CLINICO-THERAPEUTIC AND ULTRASTRUCTURAL STUDIES ON CANINE ATOPIC DERMATITIS WITH SPECIAL REFERENCE TO FILAGGRIN GENE POLYMORPHISM
Loading...
Date
2022-11-10
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
COLLEGE OF VETERINARY AND ANIMAL SCIENCES MANNUTHY, THRISSUR, KERALA VETERINARY AND ANIMAL SCIENCES UNIVERSITY
Abstract
In the present study conducted on canine atopic dermatitis, among the total 2032 dermatological cases in dogs presented to the clinics from different parts of Kerala, 245 cases were diagnosed as various allergies over a period of three years. Out of these, 63 cases were recorded as canine atopic dermatitis based on Favrot’s criteria with the exclusion of other differentials. All the 63 cases diagnosed as CAD were utilized for epidemiological as well as clinical lesion distribution pattern studies using CADESI-04 scoring system. A total of hundred animals, 50 each of atopic and healthy controls were subjected to polymorphism studies. Sixteen atopic animals, which satisfied atleast six out of eight Favrot’s criteria with alesional pruritus at onset and pruritus score above two with clinical lesional scores above 20 were selected for detailed study to reduce variations due to extent and severity of clinical signs. In the present study, occurrence rate of allergic dermatitis recorded was 13 per cent, atopic dermatitis being second to flea allergy dermatitis. Male dogs below 3 years of age were found more affected with CAD. Distribution of lesion follows a pattern in atopic dermatitis with both paws and flexural areas were affected followed by axillae and ear pinnae, which can be better utilized for diagnostic purpose.
Haemato-biochemical studies of atopic dogs revealed hypoalbuminaemia with reduced AG ratio, anaemia with leukocytosis, neutrophilia and eosinophilia. Absolute eosinophil count with positive correlation with neutrophil to lymphocyte ratio (NLR) in atopic dogs was of diagnostic significance. Serum Ig E and IL-31 were found significantly elevated in atopic dogs. The IL-31which was correlated significantly with clinical scores, indicated the role of IL-31 as key cytokine in atopic dermatitis. Invitro serum allergen testing revealed allergens such as grass mix, weeds, pollen grains of mulberry and acacia tree, house dust, house dust mites and storage mites sensitive to dogs in the region studied. Histopathological examination of atopic skin was characterized by diffuse epidermal hyperplasia with acanthosis, spongiosis and prominent rete ridges, as well as orthokeratotic hyperkeratosis as major findings. Immunohistochemical staining of filaggrin protein in lesional and non lesional skin of atopic animals exhibited faint granular staining, where as normal skin of healthy animals exhibited intense discrete staining in the stratum granulosum. Transmission electron microscopic studies revealed varying changes in the epidermis, dermis and subepidermal areas. The corneal area, epidermal cells belonging to stratum basale, stratum spinosum, stratum granulosum and stratum lucidum could be seen with retrograde changes of varying intensity. Further non keratinocyte cells that inhabit the epidermis such as melanocytes, Langerhan cells also showed changes. Dermal components were seen loosely textured and contained collagen fibrils, fibroblasts, macrophages and blood vessels. Polymorphism studies revealed 12 SNPs in the amplified fragment of exon 3 FLG, out of which 11 were novel. Genotype
frequencies revealed that one novel SNP (Exon 3: c.2584G>T) and other reported SNP (c.2337T>G) were associated with CAD. The novel variation was found to have deleterious effects on protein function as analysed by five bioinformatics tools in combination and, it was also identified as a disease causing one, which affects protein stability and function.
The treatment response was evaluated by the periodic reduction in clinical lesional score, heamato-biochemical, serum Ig E and IL-31 values. Cyclosporine @ 5mg/kg body weight was an effective and well tolerated drug for treating atopic dermatitis in dogs, with considerable improvement noticed in pruritus and skin lesions during the first month of treatment followed by tapering the dose by reducing the frequency of administration to every other day. Regular bathing with a nonirritant shampoo helped in reducing the pruritus and this might be due to the restoration of skin barrier function by its moisturizing and cleansing action. Omega-3
fatty acids could lower Ig E production in allergic individuals and could lower the overall drug requirement.
Based on the above studies, it was concluded that follow-up evaluation of these parameters could be a relevant approach to find out the therapeutic
effectiveness. A therapeutic plan should consist of both calcineurin inhibitors like cyclosporine and clinically supportive treatments with moisturising shampoos and essential fatty acids to improve epidermal barrier function in atopic skin. Further studies are warranted to uncover new therapeutic targets like filaggrin monomers or drug candidates that upregulate FLG in skin, which can provide more treatment options rather than the current symptomatic therapy, in the increasing eve of atopic dermatitis in dogs