Major advances have been made in the investigation of skin barrier dysfunction in canine AD, although many questions still remain. Skin barrier dysfunction and host-microbiome interactions are emerging as primary alterations in canine AD. Based on this review, it is clear that future studies focused on the development of drugs able to restore the skin barrier and increase the natural defences against pathogenic organisms are needed.

The development of AD in dogs is characterized by the development of a delicate balance between a variety of T-cell phenotypes and inflammatory mediators, including cytokines, chemokines and noncytokine factors.

This study demonstrated that epicutaneous application of HDM slurry to MAB dogs results in elevations of HDM-specific IgE, localized and generalized pruritic dermatitis resembling spontaneous canine AD, and histologic changes typical of IgE-driven inflammation. We feel that these results suggest that epicutaneous exposure to allergen may play an important role during both the sensitization and the perpetuation of AD, and provide support for the use of a canine model in the investigation of the pathogenesis of AD.

Background-Feline atopic syndrome (FAS) describes a spectrum of hypersensitivity disorders characterised by highly diverse clinical presentations including skin, gastrointestinal and respiratory systems. Among these disorders is feline atopic skin syndrome (FASS), in which hypersensitivity is typically associated with environmental allergens, although food allergy may coexist. Involvement of other organ systems (e.g. asthma) also may occur. Because of its highly heterogeneous clinical presentation, diagnosis of FASS can be challenging. Objectives-A subgroup of the International Committee on Allergic Diseases of Animals was tasked to summarise the most current information on the clinical presentations of FASS and to develop diagnostic guidelines. Methods and materials-Online citation databases and abstracts from international meetings were searched for publications related to feline allergic conditions. These were combined with expert opinion where necessary. Results-A total of 107 publications relevant to this review were identified. Compilation of these data enabled development of a detailed description of the clinical features of FASS and development of guidelines focusing on systematic elimination of other skin conditions with similar clinical characteristics. As allergen tests are frequently used by dermatologists to support a clinical diagnosis of FASS, a brief review of these methodologies was also performed. Conclusions and clinical importance-In a similar way to atopic dermatitis in dogs, FASS is a clinical diagnosis based on the 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 food allergy is mandatory before reaching a diagnosis of FASS.

SummaryImmunoglobulin E (IgE)-mediated late-phase reactions can be induced in atopic humans by intradermal injection of relevant allergens or anti-IgE antibodies. The histology of these reactions resembles that of naturally occurring atopic dermatitis. Strikingly similar responses can be induced in dogs, suggesting that a canine model could prove valuable for preclinical investigation of drugs targeting late-phase reactions. This study was designed to characterize the cellular, cytokine and chemokine responses after intradermal anti-IgE injection in untreated and prednisolone-treated dogs. Normal beagles were untreated or treated with prednisolone before intradermal injection of polyclonal rabbit anti-canine IgE or normal rabbit IgG. Biopsies were taken before injection and 6, 24 and 48 hr after injection. Samples were evaluated by histological and immunohistochemical staining, as well as by real-time quantitative polymerase chain reaction analysis. Dermal eosinophil and neutrophil numbers increased dramatically within 6 hr after injection of rabbit anti-canine IgE, and remained moderately elevated at 48 hr. The numbers of CD1c + and CD3 + mononuclear cells were also increased at 6 hr. The real-time quantitative polymerase chain reaction demonstrated marked increases in mRNA expression for interleukin-13 (IL-13), CCL2, CCL5 and CCL17. Levels of mRNA for IL-2, IL-4, IL-6 and IFN-c did not change within the limits of detection. Prednisolone administration suppressed the influx of neutrophils, eosinophils, CD1c + and CD3 + cells, as well as expression of IL-13, CCL2, CCL5 and CCL17. These data document the cytokine and chemokine responses to anti-IgE injection in canine skin, and they demonstrate the ability of the model to characterize the anti-inflammatory effects of a known therapeutic agent.

Considerable work has been done in recent years to provide a better definition of the clinical appearance and histopathology of canine AD. New sets of diagnostic criteria have been developed, and additional breed-associated differences in phenotypes have been demonstrated.

It is becoming clear that canine AD is genotypically complex and influenced by a variety of environmental factors. Well-designed studies with sufficient statistical power will be critical to identify the complex genetic and environmental factors involved in disease development and progression. Recognition of such factors may help to identify new targets for therapy and enable better disease prevention and management.

Laminin-332 (laminin-5) is a basement membrane heterotrimeric protein composed of alpha-3, beta-3 and gamma-2 laminin chains. Laminin-332 polypeptides are targeted by auto-antibodies in human patients with mucous membrane (cicatricial) pemphigoid or, more rarely, subepidermal vesicular diseases that resemble epidermolysis bullosa acquisita (EBA) or bullous pemphigoid (BP). The objectives of this report were to characterize the clinical, histopathological and immunological characteristics of nine dogs with auto-antibodies targeting laminin-332. Immunological investigations consisted of direct immunofluorescence (IF), indirect IF with intact and salt-split canine gingival, and salt-split normal or laminin-332-deficient human skin, immunoblotting with purified human laminin-332 and immunoblotting with recombinant NC1 domain of human collagen VII. All dogs exhibited varying degrees of skin blistering and ulceration associated with microscopic subepidermal vesiculation with or without inflammatory cells. Indirect IF established that circulating IgG auto-antibodies bound the dermal side of salt-split canine lip and human skin. In five dogs, IgG variably recognized the basement membrane of laminin-332-deficient human skin (three dogs negative, two dogs positive). In all nine dogs, IgG auto-antibodies detected purified human laminin-332 by immunoblotting. In two dogs, additional targeting of collagen VII-NC1 was present. These observations establish laminin-332 as a novel basement membrane antigen in dogs with autoimmune blistering diseases with variable clinical phenotypes. The names 'acquired junctional epidermolysis bullosa', 'anti-laminin-332 mucous membrane pemphigoid (MMP)' and 'mixed auto-immune subepidermal blistering dermatosis' are proposed for dogs with clinical signs reminiscent of EBA, MMP or BP respectively.