Alice Jeromin, B.S. Pharmacy, DVM, DACVD
Feline Atopic Skin Syndrome, formerly Cat Atopy: A Review
Feline Atopic Skin Syndrome (FASS) is the current term (as of 2021)[i] for what was formerly referred to as atopy in the cat. The new terminology encompasses what was formerly termed “nonfood/nonflea allergic dermatitis”, “feline allergic dermatitis”, and/or feline atopic-like syndrome”. For professionals in the veterinary field for several years, it was commonly known as a disease for which a long-acting steroid injection was prescribed when flea allergy was not a factor. However, the clinical use of this long-acting steroid (methylprednisolone acetate) comes with only 2 retrospective studies evaluating its use in idiopathic eosinophilic granulomas in 55 cats.[ii] In one study, 29 of the 43 cats that received no treatment achieved a complete response. In the second study, 66 out of 194 cats achieved complete response when administered 20mg/kg SQ every 2 weeks for 2-3 injections. There are numerous other options for treating this newly termed disease which is second only in occurrence to flea allergy dermatitis. Since FASS is a chronic disease, alternatives to long-acting steroid treatments that are commonly used for a disease that will likely last the cat’s lifetime need to be considered.
Earlier studies at Cornell and the University of Georgia determined that 15-17% of cats were diagnosed with FASS while a more current study indicates 12-32%.[iii] Unfortunately FASS is still poorly investigated in comparison to atopy in other species but advances in the immunopathogenesis of FASS are increasing and ongoing. Immunologically, cats with FASS (like dogs and humans) have elevated CD4+ T-lymphocytes in lesional skin which supports a role of TH-2 lymphocyte-mediated immunity.[iv] They have an increased CD4+: CD8+ ratio, increased CD1a+ Langerhans cells and CD4+ TH cells are IL-4+–all of which support a TH2 involvement (including IL-5, IL-13). A recent study demonstrates a broad array of immune secretory cytokines in FASS cats’ serum which is associated with a mixed TH1 and TH2 inflammatory response.[v] When cytokine expression in cats with allergic dermatitis or asthma were evaluated, it was concluded that feline allergic diseases exhibit different pathomechanisms from allergic diseases in other species.[vi] In dogs and humans, skin barrier function alterations exist, yet little is known about barrier function in FASS cats. IgE has been difficult to demonstrate in cats, unlike in dogs and humans, so the relevance of allergen-specific IgE in cats is still uncertain.[vii]So although there are a few similar aspects of allergy in cats, overall cats tend to differ in the pathomechanisms and clinical presentations of atopy from humans and canines.
There does not appear to be a clear breed predisposition in cats with FASS but breeds overrepresented include: Abyssinian, Persian, and Siamese with females (58.4%) outnumbering males. In my midwestern United States practice, we had an overabundance of gold or gold color containing cats with FASS—gold, gold and white, calicos, and tortoise shell cats. Unlike atopy in dogs, the age of onset of FASS in cats is variable ranging from 6 months of age to 14 years old. Most show clinical signs at <3 years of age but one study indicated 22% starting at 7 years or older.[viii] Do not rule out atopy as a differential if seeing suspected clinical signs in an older cat! House dust mite allergy is the most common allergy in dogs, cats, and people[ix] which may explain why 75% of cats present with nonseasonal disease (after ruling out food allergy, of course which is also nonseasonal).
The main clinical sign of FASS in cats is PRURITUS. This itching may result in: self-induced alopecia or lesions such as miliary dermatitis, plasma cell pododermatitis, eosinophilic granuloma complex, exfoliative lesions, seborrhea, or chin acne +/-otitis. Secondary cutaneous bacterial infections once thought to be rare in cats, are apparent in FASS cats.[x]Malassezia was isolated more frequently in allergic cats vs. nonallergic. In my practice I often found Malassezia on the chin and face possibly from the cat pawing at its chin downward from the ears, contaminating the chin with the yeast otitis which is often present. Otitis externa has been reported in 21% of FASS cats.[xi]Less common clinical signs such as respiratory (asthma), ocular (conjunctivitis), and/or gastrointestinal involvement have been reported.[xii]So unlike dogs, cats are unique in their characteristics of FASS in that they may manifest clinical signs at an older age and may have any one or more extremely variable clinical signs involving numerous areas of the body. In one Australian study, clinical distribution of lesions was as follows: head (71%), neck (51%), ventral abdomen (51%), limbs (38%), pinnae (31%), dorsum/rump (31%), and feet (16%).[xiii]
Diagnosing FASS in cats is one of exclusion. Differentials that mimic FASS include: flea allergy dermatitis (FAD), food allergy, demodicosis, Malassezia dermatitis, idiopathic ulcerative dermatitis, ectoparasites (such as Cheyletiella, Notoedres), pemphigus foliaceus, dermatophytosis, mosquito bite hypersensitivity, and hyperthyroidism. Many of these can be quickly ruled out during the physical examination (FAD, demodicosis, Malassezia, ectoparasites, pemphigus, dermatophytosis). As with any dermatological disease, a thorough history must be undertaken to find out how long the cat has had problems, response to medication, areas of the body affected, age of onset, dietary history, exposure to other pets, etc. It is important to understand that serum or intradermal skin testing to “prove” the cat has FASS is not acceptable. On either of these tests, cats may have a positive IgE reaction and not be clinical OR be clinical and not test positive! Serum and/or intradermal allergy testing is only used once the diagnosis of FASS has been determined, the results of which are used to formulate an immunotherapy solution be it injectable or sublingual. In nonseasonal affected cats, an 8-week prescription elimination diet trial is advised to rule out food allergy as clinical symptoms of FASS and food allergy may mimic one another. Food allergy in cats may also present with gastrointestinal signs as well as conjunctivitis. The incidence of FASS and food allergy together in the same patient in a recent study was low at 2.4%.[xiv]
Once the diagnosis of FASS has been achieved, therapy for that patient should be tailored to the individual cat taking into consideration the owner’s abilities, finances, whether the cat is indoor or outdoor, and personality of the cat. Thankfully treatment for FASS is multimodal involving numerous therapies and combinations of therapies—more so than what is available for atopic dogs! (Maybe having many options is poetic justice since some cats can be difficult to administer oral medications.) Options for treatment include: immunotherapy-injectable or sublingual, short-acting glucocorticoids, antihistamines, and modified cyclosporine. Oclacitinib which has been discussed in the past as an off-label treatment for FASS has recently been discouraged due to safety issues in cats in long-term studies.[xv]
Allergen-specific immunotherapy, injectable or sublingual (SLIT) is the only treatment for FASS that induces tolerance and enables reduction or complete elimination of other long-term treatments.[xvi] In other words, it can elicit a cure! In cats, studies have shown a 60-70% control rate with immunotherapy based on serum or intradermal testing.[xvii]Immunotherapy’s mechanism of action researched in humans is to induce regulatory T cells (T-reg), increase IL-10 and TNF-beta, which results in reduced TH-2 cytokines. Sublingual immunotherapy in cats is relatively new but appears to be promising. Currently 25% of veterinary dermatologists surveyed have cats on SLIT. In a study of 22 FASS cats allergic to house dust mites, 19/22 cats showed improvement after 3 months on SLIT. [xviii]Whichever method of testing to determine which allergens are to be included in the immunotherapy solution, the positives must correspond to the time of the year the cat is affected in order to be successful. It is not a matter of just including all of what is deemed positive on the test results! A down side to immunotherapy is the time lag averaging 3-8 months before seeing results. However, the safety and ultimate possible “cure” are certainly worth the effort! When initially staring immunotherapy, other oral medications such as antihistamines, modified cyclosporine, or short term, short-acting glucocorticoids may be employed. Many clients are surprised at how easy it is to administer the subcutaneous (SQ) injections once weekly (many different frequencies of administration exist ranging from twice/week to once/week to every 2 weeks to monthly) as opposed to “pilling” their cat once or twice daily. The owner must be capable of understanding what immunotherapy is and what is trying to be accomplished. An observant owner is essential as if after administering a dose of immunotherapy, the veterinarian needs to be contacted if the cat is more pruritic as a dose adjustment is needed. It is not a matter of just “flying through” the administration schedule without paying attention to how the cat is doing! Just as matching the allergen positives with the time of the year the cat is affected, equally important is an observant owner! Owners must be made aware that immunotherapy alone may not totally control their pet’s symptoms and that occasionally during increased allergen periods, supplemental medications may be needed. Along with the safety issue of immunotherapy, cost is probably the least of all the treatments when compared to the other available therapies (to be discussed below). Not only is the relatively lower cost of the allergy solution a factor when compared to oral therapies but some oral therapies require routine blood work to monitor for any changes while on the medications, adding to the expense. In our office we require yearly physical exams on our immunotherapy patients to monitor to see they are progressing well. One other personal suggestion I can make to veterinarians is to be certain to dispense 1cc syringes for SQ immunotherapy administration. Although it sounds elementary, pharmacies occasionally dispense 3cc syringes in spite of prescribing for lcc tuberculin syringes. As you can imagine, this makes a big difference in dosing, may result in dosing errors, and confuses the owner! Finally, I am proud to say that one of my clients with a FASS cat who was terrified to administer injections, overcame that fear and actually went on to become a nurse in human medicine!
What about glucocorticoid use? My own personal thought on steroids is to USE AS LITTLE AS POSSIBLE! In fact, after 30 years of clinical veterinary dermatology practice and 40 years as a pharmacist, many days it seemed my main mission was to get these pets off steroids due to their long-term adverse effects. Nothing is more satisfying than having an owner of a cat on long-term steroids that has muscle atrophy, thin skin, etc. tell me that her cat was playful again—success!! Cats are certainly more steroid tolerant than dogs but it certainly doesn’t mean to not respect their conservative use in cats. Older cats particularly can become hyperglycemic after a long-acting glucocorticoid injection and studies show that even after one injection a cat can experience heart failure.[xix] When prescribing glucocorticoids for cats, prednisolone used short term i.e., 2-4 weeks in duration at 2.5-5mg once daily initially for 3-7 days, then every 2-3 days while maintaining close communication with the owner. Most owners who themselves who have been on glucocorticoids do not want the same for their pets as they are aware of the potential adverse effects—hyperglycemia/diabetogenic, pancreatitis, muscle weakness, thin skin, hair loss, etc. If a cat has been on long term steroids and they are no longer effective, the type of steroid used should be changed to one that appears “different” to the body as tolerance has occurred. For example, instead of prednisolone, change to methylprednisolone 4mg once daily then ½ tablet every 2-3 days. If the owner has trouble “pilling” the cat, I will prescribe oral dexamethasone tablets 0.75mg to use ½ tablet once daily for 2-3 days then MWF or 2x/wk. A recent study using dexamethasone SP injection 4mg/ml administered orally at 0.2mg/kg once daily for 7 days then 2-3x/week has shown success.[xx] For those owners unable to administer oral steroids, transdermal steroids are not bioavailable! When maintaining a cat on glucocorticoids (which is not preferred) remember to monitor urinalyses and blood glucose routinely.
Antihistamines when used for FASS have conflicting results. A 2008 study using cetirizine indicated (by owners) a 41% success rate in allaying symptoms but a repeat study in 2013 showed cetirizine to be ineffective.[xxi]The main problem with ANY of the antihistamines when used in cats is the bitter taste. It may be possible to administer the first dose but hypersalivation and evasion may occur when trying to administer the second! Many owners do not understand the hypersalivation from the bitterness and think the cat is having a seizure or some other serious problem. Combining an antihistamine with an oral glucocorticoid may enable a lower use of the steroid but still requires daily or twice daily dosing. Doses of antihistamines for FASS in cats are as follows:
- Hydroxyzine HCl or pamoate 1mg/lb. body weight bid
- Chlorpheniramine 4mg ½ tablet s-bid
- Clemastine l.34mg ½ tablet bid or 0.05-0.1mg/kg bid
- Loratadine 5-10mg/cat sid
- Cetirizine 2.5mg/cat sid or 1mg/kg once daily
- Cyproheptadine 2mg/cat bid
If an owner is willing to administer daily antihistamines to an allergic cat, and if they are effective in that cat, tolerance may develop as it can in humans. I often recommend to owners to administer the antihistamine for 3 weeks on/1 week off and repeat so as to avoid tolerance. For the 1 week off, a short-acting daily or every other day glucocorticoid may be used to relieve FASS symptoms. The intent being to use as little steroid as possible by combining with the antihistamine therapy.
Modified cyclosporine liquid is an FDA approved treatment for FASS (Atopica by Elanco). In a study of 144 cats with FASS, 65.1% showed symptom relief compared to 9.2% for the 73 placebo group cats.[xxii]Modified cyclosporine at 5-7.5mg/kg once daily can be used long-term to control FASS or initially while starting oral or injectable immunotherapy. The drug has a lag time of up to 4 weeks to see efficacy and once symptoms are under control on the daily dose, it can be tapered to every other day or twice weekly successfully (70% and 50%, respectively).[xxiii]The most common side effect is gastrointestinal upset but administering the drug with food may be helpful and does not interfere with its bioavailability.[xxiv]It should be used cautiously in outdoor cats or those eating raw meat diets as toxoplasmosis recrudescence may occur particularly in toxoplasmosis naïve cats.[xxv]Since a commercially available modified cyclosporine product is available, there is no need have the oral solution compounded. In studies, compounded modified cyclosporine liquid has been shown to result in an inferior product with doubtful bioavailability and stability.[xxvi]
Oclacitinib, a Janus kinase inhibitor FDA approved for dogs, has been administered to FASS cats off-label. Short-term studies using oclacitinib have been used in allergic cats with doses ranging from lmg/kg every 12-24 hours.[xxvii]The half-life of the drug in cats is 2.3 hours compared to 4.l hours in dogs accounting for the larger dose used in cats.[xxviii]Since the safety of this drug used long term in cats has not been determined, and a recent suggestion from the manufacturer advises against its use in this species, informed owner consent with diligent monitoring should be employed should you decide to use this off-label medication. A recent report of fatal toxoplasmosis recrudescence occurred in a FIV positive cat on oclacitinib for FASS.[xxix]
Lokivetmab, the canine anti-IL-31 monoclonal antibody used in canine atopy, SHOULD NOT be used in cats. It is a caninized monoclonal antibody and if used in cats would be recognized as foreign and may cause anaphylaxis.
Finally, as mentioned earlier, a multimodal approach is necessary when treating FASS in cats. There is rarely one “go to” medication that fits every patient. The owner’s ability, finances, temperament of the cat, and whether the symptoms are seasonal or nonseasonal all have to be considered in developing a treatment plan. My preference for treatment is allergy testing and starting immunotherapy either SLIT (depends on if the owner can administer twice daily oral liquid) or once weekly injections while employing either singly or in combination a short-term, short-acting glucocorticoid, antihistamine, or modified cyclosporine. The goal is to use as little steroid as possible and in nonseasonal affected cats (usually house dust mite allergic) I avoid keeping the cat on a year-round steroid even at what is deemed by some as subjectively “low dose”. Short-acting glucocorticoids can be used daily for 3-7 days to break an itch cycle during flareups while resuming the designated current treatment plan. If a few days of a short-acting glucocorticoid does not break the itch cycle, be sure to get the patient into the office for an examination as ectoparasites may be a factor. In several FASS patients I have treated over the years, fleas or Cheyletiella have been the cause of occasional flareups in cats that have been well maintained on immunotherapy. In cats on immunotherapy that experience a flareup, the owner needs to be questioned to determine if the flareup was immediately after the injection as the dose may be too high for that time of year. If that is the case, I will have the owner skip an injection then resume at ½ the dose for the next upcoming dose. They are to report the response to that dose so it can be determined where to go from there. If the owner reports the cat improves with their pruritus for a few days after the injection, we will continue to slowly increase the dose by 0.lcc/week until we reach a successful maintenance dose. Many veterinarians are fearful of using immunotherapy for fear of making a mistake as to the dosing. There is no “written in stone” bible of immunotherapy dosing and most veterinary dermatologists use dosing as they were taught by their mentors. It is just logical that if a current dose seems to CAUSE pruritus, to cut back on the dose until a dose that does not aggravate the situation occurs.
Finally, FASS is the new terminology for what was once termed feline atopy. It describes allergic skin disease in cats associated with environmental allergies which is the second most common allergy in the cat after flea allergy dermatitis. There is no “one size fits all” treatment for cats with this disease. FASS treatment is multimodal as treatments need to be tailored both to the cat and the owner. In the past, long-acting glucocorticoid injections were administered as treatment but tolerance may develop with subsequent injections as well as cardiac and/or diabetic issues. With the emergence of new insights into the pathogenesis of this disease in cats, which differs from the disease in humans and dogs, new treatments are certainly on the horizon!
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[xv] Zoetis technical services communication, March 2022.
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[xxiii] Mueller R, et al. Treatment of the feline atopic syndrome—a systematic review. Vet Derm. 2021;32: 43-e8.
[xxiv]Atopica liquid for cats, Elanco product information.
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[xxviii] Ferrer L, et al. A pharmacokinetic study of oclacitinib maleate in six cats. Vet Derm. 2020;31(2): 134-137.
[xxix]Moore A, et al. Fatal disseminated toxoplasmosis in a feline immunodeficient virus-positive cat receiving oclacitinib for feline atopic skin syndrome. Vet Derm. May 29, 2022.