Feline atopic syndrome — An update

The International Committee on Allergic Diseases of Animals (ICADA) recently published 4 foundational review papers related to feline allergic disease (1–4). The committee performed a thorough literature review of available publications and prepared detailed guidelines on clinical signs, diagnosis, immunopathogenesis, and treatment of the newly coined Feline Atopic Syndrome (FAS).

By reviewing and summarizing all published work related to feline allergic disease, these papers provide a comprehensive overview of available scientific information for feline allergies (1–4). This work also identifies limitations in the available knowledge base, and therefore should guide future feline allergy specific research and knowledge, rather than relying on information extrapolated from allergies in dogs and humans. Following is a brief summary of the current ICADA guidelines, including proposed terminology. Interested readers are encouraged to retrieve and read the ICADA review papers (1–4).

Feline atopic syndrome (FAS)

This syndrome encompasses a variety of allergic diseases including the skin, gastrointestinal tract, and respiratory tract in cats. These disorders include allergic dermatitis, asthma/respiratory diseases, and gastrointestinal diseases that may be associated with a hypersensitivity to environmental allergens and foods, and which may coexist with flea allergy dermatitis.

Feline atopic skin syndrome (FASS)

Feline atopic skin syndrome is an inflammatory and pruritic skin syndrome of cats manifested by a spectrum of reaction patterns, that may be associated with IgE antibodies to environmental allergens. This syndrome is, therefore, the equivalent of what has previously been described as feline atopy or “nonflea nonfood-induced feline hypersensitivity dermatitis” (5).

Both flea allergy dermatitis and food allergy can present with clinical signs that overlap or are identical to FASS. Specifically excluded from the atopic designation are feline flea allergy dermatitis and mosquito-bite hypersensitivity. The spectrum of reaction patterns noted in FASS and its differential diagnoses are described later in this article. These reaction patterns are not considered specific for FASS. Irrespective of the primary disease, the reaction patterns may be exhibited either alone or in combination.

Food allergy (FA)

This etiological diagnosis refers to any clinical manifestations, including those of FASS, attributable to immunological reactivity to an ingested food item.

Flea allergy dermatitis (FAD)

One of the most important differentials for FASS is FAD. Clinical criteria have not yet been developed specifically for the diagnosis of FAD in cats, as signs of flea allergy in cats are usually not very distinctive, unlike that in dogs (2).

Note: FAD and FA in cats may manifest in any of the 4 major clinical reaction patterns, similar to FASS (5).

Feline asthma

Asthma is an eosinophilic inflammatory disease affecting the bronchioles and leading to spontaneous reversible bronchoconstriction and airway remodelling. It is manifested by acute respiratory distress or chronic coughing and expiratory wheezing and may be associated with IgE antibodies to inhaled allergens (2,3).

Diagnosis is based on history, clinical signs, thoracic imaging, bronchoalveolar lavage (BAL) sampling, and cytological examination (6,7). Cytological examination of the BAL is key for differential diagnosis from chronic bronchitis. Whereas neutrophils are markers of chronic non-allergic bronchial inflammation (feline chronic bronchitis), asthma is characterized by allergic eosinophilic inflammation. In clinically healthy cats, eosinophils comprise 6 to 7% (up to 18%) of the total BAL cell population. Consequently, bronchial eosinophilia is defined as the eosinophil count exceeding 17 to 20% (6,7).

Reaction patterns in feline allergic disease

The reaction patterns involved in FASS and its differentials, include miliary dermatitis (MD), self-inflicted alopecia/hypotrichosis (SIAH), head and neck pruritus (HNP), and eosinophilic granuloma complex (EGC) (2). Some of these reaction patterns appear to be unique for cats (2).

Miliary dermatitis (MD)

Miliary dermatitis presents as several small (typically ~1 to 2 mm) papulo-crusted dermatitis lesions, which may be present locally or be generalized. Pruritus is usually present. Patients with “non-pruritic” MD may appear clinically normal from a distance, with lesions becoming obvious only upon handling the cat and closely inspecting the skin.

Self-inflicted alopecia/hypotrichosis (SIAH)

The pruritic cat removes hairs either by repetitively licking, biting, or pulling its fur, occasionally accompanied by scratching. Swallowing of excessive hair and formation of hairballs is likely and may cause vomiting. Exuberant over-grooming may or may not be noted by the pet owner. Over-grooming usually indicates pruritus and should not be misinterpreted as a response to a stressful condition. Stress-related “psychogenic alopecia” is a differential diagnosis, but primary behavior-based over-grooming appears to be uncommon in cats. In a study of 21 cats referred for evaluation of psychogenic alopecia, a primary behavioral or psychogenic cause was demonstrated in only 2 cats (8). However, 16 of those cats were suffering from pruritic dermatitis alone, with the remaining 3 cats afflicted by pruritic disease with a superimposed behavioral component (8).

Head and neck pruritus (HNP)

Head and neck pruritus is characterized by pruritus of the face, head, and neck (Figure 1). Pruritus is often intense, resulting in varying degrees of excoriation, erosion, and ulceration. Head and neck pruritus can be particularly severe, requiring drug therapy and/or protective collars to minimize self-trauma. Blepharitis and/or corneal ulceration may occur.

Figure 1.

Feline atopic skin syndrome patient affected with head and neck pruritus, as well as facial miliary dermatitis lesions (photograph credit, Jangi Bajwa).

Eosinophilic granuloma complex (EGC)

This “complex” consists of a loosely grouped set of clinical syndromes, including:

1. Indolent ulcer (or “rodent ulcer”) — typically affects the upper lip, at or immediately adjacent to the muco-cutaneous junction, with lesions initially starting as focal ulceration on the lip margin, with progression to fibrosis and deformation. This syndrome is typically not pruritic unless complicated by bacterial infection.

2. Eosinophilic granuloma (or “linear granuloma”) — lesions can appear in various locations, typically on the rear legs as linear areas of dermal thickening on the caudal aspect of the thigh and may extend distally past the stifle fold onto the caudal crus (Figure 2). Erosion or ulceration is common. Proliferative oral lesions, especially on the tongue or hard palate, or as poorly defined chin swelling (“fat chin”) may be noted. Pruritus may be present.

3. Eosinophilic plaque — lesions may appear anywhere, most frequently on ventral abdomen and medial thighs. Lesions are characterized by circular, to oval, to serpiginous, raised, frequently eroded, or ulcerated areas. These lesions are often associated with intense pruritus, with self-inflicted damage resulting in a self-perpetuating, positive feedback of inflammation. These lesions are often complicated by secondary bacterial infections.

Figure 2.

Linear eosinophilic granuloma in a cat with suspected flea allergy dermatitis (photograph credit, Jangi Bajwa).

Feline atopic skin syndrome (FASS)

Similar to atopic dermatitis in dogs, FASS is a clinical diagnosis based on presence of compatible clinical signs and exclusion of other diseases with similar clinical features. Elimination or exclusion of fleas/flea allergy, other parasites, infections, and FA is mandatory before reaching a diagnosis of FASS (2).

In humans and dogs, atopic dermatitis is typically associated with a limited range and distribution of clinical signs. However, cutaneous lesions of FASS are far more variable in appearance and less predictable in distribution (2). Also, in contrast to humans and dogs, little is known regarding contributions of heritability to FASS. There is only some evidence for a heritable component to development of allergic dermatitis in cats from a few studies, including in the Abyssinian, Somali, Ocicat, Siamese, Persian, Maine coon, Devon rex, and Himalayan breeds (5,8–11).

A review of 10 manuscripts describing 263 cats diagnosed exclusively with FASS provided the following prevalence rates for the 4 allergic reaction patterns: 31.2% with MD; 60.1% with SIAH; 43.0% with HNP; and 25.9% with EGC (1 or more forms). Of the 263 FASS cats, 37.7% were reported as having at least 2 syndromes (2).

Of 230 cats affected by FASS, described in 7 manuscripts in which specifics regarding the presence of extra-cutaneous signs were provided, 8.3% (19 of 230) of the cats reportedly had some form of respiratory disease, including sneezing and asthma (2,5,9,12). Conjunctivitis was reported in 4.8% (11 of 230) of cats and gastrointestinal signs in 3.9% (9 of 230). Respiratory disease diagnosed as probable or definitive asthma was reported as accompanying 6 to 7% of 145 cats in 2 publications of cats diagnosed with FASS (5,9). There are additional reports describing co-existing allergic dermatitis with asthma, including evidence of improvements from intra-dermal allergy test (IDAT) based allergen specific immunotherapy (ASIT) (13). Efficacy of allergy test based ASIT for spontaneous feline asthma has been demonstrated and could be 1 of the treatments of choice for spontaneous feline asthma, so long as the causative allergens can be precisely identified by either IDAT or allergen-specific IgE serology (ASIS) (14,15). Allergy testing in cats can be pursued using IDAT and/or ASIS. As in dogs, IDAT is the “gold standard” in feline allergy medicine. Although IDAT gives immediate results and is biologically relevant, it lacks standardization (2). Furthermore, whereas ASIS is more widely available and more convenient, it only measures circulating allergen-specific IgE and does not take into account cutaneous histaminergic and non-histaminergic pathways and test reliability is variable (2).

The last of the ICADA review articles (4) includes the first systematic review of therapeutic interventions for FAS, including both FASS and feline asthma. Good evidence for efficacy of systemic glucocorticoids and cyclosporin, and limited evidence for efficacy of topical glucocorticoids, oclacitinib and ASIT, were noted for FASS. For feline asthma, there was good evidence for efficacy of oral and inhaled glucocorticoids, and limited evidence of moderate efficacy for ASIT. Evidence pointed to low-to-moderate efficacy for antihistamines, fatty acids, and palmitoyl ethanolamide for FASS. Furthermore, for feline asthma, there was low-to-moderate efficacy of mesenchymal stem cells, inhaled lidocaine and oclacitinib.

In summary, regarding feline allergic disease (1–4), some of the key conclusions include:

• feline diseases of presumed allergic etiology have some features comparable to those in human atopic diseases and canine atopic dermatitis;

• although strong evidence of a genetic basis is missing, that cats can suffer from the triad of allergic dermatitis, allergic enteritis and asthma, often in combination and with some evidence for involvement of IgE, provides justification for designating FAS and related conditions as likely atopic diseases;

• FAS is a complex syndrome, involving multiple organs including skin, gastrointestinal, and respiratory systems;

• contrary to dogs (in which the atopic disease manifests mainly with cutaneous signs), asthma may have an important role in FAS cats, often underestimated by dermatologists and general practitioners. This emphasizes the strong connection among cutaneous, gastrointestinal, and respiratory systems in allergic cats;

• inflammation noted in both FASS and feline asthma is accompanied by eosinophils and lymphocytes; these findings, together with cytokine expression, are suggestive in some cats of T-helper type 2 immune dysregulation;

• FA and FAD can both either mimic and/or contribute to FAS and FASS, and their potential role must be assessed before a diagnosis can be finalized and before deciding on a therapeutic approach;

• due to strong clinical similarities between cats with FA and cats with FASS, if perennial clinical signs are present, food allergy must be excluded via 1 or more strict food trial(s). Extra-cutaneous clinical signs can occur in both FASS- and FA-affected cats;

• good evidence is available for the efficacy of systemic glucocorticoids and cyclosporin in treatment of FASS. Good evidence for the efficacy of oral and inhaled glucocorticoids is also available for feline asthma; and

• limited evidence for the efficacy is available for other anecdotally effective treatments including allergen-specific immunotherapy and oclacitinib. For almost all therapeutic options (except for glucocorticoids and cyclosporin), more randomized controlled trials are needed.