Another itchy cat, now what (Proceedings)

The most common derm problem in cats is itchy skin disease. Often these cats have allergic skin disease with many cases related to flea allergy dermatitis, atopic dermatitis and adverse food reactions. Though uncommon in most parts of the world Demodex gatoi should always be considered as well as the role of psychogenic contributions to the dermatitis. However it is also important to recognize the role pyoderma and Malasseizia sp. play in pruritic cats, to be discussed in the session, Feline infectious skin disease, more than you realized. If lesions other than barbered alopecia are present then skin cytology is the first thing to do. If infection is present then appropriate antimicrobial therapy is indicated. Once these aspects have been dealt with then it is likely that allergic disease, food allergy or atopic dermatitis is present and lifelong management will be needed.

Demodex gatoi

Compared to Demodex cati this mite is shorter in length with a broad based blunted abdominal segment. This mite is a surface dweller in contrast to the normal follicular orientation of classic demodex from D. cati or canis. It also appears to be somewhat contagious as outbreaks have been described. Clinically there may be minimal disease and pruritus or intense pruritus. Pruritus is the main symptom though scale may also occur. Hair loss due to excessive grooming occurs and may involve the abdomen, forelegs (especially elbows), head and neck or rear legs. As such it mimics allergic disease or psychogenic dermatitis. In cats that are excessively grooming mites may be more difficult to find though in mildly affected non-pruritic cats they are usually present in abundant numbers. Scraping other normal or mildly affected cats in a household may lead to a diagnosis. Individual itchy cats have anectdotally been diagnosed with fecal flotation. Therapy has been successful with lym dyp as well as ivermectin 1mg/4-5kg eod.

Psychogenic dermatitis

In the past many cats were diagnosed as psychogenic dermatitis and in one study in France of 783 feline derm cases seen in 1992-1997 psychogenic alopecia was diagnosed in 4.7%. This is compared to the diagnosis of flea bite hypersensitivity 42.9%, food allergy 25.2% and atopy 22.4%. In recent years most dermatologist feel psychogenic dermatosis as the primary cause of hairloss and excessive grooming is rare. A study of 21 cats that had been tentatively diagnosed with psychogenic alopecia and referred to behaviorists for that problem revealed only 2 cases actually seemed to truly be psychogenic and responsive to clomipramine therapy. This study showed limited value in histopathology for making the diagnosis. Another study evaluating histopathology in self induced alopecia cats also noted that this is not a good way to separated normal from affected cats nor to determine an etiology. The problem is that psychogenic factors are known to play a role in humans with many skin diseases, but especially atopic dermatitis. Recently this has been described in dogs as well and likely occurs in cats. There may be some cats that using behavior modification drugs such as clomipramine may improve the control of atopic dermatitis.

Flea Allergy Dermatitis

In most geographic areas, FAD is often described as a common cause of skin disease in dogs and cats. A recent survey in the United Kingdom showed in veterinary clinics a prevalence of lesions compatible with FAD as 8% in cats[9]. The advent of newer more effective flea control products has been both beneficial and detrimental to clinical practice. The new products have greatly minimized the impact of flea allergy dermatitis in many practices and allowed for much more effective flea control. At the same time many clients utilizing these products no longer believe fleas can be the cause of disease, making the client acceptance of the diagnosis more problematic.

Clincial Findings

Flea can induce a variety of lesions in the cat and all these may not really be allergy mediated. For example some cats respond with twitching and itching in response to the fleas that twitch following nitenpyram therapy. Other cats may develop barbered alopecia just from "chasing down" fleas while removing them or have a psychogenic alopecia from the presence of fleas without actual allergy. However the most classic flea lesion associateded with allergy is miliary dermatitis. This lesion is typified by focal, small 1-5mm, crusted papules. Depending on the stage the lesions may appear as erythematous or hyperpigmented macules or papules. As alopecia may be absent or mild these lesions may be difficult to see and it is often stated they are felt more readily than they are seen. The lesions may be seen virtually anywhere on the body and the pattern is used to suggest which associated causes are more likely as these lesions are not specific for flea allergy but may also be seen with atopic disease, food allergy, folliculitis, cheyletiella and dermatophytosis. Of these flea allergy is the most common cause and though bacterial folliculitis is considered by some to be rare in it also should be considered whenever miliary lesions are seen. Most flea and allergic causes are associated with tissue eosinophilia which may be demonstrated cytologically. The dorsal lumbar, groin and caudal thigh areas are often affected, as in the dog but that pattern is not as typical and only one of these areas may be affected even without the dorsal lumbar area. Cervical lesions more dorsal but all around the neck is another common area affected in feline FAD and some cases will have generalized disease. Eospinophilic plaques, ulcers including lip ulcers and granulomas may also be found in flea allergy dermatitis.

Treatment for flea allergy dermatitis and flea aggravated pruritus is effective control of flea populations and prevention of exposure to adult fleas. Success may be easy in many situations but often requires an understanding flea life cycle and biology which can be found in a variety of reviews.

Modern flea control has evolved to a point where most clients can control fleas effectively with the regular monthly use of topical or systemic flea products on all dogs and cats in the house that contain one of the following: dinotefuran, imidacloprid, fipronil, metaflumizone, selamectin and spinosad. These products have high efficacy of killing adult fleas for 30 days following one application and generally if all pets in a household are treated will usually eliminate fleas from the environment. The topical adulticides fipronil, imidacloprid and selamectin have been shown to be efficacious for treating flea allergy dermatitis in dogs and cats, even when environmental treatment is not done. Fipronil in the spray formulation is often described as being more efficacious than the spot application though one study evaluating antifeeding of cat fleas on cats did not support that. Nitenpyram is the most rapid flea killing systemic product available, with the drawback of short half life. This means there is only one day duration in cats and it needs to be administered every 48 hours. It may be used when pets are known to be going into areas where fleas may be present. The newest flea products that recently have become available include two topical products approved for cats {metaflumizone (ProMeris, Fort Dodge) and dinotefuran (Vectra 3D, Summit VetPharm)} and an oral product not approved for cats, spinosad (Comfortis, Lilly).

Metaflumizone (ProMeris, Fort Dodge) is a novel insecticide that blocks the influx of sodium required to propagate a nerve impulse along the axon and dendrite of the neuron. This results in reduced feeding, loss of coordination, paralysis and death of the flea. Studies have shown excellent flea reduction up to 6 weeks with a high margin of safety.Though the speed of kill is not as quick as other products the manufactures have suggested that the product rapidly paralyzes the flea mouth parts and rapidly prevents feeding. This has not been actually proven but support comes from the data showing that by 48 hours after treatment egg production is reduced by 99.6% or greater and maintained at this level for 45 days on cats. The canine product also contains amitraz and should not be used on cats.

Dinotefuran (Vectra 3D, Summit VetPharm) is a 3rd generation neonicotinoid that is combined with pyriproxifen (insect growth hormone regulator) and was released in the United States in Feb. 08 for dogs and cats. The canine product also contains permethrin while the feline product does not. The combination of a newer generation adulticide, with an IGR and permethrin a potential flea repellent has made this an interesting product though clinical experience has not been published. Information can be found on their website http://www.summitvetpharm.com. In one presentation there were some eggs produced in challenge studies. Avoid using the canine product on cats and care should be given when using on dogs in households where treated dogs have immediate direct contact with cats.

Spinosad (Comfortis, Lilly) has been shown to be effective at killing fleas. This is in an oral chewable once monthly product currently only available in the United States and currently only approved for dogs. It may be helpful for affected cats to have dogs in the environment on spinosad as it has been shown to be 100% effective in preventing egg production for twenty one days and 98% for thirty days. This was even accomplished when dogs were exposed to large (600) numbers of fleas at each time interval tested. As a systemic internal drug not secreted onto the skin or into the environment it is FDA and not EPA regulated and not affected by shampooing or other topical therapies. This has a novel mode of action at nicotinic acetylcholine D alpha receptors with some effects on GABA resulting in nerve excitation paralysis and death of the flea. It is highly effective and starts working within 30 minutes and has 100% kill rate by 4 hr, lasting 30 days or longer. It is best given with food for the highest C max and longest duration of effectiveness. It is considered very safe and the spinosad molecule has been awarded an EPA Green chemistry award in 1999 because of its reduced impact on certain predatory beneficial insects.

In the flea allergic cat that gets exposed to adult fleas, the speed of kill becomes relevant as the longer fleas live on the FAD pet the more bites and allergens the pet is exposed to. Repellent activity is especially beneficial for decreasing allergen exposure. Topical permethrin has been shown to be very effective in reducing flea feeding on cats for 7 days though this effect was much less by 14 days and due to potential adverse reactions is no longer available for cats. Resistance to some flea products has been seen in the past. The cat flea has been described as the most resistant of the flea species, and to more types of products. Integrated pest management decreases the probability of this developing to the newer products now being used extensively. The international imidacloprid flea susceptibility monitoring program developed an invitro assay to test for the development of flea resistance. There evaluations of natural strains of fleas from around the world have shown little resistance. Complete resistance has not been described to the new insecticides though strains of fleas that are less susceptible have. More work is needed in this area.

Atopic Dermatitis

Atopic disease is becoming more commonly recognized in the cat and similar to the dog the skin form, atopic dermatitis, is the most common and appears to result from percutaneous absorbtion of allergen. However the cat appears to have more respiratory disease with atopy and some asthma cases will be atopic without any skin disease present. The atopic dermatitis cat similar to the dog is characterized by sublcinical inflammation in the skin that usually results in pruritus. The majority of the lesions seen are the result of pruritus or secondary infections. However sometimes the inflammation will leave a sign in the form of hyper or hypo pigmentation. Patterns for atopic dermatitis in the cat are not as well established as in the dog. The abdomen, groin and forelegs are the most common pattern I recognize but generalized pruritus, facial and head pruritus and even pruritic chin with acne have been seen with atopic dermatitis. Eosinophilic granuloma complex and miliary dermatitis may also be seen in atopic dermatitis cases.

The pruritus and lesions cannot be differentiated visually from many other diseases, especially food adverse reactions, Demodex gatoi, Otodectes or cheylietiella and even some cases of flea allergy or flea induced irritation. Psychogenic alopecia also has to be considered in the differential and can be difficult as stress and anxiety are known aggravators of atopic disease in humans and likely cats as well. Atopy is a type I, IgE-mediated allergic disease caused by environmental allergens. The environmental allergens are not commonly diagnosed by practitioners due to the difficulty in performing intradermal skin testing in the cat. Atopy has different manifestations and we believe it most commonly presents as atopic dermatitis though atopic rhinitis, conjunctivitis, otitis and asthma have been reported. A study in with asthmatic cats revealed that about 50% do have skin disease though not necessarily severe enough to seek veterinary care. Atopic dermatitis should be considered in any seasonally pruritic disease, but it can also present with year round signs.

The diagnosis requires demonstration of allergen specific IgE or postive intradermal testing as well as ruling out the other compatible differential diagnoses. Intradermal testing cats is more difficult than in the dog and also reactions are often slight and harder to interpet. This has left many practitioners and specialists frustrated in cases that have been well worked up and appear to be classic atopic dermatitis cats. The author is a consultant for Veterinary Allergy Reference Laboratory and has utilized this test as well as intradermal testing for instituting ASIT in cats with atopic dermatitis and atopic asthma. I prefer the VARL test over IDT in many cases because I have had more positive in suspect atopic cats while irrelevant positives appear to be less common in cats as compared to dogs. Similar to the literature about 70% of the cats respond to ASIT. In many cats ASIT ends up being preferred by the owner because they find giving injections at home more convenient than oral medications.

Therapy for atopic dermatitis has traditionally relied on corticosteroid therapy partly because cats are often described as being "resistant" to the adverse effects. Though controlled studies have not been reported it is accepted that the incidence is probably lower that in the dog and humans but adverse effects do still occur. In fact my impression is that cats are more susceptible than dogs to diabetes mellitus from chronic glucocorticoids. There are also significant numbers of atopic cats that do not respond well therefore alternative therapies are still being saught. Alternatiives to consider include antihistamines, fatty acids, allergen specific immunotherapy and cyclosporine.

If glucocorticoids are used many owners and clinicians prefer long acting injectable forms. If they are only used three times year approximately every four months then Depomedrol may be given IM at 4 mg/kg. Though systemic glucocorticoids are considered safer in cats than dogs, they still may cause serious adverse reactions and iatrogenic hyperadrenocorticism can and does occur. In the largest retrospective study of iatrogenic hyperadrenocorticism, twelve cases that met all the inclusion criteria were found at a teaching hospital during a 3.5 year time frame Diabetes mellitus, polyphagia, polydipsia, cutaneous changes, muscle wasting, pot belly, curled pinna, steroid hepatopathy, and elevated liver enzymes may all be seen in cats on glucocorticoids. Elevations in alkaline phosphatase are very rare, as cats do not make a steroid induced isoenzyme, and the half life is much shorter than in the dog Herpes virus proliferation and disease may be aggravated, made more severe or induced by glucocorticoid administration. In one study looking at 271 cats diagnosed with congestive heart failure, 12 were associated with and attributed to corticosteroid therapy. Studies in normal cats suggests this is due to volume expansion from hyperglycemia and not elevated blood pressure. In another study , seven cats treated with dexamethasone 0.55mg/kg q24h routinely demonstrated elevated fructosamine, glucosuria and decreased insulin sensitivity. One cat developed icterus by day 40, and curling of the pinna, a sign of iatrogenic hyperadrenocorticism, by day forty-eight. It is certain that glucocorticoids are not benign drugs in the feline, and they should be used with caution and in ways to minimize risk.

A variety of glucocorticoids and doseage regimens have been recommended for cats see table 1. My favorites are oral methylprednisolone and triamcinolone though due to variation in responses I have used all those in table 1 as well as prednisone which is variable absorbed in cats.

Table 1: Glucocortiocoids and induction dosages

*All oral glucocorticoids are tapered after the induction to every other day dosing (EOD) and then over time to the lowest effective EOD dose.

Antihistamines may be helpful in treating atopic cats though I do not see the 50% response rate that some have reported. My favorite two are chlorpheniramine at 2 mg q12h and cyproheptadine 2mg q12h. I have heard of or seen limited response to amitriptyline 10 mg once to twice a day, clemastine .67 mg once a day, and allegra. Cetrizine 5mg q 12-24h is considered by some to be more valuable because of its inhibition of eosinophil migration.

Allergen specific immunotherapy has been utilized for years in the management of atopic dermatitis in dogs but its use in cats has lagged behind. In dogs it is described as a mainstay of therapy. Part of the relatively lower use of ASIT in cats may reflect that the cat is perceived as "relatively resistant" to the adverse effects of glucocorticoids, it is to expensive of a therapy, or that there is less availability of tests to determine the formula for ASIT in cats. However there are reasons to prefer this method of therapy. It is the only therapy that may cure the problem or prevent the development or disease progression. Other treatments are treating symptoms or the effects of the disease. Many cats actually tolerate subcutaneous injections better than oral medications and the less frequent administration usually required is also helpful for most clients. It has been shown to be efficacious in cats and may even be more effective than in dogs The shots can be administered at home and to date there have been few if any serious side effects or reactions reported. Additionally I have actually come to prefer a serum in vitro test for cats which is in contrast to the dog, therefore what I consider the best way to test cats for what allergens to treat with is more available to practitioners.

The protocol I use in cats is different than that used in dogs. Often cats end up on smaller volume injections that many clients find easier to administer as well. The initial schedule I use is in table 1 with vial one consisting of up to 12 items. Each item is 1 ml at 1,000-2,000 PNU per ml. Vial 2 is the same 12 items but the concentration is 10,000 – 20,000 PNU per ml. If there are less than 12 items then they are all increased equally in volume until there is 12 cc. Once maintenance is reached the final volume and interval between shots is determined by each patient's response. If there is an increase in pruritus or symptoms then I decrease to the last dose that caused no reactions.

Reactions in cats are rare and serious reactions such as angioedema, or anaphylaxis have not been reported in neither the literature nor I have I personally had this happen to one of my patients. However I am aware of an anecdotal report from one veterinarian. In this case is sounded as if the cat had respiratory distress and collapsed appearing to have died but then shortly later got up and acted fine. Interestingly the owner never took the cat to the veterinarian so that this reaction can be confirmed as to type. I also have had one case that had symptoms compatible with intestinal anaphylaxis as seen in the dog.

The newest treatment being utilized for atopic cats as well as idiopathic eosinophilic granuloma complex is cyclosporine. Cyclosporin has been used for years in cats undergoing renal transplantation. Though much less in know about cyclosporine in allergic cats in recent years a number of reports have been published about the benefits of cyclosporine for a variety of skin diseases in cats which often were likely allergic in origin. There are studies of feline asthma that report the use of the drug at 10mg/kg/bid, administered with food. The mode of action of cyclosporine involves the inhibition of T-cell activation and the synthesis of various cytokines especially interleukin-2 (IL-2) and inhibits T-cell proliferation and the formation of cytotoxic lymphocytes. Cyclosporin is also thought to inhibit, via suppression of calcium-mediated signal transduction, mast cells and IgE-mediated immediate and LPR reactions, although in one study of human AD the opposite was found although the patients improved. Numerous studies have demonstrated influences on mast cells, Langerhans cells, keratinocytes, eosinophils and lymphocytes. Cyclosporin has immunosuppressive and antiproliferative effects rather than cytotoxic or myelotoxic effects. The drug is available in oil base as Sandimmune or as an emulsion or capsule formulation and consists of a microemulsion preconcentrate of cyclosporin (Neoral®; Novartis) The Neoral formulation was recently released for dogs as Atopica® by Novartis. The nice thing it is available as 10 and 25mg capsules which are most useful for cats. The recommended dose in cats with AD is 7mg/kg/day for up to 6 weeks and more work needs to be done in cats to determine optimum dosing. It is currently recommended that the drug is administered 2 hours either side of a meal, while humans should receive it with food. Adverse reactions of vomiting and diarrhea are similar to the dog and it appears liver and kidney disease is rare. Different from the dog is the relative lack of gingivitis occasional case of upper respiratory infection and rare report of systemic fatal toxoplasmosis.

Food adverse reactions in the cat.

Food allergy or food adverse reactions in the cat is more likely to have severe pruritus and associated excoriations and crusting. This may reflect a preferred pattern of neck and head that the cat can not itch by licking but only by scratching with claws or rubbing against surfaces. This often results in more linear excoriations and cutaneous damage. Even when abdominal disease is the major pattern erythema is often present. Food allergy will be non seasonal and may have associated gastrointestinal symptoms. In one study of cats with chronic gastrointestinal disease 25% of those considered food sensitive had concurrent dermatitis and 40% of ten cats with gi disease and skin disease had food sensitivity. It is also more common in Siamese cats though any breed may be affected.

Diagnosis requires elimination diet trials and provocation testing. The home cooked diet is optimal as this is the best control of limiting the ingredients fed to the cat. A new protein and carbohydrate as the only food source is the primary goal. The biggest drawback is that the diet is not balanced, nutritious, and in the cat a major problem is home cooked may not be as palatable as the commercial diets. In the cat the concern with protein levels also makes a vegetarian diet a poor option and generally they are inpalatable as well. The poor nutrition of the home prepared diet means that this type of diet trial is limited to the 8 weeks and not to be done in young cats. Generally I mix one protein and one carbohydrate with about 2/3 protein and 1/3 carbohydrate. Some cats will not eat carbohydrates so most all protein will be fed.

Realizing they are not as efficacious many clients will still prefer to use a commercial cat food for the elimination diet. The newest trend in commercial hypoallergenic diets is the use of hydrolyzed protein sources. There is only one made for cats and that is Hills Science diet ZD, which is not truly all hydrolyzed as it uses rice protein and rice and this may be an offending allergen in some cats. The theory behind these diets is that food allergy is generally to large complex proteins or glycoproteins. By hydrolyzing foods to sizes smaller than this the diet will no longer be allergenic. There is work in humans to suggest this is the case however little documentation of this has been done in dogs and none in cats. Some dogs have been documented to react to either corn starch or the hydrolyzed soy. Additionally if some of our food reaction cats are not allergic in pathogenesis then this theory of low molecular weight protein may not apply even though it could be true in true allergic induced disease. Other options are commercial diets that are formulated with the major protein and carbohydrate source being ones the pet was not previously being fed. There are the innovative diets with rabbit or duck as protein and potatoes and peas carbohydrates.

Provocation testing

The true confirmation of food adverse reaction requires that feeding the offending diet can induce symptoms (provocation testing). After symptoms have improved significantly or been eliminated the pet should be challenged with the diet being fed prior to the diet trial. If there is no increase in symptoms then all other treats etc should be fed. Each challenge should be given only until a recurrence is obvious to the client or for 7 days. If there is no recurrence after 7 days that food is not likely to be the problem. One study evaluated food sensitivity in 55 cats with chronic gastrointestinal disease that was not attributed to any infectious, neoplastic, metabolic, viral or obstructive disease. Of these 55 cats 27 responded favorable to restricted protein and rice diets fed for 4 weeks. However only 16 were able to be confirmed food sensitive by provocation testing as 11 stayed improved when challenged with their original diet. If there is a recurrence of symptoms, which most commonly is just an increase in pruritus, then the elimination diet is again fed until the symptoms again resolve. This will usually occur rapidly if the exacerbation is noted in the first two or three days on the challenge. With true allergy I suspect symptoms recur rapidly and in my experience most well confirmed food allergies are worse in one or two days. The next step is to try and determine what ingredients the pet is allergic to. Many clients are resistant to this proposal until I explain the value for them. Some pets will develop new allergies and by doing multiple challenges the client will not have to start totally over to determine what else the pet can eat. Additionally by knowing what foods the pet is not sensitive to more feeding options become available. This is particularly helpful for the long-term management of the case especially when multiple pets are in the household.

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