The expert summary: characterisation of the serum cytokine profile in feline atopic skin syndrome
C.Vargo, R. Gogal, J. Barber, M. Austel and F. Banovic
Veterinary Dermatology 2021;32(5):485-e133. https://doi.org/10.1111/vde.12994
Summary by: Dr Sébastien Viaud, DVM, Dip ECVD, Specialist in Veterinary Dermatology, Clinique Aquivet, Eysines
Introduction:
Feline atopic skin syndrome (FASS) is a common inflammatory and pruritic dermatosis of the cat, including the classic lesion patterns of feline extensive alopecia, cervicofacial pruritus, feline eosinophilic granuloma lesions and miliary dermatitis. Contrary to the results of work carried out in humans and dogs, little data is available to date on the various cytokines involved in FASS, yet it is essential to determine the immunological pathways of this syndrome to understand its pathophysiology and develop appropriate treatments.
Aims of the study :
Evaluate the differences in cytokine profiles between cats with FASS and healthy cats.
Correlate the various serum markers identified, according to the severity of FASS, using a clinical scoring system.
Materials and methods :
Thirteen cats with FASS and 12 healthy controls
Exclusion of any type of allergy (DAPP, food allergy) other than FASS, any infectious complication and any potential parasitic dermatosis.
Measurements of lesion scores (SCORFAD = SCORing Feline Allergic Dermatitis) and pruritus (visual analogue scale with a minimum of 4/10 required) for cats with FASS
Measurement of 19 markers (cytokines, chemokines and growth factors) using cat-specific multiplex tests (FCYTMAG-20K-PMX Feline Cytokine/Chemokine Magnetic Bead Panel Premixed 19-Plex, EMD) in healthy cats versus cats with FASS.
Results :
Patients with HTF showed:
- a significant increase in serum concentrations of gamma interferon (IFN-?) and various interleukins (IL-2, IL-13 and IL-18)
- a significant increase in serum cytokine/chemokine concentrations involved in inflammation and chemotaxis (IL-8, CCL5, CCL2 and CXCL12)
- an increase in growth factors: SCF (stem cell factor) and Flt3L (Fms-related tyrosine kinase 3 ligand, responsible for regulating the development and activation of dendritic cells)
- a significant positive correlation between SCORFAD and serum Flt3L levels (which could make it an interesting diagnostic and/or therapeutic follow-up marker).
These results show similarities between cats with FASS and atopic humans and dogs:
- a mixed Th1/Th2 inflammatory serological profile
- high serum levels of certain key cytokines, notably IL-13. This Th-2 cytokine, which has been shown to be involved in the pathophysiology of atopic dermatitis in humans, has a pruritogenic action and acts in a deleterious way on the epidermal barrier and on the production of antimicrobial peptides.
Finally, this study seems to suggest that an inflammation localised to the skin can spread to the bloodstream and have systemic repercussions.
Limitations:
- a relatively small number of people, even though the results show homogeneous and comparable trends
- a limited number of markers measured compared with comparable studies in humans
- markers measured in serum and not in the skin, making it impossible to determine whether the markers measured are directly involved in HTF mechanisms in the skin
Conclusion:
This study suggests, contrary to previous studies in allergic cats, that there is indeed a change in the cytokine profile in cats with FASS and that this inflammatory profile is comparable to that found in atopic humans and dogs.
Although from the point of view of lesions, their diversity and distribution, the term "feline atopic dermatitis" remains debatable and debated, given the marked differences with its human or canine equivalents, does the information provided by this study constitute the beginnings of evidence for the existence of "feline atopic dermatitis", at least from a pathophysiological point of view?Future studies should increase the cohorts of cats studied, increase the number of markers studied and extend the study of these same markers and their variations to the skin (and in particular to injured areas) in order to answer this question.
Literature review: can we talk about atopy in cats?
In dogs, atopic dermatitis is clearly defined as a disease associated with IgE antibodies most often directed against environmental allergens (Halliwell R., 2006). In cats, members of the ICADA (International Committee on Allergic Diseases of Animals) have recently published a number of articles updating and proposing a new nomenclature.
Allergic diseases in cats
There are several clinical forms (Santoro et al., 2021):
A skin disease with four different patterns. Miliary dermatitis is characterised by papules, generally surrounded by crusts, of varying extent. Self-induced alopecia is characterised by voluntary hair removal. Cervico-facial pruritus is intense in these areas, leading to significant secondary lesions. Finally, the complex of eosinophilic granulomas is itself subdivided into three syndromes: the indolent ulcer with labial involvement, the granuloma formed by linear nodules of variable location evolving towards erosion or ulceration and frequently associated with oral lesions, and finally a plaque-like form, generally very pruritic and usually located ventrally and on the inner surface of the thighs.
A respiratory disease, feline asthma, characterised by acute signs (dyspnoea, open-mouthed breathing, tachypnoea and hyperpnoea, pallor, even cyanosis in the most severe cases) or chronic signs (frequent dyspnoea, wheezing, chronic cough, intolerance to exercise).
Digestive disease, with vomiting, diarrhoea, weight loss and dysorexia. These signs may be associated with one or other of the previous two conditions, and in particular with urticaria, non-itchy nodules and pododermatitis.
Mechanisms in cats: similarities and differences
The mechanisms of canine atopic dermatitis (Chaudhary et al., 2019) are not superimposable in cats. A study of 22 allergic cats and 21 controls indicates that expression of cutaneous or serum interleukin (IL)-31 is not significantly increased. However, a unit of its receptor, OSMR-β (Oncostatin M Receptor) was expressed (Older et al, 2021). The same publication indicates that serum IL-31 is not significantly increased in asthmatics. According to Vargo et al (2021), IL-2, IL-13 and IL-18 are increased. In dogs, IL-4, IL-5, IL-10, IL-13 and IL-31 are increased (Nuttall et al. 2019).
The involvement of IgE is not systematic, although it is often implicated in allergic diseases (Halliwell et al., A and B).
A new terminology for cat allergy?
Recently, Halliwell et al (2021) proposed a new nomenclature for feline diseases associated with environmental allergens:
Feline Atopic Syndrome (FAS) describes all allergic diseases of the skin, gastrointestinal and respiratory tracts,
Feline Atopic Skin Syndrome (FASS), which is specific to the skin.
The existence of feline allergic diseases is no longer in doubt. Although the debate is not over - but will it ever be? -some dermatology specialists believe that there are enough similarities between human or canine diseases and cat ailments to consider using the term atopic in this species, even if the use of "atopic dermatitis" remains in question for others.
References:
Chaudhary SK, Singh SK, Kumari P, Kanwal S, Soman SP, Choudhury S, Garg SK. Alterations in circulating concentrations of IL-17, IL-31 and total IgE in dogs with atopic dermatitis. Vet Dermatol. 2019 Oct;30(5):383-e114. https://pubmed.ncbi.nlm.nih.gov/31218782/
Halliwell R. Revised nomenclature for veterinary allergy. Vet Immunol Immunopathol . 2006 Dec 15;114(3 4):207 8. https://pubmed.ncbi.nlm.nih.gov/17005257/
Halliwell R, Pucheu-Haston CM, Olivry T, Prost C, Jackson H, Banovic F, Nuttall T, Santoro D, Bizikova P, Mueller RS. Feline allergic diseases: introduction and proposed nomenclature. Vet Dermatol. 2021 Feb;32(1):8-e2. https://pubmed.ncbi.nlm.nih.gov/33470016/
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Nuttall TJ, Marsella R, Rosenbaum MR, Gonzales AJ, Fadok VA. Update on pathogenesis, diagnosis, and treatment of atopic dermatitis in dogs. J Am Vet Med Assoc. 2019 Jun 1;254(11):1291-1300. https://pubmed.ncbi.nlm.nih.gov/31067173/
Older CE, Diesel AB, Heseltine JC, Friedeck A, Hedke C, Pardike S, Breitreiter K, Rossi MA, Messamore J, Bammert G, Gonzales AJ, Rodrigues Hoffmann A. Cytokine expression in feline allergic dermatitis and feline asthma. Vet Dermatol. 2021 Dec;32(6):613-e163. https://pubmed.ncbi.nlm.nih.gov/34519120/
Santoro D, Pucheu-Haston CM, Prost C, Mueller RS, Jackson H. Clinical signs and diagnosis of feline atopic syndrome: detailed guidelines for a correct diagnosis. Vet Dermatol. 2021 Feb;32(1):26-e6. https://pubmed.ncbi.nlm.nih.gov/33470017/
Vargo C, Gogal R, Barber J, Austel M, Banovic F. Characterisation of the serum cytokine profile in feline atopic skin syndrome. Vet Dermatol. 2021 Oct;32(5):485-e133. https://pubmed.ncbi.nlm.nih.gov/34180094/