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.     

Evaluation of a human generic formulation of ciclosporin in the treatment of canine atopic dermatitis with in vitro assessment of the functional capacity of phagocytic cells

To compare the efficacy, tolerability and safety of a generic formulation of ciclosporin for human beings with prednisone in the treatment of canine atopic dermatitis), human generic ciclosporin A (hgCsA) (5 mg/kg daily) and prednisone (1 mg/kg daily for seven days, followed by 1 mg/kg every second day) were administered to 13 and seven dogs with atopic dermatitis, respectively, for 42 days. Skin changes were assessed using a modified canine atopic dermatitis extent and severity index (mCADESI-01) and a pruritus intensity scale system. The in vitro functional capacity of phagocytic cells was assessed using the tetrazolium reductase activity and zymosan-stimulated tetrazolium reductase activity tests, as well as measurements of the percentage phagocytic activity and the ingestion capacity of phagocytic cells. Haematological and biochemical parameters were also monitored. There was a greater than or equal to 50 per cent reduction from the baseline in mCADESI-01 scores in 84.6 and 100 per cent of dogs, and a greater than or equal to 50 per cent reduction from the baseline in pruritus scores in 76.9 and 85.7 per cent of dogs, treated with hgCsA and prednisone, respectively. No important adverse physical, haematological or biochemical effects occurred with either drug and no statistically significant changes were detected in any of the four tests assessing the functional activity of phagocytes. The generic formulation of ciclosporin was effective in reducing the severity of physical signs of canine atopic dermatitis and was well tolerated.     

Fatty acid composition of serum lipids in atopic and healthy dogs

Fatty acids are increasingly used in the treatment of canine atopic dermatitis and their beneficial effects are documented in several prospective, controlled studies. Results from recent studies have indicated that atopic dogs have disordered fat metabolism, due to decreased desaturase activity. To further clarify these possible abnormalities, we examined serum fatty acid patterns in dogs with atopic dermatitis and normal controls. Atopic dermatitis was diagnosed according to the diagnostic criteria proposed by Willemse, after elimination of other possible causes of pruritic dermatitis. Both the relative and the absolute amounts of fatty acids in sera were determined by gas chromatography. Differences in the serum fatty acid pattern indicating a reduction in desaturase activity were not detected in atopic dogs when compared with controls.     

The ACVD task force on canine atopic dermatitis (XXII): nonsteroidal anti-inflammatory pharmacotherapy.

The pharmacotherapy of canine atopic dermatitis has relied primarily on the use of glucocorticoids and anti-histamines. During the last decade, other anti-inflammatory drugs have been investigated in clinical trials. This paper will review the studies using misoprostol, cyclosporine, tacrolimus, phosphodiesterase inhibitors, capsaicin, leukotriene inhibitors and serotonin-reuptake inhibitors for treatment of dogs with atopic dermatitis. For each drug the mechanism of action, the rationale for use in atopic dermatitis, the clinical efficacy, reported adverse effects and strength of recommendation for treatment of canine atopic dermatitis are described. At the time of this writing, there is fair evidence to support the recommendation for using cyclosporine, misoprostol and pentoxifylline for treatment of canine atopic dermatitis. This recommendation can be strengthened by the performance of additional blinded randomized controlled trials with larger number of dogs. In contrast, there is insufficient evidence to recommend for or against treatment with tacrolimus, leukotriene inhibitors, serotonin-reuptake antagonists and capsaicin.     

Owner assessment of therapeutic interventions for canine atopic dermatitis: a long-term retrospective analysis

Background – Canine atopic dermatitis is a frequent diagnosis in veterinary medicine; however, the long‐term prognosis for canine atopic dermatitis has not been evaluated in a systematic fashion. Hypothesis/Objectives – To compare the relative efficacy of commonly used therapies for canine atopic dermatitis in two groups of dogs over 5 and 10 year time periods. Animals – Dogs were identified from the medical record database of a privately owned veterinary dermatology practice in the USA. Methods – Clients completed a four‐part, 28‐question, Internet‐based survey. Surveys were included in the analysis if one entire section was completed. Each question was completed independently of the answers to other questions. Results – Several respondents failed to complete all questions. Some respondents answered similar questions with contradictory answers. Each question was analysed individually. A total of 136 owner surveys were completed, 39 from the 10 year and 97 from the 5 year study dogs. Eighty‐five of 135 respondents indicated that their pet was receiving some form of medical therapy for atopic dermatitis at the time of the survey. Thirty of 90 respondents (33.3%) indicated that their dog improved during a dietary trial. Five dogs met the study’s definition for clinical cure. All five of these dogs had been treated with allergen‐specific immunotherapy. Conclusions and clinical importance – This study revealed that clients believe antihistamines can be a useful part of multimodal therapy for canine atopic dermatitis. The results also demonstrated that a significant number of canines benefited from dietary modification. In addition, allergen‐specific immunotherapy was the only treatment to induce true clinical remission of atopic dermatitis.     

犬特应性皮炎及其治疗药物的研究进展

犬特应性皮炎是一种具有遗传倾向的过敏性皮肤病。由于近年来我国养犬数量不断增加,犬特应性皮炎成为宠物临床上的常见疾病,严重危害了宠物犬的身体健康。该病病因复杂,大致可概括为遗传因素、环境因素、皮肤屏障功能失调、免疫功能失调和微生物菌群失调五个方面,且由于其临床症状与其他过敏反应、炎症反应相似,难以确诊,需要通过多种临床反应共同判定。随着小动物诊疗的不断发展,犬特应性皮炎治疗在以往基础疗法上又增加了使用抗炎止痒药物、JAK通路抑制药物、生物制品药物和PED-4 选择性抑制剂等治疗方式。本文综述了近年来犬特应性皮炎的病因、临床症状、诊断方法和治疗方法方面的研究进展,以期为犬特应性皮炎的治疗提供借鉴和参考。     

Molecular cloning of canine interleukin-31 and its expression in various tissues

The newly discovered cytokine, interleukin-31 (IL-31), belongs to the short-chain cytokine group. It was reported that transgenic expression of IL-31-induced pruritus, similar to atopic dermatitis, in mice, further, excessive amounts of IL-31 was also expressed in the skin from human patients with atopic dermatitis as compared to that from normal people. In this study, canine IL-31 was molecularly cloned from concanavalin A-stimulated canine peripheral blood mononuclear cells (PBMCs), and its nucleotide sequence was determined. Canine IL-31 contains 4 alpha-helix structures characteristic of the IL-31 family, and the amino acid identity of canine IL-31 with those of human or mouse is 54% and 28%, respectively. Furthermore, we detected low levels of canine IL-31 in the thymus, testis, spleen, and kidneys, but not in the skin of atopic dogs.     

The effect of nematode administration on canine atopic dermatitis

Canine atopic dermatitis is a common disease and is considered as an animal model of the human disease. Immunomodulation by helminths is reported in several species. The aim of this study was to determine whether nematodes have an immunomodulatory effect on atopic dermatitis in dogs. In the pilot study, 12 atopic dogs were infected with either embryonated eggs of Trichuris vulpis (500 and 2500 eggs in 3 dogs each) or L3 larvae of Uncinaria stenocephala (100, 500 and 2500 eggs in 2 dogs each), respectively, for 3 months. Pruritus was evaluated with visual analogue scales and clinical lesions with the canine atopic dermatitis extent and severity index (CADESI). Skin biopsies were obtained for histopathology at the beginning and end of the study. In the subsequent placebo-controlled, double-blinded, randomised study, 21 dogs received either 2500 embryonated T. vulpis eggs or placebo and were evaluated similarly. In addition, allergen-specific serum IgE concentrations were determined. All dogs in the pilot study improved in their lesion scores, most in their pruritus scores. The cutaneous inflammatory infiltrate did not change significantly. In the subsequent randomised study, there was no significant difference between placebo and Trichuris administration in regard to pruritus or CADESI. IgE concentrations also did not change significantly. Infection with T. vulpis did not significantly change clinical signs of canine atopic dermatitis.     

The ACVD task force on canine atopic dermatitis (I): incidence and prevalence.

There is an increasing incidence of atopic diseases (asthma, allergic rhinitis and atopic dermatitis) in humans, especially in developed countries. Although there is a genetic predisposition to the development of these diseases, the rapid rise in incidence is suspected to be caused by environmental rather than genetic factors. Neither the incidence nor the prevalence of atopic dermatitis in the general canine population has been studied. As many of the environmental factors associated with the increasing incidence of atopic dermatitis in humans are consistently found in the environment of dogs, it would seem likely that a similar increase in the incidence of this disease would be occurring also in dogs. Epidemiological studies of canine atopic dermatitis are needed to characterize the incidence and prevalence of atopic dermatitis, and to further study the factors that contribute to the development of this disease.     

Serum antibodies to Malassezia yeasts in canine atopic dermatitis

Significant numbers of humans with atopic dermatitis develop Malassezia-specific IgE. Immediate skin-test reactivity to Malassezia has been demonstrated in atopic dogs. The aim of this study was to compare the serum IgG and IgE response to Malassezia in atopic dogs with and without clinical evidence of Malassezia dermatitis and/or otitis, nonatopic dogs with clinical evidence of Malassezia dermatitis and/or otitis and healthy dogs. Cytology was used to diagnose clinically significant Malassezia dermatitis and otitis. Contact plate cultures confirmed the validity of this technique. Reproducible enzyme-linked immunosorbent assays for Malassezia-specific IgG and IgE in canine serum were established. Atopic dogs had significantly higher serum IgG and IgE levels than either healthy dogs or nonatopic dogs with clinical evidence of Malassezia dermatitis and/or otitis. There was no significant difference in IgG and IgE levels between atopic dogs with and without clinical evidence of Malassezia dermatitis and/or otitis. The implications of these findings in the pathogenesis and management of canine atopic dermatitis are discussed.     

Double-blinded, placebo-controlled, cross-over pilot study on the efficacy of zileuton for canine atopic dermatitis

Nine dogs meeting the diagnostic criteria for canine atopic dermatitis were enrolled in a double-blind, placebo-controlled, cross-over clinical trial. In this pilot study, zileuton (a 5-lipoxygenase inhibitor) given orally at 2 mg kg(-1) three times daily for 4 weeks significantly decreased erythema in dogs with atopic dermatitis but had no effect on pruritus. Zileuton was well tolerated and no adverse clinical signs were noted. However, one dog developed mild alanine aminotransaminase elevation, which resolved within 1 week of discontinuation of therapy. Monitoring of alanine aminotransaminase may be necessary in dogs receiving zileuton. Further studies with larger number of dogs are needed to evaluate the efficacy of zileuton as treatment for canine atopic dermatitis.     

Food hypersensitivity dermatitis in the dog: diagnostic possibilities

Dogs with food hypersensitivity usually develop chronic pruritic dermatoses virtually indistinguishable from atopic dermatitis. These reactions are often called food allergy but the pathogenesis is poorly characterized. Several studies have addressed the incidence of canine adverse reactions to food but the outcomes were conflicting. The gold standard for the diagnosis of such a condition is the restricted dietary trial and the subsequent provocation challenge. Some attempts have been made to develop serological tests but none of these tests accurately predicted canine food sensitivity. The aim of the present study was to determine the incidence of food hypersensitivity dermatitis and to evaluate a newly developed serological test for the diagnosis of food allergy in dogs. Only 9% of 55 dogs with dermatological signs compatible with food hypersensitivity or atopic dermatitis have been diagnosed as food hypersensitive dogs.The repeatability of the serological test has shown to be insufficient.     

Effects of cyclosporin A and cilomilast on activated canine, murine and human keratinocytes

The calcineurin inhibitor cyclosporin A and the phosphodiesterase 4 inhibitor cilomilast exhibit potent immunomodulatory properties which make them interesting therapeutics for the treatment of skin disorders like canine and human atopic dermatitis. Cyclosporin A and phosphodiesterase 4 inhibitors have already demonstrated clinical efficacy in the therapy of canine and human atopic dermatitis. Their direct impact on keratinocytes, especially canine keratinocytes, is less obvious. Thus, an investigation was carried out to ascertain whether cyclosporin A and cilomilast modulate keratinocyte proliferation and secretion of proinflammatory mediators. Cyclosporin A inhibited canine and murine keratinocyte proliferation, whereas cilomilast had no affect. Cyclosporin A and cilomilast reduced the lipopolysaccharide-induced prostaglandin E2 synthesis in canine and murine keratinocytes. Both immunomodulators also inhibited the production of the CXC chemokine KC and CCL2 in the murine keratinocyte cell line MSC-P5. The two immunomodulators also significantly reduced the interferon-gamma-induced production of interferon-gamma-inducible protein 10 in human keratinocytes (HaCaT cells). Thus, cyclosporin A and cilomilast directly modulate keratinocyte functions which might contribute to the anti-inflammatory and immunomodulatory action of these compounds in the treatment of allergic skin diseases.     

The efficacy of commercially available veterinary diets recommended for dogs with atopic dermatitis

The classical treatments for dogs with atopic dermatitis have traditionally been oral antipruritic drugs, allergen-specific immunotherapy and topical therapy. Fifty dogs with atopic dermatitis were included in this multicentred, double-blinded, randomized study to compare clinical response to an 8-week period of feeding one of three commercial veterinary foods marketed for dogs with atopic dermatitis (diets A-C) or a widely distributed supermarket food (diet D). Atopic dermatitis was diagnosed using Willemse's criteria and through the exclusion of differential diagnoses. Fourteen dogs were assigned to diet A and 12 dogs each to diet B, C or D. Flea and tick control using a monthly fipronil spot-on product was administered for a minimum of 4 weeks prior to inclusion in the study and during the study period. Evaluations were made monthly. These included lesion scores, using an established scoring system (canine atopic dermatitis extent and severity index, CADESI-03) and owner evaluation of pruritus level using a visual analogue scale. After 8 weeks on the new diets, there was a significant improvement in CADESI and pruritus scores with diet B (Wilcoxon test, P = 0.043 and paired t-test, P = 0.012, respectively), in pruritus scores with diet A (paired t-test, P = 0.019) and in CADESI scores with diet D (Wilcoxon test, P = 0.037). No significant changes were detected with diet C. Based on the results of this study, in addition to the conventional therapies, changing the diet of dogs with atopic dermatitis may be a useful adjunctive therapeutic measure.     

Adherence by Staphylococcus intermedius to canine keratinocytes in atopic dermatitis

The adherence of Staphylococcus intermedius to canine keratinocytes in normal dogs was compared to that in dogs suffering from atopic dermatitis, primary seborrhoea and bacterial pyoderma. Statistically significant greater adherence by S. intermedius to keratinocytes occurred in atopic dogs and dogs suffering from pyoderma when compared with the normal group (P < 0.01) and dogs suffering from primary seborrhoea (P < 0.05). This is similar to the results of a study of human atopic dermatitis by Cole and Silverberg (1986) who demonstrated increased adherence by S. aureus to keratinocytes from atopic dermatitis patients when compared with adherence to keratinocytes in a variety of non-atopic dermatoses. This increased adherence by pathogenic staphylococci to keratinocytes may in part explain the high incidence of staphylococcal pyoderma seen in both canine and human patients suffering from atopic dermatitis.     

Peripheral blood mononuclear cell responses to major and minor Dermatophagoides allergens in canine atopic dermatitis.

Atopic dermatitis is a chronic inflammatory and pruritic skin disease commonly seen in dogs and humans. Most cases involve hypersensitivity to the house dust mites (HDM) Dermatophagoides farinae and Dermatophagoides pteronyssinus. Human atopic dermatitis is associated with the HDM derived allergens Der f 1 and 2, and Der p 1 and 2. Serological data, however, suggest that a 98/104kD protein is the most important allergen in dogs with atopic dermatitis. The aim of this study was to characterise the specificity of circulating T-cells in canine atopic dermatitis for HDM derived allergens. Peripheral blood mononuclear cells (PBMCs) from dogs with atopic dermatitis that were skin test positive for D. farinae and D. pteronyssinus were cultured with crude extracts of D. farinae, D. pteronyssinus and D. microceras, a 98/104kD allergen purified from D. farinae, Der f 1 and Der f 2. There was significantly greater responsiveness of PBMCs to the D. farinae and D. pteronyssinus extracts compared to the D. microceras extract, and similarly to the purified 98/104kD allergen compared to Der f 1 and Der f 2. The close association between serological findings and PBMC proliferation implies that the 98/104kD HDM protein is a major target of immune recognition and that T-cells also participate in the pathogenesis of canine atopic dermatitis by supporting IgE production.     

A randomized comparative clinical trial of recombinant canine interferon-gamma (KT-100) in atopic dogs using antihistamine as control

Recombinant canine interferon-gamma (KT-100) or topical antihistamine (diphenhydramine: DH) was administered to dogs with atopic dermatitis (AD) for 4 weeks and their efficacies were compared using pruritus, excoriation, erythema and alopecia as evaluation criteria. Clinical studies on 92 atopic dogs (KT-100 group: 63, DH group: 29) were conducted at 18 animal hospitals in Japan. KT-100 was administered subcutaneously once a day three times a week on alternating days for 4 weeks. DH was administered topically twice daily for 4 weeks. The efficacy rates of the KT-100 group on day 28 were 72.1% for pruritus, 73.8% for excoriation, 75.4% for erythema and 60.7% for alopecia, which were significantly higher than those of the DH group (20.7% for pruritus, 27.6% for excoriation, 24.1% for erythema and 24.1% for alopecia).     

A comparison of adherence by four strains of Staphylococcus intermedius and Staphylococcus hominis to canine corneocytes collected from normal dogs and dogs suffering from atopic dermatitis

The aim of this study was to compare the adherence of four strains of Staphylococcus intermedius and a single strain of Staphylococcus hominis to corneocytes from both normal dogs and dogs suffering from atopic dermatitis. Cells from the skin surface, corneocytes, were collected from 10 normal dogs and 10 dogs suffering from atopic dermatitis. Four strains of S. intermedius, three isolated from canine pyoderma skin lesions (strains A, B and C), and one isolated form from canine synovial membrane sample from a case of septic arthritis (strain D) were compared. S. hominis, which is not normally associated with canine disease, was also evaluated for its ability to adhere to canine corneocytes. S. hominis did not adhere to canine corneocytes. All four strains of S. intermedius adhered well to canine corneocytes collected from both normal and atopic dogs. All strains of S. intermedius showed statistically greater adherence to corneocytes collected from atopic dogs compared with those collected from normal dogs. It was concluded that the adherence assay employed here showed that S. hominis does not adhere to canine corneocytes, S. intermedius adheres preferentially to atopic corneocytes.