Peter B. Hill

Survey of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice

A survey was made of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice in the UK. Out of 3707 small animal consultations in general practice that were observed and recorded, 795 (21·4 per cent) involved animals that had a dermatological problem. In dogs and exotic species, pruritus was the most common presenting sign, accounting for 30 to 40 per cent of the dermatological consultations. In cats, cutaneous swellings were the most common presentation (36 per cent). A diagnosis or recommendation for treatment was made on the basis of the presenting clinical signs and physical examination alone in 576 (72 per cent) of the cases, and various diagnostic tests were performed in the other cases. In dogs, parasitic infestations, bacterial infections and neoplasia accounted for the majority of the diagnoses. In cats, parasites and bacterial infections were the most common. In exotic species, parasites accounted for over 80 per cent of the dermatological diagnoses. In dogs, the most common final diagnoses were otitis, pyoderma, anal sac impaction, flea infestation and atopic dermatitis. In cats, abscesses, flea infestation, and otitis were the most common diagnoses. In exotic species, the most common diagnosis was an unspecified mite infestation. Systemic antibiotics were prescribed in 196 cases (25 per cent), systemic glucocorticoids were prescribed in 162 cases (20 per cent) and treatment with an ectoparasiticide was prescribed in 167 cases (21 per cent).

Expression of Th1, Th2 and immunosuppressive cytokine gene transcripts in canine atopic dermatitis

Background Atopic dermatitis is a common inflammatory skin disease of humans and dogs. Human atopic dermatitis is associated with Th2‐type responses, although Th1 cytokines can be identified in chronic lesions. In contrast, tolerance to environmental allergens in healthy individuals is mediated by regulatory T cells.

The ACVD task force on canine atopic dermatitis (IV): environmental allergens

Numerous environmental allergens have been incriminated in the pathogenesis of canine atopic dermatitis (AD). These include dust and storage mite antigens, house dust, pollens from grasses, trees and weeds, mould spores, epidermal antigens, insect antigens, and miscellaneous antigens such as kapok. In this paper, we review the literature concerning the allergens that have been reported to contribute to canine AD. We conclude that attempts to identify the relevant canine antigens in the past have been plagued by a lack of standardisation of extracts and techniques, and the presence of false-positive and -negative reactions in allergy tests. Until these problems are rectified, it is unlikely that we will be able to provide a list of major and minor antigens for dogs. Hence, we recommend that future studies should be aimed at determining the major patterns of reactivity and cross-reactivity to specific protein allergens within antigenic extracts using electrophoresis and immunoblotting techniques. Once this information becomes available, it may be possible to use a selection of genetically engineered, highly pure antigens for both diagnostic and therapeutic purposes in canine allergy investigations. The use of such antigens will allow standardisation of canine allergy testing and immunotherapy so that the reliability and efficacy of these procedures can be objectively assessed.

Concentrations of total serum IgE, IgA, and IgG in atopic and parasitized dogs.

Concentrations of total serum IgE, IgA, and IgG were measured in 36 atopic and 16 parasitized dogs, and compared them with 30 healthy control dogs. IgE was measured using enzyme-linked immunosorbent assay. IgA and IgG were measured using radial immunodiffusion assays. Mean total serum immunoglobulin (Ig) E concentrations in healthy, atopic and parasitized dogs were 7.1 units (U) ml-1, 5.8 U ml-1 and 14.3 U ml-1, respectively. Mean total serum IgA concentrations in the same groups were 103.3 mg dl-1, 63.2 mg dl-1 and 67.3 mg dl-1, respectively. Mean total serum IgG concentrations were 1066 mg dl-1, 1621 mg dl-1 and 1480 mg dl-1 in the three groups. There was no significant difference in IgE concentrations between these groups of dogs. IgA levels were significantly lower in atopic and parasitized dogs compared with healthy dogs (P < or = 0.05), whereas IgG levels were significantly higher in the atopic and parasitized dogs (P < or = 0.005). These results suggest that measurement of total serum IgE would be of no benefit in the preliminary clinical investigation of a suspected atopic dog. The lower IgA and higher IgG concentrations in both atopic and parasitized dogs suggest that similar regulatory mechanisms governing immunoglobulin synthesis occur in canine allergic and parasitic disease, promoting IgG synthesis but down-regulating IgA production.

T-helper 1, T-helper 2 and immunosuppressive cytokines in canine atopic dermatitis.

Atopic dermatitis is a common inflammatory skin disease of humans and dogs. Human atopic dermatitis is associated with T-helper (Th) 2 type responses, although Th1 cytokines are present in chronic lesions. This study used semi-quantitative reverse transcriptase polymerase chain reactions to determine the expression of gene transcripts for immunosuppressive cytokines (transforming growth factor beta [TGFbeta] and interleukin [IL]-10), Th2 type cytokines (IL-4 and IL-6) and Th1 type cytokines (interferon gamma [IFNgamma], tumour necrosis factor alpha [TNFalpha], IL-2 and IL-12) in lesional atopic, non-lesional atopic and healthy canine skin. Canine atopic dermatitis was associated with over-expression of IL-4 mRNA and reduced transcription of TGFbeta compared to healthy skin (ANOVA, p<0.05). Higher levels of IFNgamma, TNFalpha and IL-2 mRNA were seen in lesional compared to non-lesional and healthy skin (p<0.05). There were no significant differences in IL-10, IL-6 or IL-12 transcription. This is the first report to demonstrate that canine atopic dermatitis is associated with over-production of IL-4 and under expression of TGFbeta.

Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification.

BackgroundCanine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The variation in clinical presentations, due to genetic factors, extent of the lesions, stage of the disease, secondary infections, as well as resemblance to other non-atopic related skin diseases, can complicate a diagnosis of canine AD. A sub-group of the International Committee for Allergic Diseases in Animals (ICADA) was tasked with the development of a set of practical guidelines that can be used to assist practitioners and researchers in the diagnosis of canine AD. Online citation databases and abstracts from international meetings were searched for publications related to the topic, and combined with expert opinion where necessary. The final set of guidelines was approved by the entire ICADA committee.ResultsA total of 81 publications relevant for this review were identified. The guidelines generated focus on three aspects of the diagnostic approach:1.Ruling out of other skin conditions with clinical signs resembling, or overlapping with canine AD.2.Detailed interpretation of the historical and clinical features of patients affected by canine AD.3.Allergy testing by intradermal versus allergen-specific IgE serum testing.ConclusionsThe diagnosis of canine AD is based on meeting clinical criteria and ruling out other possible causes with similar clinical signs. Flea combing, skin scraping and cytology should be performed, where necessary, as part of a thorough work-up. Elimination diet trials are required for patients with perennial pruritus and/or concurrent gastrointestinal signs. Once a clinical diagnosis of canine AD is made, allergy testing can be performed to identify potential causative allergens for allergen-specific immunotherapy.

Validation of the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-4, a simplified severity scale for assessing skin lesions of atopic dermatitis in dogs

BACKGROUND Severity scales are used to grade skin lesions in clinical trials for treatment of dogs with atopic dermatitis (AD). At this time, only two scales have been validated, namely the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-3 and the Canine Atopic Dermatitis Lesion Index (CADLI). However, the high number of assessed sites makes the CADESI-3 impractical. HYPOTHESIS/OBJECTIVES The aim of this study was to develop and validate a fourth version of the CADESI that is simpler and quicker to administer. METHODS Body sites, lesions and severity grades were revised by members of the International Committee on Allergic Diseases of Animals (ICADA). The newly designed CADESI-4 was tested for its validity (i.e. content, construct and criterion), reliability (i.e. inter- and intra-observer reliability and internal consistency), responsiveness (i.e. sensitivity to change) and time to administer. Disease severity benchmarks were chosen using receiver operating characteristic methodology. RESULTS The CADESI-4 was simplified in comparison to its previous version to comprise 20 body sites typically affected in atopic dogs. Three lesions (erythema, lichenification and alopecia/excoriation) were scored from 0 to 3 at each site. The CADESI-4 had satisfactory validity, reliability and sensitivity to change. On average, the time to administer a CADESI-4 was one-third that of a CADESI-3. Proposed benchmarks for mild, moderate and severe AD skin lesions are 10, 35 and 60, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE The CADESI-4 is simpler to use and quicker to administer than its previous version. The ICADA recommends the CADESI-4 instead of the CADESI-3 to score skin lesions of AD in dogs enrolled in clinical trials.

The ACVD task force on canine atopic dermatitis (VIII): is the epidermal lipid barrier defective?

In humans with atopic dermatitis (AD), it is suspected that the epidermal lipid barrier is abnormal because of combined insufficient extrusion of lipid-containing organelles into the superficial epidermal intercellular spaces as well as skin lipid metabolic defects. To date, studies investigating skin hydration and lipids in atopic dogs are scarce and unfortunately have yielded conflicting data. Whether or not dogs with AD exhibit dry skin and an inadequate stratum corneum barrier, therefore, remains the subject of speculation.

The ACVD task force on canine atopic dermatitis (VI): IgE-induced immediate and late-phase reactions, two inflammatory sequences at sites of intradermal allergen injections

Intradermal testing is a common diagnostic procedure used in the evaluation of dogs with suspected atopic dermatitis (AD). To do this, most investigators assess the appearance of wheals that develop at the sites of intradermal allergen injections. However, wheals are rarely seen in dogs with naturally occurring AD. Furthermore, infiltration of inflammatory cells into the injection sites can occur 6-24h later, a phenomenon known as the late-phase reaction. The histological appearance of these late-phase reactions closely approximates that seen in the natural disease, suggesting that they might be more relevant than the immediate reactions. In this paper, we review the literature on immediate and late-phase reactions and re-assess the evidence for using current intradermal testing procedures as a diagnostic test in dogs.

Stem cell factor enhances immunoglobulin E-dependent mediator release from cultured rat bone marrow-derived mast cells: activation of previously unresponsive cells demonstrated by a novel ELISPOT assay.

Mucosal mast cells (MMC) are important effector cells in the immune response against gastrointestinal nematodes. We used cultured rat bone marrow‐derived mast cells (BMMC) as an in vitro model of MMC to study the effects of the multifunctional cytokine stem cell factor (SCF) on immunoglobulin E (IgE)‐dependent secretion of granule mediators. SCF (≤1000 ng/ml) was not a direct secretagogue for these cells, but it significantly enhanced IgE‐mediated secretion of the granule constituents rat mast cell protease‐II (RMCP‐II) and β‐hexosaminidase from mature BMMC in a dose‐dependent manner (>10 ng/ml). Maximum up‐regulation of secretion occurred after cells were pretreated with SCF (50 ng/ml) for 5 minutes before challenge with anti‐IgE, but the effect then declined and was absent in cells incubated with the cytokine for 3 to 24 h. In a novel ELISPOT assay developed to identify individual BMMC secreting RMCP‐II, the proportion of mature BMMC responding to anti‐IgE was significantly increased by treatment with SCF. To investigate this effect further, the percentage release of RMCP‐II and β‐hexosaminidase from populations of mature BMMC was directly compared to the proportion of individual cells releasing RMCP‐II as detected by ELISPOT. The release of both mediators was enhanced by SCF, and the increased percentage release reflected both an increased proportion of secreting cells, and enhanced mediator release from individual cells. These results suggest that SCF can enhance IgE‐dependent mediator release from BMMC not only by augmenting the secretory response from individual cells, but also by activating previously unresponsive cells.