How I approach… Feline atopic skin syndrome

Introduction

Feline dermatology has advanced in the last few years with regard to disease recognition, better understanding of pathogenesis of existing diseases, and new treatment options. Furthermore, the terminology for feline allergic skin disease has been recently updated, and the term Feline Atopic Skin Syndrome, or FASS, is now employed in reference to allergic skin disease triggered by environmental allergens. FASS is challenging to diagnose, since various allergic skin diseases can present clinically with one or a combination of the following reaction patterns:

• miliary dermatitis, 
• self-induced alopecia, 
• eosinophilic granuloma complex, 
• head and neck pruritus.

The skin reacts in these “patterns” to different underlying causes, but they look clinically identical. These reaction patterns can even be similar on histopathology, which may make the diagnosis very complex, causing frustration to both the cat’s owner and the clinician. Because dermatitis due to fleas or adverse food reactions can also present with these cutaneous patterns it is crucial to rule them out when diagnosing FASS. In addition, other pruritic skin conditions, including parasitic (Demodex gatoi, Otodectes cynotis, Notoedres cati, Cheyletiella blakei), infectious (Malassezia dermatitis, superficial pyoderma, dermatophytosis), and autoimmune skin diseases (pemphigus foliaceus) need to be evaluated and ruled out or treated. 

Miliary dermatitis

Miliary dermatitis, or papulocrustous dermatitis, is characterized clinically by numerous, small, localized or generalized erythematous and crusted papules (Figure 1). It is the most common feline presentation in small animal dermatology, and the lesions can often be detected on palpation of the skin, especially in long-haired cats. The presence, extent and severity of pruritus, presence of skin lesions in animals or people in contact with the patient, seasonality, and response to previous medications are helpful when developing a list of differential diagnoses. 

Self-inflicted alopecia

This can be caused by a variety of conditions; hypersensitivity dermatitis is often involved, although very rarely psychogenic problems can lead to self-inflicted alopecia (Figure 2). Nevertheless, a combination of behavioral and allergic factors is frequently seen, particularly in overanxious breeds such as Siamese or Abyssinians. Hair loss can also be associated with telogen effluvium or hormonal disease such as hyperthyroidism or other internal problems. Infectious and parasitic diseases should also be considered, as mentioned previously. If the pet owner does not observe excessive grooming, a trichogram can be performed to evaluate the tips of the hair shafts; if these are broken, the alopecia is likely self-inflicted. Skin cytology, skin scrapings, direct examination of the hair, Wood’s lamp examination and fungal cultures should be performed to rule in/out the possible differential diagnosis. 

Eosinophilic granuloma complex

This consists of eosinophilic plaques or granulomas and/or indolent ulcers. Indolent ulcers appear as a unilateral or bilateral erosive to ulcerated lesions of the upper lip (Figure 3). The well-circumscribed ulcers with raised borders are rarely painful or pruritic and do not cause major discomfort to the cat. The differential diagnoses are neoplastic diseases (such as squamous cell carcinoma) and infectious ulcers. Diagnosis is confirmed by biopsy, with prior antimicrobial treatment recommended if cytology is indicative of infection. Eosinophilic plaques are raised, erythematous, exudative and severely pruritic lesions that occur typically on the ventral abdomen or medial and caudal aspect of the thighs, and less frequently on the face and neck. Eosinophilic granulomas are non-pruritic, raised, firm, yellowish, linear to nodular lesions that occur most commonly on the caudal thighs (linear), oral cavity, interdigital spaces and chin (nodular). Differential diagnoses of both eosinophilic plaques and granulomas include neoplastic, bacterial and fungal etiologies.

Diagnostic tests include skin cytology and biopsy, and once the diagnosis has been confirmed, the underlying cause needs to be identified and treated. If infectious and neoplastic causes have been ruled out, an allergic etiology is more likely.

Head and neck pruritus

Head and neck pruritus in the cat is often associated with significant self-trauma, alopecia, erosions, crusts and ulceration (Figure 4). Differential diagnoses include allergies, as well as ectoparasites and infectious (bacterial, fungal, viral) dermatoses. Often the eroded or ulcerated lesions are secondarily infected with bacteria or yeast organisms, which need to be identified by cytology and treated appropriately. An elimination diet trial, ectoparasite treatment trial and flea control are important parts of the work-up. If no improvement is seen, biopsy and PCR testing for viral diseases (e.g., herpesvirus) may be considered. 

Flea allergy and differentials

Since flea allergy dermatitis is the most common type of allergic dermatitis in the cat, if pruritus is present, this is the first condition I like to rule out. Pruritus is variable, but it can be severe, resulting in severe excoriations and secondary pyoderma. There are a variety of flea products now on the market, and some of these which contain isoxazolines are not only effective for flea infestations, but other ectoparasites as well, including otodectes, notoedres, demodex and cheyletiella mites. These are generally spot-on preparations, but an oral medication containing lotilaner is also available. It is worth noting that the US FDA has released a fact sheet for pet owners and veterinarians about isoxazolines and their potential adverse events, which states “isoxazoline products have been associated with neurologic adverse reactions, including muscle tremors, ataxia, and seizures in some dogs and cats”. When performing a treatment trial for parasitic skin diseases, ideally all animals in the household should be treated simultaneously. Environmental flea control can be recommended if considered necessary (e.g., multiple pet households or densely populated pet areas); insect growth regulators such as methoprene or pyriproxifen can be safe and effective options for environmental control. 

Although D. gatoi is not a common diagnosis, it is also important to be considered as a differential, and lime sulfur dips performed for at least six weeks can be effective if the mite is identified. Recently, treatment with a commercial spot-on preparation containing 10% imidacloprid/1% moxidectin at the manufacturer-recommended dose per body weight applied once a week (off label) has been reported to be effective 1, with resolution of the clinical signs after eight weeks of treatment. In this report, two additional treatments were recommended after resolution of the clinical signs. Fluralaner has also recently been reported as effective for the treatment of D. gatoi in two affected cats, with the animals receiving the oral chews available for dogs at a dose of 26-34 mg/kg 2. However, fluralaner is now available as a topical solution approved for use in cats in many countries.

If the pruritus is severe, a short course of oral glucocorticoids can be used to break the itch-scratch cycle. Prednisolone/prednisone is a good initial choice; I usually start with approximately 1 mg/kg every 24 hours for 3 to 5 days, then every 48 hours for 3 to 5 days, and then discontinue it. 

I usually schedule a recheck appointment for four weeks; at that point, cats with flea allergy will be significantly improved.

Further diagnostics 

Skin cytology to evaluate for the presence of secondary infections is also indicated at the initial evaluation. The findings will also help in the diagnosis of pemphigus foliaceus (PF) (Figure 5), as the presence of significant number of acantholytic keratinocytes will raise suspicion of the condition; ruling out infectious causes, along with histopathology findings, will help confirm a diagnosis of PF. Dermatophytosis can also present as miliary dermatitis, and its diagnosis is based on Wood’s lamp examination, direct examination of the hair, and fungal culture. Importantly, since dermatophytosis can clinically mimic so many other skin diseases, it should be considered and ruled out in all cats presenting with dermatologic disease.

Dermatitis due to adverse food reactions is also a very important differential diagnosis for a cat presenting with any of the above-mentioned cutaneous reaction patterns. Currently, the most accurate way to diagnose or rule out an adverse food reaction, including food allergies, is performing a food elimination trial. Such a trial is very simple in concept, but usually difficult to implement, especially for cat owners. Food options include limited ingredient diets (commercial or homemade) and hydrolyzed protein diets. Note, however, that most hydrolyzed diets currently available have proteins of molecular weight between 6-12 kD, except for one commercial diet, which is ≤ 1 kD*. I personally prefer a limited ingredient diet (chosen based on previous dietary history) or Ultamino, but eventually the cat will determine “the ideal diet” based on what they decide to eat. The selected food should be fed exclusively for a minimum of 8 weeks; a recent evidence-based analysis concluded that for diagnosing adverse food reactions in more than 90% of dogs and cats, elimination diet trials should last for at least this period 3. At the end of 8 weeks, if the clinical signs have improved, the cat should be “challenged” with the original diet (for up to 2 weeks) and observed for recurrence or worsening of the clinical signs. If the clinical signs recur, and then resolve with the re-introduction of the diet used during the trial, this then confirms a diagnosis of adverse food reaction. Dedicated pet owners may choose to perform a “sequential challenge” to identify the offending protein, whereby one new protein is added to the diet every two weeks. Once the offending protein is identified, it must be avoided in the future. If using a home-cooked diet, seek advice from a veterinary nutritionist for long-term use to assure that the diet is balanced.

* Ultamino/Anallergenic (Royal Canin) 

If none of these diagnostic tests/trials has led to a definitive diagnosis, then hypersensitivity to environmental allergens is the more likely diagnosis. At this point, the client has the choice of either pursuing symptomatic therapy, and/or allergen-specific immunotherapy (ASIT).

Therapy for FASS

Allergen-specific immunotherapy

To formulate ASIT, the offending allergens need to be identified, and allergy testing is recommended (via skin and/or serum allergy testing) if the clients choose to manage their cats with this option. Approximately 60-75% of patients have a good to excellent response to ASIT, but it may take up to a year before a clinical response is seen, and adjunctive symptomatic therapy is often needed during the first 6-12 months of treatment. Once ASIT successfully controls the clinical signs, other therapies can be tapered and often discontinued. Premature treatment discontinuation is a relatively common cause of treatment failure, and in our practice a year’s supply of ASIT is dispensed, making early discontinuation less likely. 

Whilst ASIT is a relatively safe and well-tolerated treatment for cats diagnosed with FASS, client education and routine follow ups are essential for treatment success; allergy companies are a good resource for client education brochures and technical assistance. The clinic’s veterinary technicians can also provide excellent support to clients during their pet’s treatment. Referral to a veterinary dermatologist for testing and ASIT implementation is always a good option. 

Symptomatic therapy

Most commonly used symptomatic therapies include fatty acids, antihistamines, glucocorticoids, and cyclosporine. Fatty acid supplementation and antihistamines have a success rate of approximately 25%, although given together they have a synergistic effect which may increase the success rate. Chlorpheniramine (2-4 mg PO per cat q12h), hydroxyzine (10 mg PO per cat q12h); clemastine (0.68 mg PO per cat q12h) are the antihistamines I use more commonly. Amitriptyline is a tricyclic antidepressant, with antihistaminic, anti-inflammatory and sedative actions, which can be given orally or intradermally; the latter may be beneficial for cat/pet owners who have difficulty medicating their cats. I start amitriptyline at 10 mg per cat q24h. Although not common, adverse effects to antihistamines in cats include sedation, hypersalivation, urinary retention, anorexia, vomiting/nausea and dysrhythmias, so it is important to evaluate for any pre-existing problem that may increase the risk of developing these side effects and monitor during treatment. Pre-treatment bloodwork and urinalysis and monitoring every 6 months is recommended. 

Glucocorticoids are used frequently in various formulations, and glucocorticoid-induced adverse effects are less common in cats than in dogs, although marked and unique problems may occur. Several studies have documented cardiovascular risks associated with glucocorticoid use in cats; for example, an association between long-acting depot corticosteroids (e.g., methylprednisolone acetate) and the development of congestive heart failure in cats without pre-existing cardiac disease has been seen 4. Diabetes is also a relatively common side effect; in one study, up to 75% of cats showed hyperglycemia after a single 5 mg/kg subcutaneous injection of methylprednisolone acetate 5. Diabetes may be transient or permanent after discontinuation of therapy. 

Prednisolone or methylprednisolone can be started at 0.5-1 mg/kg PO q24h for 5-7 days, then on alternate days at the lower effective dose. If the cat cannot be well-controlled with ≤ 0.5 mg/kg q48h or less, alternative therapies may need to be evaluated. If prednisolone is not effective, triamcinolone or dexamethasone can be tried. Triamcinolone can be started at 0.2 mg/kg PO q24 for 5-7 days, then tapered to lowest effective dose, ideally ≤ 0.08 mg/kg q48-72h. Dexamethasone is started at 0.25-1 mg per cat PO q24h for 5-7 days, then tapered to lowest effective dose, ideally ≤ 0.125 mg q48-72h. Complete blood count (CBC), chemistry profile and urinalysis are recommended to be performed at baseline and every 6-12 months in cats receiving maintenance glucocorticoid dosing.

For long-term control of pruritus in a cat with FASS, I prefer cyclosporine (CsA); studies have shown it to be an effective and safe treatment option 6, and I usually start at 5-7 mg/kg every 24h; a recent study suggested 7 mg/kg as the optimal dose 7. Initial improvement can be seen by the second week of treatment, but it may take 4-6 weeks for a full response. Treatment is usually well-tolerated; vomiting and/or diarrhea may occur, but in most cases signs resolve without discontinuation of treatment. Although a rare complication, fatal toxoplasmosis has been reported 8. It is recommended to exclude seronegative outdoor cats from treatment; cats seropositive to Toxoplasma seem to be protected from acute fatal disease. The decision to treat seropositive cats should consider possible relapses, and potential complications need to be discussed with the client. The same survey tests (at the same interval) recommended for cats on glucocorticoids are also recommended for those receiving maintenance CsA therapy.

Other treatment options

Oclacitinib, a Janus kinase inhibitor, has been used off-label for the treatment of FASS. Pharmacokinetic studies showed that this drug is absorbed and eliminated faster in cats than in dogs 9, therefore a shorter dosing interval and higher dose may be needed in cats. A safety study performed in healthy cats given 1 or 2 mg/kg q12h for 28 days reported vomiting and soft stools in the cats given 2 mg/kg 10. In a methylprednisolone-controlled study, oclacitinib given at 0.7-1.2 mg/kg q12h was as effective as methylprednisolone controlling the clinical signs of FASS 11. No long-term safety studies have been performed in cats receiving oclacitinib, so this and its off-label use should be discussed with clients before initiating treatment. Reported side effects include anemia, vomiting, and an increase in ALT, creatinine, BUN, and soft stools in Giardia-positive individuals 9. There is one report of acute fatal toxoplasmosis in a cat receiving oclacitinib 12. 

Maropitant is a neurokinin-1 receptor antagonist (NK-1 R), which inhibits the action of substance P. Substance P activates receptors in mast cells and sensory neurons, causing itch. Maropitant has been used orally at 2.2 mg/kg q24h for the control of FASS in an open study 13, with owners reporting good to excellent response in 83.3% of the cases after a 4-week course. Oral maropitant citrate is not labeled for use in cats in the United States, and no long-term safety studies have been performed in cats receiving this drug, so again this and its off-label use should be discussed with clients before initiating treatment. A recent clinical trial indicated that transdermal application of maropitant in cats experiencing vomiting may be a good and effective alternative; however, further studies are needed to determine dosing and pharmacokinetics 14. 

Cannabinoids are biologically active substances similar to the primary psychoactive compound found in Cannabis sativa. They can be plant-derived, synthetic, or endogenous (endocannabinoids). Endocannabinoids are naturally produced by the body and include arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and N-palmitoylethanolamide (PEA). Endocannabinoids bind to cannabinoid (CB)1 and 2 receptors. The activation of CB2 receptors on mast cells decreases the release of inflammatory cytokines such as IL-2, and upregulates IL-10, an anti-inflammatory cytokine. Cannabinoid receptors can also be found in skin sensory nerve fibers, and activation of these receptors may reduce the sensation of pruritus. A recent study showed increased expression of CB1 and CB2 in cats with allergies when compared to healthy cats, suggesting that the use of cannabinoid receptor agonists like PEA may be useful in the treatment of FASS 15. Some countries now have a licensed cannabinoid available; for example, one product now marketed in the USA is a powdered, flavorless and odorless supplement, containing 60 mg of PEA per 2 mL scoop; the recommended dose is one scoop/day in cats up to 4 kg (9 lb.) and 1½ scoops/day in cats weighting more than 4 kg. This product can be sprinkled on food and is well-tolerated with minimal side effects.

Gabapentin is a neuroactive agent used to treat neuropathic pain. Chronic pruritus causes neuronal sensitization, with hypersensitivity of sensory neurons to itch stimuli. Gabapentinoids such as gabapentin and pregabalin have been used for neuropathic forms of chronic pruritus in people with good response. Gabapentin has been used in cats for treatment of feline hyperesthesia syndrome, either as sole therapy or in combination with other anti-pruritic therapy 16. I start this treatment at 10 mg/kg PO every 12 hours, often in combination with PEA, or as a glucocorticoid-sparing treatment. Reported side effects, although uncommon, include sedation, ataxia, weakness and muscle tremors. 

Conclusion

Since feline dermatological conditions tend to present with a relatively few classic patterns, the differential diagnosis can be problematic. A rigorous systematic approach, coupled with a few simple diagnostic tests, can often identify the more common causes. Treatment options are varied and will depend ultimately on the etiology, but good flea control and a sensible anti-pruritic regime can often help cats with a skin allergy to enjoy a good quality of life. 

Further reading

• Kirk’s Current Veterinary Therapy XV, 1^st ed. Bonagura J, Twedt DC (eds). Oxford, Elsevier Saunders 2014.
• Feline Dermatology: cats are not small dogs. Today’s Veterinary Practice. November/December 2013.
• 2023 AAHA Management of Allergic Skin Diseases in Dogs and Cats Guidelines. J. Am. Anim. Hosp. Assoc. 2023;59(6):255-284.
• Mueller RS, Nuttal T, Prost C, et al. Treatment of the feline atopic syndrome – a systematic review. Vet. Dermatol. 2021;32:43-e8.