Cyclosporine Therapy In Veterinary Dermatology
Cyclosporine has been used to treat a number of recalcitrant skin diseases.
Canine atopic dermatitis, at far left, tends to worsen with age. Intervening early may prevent the disease from progressing to the severity exhibited by this patient. The treatment of feline eosinophilic granuloma complex lesions, right, is one of many off-label uses of cyclosporine.
Photo Copyright Jon D. Plant/Banfield, The Pet Hospital
Treating canine and feline dermatoses with cyclosporine has been the subject of great interest in recent years.1
Many studies have focused on canine atopic dermatitis, and now there is substantial evidence that cyclosporine is efficacious in treating this common condition.2
In addition, cyclosporine has been used to treat a number of recalcitrant skin diseases, ranging from canine perianal fistulas to feline eosinophilic granuloma complex.
Cyclosporine is a potent immunomodulating polypeptide originally isolated from the soil fungus Tolypocladium inflatum. By inhibiting the production of IL-2, IL-4 and other cytokines, cyclosporine is effective in controlling the inflammation associated with many allergic and immune-mediated skin diseases.
Atopica (cyclosporine, modified; Novartis Animal Health, Inc.) was approved for the treatment of canine atopic dermatitis in 2003. It is available in 10 mg, 25 mg, 50 mg and 100 mg capsules.
Compared to the original form, this micro-emulsified version of cyclosporine increases the oral bioavailability and consistency of absorption in dogs.3
Food in the gastrointestinal tract decreases absorption by about 20 percent. The drug is metabolized primarily in the liver by the cytochrome P450 enzyme CYP3A4. Drugs metabolized by the same system have the potential to increase or decrease serum cyclosporin levels.
Compared to the original form, this micro-emulsified version of cyclosporine increases the oral bioavailability and consistency of absorption in dogs.
The hallmark symptom of canine atopic dermatitis is pruritus, which often varies in severity with seasonal changes.
Pruritus may have a negative effect on quality of life and the human-pet bond and is a leading reason that clients seek veterinary care for their dogs.
Traditional treatment modalities have included antihistamines, glucocorticoids and allergen-specific immunotherapy (hyposensitization)—each is fraught with limitations. Atopica provides veterinarians with a therapeutic option that avoids some of these. Specifically, the drug is more effective than antihistamines, causes fewer side effects than long-term glucocorticoid therapy and has a quicker onset of activity than allergen-specific immunotherapy.
It should not be reserved for treating atopic dogs when everything else has failed. By intervening early with an effective therapeutic, we may inhibit the usual progression to more severe disease. The recommended starting dose is 5 mg/kg every 24 hours, given on an empty stomach.
Thelen, et al, reported that the clinical response of atopic dogs to cyclosporine was not affected by administering the medication with food.4 I recommend administration with food for the first week to minimize gastrointestinal side effects. After four weeks of therapy, many dogs are controlled with a dose of 5 mg/kg every 48 hours, significantly reducing the cost of long-term therapy.
Potential adverse effects from cyclosporine include vomiting, diarrhea, gingival hyperplasia and cutaneous papillomatosis. These are generally transient and managed with a reduction in the dose.
Cyclosporine may also be useful for the management of allergic feline dermatoses,5,6 including cats with atopy, eosinophilic granuloma complex lesions (eosinophilic plaque, eosinophilic granuloma or indolent ulcer) and idiopathic pruritus.
A fair to excellent response was observed in the majority of the 33 cats in the two reports cited, with doses ranging from 3.6 to 13.3 mg/kg/day.
Although generally well-tolerated, cyclosporine is not approved for use in cats. Rare cases have developed fatal toxoplasmosis after receiving cyclosporine therapy. At this time, it should probably be used only as a last resort.
Cyclosporine has received much attention for the treatment of perianal fistulas of German shepherd dogs, which were once considered principally surgical conditions. Cyclosporine is now used in many cases.
Reported doses have ranged widely and an optimal dose has not been established for this off-label usage. A dose of 5 mg/kg/day was found to be more effective than 2 mg/kg/day.7 Some authors have reported success with lower doses of cyclosporine co-administered with ketoconazole. In general, the response of perianal fistulas to cyclosporine is variable and sometimes incomplete.
Autoimmune or idiopathic skin diseases are variably responsive to cyclosporine therapy. When reported, the number of cases included is usually only one or two. Failure to respond is often not published—an exception being the failure of five dogs with pemphigus foliaceus to respond to cyclosporine.8
As more controlled clinical trials are published, the list of indications for cyclosporine in small pet dermatology is sure to grow.
Dr. Plant, Dipl. ACVD, is a dermatology specialist at Banfield, The Pet Hospital, in Portland, Ore.
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2. Steffan J, Favrot C, Mueller R. A systematic review and meta-analysis of the efficacy and safety of cyclosporin for the treatment of atopic dermatitis in dogs. Vet Dermatol 2006 (17)1: 3-16.
3. Gaugere E, Steffan J, Olivry T. Cyclosporin A: a new drug in the field of canine dermatology. Vet Dermatol 2004 (15)2: 61-74.
4. Thelen A, Mueller RS, Linek M, Peters S, Stechmann K, Steffan J. Influence of food intake on the clinical response to cyclosporin A in canine atopic dermatitis. Vet Record 2006 (159)25:854-6.
5. Noli C, Scarampella F. Prospective open pilot study on the use of ciclosporin for feline allergic skin disease. J Small Anim Pract 2006 (47)8:434-8.
6. Vercelli A, Raviri B, Cornegliani L. The use of oral cyclosporin to treat feline dermatoses: a retrospective analysis of 23 cases. Vet Dermatol 2006 (17)3: 201-6.
7. House AK, Guitian J, Gregory SP, Hardie RJ. Evaluation of the effect of two dose rates of cyclosporine on the severity of perianal fistulae lesions and associated clinical signs in dogs. Vet Surg 2006 (35)6:543-9
8. Olivry T, Rivierre C, Murphy KM. Efficacy of cyclosporine for treatment induction of canine pemphigus foliaceus. Vet Record 2003 (152)2: 53-4.