Azathioprine and chlorambucil
Azathioprine at 2 mg/kg daily for one week and then at 1 mg/kg every other day may be instituted at the beginning of prednisone
therapy in dogs to allow more rapid tapering of prednisone, thus minimizing prednisone-related adverse effects. Azathioprine
can also be added to therapy for dogs that are not responding to prednisone alone. A CBC and hepatic serum chemistry profile
should be performed one week after initiating azathioprine therapy and then monthly while the dog receives azathioprine to
monitor for adverse effects.
If additional immune suppression is needed in cats, chlorambucil can be given.
Lithium carbonate (10 mg/kg orally b.i.d.) is used in dogs for chemotherapy-associated neutropenia14 and may play a role in treating immune-mediated neutropenia. It causes a nonspecific stimulation of neutrophil production.31
Therapy in people
In people, use of recombinant granulocyte-colony stimulating factor has revolutionized therapy.32
Corticosteroids are typically contraindicated because of their affects on immunity, growth, and normal adrenal gland function
in children affected with immune-mediated neutropenia. Short courses of corticosteroids, intermittent antibiotics, and intravenous
IgG are core to therapy in children until disease remission occurs spontaneously. Administering human recombinant granulocyte-colony
stimulating factor in dogs can lead to neutropenia because dogs may develop antibodies to it. These antibodies may then cross-react
with endogenous canine granulocyte-colony stimulating factor, impairing neutrophil production in the bone marrow. Antibodies
tend to develop within three weeks of initiating therapy.33 Canine recombinant granulocyte-colony stimulating factor is not commercially available, and given the induction of antineutrophil
antibodies, it is contraindicated.34
The prognosis for remission is good, with 100% of dogs achieving normal neutrophil counts after 1 to 18 days of prednisone
therapy in one retrospective study.6 In the published case reports, loss of remission once medication was discontinued was frequently, but not always, reversed
with re-institution of therapy.2,11
Although not commonly recognized, immune-mediated neutropenia should be a differential diagnosis in neutropenic patients that
after a diagnostic work-up have no other apparent reason for their neutropenia. These patients tend to be younger and have
fairly profound neutropenias that often lack toxic change. Response to immunosuppression can be fast and dramatic and is used
to confirm the diagnosis since no diagnostic test for antineutrophil antibodies is validated in animals. The validation of
a canine and feline antineutrophil antibody test is needed.
Belle Marie D. Nibblett, DVM
Anthony P. Carr, Dr. med. vet., DACVIM (small animal internal medicine)
Department of Small Animal Clinical Sciences
Western College of Veterinary Medicine
University of Saskatchewan
Saskatoon, SK S7N 5B4
1. Smith G. Neutrophils. In: Feldman BF, Zinkl JG, Jain NC, eds. Schalm's veterinary hematology. 5th ed. Oxford, England: Blackwell Publishing, 2000;281-295.
2. McManus P, Litwin C, Barber L. Immune-mediated neutropenia in 2 dogs. J Vet Intern Med 1999;13:372-374.
3. Perkins MC, Canfield P, Churcher RK, et al. Immune-mediated neutropenia suspected in five dogs. Aust Vet J 2004;82:52-57.
4. Maddison JE, Hoff B, Johnson RP. Steroid responsive neutropenia in a dog. J Am Anim Hosp Assoc 1983;19:881-886.
5. Alexander JW, Jones JB, Michel RL. Recurrent neutropenia in a Pomeranian: a case report. J Am Anim Hosp Assoc 1981;17:841-844.