Atopy frustrating to manage, but treatment strategies exist

Atopy can be a frustrating diagnosis because other dermatological conditions can present with the same signs. But once, you have an established diagnosis, treatment strategies do exist, including cyclosporine and immunotherapy.

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Originally used as an anti-rejection drug in humans, cyclosporine acts by suppressing T-helper and T-suppressor cells, as well as inhibiting IL-2. The end result is an inhibition of antigen presentation, mast and eosinophil cell production and activation, inhibition of histamine and prostaglandin release from mast cells and an overall reduction in epidermal hyperplasia. Its main advantage is an alternative to steroid use for canine atopy. Cyclosporine also has been used successfully in treating metatarsal fistulas of the German Shepherd, sterile nodular panniculitis, granulomatous meningoencephalitis, sebaceous adenitis, perineal fistulas, pemphigus foliaceus, pemphigus erythematosus, erythema multiforme, sterile pyogranuloma syndrome, proliferative otitis of the American Cocker Spaniel and cutaneous lupus. In cats, it has been used successfully in the treatment of feline atopy, renal transplants, eosinophilic granuloma complex and idiopathic facial dermatitis of the Persian cat. It is not FDA approved for use in cats.

Cyclosporine is metabolized by the liver and is absorbed best when given on an empty stomach. However, vomiting is the main side effect of the drug, and we suggest administering it with a small amount of a fatty food. I always tell clients I would rather their dog receive 80 percent of the drug (when given with food), than 0 percent if vomiting occurs when administered on an empty stomach. The usual dose is 5mg/kg/day administered as a single dose. We have started some patients with sensitive stomachs at a lower dose and administered the drug with food to be sure they could tolerate it, then gradually build up to the normal dose. Some patients will respond to a lower dose that thereby alleviates gastrointestinal problems and is less expensive for the owner.

Other considerations

Other side effects include diarrhea (sometimes due to bacterial overgrowth), otitis externa, urinary tract infection, anorexia, lethargy, gingival hyperplasia, increased hair-coat growth, psoriasiform lichenoid dermatosis and lymphadenopathy. Our clinic also has seen and reported bacterial pyoderma in four patients and a peripheral neuropathy associated with cyclosporine use. The latter occurred after using the drug for a year in an 8-year-old Bichon Frise. Clinical response varies as some patients will respond immediately, i.e. in three days, whereas others can take up to 60 days. In an original study we participated in, 74 percent of patients improved in the first 30 days, where 24 percent of patients receiving placebo improved. I explain to clients that to give the drug a fair trial, they should wait at least 30-60 days before attempting other therapies. Many patients once controlled on daily therapy will be able to reduce the drug to every-other day administration, and that helps with the expense.

Making the diagnosis

It's important to make sure the patient is atopic prior to treatment. This seems elementary, but several diseases present with the same signs and symptoms of atopy, including bacterial pyoderma, flea allergy, scabies, Cheyletiella mites, Malassezia dermatitis and food allergy. After eliminating or treating for the above differentials, the five clinical criteria as devised by Prelaud should be considered when achieving a diagnosis of atopy: steroid-sensitive pruritus, pinnal erythema, bilateral erythematous pododermatitis of the forefeet, cheilitis, and signs beginning between 6 months of age and 3 years of age. Skin or blood testing for allergy is not required to make a diagnosis of atopy, only to determine what allergens to avoid or include in the immunotherapy should that therapy be initiated. In fact, we all have patients that meet the atopic requirements yet will not test positive on skin or blood testing for various reasons. It is important to rule out the differential diagnoses for atopy to help rule "in" atopy in order to have success in using the drug.

Laboratory monitoring

There are differences in what laboratory monitoring should be performed pre-therapy and while the patient is on the drug. There are no "set" recommendations. In our office, we usually check a complete blood count and serum profile prior to starting the drug, then every six to 12 months afterwards. It also depends on if the patient is on the medication seasonally or non-seasonally. Another area of question is in therapeutic monitoring of cyclosporine trough levels.

The drug level can increase over time because of saturation of tissue binding sites. It would seem prudent to monitor cyclosporine levels in patients where the drug did not appear effective or in those with signs of toxicity i.e. liver/kidney enzyme elevations, gingival hyperplasia, neuropathies, etc.

If administered with other drugs, cyclosporine can interfere with (or be interfered with) other drugs. Probably the most well-known interaction is when administered with ketoconazole, cyclosporine levels will be increased. This drug interaction is sometimes purposely used to an advantage in that less cyclosporine can be used. Cyclosporine can inhibit p-glycoprotein-the multi-drug resistance efflux pump and enhance the absorption of drugs, such as digoxin and immodium. Cyclosporine concentrations can be increased when administered with other drugs, such as diltiazem, erythromycin and metoclopramide. Anticonvulsants, such as phenobarbital can decrease cyclosporine concentrations.

Immunotherapy is still the therapy of choice in our office for long-term treatment of atopy because long-term adverse effects of cyclosporine are yet to be determined. Cyclosporine is useful as the sole treatment for atopy or used initially in combination with immunotherapy to provide the patient with some relief. In the atopic patient with bacterial pyoderma, the pyoderma should be treated before starting cyclosporine therapy.

The drug is contraindicated in patients with known neoplasia and might potentiate subclinical toxoplasmosis in cats. Its main drawback, particularly in larger dogs, is its expense, but it is another option to offer the owner in the treatment of canine atopy.