Prevalence of positive reactions in intradermal and IgE serological allergy tests in dogs from South Australia, and the subsequent outcome of allergen-specific immunotherapy.

OBJECTIVE: To determine the prevalence of positive allergen reactions in intradermal and IgE serological tests in dogs presenting to a dermatology referral centre in South Australia and the clinical efficacy of subsequent allergen-specific immunotherapy. DESIGN: Retrospective study. METHODS: Results from 108 intradermal allergy tests, 25 IgE serological assays and immunotherapy outcomes in 37 dogs were retrospectively analysed. Immunotherapy outcomes were determined as excellent, good, modest or failure using a global assessment of efficacy matrix which incorporated pruritus scores, lesion severity, medication requirements, and owner and clinician opinion. RESULTS: The most common positive reactions in intradermal allergy tests were Red clover (59%), Dermatophagoides farinae (29%), Tyrophagus putrescentiae (28%), Yellow dock (25%) and Malassezia pachydermatis (24%). In the IgE serological tests, Yorkshire fog grass (40%), Yellow dock (36%), Kentucky bluegrass (36%) and T. putrescentiae (36%) were the most commonly reported positive results. The outcome of allergen-specific immunotherapy was judged to be excellent in 20% of dogs, good in 15%, modest in 18% and a failure in 47%. CONCLUSION: As has been reported in other geographical areas, environmental mites and plant pollens frequently gave positive reactions in allergy tests in South Australia. However, the prevalence of individual allergen reactions differed between intradermal and IgE serological tests, with M. pachydermatis being identified as a common cause of hypersensitivity in intradermal tests but not in IgE serological assays. Immunotherapy was judged to be a beneficial treatment in 35% of dogs but was essentially unsuccessful in 65%.

Further validation of a pruritus severity scale for use in dogs.

A scale to assess the severity of pruritus in dogs was further validated. Comparison of the scale with one containing visible numerical markings demonstrated that owners were heavily influenced by the presence of numbers, resulting in a loss of the scale's ability to generate continuous data. The presence of a traditional visual analogue scale was therefore essential. The scale was tested on 713 owners who presented their dogs for veterinary attention. Pruritus scores in 408 dogs with skin disease covered the full range of possible values (0 to 10). In 305 dogs with no skin disease, 90 owners gave a score greater than zero. Comparison of the scores seen in pruritic dogs, and dogs with no evidence of skin disease, allowed a 'normal range' of 0-1.9 to be established. The scale was able to discriminate between conditions typically regarded as pruritic or non-pruritic. When the scale was assessed for its ability to detect changes in pruritus score following treatment, a median reduction of 4.4 points was observed. The scale was also used to determine what magnitude of response owners would expect following treatment of their pruritic dogs. Only 12% would have been satisfied with a 50% reduction, a figure that is typically quoted as a satisfactory response in clinical trials of anti-pruritic drugs. As a result, alternative methods of assessing clinical trials are proposed. This study has shown the scale to be a valuable tool for clinical assessment of patients, and for monitoring treatment responses in clinical trials.

Pilot study of the effect of individualised homeopathy on the pruritus associated with atopic dermatitis in dogs.

Twenty dogs with confirmed atopic dermatitis were treated with homeopathy. In the first phase of this pilot study, all of the dogs were treated by a veterinary homeopath with individualised remedies prescribed on the basis of the dog's cutaneous signs and constitutional characteristics. The response to treatment was assessed by scoring the severity of pruritus from 0 to 10 on a validated scale. The dogs were evaluated at monthly intervals for at least two months. In 15 cases, the owners reported no improvement following homeopathic treatment. In the other five cases, the owners believed that the homeopathic treatment was associated with a substantial improvement, and reported reductions in pruritus scores ranging from 64 to 100 per cent. These five dogs were selected for the second phase of the study, in which homeopathic remedies were tested against placebos in a randomised and blinded trial. In one of these dogs, atopic dermatitis resolved completely and so this dog could not participate in phase 2; another dog was euthanased because of status epilepticus before phase 2 could be started. In the remaining three cases, the owners correctly distinguished between the placebo and homeopathic remedies, and reported reductions in the pruritus score of 0, 0.2 and 0.8 following placebo treatment and 4.3, 2.4 and 3.0, respectively, following the remedy.

Dermal arteritis of the nasal philtrum: surgery as an alternative to long-term medical therapy in two dogs.

Two dogs were presented with dermal arteritis of the nasal philtrum associated with repeated episodes of bleeding. Described treatment for this condition consists of long-term, usually life-long medication with various combinations of immune suppressant and anti-inflammatory medication. This paper describes a novel surgical approach to the condition that induced long-term remission in both cases.

Immunoglobulin G responses in 21 dogs with skin diseases to antigens from different isolates of Staphylococcus intermedius.

The aim of this study was to characterise the immunoglobulin G (IgG) response in 21 dogs with or without pyoderma to antigens from six isolates of Staphylococcus intermedius. The staphylococcal proteins were separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis, transferred electrophoretically on to a membrane and subjected to immunoblotting with the dogs' serum. Gels containing separated proteins from the six isolates revealed 29 to 33 distinct bands with molecular weights ranging from 20 to 230 kDa. All the dogs' sera contained IgG that recognised 12 to 24 bands (mean 17), regardless of whether the dogs had pyoderma. The recognised proteins had molecular weights ranging from 20 to 198 kDa but the majority had molecular weights below 75 kDa. The most intense band in all six isolates had a molecular weight of 28 to 29 kDa. The antibody responses to the six isolates were essentially similar except that there were significantly more bands in the response to isolate 2 than to isolate 6, and occasional differences in the intensity of individual bands. All 21 dogs mounted an IgG response to multiple antigens in S intermedius, which differed only marginally between the six isolates. This lack of variation provides evidence that the host's response to different isolates of S intermedius is not a major factor in canine pyoderma.

Epidermolysis bullosa acquisita in a Great Dane.

Autoimmune subepidermal blistering diseases in dogs were all classified as bullous pemphigoid until 1998. Since then, refinements in reagents and immunological techniques have allowed diseases which are histologically similar but which have a different molecular pathogenesis to be described. This report describes the first case of one such disease, epidermolysis bullosa acquisita, to be documented in the UK. The dog presented with a severe blistering and ulcerative disease affecting the oral cavity, pinnae and distal limbs. The diagnosis was confirmed by histopathology and direct and indirect immunofluorescent demonstration of immunoglobulin G reactivity to basement membrane antigens. Treatment with glucocorticoids, azathioprine, colchicine and an intravenous infusion of immunoglobulins resulted in complete resolution. The drugs were discontinued 12 months after the start of treatment and the dog remained in remission.

Requirement for additional treatment for dogs with atopic dermatitis undergoing allergen-specific immunotherapy.

Allergen-specific immunotherapy (ASIT) is one of the main treatments for atopic dermatitis in dogs, but it often requires additional treatments such as antibacterial and antifungal therapy for secondary bacterial and yeast infections, or antipruritic drugs to control the clinical signs or treat the adverse effects of the immunotherapy. Twenty-seven dogs enrolled in a study of ASIT were clinically assessed four times over a period of nine months; their requirement for treatment for secondary bacterial and yeast infections, for the administration of glucocorticoids as additional antipruritic therapy, and for the treatment of any adverse effects of the ASIT were evaluated. Twenty (74 per cent) of the dogs were treated for superficial bacterial pyoderma, 18 (66.6 per cent) required treatment for Malassezia species dermatitis on one or more occasions, eight (29.6 per cent) required treatment for otitis externa due to Malassezia species or bacteria, and eight required glucocorticoids to control their clinical signs. Five (18.5 per cent) of the dogs experienced adverse effects due to the ASIT and two required treatment with antihistamines (H1 receptor antagonists) in order to continue with the ASIT.

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).

The immunopathogenesis of staphylococcal skin infections - A review.

Staphylococcus aureus and S. pseudintermedius are the major causes of bacterial skin disease in humans and dogs. These organisms can exist as commensals on the skin, but they can also cause severe or even devastating infections. The immune system has evolved mechanisms to deal with pathogenic microorganisms and has strategies to combat bacteria of this type. What emerges is a delicate "peace" between the opposing sides, but this balance can be disrupted leading to a full blown "war". In the ferocious battle that ensues, both sides attempt to get the upper hand, using strategies that are comparable to those used by modern day armies. In this review article, the complex interactions between the immune system and the organisms are described using such military analogies. The process is described in a sequential manner, starting with the invasion itself, and progressing to the eventual battlezone in which there are heavy casualties on both sides. By the end, the appearance of a simple pustule on the skin surface will take on a whole new meaning.

Gonadotrophin release and meat consumption in vegetarian women.

Many factors including diet modify the hypothalamic-pituitary axis and menstrual periodicity. We have determined the effect of a daily meat or a soybean supplement in rural vegetarian Black women on the length of the menstrual cycle and the episodic and luteinizing releasing hormone stimulated release of luteinizing hormone. The daily meat but not soybean supplement increased the length of the menstrual cycle (p less than or equal to 0.01), increased the release of LH (p less than or equal to 0.01), and decreased the stimulated release of LH in the luteal phase (p less than or equal to 0.01). These changes are opposite to those reported previously in the Caucasian women fed a meatless diet. Thus addition of meat in the diet modifies the episodic release of gonadotrophins and follicular maturation. The importance of a carbohydrate diet preferentially maintaining CNS-rhythmicity is suggested.

The involvement of intracellular Ca(2+) in 5-HT(1B/1D) receptor-mediated contraction of the rabbit isolated renal artery.

5-Hydroxytryptamine(1B/1D) (5-HT(1B/1D)) receptor coupling to contraction was investigated in endothelium-denuded rabbit isolated renal arteries, by simultaneously measuring tension and intracellular [Ca(2+)], and tension in permeabilized smooth muscle cells. In intact arterial segments, 1 nM - 10 microM 5-HT failed to induce contraction or increase the fura-2 fluorescence ratio (in the presence of 1 microM ketanserin and prazosin to block 5-HT(2) and alpha(1)-adrenergic receptors, respectively). However, in vessels pre-exposed to either 20 mM K(+) or 30 nM U46619, 5-HT stimulated concentration-dependent increases in both tension and intracellular [Ca(2+)]. 1 nM - 10 microM U46619 induced concentration-dependent contractions. In the presence of nifedipine (0.3 and 1 microM) the maximal contraction to U46619 (10 microM) was reduced by around 70%. The residual contraction was abolished by the putative receptor operated channel inhibitor, SKF 96365 (2 microM). With 0.3 microM nifedipine present, 100 nM U46619 evoked similar contraction to 30 nM U46619 in the absence of nifedipine, but contraction to 5-HT (1 nM - 10 microM) was abolished. In permeabilized arterial segments, 10 mM caffeine, 1 microM IP(3) or 100 microM phenylephrine, each evoked transient contractions by releasing Ca(2+) from intracellular stores, whereas 5-HT had no effect. In intact arterial segments pre-stimulated with 20 mM K(+), 5-HT-evoked contractions were unaffected by 1 microM thapsigargin, which inhibits sarco- and endoplasmic reticulum calcium-ATPases. In vessels permeabilized with alpha-toxin and then pre-contracted with Ca(2+) and GTP, 5-HT evoked further contraction, reflecting increased myofilament Ca(2+)-sensitivity. Contraction linked to 5-HT(1B/1D) receptor stimulation in the rabbit renal artery can be explained by an influx of external Ca(2+) through voltage-dependent Ca(2+) channels and sensitization of the contractile myofilaments to existing levels of Ca(2+), with no release of Ca(2+) from intracellular stores.

Effect of a vegetarian diet and dexamethasone on plasma prolactin, testosterone and dehydroepiandrosterone in men and women.

This study reports the effect of a vegetarian diet and dexamethasone administration on the hormone status of healthy Caucasian men and premenopausal women. A lower nocturnal release of prolactin and testosterone occurred in men fed a vegetarian diet, while in women, dexamethasone administration decreased the nocturnal release of prolactin and caused a greater decrease of plasma dehydroepiandrosterone (DHEA). These results show that diet modification can induce hormonal changes, If similar changes occur in patients with breast and/or prostatic cancer, diet modification may be of benefit in these patients with tumors known to be hormonally dependent.

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.

The ACVD task force on canine atopic dermatitis (V): biology and role of inflammatory cells in cutaneous allergic reactions.

Numerous inflammatory cells are thought to play a role in the pathogenesis of canine atopic dermatitis (AD) although, in the past, mast cells were considered the most important. However, evidence for this assumption is lacking. In this paper, we review the literature concerning the role of inflammatory cells in allergic reactions and conclude that a complex interplay exists between a wide variety of cell types. Thus, on the basis of the available evidence, the cells that appear to be the most important in the pathogenesis of canine AD are Langerhans' cells and dermal dendritic cells (both responsible for antigen processing and presentation), B-lymphocytes (responsible for reaginic antibody production), allergen-specific helper T-lymphocytes (responsible for cytokine production leading to activation of B-cells and other inflammatory cells) and mast cells (production of inflammatory mediators leading to inflammation).

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 (IX): the controversy surrounding the route of allergen challenge in canine atopic dermatitis.

For decades, the dogma that environmental allergens trigger cutaneous inflammation led to the denomination of canine atopic dermatitis as "allergic inhalant dermatitis". Definitive proof for a respiratory route of allergen challenge is lacking, however. Recent observations suggest, in fact, that skin inflammation could occur because of epidermal allergenic contact. The aim of this paper is to review the evidence published in favor and against the two suspected routes of allergen provocation.

The ACVD task force on canine atopic dermatitis (XVIII): histopathology of skin lesions.

For years, the histopathology of skin lesions of canine atopic dermatitis was deemed non-specific for this diagnosis. However, more recent studies have established that canine atopic skin lesions exhibit an inflammatory pattern characterized as a chronic, hyperplastic and spongiotic, mixed perivascular dermatitis. The nature of epidermal and dermal inflammatory cell infiltrates has now been characterized using modern immunological techniques. Epitheliotropic cells include Langerhans' cells, T-lymphocytes and rare eosinophils. Dermal cells are composed of mast cells, dermal antigen-presenting cells, T-lymphocytes and occasional intact and degranulated eosinophils. This paper provides an historical review of the landmark papers that have elucidated the pathology of canine atopic dermatitis.

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.

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.

Peripheral blood mononuclear cell responses to Dermatophagoides farinae in canine atopic dermatitis.

Atopic dermatitis is a chronic inflammatory and pruritic skin disease commonly seen in dogs and humans that is characterised by the presence of allergen-specific IgE. Data from skin tests and serological analysis suggest that the house dust mite Dermatophagoides farinae is the most important allergen in dogs with atopic dermatitis. The aim of this study was to determine if D. farinae specific peripheral blood mononuclear cell (PBMC) responses could be detected in dogs with atopic dermatitis. PBMCs were isolated by the density centrifugation from dogs with atopic dermatitis that were skin test positive for D. farinae, dogs with atopic dermatitis that were skin test negative for D. farinae, and healthy dogs. Cells were cultured with increasing concentrations of the D. farinae extract, no antigen, vaccine antigens or concanavalin A (ConA). There was significantly greater responsiveness of PBMCs from the D. farinae positive dogs than from either the D. farinae negative or healthy dogs (ANOVA, P<0.05). In contrast, no significant differences were observed in the control responses between the three groups. This is the first study to demonstrate that D. farinae specific circulating memory cells are involved in the pathogenesis of canine house dust mite hypersensitivity.