complete blood counts and serum chemistry profiles
must be performed regularly while a patient is receiving cyclosporine therapy. In cats receiving cyclosporine, elevated liver
enzyme activities can be a sign of toxoplasmosis.59
In a small pilot study, cyclosporine monotherapy at 5 to 10 mg/kg/day was ineffective in managing pemphigus foliaceus signs
in four out of five dogs.60 Since the publication of that initial study, there have been anecdotal reports of using cyclosporine at 10 mg/kg/day or
greater to manage pemphigus foliaceus in dogs, especially those with milder presentations.
Cyclosporine is more effective for pemphigus foliaceus when used in combination with other therapies. In three dogs with pemphigus
foliaceus already receiving azathioprine and glucocorticoids, oral cyclosporine at 7.5 to 10 mg/kg/day was used with oral
ketoconazole at 2.5 to 5 mg/kg/day to successfully induce remission.61 The ketoconazole was used to increase cyclosporine concentrations. All dogs were then able to have glucocorticoids discontinued
within three to 12 weeks of adding the cyclosporine and ketoconazole. Signs did not worsen when the glucocorticoids were discontinued.
Cyclosporine was used successfully with prednisone to induce remission of pemphigus foliaceus signs in another study involving
five dogs.62 Initial doses ranged from 1 to 2.6 mg/kg/day and 5 to 18 mg/kg/day for the prednisone and cyclosporine, respectively. While
the initial cyclosporine dose was maintained in each patient, the prednisone dose was then tapered to 0.5 mg/kg every other
day with no relapse of signs. The cyclosporine was continued and eventually tapered to 3 to 4 mg/kg every other day. No studies
exist on using cyclosporine to manage feline pemphigus foliaceus, but we have used cyclosporine to manage some patients.
In our experience, cyclosporine can take weeks to have a clinical effect on pemphigus foliaceus lesions. This delayed effect
may be because of cyclosporine's action on T lymphocytes, the cells that drive the autoimmune reaction, without direct effect
on autoantibodies that cause the skin lesions. Thus, if cyclosporine is used with glucocorticoids to manage pemphigus foliaceus
signs, do not reduce the dose or frequency of glucocorticoids immediately after starting cyclosporine.
Tacrolimus, another calcineurin inhibitor, has been used topically for conditions such as localized atopy in dogs63 and people. In dogs with a form of superficial pemphigus (pemphigus erythematosus), applying tacrolimus 0.1% as a thin film
on facial lesions twice a day helped manage clinical signs.64 In that study, tacrolimus was used as the sole therapy in one dog with superficial pemphigus, while the other dog was also
managed with systemic immunosuppressive medications. Of note is that pemphigus erythematosus is suspected to be a crossover
between discoid lupus and pemphigus foliaceus. It is possible that the nasal lesions of pemphigus erythematosus that responded
to tacrolimus were the lupus-like lesions. In our opinion, in general, pemphigus foliaceus does not appear to respond to tacrolimus
Tacrolimus can cause a pruritic or burning sensation during the initial few days of application in people, and signs of pruritus
and irritation have been observed in dogs with initial use.63 These signs typically resolve despite continuation of therapy. In 2005, the tacrolimus label was changed to include a warning
that some people have developed cancer while receiving this medication. Clients should wear gloves when applying this medication.