A clinical approach to feline atopic dermatitis

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Accurately diagnosing and managing dermatologic disease in clinical practice can be a long and difficult process, especially in feline patients. The pruritic cat is challenging even for board certified dermatologists.Cats are masters of disguise and landing the definitive diagnosis of atopic dermatitis can take time. Feline allergic dermatitis is defined as a hypersensitivity reaction to insect/flea bite, food allergens or environmental allergens. A thorough history, clinical examination, diagnostic work up and treatment trials are all necessary to determine the cause of the pruritus.The goal to successfully treating and preventing pruritus is the identification and control of the specific underlying disease process.Feline atopic dermatitis in is only diagnosed once all other causes of pruritus have been excluded.

My approach to the pruritic cat always starts with an extensive history. This may be the longest part of the initial consult. Dermatological history should include the age at acquisition of the pet. Knowing the age at onset of clinical signs and skin lesions can further narrow down many forms of dermatological diseases. In most cases, atopic dermatitis will initially occur in patients over age 1 year (but can range from ages 1 to 4 years). In patients under age 1 year or over age 6 years at onset of clinical signs, I will be ruling out food allergy, ectoparasites, and dermatophytosis prior to further work up of atopy. Additionally, in my history, I will focus on asking if the pet is showing signs of pruritus associated with the skin or hair changes. It may be difficult for owners to associate the clinical signs of ‘itching’ in the feline pet. Listing out the signs of pruritus to the owner can be very helpful. Clinical signs of pruritus in the cat include licking, scratching, chewing, head shaking, paw licking, nail biting, pulling out hair. Additionally, cats are secretive lickers and specifically asking about frequent hair balls (in vomit or feces) could indicate over grooming patterns.

History Taking

During the history taking, it is also important to ask about local environment. Does the cat primarily live indoors, outdoors, or a combination of the 2, in attempt to help determine possible exposure to various allergens, insects, or infectious organism. Inquiring about any affected in-contact animals will aide in evaluation of contagious organisms such as fleas and mites. I will always evaluate previous medication history to gain information about any seasonality to when medications are being used, antibiotic exposure, and response to therapy. I believe it is always good to know what medications help, but sometimes equally important, what medications did not help alleviate clinical signs or the pruritus. For example, in most patients with early atopy, they will initially have reduction in itch while receiving corticosteroids. A patient that gets worse on prednisone increases suspicion for an infectious cause of pruritus, most specifically dermatophytosis.

Distribution Patterns

For many dermatological diseases, we discuss distribution patterns to narrow down the underlying cause or disease. However, these are not as specific in our feline patients. Feline distribution patterns include head and neck pruritus, eosinophilic granuloma complex (indolent ulcer, eosinophilic linear granuloma, eosinophilic plaques), symmetric or self-induced alopecia, and milliary dermatitis. When we have a patient that fits 1 of these patterns, we may have allergic dermatitis, but it is not specific. For example, a patient with head and neck pruritus may have atopy, food allergy, or an ectoparasitic infection. Additionally, allergic cats do not have as many chronic changes to the skin with atopy as dogs. Erythema is not always present with feline allergic dermatitis lesions, and especially with self-induced alopecia. Additionally, crusting, scaling or hyperplasia of the skin would be considered unusual in early cases of feline allergic dermatitis. When there is severe crusting or scaling on a feline patient, I look for ectoparasites (notoedres, cheyletiella, demodex sp), autoimmune disease (pemphigus foliaceous), or immune mediated skin disease (thymoma, cutaneous lymphoma, sebaceous adenitis).

Physical and dermatological examinations should be thorough and extensive. A trichogram and cytology are a constant in my exam. Especially in cases of alopecia, a trichogram will determine fracturing of the hair shaft consistent with licking or self-trauma. This is especially important if the owner does not know if the patient is pruritic. Skin cytology of eroded lesions would be used to look for eosinophils to suggest eosinophilic granuloma complex and look for secondary pyoderma. Allergic cats with ulcerative eosinophilic plaques will often have a secondary staphylococcal infection from self-trauma and inflammation. Yeast dermatitis would be less expected in most cases of feline allergic dermatitis. This contrasts with our allergic canine patients where yeast dermatitis is very common with atopy. Recurrent bilateral otitis externa is common with feline allergic dermatitis. However, an otoscopic evaluation is always recommended as feline patients, in contrast to our canine patients, will more commonly have otitis from nonallergic causes such as ceruminous cystadenomas, polyps, or neoplastic masses in the ears.

Testing and Management

Upon reaching the diagnosis of nonflea, nonfood induced hypersensitivity dermatitis (NFNFIHD), we can start discussing intradermal allergy testing (IDT) or medical management options.¹ Options for allergy testing for diagnosis of atopic dermatitis include intradermal allergy testing or serological allergy testing. Intradermal allergy testing is considered the gold standard in which small amounts of specific environmental allergens such as pollens, molds, epithelial extracts, or insects are injected into the dermis at specific concentrations for to determine reactions.

Interpretation of the cutaneous reactions after intradermal testing in the cat is sometimes more difficult as compared to the dog. Intravenous fluorescein may be used to highlight positive reactions. Serological assays based on enzyme-linked immunosorbent assay (ELISA) are more readily available for identification of serum allergen-specific IgE to the general practitioner. However, clinical validity of these assays has been questioned due to poor correlation with IDT results and lack of standardization between labs. It is common in feline patients that these serological tests are negative or have small number of positive reactions. When interpreting either the intradermal allergy test or the serological test, it is recommended that the positive reactions correlate to clinical disease and are consistent with the seasonality, or no seasonality, in that patient. In my experience, allergy serological testing in feline patients is helpful with nonseasonal allergens, but often come up negative for seasonal allergens.

The goal of intradermal allergy testing is to formulate allergen specific immunotherapy (ASIT).ASIT is the practice of administering gradually increasing quantities of an allergenic extract to an allergic patient to decrease reactions associated with subsequent exposure to the causative allergen. Although the exact mechanism whereby ASIT effectively controls allergy is not fully understood, it is believed to work by altering the TH1/TH2/TH17 and Treg balance which effectively regulates the immune response to subsequent allergen exposure.²

If IDT and ASIT are elected, then we have the option for either injectable or sublingual administration. Overall, most feline patients are extremely willing to accept weekly injections over oral medications for long term therapy. However, a portion of feline atopic patients, or the client, prefer sublingual immunotherapy which has been more widely available in recent years.

Communication and Long-term Planning

Communication with owners is essential in determining the most effectively modality to treat their pet in the long term. Feline patients are unfortunately notorious for being difficult medicators. One of the most important goals for successful long-term management in atopic dermatitis is finding a treatment plan that will be carried through by the owner, is effective in controlling the pruritus, is feasible financially and is safe for long term use. Maintaining the bond between cat and owner will also be part of a successful long-term plan. Always ask the owner if they can medicate their pet and what is the best way to do so. For example, would oral liquid medications, oral tablet medications, transdermal medications or injections be best tolerated for an extended period. Transdermal medications are often possible for feline owners to administer but are recommended with caution as transdermal absorption of most drugs is limited. Management of feline atopic dermatitis requires a multimodality approach:

1. Identify specific form of allergy
2. Perform intradermal or serological allergy testing
3. Formulate allergen specific immunotherapy
4. Start anti-pruritic therapy- antihistamines, topical therapy, or low dose immune modulatory or anti-inflammatory medications
5. Continue routine follow up exams.

Glucocorticoids

Systemic medications that can be added in with ASIT for the management of feline atopic dermatitis includes, but is not limited to, the following: glucocorticoids (prednisolone, methylprednisolone, dexamethasone, triamcinolone, depomedrol injection). Glucocorticoids typically provide fast relief of itch in early cases of atopic dermatitis but may start to lose efficacy over time. They come in various administration forms including tablets, injection, and liquid, which allow owners to choose what is most feasible. However, glucocorticoids often need to be used at higher doses to effectively manage dermatologic disease and may have a myriad of possible adverse effects with prolonged use. In the feline patient, cutaneous atrophy and follicular atrophy or alopecia is a cutaneous adverse effect of extended steroid therapy.Additional adverse effects include polydipsia, polyuria, increased infections (skin, respiratory or urinary), hyperglycemia, azotemia, and hepatopathy. When using a glucocorticoid for the skin, the ideal would be to use the mildest form at the lowest dose that keeps the patient comfortable.Mild itch (2-3/10) on the itch threshold is acceptable. Striving for 0/10 means we are likely on too high of a dose for safe long-term management.

Inhibitors

Atopica (modified cyclosporine) is a calcineurin inhibitor which inhibits T-lymphocytes. The veterinary approved product for cats is cyclosporine oral solution (Atopica for Cats; Elanco) is an ultra-micronized emulsion and is typically easier to dose for feline patients. Modified cyclosporine can take up to 6 weeks to take effect in atopic feline patients at 7 mg/kg/day dosing. Once at steady state (typically at 4-6 weeks on therapy), modified cyclosporine can be slowly tapered to the lowest effective dosing (every other day to twice weekly in many patients).³ This may be a safer long-term therapy for feline patients, over prednisolone, as it has less effect on the blood glucose level and is safe for patients with concurrent cardiac disease. However, the liquid has a bitter taste and can result in hypersalivation, vomiting or hyporexia to anorexia in some patients. Additionally, once the bottle of cyclosporine oral solution is opened to air it degrades quickly (11 weeks for the 17 ml bottle and 8 weeks for the 5 ml bottle).This is important to consider as the patients is tapered down on the dosing to ensure continued efficacy of the product. A physical examination and serum chemistry panel at 6 weeks followed by every 6-8 months is recommended while on therapy. Additionally, avoidance of raw food diets and hunting outside is necessary while on therapy is best prevent certain infectious disease.

Oclacitinib (Apoquel; Zoetis) is a novel Janus kinase inhibitor labeled for control of pruritus related to allergic dermatitis in canine patients.⁴ Its use in feline patients is considered extra label. However, there are several studies looking at the dosing and efficacy of this therapy in the feline patient. My clinical experience with the product in feline allergic cases agrees with the reported <50% response rates in feline patients at a dose of 0.4-0.6 mg/kg orally twice daily for two weeks then decreasing to once daily dosing.⁵ Additional doses for oclacitinib in the cat have been published as 1 mg/kg twice daily in feline mastocytosis, 0.5-1 mg/kg twice daily for feline asthma and 1 mg/kg twice daily for allergic dermatitis.^6-8 Overall, oclacitinib is typically well tolerated by the feline patient with weight loss being most reported adverse effect.5 Blood work monitoring to include renal values and sDMA value is recommended with long term use in feline patients. Avoidance of raw food diet and screening for feline immunodeficiency virus and feline leukemia virus would be recommended prior to starting this therapy.⁵ It is available as a tablet form and overall safe to use in diabetic and cardiac patients but no long-term studies on safety have been done in the cat.

Antihistamine

Antihistamines can be a safe, low cost and effective adjunctive agents in managing feline atopic dermatitis. I would typically use either chlorpheniramine 2 mg by mouth twice daily or cetirizine 5 mg by mouth twice daily in my feline patients. They are often best when used with other therapies including glucocorticoids or modified cyclosporine. Over time, while on allergen specific immunotherapy, many patients may be well maintained on antihistamines alone. First- generation antihistamines like chlorpheniramine may hold some sedative effect. However, this is usually mild and transient with extended use. Second generation antihistamines like cetirizine may have less sedation associated with use and can potentially better stabilize eosinophils and peripheral H1-receptors.

Concurrent Medication

Finally, gabapentin may be a helpful medication in feline allergic skin disease as a sole or concurrent medication. The exact mechanism of gabapentin is not fully understood; however, it has been found to be safe and often effective for stress, discomfort, and hyperesthesia in the feline patient. The dosing is 5-10 mg/kg every 8-12 hours in the cat, can take up to 1-2 months to see maximum benefit, and should slowly be weaned off with extended use.⁹

Conclusion

In conclusion, feline atopic dermatitis is a long-term disease process that is not curable but is manageable. We should strive to provide the patient with the best quality of life and a trusting relationship with the owner while minimizing side effects of therapy. Continuous client communication, individual adjustments and follow up examinations will provide better long-term control of feline atopic dermatitis.

Noel Radwanski, DVM, DACVD, is board certified in veterinary dermatology, at BluePearl Specialty and Emergency Pet Hospital. She has a particular interest in autoimmune skin disease, ear disease, horse dermatology and allergies, and minimally invasive laser surgery of the skin, external ear canal and middle ear.

References

1. Hobi, S, Linek M, Marignac G, et al. Clinical characteristics and causes of pruritus in cats: a muticentre study on feline hypersensitivity–associated dermatosis. Vet Dermatol 2011; 22: 406-413.
2. Keppel KE, Campbell KL, Zuckermann FA et al. Quantification of canine regulatory T-cell populations, serum interleukin-10 and allergen-specific IgE concentrations in healthy control dogs and canine atopic patients receiving allergen-specific immunotherapy. Vet Immunol Immunopathol 2008; 123: 332– 344.
3. Steffan J, Roberts E, Cannon A, et al. Dose tapering for cyclosporine in cats with nonflea-induced hypersensitivity dermatitis. Vet Dermatol 2013; 24: 315-322.
4. Cosgrove SB, Wren JA, Cleaver DM et al.Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis.Vet Dermatol 2013: 24:479-487.
5. Ortalda C, Noli C, Colombo S et al. Oclacitinib in feline nonflea, non-food-induced hypersensitivity dermatitis: results of a small prospective pilot study of client- owned cats.Vet Dermatol 2015; 26: 235-e52.
6. Frank RK, Galvan BA, Shoell RA et al. The use of oclacitinib (Apoquel; Zoetis) for the treatment of cutaneous mastocytosis in a cat.Vet Dermatol 2014; 25: 153. (abstract)
7. Chang CH, Dobam JR, Cohn LA et al. An experimental janus kinase (JAK) inhibitor suppresses eosinophilic airway inflammation in experimental feline asthma. In: Proceedings of the American College of Veterinary Internal Medicine Forum. Seattle, WA, USA: 2013.
8. Noli C, Matricoti I, Schievano C. A double-blinded, randomized, methylprednisolone-controlled study on the efficacy of oclacitinib in the management of pruritus in cats with nonflea nonfood-induced hypersensitivity dermatitis. Vet Dermatol 2019; 30:110-e30.
9. VanHaaften KA, Eichstadt Forsythe LR, Stelow EA et al. Effects of a single pre-appointment dose of gabapentin on signs of stress in cats during transportation and veterinary examination. J Am Vet Med Assoc 2017: 251: 1175-1182.