The past year, 2021, has definitely been very dedicated to the cat and its allergic conditions.

Unlike for human and canine atopic dermatitis (CAD), a very low number of publications were published regarding the immunopathogenesis of feline allergic syndrome.

For that reason, it is always exciting when new investigations are developed and questions regarding the mysteries of the allergic disease in cats are answered.

Allergic dermatitis in cats is quite exceptional, not only in what concerns the clinical signs, but also with regards to its pathomechanisms.

Cats potentially lack immunoglobulin E (IgE) involvement, and differ in the immunological profile when compared to people and dogs¹.

In dogs and humans, interleukin-31 (IL-31), a pruritogenic cytokine, has drawn a lot of attention for its role in pruritus and atopic inflammation².

It was found that the serum IL-31 concentration in atopic dogs was increased compared to that in healthy dogs^3,4, and a specific IL-31 neutralising monoclonal antibody was found to reduce IL-31-induced pruritus in these animals⁵. In cats, questions exist if IL-31 would have a similar role in the development of pruritus and if, similarly to dogs, molecules for the blockade/inactivation of this cytokine would be as effective as it is in canine patients.

Several studies have been carried to investigate the role of IL-31 in allergic skin disease in cats.

In one study, recombinant feline IL-31 was injected in healthy cats, which resulted in the development of pruritus⁶.

One abstract also demonstrated higher circulating serum concentrations of IL-31 in cats with allergic dermatitis when compared to healthy controls⁷. Altogether, these studies suggest that targeting IL-31 could be a promising treatment option.

Last year, a group of investigators developed research to determine whether IL-31 would have a clear role in feline allergic dermatitis. They evaluated the concentrations of IL-31 in the skin and serum of cats affected by allergic dermatitis and asthma¹.

Other Th2 cytokines were also investigated. IL-31 was found in low quantities or even undetectable in most skin samples¹.

Although serum IL-31 was detected in a larger number of cats with allergic dermatitis than healthy cats, and concentrations appeared to be higher in cats with allergies, this difference was not statistically significant¹.

Cats affected by asthma also exhibited insignificantly higher concentrations of IL-31 in the serum¹. This study provides some evidence that the allergic condition in cats can be quite distinct from the disease in dogs¹. Although IL-31 appears to play quite a different role in allergy in cats, it does not rule out that targeting molecules within the IL-31 pathway may still be valuable¹. In fact, in the study presented by Fleck et al (2013), oclacitinib effectively treated IL-31-induced pruritus in cats⁶.

Immunotherapy

Atopic dermatitis (AD) is one of the most common canine skin diseases, affecting 3% to 15% of the population⁸.

To date, allergen-specific immunotherapy (ASIT) is the only treatment for atopic dermatitis in dogs that appears to have the potential to normalise the dysregulated immune response and thus slow the progression of the disease⁹.

It is, however, ineffective in some dogs and only partially effective in many cases¹⁰.

Commercial serum allergen-specific IgE tests are commonly used in veterinary medicine for the formulation of ASIT prescriptions for dogs with AD; however, it is not uncommon for these in vitro tests to deliver results inconsistent with a dog’s history of disease (for example, when dogs show strong positive reactions to seasonal allergens when they are not specially symptomatic in that time of year).

In people, IgE reactivity against highly antigenic, carbohydrate structures commonly found on plant and insect allergens was identified¹¹. These structures, known as cross-reactive carbohydrate determinants (CCD)¹², were considered a source of cross-reactivity in IgE serological tests, leading to false positive reactions for in vitro allergen tests and to the inclusion of irrelevant allergens in ASIT formulation¹¹.

In a study performed in atopic dogs, anti-CCD IgE was detected in 24% of the sera samples. These dogs had strong serological reactivity to grass pollens¹³.

In another study, results of an intradermal test (IDT) and a serum test for allergen-specific IgE, with and without blocking anti-CCD IgE, were compared to assess the agreement between the tests performed¹⁴.

In dogs with negative anti-CCD IgE samples, the agreement between the results of the serum test and the IDT was substantial, while dogs with positive anti-CCD IgE samples showed no agreement between serum and skin testing¹⁴.

Blocking anti-CCD IgE in those samples resulted in a fair agreement between the tests¹⁴. Also, anti-CCD IgE positive sera had multiple positive results for grass and weed allergens, and blocking decreased them markedly¹⁴. Overall, the results of these studies suggest blocking anti-CCD IgE before serological testing could improve the relevance and accuracy of allergen specific IgE tests.

Consequently, better-targeted immunotherapy formulations can be developed with a greater efficacy of ASIT in canine patients¹⁵.

Oclacitinib

Oclacitinib is a Janus-kinase inhibitor (JAKinib) approved for the treatment of canine pruritic and allergic skin diseases¹⁶.

JAKinibs have broad anti-inflammatory and immunosuppressive effects through alteration of lymphocyte and natural killer cell proliferation, differentiation, function and/or survival, and through inhibition of receptors responsible for signalling of multiple inflammatory mediators¹⁶.

In humans, JAKinibs are approved for the treatment of multiple immune mediated diseases such as rheumatoid arthritis and psoriasis¹⁷. In dogs, oclacitinib has also been used off-label to successfully treat several autoimmune and immune-mediated conditions.

In 2017, Aymeric and Bensignor presented a case of a five-year-old German shepherd cross-breed with refractory subepidermal blistering dermatosis¹⁸.

This dog had been treated with prednisolone at 1.2mg/kg twice daily; however, developed severe adverse effects and relapse, when the prednisolone dose was reduced.

A complete resolution of clinical signs was noted after one month of oclacitinib therapy at 0.5mg/kg twice a day and no relapse was observed after 12 months of treatment¹⁸.

Oclacitinib has also shown to be effective in the management of vasculopathic conditions, which are presumed to be of immune-mediated origin. Vercelli and Cornegliani first described the effectiveness of oclacitinib in idiopathic ear-tip vasculitis unresponsive to previous treatments¹⁹.

In 2018, Pulsoni et al described treatment success in two dogs with juvenile onset ischemic dermatopathy²⁰, and later Levy et al described four cases of juvenile-onset ischaemic dermatopathy that were treatment refractory, and rapidly and durably responded to oclacitinib administration²¹.

Recent reports published revealed the efficacy of oclacitinib also in hyperkeratotic erythema multiforme in two dogs and in a case of pemphigus foliaceus in cat^22,23.

Oclacitinib’s mechanism of action in these cases is unknown and only speculative; however, its effectiveness in the presented conditions makes this therapeutic option very promising when managing cutaneous immune-mediated conditions.